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Since my pregnancy, 2 years ago, I suffered from daily migraines. My doctors
thought these were due to hormonal changes and could only recommend pain
medication. Of course, I could not risk harm to my unborn baby by taking it. But
16 months after my son, Zachary's birth, the headaches were no better. It was
hard for Zachary to understand why mommy didn't want to do anything but lay on
the couch some days. After taking Limu Moui for 1 day, my headache was gone!
Zachary and I have so much more fun now. I will even take it during my next
pregnancy. I want to tell everyone I come into contact with about Limu Moui
because it has changed my life!
Chastity T., Cordova, TN

I am 42 years old and was diagnosed with Multiple Sclerosis in 1998. I
experienced episodes of weakness and progression of the disease. I went through
physical therapy and medications, feeling better at times and then another
episode would leave me feeling weak and numb. The last episode was so fast and
progressive that I became wheelchair bound, weak and with no feeling from the
waist down. I could not even hold my grandbaby. I was never this debilitated
before and was convinced I would die. On May 8th, I started taking about 2
tablespoons of Limu Moui, twice a day, and within one month, I was out of the
wheelchair and walking without a brace or cane. I even resumed my housework and
cooking supper. Next week, I intend to start driving again. I feel generally
good and have an increase in energy. My physical therapist commented that he'd
never seen anyone progress so quickly from how debilitated I was. I will never
be without Limu Moui!
Theresa C., Dequincy, LA

My husband, who is in construction, is exposed to the elements 8 to 10 hours a
day and suffered from constant sinus headaches. After taking Limu Moui, he
rarely suffers at all now! In addition, my pain from carpal tunnel syndrome in
my right arm and a bulging disc in my back are gone. I no longer need the brace
for my arm and I can sleep so much better at night. Limu Moui is a blessing to
the entire world!
LeJoyce A., Arcadia, LA

I have had severe fever blisters, caused by Herpes virus, on my lower lip for as
long as I can remember. These typically begin with a tingling sensation in a
small area and progress until 1/4 to 1/2 of my lower lip is swollen, red, and
bleeding. Ultimately, the lesion becomes painful throughout the typical 3 to
5-week duration and is quite unsightly and embarrassing. Upon feeling the
familiar sensation begin, I immediately applied Limu Moui directly onto the
emerging blister to see what would happen. After 4 days of applying it twice a
day, the blister was going away and never surfaced! I was amazed, as I have
never experienced this quick of a recovery from this repulsive ailment.
Mark K. Springfield, MO

I am 39 and have had asthma most of my life, starting as a small child and
becoming worse in my early 20's. Though detrimental to my internal organs, I've
used 3 different steroid based medications twice a day to keep this disease
under control and have visited the emergency room 3 times over the last 15
years. Since the day I started taking Limu Moui, I have not used any
prescription medication and I can breathe! I can now have a normal life. This is
a gift from above and it is now my duty to share my blessing!
Gary R., Sedro Woolley, WA

I have had ulcers since I was 15 years old and inflammation of the stomach
lining most of my adult life. Because of extreme heartburn, I had to take Zantac
with every meal and sometimes even between meals. Since I started taking Limu
Moui, I have not had to take Zantac. In additional, my energy level and general
well being have dramatically improved.
Nileen B., Sedro Wooley, WA

I have been on Avapro and Toprol, blood pressure medication since my open heart
surgery a year ago. My blood pressure still remained at around 179/100 or
179/120. The lowest it had ever reached was 158/90. With my doctor's approval, I
started taking 2 tablespoons per day of Limu Moui. After the second day on the
product, my blood pressure dropped to 116/66 and my doctor cut my medication
dosage in half. Three days later, he took me off Avapro completely and reduced
my dosage of Toprol even more and will take me off it completely in 2 more days.
My blood pressure has stayed consistently between 116/66 and 118/66. I am no
longer sleepy, have more energy, feel calmer, my head is clearer and my heart no
longer pounds. I will never stop taking Limu Moui and it's just a matter of time
before my doctor is in the business!
Phil R., Minden, LA

I've had rheumatoid arthritis since 1980 and in spite of having tried every kind
of medication imaginable--from Gold injections and steroids, to Methotrexate and
Remicade -- I still had to live with many physical limitations. These included
being unable to turn the car keys, raise my arms over my head, get up and down
from a sitting position, morning stiffness, low energy and little to no strength
in my hands and wrists. I began to see results after 1 week on Limu Moui and it
has continued ever since. Recently I spent 3 days, rolling paint up to the
ceiling and wallpapering. I also mowed an acre of land for 2-1/2 hours with a
tractor that has no power steering. Not only was I not sore the next day, I
drove into the city and took a CPR and First Aid Class. I'm doing things I have
not done in 15 years.
Nancy O'C., Pleasant Hill, MO

Our 6-year old daughter, Christina, has had breathing problems since the day she
was born. Ever since a near death experience when she was 6 weeks old, she has
had to use a Breathalyzer on many occasions. Recently, we had to cut a weekend
trip short and return home due to the breathing problems Christina was having
from the high spring time pollen content. We decided to try Limu Moui because
the traditional medications she was taking were not clearing her up completely.
After 4 days, all signs of Christina's pneumonia were gone and all her other
symptoms cleared up, as well. Our whole family is now on the product and we have
noticed many other benefits, after approximately 4 days of use.
David L., Shreveport, LA

I suffered from fibromyalgia and chronic fatigue syndrome, both causing constant
pain, especially after any kind of strenuous exertion, or when the weather
changed. I was taking at least 6 Ibuprofen a day and 2 or 3 Tylenol PM for pain
and to sleep at night. After 2 weeks on Limu Moui, I am not taking either one of
those medications, and my pain during the day has all but disappeared, my energy
level is "out the roof" and I am sleeping very well at night.
Rebecca S., Oak Ridge, LA

My father-in-law has diabetes, which was out of control. He had been taking oral
medication, but when his blood sugar level reached between 200 and 350, the
doctor had put him on insulin shots. His first week on Limu Moui, he took 2
tablespoons, 2 times a day. The second week, he increased it to 2 tablespoons, 3
times a day. After checking his blood sugar level, he found it had dropped to
140 and remains between 150 and 160.
Jeff B., Liberty, TX

I have had chronic sleep problems for the past 20 years and have spent many
hours tossing and turning and staring at the ceiling till daybreak. I chose to
get off the prescription medication my doctor prescribed years ago and no over
the counter aids helped. After hearing friends and family say they were sleeping
better at night because of Limu Moui I began taking it. After 3 nights, I
noticed a total change in my sleeping. What a joy it is to wake up and find it's
morning! I feel rested during the day and feel a sense of well being and
happiness from the product. Limu Moui is a real blessing!
Sally H., Heflin, LA

My health issues included allergy and sinus problems for which I had to take
medication, including a 12-hour nasal spray, every 3 to 4 hours. In addition, I
was taking Prilosec for a severe problem with indigestion and heartburn, which I
experienced with even one bit of any kind of food. After just 3 days on Limu
Moui, my allergies and sinus problems were gone and I was able to get a good
night's sleep, without any medication. I am also completely off the Prilosec and
have no more indigestion symptoms. I have not felt better in a long time!
Alton W., Oake Grove, LA

For 13 years, my daughter has been suffering from asthma and a chronic cough
every night. After 5 days on Limu Moui, I noticed she was not coughing at night.
For the last 46 days, she has not coughed, wheezed, or had to use the inhaler!
The product has been a blessing to her and she will take it for the rest of her
life!
Bonita W., Sugarland, TX

I am legally blind due to diabetes and I suffer from congestive heart failure. I
have had several heart attacks and 4 angioplasty surgeries. I also have
shortness of breath, poor circulation, bad lungs, poor kidney control and sleep
apnea, to name a few of my ailments. My blood sugar ranged from 200-450,
sometimes even higher. I was about to start kidney dialysis because of the
kidney failure. After taking Limu Moui for 3 days, I felt noticeably improved.
My blood sugar has dropped to between 130 and 170, I am able to get up without
aid, and am much more active. Before, I could barely walk 50 feet, from the
house to the mailbox, and now, I have been walking 7 blocks at a time. In
addition, I have more energy, less shortness of breath and control of my
kidneys. I have done nothing different from before, except take Limu Moui.
Edward W., Cullman, AL

I was in extreme pain following knee replacement surgery in January and physical
therapy was an excruciating experience. Twice a day, I had to take 200-500 mg of
Extra Strength Tylenol, 250 mg of Ultram and 50 mg of Percoset, totaling 2300 mg
of pain medication, daily. I began taking Limu Moui on March 31, 2001 and 4
weeks later, the last week in April, I began to notice that my pain was almost
gone. Consequently, I stopped taking all pain medication, except one 50 mg
tablet of Ultram at bedtime. Even though physical therapy is still painful, I
find that my pain subsides about 30 minutes after taking Limu Moui.
Robert W., Springfield, MO

I was plagued with year round sinus related problems, including infection,
bronchitis and laryngitis, especially in the spring and fall. This would deplete
my energy and wellness and cause me to miss work as a sign language interpreter,
causing hardship on my colleagues and deaf students, who depended on me. For
years, I tried medications, nasal sprays and herbal remedies. Within 3 days of
using Limu Moui, I was able to breathe freely and now take no medication.
Vicki W., Springfield, MO

J Cosmet Sci 2002 Jan-Feb;53(1):1-9 Related Articles, Books, LinkOut


Treatment of human skin with an extract of Fucus vesiculosus changes its
thickness and mechanical properties.

Fujimura T, Tsukahara K, Moriwaki S, Kitahara T, Sano T, Takema Y.

Biological Science Laboratories, Kao Corporation, 2606 Akabane, Ichikai-machi,
Haga-gun, Tochigi 321-3497, Japan.

Recently the researchers found that an extract of Fucus vesiculosus, which is a
type of seaweed, promotes the contraction of fibroblast-populated collagen gels
through increased expression of integrin molecules. In this study, they
investigated the effects of topical application of an aqueous extract of this
alga on the thickness and the mechanical properties of human skin. A gel
formulation that included 1% of the extract was applied topically to human cheek
skin twice daily for five weeks. A significant decrease in skin thickness
measured by B-mode ultrasound was elicited, as was a significant improvement in
elasticity measured with a Cutometer as compared with controls. In cheek skin,
the thickness normally increases and the elasticity usually decreases with age.
These results suggest that the Fucus vesiculosus extract possesses anti-aging
activities and should be useful for a variety of cosmetics.

Publication Types:
Clinical Trial
Controlled Clinical Trial

PMID: 11917251 [PubMed - indexed for MEDLINE]



1: Biol Pharm Bull 2000 Oct;23(10):1180-4 Related Articles, Books, LinkOut


Fucoidan is the active component of fucus vesiculosus that promotes contraction
of fibroblast-populated collagen gels.

Fujimura T, Shibuya Y, Moriwaki S, Tsukahara K, Kitahara T, Sano T, Nishizawa Y,
Takema Y.

Biological Science Laboratories, Kao Corporation, Haga, Tochigi, Japan.
301620@...

The fibroblast-populated collagen gel culture method has been evaluated as a
dermal model of wound contraction and granulation in tissues during the wound
healing process and as an in vitro model of dermal tissue. We previously
reported that an extract of Fucus vesiculosus promoted fibroblast-populated
collagen gel contraction and that the promotion of the gel contraction was due
to the increased expression of integrin alpha2beta1 on the surface of the
fibroblasts. In this study, we investigated the active component of the extract
of this alga using extraction and fractionation techniques. Water extraction of
the alga was followed by precipitation with excess ethanol and then gel
filtration with the boundary molecular weight of 30,000. The high molecular
weight fraction obtained from gel filtration was fractionated by ion exchange
chromatography on diethylaminoethyl cellulose column to give active fractions
that have more polar properties. These polar, high molecular weight fractions
which contained molecules with fucose and sulfate groups showed significant gel
contraction-promoting activity and integrin expression-enhancing activity, and
were estimated to be the sulfated-polysaccharide fucoidan. Commercially
available fucoidan showed similar activities to the above-described fraction of
this alga. Although it remains necessary to precisely identify the specific
active component, the above results indicate that fucoidan is the active
component which promotes collagen gel contraction, and also indicate the
possibility that it dose so by enhancing the integrin alpha2beta1 expression.

PMID: 11041247 [PubMed - indexed for MEDLINE]

Immunological analysis of inhibition of lung metastases by fucoidan (GIV-A)
prepared from brown seaweed Sargassum thunbergii.

Itoh H, Noda H, Amano H, Ito H.

Laboratory of Marine Biochemistry, Faculty of Bioresources, Mie University, Tsu,
Japan.

The antimetastatic effect of GIV-A (fucoidan) and/or 5-FU was examined in an
experimental model of lung metastases induced by Lewis lung carcinoma in mice.
Injection of GIV-A i.p. after removal of the implanted primary tumor inhibited
the development of lung metastases. Combination treatment with GIV-A and 5-FU
inhibited significantly the lung metastases. The number of peritoneal
macrophages, total cells and macrophages in the lung increased in mice treated
with GIV-A. Binding of the third component of complement (C3) cleavage products
(C3b) to the C3 receptor on peritoneal macrophages after i.v. injection of GIV-A
was enhanced, as shown by the fluorescent antibody technique. Lung metastases
were inhibited by i.v. injection of peritoneal macrophages activated with GIV-A.
GIV-A depressed aniline hydroxylase and aminopyrine demethylase activities of
the hepatic microsomal drug-metabolizing system in tumor-bearing mice. Moreover,
the concentration of 5-FU in the tissues (lung, liver, kidney, spleen and blood)
was increased significantly by coadministration of GIV-A. The picryl
chloride-induced delayed type hypersensitivity (PC-DTH) response in mice was
depressed after the implantation of tumor and treatment with 5-FU. GIV-A
restored the suppression of PC-DTH by 5-FU, but did not increase the PC-DTH of
normal mice. GIV-A not only enhanced the degree of spleen cell-mediated sheep
red blood cell (SRBC) hemolysis (quantitative hemolysis of SRBC), the indexes of
the spleen and thymus and the number of spleen cells, but also restored the
suppressive effect of 5-FU. In the group receiving GIV-A, the percentages of
splenic Thy1.2-, L3T4- and asialo GM1-positive cells were significantly
increased as compared with the tumor-bearing mice treated with saline.
Furthermore, the L3T4+/Lyt2+ ratio showed a tendency to increase, and the
Lyt2+/Thy1.2+ ratio was decreased. These results suggest that the antitumor
effect of GIV-A may be correlated with the changing pattern of the Thy1.2-,
L3T4- and asialo GM1-positive cells, C3 activation, macrophage activation and
depression of the hepatic microsomal drug-metabolizing system. These findings
raise the possibility that GIV-A may have clinical value in the prevention of
cancer metastasis.

PMID: 8572581 [PubMed - indexed for MEDLINE]


  Anticancer Res 1996 May-Jun;16(3A):1213-8 Related Articles, Books, LinkOut


Antitumor and antiproliferative effects of a fucan extracted from ascophyllum
nodosum against a non-small-cell bronchopulmonary carcinoma line.

Riou D, Colliec-Jouault S, Pinczon du Sel D, Bosch S, Siavoshian S, Le Bert V,
Tomasoni C, Sinquin C, Durand P, Roussakis C.

ISOMer (Institut des Substances et Organismes de la Mer), SMAB, Laboratoire de
Pharmacologie Marine, Faculte de Pharmacie, Nantes, France.

Fucans, sulfated polysaccharides extracted from brown seaweeds, have been shown
to be endowed with inhibitory effects cell growth in various experimental
models. We studied both the antiproliferative and antitumor properties of a
fucoidan extract (HF) obtained from the brown seaweed Ascophyllum nodosum on a
cell line derived from a non-small-cell human bronchopulmonary carcinoma
(NSCLC-N6), this type of carcinoma is particularly chemo-resistant. HF exerts in
vitro a reversible antiproliferative activity with a block observed in the G1
phase the cell cycle. Studies performed with the NSCLC-bearing nude mice show
antitumor activity at subtoxic doses. These preliminary results indicate that HF
exhibits inhibitory effect both in vitro and in vivo and is very potent
antitumor agent in cancer therapy.

PMID: 8702239 [PubMed - indexed for MEDLINE]

Ann Plast Surg 2001 Nov;47(5):540-6 Related Articles, Books, LinkOut


Protective effect of fucoidin (a neutrophil rolling inhibitor) on ischemia
reperfusion injury: experimental study in rat epigastric island flaps.

Cetin C, Kose AA, Aral E, Colak O, Ercel C, Karabagli Y, Alatas O, Eker A.

Department of Plastic & Reconstructive Surgery, Osmangazi University Medical
Faculty, Eskisehir, Turkey.

The objective of this study was to examine whether a decrease in
neutrophil-mediated tissue injury using Fucoidin, a nontoxic neutrophil rolling
inhibitor, would improve flap survival in an island flap model after
ischemia-reperfusion. Myeloperoxidase activity (an indirect index of tissue
neutrophil count) and malondialdehyde (an indicator of lipid peroxidation), the
degree of neutrophil infiltration by direct counting, and macroscopic flap
survival were assessed in the flap after arterial ischemia-reperfusion.
Epigastric island skin flaps were elevated in 56 rats. The first group of 21
rats was subjected to 6 hours of arterial ischemia. The second group of 21 rats
was subjected to 10 hours of arterial ischemia, and the rest of the rats were
used as nonischemic controls (sham flaps). For inhibiting neutrophil rolling, a
nontoxic polysaccharide agent-Fucoidin-was used. Each ischemic group was divided
further into three subgroups: Subgroup I (control rats) received saline,
subgroup II received 10 mg per kilogram Fucoidin, and subgroup III received 25
mg per kilogram Fucoidin before reperfusion. The results were evaluated as
tissue neutrophil counts, tissue malondialdehyde content, tissue myeloperoxidase
activity, and flap survival. Neutrophil counts and tissue myeloperoxidase
activity were decreased significantly (p <0.001) in subgroup III, but lipid
peroxidation by means of tissue malondialdehyde content was not affected by
Fucoidin administration. The authors conclude that administration of Fucoidin
before reperfusion can limit tissue injury apparently by inhibiting neutrophil
rolling in a dose-dependent manner.

PMID: 11716267 [PubMed - indexed for MEDLINE]

J Nutr Sci Vitaminol (Tokyo) 1999 Jun;45(3):325-36 Related Articles, Books,
LinkOut


Inhibitory effect of Cladosiphon fucoidan on the adhesion of Helicobacter pylori
to human gastric cells.

Shibata H, KimuraTakagi I, Nagaoka M, Hashimoto S, Sawada H, Ueyama S, Yokokura
T.

Yakult Central Institute for Microbiological Research, Tokyo, Japan.

We studied the inhibitory effect of Cladosiphon fucoidan on the attachment of
Helicobacter pylori (H. pylori), a gastroduodenal pathogen, to human gastric
cell lines. The bacterial binding in these cell lines was inhibited more by
Cladosiphon fucoidan (IC50 = 16-30 mg/mL), than by the fucoidan from Fucus (IC50
> 30 mg/mL). Dextran sulfate, another sulfated polysaccharide, did not inhibit
the binding at all. Pre-incubating the bacterial suspension with fucoidans
reinforced the inhibitory ability of these components, and reduced the IC50
value of Cladosiphon fucoidan to approximately 1 mg/mL. However, the binding was
not inhibited by pre-treatment of gastric cells with these components. It was
also shown that this fucoidan blocks both Leb- and sulfatide-mediated attachment
of H. pylori to gastric cells. Furthermore, fucoidan-binding proteins were found
on the H. pylori cell surface by Western blot analysis. Thus, the inhibitory
effect exerted by Cladosiphon fucoidan on binding between H. pylori and gastric
cells might result from the coating with this component of the bacterial
surface.

PMID: 10524351 [PubMed - indexed for MEDLINE]



Biomed Mater Eng 2001;11(1):55-61 Related Articles, Books, LinkOut


Effect of oligofucose derivatives on acetic acid-induced gastric ulcer in rats.

Shibata H, Nagaoka M, Takagi IK, Hashimoto S, Aiyama R, Yokokura T.

Yakult Central Institute for Microbiological Research, Kunitachi, Tokyo, Japan.
hideyuki-shibata@...

