Having problems with message search?
All,
vvigwimail@yahoogroups.com
Renewed evidence suggests statin/Parkinson's link
  |
Reuters Health
Tuesday, January 16, 2007
WASHINGTON (Reuters) - New research showing a strong link between Parkinson's disease and low levels of low density lipoprotein (LDL), the "bad" cholesterol, are so worrying that U.S. researchers are launching a study to look into it.
The team at the University of North Carolina is planning clinical trials involving thousands of people to see whether statin drugs, which lower low LDL levels, might actually trigger Parkinson's in some people.
Other research has for several years suggested that people with abnormally low levels of LDL might be at higher risk of Parkinson's disease.
Xuemei Huang and colleagues found that patients with low levels of LDL cholesterol are at least 3.5 times more likely to develop Parkinson's disease than those with higher LDL levels.
Reporting in the journal Chemistry & Industry, the investigators said they plan a bigger study of patients taking statins, the biggest-selling drugs in the world.
"I am very concerned, which is why I am planning a 16,000-patient prospective study to examine the possible role of statins," Huang said in a statement.
In a prospective study, patients are evaluated and observed from one time point to another for any changes, such as the progression or development of a disease. This differs from a retrospective study in which patient records are evaluated rather than the patients' themselves.
Huang noted some other studies showed that people with APOE2, a gene that causes naturally low cholesterol, have a higher risk of Parkinson's. Another variation of the gene, APOE4, is associated with a risk of Alzheimer's disease.
British heart experts expressed alarm about the report and said heart patients should not stop taking statins.
"We are concerned that any suggestion of a link between statins and Parkinson's disease would unnecessarily scare the millions of people benefiting from statins in the U.K.," said Dr. Peter Weissberg, medical director of the British Heart Foundation.
"There is no evidence to suggest that statins cause Parkinson's disease. There is, however, overwhelming evidence that statins save lives by preventing heart attacks and strokes."
Parkinson's is an incurable brain illness that can paralyze patients. Patients may also have difficulty walking and talking and may shake uncontrollably at times.
According to the National Institutes of Health, Parkinson's affects at least 500,000 people in the United States alone. But heart disease affects 70 million Americans, according to the U.S. Centers for Disease Control and Prevention, and kills more than 910,000 each year.
Reuters Health
|
More on: |
Worldwide Parkinson's Cases Will Double In Next 25 Years
Science Daily — The number of individuals with Parkinson's disease in 15 of the world's largest nations will double over the next generation, according to a study published in the January 30 issue of the journal Neurology. The study highlights the significant challenge facing countries with rapidly growing economies, particularly in Asia, many of which are ill prepared to meet this impending public health threat.
| Advertise on this site |
Read how I overcame Parkinsons and revealed a huge medical blunder
www.parkinsons-success.com
Raising Glutathione can Help - Free booklet explains how it works!
GlutathioneMiracle.com
Research biomarkers for Alzheimers Parkinsons, Huntington's & more
www.chemicon.com
In recent years, a great deal of resources and energy have been focused on confronting infectious diseases such as HIV, malaria, and tuberculosis. This is highlighted by high-profile private investments in these areas by organizations such as the Gates Foundation. However, while infectious diseases have attracted the greatest attention from international donors, it is non-communicable chronic diseases, such as Parkinson's, that represent a far greater burden in terms of economic and social cost to developing nations.
University of Rochester neurologist Ray Dorsey, M.D., and a team of researchers examined the projected population growth in the five largest countries in Western Europe (France, Spain, Germany, the United Kingdom, and Italy) and the 10 most populous nations worldwide (China, India, Indonesia, the United States, Brazil, Pakistan, Bangladesh, Nigeria, Japan, and Russia). They then projected the prevalence of the disease by age group in each country. Their research estimates that the number of individuals with Parkinson's disease in these 15 countries will grow from 4.1 to 8.7 million by the year 2030. While the number of individuals with the disease will nearly double in the United States to 610,000, the greatest growth will occur in developing countries in Asia. By 2030, an estimated 5 million people in China will have the disease.
"The bulk of the growth in Parkinson's disease in the next 25 years will not be in the United States and Europe but in other places, namely China, where Parkinson's may not be viewed as a major public health problem," said Dorsey. "Moreover, this growth will occur in societies where there is very limited infrastructure in place to diagnose individuals, much less address their medical needs or the societal impact."
Parkinson's disease is a degenerative disorder of the central nervous system that impairs motor skills and walking. Despite the fact that the disease is treatable with a combination of medications, therapy and exercise, many individuals in the developing world do not receive appropriate care and may not even be aware of their diagnosis. Dorsey and his colleagues noted that in door-to-door surveys in Bolivia, for example, none of the individuals who were found to have Parkinson's disease had ever seen a physician for their problem.