This study attempted to enhance the anti-ulcer activity of fucoidan from
Cladosiphon okamuranus TOKIDA by chemical modification with a hydrophobic group.
The suitable number of fucose residues in the effective compound was also
clarified to obtain a compound of constant quality. Degraded fucoidans were
coupled with several hydrophobic groups via Schiff bases, and their anti-ulcer
activities were determined by acetic acid-induced ulcer models in rats.
Size-fractionated oligofucose was also modified and assayed for anti-ulcer
activity. Among the modified oligofucoses, only the oligofucose-dodecylaniline
combination (OFDA) significantly promoted ulcer healing. The effective dose was
0.2 mg/kg/d. The most suitable number of fucose residues in the compound for the
anti-ulcer activity was determined to be around 12. We succeeded in enhancing
the anti-ulcer activity of Cladosiphon fucoidan by modification with
dodecylaniline. The activity of this compound was comparable or greater than
that of typical anti-ulcer agents. By determination of the optimal OF chain
length for the anti-ulcer activity of OFDA, it became possible to obtain OFDA of
constant quality.

PMID: 11281579 [PubMed - indexed for MEDLINE]

Experientia 1989 Oct 15;45(10):996-8 Related Articles, Books, LinkOut


Further characterization of sulfated homopolysaccharides as anti-HIV agents.

Sugawara I, Itoh W, Kimura S, Mori S, Shimada K.

Department of Pathology, University of Tokyo, Japan.

Fucoidan and dextran sulfate showed anti-HIV activities against mononuclear
cells from AIDS patients, and they abrogated HIV reverse transcriptase (RT)
activity by interacting with the HIV envelope in the membranes of target cells.
Furthermore, they showed a synergistic effect with azidothymidine (AZT).

PMID: 2478388 [PubMed - indexed for MEDLINE




Phytomedicine 1999 Nov;6(5):335-40 Related Articles, Books, LinkOut


Antiviral properties of fucoidan fractions from Leathesia difformis.

Feldman SC, Reynaldi S, Stortz CA, Cerezo AS, Damont EB.

Departamento de Quimica Organica-CIHIDECAR, Facultad de Ciencias Exactas y
Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Argentina.

Three fractions of fucoidans isolated from the brown seaweed Leathesia difformis
(Ee, Ec and Ea) were found to be selective antiviral agents against herpes
simplex virus (HSV) types 1 and 2 and human cytomegalovirus. Fraction Ea was the
most active, with IC50 values in the range 0.5-1.9 microg/ml without affecting
cell viability at concentrations up to 400 microg/ml. The antiherpetic activity
of Ea was assessed by three different methods, plaque reduction, inhibition of
virus yield and prevention of HSV-2 induced shut-off of cell protein synthesis,
demonstrating that the inhibitory effect was independent of the antiviral assay
and the multiplicity of infection. The mode of action of Ea could be ascribed to
an inhibitory action on virus adsorption. The fucoidans did not inhibit the
blood coagulation process even at concentrations exceeding more than 100 times
the IC50 value.

PMID: 11962540 [PubMed - indexed for MEDLINE]




Gen Pharmacol 1997 Oct;29(4):497-511 Related Articles, Books, LinkOut


Sulfated polysaccharides extracted from sea algae as potential antiviral drugs.

Witvrouw M, De Clercq E.

Rega institute for Medical Research, Katholieke Universiteit Leuven, Belgium.

The inhibitory effects of polyanionic substances on the replication of herpes
simplex virus (HSV) and other viruses were reported almost four decades ago.
However, these observations did not generate much interest, because the
antiviral action of the compounds was considered to be largely nonspecific.
Shortly after the identification of human immunodeficiency virus (HIV) as the
causative agent of the acquired immune deficiency syndrome (AIDS) in 1984,
heparin and other sulfated polysaccharides were found to be potent and selective
inhibitors of HIV-1 replication in cell culture. Since 1988, the activity
spectrum of the sulfated polysaccharides has been shown to extend to various
enveloped viruses, including viruses that emerge as opportunistic pathogens
(e.g., herpes simplex virus [HSV] and cytomegalovirus [CMV]) in immunosuppressed
(e.g., AIDS) patients. As potential anti-HIV drug candidates, sulfated
polysaccharides offer a number of promising features. They are able to block HIV
replication in cell culture at concentrations as low as 0.1 to 0.01 microgram
ml-1 without toxicity to the host cells at concentrations up to 2.5 mg ml-1. We
noted that some polysulfates show a differential inhibitory activity against
different HIV strains, suggesting that marked differences exist in the target
molecules with which polysulfates interact. They not only inhibit the cytopathic
effect of HIV, but also prevent HIV-induced syncytium (giant cell) formation.
Furthermore, experiments carried out with dextran sulfate samples of increasing
molecular weight and with sulfated cyclodextrins of different degrees of
sulfation have shown that antiviral activity increases with increasing molecular
weight and degree of sulfation. A sugar backbone is not strictly needed for the
anti-HIV activity of polysulfates because sulfated polymers composed of a
carbon-carbon backbone have also proved to be highly efficient anti-HIV agents
in vitro. Other, yet to be defined, structural features may also play an
important role. Sulfated polysaccharides may act synergistically with other
anti-HIV drugs (e.g., azidothymidine [AZT]). They are known to lead very slowly
to virus-drug resistance development and they show activity against HIV mutants
that have become resistant to reverse transcriptase inhibitors, such as AZT,
tetrahydro-imidazo [4,5,l-jk] [1,4]-benzodiazepin-2(1H)-thione (TIBO) and
others. From studies on their mechanism of action we concluded that polysulfates
exert their anti-HIV activity by shielding off the positively charged sites in
the V3 loop of the viral envelope glycoprotein (gp120). The V3 loop is necessary
for virus attachment to cell surface heparan sulfate, a primary binding site,
before more specific binding occurs to the CD4 receptor of CD4+ cells. This
general mechanism also explains the broad antiviral activity of polysulfates
against enveloped viruses. Variations in the viral envelope glycoprotein region
may result in differences in the susceptibility of different enveloped viruses
to compounds that interact with their envelope glycoproteins. The efficacy of
polysulfates in the therapy and/or prophylaxis of retroviral infections and
opportunistic infections remains to be demonstrated both in animal models and
humans. It is important to consider not only treatment of patients who are
already infected with HIV, but also prophylaxis and protection from HIV and/or
other virus infections. Because (i) sexual transmission is responsible for the
large majority of HIV infections worldwide; (ii) this transmission is mostly
mediated via mononuclear cells that infect epithelial cells of the genital
tract; and because (iii) polysulfates effectively inhibit cell-cell adhesion,
polysulfates may be considered as potentially effective in a vaginal formulation
to protect against HIV infection.

Publication Types:
Review
Review, Tutorial

PMID: 9352294 [PubMed - indexed for MEDLINE]




Biomed Pharmacother 1996;50(5):207-15 Related Articles, Books, LinkOut


Chemotherapy of human immunodeficiency virus (HIV) infection: anti-HIV agents
targeted at early stages in the virus replicative cycle.

De Clercq E.

Rega Institute for Medical Research, Katholieke Universiteit Leuven, Belgium.

Several compounds have been identified that inhibit an early stage in the
replicative cycle of the human immunodeficiency virus (HIV): i) virus
adsorption: polysulfates, polysulfonates, polycarboxylates, polyphosphates, and
polyoxometalates; or ii) virus-cell fusion: plant lectins, negatively charged
albumins and betulinic acid derivatives; iii) virus fusion/uncoating: bicyclam
derivatives; iv) reverse transcription: dideoxynucleoside analogues, acyclic
nucleoside phosphonates and non-nucleoside reverse transcriptase inhibitors. In
principle, HIV may develop resistance to any of these specific anti-HIV agents.
However, virus breakthrough can be completely prevented if these agents, alone
or in combination, are added to the HIV-infected cells from the beginning at
sufficiently high ('knock-out') concentrations.

Publication Types:
Review
Review, Tutorial

PMID: 8949401 [PubMed - indexed for MEDLINE

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On your 5th level, you get 12 dollars.

4.For every 5 you sign up in a month,
  you get and extra
  120 to 150 dollars. example: sign up
  10 get and extra
240 to 300 dollars.

5. After the FIVE levels You also get
  a portion of 2
  precent of the total production of
all those on your
level in the company.
6. That not all. Your Upline will
sign up the first
five for you. You supply the names.
  We'll do it. And
  we will continue till you say uncle!

My ID 1236501
For more information call:
501-612-5890   or email
billts@...
http://Bill.limupro.com

P.S. Ask about my company, product
and timing.

Control the input, and you will master
  the output
www.freenetleads.com/free/4791980sul

http://www.trafficswarm.com/go.cgi?46941

Bill

Sharing What Physicians Are Saying

Dr. Kyosuke Owa on Fucoidan
In research studies, the main health enhancing
ingredient in
  LIMUI, Fucoidan, has been shown to
have many
healthful benefits.

According to prominent Japanese researcher Dr.
Kyosuke Owa,
Fucoidan is said to
"Contain the same healing antibodies as mother's
milk,
providing essential amino acids and a balanced diet
of
minerals necessary to boost the immune system."
"Encourage the regeneration of new cells,
increasing cellular
immunity and giving the body additional 'firepower'
against
diseases."
"Not only aids in the development of new cells, but
it
encourages the regeneration of what are called
Natural Killer
Cells. These cells are found on the front lines
defending our
bodies from disease."

For centuries, the people of Tonga have benefited
from the
amazing health properties of Limu Moui. Now, thanks
to Dr.
Owa's extensive research on Fucoidan, it becomes
clear why it
is our mission to share  LIMUI with the
world.

Dr. Derrick M. DeSilva, Jr., M.D.
Nationally recognized as an expert in the vital
area of
nutrition as it relates to health, Dr. DeSilva
maintains that
disease is caused by nutrient deficiency brought on
by such
factors as poor diets, depleted nutrients in food,
dieting,
medications, oxidation and stress.
Because Limu Moui, the key ingredient in ROYAL
TONGAN LIMUT,
absorbs a rich bounty of 77+ nutrients from
pristine ocean
waters, Dr. DeSilva truly believes that it's
the "PERFECT
FOOD."

Dr. DeSilva believes  LIMUI works
because:
Its main ingredient Limu Moui is the "perfect
food" because
it absorbs a rich bounty of some 77 + nutrients
from
pristine ocean waters.


Limu Moui replaces nutrients lost from all the
different
causes of deficiency.


Oxidation, which is like rusting, is a cause of
disease.
Think about the last time you cut an apple. It
starts to
turn brown from oxidation...but if you pour ROYAL
TONGAN
LIMUT on it, it will NOT turn brown!


INTESTINES: 60% of our immune system resides in
our
intestine and 80% to 90% of those who suffer from
intestinal
problems also have allergies. So, if you "fix"
your
digestive system, you help "fix" your immune
system. Limu
Moui is very beneficial to the digestive system.


CHOLESTEROL: Cholesterol is made in the liver, so
if you can
keep the liver clean it will help with
cholesterol. Limu
Moui helps the liver.


CANCER: Limu Moui may make cancer cells pop (self-
destruct)
and stop cell division. Harvard School of Public
health
says: "Fucoidan in Limu Moui reduces plasmal
cholesterol and
the building of dangerous steroids to breast
tissue." Also,
chlorine in water has been attributed to breast
cancer. Limu
Moui contains substances like Magnesium and
Calcium, which
help dispel effects of chlorine.


BLOOD SUGAR: Fucoidan coats the GI system to
prevent
problems.


ARTHRITIS: Limu Moui lubricates joints to make
them more
flexible and thereby eliminating pain of
arthritis, etc.


MOOD DISORDERS: Mood disorders are affected by
essential
fatty acid deficiency, which is replenished by
Limu Moui.
Dr. DeSilva recommends for ADD/ADHD kids to take
them off
carbohydrates, sugar, processed foods and Ritelin
and put
them on  LIMUI!


BLOOD PRESSURE: Limu Moui addresses all three
areas that
affect blood pressure, for which people normally
have to
take different medications.


HEADACHES: No one should suffer from headaches
and ROYAL
TONGAN LIMUI has the properties to address them,
along with
an increased intake of water.




According to Dr. DeSilva, the people who should
use ROYAL
TONGAN LIMUI include:
Every one of us


Anyone on Medication


Anyone who eats poorly


Anyone under stress


Anyone who wants to feel better


ANYONE WHO IS BREATHING!

For more information call:
Bill Sullivan 501-612-5890
             or visit
http://thelimuman,originallimu.com   TODAY

USE MY ID PLEASE, 1236501

J Ethnopharmacol 1989 Nov;27(1-2):35-43
Hypoglycemic activity of several seaweed extracts.
Lamela M, Anca J, Villar R, Otero J, Calleja JM
Departamento de Farmacologia, Farmacia y Tecnologia Farmaceutica, Facultad de
Farmacia, Universidad de Santiago de Compostela, Spain.

The hypoglycemic activity of several seaweed extracts on rabbits was studied.
Ethanol extracts of Laminaria ochroleuca, Saccorhiza polyschides and Fucus
vesiculosus were administered orally to normal animals and their effects on
glycemia and triglyceridemia evaluated. Crude polysaccharides and protein
solutions from Himanthalia elongata and Codium tomentosum were also assayed.
Polysaccharides and proteins from H. elongata caused a significant reduction in
blood glucose 8 h after intravenous administration. A case of 5 mg/kg of crude
polysaccharide lowered glycemia about 18% in normal rabbits and by about 50% in
alloxan-diabetic animals, while the protein solution lowered glycemia in
diabetic rabbits by about 30%.

PMID: 2615424, UI: 90135222

Hello, Denton and Katheryn. Here is some really good information On the Brain
and Nutrition. I have the areas that mention Alzheimers  the word Lit-up in Las
vagas Blinking lights.



Bill





Basic Neurochemistry  Part Five. Metabolism  33. Nutrition and Brain Function

Nutrition and Functional Neurochemistry


The availability of some nutrients can have immediate effects on behavior,
especially on the ability to respond to stimulation. Several studies suggest
that brain function, including cognitive processing, responds to changes in
nutrients.

Nutrition can influence neurotransmitter concentrations and associated behaviors


Important neurotransmitters are synthesized from compounds which are essential
dietary constituents. For instance, norepinephrine (NE) and serotonin are formed
from the essential amino acids tyrosine and tryptophan, respectively. However,
elevation of a precursor in the blood does not necessarily elevate its
concentration in the brain. For example, increasing the blood concentration of
large neutral amino acids such as phenylalanine, as occurs in phenylketonuria
(see Chap. 44), reduces tryptophan uptake into the brain because these two
compounds share a common carrier across the bloodbrain barrier (see Chap. 32).
Furthermore, the response to an increased concentration of precursor often
depends on the demand, such as firing frequency of the neurons. Enhanced
precursor availability may matter only when physiological demand is increased.

Choline for acetylcholine (ACh) synthesis can be obtained from either brain
choline, the phosphatidylcholine in the membranes or serum choline (Table 33-1).
It is taken up by a high-affinity choline-uptake system at the synapse (see
Chap. 11). Although choline can be made in the body, its synthesis can be
limited by the availability of "single-carbon" units in the diet. Ingestion of
choline together with phosphatidylcholine can increase brain choline and ACh
concentrations and enhance the ability of ACh synthesis to increase upon demand.
For example, increased dietary choline permits the brain to make excess ACh
following stimulation with atropine. Dietary phosphatidylcholine simultaneously
increases memory and the ACh content of the brains of "demented" mice, which
normally have reduced brain ACh concentrations [1]. Increasing choline
prenatally and postnatally improves the working and reference memory of young
rats.

Glucose normally provides the acetyl moiety of ACh. Extensive evidence indicates
that relatively modest increases in circulating glucose concentrations can also
increase ACh release and has been claimed to enhance learning and memory. The
relative safety of glucose administration has permitted tests of its effects on
cognitive functions in humans. Glucose enhances learning and memory in healthy
aged humans and improves several other cognitive functions in subjects with
severe cognitive pathologies, including individuals with Alzheimer's disease and
Down's syndrome. Thus, moderate increases in circulating glucose concentrations
may have robust and broad influences on brain functions that span many neural
and behavioral measures and cross readily from rodents to humans. Considerable
evidence suggests that these effects are mediated via ACh. Increasing glucose
availability can increase the amount of ACh released during conditions of
increased demand [2] (Fig. 33-1) (see also Chaps. 11 and 31).

Tryptophan, like tyrosine, crosses the bloodbrain barrier predominantly by the
carrier system for long-chain neutral amino acids. As a result, a protein-rich
meal can actually increase blood tryptophan but reduce the passage of tryptophan
into the brain by elevating at the same time the concentrations of other amino
acids, such as phenylalanine, that compete for that carrier. Serotonin
(5-hydroxytryptamine, 5-HT) synthesis depends on brain tryptophan, which in turn
depends on blood tryptophan concentrations, which can be manipulated by varying
the diet (Table 33-1). Elevating tryptophan in the brain produces
physiologically important changes in the serotonergic system (see Chap. 13).
Animals that are poor in brain tryptophan have a heightened sensitivity to
painful stimuli that can be reversed with tryptophan ingestion, which rapidly
elevates brain serotonin. Therapeutically, tryptophan has been reported to be
useful in treating subgroups of patients with depression, sleeplessness or
hyperactive behaviors.

Tyrosine is the precursor of NE and epinephrine (Table 33-1). Increasing
tyrosine reduces blood pressure in both normotensive and hypertensive animals.
The action of tyrosine on blood pressure occurs via CNS mechanisms since
co-administering other large neutral amino acids that reduce the uptake of
tyrosine into the brain blocks the effect. The antihypertensive action of
tyrosine appears to be mediated by an acceleration in NE or epinephrine release
within the CNS; injection of tyrosine produces a concurrent increase in brain
concentrations of 3-methoxy-4-hydroxyphenylethylglycol sulfate, a catecholamine
metabolite [3]. Tyrosine induces increased NE and alters NE and a and b receptor
densities in hippocampus, providing further evidence of its physiological role.
Furthermore, dietary restriction to 40% of normal food intake diminishes maze
performance, and this effect can be reversed by administration of tyrosine.

Nutrition can influence brain energy reserve


Brain energy is more resistant to changes in fasting or overfeeding than that in
liver or muscle. For example, severe fasting decreases liver ATP concentrations
and ATP: phosphocreatine ratios, while brain energy metabolism is preserved.
However, brain energy metabolism can be manipulated by diet. A high-fat (90% of
caloric value), carbohydrate-free ketogenic diet low in protein (10%) does not
significantly alter regional brain glucose utilization or cerebral
concentrations of glucose, glycogen, lactate or citrate. However, a
high-carbohydrate diet (78%) low in fat (12%) and low in protein (10%) markedly
decreases brain glucose utilization and increases cerebral concentrations of
glucose 6-phosphate. These findings indicate that long-term, moderate ketonemia
does not significantly alter brain glucose phosphorylation. However, even
marginal protein dietary deficiency when coupled with a carbohydrate-rich diet
depresses cerebral glucose utilization to a degree often seen in metabolic
encephalopathies (see Chap. 38) [4].

Carnitine participates in mitochondrial reactions. Like choline, it can be
synthesized by mammals if dietary sources of one-carbon groups are adequate. It
participates in the transfer of acyl groups across mitochondrial membranes
(Chap. 42). These include acetyl groups for ACh synthesis. Both carnitine and
acetylcarnitine cross the bloodbrain barrier (BBB), but the more lipid-soluble
acetyl-l-carnitine has been described as having a variety of effects on the
nervous system in experimental animals not seen with carnitine.

Hereditary deficits in the ability to transport carnitine or to synthesize its
acyl derivatives have been associated with diseases of skeletal and cardiac
muscle and, to a variable extent, with metabolic encephalopathy (see Chap. 34).
Secondary deficiency of carnitine has been described in a number of disorders of
mitochondrial oxidation, due in part to the detoxification and urinary excretion
of potentially damaging short-chain acids as the carnitine derivatives [5]. The
anticonvulsant valproic acid can increase carnitine requirements in susceptible
individuals [6]. Treatment with acetylcarnitine has been reported to slow the
progression of Alzheimer's disease [7].

Vitamins can regulate normal neuronal activity


Many vitamins function as cofactors in fundamental pathways, such as glycolysis,
the Krebs cycle, the respiratory chain and amino acid metabolism. Although all
tissues have these vitamin-dependent pathways, they take on increased importance
in the brain because of its high metabolic rate and dependence on continuous
metabolism. In fact, the discovery of vitamins was closely linked to the
sensitivity of the brain to deficiency, specifically that of thiamine [8].
Furthermore, in the brain these pathways are linked to neurotransmitter
synthesis.

Vitamin B1 (thiamine) is critical to normal brain function. Thiamine
pyrophosphate (TPP) functions as a cofactor of key enzymes of the Krebs cycle:
the pyruvate and a-ketoglutarate dehydrogenase complexes (PDHC and KGDHC,
respectively), the branched-chain dehydrogenase complex (BCDHC) and the pentose
shunt enzyme transketolase (TK) (Table 33-2). These dehydrogenase complexes
share a common enzyme component, lipoamide dehydrogenase. TK rearranges sugars
(see Chap. 31). A kinase can convert a membrane-bound form of TPP to thiamine
triphosphate (TTP), and a specific phosphatase hydrolyzes TTP to the
diphosphate. TTP appears to play a role in nerve membrane function, notably in
Na+ gating. The cDNAs for a number of TPP-requiring enzymes have been obtained,
and a TPP-binding motif has been proposed that is partially conserved in yeast,
rat and human.

Thiamine deficiency is a classical and well-studied example of the interaction
of nutrition with brain function. Research on thiamine deficiency continues to
attract considerable interest. In developed countries, clinically significant
thiamine deficiency is rare except as a complication of severe alcoholism or
other conditions that impair nutrition [9]. It is more common in developing
countries in which polished rice is the staple grain. It can be detected by
measuring the "TPP effect," the percentage increase in red cell TK activity upon
addition of exogenous TPP in vitro, and has been widely used in laboratory as
well as in epidemiological studies of thiamine deficiency.

After 5 to 6 days of a diet deficient in thiamine, healthy young men developed a
nonspecific syndrome of lassitude, irritability, muscle cramps and
electrocardiographic changes, which were reversed by dietary thiamine.

Prolonged thiamine deficiency frequently leads to damage to peripheral nerves
(see Chap. 36). This neuropathy tends to be worse distally than proximally,
involves myelin more than axons and is often painful. The neuropathy may be
linked to deficiencies in multiple water-soluble vitamins known for historical
reasons as the vitamin B complex.

Wernicke-Korsakoff syndrome consists of an acute (Wernicke) phase and a chronic
(Korsakoff) phase [9]. The acute syndrome consists of staggering gait, paralysis
of eye movements and confusion, associated with small hemorrhages along the
third and fourth ventricles and with reduced cerebral metabolic rate as measured
by cerebral blood flow. Injections of thiamine can be lifesaving, with clinical
improvement often evident within minutes. It is believed that prompt treatment
with thiamine can prevent the onset of the chronic Korsakoff phase. In
Korsakoff's syndrome, a striking loss of working memory accompanies relatively
little loss of reference memory (see Chap. 50). Affected patients
characteristically make up stories, or confabulate, in response to leading
questions. In this phase, patients do not respond to thiamine treatment. The
neuropathological lesions responsible for Korsakoff's syndrome have been
debated; severe damage to the cholinergic neurons of the nucleus basalis complex
has been reported.

Thiamine requirements can be altered genetically or environmentally. Among
genetic disorders, thiamine-dependent maple syrup urine disease is due to a
reduced affinity of BCDHC for TPP (see Chap. 44). A rare form of lactate
acidosis is due to reduced affinity of PDHC for TPP. Both disorders respond to
treatment with large doses of thiamine. Wernicke-Korsakoff syndrome is
associated with a variant form of TK having a decreased affinity for TPP [9].
This variation, which may be more common in chronic alcoholics, puts patients at
risk when on a diet marginal or deficient in thiamine. Subacute necrotizing
encephalomyelopathy (SNE) of Leigh is an uncommon, autosomal recessive disorder
in which the neuropathology resembles Wernicke-Korsakoff syndrome. Patients with
SNE in whom a defect in PDHC has been documented at the cDNA level have been
described. The role of thiamine in this disorder is controversial.

Environmentally, a number of dietary constituents are known to impair the
absorption of thiamine, including ethanol. Severe illness or injury also has
been reported to increase thiamine requirements. Rarely, patients have been
found who are intolerant to very large doses of thiamine. Thiamine-dependent
enzymes are reduced in the brains of patients with a variety of
neurodegenerative diseases, including Alzheimer's, Huntington's and Parkinson's
diseases.

Thiamine-deficient animals model many aspects of human thiamine deficiency [10].
Experimentally, thiamine deficiency is frequently induced by the combination of
a thiamine-deficient diet and a thiamine antagonist, either pyrithiamine or
oxythiamine. However, pyrithiamine can directly inhibit action potentials and
oxythiamine does not enter the brain efficiently. In the pyrithiamine model in
mice, abnormal neuropsychological responses develop within 5 to 7 days, gross
neurological abnormalities in 8 to 9 days and death usually by 10 to 11 days.
Strain significantly modifies the response to experimental thiamine deficiency
in mice (Fig. 33-2). In rats, abnormalities of motor performance occur by day 3,
additional neurological symptoms by day 12 and death within 2 weeks. Thiamine
deficiency leads to a selective cell death that is accompanied by accumulation
of amyloid precursor protein in surrounding neurons. It causes severe memory
disruption and loss of cholinergic function. The activities of
thiamine-dependent enzymes decline in early stages of thiamine deficiency, but
surprisingly, selective cell death is not related to the cellular or regional
distribution of thiamine-dependent enzymes or to their response to thiamine
deficiency. Instead, the general reduction in thiamine-dependent enzymes
predisposes particular brain regions to other insults. The earliest known change
that reflects selective vulnerability is an alteration in the BBB that is
accompanied by oxidative stress, which causes increased ferritin and iron
deposition, and induction of nitric oxide synthase. The results suggest that
cerebrovascular endothelial cells of these brain regions may be particularly
vulnerable to thiamine deficiency [10].

Vitamin B3 (niacin) deficiency in humans leads to pellagra, which is
characterized by dementia, dermatitis, diarrhea and eventually death. The
deficiency was recognized in the eighteenth century, shortly after the
introduction of American corn (maize) into Europe [8].

Niacin and niacinamide refer to nicotinic acid and its amide, respectively.
Although these pyrimidine derivatives can be synthesized from tryptophan in
mammals, perhaps at least in part by intestinal bacteria, 60 mg of dietary
tryptophan are required to synthesize 1 mg of the vitamin. Niacin is considered
to be a vitamin because most human diets do not contain enough tryptophan to
fulfill the normal human requirement for the vitamin of 10 to 30 mg/day.

Hartnup's syndrome is a hereditary disorder in which tryptophan transport is
impaired and requirements for dietary niacin increase. Phenylketonuria and
hyperphenylalaninemia can increase niacin requirements by increasing the
concentrations of amino acids that compete with tryptophan for transport systems
(see also Chap. 44). A high-corn diet predisposes to niacin deficiency since the
major storage protein of American corn (zein) has relatively little tryptophan
relative to other amino acids that compete for the same carrier. Addition of
purified niacin to the diet has largely abolished pellagra, which was once a
common disease in areas where corn was a dietary staple.

Niacin is incorporated into the coenzymes NAD+ and NADP+ and their reduced
forms. These cofactors are involved in numerous oxidation/reduction reactions,
including the coupling of the Krebs cycle to the respiratory chain.
Antimetabolites, particularly 6-aminonicotinamide and 3-acetylpyridine, have
been particularly useful in determining the role of niacin deficiency in the
brain in experimental animals. Newborn mice that received a single
intraperitoneal injection of 6-aminonicotinamide consistently developed lesions
in the CNS, the skin and the intestinal tract. Anterior horn cells in the spinal
cord as well as motor neurons in the brain exhibit the ultrastructural features
of neuronal chromatolysis, while glial and ependymal cells show edematous
changes. 3-Acetylpyridine administration leads to selective neuropathological
lesions in the brainstem. Although the pathological features of
antimetabolite-treated mice are not identical to those of human pellagra,
possible contributory mechanisms in the development of pellagra lesions,
including dementia and selective cell loss, may be elucidated with this
experimental model [11].

Vitamin B6 (pyridoxine) is necessary for the biosynthesis of several
neurotransmitters. It is a pyridine derivative that can exist as an alcohol,
amine or aldehyde. The concentration in brain is normally about 100-fold higher
than that in the blood. The active coenzyme is the phosphorylated derivative
pyridoxal phosphate, which readily forms Schiff bases. This coenzyme
participates in decarboxylation reactions, including those that form GABA from
glutamate, 5-HT from 5-hydroxytryptophan and probably DOPA from
dihydroxyphenylalanine. It is also involved in transaminations, including that
converting a-ketoglutarate to glutamate. The conversion of tryptophan to
nicotinamide requires pyridoxyl phosphate as a cofactor, and the excretion of
xanthurenic acid after a tryptophan load is widely used to test the adequacy of
pyridoxine nutriture. In vitamin B6 deficiency in rats, biochemical and
morphological abnormalities, including decreased dendritic arborization and
reduced numbers of myelinated axons and synapses, are associated with behavioral
changes, such as epileptiform seizures and movement disorders. Reduced seizure
threshold and delayed neuronal recovery are related to the significantly reduced
brain regional GABA and elevated glutamate concentrations in
pyridoxine-deficient rats [12]. In addition, vitamin B6 deficiency during
gestation and lactation alters the function of N-methyl-d-aspartate (NMDA)
receptors.

Pyridoxine deficiency has occurred in human infants fed a formula from which
vitamin B6 had been inadvertantly omitted. The prominent finding was intractable
seizures which responded promptly to injections of the vitamin. Deficiency of
pyridoxine can contribute to the polyneuropathy of B-complex deficiency.
However, very large doses of pure pyridoxine can lead to a persistant sensory
neuropathy [13] (Chap. 36).

Like those of other nutrients, requirements for pyridoxine can be altered by
genetic or environmental factors and are increased in a number of disorders of
the nervous system [8,14,15]. Treatment of "pyridoxine-deficient" infants may
require doses of pyridoxine several hundredfold the normal daily requirement.
Maintenance with doses at least tenfold the normal requirement typically permits
normal development if irreversible brain damage has not yet occurred. It has
been suggested that mild forms of pyridoxine dependence may be a relatively
common cause of intractable seizures and mental retardation, but neurochemical
studies of these patients are limited. In homocystinuria and cystothioninuria,
two disorders of amino acid metabolism, some patients respond to large doses of
pyridoxine. In these patients, the mutations appear to reduce the affinity of
the relevant enzymes for pyridoxal phosphate (see Chap. 44).

Environmentally, hydrazides and oximes can increase pyridoxine requirements.
Large doses of pyridoxine are routinely given with the antituberculous
medication isonicotinic hydrazide, to prevent drug-induced neuropathy.

Vitamin B12 (cobalamin) deficiency is commonly associated with neurological
syndromes. The cobalamins are a series of porphyrin-like compounds [16]. The
active forms contain a cobalt ion linked to one of the methylene groups. The
cobalamins are synthesized by many microorganisms but not by higher plants or
animals. A rich dietary source is meat, particularly liver. Effective absorption
requires a series of transport proteins, including a glycoprotein intrinsic
factor secreted by gastric parietal cells. Conversion to the active coenzymes
adenosylcobalamin and methylcobalamin requires at least two reductase reactions
and an adenosyltransferase step. The reductases are flavoproteins that require
NAD+ as a cofactor. Thus, B12 metabolism involves at least three vitamins: B12
itself, niacin and riboflavin. Body stores of cobalamins are normally large
enough to maintain health for over 2 years without a dietary source of the
vitamin.

Cobalamins have two well-established biochemical functions. Adenosylcobalamin is
the cofactor for the mutase that converts methylmalonyl CoA to succinyl CoA.
This reaction is part of the pathway of metabolism of propionic acid, which
itself derives from the metabolism of odd-chain fatty acids and from certain
amino acids. Methylcobalamin is the cofactor for the methyltransferase that
converts homocysteine to the amino acid methionine. This reaction is important
in folate metabolism as well. Its impairment appears to foster folate deficiency
by an accumulation of N5-methyltetrahydrofolate in a "folate trap." Deficiency
of cobalamins or of folate or of both can restrict the supply of metabolically
available one-carbon groups for metabolic pathways, including those of nucleic
acid synthesis.

Cobalamin deficiencies are relatively common clinically [16]. Pure dietary
deficiency responding promptly to treatment with oral cobalamins has been
described in a few children of strict vegan mothers. A more common syndrome is
caused by failure of absorption due to an inadequate supply of the glycoprotein
intrinsic factor, usually on an autoimmune basis. The most characteristic
abnormality is pernicious anemia, characterized by enlarged erythrocytes, called
megaloblasts, and abnormal leukocytes. Neurological symptoms occur in many of
these patients and can precede the hematological changes [17].

Combined system disease is the most common B12-mediated neurological syndrome.
Affected patients develop unpleasant tingling sensations (paresthesias),
followed by loss of vibratory sensation, particularly in the legs, and spastic
weakness. The characteristic neuropathology is a spongy demyelination in the
long tracts of the spinal cord, particularly prominent in the posterior columns
as well as corticospinal tracts. Combined system disease responds poorly to
treatment with cobalamins.

Cobalamin deficiency is characteristically associated with malaise that does
respond dramatically to treatment, even before the hematological response is
evident. Relatively low serum concentrations of B12 have been reported in
subgroups of psychiatric patients, including patients with Alzheimer's disease,
but responses to treatment with the vitamin have, in general, not been dramatic.
Recent studies indicate that elevated concentrations of serum or cerebrospinal
fluid methylmalonate can identify patients whose neuropsychiatric manifestations
benefit from B12 treatment, even though the amounts of vitamin in serum are not
in the deficient range [17].

Whether the damage to the nervous system relates to decreased activity of the
methylmalonyl mutase or of the methyltransferase or of both remains unsettled.
Increased excretion of methylmalonate has been reported to be a marker for
patients whose neuropsychiatric manifestations will improve with B12 treatment,
but clinically normal children with a mutase deficiency are known. Children with
homocystinuria and related disorders do not develop the clinical or pathological
stigmata of combined system disease (see Chap. 44). An infant with an apparent
reduction in methyltransferase activity was clinically normal when reported at
age 1 year. Patients with severe inherited deficiencies in the activities of
both enzymes secondary to a defect in the metabolism of the cobalamins do
develop profound disease of the nervous system, with some characteristics of
combined system disease.

As with other nutrients, requirements for cobalamin can be modified by genetic
and environmental influences. Genetic factors apparently predispose to intrinsic
factor deficiencies with resultant cobalamin deficiency. Furthermore, at least
six different inherited methylmalonic acidurias have been described [16]:
absence of the mutase, decreased affinity of the mutase for adenosylcobalamin,
deficiency of mitochondrial cobalamin reductase, deficiency of a mitochondrial
cobalamin adenyltransferase and two distinguishable defects associated with
abnormal cytosolic metabolism of cobalamin (see Chap. 44). Other conditions
leading to increased cobalamin requirements include surgical removal of the
stomach, excessive destruction of cobalamins in the gut by bacteria in a blind
loop or destruction by certain kinds of intestinal tapeworm.

Folic acid contains a pterin moiety linked to para-aminobenzoic acid, which is
linked to one or more glutamate residues [18]. It plays a key role in the
transfer of one-carbon (active methylene) groups, including the conversion of
serine to glycine and the cobalamin-dependent transfer from homocysteine to
methionine. Dietary deficiency of folate with normal cobalamin leads to anemia
without significant neurological signs. However, both genetic and environmental
disorders of folate metabolism have been associated with disease of the nervous
system. Genetic defects in the relevant enzyme reactions are discussed further
in Chapter 44.

Genetic disorders of folate absorption, intraconversion and utilization are rare
[18]. They have occasionally been associated with phenocopies of well-known
psychiatric syndromes. A boy with apparent deficiency of hepatic dihydrofolate
reductase was treated with folate and developed a sociopathic personality in his
teens. A folate-responsive form of mental retardation with catatonia has been
described in an adolescent girl with N5,10-methylenetetrahydrofolic acid
reductase deficiency. Her younger sister was mentally impaired with "psychosis";
an unrelated boy with a defect of the same enzyme had seizures and proximal
muscle weakness without notable psychiatric problems. Most patients with
glutamate formiminotransferase deficiency have had a syndrome of psychomotor
retardation in infancy, but a few have been entirely normal clinically.

Environmentally, a number of common medications, including phenytoin and certain
antitumor agents, increase requirements for dietary folate. Treatment with
folate can mask the hematological signs of cobalamin deficiency without
affecting the progressive damage to the nervous system.

Pantothenic acid is a substituted hydroxybutyric acid that is a constituent of
CoA [19]. Experimental induction of pantothenic acid deficiency leads to signs
of peripheral nerve damage, for example, demyelination in laboratory animals and
paresthesias in humans. Late signs of CNS damage in animals may relate as well
to the adrenal failure that is a prominent part of the syndrome.

The brain depends on select vitamins and closely related compounds as
antioxidants to control potentially damaging free radicals


The main antioxidants in brain are vitamin E (tocopherol), vitamin C (ascorbic
acid) and glutathione (Table 33-2). The first two can be easily manipulated by
diet, whereas the latter is more difficult to control. Dietary a-lipoate appears
to be a useful compound to regenerate the antioxidant capacity of these other
compounds (see below). Dietary manipulation of antioxidants has practical
implications for brain function. Aging has been associated with free radical
damage in the brain (see Chap. 34). In aged patients tested over a 22-year
period, free recall, recognition and vocabulary correlated positively with
ascorbic acid and b-carotene in blood, even after controlling for possible
confounding variables, such as age, education and gender. These results indicate
the important role played by antioxidants in brain aging and may have
implications for prevention of progressive cognitive impairments [20].

Vitamin E (a-tocopherol) deficiency produces a characteristic neurological
syndrome. It presumably results from increased oxidative stress arising from a
reduction in antioxidant capacity. Vitamin E deficiency in neural tissues
increases endogenous lipid peroxidation, as evidenced in brain tissues by the
appearance of thiobarbituric acid-reactive substances such as malondialdehyde.
The brain is more susceptible to the deficiency than muscle. Within the brain,
the cortex, striatum and cerebellum are the most sensitive regions. Isolated
fractions from myelinated nerve tracts show that the axoplasmic membranes and
organelles are particularly vulnerable to oxidative stress [21]. Vitamin E
deficiency reduces tyrosine hydroxylase-immunopositive neurons in the substantia
nigra but not in the adjacent ventral tegmental area. The enhanced sensitivity
of the nigrostriatal pathway to oxidative stress could have important
implications for the pathogenesis of Parkinson's disease (see Chap. 45). A diet
deficient in vitamin E increases glutamate and GABA and decreases tryptophan
concentrations in the substantia nigra. The increase of nigral glutamate
suggests possible links to degenerative processes through glutamatergic
excitotoxicity. These results suggest that vitamin E may play a significant role
in the degeneration of the substantia nigra and that this tissue may be
particularly sensitive to oxidative stress. Furthermore, these findings support
the widely held view that oxidative stress in the substantia nigra is important
in the pathophysiology of Parkinson's disease.

Vitamin C (ascorbate) deficiency leads to extensive oxidative damage of proteins
and protein loss in the microsomes, as evidenced by accumulation of carbonyl
groups on proteins as well as tryptophan loss. This oxidative damage is reversed
by ascorbate therapy. Ascorbate deficiency also leads to lipid peroxidation in
microsomes, as evidenced by accumulation of conjugated dienes, malondialdehyde
and fluorescent pigment. Lipid peroxides disappear after ascorbate therapy but
not after treatment with vitamin E. These results indicate that vitamin C may
exert a powerful protection against degenerative changes in the brain associated
with oxidative damage [22].