The growth in chronic diseases such as Parkinson's is one of the unfortunate byproducts of development. Economic growth and the corresponding improvements in health care and education are increasing the life expectancy of individuals in the developing world. In terms of the rise in chronic diseases, the key factor is not overall population growth but rather the number of people over age 65 and thus at risk of developing Parkinson's and other chronic conditions. Furthermore, as income grows, so too does health care spending which, in turn, increases the duration of illness and the overall number of people with a particular disease.
Without the proper systems of medical treatment and social support, chronic diseases can cause significant economic displacement in the form of lost productivity. According to the World Health Organization, China, India, and Russia could forego between $200 billion and $550 billion in national income over the next 10 years as a result of only three chronic diseases: heart disease, stroke and diabetes. Furthermore, 60 percent of deaths worldwide are the result of chronic disease, more than double all infectious diseases, maternal and infant conditions, and nutritional deficiencies combined.
"Understanding and predicting the burden of disease is critical to guiding future health, social and economic policy," said Dorsey. "The challenge for these developing countries that currently don't have the infrastructure in place to care for the small burden they have now is how they will develop this capacity over time recognizing that the costs will grow."
Note: This story has been adapted from a news release issued by University of Rochester Medical Center
Then we have ground breaking research happenning. This development makes me think two things: We need to identify and have a list of researchers and organizations that we add to our contact list to keep informed of their research and for them to be aware of veterans and hopefully work to include veteran sample population in their research. Also we need to keep these leading researchers aware of funding availability for Veterans Research re DOD and VA and encourage them to become involved by submitting letters of intent, etc.
Autoimmune Disease Breakthrough Gained By Identification Of 30 Errant Genes
Main Category: Immune System / Vaccines NewsArticle Date: 29 Jan 2007 - 0:00 PST
| email this article | printer friendly | view or write opinions |
|
Article Also Appears In
| |
 |
 |
 | |
|
Useful Article? | |
A report in the January issue of Nature magazine announces that one more step in understanding what may cause the body to attack itself in its war against autoimmune disease has been discovered by researchers at the Massachusetts Institute of Technology's Whitehead Institute, says the Autoimmune Related Diseases Association (AARDA), a national nonprofit patient advocacy organization.
What happens in certain cases to cause the body's immune system to go wild with an over reaction when it encounters invading viruses or bacteria, thus resulting in one or more autoimmune diseases--such as rheumatoid arthritis, lupus, multiple sclerosis, thyroid disease (Graves', Hashimoto's), juvenile (type 1) diabetes?
Researchers Richard Young and Alexander Marson, an M.D./Ph.D. student working in Young's laboratory, have reported discovering 30 genes that go awry in autoimmune diseases. According to Young, the regulatory T cells (called "T regs") that normally control the immune system may have genetic defects. In that case, the T regs protective powers are weakened.
The "brain" of the T regs is a protein called Foxp3. It can send the message to increase or decrease the production of other genes. Dr. Marson, study lead author, said, "We identified a set of roughly 30 genes that are clearly regulated by Foxp3 and, surprisingly, a lot of them are suppressed by Foxp3." Mutation in more of the genes, PTPN22, is associated with a number of autoimmune disorders. It is speculated that altering the Foxp3 gene might be one way to reach a cure of autoimmune diseases.
Two significant implications have emerged from this research. Marson commented, "One is that we've identified this core set of genes that are probably likely to play key roles in preventing autoimmune more disease." He added, "The second implication, which is maybe more long-term, is that we hope that identifying these targets will allow us to screen for drugs to mimic the function of Foxp3 and, thus, treat autoimmune disease."
Autoimmune disease pioneer Noel R. Rose, M.D., Director of the Johns Hopkins Center for Autoimmune Disease Research, says that treating autoimmune disorders will require enhancing either the number or effectiveness of regulatory T cells. He remarked that the MIT study is "certainly important in trying to understand how these regulatory T cells work." He cautions, "Whether this will have important functional implications, only time will tell."
Commenting on the study results, Virginia Ladd, AARDA president and executive director, observes, "The discovery adds weight to the reason why autoimmune diseases should be considered a disease category similar to the way that cancer is viewed rather than as singular diseases." She adds, "It also lends proof to the genetic connection among these diseases and an understanding as to why these diseases run in families."
Ms. Ladd points out that the public is unaware of the genetic connection among various autoimmune diseases, and patients are seldom queried by healthcare professionals regarding the family history in autoimmune disease. AARDA is pressing for federal legislation that would bring more awareness to autoimmune diseases and the fact that collectively they affect millions of Americans.
American Autoimmune Related Diseases Association (AARDA)
Michigan National Bank Bldg., 15475 Gratiot Ave.