Oxidation of vitamin E and C is maintained by glutathione, the predominant thiol
antioxidant in the brain. Glutathione cannot be directly manipulated by diet,
whereas the metabolic antioxidant a-lipoate can be absorbed from the diet and
cross the BBB to reduce oxidized glutathione and vitamins A and C (Fig. 33-3).
a-Lipoate is taken up and reduced in cells and tissues to dihydrolipoate, which
is also exported to the extracellular space; hence, protection is afforded to
both intracellular and extracellular environments. Both a-lipoate and
dihydrolipoate are potent antioxidants that regenerate other antioxidants, like
vitamins C and E, and raise intracellular glutathione concentrations. Protective
effects by antioxidants have been reported in cerebral ischemiareperfusion,
excitotoxic amino acid brain injury, mitochondrial dysfunction, diabetes and
diabetic neuropathy, inborn errors of metabolism and other causes of acute or
chronic damage to the brain or neural tissue. Thus, a-lipoate administration may
prove to be an effective treatment in numerous neurodegenerative disorders [20].

Trace nutrients in the diet have a vital role in maintaining normal brain
function


Zinc (Zn2+) influences numerous cellular functions, including immune mechanisms,
actions of several hormones and enzyme activities. More than 200 enzymes are
known to be Zn2+-dependent, including mRNA-editing enzymes, superoxide
dismutase, metalloproteins and a "Zn2+-finger" family of sequence-specific
DNA-binding proteins that regulate transcription. Metallothionein binds excess
Zn2+, thus maintaining its steady-state concentration and preventing inhibition
of an extensive number of sulfhydryl-containing enzymes and receptor sites;
hence, it protects against metal-related neurotoxicity. Metallothionein donates
Zn2+ to an extensive number of Zn2+-activated, pyridoxal phosphate-mediated
biochemical reactions. The complex nature of the interactions of Zn2+ with
multiple enzymes is exemplified by the observation that epileptic seizures that
are blocked by GABA can be blocked by either deficiency or excess of either Zn2+
or pyridoxal phosphate. A proposed explanation of these observations is that at
physiological concentrations Zn2+ stimulates the activity of hippocampal
pyridoxal kinase, enhancing the formation of pyridoxal phosphate and of GABA via
glutamate decarboxylase formation, whereas at higher doses Zn2+ inhibits the
activity of glutamate decarboxylase by preventing the binding of pyridoxal
phosphate [23]. Severe Zn2+ deficiency during the period of rapid brain growth
has effects similar to that seen with protein-calorie malnourishment, including
altered regulation of emotions; food motivation; lethargy (reduced activity and
responsiveness), and deficits in learning, attention and memory. In addition to
the many deficits produced by Zn2+ deficiency in the brain, the severe effect of
Zn2+ deficiency on other tissues leads to additional peripheral mechanisms that
alter brain function [24]. Although Zn2+ is essential at low concentrations,
higher concentrations are toxic. For example, high Zn2+ concentrations enhance
and prolong the firing rate of neurons, significantly depress paired-pulse
potentiation, block the action of NMDA on cortical neurons, enhance quisqualate
receptor-mediated injury and inhibit the Ca2+-dependent release of transmitter
by inhibiting the entry of Ca2+ into nerve terminals.

Copper is an integral component of multiple cellular enzymes, including the
cytochromes and superoxide dismutase. Copper deficiency produces clinical signs
analogous to those of Par-kinson's disease and results in low dopamine
concentration in the corpus striatum. Neuropathology in experimental animals
occurs in only part of the copper-deficient population and is dam- and
litter-related, suggesting the presence of a genetic component that alters the
response to copper deficiency. Insight into the role of copper in brain function
is provided by two genetic diseases.

Wilson's disease is an inherited disorder that leads to copper accumulation,
causing damage primarily to the liver and the brain (see Box 45-1). Psychiatric
and behavioral abnormalities occur in 30 to 100% of Wilson's disease patients
and are often the initial symptoms. The most common of the psychiatric and
behavioral manifestations include personality changes, such as irritability and
low anger threshold; depression, sometimes leading to suicidal ideation and
attempts; and deteriorating academic and work performance, which is present in
almost all neurologically affected patients [25].

Menke's disease is caused by a genetic deficiency of serum copper and of
copper-dependent enzymes and is characterized by neurological degeneration and
mental retardation, connective tissue and vascular defects, brittle and
depigmented hair and death in early childhood (see Box 45-1). Despite excessive
accumulation of the metal in various tissues, a functional copper deficiency is
evident, caused by a defective intracellular copper-transport protein. A large
amount of copper accumulates in the organelle-free cytoplasm, whereas
mitochondria are in a state of copper deficiency, indicating that the Menke's
mutation probably affects copper transport from the cytosol to the intracellular
organelles [26]. Brindled is a murine mutation that produces similar
copper-transport deficits, and studies of this animal model show that the copper
deficit in organelles causes reductions in critical copper-dependent enzymes,
such as cytochrome oxidase. It has been hypothesized that the Wilson's disease
gene is a copper-transporting ATPase with homology to the Menke's disease gene.
Dietary copper deficiency can affect brain development [27] (see below).

Selenium is vital in maintaining the antioxidant capacity of the brain.
Glutathione peroxidase is a selenium-dependent enzyme that is important for
maintaining the antioxidant capacity of brain glutathione (Fig. 33-2) and is
reduced in selenium-deficient animals. Selenium supplementation significantly
elevates Na,K-ATPase activity and significantly decreases lipid peroxide
formation. Since Na,K-ATPase activity is known to be inhibited by oxygen free
radicals, selenium supplementation appears to exert its beneficial effect on the
Na,K-ATPase activity by preventing free radical-induced damage. Selenium
significantly reduces the production of thiobarbituric acid-reactive substances,
a measure of lipid peroxidation, in response to an oxidative challenge in blood
and different regions of the brain [28]. Selenium deficiency increases dopamine
turnover in the substantia nigra but not in the striatum. These results suggest
that dietary selenium protects the brain, particularly the substantia nigra,
against oxidative damage.

Trace compounds are also important in brain function. Chromium-deficient
patients develop severe diabetic symptoms, including glucose intolerance, weight
loss, impaired energy utilization and nerve and brain disorders. Low dietary
boron is reported to cause significantly poorer performance on various cognitive
and psychomotor tasks. Additional research is likely to reveal additional trace
components of the diet that may be critical to normal brain function.



(c) 1999 by American Society for Neurochemistry
Published by Lippincott Williams and Wilkins.

Ann Plast Surg 2001 Nov;47(5):540-6 Related Articles, Books, LinkOut


Protective effect of fucoidin (a neutrophil rolling inhibitor) on ischemia
reperfusion injury: experimental study in rat epigastric island flaps.

Cetin C, Kose AA, Aral E, Colak O, Ercel C, Karabagli Y, Alatas O, Eker A.

Department of Plastic & Reconstructive Surgery, Osmangazi University Medical
Faculty, Eskisehir, Turkey.

The objective of this study was to examine whether a decrease in
neutrophil-mediated tissue injury using Fucoidin, a nontoxic neutrophil rolling
inhibitor, would improve flap survival in an island flap model after
ischemia-reperfusion. Myeloperoxidase activity (an indirect index of tissue
neutrophil count) and malondialdehyde (an indicator of lipid peroxidation), the
degree of neutrophil infiltration by direct counting, and macroscopic flap
survival were assessed in the flap after arterial ischemia-reperfusion.
Epigastric island skin flaps were elevated in 56 rats. The first group of 21
rats was subjected to 6 hours of arterial ischemia. The second group of 21 rats
was subjected to 10 hours of arterial ischemia, and the rest of the rats were
used as nonischemic controls (sham flaps). For inhibiting neutrophil rolling, a
nontoxic polysaccharide agent-Fucoidin-was used. Each ischemic group was divided
further into three subgroups: Subgroup I (control rats) received saline,
subgroup II received 10 mg per kilogram Fucoidin, and subgroup III received 25
mg per kilogram Fucoidin before reperfusion. The results were evaluated as
tissue neutrophil counts, tissue malondialdehyde content, tissue myeloperoxidase
activity, and flap survival. Neutrophil counts and tissue myeloperoxidase
activity were decreased significantly (p <0.001) in subgroup III, but lipid
peroxidation by means of tissue malondialdehyde content was not affected by
Fucoidin administration. The authors conclude that administration of Fucoidin
before reperfusion can limit tissue injury apparently by inhibiting neutrophil
rolling in a dose-dependent manner.

PMID: 11716267 [PubMed - indexed for MEDLINE]

Hear Powerful Testimonies
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Mark K. Springfield, MO

I am 39 and have had asthma most of my life, starting as a small child and
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Gary R., Sedro Woolley, WA

I have had ulcers since I was 15 years old and inflammation of the stomach
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Nileen B., Sedro Wooley, WA

I have been on Avapro and Toprol, blood pressure medication since my open heart
surgery a year ago. My blood pressure still remained at around 179/100 or
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My blood pressure has stayed consistently between 116/66 and 118/66. I am no
longer sleepy, have more energy, feel calmer, my head is clearer and my heart no
longer pounds. I will never stop taking Limu Moui and it's just a matter of time
before my doctor is in the business!
Phil R., Minden, LA

I've had rheumatoid arthritis since 1980 and in spite of having tried every kind
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Nancy O'C., Pleasant Hill, MO

Our 6-year old daughter, Christina, has had breathing problems since the day she
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David L., Shreveport, LA

I suffered from fibromyalgia and chronic fatigue syndrome, both causing constant
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Jeff B., Liberty, TX

I have had chronic sleep problems for the past 20 years and have spent many
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Sally H., Heflin, LA

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Bonita W., Sugarland, TX

I am legally blind due to diabetes and I suffer from congestive heart failure. I
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kidney failure. After taking Limu Moui for 3 days, I felt noticeably improved.
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Edward W., Cullman, AL

I was in extreme pain following knee replacement surgery in January and physical
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Robert W., Springfield, MO

I was plagued with year round sinus related problems, including infection,
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using Limu Moui, I was able to breathe freely and now take no medication.
Vicki W., Springfield, MO

J Cosmet Sci 2002 Jan-Feb;53(1):1-9 Related Articles, Books, LinkOut


Treatment of human skin with an extract of Fucus vesiculosus changes its
thickness and mechanical properties.

Fujimura T, Tsukahara K, Moriwaki S, Kitahara T, Sano T, Takema Y.

Biological Science Laboratories, Kao Corporation, 2606 Akabane, Ichikai-machi,
Haga-gun, Tochigi 321-3497, Japan.

Recently the researchers found that an extract of Fucus vesiculosus, which is a
type of seaweed, promotes the contraction of fibroblast-populated collagen gels
through increased expression of integrin molecules. In this study, they
investigated the effects of topical application of an aqueous extract of this
alga on the thickness and the mechanical properties of human skin. A gel
formulation that included 1% of the extract was applied topically to human cheek
skin twice daily for five weeks. A significant decrease in skin thickness
measured by B-mode ultrasound was elicited, as was a significant improvement in
elasticity measured with a Cutometer as compared with controls. In cheek skin,
the thickness normally increases and the elasticity usually decreases with age.
These results suggest that the Fucus vesiculosus extract possesses anti-aging
activities and should be useful for a variety of cosmetics.

Publication Types:
Clinical Trial
Controlled Clinical Trial

PMID: 11917251 [PubMed - indexed for MEDLINE]



1: Biol Pharm Bull 2000 Oct;23(10):1180-4 Related Articles, Books, LinkOut


Fucoidan is the active component of fucus vesiculosus that promotes contraction
of fibroblast-populated collagen gels.

Fujimura T, Shibuya Y, Moriwaki S, Tsukahara K, Kitahara T, Sano T, Nishizawa Y,
Takema Y.

Biological Science Laboratories, Kao Corporation, Haga, Tochigi, Japan.
301620@...

The fibroblast-populated collagen gel culture method has been evaluated as a
dermal model of wound contraction and granulation in tissues during the wound
healing process and as an in vitro model of dermal tissue. We previously
reported that an extract of Fucus vesiculosus promoted fibroblast-populated
collagen gel contraction and that the promotion of the gel contraction was due
to the increased expression of integrin alpha2beta1 on the surface of the
fibroblasts. In this study, we investigated the active component of the extract
of this alga using extraction and fractionation techniques. Water extraction of
the alga was followed by precipitation with excess ethanol and then gel
filtration with the boundary molecular weight of 30,000. The high molecular
weight fraction obtained from gel filtration was fractionated by ion exchange
chromatography on diethylaminoethyl cellulose column to give active fractions
that have more polar properties. These polar, high molecular weight fractions
which contained molecules with fucose and sulfate groups showed significant gel
contraction-promoting activity and integrin expression-enhancing activity, and
were estimated to be the sulfated-polysaccharide fucoidan. Commercially
available fucoidan showed similar activities to the above-described fraction of
this alga. Although it remains necessary to precisely identify the specific
active component, the above results indicate that fucoidan is the active
component which promotes collagen gel contraction, and also indicate the
possibility that it dose so by enhancing the integrin alpha2beta1 expression.

PMID: 11041247 [PubMed - indexed for MEDLINE]

J Nutr Sci Vitaminol (Tokyo) 1999 Jun;45(3):325-36 Related Articles, Books,
LinkOut


Inhibitory effect of Cladosiphon fucoidan on the adhesion of Helicobacter pylori
to human gastric cells.

Shibata H, KimuraTakagi I, Nagaoka M, Hashimoto S, Sawada H, Ueyama S, Yokokura
T.

Yakult Central Institute for Microbiological Research, Tokyo, Japan.

We studied the inhibitory effect of Cladosiphon fucoidan on the attachment of
Helicobacter pylori (H. pylori), a gastroduodenal pathogen, to human gastric
cell lines. The bacterial binding in these cell lines was inhibited more by
Cladosiphon fucoidan (IC50 = 16-30 mg/mL), than by the fucoidan from Fucus (IC50
> 30 mg/mL). Dextran sulfate, another sulfated polysaccharide, did not inhibit
the binding at all. Pre-incubating the bacterial suspension with fucoidans
reinforced the inhibitory ability of these components, and reduced the IC50
value of Cladosiphon fucoidan to approximately 1 mg/mL. However, the binding was
not inhibited by pre-treatment of gastric cells with these components. It was
also shown that this fucoidan blocks both Leb- and sulfatide-mediated attachment
of H. pylori to gastric cells. Furthermore, fucoidan-binding proteins were found
on the H. pylori cell surface by Western blot analysis. Thus, the inhibitory
effect exerted by Cladosiphon fucoidan on binding between H. pylori and gastric
cells might result from the coating with this component of the bacterial
surface.

PMID: 10524351 [PubMed - indexed for MEDLINE]



Biomed Mater Eng 2001;11(1):55-61 Related Articles, Books, LinkOut


Effect of oligofucose derivatives on acetic acid-induced gastric ulcer in rats.

Shibata H, Nagaoka M, Takagi IK, Hashimoto S, Aiyama R, Yokokura T.

Yakult Central Institute for Microbiological Research, Kunitachi, Tokyo, Japan.
hideyuki-shibata@...

This study attempted to enhance the anti-ulcer activity of fucoidan from
Cladosiphon okamuranus TOKIDA by chemical modification with a hydrophobic group.
The suitable number of fucose residues in the effective compound was also
clarified to obtain a compound of constant quality. Degraded fucoidans were
coupled with several hydrophobic groups via Schiff bases, and their anti-ulcer
activities were determined by acetic acid-induced ulcer models in rats.
Size-fractionated oligofucose was also modified and assayed for anti-ulcer
activity. Among the modified oligofucoses, only the oligofucose-dodecylaniline
combination (OFDA) significantly promoted ulcer healing. The effective dose was
0.2 mg/kg/d. The most suitable number of fucose residues in the compound for the
anti-ulcer activity was determined to be around 12. We succeeded in enhancing
the anti-ulcer activity of Cladosiphon fucoidan by modification with
dodecylaniline. The activity of this compound was comparable or greater than
that of typical anti-ulcer agents. By determination of the optimal OF chain
length for the anti-ulcer activity of OFDA, it became possible to obtain OFDA of
constant quality.

PMID: 11281579 [PubMed - indexed for MEDLINE]

Ann Plast Surg 2001 Nov;47(5):540-6 Related Articles, Books, LinkOut


Protective effect of fucoidin (a neutrophil rolling inhibitor) on ischemia
reperfusion injury: experimental study in rat epigastric island flaps.

Cetin C, Kose AA, Aral E, Colak O, Ercel C, Karabagli Y, Alatas O, Eker A.

Department of Plastic & Reconstructive Surgery, Osmangazi University Medical
Faculty, Eskisehir, Turkey.

The objective of this study was to examine whether a decrease in
neutrophil-mediated tissue injury using Fucoidin, a nontoxic neutrophil rolling
inhibitor, would improve flap survival in an island flap model after
ischemia-reperfusion. Myeloperoxidase activity (an indirect index of tissue
neutrophil count) and malondialdehyde (an indicator of lipid peroxidation), the
degree of neutrophil infiltration by direct counting, and macroscopic flap
survival were assessed in the flap after arterial ischemia-reperfusion.
Epigastric island skin flaps were elevated in 56 rats. The first group of 21
rats was subjected to 6 hours of arterial ischemia. The second group of 21 rats
was subjected to 10 hours of arterial ischemia, and the rest of the rats were
used as nonischemic controls (sham flaps). For inhibiting neutrophil rolling, a
nontoxic polysaccharide agent-Fucoidin-was used. Each ischemic group was divided
further into three subgroups: Subgroup I (control rats) received saline,
subgroup II received 10 mg per kilogram Fucoidin, and subgroup III received 25
mg per kilogram Fucoidin before reperfusion. The results were evaluated as
tissue neutrophil counts, tissue malondialdehyde content, tissue myeloperoxidase
activity, and flap survival. Neutrophil counts and tissue myeloperoxidase
activity were decreased significantly (p <0.001) in subgroup III, but lipid
peroxidation by means of tissue malondialdehyde content was not affected by
Fucoidin administration. The authors conclude that administration of Fucoidin
before reperfusion can limit tissue injury apparently by inhibiting neutrophil
rolling in a dose-dependent manner.

PMID: 11716267 [PubMed - indexed for MEDLINE]

Immunological analysis of inhibition of lung metastases by fucoidan (GIV-A)
prepared from brown seaweed Sargassum thunbergii.

Itoh H, Noda H, Amano H, Ito H.

Laboratory of Marine Biochemistry, Faculty of Bioresources, Mie University, Tsu,
Japan.

The antimetastatic effect of GIV-A (fucoidan) and/or 5-FU was examined in an
experimental model of lung metastases induced by Lewis lung carcinoma in mice.
Injection of GIV-A i.p. after removal of the implanted primary tumor inhibited
the development of lung metastases. Combination treatment with GIV-A and 5-FU
inhibited significantly the lung metastases. The number of peritoneal
macrophages, total cells and macrophages in the lung increased in mice treated
with GIV-A. Binding of the third component of complement (C3) cleavage products
(C3b) to the C3 receptor on peritoneal macrophages after i.v. injection of GIV-A
was enhanced, as shown by the fluorescent antibody technique. Lung metastases
were inhibited by i.v. injection of peritoneal macrophages activated with GIV-A.
GIV-A depressed aniline hydroxylase and aminopyrine demethylase activities of
the hepatic microsomal drug-metabolizing system in tumor-bearing mice. Moreover,
the concentration of 5-FU in the tissues (lung, liver, kidney, spleen and blood)
was increased significantly by coadministration of GIV-A. The picryl
chloride-induced delayed type hypersensitivity (PC-DTH) response in mice was
depressed after the implantation of tumor and treatment with 5-FU. GIV-A
restored the suppression of PC-DTH by 5-FU, but did not increase the PC-DTH of
normal mice. GIV-A not only enhanced the degree of spleen cell-mediated sheep
red blood cell (SRBC) hemolysis (quantitative hemolysis of SRBC), the indexes of
the spleen and thymus and the number of spleen cells, but also restored the
suppressive effect of 5-FU. In the group receiving GIV-A, the percentages of
splenic Thy1.2-, L3T4- and asialo GM1-positive cells were significantly
increased as compared with the tumor-bearing mice treated with saline.
Furthermore, the L3T4+/Lyt2+ ratio showed a tendency to increase, and the
Lyt2+/Thy1.2+ ratio was decreased. These results suggest that the antitumor
effect of GIV-A may be correlated with the changing pattern of the Thy1.2-,
L3T4- and asialo GM1-positive cells, C3 activation, macrophage activation and
depression of the hepatic microsomal drug-metabolizing system. These findings
raise the possibility that GIV-A may have clinical value in the prevention of
cancer metastasis.

PMID: 8572581 [PubMed - indexed for MEDLINE]


  Anticancer Res 1996 May-Jun;16(3A):1213-8 Related Articles, Books, LinkOut


Antitumor and antiproliferative effects of a fucan extracted from ascophyllum
nodosum against a non-small-cell bronchopulmonary carcinoma line.

Riou D, Colliec-Jouault S, Pinczon du Sel D, Bosch S, Siavoshian S, Le Bert V,
Tomasoni C, Sinquin C, Durand P, Roussakis C.

ISOMer (Institut des Substances et Organismes de la Mer), SMAB, Laboratoire de
Pharmacologie Marine, Faculte de Pharmacie, Nantes, France.

Fucans, sulfated polysaccharides extracted from brown seaweeds, have been shown
to be endowed with inhibitory effects cell growth in various experimental
models. We studied both the antiproliferative and antitumor properties of a
fucoidan extract (HF) obtained from the brown seaweed Ascophyllum nodosum on a
cell line derived from a non-small-cell human bronchopulmonary carcinoma
(NSCLC-N6), this type of carcinoma is particularly chemo-resistant. HF exerts in
vitro a reversible antiproliferative activity with a block observed in the G1
phase the cell cycle. Studies performed with the NSCLC-bearing nude mice show
antitumor activity at subtoxic doses. These preliminary results indicate that HF
exhibits inhibitory effect both in vitro and in vivo and is very potent
antitumor agent in cancer therapy.

PMID: 8702239 [PubMed - indexed for MEDLINE]

Sharing What Physicians Are Saying

Dr. Kyosuke Owa on Fucoidan
In research studies, the main health enhancing
ingredient in
  LIMUI, Fucoidan, has been shown to
have many
healthful benefits.

According to prominent Japanese researcher Dr.
Kyosuke Owa,
Fucoidan is said to
"Contain the same healing antibodies as mother's
milk,
providing essential amino acids and a balanced diet
of
minerals necessary to boost the immune system."
"Encourage the regeneration of new cells,
increasing cellular
immunity and giving the body additional 'firepower'
against
diseases."
"Not only aids in the development of new cells, but
it
encourages the regeneration of what are called
Natural Killer
Cells. These cells are found on the front lines
defending our
bodies from disease."

For centuries, the people of Tonga have benefited
from the
amazing health properties of Limu Moui. Now, thanks
to Dr.
Owa's extensive research on Fucoidan, it becomes
clear why it
is our mission to share  LIMUI with the
world.

Dr. Derrick M. DeSilva, Jr., M.D.
Nationally recognized as an expert in the vital
area of
nutrition as it relates to health, Dr. DeSilva
maintains that
disease is caused by nutrient deficiency brought on
by such
factors as poor diets, depleted nutrients in food,
dieting,
medications, oxidation and stress.
Because Limu Moui, the key ingredient in ROYAL
TONGAN LIMUT,
absorbs a rich bounty of 77+ nutrients from
pristine ocean
waters, Dr. DeSilva truly believes that it's
the "PERFECT
FOOD."

Dr. DeSilva believes  LIMUI works
because:
Its main ingredient Limu Moui is the "perfect
food" because
it absorbs a rich bounty of some 77 + nutrients
from
pristine ocean waters.


Limu Moui replaces nutrients lost from all the
different
causes of deficiency.


Oxidation, which is like rusting, is a cause of
disease.
Think about the last time you cut an apple. It
starts to
turn brown from oxidation...but if you pour ROYAL
TONGAN
LIMUT on it, it will NOT turn brown!


INTESTINES: 60% of our immune system resides in
our
intestine and 80% to 90% of those who suffer from
intestinal
problems also have allergies. So, if you "fix"
your
digestive system, you help "fix" your immune
system. Limu
Moui is very beneficial to the digestive system.


CHOLESTEROL: Cholesterol is made in the liver, so
if you can
keep the liver clean it will help with
cholesterol. Limu
Moui helps the liver.


CANCER: Limu Moui may make cancer cells pop (self-
destruct)
and stop cell division. Harvard School of Public
health
says: "Fucoidan in Limu Moui reduces plasmal
cholesterol and
the building of dangerous steroids to breast
tissue." Also,
chlorine in water has been attributed to breast
cancer. Limu
Moui contains substances like Magnesium and
Calcium, which
help dispel effects of chlorine.


BLOOD SUGAR: Fucoidan coats the GI system to
prevent
problems.


ARTHRITIS: Limu Moui lubricates joints to make
them more
flexible and thereby eliminating pain of
arthritis, etc.


MOOD DISORDERS: Mood disorders are affected by
essential
fatty acid deficiency, which is replenished by
Limu Moui.
Dr. DeSilva recommends for ADD/ADHD kids to take
them off
carbohydrates, sugar, processed foods and Ritelin
and put
them on  LIMUI!


BLOOD PRESSURE: Limu Moui addresses all three
areas that
affect blood pressure, for which people normally
have to
take different medications.


HEADACHES: No one should suffer from headaches
and ROYAL
TONGAN LIMUI has the properties to address them,
along with
an increased intake of water.




According to Dr. DeSilva, the people who should
use ROYAL
TONGAN LIMUI include:
Every one of us


Anyone on Medication


Anyone who eats poorly


Anyone under stress


Anyone who wants to feel better


ANYONE WHO IS BREATHING!

For more information call:
Bill Sullivan 501-612-5890
             or visit
http://thelimuman,originallimu.com   TODAY

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MAKE 200 DOLLARS (PLUS) 1ST DAY

I have a better one for you. With my
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How money is made is presented below,
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A. SIGN UP
B. SUPPLY email addresses or phone
numbers. (I'll do the
  selling.)
C. Collect checks of 235 to 260 dollars
  for each five I
sell in a 30 day period. (I sell 20
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to 1040 dollars TODAY)
D.Those I sell provide you with residual
  income build-up.

Some are making 50 thousand plus after
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  you get and extra
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Experientia 1989 Oct 15;45(10):996-8 Related Articles, Books, LinkOut


Further characterization of sulfated homopolysaccharides as anti-HIV agents.

Sugawara I, Itoh W, Kimura S, Mori S, Shimada K.

Department of Pathology, University of Tokyo, Japan.

Fucoidan and dextran sulfate showed anti-HIV activities against mononuclear
cells from AIDS patients, and they abrogated HIV reverse transcriptase (RT)
activity by interacting with the HIV envelope in the membranes of target cells.
Furthermore, they showed a synergistic effect with azidothymidine (AZT).

PMID: 2478388 [PubMed - indexed for MEDLINE




Phytomedicine 1999 Nov;6(5):335-40 Related Articles, Books, LinkOut


Antiviral properties of fucoidan fractions from Leathesia difformis.

Feldman SC, Reynaldi S, Stortz CA, Cerezo AS, Damont EB.

Departamento de Quimica Organica-CIHIDECAR, Facultad de Ciencias Exactas y
Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Argentina.

Three fractions of fucoidans isolated from the brown seaweed Leathesia difformis
(Ee, Ec and Ea) were found to be selective antiviral agents against herpes
simplex virus (HSV) types 1 and 2 and human cytomegalovirus. Fraction Ea was the
most active, with IC50 values in the range 0.5-1.9 microg/ml without affecting
cell viability at concentrations up to 400 microg/ml. The antiherpetic activity
of Ea was assessed by three different methods, plaque reduction, inhibition of
virus yield and prevention of HSV-2 induced shut-off of cell protein synthesis,
demonstrating that the inhibitory effect was independent of the antiviral assay
and the multiplicity of infection. The mode of action of Ea could be ascribed to
an inhibitory action on virus adsorption. The fucoidans did not inhibit the
blood coagulation process even at concentrations exceeding more than 100 times
the IC50 value.

PMID: 11962540 [PubMed - indexed for MEDLINE]




Gen Pharmacol 1997 Oct;29(4):497-511 Related Articles, Books, LinkOut


Sulfated polysaccharides extracted from sea algae as potential antiviral drugs.

Witvrouw M, De Clercq E.

Rega institute for Medical Research, Katholieke Universiteit Leuven, Belgium.

The inhibitory effects of polyanionic substances on the replication of herpes
simplex virus (HSV) and other viruses were reported almost four decades ago.
However, these observations did not generate much interest, because the
antiviral action of the compounds was considered to be largely nonspecific.
Shortly after the identification of human immunodeficiency virus (HIV) as the
causative agent of the acquired immune deficiency syndrome (AIDS) in 1984,
heparin and other sulfated polysaccharides were found to be potent and selective
inhibitors of HIV-1 replication in cell culture. Since 1988, the activity
spectrum of the sulfated polysaccharides has been shown to extend to various
enveloped viruses, including viruses that emerge as opportunistic pathogens
(e.g., herpes simplex virus [HSV] and cytomegalovirus [CMV]) in immunosuppressed
(e.g., AIDS) patients. As potential anti-HIV drug candidates, sulfated
polysaccharides offer a number of promising features. They are able to block HIV
replication in cell culture at concentrations as low as 0.1 to 0.01 microgram
ml-1 without toxicity to the host cells at concentrations up to 2.5 mg ml-1. We
noted that some polysulfates show a differential inhibitory activity against
different HIV strains, suggesting that marked differences exist in the target
molecules with which polysulfates interact. They not only inhibit the cytopathic
effect of HIV, but also prevent HIV-induced syncytium (giant cell) formation.
Furthermore, experiments carried out with dextran sulfate samples of increasing
molecular weight and with sulfated cyclodextrins of different degrees of
sulfation have shown that antiviral activity increases with increasing molecular
weight and degree of sulfation. A sugar backbone is not strictly needed for the
anti-HIV activity of polysulfates because sulfated polymers composed of a
carbon-carbon backbone have also proved to be highly efficient anti-HIV agents
in vitro. Other, yet to be defined, structural features may also play an
important role. Sulfated polysaccharides may act synergistically with other
anti-HIV drugs (e.g., azidothymidine [AZT]). They are known to lead very slowly
to virus-drug resistance development and they show activity against HIV mutants
that have become resistant to reverse transcriptase inhibitors, such as AZT,
tetrahydro-imidazo [4,5,l-jk] [1,4]-benzodiazepin-2(1H)-thione (TIBO) and
others. From studies on their mechanism of action we concluded that polysulfates
exert their anti-HIV activity by shielding off the positively charged sites in
the V3 loop of the viral envelope glycoprotein (gp120). The V3 loop is necessary
for virus attachment to cell surface heparan sulfate, a primary binding site,
before more specific binding occurs to the CD4 receptor of CD4+ cells. This
general mechanism also explains the broad antiviral activity of polysulfates
against enveloped viruses. Variations in the viral envelope glycoprotein region
may result in differences in the susceptibility of different enveloped viruses
to compounds that interact with their envelope glycoproteins. The efficacy of
polysulfates in the therapy and/or prophylaxis of retroviral infections and
opportunistic infections remains to be demonstrated both in animal models and
humans. It is important to consider not only treatment of patients who are
already infected with HIV, but also prophylaxis and protection from HIV and/or
other virus infections. Because (i) sexual transmission is responsible for the
large majority of HIV infections worldwide; (ii) this transmission is mostly
mediated via mononuclear cells that infect epithelial cells of the genital
tract; and because (iii) polysulfates effectively inhibit cell-cell adhesion,
polysulfates may be considered as potentially effective in a vaginal formulation
to protect against HIV infection.

Publication Types:
Review
Review, Tutorial

PMID: 9352294 [PubMed - indexed for MEDLINE]




Biomed Pharmacother 1996;50(5):207-15 Related Articles, Books, LinkOut


Chemotherapy of human immunodeficiency virus (HIV) infection: anti-HIV agents
targeted at early stages in the virus replicative cycle.

De Clercq E.

Rega Institute for Medical Research, Katholieke Universiteit Leuven, Belgium.

Several compounds have been identified that inhibit an early stage in the
replicative cycle of the human immunodeficiency virus (HIV): i) virus
adsorption: polysulfates, polysulfonates, polycarboxylates, polyphosphates, and
polyoxometalates; or ii) virus-cell fusion: plant lectins, negatively charged
albumins and betulinic acid derivatives; iii) virus fusion/uncoating: bicyclam
derivatives; iv) reverse transcription: dideoxynucleoside analogues, acyclic
nucleoside phosphonates and non-nucleoside reverse transcriptase inhibitors. In
principle, HIV may develop resistance to any of these specific anti-HIV agents.
However, virus breakthrough can be completely prevented if these agents, alone
or in combination, are added to the HIV-infected cells from the beginning at
sufficiently high ('knock-out') concentrations.

Publication Types:
Review
Review, Tutorial

PMID: 8949401 [PubMed - indexed for MEDLINE

Hear Powerful Testimonies
Like These Every Monday Evening 8:30PM CST TOLL FREE 212-990-8000   6688#


Since my pregnancy, 2 years ago, I suffered from daily migraines. My doctors
thought these were due to hormonal changes and could only recommend pain
medication. Of course, I could not risk harm to my unborn baby by taking it. But
16 months after my son, Zachary's birth, the headaches were no better. It was
hard for Zachary to understand why mommy didn't want to do anything but lay on
the couch some days. After taking Limu Moui for 1 day, my headache was gone!
Zachary and I have so much more fun now. I will even take it during my next
pregnancy. I want to tell everyone I come into contact with about Limu Moui
because it has changed my life!
Chastity T., Cordova, TN

I am 42 years old and was diagnosed with Multiple Sclerosis in 1998. I
experienced episodes of weakness and progression of the disease. I went through
physical therapy and medications, feeling better at times and then another
episode would leave me feeling weak and numb. The last episode was so fast and
progressive that I became wheelchair bound, weak and with no feeling from the
waist down. I could not even hold my grandbaby. I was never this debilitated
before and was convinced I would die. On May 8th, I started taking about 2
tablespoons of Limu Moui, twice a day, and within one month, I was out of the
wheelchair and walking without a brace or cane. I even resumed my housework and
cooking supper. Next week, I intend to start driving again. I feel generally
good and have an increase in energy. My physical therapist commented that he'd
never seen anyone progress so quickly from how debilitated I was. I will never
be without Limu Moui!
Theresa C., Dequincy, LA

My husband, who is in construction, is exposed to the elements 8 to 10 hours a
day and suffered from constant sinus headaches. After taking Limu Moui, he
rarely suffers at all now! In addition, my pain from carpal tunnel syndrome in
my right arm and a bulging disc in my back are gone. I no longer need the brace
for my arm and I can sleep so much better at night. Limu Moui is a blessing to
the entire world!
LeJoyce A., Arcadia, LA

I have had severe fever blisters, caused by Herpes virus, on my lower lip for as
long as I can remember. These typically begin with a tingling sensation in a
small area and progress until 1/4 to 1/2 of my lower lip is swollen, red, and
bleeding. Ultimately, the lesion becomes painful throughout the typical 3 to
5-week duration and is quite unsightly and embarrassing. Upon feeling the
familiar sensation begin, I immediately applied Limu Moui directly onto the
emerging blister to see what would happen. After 4 days of applying it twice a
day, the blister was going away and never surfaced! I was amazed, as I have
never experienced this quick of a recovery from this repulsive ailment.
Mark K. Springfield, MO

I am 39 and have had asthma most of my life, starting as a small child and
becoming worse in my early 20's. Though detrimental to my internal organs, I've
used 3 different steroid based medications twice a day to keep this disease
under control and have visited the emergency room 3 times over the last 15
years. Since the day I started taking Limu Moui, I have not used any
prescription medication and I can breathe! I can now have a normal life. This is
a gift from above and it is now my duty to share my blessing!
Gary R., Sedro Woolley, WA

I have had ulcers since I was 15 years old and inflammation of the stomach
lining most of my adult life. Because of extreme heartburn, I had to take Zantac
with every meal and sometimes even between meals. Since I started taking Limu
Moui, I have not had to take Zantac. In additional, my energy level and general
well being have dramatically improved.
Nileen B., Sedro Wooley, WA

I have been on Avapro and Toprol, blood pressure medication since my open heart
surgery a year ago. My blood pressure still remained at around 179/100 or
179/120. The lowest it had ever reached was 158/90. With my doctor's approval, I
started taking 2 tablespoons per day of Limu Moui. After the second day on the
product, my blood pressure dropped to 116/66 and my doctor cut my medication
dosage in half. Three days later, he took me off Avapro completely and reduced
my dosage of Toprol even more and will take me off it completely in 2 more days.
My blood pressure has stayed consistently between 116/66 and 118/66. I am no
longer sleepy, have more energy, feel calmer, my head is clearer and my heart no
longer pounds. I will never stop taking Limu Moui and it's just a matter of time
before my doctor is in the business!
Phil R., Minden, LA

I've had rheumatoid arthritis since 1980 and in spite of having tried every kind
of medication imaginable--from Gold injections and steroids, to Methotrexate and
Remicade -- I still had to live with many physical limitations. These included
being unable to turn the car keys, raise my arms over my head, get up and down
from a sitting position, morning stiffness, low energy and little to no strength
in my hands and wrists. I began to see results after 1 week on Limu Moui and it
has continued ever since. Recently I spent 3 days, rolling paint up to the
ceiling and wallpapering. I also mowed an acre of land for 2-1/2 hours with a
tractor that has no power steering. Not only was I not sore the next day, I
drove into the city and took a CPR and First Aid Class. I'm doing things I have
not done in 15 years.
Nancy O'C., Pleasant Hill, MO

Our 6-year old daughter, Christina, has had breathing problems since the day she
was born. Ever since a near death experience when she was 6 weeks old, she has
had to use a Breathalyzer on many occasions. Recently, we had to cut a weekend
trip short and return home due to the breathing problems Christina was having
from the high spring time pollen content. We decided to try Limu Moui because
the traditional medications she was taking were not clearing her up completely.
After 4 days, all signs of Christina's pneumonia were gone and all her other
symptoms cleared up, as well. Our whole family is now on the product and we have
noticed many other benefits, after approximately 4 days of use.
David L., Shreveport, LA

I suffered from fibromyalgia and chronic fatigue syndrome, both causing constant
pain, especially after any kind of strenuous exertion, or when the weather
changed. I was taking at least 6 Ibuprofen a day and 2 or 3 Tylenol PM for pain
and to sleep at night. After 2 weeks on Limu Moui, I am not taking either one of
those medications, and my pain during the day has all but disappeared, my energy
level is "out the roof" and I am sleeping very well at night.
Rebecca S., Oak Ridge, LA

My father-in-law has diabetes, which was out of control. He had been taking oral
medication, but when his blood sugar level reached between 200 and 350, the
doctor had put him on insulin shots. His first week on Limu Moui, he took 2
tablespoons, 2 times a day. The second week, he increased it to 2 tablespoons, 3
times a day. After checking his blood sugar level, he found it had dropped to
140 and remains between 150 and 160.
Jeff B., Liberty, TX

I have had chronic sleep problems for the past 20 years and have spent many
hours tossing and turning and staring at the ceiling till daybreak. I chose to
get off the prescription medication my doctor prescribed years ago and no over
the counter aids helped. After hearing friends and family say they were sleeping
better at night because of Limu Moui I began taking it. After 3 nights, I
noticed a total change in my sleeping. What a joy it is to wake up and find it's
morning! I feel rested during the day and feel a sense of well being and
happiness from the product. Limu Moui is a real blessing!
Sally H., Heflin, LA

My health issues included allergy and sinus problems for which I had to take
medication, including a 12-hour nasal spray, every 3 to 4 hours. In addition, I
was taking Prilosec for a severe problem with indigestion and heartburn, which I
experienced with even one bit of any kind of food. After just 3 days on Limu
Moui, my allergies and sinus problems were gone and I was able to get a good
night's sleep, without any medication. I am also completely off the Prilosec and
have no more indigestion symptoms. I have not felt better in a long time!
Alton W., Oake Grove, LA

For 13 years, my daughter has been suffering from asthma and a chronic cough
every night. After 5 days on Limu Moui, I noticed she was not coughing at night.
For the last 46 days, she has not coughed, wheezed, or had to use the inhaler!
The product has been a blessing to her and she will take it for the rest of her
life!
Bonita W., Sugarland, TX

I am legally blind due to diabetes and I suffer from congestive heart failure. I
have had several heart attacks and 4 angioplasty surgeries. I also have
shortness of breath, poor circulation, bad lungs, poor kidney control and sleep
apnea, to name a few of my ailments. My blood sugar ranged from 200-450,
sometimes even higher. I was about to start kidney dialysis because of the
kidney failure. After taking Limu Moui for 3 days, I felt noticeably improved.
My blood sugar has dropped to between 130 and 170, I am able to get up without
aid, and am much more active. Before, I could barely walk 50 feet, from the
house to the mailbox, and now, I have been walking 7 blocks at a time. In
addition, I have more energy, less shortness of breath and control of my
kidneys. I have done nothing different from before, except take Limu Moui.
Edward W., Cullman, AL

I was in extreme pain following knee replacement surgery in January and physical
therapy was an excruciating experience. Twice a day, I had to take 200-500 mg of
Extra Strength Tylenol, 250 mg of Ultram and 50 mg of Percoset, totaling 2300 mg
of pain medication, daily. I began taking Limu Moui on March 31, 2001 and 4
weeks later, the last week in April, I began to notice that my pain was almost
gone. Consequently, I stopped taking all pain medication, except one 50 mg
tablet of Ultram at bedtime. Even though physical therapy is still painful, I
find that my pain subsides about 30 minutes after taking Limu Moui.
Robert W., Springfield, MO

I was plagued with year round sinus related problems, including infection,
bronchitis and laryngitis, especially in the spring and fall. This would deplete
my energy and wellness and cause me to miss work as a sign language interpreter,
causing hardship on my colleagues and deaf students, who depended on me. For
years, I tried medications, nasal sprays and herbal remedies. Within 3 days of
using Limu Moui, I was able to breathe freely and now take no medication.
Vicki W., Springfield, MO

J Cosmet Sci 2002 Jan-Feb;53(1):1-9 Related Articles, Books, LinkOut


Treatment of human skin with an extract of Fucus vesiculosus changes its
thickness and mechanical properties.