Detroit, MI 48205
United States
http://www.aarda.org/
 |
|
© Newswise. |
|
Autoimmune Disease Breakthrough Gained by Identification of 30 Errant Genes
Newswise — A report in the January issue of Nature magazine announces that one more step in understanding what may cause the body to attack itself in its war against autoimmune disease has been discovered by researchers at the Massachusetts Institute of Technology's Whitehead Institute, says the Autoimmune Related Diseases Association (AARDA), a national nonprofit patient advocacy organization. Researchers Richard Young and Alexander Marson, an M.D./Ph.D. student working in Young's laboratory, have reported discovering 30 genes that go awry in autoimmune diseases. According to Young, the regulatory T cells (called “T regs”) that normally control the immune system may have genetic defects. In that case, the T regs protective powers are weakened. The "brain" of the T regs is a protein called Foxp3. It can send the message to increase or decrease the production of other genes. Dr. Marson, study lead author, said, "We identified a set of roughly 30 genes that are clearly regulated by Foxp3 and, surprisingly, a lot of them are suppressed by Foxp3." Mutation in more of the genes, PTPN22, is associated with a number of autoimmune disorders. It is speculated that altering the Foxp3 gene might be one way to reach a cure of autoimmune diseases. Two significant implications have emerged from this research. Marson commented, "One is that we've identified this core set of genes that are probably likely to play key roles in preventing autoimmune more disease." He added, "The second implication, which is maybe more long-term, is that we hope that identifying these targets will allow us to screen for drugs to mimic the function of Foxp3 and, thus, treat autoimmune disease." Autoimmune disease pioneer Noel R. Rose, M.D., Director of the Johns Hopkins Center for Autoimmune Disease Research, says that treating autoimmune disorders will require enhancing either the number or effectiveness of regulatory T cells. He remarked that the MIT study is "certainly important in trying to understand how these regulatory T cells work." He cautions, "Whether this will have important functional implications, only time will tell." Commenting on the study results, Virginia Ladd, AARDA president and executive director, observes, “The discovery adds weight to the reason why autoimmune diseases should be considered a disease category similar to the way that cancer is viewed rather than as singular diseases.” She adds, “It also lends proof to the genetic connection among these diseases and an understanding as to why these diseases run in families.” Ms. Ladd points out that the public is unaware of the genetic connection among various autoimmune diseases, and patients are seldom queried by healthcare professionals regarding the family history in autoimmune disease. AARDA is pressing for federal legislation that would bring more awareness to autoimmune diseases and the fact that collectively they affect millions of Americans. The American Autoimmune Related Diseases Association is the only national organization dedicated to addressing the problem of autoimmunity, the major cause of chronic illness. For more information, please visit AARDA’s Web site at http://www.aarda.org or call 586-776-5903 or 888-856-9433. | ||||||||||||||||
-
This next article....re have we circulated this information to veterans with MS! Knowledge is power!. Also we need to again identify drs and researchers for us to reach out and keep them informed re Veteran needs, research funds, need to include veterans in treatment and sample populations!This is what saved Col Smith's life
Dear Mayo Clinic: I have an acquaintance whose multiple sclerosis was more or less "cured" with plasma exchange. Yet Mayo Clinic's Web site says that plasma exchange is used mostly as a last resort. Why wouldn't you offer it to every MS patient? - Vulcan, Mich. Answer (from Dr. Brian Weinshenker at the Mayo Clinic in Minnesota): Although it's good to hear that your acquaintance experienced favorable results with plasma exchange, it is not a cure. A course of plasma-exchange treatments, which typically takes about two weeks, does lower antibody levels, which are considered the culprit in some MS cases - but for less than three months. And there is no convincing evidence that plasma exchange prevents attacks of neurological difficulty, the sudden periods of acute MS symptoms, also known as episodes, or exacerbations that are characteristic of the disease. Furthermore, plasma exchange is not advisable for every patient experiencing such an attack. Most MS patients respond well to intravenous corticosteroid drugs, such as methylprednisolone (Solu-Medrol), which constitute the first-line treatment for relieving flare-ups. These medications not only are effective most of the time but also are easier, safer and less expensive to administer than plasma exchange, which is reserved as a "rescue" treatment for the under 5 percent or so of patients who manifest severe symptoms and fail to improve satisfactorily with corticosteroid treatment. Other demyelinating diseases, such as neuromyelitis optica, the symptoms of which overlap with MS, more commonly produce very severe symptoms that require plasma exchange. MS, a chronic illness that affects the central nervous system, is generally believed to be an autoimmune disease, in which the immune system's antibodies and white blood cells attack the brain's myelin (tissue that surrounds nerves) as if it's a foreign substance. This destructive process causes inflammation and injury not only to the myelin sheath itself but also to the underlying nerves, resulting in multiple areas of scarring (sclerosis). Eventually, the damage can slow or block the nerve signals that control coordination, strength, sensation and vision. Plasma exchange (also called plasmapheresis) is based on the idea that replacing the MS patient's plasma may remove destructive factors, including the antibodies that attack myelin. This procedure involves removing some of the person's blood and mechanically separating the blood cells from the fluid (plasma). The blood cells then are mixed with a replacement protein solution, typically albumin or a synthetic plasmalike fluid, and the new blood-containing solution is returned to the patient's body. Your acquaintance is probably among the minority of MS patients who had an attack but failed to respond to corticosteroids. For people in this situation, plasma exchange may seem like a godsend. In our research at Mayo Clinic, 42 percent of drug-resistant subjects showed significant improvement with plasma exchange, which compared to a 5 percent response rate among those who received placebo plasma exchange. Please note, however, that plasma exchange has not been demonstrated to be any better than the first-line corticosteroid treatment. It is better to prevent attacks of MS rather than to try to relieve symptoms after the fact. That's why a common approach now is to treat the patient with "disease-modifying medications" that tend to reduce the frequency of flare-ups, although these treatments are partially effective and don't work for everyone. The best known among them are interferon beta-1b (Betaseron) and interferon beta-1a (Avonex, Rebif), which are genetically engineered copies of proteins that occur naturally in the body. While these beta interferons help regulate the immune system, it is uncertain which of their many actions leads to a reduction in disease activity and what the extent of their long-term benefits may be. An alternative to beta interferons is glatiramer acetate (Copaxone), which promotes the production of certain proteins, called cytokines, that can reduce the intensity of inflammation in the brain. All of these drugs are administered by injection. So although there is no cure for MS as yet, plasma exchange is an important new way of limiting the consequences of severe attacks when standard treatments fail.• To submit a question, write to medicaledge@... or to Medical Edge from Mayo Clinic, c/o Tribune Media Services, 2225 Kenmore Ave., Suite 114, Buffalo, N.Y., 14207. For health information, visit www.mayoclinic The next article is just another for information and we need to all come together as veterans and help each other no matter what state. We need a group that focuses on making connections with other groups that form and developing a shared communication newsletter and personal contacts. In order to really make change we must unite and cooperate with all!
| Retired U.S. Air Force Maj. Rick Briggs has shifted his focus from providing protective headgear for troops overseas to ensuring proper care for troops returning home to Michigan with head injuries. The Brighton man is still director of the Michigan chapter of Operation Helmet, but recently took command of Head Injured Survivors of America — a nonprofit organization that will provide financial and other aid to Michigan war veterans with traumatic brain injuries.
"It was a natural fit. I already had a lot of contacts in the private sector and the political arena," Briggs said of his new role as head of HIS. "It's all about caring for the troops." The organization will holds its first major fundraising event in May. The need for such an organization is great, said Briggs, a veteran of the Gulf War whose son is on duty with the Michigan Army National Guard in Iraq. For one thing, 65 percent of hospitalized veterans suffer some form of traumatic brain injury, such as closed-head injuries and comas, according to 2006 military data. Briggs said federal funding for traumatic brain injuries is minimal when compared to federal dollars expended on problems such as cancer, HIV/AIDS and multiple sclerosis. He said annual federal funding for people with head injuries works out to an average of $2.55 per victim. That's a significant point, Briggs said, considering there were 1.4 million traumatic brain injuries in the United States according to a 2003 report, while there were 176,300 cases of cancer; 51,334 cases of HIV or AIDS; and 10,400 cases of multiple sclerosis. "It's four times as many people suffering with all the others combined, and it's only getting pennies," he said of funding for head trauma. Briggs, who still runs Operation Helmet's Michigan chapter, said the Army is almost fully equipped with ballistic lining pad kits similar to those created by Operation Helmet. He said the Marine Corps and Navy have yet to fully adopt the equipment. Contact Daily Press & Argus reporter Christopher Behnan at (517) 548-7108 or at cbehnan@....
Originally published January 29, 2007
TO a new area.......Vitamin D effects re depleted uranium......this is important and we might need to research getting VITAMIN D measurements of Gulf War Veterans that we know were definitely exposed. Or push for this testing to be done using the patients that went to DOD for DU testing! WE also need to use these research articles to provide education to VSO service officers and to the Senators and Reps. WE need newsletter that addresses the findings and what other steps could be taken re research, clinical care, and for Senators and reps to be kept informed! | ||||||||||||
In vivo effects of chronic contamination with depleted uranium on vitamin D(3) metabolism in rat.
Institute for Radiological Protection and Nuclear Safety, Radiological Protection and Human health Division, Radiobiology and Epidemiology Department, Laboratory of Experimental Toxicology, BP no. 17, F-92262 Fontenay-aux-Roses CEDEX, France.