Fujimura T, Tsukahara K, Moriwaki S, Kitahara T, Sano T, Takema Y.

Biological Science Laboratories, Kao Corporation, 2606 Akabane, Ichikai-machi,
Haga-gun, Tochigi 321-3497, Japan.

Recently the researchers found that an extract of Fucus vesiculosus, which is a
type of seaweed, promotes the contraction of fibroblast-populated collagen gels
through increased expression of integrin molecules. In this study, they
investigated the effects of topical application of an aqueous extract of this
alga on the thickness and the mechanical properties of human skin. A gel
formulation that included 1% of the extract was applied topically to human cheek
skin twice daily for five weeks. A significant decrease in skin thickness
measured by B-mode ultrasound was elicited, as was a significant improvement in
elasticity measured with a Cutometer as compared with controls. In cheek skin,
the thickness normally increases and the elasticity usually decreases with age.
These results suggest that the Fucus vesiculosus extract possesses anti-aging
activities and should be useful for a variety of cosmetics.

Publication Types:
Clinical Trial
Controlled Clinical Trial

PMID: 11917251 [PubMed - indexed for MEDLINE]



1: Biol Pharm Bull 2000 Oct;23(10):1180-4 Related Articles, Books, LinkOut


Fucoidan is the active component of fucus vesiculosus that promotes contraction
of fibroblast-populated collagen gels.

Fujimura T, Shibuya Y, Moriwaki S, Tsukahara K, Kitahara T, Sano T, Nishizawa Y,
Takema Y.

Biological Science Laboratories, Kao Corporation, Haga, Tochigi, Japan.
301620@...

The fibroblast-populated collagen gel culture method has been evaluated as a
dermal model of wound contraction and granulation in tissues during the wound
healing process and as an in vitro model of dermal tissue. We previously
reported that an extract of Fucus vesiculosus promoted fibroblast-populated
collagen gel contraction and that the promotion of the gel contraction was due
to the increased expression of integrin alpha2beta1 on the surface of the
fibroblasts. In this study, we investigated the active component of the extract
of this alga using extraction and fractionation techniques. Water extraction of
the alga was followed by precipitation with excess ethanol and then gel
filtration with the boundary molecular weight of 30,000. The high molecular
weight fraction obtained from gel filtration was fractionated by ion exchange
chromatography on diethylaminoethyl cellulose column to give active fractions
that have more polar properties. These polar, high molecular weight fractions
which contained molecules with fucose and sulfate groups showed significant gel
contraction-promoting activity and integrin expression-enhancing activity, and
were estimated to be the sulfated-polysaccharide fucoidan. Commercially
available fucoidan showed similar activities to the above-described fraction of
this alga. Although it remains necessary to precisely identify the specific
active component, the above results indicate that fucoidan is the active
component which promotes collagen gel contraction, and also indicate the
possibility that it dose so by enhancing the integrin alpha2beta1 expression.

PMID: 11041247 [PubMed - indexed for MEDLINE]

J Nutr Sci Vitaminol (Tokyo) 1999 Jun;45(3):325-36 Related Articles, Books,
LinkOut


Inhibitory effect of Cladosiphon fucoidan on the adhesion of Helicobacter pylori
to human gastric cells.

Shibata H, KimuraTakagi I, Nagaoka M, Hashimoto S, Sawada H, Ueyama S, Yokokura
T.

Yakult Central Institute for Microbiological Research, Tokyo, Japan.

We studied the inhibitory effect of Cladosiphon fucoidan on the attachment of
Helicobacter pylori (H. pylori), a gastroduodenal pathogen, to human gastric
cell lines. The bacterial binding in these cell lines was inhibited more by
Cladosiphon fucoidan (IC50 = 16-30 mg/mL), than by the fucoidan from Fucus (IC50
> 30 mg/mL). Dextran sulfate, another sulfated polysaccharide, did not inhibit
the binding at all. Pre-incubating the bacterial suspension with fucoidans
reinforced the inhibitory ability of these components, and reduced the IC50
value of Cladosiphon fucoidan to approximately 1 mg/mL. However, the binding was
not inhibited by pre-treatment of gastric cells with these components. It was
also shown that this fucoidan blocks both Leb- and sulfatide-mediated attachment
of H. pylori to gastric cells. Furthermore, fucoidan-binding proteins were found
on the H. pylori cell surface by Western blot analysis. Thus, the inhibitory
effect exerted by Cladosiphon fucoidan on binding between H. pylori and gastric
cells might result from the coating with this component of the bacterial
surface.

PMID: 10524351 [PubMed - indexed for MEDLINE]



Biomed Mater Eng 2001;11(1):55-61 Related Articles, Books, LinkOut


Effect of oligofucose derivatives on acetic acid-induced gastric ulcer in rats.

Shibata H, Nagaoka M, Takagi IK, Hashimoto S, Aiyama R, Yokokura T.

Yakult Central Institute for Microbiological Research, Kunitachi, Tokyo, Japan.
hideyuki-shibata@...

This study attempted to enhance the anti-ulcer activity of fucoidan from
Cladosiphon okamuranus TOKIDA by chemical modification with a hydrophobic group.
The suitable number of fucose residues in the effective compound was also
clarified to obtain a compound of constant quality. Degraded fucoidans were
coupled with several hydrophobic groups via Schiff bases, and their anti-ulcer
activities were determined by acetic acid-induced ulcer models in rats.
Size-fractionated oligofucose was also modified and assayed for anti-ulcer
activity. Among the modified oligofucoses, only the oligofucose-dodecylaniline
combination (OFDA) significantly promoted ulcer healing. The effective dose was
0.2 mg/kg/d. The most suitable number of fucose residues in the compound for the
anti-ulcer activity was determined to be around 12. We succeeded in enhancing
the anti-ulcer activity of Cladosiphon fucoidan by modification with
dodecylaniline. The activity of this compound was comparable or greater than
that of typical anti-ulcer agents. By determination of the optimal OF chain
length for the anti-ulcer activity of OFDA, it became possible to obtain OFDA of
constant quality.

PMID: 11281579 [PubMed - indexed for MEDLINE]

Immunological analysis of inhibition of lung metastases by fucoidan (GIV-A)
prepared from brown seaweed Sargassum thunbergii.

Itoh H, Noda H, Amano H, Ito H.

Laboratory of Marine Biochemistry, Faculty of Bioresources, Mie University, Tsu,
Japan.

The antimetastatic effect of GIV-A (fucoidan) and/or 5-FU was examined in an
experimental model of lung metastases induced by Lewis lung carcinoma in mice.
Injection of GIV-A i.p. after removal of the implanted primary tumor inhibited
the development of lung metastases. Combination treatment with GIV-A and 5-FU
inhibited significantly the lung metastases. The number of peritoneal
macrophages, total cells and macrophages in the lung increased in mice treated
with GIV-A. Binding of the third component of complement (C3) cleavage products
(C3b) to the C3 receptor on peritoneal macrophages after i.v. injection of GIV-A
was enhanced, as shown by the fluorescent antibody technique. Lung metastases
were inhibited by i.v. injection of peritoneal macrophages activated with GIV-A.
GIV-A depressed aniline hydroxylase and aminopyrine demethylase activities of
the hepatic microsomal drug-metabolizing system in tumor-bearing mice. Moreover,
the concentration of 5-FU in the tissues (lung, liver, kidney, spleen and blood)
was increased significantly by coadministration of GIV-A. The picryl
chloride-induced delayed type hypersensitivity (PC-DTH) response in mice was
depressed after the implantation of tumor and treatment with 5-FU. GIV-A
restored the suppression of PC-DTH by 5-FU, but did not increase the PC-DTH of
normal mice. GIV-A not only enhanced the degree of spleen cell-mediated sheep
red blood cell (SRBC) hemolysis (quantitative hemolysis of SRBC), the indexes of
the spleen and thymus and the number of spleen cells, but also restored the
suppressive effect of 5-FU. In the group receiving GIV-A, the percentages of
splenic Thy1.2-, L3T4- and asialo GM1-positive cells were significantly
increased as compared with the tumor-bearing mice treated with saline.
Furthermore, the L3T4+/Lyt2+ ratio showed a tendency to increase, and the
Lyt2+/Thy1.2+ ratio was decreased. These results suggest that the antitumor
effect of GIV-A may be correlated with the changing pattern of the Thy1.2-,
L3T4- and asialo GM1-positive cells, C3 activation, macrophage activation and
depression of the hepatic microsomal drug-metabolizing system. These findings
raise the possibility that GIV-A may have clinical value in the prevention of
cancer metastasis.

PMID: 8572581 [PubMed - indexed for MEDLINE]


  Anticancer Res 1996 May-Jun;16(3A):1213-8 Related Articles, Books, LinkOut


Antitumor and antiproliferative effects of a fucan extracted from ascophyllum
nodosum against a non-small-cell bronchopulmonary carcinoma line.

Riou D, Colliec-Jouault S, Pinczon du Sel D, Bosch S, Siavoshian S, Le Bert V,
Tomasoni C, Sinquin C, Durand P, Roussakis C.

ISOMer (Institut des Substances et Organismes de la Mer), SMAB, Laboratoire de
Pharmacologie Marine, Faculte de Pharmacie, Nantes, France.

Fucans, sulfated polysaccharides extracted from brown seaweeds, have been shown
to be endowed with inhibitory effects cell growth in various experimental
models. We studied both the antiproliferative and antitumor properties of a
fucoidan extract (HF) obtained from the brown seaweed Ascophyllum nodosum on a
cell line derived from a non-small-cell human bronchopulmonary carcinoma
(NSCLC-N6), this type of carcinoma is particularly chemo-resistant. HF exerts in
vitro a reversible antiproliferative activity with a block observed in the G1
phase the cell cycle. Studies performed with the NSCLC-bearing nude mice show
antitumor activity at subtoxic doses. These preliminary results indicate that HF
exhibits inhibitory effect both in vitro and in vivo and is very potent
antitumor agent in cancer therapy.

PMID: 8702239 [PubMed - indexed for MEDLINE]

Ann Plast Surg 2001 Nov;47(5):540-6 Related Articles, Books, LinkOut


Protective effect of fucoidin (a neutrophil rolling inhibitor) on ischemia
reperfusion injury: experimental study in rat epigastric island flaps.

Cetin C, Kose AA, Aral E, Colak O, Ercel C, Karabagli Y, Alatas O, Eker A.

Department of Plastic & Reconstructive Surgery, Osmangazi University Medical
Faculty, Eskisehir, Turkey.

The objective of this study was to examine whether a decrease in
neutrophil-mediated tissue injury using Fucoidin, a nontoxic neutrophil rolling
inhibitor, would improve flap survival in an island flap model after
ischemia-reperfusion. Myeloperoxidase activity (an indirect index of tissue
neutrophil count) and malondialdehyde (an indicator of lipid peroxidation), the
degree of neutrophil infiltration by direct counting, and macroscopic flap
survival were assessed in the flap after arterial ischemia-reperfusion.
Epigastric island skin flaps were elevated in 56 rats. The first group of 21
rats was subjected to 6 hours of arterial ischemia. The second group of 21 rats
was subjected to 10 hours of arterial ischemia, and the rest of the rats were
used as nonischemic controls (sham flaps). For inhibiting neutrophil rolling, a
nontoxic polysaccharide agent-Fucoidin-was used. Each ischemic group was divided
further into three subgroups: Subgroup I (control rats) received saline,
subgroup II received 10 mg per kilogram Fucoidin, and subgroup III received 25
mg per kilogram Fucoidin before reperfusion. The results were evaluated as
tissue neutrophil counts, tissue malondialdehyde content, tissue myeloperoxidase
activity, and flap survival. Neutrophil counts and tissue myeloperoxidase
activity were decreased significantly (p <0.001) in subgroup III, but lipid
peroxidation by means of tissue malondialdehyde content was not affected by
Fucoidin administration. The authors conclude that administration of Fucoidin
before reperfusion can limit tissue injury apparently by inhibiting neutrophil
rolling in a dose-dependent manner.

PMID: 11716267 [PubMed - indexed for MEDLINE]

Experientia 1989 Oct 15;45(10):996-8 Related Articles, Books, LinkOut


Further characterization of sulfated homopolysaccharides as anti-HIV agents.

Sugawara I, Itoh W, Kimura S, Mori S, Shimada K.

Department of Pathology, University of Tokyo, Japan.

Fucoidan and dextran sulfate showed anti-HIV activities against mononuclear
cells from AIDS patients, and they abrogated HIV reverse transcriptase (RT)
activity by interacting with the HIV envelope in the membranes of target cells.
Furthermore, they showed a synergistic effect with azidothymidine (AZT).

PMID: 2478388 [PubMed - indexed for MEDLINE




Phytomedicine 1999 Nov;6(5):335-40 Related Articles, Books, LinkOut


Antiviral properties of fucoidan fractions from Leathesia difformis.

Feldman SC, Reynaldi S, Stortz CA, Cerezo AS, Damont EB.

Departamento de Quimica Organica-CIHIDECAR, Facultad de Ciencias Exactas y
Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Argentina.

Three fractions of fucoidans isolated from the brown seaweed Leathesia difformis
(Ee, Ec and Ea) were found to be selective antiviral agents against herpes
simplex virus (HSV) types 1 and 2 and human cytomegalovirus. Fraction Ea was the
most active, with IC50 values in the range 0.5-1.9 microg/ml without affecting
cell viability at concentrations up to 400 microg/ml. The antiherpetic activity
of Ea was assessed by three different methods, plaque reduction, inhibition of
virus yield and prevention of HSV-2 induced shut-off of cell protein synthesis,
demonstrating that the inhibitory effect was independent of the antiviral assay
and the multiplicity of infection. The mode of action of Ea could be ascribed to
an inhibitory action on virus adsorption. The fucoidans did not inhibit the
blood coagulation process even at concentrations exceeding more than 100 times
the IC50 value.

PMID: 11962540 [PubMed - indexed for MEDLINE]




Gen Pharmacol 1997 Oct;29(4):497-511 Related Articles, Books, LinkOut


Sulfated polysaccharides extracted from sea algae as potential antiviral drugs.

Witvrouw M, De Clercq E.

Rega institute for Medical Research, Katholieke Universiteit Leuven, Belgium.

The inhibitory effects of polyanionic substances on the replication of herpes
simplex virus (HSV) and other viruses were reported almost four decades ago.
However, these observations did not generate much interest, because the
antiviral action of the compounds was considered to be largely nonspecific.
Shortly after the identification of human immunodeficiency virus (HIV) as the
causative agent of the acquired immune deficiency syndrome (AIDS) in 1984,
heparin and other sulfated polysaccharides were found to be potent and selective
inhibitors of HIV-1 replication in cell culture. Since 1988, the activity
spectrum of the sulfated polysaccharides has been shown to extend to various
enveloped viruses, including viruses that emerge as opportunistic pathogens
(e.g., herpes simplex virus [HSV] and cytomegalovirus [CMV]) in immunosuppressed
(e.g., AIDS) patients. As potential anti-HIV drug candidates, sulfated
polysaccharides offer a number of promising features. They are able to block HIV
replication in cell culture at concentrations as low as 0.1 to 0.01 microgram
ml-1 without toxicity to the host cells at concentrations up to 2.5 mg ml-1. We
noted that some polysulfates show a differential inhibitory activity against
different HIV strains, suggesting that marked differences exist in the target
molecules with which polysulfates interact. They not only inhibit the cytopathic
effect of HIV, but also prevent HIV-induced syncytium (giant cell) formation.
Furthermore, experiments carried out with dextran sulfate samples of increasing
molecular weight and with sulfated cyclodextrins of different degrees of
sulfation have shown that antiviral activity increases with increasing molecular
weight and degree of sulfation. A sugar backbone is not strictly needed for the
anti-HIV activity of polysulfates because sulfated polymers composed of a
carbon-carbon backbone have also proved to be highly efficient anti-HIV agents
in vitro. Other, yet to be defined, structural features may also play an
important role. Sulfated polysaccharides may act synergistically with other
anti-HIV drugs (e.g., azidothymidine [AZT]). They are known to lead very slowly
to virus-drug resistance development and they show activity against HIV mutants
that have become resistant to reverse transcriptase inhibitors, such as AZT,
tetrahydro-imidazo [4,5,l-jk] [1,4]-benzodiazepin-2(1H)-thione (TIBO) and
others. From studies on their mechanism of action we concluded that polysulfates
exert their anti-HIV activity by shielding off the positively charged sites in
the V3 loop of the viral envelope glycoprotein (gp120). The V3 loop is necessary
for virus attachment to cell surface heparan sulfate, a primary binding site,
before more specific binding occurs to the CD4 receptor of CD4+ cells. This
general mechanism also explains the broad antiviral activity of polysulfates
against enveloped viruses. Variations in the viral envelope glycoprotein region
may result in differences in the susceptibility of different enveloped viruses
to compounds that interact with their envelope glycoproteins. The efficacy of
polysulfates in the therapy and/or prophylaxis of retroviral infections and
opportunistic infections remains to be demonstrated both in animal models and
humans. It is important to consider not only treatment of patients who are
already infected with HIV, but also prophylaxis and protection from HIV and/or
other virus infections. Because (i) sexual transmission is responsible for the
large majority of HIV infections worldwide; (ii) this transmission is mostly
mediated via mononuclear cells that infect epithelial cells of the genital
tract; and because (iii) polysulfates effectively inhibit cell-cell adhesion,
polysulfates may be considered as potentially effective in a vaginal formulation
to protect against HIV infection.

Publication Types:
Review
Review, Tutorial

PMID: 9352294 [PubMed - indexed for MEDLINE]




Biomed Pharmacother 1996;50(5):207-15 Related Articles, Books, LinkOut


Chemotherapy of human immunodeficiency virus (HIV) infection: anti-HIV agents
targeted at early stages in the virus replicative cycle.

De Clercq E.

Rega Institute for Medical Research, Katholieke Universiteit Leuven, Belgium.