The extensive use of depleted uranium (DU) in today's society results in the increase of the number of human population exposed to this radionuclide. The aim of this work was to investigate in vivo the effects of a chronic exposure to DU on vitamin D(3) metabolism, a hormone essential in mineral and bone homeostasis. The experiments were carried out in rats after a chronic contamination for 9 months by DU through drinking water at 40 mg/L (1 mg/rat/day). This dose corresponds to the double of highest concentration found naturally in Finland. In DU-exposed rats, the active vitamin D (1,25(OH)(2)D(3)) plasma level was significantly decreased. In kidney, a decreased gene expression was observed for cyp24a1, as well as for vdr and rxralpha, the principal regulators of CYP24A1. Similarly, mRNA levels of vitamin D target genes ecac1, cabp-d28k and ncx-1, involved in renal calcium transport were decreased in kidney. In the brain lower levels of messengers were observed for cyp27a1 as well as for lxrbeta, involved in its regulation. In conclusion, this study showed for the first time that DU affects both the vitamin D active form (1,25(OH)(2)D(3)) level and the vitamin D receptor expression, and consequently could modulate the expression of cyp24a1 and vitamin D target genes involved in calcium homeostasis.
PMID: 17118558 [PubMed - in process
WE go from research on DU to research on sarin. Would like to have comment from DR Hailey of how these findings relate to his findings. I would also like to know if the VA or any major medical center has the equipment needed to replicate this study on Gulf War Veterans? WE need the army engineers that blew up Kamishea to be tested with this same method!!!!
Human brain structural change related to acute single exposure to sarin.
Department of Neuropsychiatry, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
OBJECTIVE: This study aimed to identify persistent morphological changes subsequent to an acute single-time exposure to sarin, a highly poisonous organophosphate, and the neurobiological basis of long-lasting somatic and cognitive symptoms in victims exposed to sarin. METHODS: Thirty-eight victims of the 1995 Tokyo subway sarin attack, all of whom had been treated in an emergency department for sarin intoxication, and 76 matched healthy control subjects underwent T1-weighted and diffusion tensor magnetic resonance imaging (DTI) in 2000 to 2001. Serum cholinesterase (ChE) levels measured immediately and longitudinally after the exposure and the current severity of chronic reports in the victims were also evaluated. RESULTS: The voxel-based morphometry exhibited smaller than normal regional brain volumes in the insular cortex and neighboring white matter, as well as in the hippocampus in the victims. The reduced regional white matter volume correlated with decreased serum cholinesterase levels and with the severity of chronic somatic complaints related to interoceptive awareness. Voxel-based analysis of diffusion tensor magnetic resonance imaging further demonstrated an extensively lower than normal fractional anisotropy in the victims. All these findings were statistically significant (corrected p < 0.05). INTERPRETATION: Sarin intoxication might be associated with structural changes in specific regions of the human brain, including those surrounding the insular cortex, which might be related to elevated subjective awareness of internal bodily status in exposed individuals. Ann Neurol 2006.
PMID: 17187377 [PubMed - as supplied by publisher]
This research combined with other research could very definitely lead us to some potential treatment modalities that already exists!---antioxidants and glutamine......It is being done by environmental medicine people! Why doesn't the VA try a sample treatment project for clinical based improvement in care for gulf war veterans? They could send a group of veterans to DR Rhea by fee basis. They could send drs to be trained by Dr Rhea and then institute a program in several VAs......These are things that DR Rhea offerred the VA back in 1990-91. Why is his offer being shuned? A number of gulf war veterans have been treated by DR Rhea or other environmental doctors. We need an email group set up for those that have tried this! Any volunteers?
A search for cellular and molecular mechanisms involved in depleted uranium (DU) toxicity.
Faculty of Pharmacy and Pharmaceutical Research Center, Shaheed Beheshti University of Medical Sciences, Tehran, Iran. j.pourahmadjaktaji@...
Addition of U(VI) (uranyl acetate) to isolated rat hepatocytes results in rapid glutathione oxidation, reactive oxygen species (ROS) formation, lipid peroxidation, decreased mitochondrial membrane potential, and lysosomal membrane rupture before hepatocyte lysis occurred. Cytotoxicity was prevented by ROS scavengers, antioxidants, and glutamine (ATP generator). Hepatocyte dichlorofluorescein oxidation was inhibited by mannitol (a hydroxyl radical scavenger) or butylated hydroxyanisole and butylated hydroxytoluene (antioxidants). Glutathione depleted hepatocytes were resistant to U(VI) toxicity and much less dichlorofluorescein oxidation occurred. Reduction of U(VI) by glutathione or cysteine in vitro was also accompanied by oxygen uptake and was inhibited by Ca(II) (a U(IV) or U(VI) reduction inhibitor). U(VI)-induced cytotoxicity and ROS formation was also inhibited by Ca(II), which suggests that U(IV) and U(IV) GSH mediate ROS formation in isolated hepatocytes. The U(VI) reductive mechanism required for toxicity has not been investigated. Cytotoxicity was also prevented by cytochrome P450 inhibitors, particularly CYP 2E1 inhibitors, but not inhibitors of DT diaphorase or glutathione reductase. This suggests that P450 reductase and reduced cytochrome P450 contributes to U(VI) reduction to U(IV). In conclusion, U(VI) cytotoxicity is associated with mitochondrial/lysosomal toxicity by the reduced biological metabolites and ROS. Copyright 2006 Wiley Periodicals, Inc.
PMID: 16841314 [PubMed - indexed for MEDLINE]
Related Links
- Biological reactive intermediates that mediate chromium (VI) toxicity. [Adv Exp Med Biol. 2001] PMID: 11764936
- A comparison of hepatocyte cytotoxic mechanisms for chromate and arsenite. [Toxicology. 2005] PMID: 15588934
- Glutathione depletion and the production of reactive oxygen species in isolated hepatocyte suspensions. [Chem Biol Interact. 2000] PMID: 10967318
- Molecular mechanisms of tirapazamine (SR 4233, Win 59075)-induced hepatocyte toxicity under low oxygen concentrations. [Br J Cancer. 1995] PMID: 7710944
- Lysosomal oxidative stress cytotoxicity induced by nitrofurantoin redox cycling in hepatocytes. [Adv Exp Med Biol. 2001] PMID: 11764951
- See all Related Articles...
BXT-51072 [antioxidant]
similar to ebselen; could this product be useful for us?
Dear members of the group
I refer to the article below, the product [BXT-51072] is developed by
OXIS International Inc . 323 Vintage Park Drive, Suite B . Foster
City, CA 94404-1136 . USA.
In the [recent] past we did have a discussion about ebselen [on this
board]: [Circ Res. 2004 Feb 20;94(3):377-
Prevention and reversal of premature endothelial cell senescence and
vasculopathy in obesity-induced diabetes by ebselen.] Prof. M. Pall
comments on this discussion was that Ebselen is a peroxynitrite
scavenger.
I need to emphasise that these suggestions /interpretations are done
by myself [as a severe patient]; I do not have any professional
medical background [just highly motivated to become better].
For that reason, a [professional] comment on these
statements/suggesti
Greetings
Gerard
Europe
BXT-51072 protects cells against peroxide damage by supplementing the
natural endogenous glutathione peroxidase levels with an exogenous
low molecular weight mimic. BXT-51072, like native GPx, catalyzes the
reduction of hydroperoxides to less toxic species using glutathione
(GSH) as the reducing agent. In the case of hydrogen peroxide (H2O2),
water is the reduction product, while organic hydroperoxides (ROOH)
are reduced to the corresponding alcohol (ROH) and water. The other
product of the reaction, oxidized glutathione (GSSG), is recycled
back to the reduced form via the enzyme NADPH-dependent glutathione
reductase.
Kinetic and tissue culture studies show that BXT-51072 acts as an
efficient glutathione peroxidase mimic to protect cells from peroxide
mediated damage and inhibits the activity of a variety of
inflammatory mediators. In fact these studies have identified BXT
51072 to be one of the more potent inhibitors of NFƒÛB mediated gene
transcription reported to date. Animal studies have demonstrated the
effectiveness of BXT-51072 in both preventative and therapeutic
models of inflammatory bowel disease.
Because of its ability to protect cells from the damaging effects of
hydrogen peroxides and other organic hydroperoxides, as well as its
ability to suppress activation of secondary inflammatory mediators,
BXT-51072 represents a potentially unique therapeutic agent for use
in a wide variety of inflammatory disease states.
BXT-51072 is initially being developed for use in the treatment of
inflammatory bowel diseases, and has already demonstrated efficacy in
a preliminary Phase 2 study ulcerative colitis patients, but is
likely to have activity in other inflammatory conditions.
This compound is the first of a class of potent catalytic
antioxidants and demonstrates a novel combination of pharmacological
actions, namely, catalytic free radical neutralising capabilities
plus down-regulation of the gene transcription which leads to the
production of a wide array of inflammatory mediators. By interacting
in this way with both primary and secondary processes in the cascade
initiated by oxidative stress, BXT-51072 holds real potential for
efficacy in a variety of inflammatory and degenerative diseases and
has already demonstrated efficacy in a Phase II clinical trial in
ulcerative colitis.