Several compounds have been identified that inhibit an early stage in the
replicative cycle of the human immunodeficiency virus (HIV): i) virus
adsorption: polysulfates, polysulfonates, polycarboxylates, polyphosphates, and
polyoxometalates; or ii) virus-cell fusion: plant lectins, negatively charged
albumins and betulinic acid derivatives; iii) virus fusion/uncoating: bicyclam
derivatives; iv) reverse transcription: dideoxynucleoside analogues, acyclic
nucleoside phosphonates and non-nucleoside reverse transcriptase inhibitors. In
principle, HIV may develop resistance to any of these specific anti-HIV agents.
However, virus breakthrough can be completely prevented if these agents, alone
or in combination, are added to the HIV-infected cells from the beginning at
sufficiently high ('knock-out') concentrations.

Publication Types:
Review
Review, Tutorial

PMID: 8949401 [PubMed - indexed for MEDLINE

Sharing What Physicians Are Saying

Dr. Kyosuke Owa on Fucoidan
In research studies, the main health enhancing
ingredient in
  LIMUI, Fucoidan, has been shown to
have many
healthful benefits.

According to prominent Japanese researcher Dr.
Kyosuke Owa,
Fucoidan is said to
"Contain the same healing antibodies as mother's
milk,
providing essential amino acids and a balanced diet
of
minerals necessary to boost the immune system."
"Encourage the regeneration of new cells,
increasing cellular
immunity and giving the body additional 'firepower'
against
diseases."
"Not only aids in the development of new cells, but
it
encourages the regeneration of what are called
Natural Killer
Cells. These cells are found on the front lines
defending our
bodies from disease."

For centuries, the people of Tonga have benefited
from the
amazing health properties of Limu Moui. Now, thanks
to Dr.
Owa's extensive research on Fucoidan, it becomes
clear why it
is our mission to share  LIMUI with the
world.

Dr. Derrick M. DeSilva, Jr., M.D.
Nationally recognized as an expert in the vital
area of
nutrition as it relates to health, Dr. DeSilva
maintains that
disease is caused by nutrient deficiency brought on
by such
factors as poor diets, depleted nutrients in food,
dieting,
medications, oxidation and stress.
Because Limu Moui, the key ingredient in ROYAL
TONGAN LIMUT,
absorbs a rich bounty of 77+ nutrients from
pristine ocean
waters, Dr. DeSilva truly believes that it's
the "PERFECT
FOOD."

Dr. DeSilva believes  LIMUI works
because:
Its main ingredient Limu Moui is the "perfect
food" because
it absorbs a rich bounty of some 77 + nutrients
from
pristine ocean waters.


Limu Moui replaces nutrients lost from all the
different
causes of deficiency.


Oxidation, which is like rusting, is a cause of
disease.
Think about the last time you cut an apple. It
starts to
turn brown from oxidation...but if you pour ROYAL
TONGAN
LIMUT on it, it will NOT turn brown!


INTESTINES: 60% of our immune system resides in
our
intestine and 80% to 90% of those who suffer from
intestinal
problems also have allergies. So, if you "fix"
your
digestive system, you help "fix" your immune
system. Limu
Moui is very beneficial to the digestive system.


CHOLESTEROL: Cholesterol is made in the liver, so
if you can
keep the liver clean it will help with
cholesterol. Limu
Moui helps the liver.


CANCER: Limu Moui may make cancer cells pop (self-
destruct)
and stop cell division. Harvard School of Public
health
says: "Fucoidan in Limu Moui reduces plasmal
cholesterol and
the building of dangerous steroids to breast
tissue." Also,
chlorine in water has been attributed to breast
cancer. Limu
Moui contains substances like Magnesium and
Calcium, which
help dispel effects of chlorine.


BLOOD SUGAR: Fucoidan coats the GI system to
prevent
problems.


ARTHRITIS: Limu Moui lubricates joints to make
them more
flexible and thereby eliminating pain of
arthritis, etc.


MOOD DISORDERS: Mood disorders are affected by
essential
fatty acid deficiency, which is replenished by
Limu Moui.
Dr. DeSilva recommends for ADD/ADHD kids to take
them off
carbohydrates, sugar, processed foods and Ritelin
and put
them on  LIMUI!


BLOOD PRESSURE: Limu Moui addresses all three
areas that
affect blood pressure, for which people normally
have to
take different medications.


HEADACHES: No one should suffer from headaches
and ROYAL
TONGAN LIMUI has the properties to address them,
along with
an increased intake of water.




According to Dr. DeSilva, the people who should
use ROYAL
TONGAN LIMUI include:
Every one of us


Anyone on Medication


Anyone who eats poorly


Anyone under stress


Anyone who wants to feel better


ANYONE WHO IS BREATHING!

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J Ethnopharmacol 1989 Nov;27(1-2):35-43
Hypoglycemic activity of several seaweed extracts.
Lamela M, Anca J, Villar R, Otero J, Calleja JM
Departamento de Farmacologia, Farmacia y Tecnologia Farmaceutica, Facultad de
Farmacia, Universidad de Santiago de Compostela, Spain.

The hypoglycemic activity of several seaweed extracts on rabbits was studied.
Ethanol extracts of Laminaria ochroleuca, Saccorhiza polyschides and Fucus
vesiculosus were administered orally to normal animals and their effects on
glycemia and triglyceridemia evaluated. Crude polysaccharides and protein
solutions from Himanthalia elongata and Codium tomentosum were also assayed.
Polysaccharides and proteins from H. elongata caused a significant reduction in
blood glucose 8 h after intravenous administration. A case of 5 mg/kg of crude
polysaccharide lowered glycemia about 18% in normal rabbits and by about 50% in
alloxan-diabetic animals, while the protein solution lowered glycemia in
diabetic rabbits by about 30%.

PMID: 2615424, UI: 90135222

Hello, Denton and Katheryn. Here is some really good information On the Brain
and Nutrition. I have the areas that mention Alzheimers  the word Lit-up in Las
vagas Blinking lights.



Bill





Basic Neurochemistry  Part Five. Metabolism  33. Nutrition and Brain Function

Nutrition and Functional Neurochemistry


The availability of some nutrients can have immediate effects on behavior,
especially on the ability to respond to stimulation. Several studies suggest
that brain function, including cognitive processing, responds to changes in
nutrients.

Nutrition can influence neurotransmitter concentrations and associated behaviors


Important neurotransmitters are synthesized from compounds which are essential
dietary constituents. For instance, norepinephrine (NE) and serotonin are formed
from the essential amino acids tyrosine and tryptophan, respectively. However,
elevation of a precursor in the blood does not necessarily elevate its
concentration in the brain. For example, increasing the blood concentration of
large neutral amino acids such as phenylalanine, as occurs in phenylketonuria
(see Chap. 44), reduces tryptophan uptake into the brain because these two
compounds share a common carrier across the bloodbrain barrier (see Chap. 32).
Furthermore, the response to an increased concentration of precursor often
depends on the demand, such as firing frequency of the neurons. Enhanced
precursor availability may matter only when physiological demand is increased.

Choline for acetylcholine (ACh) synthesis can be obtained from either brain
choline, the phosphatidylcholine in the membranes or serum choline (Table 33-1).
It is taken up by a high-affinity choline-uptake system at the synapse (see
Chap. 11). Although choline can be made in the body, its synthesis can be
limited by the availability of "single-carbon" units in the diet. Ingestion of
choline together with phosphatidylcholine can increase brain choline and ACh
concentrations and enhance the ability of ACh synthesis to increase upon demand.
For example, increased dietary choline permits the brain to make excess ACh
following stimulation with atropine. Dietary phosphatidylcholine simultaneously
increases memory and the ACh content of the brains of "demented" mice, which
normally have reduced brain ACh concentrations [1]. Increasing choline
prenatally and postnatally improves the working and reference memory of young
rats.

Glucose normally provides the acetyl moiety of ACh. Extensive evidence indicates
that relatively modest increases in circulating glucose concentrations can also
increase ACh release and has been claimed to enhance learning and memory. The
relative safety of glucose administration has permitted tests of its effects on
cognitive functions in humans. Glucose enhances learning and memory in healthy
aged humans and improves several other cognitive functions in subjects with
severe cognitive pathologies, including individuals with Alzheimer's disease and
Down's syndrome. Thus, moderate increases in circulating glucose concentrations
may have robust and broad influences on brain functions that span many neural
and behavioral measures and cross readily from rodents to humans. Considerable
evidence suggests that these effects are mediated via ACh. Increasing glucose
availability can increase the amount of ACh released during conditions of
increased demand [2] (Fig. 33-1) (see also Chaps. 11 and 31).

Tryptophan, like tyrosine, crosses the bloodbrain barrier predominantly by the
carrier system for long-chain neutral amino acids. As a result, a protein-rich
meal can actually increase blood tryptophan but reduce the passage of tryptophan
into the brain by elevating at the same time the concentrations of other amino
acids, such as phenylalanine, that compete for that carrier. Serotonin
(5-hydroxytryptamine, 5-HT) synthesis depends on brain tryptophan, which in turn
depends on blood tryptophan concentrations, which can be manipulated by varying
the diet (Table 33-1). Elevating tryptophan in the brain produces
physiologically important changes in the serotonergic system (see Chap. 13).
Animals that are poor in brain tryptophan have a heightened sensitivity to
painful stimuli that can be reversed with tryptophan ingestion, which rapidly
elevates brain serotonin. Therapeutically, tryptophan has been reported to be
useful in treating subgroups of patients with depression, sleeplessness or
hyperactive behaviors.

Tyrosine is the precursor of NE and epinephrine (Table 33-1). Increasing
tyrosine reduces blood pressure in both normotensive and hypertensive animals.
The action of tyrosine on blood pressure occurs via CNS mechanisms since
co-administering other large neutral amino acids that reduce the uptake of
tyrosine into the brain blocks the effect. The antihypertensive action of
tyrosine appears to be mediated by an acceleration in NE or epinephrine release
within the CNS; injection of tyrosine produces a concurrent increase in brain
concentrations of 3-methoxy-4-hydroxyphenylethylglycol sulfate, a catecholamine
metabolite [3]. Tyrosine induces increased NE and alters NE and a and b receptor
densities in hippocampus, providing further evidence of its physiological role.
Furthermore, dietary restriction to 40% of normal food intake diminishes maze
performance, and this effect can be reversed by administration of tyrosine.

Nutrition can influence brain energy reserve


Brain energy is more resistant to changes in fasting or overfeeding than that in
liver or muscle. For example, severe fasting decreases liver ATP concentrations
and ATP: phosphocreatine ratios, while brain energy metabolism is preserved.
However, brain energy metabolism can be manipulated by diet. A high-fat (90% of
caloric value), carbohydrate-free ketogenic diet low in protein (10%) does not
significantly alter regional brain glucose utilization or cerebral
concentrations of glucose, glycogen, lactate or citrate. However, a
high-carbohydrate diet (78%) low in fat (12%) and low in protein (10%) markedly
decreases brain glucose utilization and increases cerebral concentrations of
glucose 6-phosphate. These findings indicate that long-term, moderate ketonemia
does not significantly alter brain glucose phosphorylation. However, even
marginal protein dietary deficiency when coupled with a carbohydrate-rich diet
depresses cerebral glucose utilization to a degree often seen in metabolic
encephalopathies (see Chap. 38) [4].

Carnitine participates in mitochondrial reactions. Like choline, it can be
synthesized by mammals if dietary sources of one-carbon groups are adequate. It
participates in the transfer of acyl groups across mitochondrial membranes
(Chap. 42). These include acetyl groups for ACh synthesis. Both carnitine and
acetylcarnitine cross the bloodbrain barrier (BBB), but the more lipid-soluble
acetyl-l-carnitine has been described as having a variety of effects on the
nervous system in experimental animals not seen with carnitine.

Hereditary deficits in the ability to transport carnitine or to synthesize its
acyl derivatives have been associated with diseases of skeletal and cardiac
muscle and, to a variable extent, with metabolic encephalopathy (see Chap. 34).
Secondary deficiency of carnitine has been described in a number of disorders of
mitochondrial oxidation, due in part to the detoxification and urinary excretion
of potentially damaging short-chain acids as the carnitine derivatives [5]. The
anticonvulsant valproic acid can increase carnitine requirements in susceptible
individuals [6]. Treatment with acetylcarnitine has been reported to slow the
progression of Alzheimer's disease [7].

Vitamins can regulate normal neuronal activity


Many vitamins function as cofactors in fundamental pathways, such as glycolysis,
the Krebs cycle, the respiratory chain and amino acid metabolism. Although all
tissues have these vitamin-dependent pathways, they take on increased importance
in the brain because of its high metabolic rate and dependence on continuous
metabolism. In fact, the discovery of vitamins was closely linked to the
sensitivity of the brain to deficiency, specifically that of thiamine [8].
Furthermore, in the brain these pathways are linked to neurotransmitter
synthesis.

Vitamin B1 (thiamine) is critical to normal brain function. Thiamine
pyrophosphate (TPP) functions as a cofactor of key enzymes of the Krebs cycle:
the pyruvate and a-ketoglutarate dehydrogenase complexes (PDHC and KGDHC,
respectively), the branched-chain dehydrogenase complex (BCDHC) and the pentose
shunt enzyme transketolase (TK) (Table 33-2). These dehydrogenase complexes
share a common enzyme component, lipoamide dehydrogenase. TK rearranges sugars
(see Chap. 31). A kinase can convert a membrane-bound form of TPP to thiamine
triphosphate (TTP), and a specific phosphatase hydrolyzes TTP to the
diphosphate. TTP appears to play a role in nerve membrane function, notably in
Na+ gating. The cDNAs for a number of TPP-requiring enzymes have been obtained,
and a TPP-binding motif has been proposed that is partially conserved in yeast,
rat and human.

Thiamine deficiency is a classical and well-studied example of the interaction
of nutrition with brain function. Research on thiamine deficiency continues to
attract considerable interest. In developed countries, clinically significant
thiamine deficiency is rare except as a complication of severe alcoholism or
other conditions that impair nutrition [9]. It is more common in developing
countries in which polished rice is the staple grain. It can be detected by
measuring the "TPP effect," the percentage increase in red cell TK activity upon
addition of exogenous TPP in vitro, and has been widely used in laboratory as
well as in epidemiological studies of thiamine deficiency.

After 5 to 6 days of a diet deficient in thiamine, healthy young men developed a
nonspecific syndrome of lassitude, irritability, muscle cramps and
electrocardiographic changes, which were reversed by dietary thiamine.

Prolonged thiamine deficiency frequently leads to damage to peripheral nerves
(see Chap. 36). This neuropathy tends to be worse distally than proximally,
involves myelin more than axons and is often painful. The neuropathy may be
linked to deficiencies in multiple water-soluble vitamins known for historical
reasons as the vitamin B complex.

Wernicke-Korsakoff syndrome consists of an acute (Wernicke) phase and a chronic
(Korsakoff) phase [9]. The acute syndrome consists of staggering gait, paralysis
of eye movements and confusion, associated with small hemorrhages along the
third and fourth ventricles and with reduced cerebral metabolic rate as measured
by cerebral blood flow. Injections of thiamine can be lifesaving, with clinical
improvement often evident within minutes. It is believed that prompt treatment
with thiamine can prevent the onset of the chronic Korsakoff phase. In
Korsakoff's syndrome, a striking loss of working memory accompanies relatively
little loss of reference memory (see Chap. 50). Affected patients
characteristically make up stories, or confabulate, in response to leading
questions. In this phase, patients do not respond to thiamine treatment. The
neuropathological lesions responsible for Korsakoff's syndrome have been
debated; severe damage to the cholinergic neurons of the nucleus basalis complex
has been reported.

Thiamine requirements can be altered genetically or environmentally. Among
genetic disorders, thiamine-dependent maple syrup urine disease is due to a
reduced affinity of BCDHC for TPP (see Chap. 44). A rare form of lactate
acidosis is due to reduced affinity of PDHC for TPP. Both disorders respond to
treatment with large doses of thiamine. Wernicke-Korsakoff syndrome is
associated with a variant form of TK having a decreased affinity for TPP [9].
This variation, which may be more common in chronic alcoholics, puts patients at
risk when on a diet marginal or deficient in thiamine. Subacute necrotizing
encephalomyelopathy (SNE) of Leigh is an uncommon, autosomal recessive disorder
in which the neuropathology resembles Wernicke-Korsakoff syndrome. Patients with
SNE in whom a defect in PDHC has been documented at the cDNA level have been
described. The role of thiamine in this disorder is controversial.

Environmentally, a number of dietary constituents are known to impair the
absorption of thiamine, including ethanol. Severe illness or injury also has
been reported to increase thiamine requirements. Rarely, patients have been
found who are intolerant to very large doses of thiamine. Thiamine-dependent
enzymes are reduced in the brains of patients with a variety of
neurodegenerative diseases, including Alzheimer's, Huntington's and Parkinson's
diseases.

Thiamine-deficient animals model many aspects of human thiamine deficiency [10].
Experimentally, thiamine deficiency is frequently induced by the combination of
a thiamine-deficient diet and a thiamine antagonist, either pyrithiamine or
oxythiamine. However, pyrithiamine can directly inhibit action potentials and
oxythiamine does not enter the brain efficiently. In the pyrithiamine model in
mice, abnormal neuropsychological responses develop within 5 to 7 days, gross
neurological abnormalities in 8 to 9 days and death usually by 10 to 11 days.
Strain significantly modifies the response to experimental thiamine deficiency
in mice (Fig. 33-2). In rats, abnormalities of motor performance occur by day 3,
additional neurological symptoms by day 12 and death within 2 weeks. Thiamine
deficiency leads to a selective cell death that is accompanied by accumulation
of amyloid precursor protein in surrounding neurons. It causes severe memory
disruption and loss of cholinergic function. The activities of
thiamine-dependent enzymes decline in early stages of thiamine deficiency, but
surprisingly, selective cell death is not related to the cellular or regional
distribution of thiamine-dependent enzymes or to their response to thiamine
deficiency. Instead, the general reduction in thiamine-dependent enzymes
predisposes particular brain regions to other insults. The earliest known change
that reflects selective vulnerability is an alteration in the BBB that is
accompanied by oxidative stress, which causes increased ferritin and iron
deposition, and induction of nitric oxide synthase. The results suggest that
cerebrovascular endothelial cells of these brain regions may be particularly
vulnerable to thiamine deficiency [10].

Vitamin B3 (niacin) deficiency in humans leads to pellagra, which is
characterized by dementia, dermatitis, diarrhea and eventually death. The
deficiency was recognized in the eighteenth century, shortly after the
introduction of American corn (maize) into Europe [8].

Niacin and niacinamide refer to nicotinic acid and its amide, respectively.
Although these pyrimidine derivatives can be synthesized from tryptophan in
mammals, perhaps at least in part by intestinal bacteria, 60 mg of dietary
tryptophan are required to synthesize 1 mg of the vitamin. Niacin is considered
to be a vitamin because most human diets do not contain enough tryptophan to
fulfill the normal human requirement for the vitamin of 10 to 30 mg/day.

Hartnup's syndrome is a hereditary disorder in which tryptophan transport is
impaired and requirements for dietary niacin increase. Phenylketonuria and
hyperphenylalaninemia can increase niacin requirements by increasing the
concentrations of amino acids that compete with tryptophan for transport systems
(see also Chap. 44). A high-corn diet predisposes to niacin deficiency since the
major storage protein of American corn (zein) has relatively little tryptophan
relative to other amino acids that compete for the same carrier. Addition of
purified niacin to the diet has largely abolished pellagra, which was once a
common disease in areas where corn was a dietary staple.

Niacin is incorporated into the coenzymes NAD+ and NADP+ and their reduced
forms. These cofactors are involved in numerous oxidation/reduction reactions,
including the coupling of the Krebs cycle to the respiratory chain.
Antimetabolites, particularly 6-aminonicotinamide and 3-acetylpyridine, have
been particularly useful in determining the role of niacin deficiency in the
brain in experimental animals. Newborn mice that received a single
intraperitoneal injection of 6-aminonicotinamide consistently developed lesions
in the CNS, the skin and the intestinal tract. Anterior horn cells in the spinal
cord as well as motor neurons in the brain exhibit the ultrastructural features
of neuronal chromatolysis, while glial and ependymal cells show edematous
changes. 3-Acetylpyridine administration leads to selective neuropathological
lesions in the brainstem. Although the pathological features of
antimetabolite-treated mice are not identical to those of human pellagra,
possible contributory mechanisms in the development of pellagra lesions,
including dementia and selective cell loss, may be elucidated with this
experimental model [11].