In general terms, many studies looked at exercise intolerance to try to
define what happens in the body. The researchers and clinical scientists
are developing methods to measure cardiovascular, and cardiopulmonary
health in CFS patients. This relates to oxygen consumption. Several papers
in the main session and in the poster sessions showed that CFS patients
ability to do work (bike, treadmill) is impaired if one measures how much
oxygen is used for the task. It's a mathematical computation based on
(age?) and body weight. Control groups varied. Normal, deconditioned and
those patients with primary depression were compared to CFS patients. One
interesting study showed that CFS patients will show extreme abnormalities
in a next day, second session of exercise. CFS patients do not recover in
24 hours = intolerance.
Patients understand "overdoing" and "payback," but in research it is
wonderful to see US and international scientists defining methods to show
what we experience. Over and over again, I heard...THIS is a very abnormal
finding. In addition, one study showed that both mental and physical energy
expended can cause impairment.
What to do about it? Graded exercise therapy is ill advised. If a patient
has abnormal oxygen consumption, muscles will not have enough O2. If you
push yourself, this will start a cascade of events that lead to
relapse. Yet, any kind of movement helps the body maintain some activity
tolerance and allows those chemicals recycled in muscle contraction to be
stimulated.
Along the same lines, it was hopeful to see several studies on cardiac
involvement and CFS. This would include work on viruses that seem to target
heart tissue (Martin Lerner), Inflammation and Arterial stiffness in
patients predictive of cardiovasular risk (Vance Spence), and the complex
lecture by Paul Cheney on "Diastolic Dysfunction in the Chronic Fatigue
Syndrome enhanced by Tilt-echocardiography."
Immunology/Infectious disease studies are back! One researcher new to CFS,
presented a wonderful explanation of MD training and the infectious disease
model. Jose Montoya, Stanford University School of Medicine, said that
traditional training wraps around a short course disease model. A person
gets very ill, is treated if possible, then lives or dies. Disease with an
infectious onset resulting in long term, chronic illness is not common and
is not emphasized in medical school training.
So why chronic illness with infectious onset? Scientists need to look at
gene variance and to try to find abnormalities and commonalities in CFS
patients to see the disease process. Montoya also discussed the changing
view of viruses. It was thought that one virus = one type of illness.(EBV
causes mononucleosis.) Apparently, with much more study on viral infection,
viruses in general, and the discovery of new viruses, we know that several
kinds of viruses or a combination can cause very similar illnesses. Viruses
mutate, and viruses adapt to the host. (That would be you and me.)
Genetics/Proteomics. How is the variability of the host reaction to viral
infection related to genetics? Again, investigations in this area surge
forward in all countries. Because the information is very technical and I
have no background, I cannot address this. However, the surge represents
keys unlocking doors for people with CFS.
Proteomics focuses on the structural and functional properties of proteins
and their expression. One investigation poses that a specific CFS related
proteome (like a profile) suggests a common pathophysiology for CFS, FM and
Persian Gulf War Illness. This research is a collaboration among three
academic institutions, Federal Institute of Technology, Zurich,
Switzerland, University of Michingan, Ann Arbor and Georgetown University
(PI James Baraniuk).
Chronic fatigue is not all in the mind
- 21 July 2005
- NewScientist.com news service
- Rowan Hooper
Tools
Related Articles
- The disease that never was?
- 06 November 2004
- Coughs and sneezes spread mind diseases
- 06 November 2004
- Brain not body makes athletes feel tired
- 29 July 2004
- Search New Scientist
- Contact us
Web Links
 |
AT LONG last, we are beginning to get to grips with chronic fatigue syndrome. Differences in gene expression have been found in the immune cells of people with the disease, a discovery that could lead to a blood test for the disorder and perhaps even to drugs for treating it.
The symptoms of chronic fatigue syndrome have been compared to those of a really bad hangover: extreme weakness, inability to think straight, disrupted sleep and headache. But unlike a hangover, the symptoms linger for years, devastating people's lives.
While nobody doubts CFS exists, just about every aspect of it is controversial. Some say it is the same as myalgic encephalomyelitis, or ME; others disagree. Many specialists are convinced it does have a biological basis, but pinning down physical abnormalities common to all patients has proved tough. People with CFS have often received little sympathy from doctors who dismiss it as "all in the mind".
”The study shows some aspects of chronic fatigue syndrome may be understood in molecular terms. It is not a 'made-up' illness
Now Jonathan Kerr's team, which is moving to St George's University of London, has compared levels of gene expression in the white blood cells of 25 healthy individuals with those in 25 patients diagnosed as having CFS according to strict criteria. The researchers found differences in 35 of the 9522 genes they analysed using DNA chip technology.
The few similar studies done in the past have produced conflicting results, so the team double-checked their results using a more accurate method called real-time PCR. That confirmed that 15 of the genes were up to four times as active in people with CFS, while one gene was less active. The results will appear in the Journal of Clinical Pathology next month.
Kerr is repeating the study in 1000 CFS patients and healthy controls, this time looking at 47,000 gene products. So far, the larger study backs up the earlier results, he told New Scientist.
If Kerr really has succeeded where many have failed, and identified clear physical changes in people with CFS, the lingering opinion that it is "all in the mind" could finally be laid to rest. "This exciting new work shows that some aspects of this complex illness may be understandable in molecular terms, and that CFS is not a 'made up' illness," says Russell Lane, a neurologist at Charing Cross Hospital in London.
It should also be possible to develop a blood test for CFS. The team has already discovered differences in blood proteins related to the changes in gene expression.
Kerr hopes the work might even lead to treatments. "We have shown that a significant part of the pathogenesis resides in the white blood cells and in their activity," he says. "It will open the door to development of pharmacological interventions."
Several of the genes identified by the team in CFS play important roles in mitochondria, the power factories of our cells. "The involvement of such genes does seem to fit with the fact that these patients lack energy and suffer from fatigue," Kerr says.
One of these gene products, EIF4G1, is involved in protein production in mitochondria. It is hijacked by some viruses, so cells may compensate by ramping up gene expression. "I am excited by the paper," says Basant Puri, a CFS expert at Hammersmith Hospital in London. "The group's finding of upregulation of EIF4G1 is consistent with subclinical persistent viral infection."
This fits in with the idea that CFS is sometimes triggered by viruses such as Epstein-Barr, Q fever, enteroviruses and parvovirus B19. "CFS often begins with a flu-like illness which never goes away," Kerr says.
Of the other genes whose expression varies in CFS patients, some are involved in regulating the activity of the immune system. Others play important roles in nerve cells, including a gene called NTE, which codes for an enzyme affected by organophosphates and nerve gases.
Journal reference: Journal of Clinical Pathology (vol 58, p 823, 860)
- For exclusive news and expert analysis every week subscribe to New Scientist Print Edition
- For what's in New Scientist magazine this week see contents
- Search all stories
- Contact us about this story
- Sign up for our free newsletter
E-mail this to a friend 
Printable version |
Chronic fatigue gene signs found | ||
CFS, or ME, makes people feel extremely tired, and can cause weakness, headaches, and disrupted sleep. Scientists, now based at St George's Hospital, London, found differences in the way genes are expressed in white blood cells of people with CFS/ME. But others say the New Scientist findings may not explain all cases. It is also due to be published in the Journal of Clinical Pathology. The scientists say their findings fit with the understanding that a virus, such as Epstein-Barr, may trigger CFS/ME, because that illness might alter how genes are expressed. CFS/ME often first appears as a flu-like illness, but does not then go away. 'Hijacked' The researchers compared levels of gene expression in the white blood cells of 25 healthy people and 25 who had CFS using DNA chip technology. They found differences in the behaviour of 35 of the 9,522 genes they analysed. Further genetic testing showed 15 of the genes were up to four times more active in people with CFS, while one gene was less active. Several genes the team pinpointed play important roles in mitochondria, the "powerhouse" of cells. One of the products of these genes is EIF4G1, which is involved in the protein production in mitochondria. EIF4G1 is hijacked by some viruses, so cells may compensate by increasing gene expression. The genetic differences lead to changes in how blood proteins behave which could allow the development of a blood test for CFS, the team say. Other genes are involved in regulating the immune system or playing important roles in nerve cells. The team will now carry out further research on 1,000 CFS patients and healthy people. Not 'made-up' Dr Jonathan Kerr who led the research team, which is currently in the process of moving to St George's, said: "The involvement of such genes does seem to fit with the fact that these patients lack energy and suffer from fatigue." He added the work could also potentially lead to a treatment for the condition. "We have shown that a significant part
| ||
Scottish scientists find 'key to curing ME'
A REMEDY for the debilitating condition ME, once derided as "yuppie flu", could be available in as little as a year after groundbreaking Scottish research.
A Glasgow University team has discovered a malfunction in sufferers' genes which appears to prompt their immune system to "work overtime", making patients extremely tired.
The lead scientist, Dr John Gow, said a cocktail of drugs could be used to "turn off" the genes, allowing patients to live "a fairly normal" life.
The university has already patented the genes involved as a means of diagnosing the condition, also known as chronic fatigue syndrome (CFS), quickly and cheaply.
The disease has gradually gained acceptance and in 2002, Professor Sir Liam Donaldson, the chief medical officer for England and Wales, said that "CFS/ME should be classed alongside other diseases such as multiple sclerosis and motor neurone disease".
Dr Gow, a senior lecturer in clinical neuroscience at the university, mapped all 33,000 gen
(Message over 64k, truncated.)
Offline 
Send Email