Vitamin B6 (pyridoxine) is necessary for the biosynthesis of several
neurotransmitters. It is a pyridine derivative that can exist as an alcohol,
amine or aldehyde. The concentration in brain is normally about 100-fold higher
than that in the blood. The active coenzyme is the phosphorylated derivative
pyridoxal phosphate, which readily forms Schiff bases. This coenzyme
participates in decarboxylation reactions, including those that form GABA from
glutamate, 5-HT from 5-hydroxytryptophan and probably DOPA from
dihydroxyphenylalanine. It is also involved in transaminations, including that
converting a-ketoglutarate to glutamate. The conversion of tryptophan to
nicotinamide requires pyridoxyl phosphate as a cofactor, and the excretion of
xanthurenic acid after a tryptophan load is widely used to test the adequacy of
pyridoxine nutriture. In vitamin B6 deficiency in rats, biochemical and
morphological abnormalities, including decreased dendritic arborization and
reduced numbers of myelinated axons and synapses, are associated with behavioral
changes, such as epileptiform seizures and movement disorders. Reduced seizure
threshold and delayed neuronal recovery are related to the significantly reduced
brain regional GABA and elevated glutamate concentrations in
pyridoxine-deficient rats [12]. In addition, vitamin B6 deficiency during
gestation and lactation alters the function of N-methyl-d-aspartate (NMDA)
receptors.

Pyridoxine deficiency has occurred in human infants fed a formula from which
vitamin B6 had been inadvertantly omitted. The prominent finding was intractable
seizures which responded promptly to injections of the vitamin. Deficiency of
pyridoxine can contribute to the polyneuropathy of B-complex deficiency.
However, very large doses of pure pyridoxine can lead to a persistant sensory
neuropathy [13] (Chap. 36).

Like those of other nutrients, requirements for pyridoxine can be altered by
genetic or environmental factors and are increased in a number of disorders of
the nervous system [8,14,15]. Treatment of "pyridoxine-deficient" infants may
require doses of pyridoxine several hundredfold the normal daily requirement.
Maintenance with doses at least tenfold the normal requirement typically permits
normal development if irreversible brain damage has not yet occurred. It has
been suggested that mild forms of pyridoxine dependence may be a relatively
common cause of intractable seizures and mental retardation, but neurochemical
studies of these patients are limited. In homocystinuria and cystothioninuria,
two disorders of amino acid metabolism, some patients respond to large doses of
pyridoxine. In these patients, the mutations appear to reduce the affinity of
the relevant enzymes for pyridoxal phosphate (see Chap. 44).

Environmentally, hydrazides and oximes can increase pyridoxine requirements.
Large doses of pyridoxine are routinely given with the antituberculous
medication isonicotinic hydrazide, to prevent drug-induced neuropathy.

Vitamin B12 (cobalamin) deficiency is commonly associated with neurological
syndromes. The cobalamins are a series of porphyrin-like compounds [16]. The
active forms contain a cobalt ion linked to one of the methylene groups. The
cobalamins are synthesized by many microorganisms but not by higher plants or
animals. A rich dietary source is meat, particularly liver. Effective absorption
requires a series of transport proteins, including a glycoprotein intrinsic
factor secreted by gastric parietal cells. Conversion to the active coenzymes
adenosylcobalamin and methylcobalamin requires at least two reductase reactions
and an adenosyltransferase step. The reductases are flavoproteins that require
NAD+ as a cofactor. Thus, B12 metabolism involves at least three vitamins: B12
itself, niacin and riboflavin. Body stores of cobalamins are normally large
enough to maintain health for over 2 years without a dietary source of the
vitamin.

Cobalamins have two well-established biochemical functions. Adenosylcobalamin is
the cofactor for the mutase that converts methylmalonyl CoA to succinyl CoA.
This reaction is part of the pathway of metabolism of propionic acid, which
itself derives from the metabolism of odd-chain fatty acids and from certain
amino acids. Methylcobalamin is the cofactor for the methyltransferase that
converts homocysteine to the amino acid methionine. This reaction is important
in folate metabolism as well. Its impairment appears to foster folate deficiency
by an accumulation of N5-methyltetrahydrofolate in a "folate trap." Deficiency
of cobalamins or of folate or of both can restrict the supply of metabolically
available one-carbon groups for metabolic pathways, including those of nucleic
acid synthesis.

Cobalamin deficiencies are relatively common clinically [16]. Pure dietary
deficiency responding promptly to treatment with oral cobalamins has been
described in a few children of strict vegan mothers. A more common syndrome is
caused by failure of absorption due to an inadequate supply of the glycoprotein
intrinsic factor, usually on an autoimmune basis. The most characteristic
abnormality is pernicious anemia, characterized by enlarged erythrocytes, called
megaloblasts, and abnormal leukocytes. Neurological symptoms occur in many of
these patients and can precede the hematological changes [17].

Combined system disease is the most common B12-mediated neurological syndrome.
Affected patients develop unpleasant tingling sensations (paresthesias),
followed by loss of vibratory sensation, particularly in the legs, and spastic
weakness. The characteristic neuropathology is a spongy demyelination in the
long tracts of the spinal cord, particularly prominent in the posterior columns
as well as corticospinal tracts. Combined system disease responds poorly to
treatment with cobalamins.

Cobalamin deficiency is characteristically associated with malaise that does
respond dramatically to treatment, even before the hematological response is
evident. Relatively low serum concentrations of B12 have been reported in
subgroups of psychiatric patients, including patients with Alzheimer's disease,
but responses to treatment with the vitamin have, in general, not been dramatic.
Recent studies indicate that elevated concentrations of serum or cerebrospinal
fluid methylmalonate can identify patients whose neuropsychiatric manifestations
benefit from B12 treatment, even though the amounts of vitamin in serum are not
in the deficient range [17].

Whether the damage to the nervous system relates to decreased activity of the
methylmalonyl mutase or of the methyltransferase or of both remains unsettled.
Increased excretion of methylmalonate has been reported to be a marker for
patients whose neuropsychiatric manifestations will improve with B12 treatment,
but clinically normal children with a mutase deficiency are known. Children with
homocystinuria and related disorders do not develop the clinical or pathological
stigmata of combined system disease (see Chap. 44). An infant with an apparent
reduction in methyltransferase activity was clinically normal when reported at
age 1 year. Patients with severe inherited deficiencies in the activities of
both enzymes secondary to a defect in the metabolism of the cobalamins do
develop profound disease of the nervous system, with some characteristics of
combined system disease.

As with other nutrients, requirements for cobalamin can be modified by genetic
and environmental influences. Genetic factors apparently predispose to intrinsic
factor deficiencies with resultant cobalamin deficiency. Furthermore, at least
six different inherited methylmalonic acidurias have been described [16]:
absence of the mutase, decreased affinity of the mutase for adenosylcobalamin,
deficiency of mitochondrial cobalamin reductase, deficiency of a mitochondrial
cobalamin adenyltransferase and two distinguishable defects associated with
abnormal cytosolic metabolism of cobalamin (see Chap. 44). Other conditions
leading to increased cobalamin requirements include surgical removal of the
stomach, excessive destruction of cobalamins in the gut by bacteria in a blind
loop or destruction by certain kinds of intestinal tapeworm.

Folic acid contains a pterin moiety linked to para-aminobenzoic acid, which is
linked to one or more glutamate residues [18]. It plays a key role in the
transfer of one-carbon (active methylene) groups, including the conversion of
serine to glycine and the cobalamin-dependent transfer from homocysteine to
methionine. Dietary deficiency of folate with normal cobalamin leads to anemia
without significant neurological signs. However, both genetic and environmental
disorders of folate metabolism have been associated with disease of the nervous
system. Genetic defects in the relevant enzyme reactions are discussed further
in Chapter 44.

Genetic disorders of folate absorption, intraconversion and utilization are rare
[18]. They have occasionally been associated with phenocopies of well-known
psychiatric syndromes. A boy with apparent deficiency of hepatic dihydrofolate
reductase was treated with folate and developed a sociopathic personality in his
teens. A folate-responsive form of mental retardation with catatonia has been
described in an adolescent girl with N5,10-methylenetetrahydrofolic acid
reductase deficiency. Her younger sister was mentally impaired with "psychosis";
an unrelated boy with a defect of the same enzyme had seizures and proximal
muscle weakness without notable psychiatric problems. Most patients with
glutamate formiminotransferase deficiency have had a syndrome of psychomotor
retardation in infancy, but a few have been entirely normal clinically.

Environmentally, a number of common medications, including phenytoin and certain
antitumor agents, increase requirements for dietary folate. Treatment with
folate can mask the hematological signs of cobalamin deficiency without
affecting the progressive damage to the nervous system.

Pantothenic acid is a substituted hydroxybutyric acid that is a constituent of
CoA [19]. Experimental induction of pantothenic acid deficiency leads to signs
of peripheral nerve damage, for example, demyelination in laboratory animals and
paresthesias in humans. Late signs of CNS damage in animals may relate as well
to the adrenal failure that is a prominent part of the syndrome.

The brain depends on select vitamins and closely related compounds as
antioxidants to control potentially damaging free radicals


The main antioxidants in brain are vitamin E (tocopherol), vitamin C (ascorbic
acid) and glutathione (Table 33-2). The first two can be easily manipulated by
diet, whereas the latter is more difficult to control. Dietary a-lipoate appears
to be a useful compound to regenerate the antioxidant capacity of these other
compounds (see below). Dietary manipulation of antioxidants has practical
implications for brain function. Aging has been associated with free radical
damage in the brain (see Chap. 34). In aged patients tested over a 22-year
period, free recall, recognition and vocabulary correlated positively with
ascorbic acid and b-carotene in blood, even after controlling for possible
confounding variables, such as age, education and gender. These results indicate
the important role played by antioxidants in brain aging and may have
implications for prevention of progressive cognitive impairments [20].

Vitamin E (a-tocopherol) deficiency produces a characteristic neurological
syndrome. It presumably results from increased oxidative stress arising from a
reduction in antioxidant capacity. Vitamin E deficiency in neural tissues
increases endogenous lipid peroxidation, as evidenced in brain tissues by the
appearance of thiobarbituric acid-reactive substances such as malondialdehyde.
The brain is more susceptible to the deficiency than muscle. Within the brain,
the cortex, striatum and cerebellum are the most sensitive regions. Isolated
fractions from myelinated nerve tracts show that the axoplasmic membranes and
organelles are particularly vulnerable to oxidative stress [21]. Vitamin E
deficiency reduces tyrosine hydroxylase-immunopositive neurons in the substantia
nigra but not in the adjacent ventral tegmental area. The enhanced sensitivity
of the nigrostriatal pathway to oxidative stress could have important
implications for the pathogenesis of Parkinson's disease (see Chap. 45). A diet
deficient in vitamin E increases glutamate and GABA and decreases tryptophan
concentrations in the substantia nigra. The increase of nigral glutamate
suggests possible links to degenerative processes through glutamatergic
excitotoxicity. These results suggest that vitamin E may play a significant role
in the degeneration of the substantia nigra and that this tissue may be
particularly sensitive to oxidative stress. Furthermore, these findings support
the widely held view that oxidative stress in the substantia nigra is important
in the pathophysiology of Parkinson's disease.

Vitamin C (ascorbate) deficiency leads to extensive oxidative damage of proteins
and protein loss in the microsomes, as evidenced by accumulation of carbonyl
groups on proteins as well as tryptophan loss. This oxidative damage is reversed
by ascorbate therapy. Ascorbate deficiency also leads to lipid peroxidation in
microsomes, as evidenced by accumulation of conjugated dienes, malondialdehyde
and fluorescent pigment. Lipid peroxides disappear after ascorbate therapy but
not after treatment with vitamin E. These results indicate that vitamin C may
exert a powerful protection against degenerative changes in the brain associated
with oxidative damage [22].

Oxidation of vitamin E and C is maintained by glutathione, the predominant thiol
antioxidant in the brain. Glutathione cannot be directly manipulated by diet,
whereas the metabolic antioxidant a-lipoate can be absorbed from the diet and
cross the BBB to reduce oxidized glutathione and vitamins A and C (Fig. 33-3).
a-Lipoate is taken up and reduced in cells and tissues to dihydrolipoate, which
is also exported to the extracellular space; hence, protection is afforded to
both intracellular and extracellular environments. Both a-lipoate and
dihydrolipoate are potent antioxidants that regenerate other antioxidants, like
vitamins C and E, and raise intracellular glutathione concentrations. Protective
effects by antioxidants have been reported in cerebral ischemiareperfusion,
excitotoxic amino acid brain injury, mitochondrial dysfunction, diabetes and
diabetic neuropathy, inborn errors of metabolism and other causes of acute or
chronic damage to the brain or neural tissue. Thus, a-lipoate administration may
prove to be an effective treatment in numerous neurodegenerative disorders [20].

Trace nutrients in the diet have a vital role in maintaining normal brain
function


Zinc (Zn2+) influences numerous cellular functions, including immune mechanisms,
actions of several hormones and enzyme activities. More than 200 enzymes are
known to be Zn2+-dependent, including mRNA-editing enzymes, superoxide
dismutase, metalloproteins and a "Zn2+-finger" family of sequence-specific
DNA-binding proteins that regulate transcription. Metallothionein binds excess
Zn2+, thus maintaining its steady-state concentration and preventing inhibition
of an extensive number of sulfhydryl-containing enzymes and receptor sites;
hence, it protects against metal-related neurotoxicity. Metallothionein donates
Zn2+ to an extensive number of Zn2+-activated, pyridoxal phosphate-mediated
biochemical reactions. The complex nature of the interactions of Zn2+ with
multiple enzymes is exemplified by the observation that epileptic seizures that
are blocked by GABA can be blocked by either deficiency or excess of either Zn2+
or pyridoxal phosphate. A proposed explanation of these observations is that at
physiological concentrations Zn2+ stimulates the activity of hippocampal
pyridoxal kinase, enhancing the formation of pyridoxal phosphate and of GABA via
glutamate decarboxylase formation, whereas at higher doses Zn2+ inhibits the
activity of glutamate decarboxylase by preventing the binding of pyridoxal
phosphate [23]. Severe Zn2+ deficiency during the period of rapid brain growth
has effects similar to that seen with protein-calorie malnourishment, including
altered regulation of emotions; food motivation; lethargy (reduced activity and
responsiveness), and deficits in learning, attention and memory. In addition to
the many deficits produced by Zn2+ deficiency in the brain, the severe effect of
Zn2+ deficiency on other tissues leads to additional peripheral mechanisms that
alter brain function [24]. Although Zn2+ is essential at low concentrations,
higher concentrations are toxic. For example, high Zn2+ concentrations enhance
and prolong the firing rate of neurons, significantly depress paired-pulse
potentiation, block the action of NMDA on cortical neurons, enhance quisqualate
receptor-mediated injury and inhibit the Ca2+-dependent release of transmitter
by inhibiting the entry of Ca2+ into nerve terminals.

Copper is an integral component of multiple cellular enzymes, including the
cytochromes and superoxide dismutase. Copper deficiency produces clinical signs
analogous to those of Par-kinson's disease and results in low dopamine
concentration in the corpus striatum. Neuropathology in experimental animals
occurs in only part of the copper-deficient population and is dam- and
litter-related, suggesting the presence of a genetic component that alters the
response to copper deficiency. Insight into the role of copper in brain function
is provided by two genetic diseases.

Wilson's disease is an inherited disorder that leads to copper accumulation,
causing damage primarily to the liver and the brain (see Box 45-1). Psychiatric
and behavioral abnormalities occur in 30 to 100% of Wilson's disease patients
and are often the initial symptoms. The most common of the psychiatric and
behavioral manifestations include personality changes, such as irritability and
low anger threshold; depression, sometimes leading to suicidal ideation and
attempts; and deteriorating academic and work performance, which is present in
almost all neurologically affected patients [25].

Menke's disease is caused by a genetic deficiency of serum copper and of
copper-dependent enzymes and is characterized by neurological degeneration and
mental retardation, connective tissue and vascular defects, brittle and
depigmented hair and death in early childhood (see Box 45-1). Despite excessive
accumulation of the metal in various tissues, a functional copper deficiency is
evident, caused by a defective intracellular copper-transport protein. A large
amount of copper accumulates in the organelle-free cytoplasm, whereas
mitochondria are in a state of copper deficiency, indicating that the Menke's
mutation probably affects copper transport from the cytosol to the intracellular
organelles [26]. Brindled is a murine mutation that produces similar
copper-transport deficits, and studies of this animal model show that the copper
deficit in organelles causes reductions in critical copper-dependent enzymes,
such as cytochrome oxidase. It has been hypothesized that the Wilson's disease
gene is a copper-transporting ATPase with homology to the Menke's disease gene.
Dietary copper deficiency can affect brain development [27] (see below).

Selenium is vital in maintaining the antioxidant capacity of the brain.
Glutathione peroxidase is a selenium-dependent enzyme that is important for
maintaining the antioxidant capacity of brain glutathione (Fig. 33-2) and is
reduced in selenium-deficient animals. Selenium supplementation significantly
elevates Na,K-ATPase activity and significantly decreases lipid peroxide
formation. Since Na,K-ATPase activity is known to be inhibited by oxygen free
radicals, selenium supplementation appears to exert its beneficial effect on the
Na,K-ATPase activity by preventing free radical-induced damage. Selenium
significantly reduces the production of thiobarbituric acid-reactive substances,
a measure of lipid peroxidation, in response to an oxidative challenge in blood
and different regions of the brain [28]. Selenium deficiency increases dopamine
turnover in the substantia nigra but not in the striatum. These results suggest
that dietary selenium protects the brain, particularly the substantia nigra,
against oxidative damage.

Trace compounds are also important in brain function. Chromium-deficient
patients develop severe diabetic symptoms, including glucose intolerance, weight
loss, impaired energy utilization and nerve and brain disorders. Low dietary
boron is reported to cause significantly poorer performance on various cognitive
and psychomotor tasks. Additional research is likely to reveal additional trace
components of the diet that may be critical to normal brain function.



(c) 1999 by American Society for Neurochemistry
Published by Lippincott Williams and Wilkins.

Ann Plast Surg 2001 Nov;47(5):540-6 Related Articles, Books, LinkOut


Protective effect of fucoidin (a neutrophil rolling inhibitor) on ischemia
reperfusion injury: experimental study in rat epigastric island flaps.

Cetin C, Kose AA, Aral E, Colak O, Ercel C, Karabagli Y, Alatas O, Eker A.

Department of Plastic & Reconstructive Surgery, Osmangazi University Medical
Faculty, Eskisehir, Turkey.

The objective of this study was to examine whether a decrease in
neutrophil-mediated tissue injury using Fucoidin, a nontoxic neutrophil rolling
inhibitor, would improve flap survival in an island flap model after
ischemia-reperfusion. Myeloperoxidase activity (an indirect index of tissue
neutrophil count) and malondialdehyde (an indicator of lipid peroxidation), the
degree of neutrophil infiltration by direct counting, and macroscopic flap
survival were assessed in the flap after arterial ischemia-reperfusion.
Epigastric island skin flaps were elevated in 56 rats. The first group of 21
rats was subjected to 6 hours of arterial ischemia. The second group of 21 rats
was subjected to 10 hours of arterial ischemia, and the rest of the rats were
used as nonischemic controls (sham flaps). For inhibiting neutrophil rolling, a
nontoxic polysaccharide agent-Fucoidin-was used. Each ischemic group was divided
further into three subgroups: Subgroup I (control rats) received saline,
subgroup II received 10 mg per kilogram Fucoidin, and subgroup III received 25
mg per kilogram Fucoidin before reperfusion. The results were evaluated as
tissue neutrophil counts, tissue malondialdehyde content, tissue myeloperoxidase
activity, and flap survival. Neutrophil counts and tissue myeloperoxidase
activity were decreased significantly (p <0.001) in subgroup III, but lipid
peroxidation by means of tissue malondialdehyde content was not affected by
Fucoidin administration. The authors conclude that administration of Fucoidin
before reperfusion can limit tissue injury apparently by inhibiting neutrophil
rolling in a dose-dependent manner.

PMID: 11716267 [PubMed - indexed for MEDLINE]