Chronic fatigue syndrome is accompanied by an IgM-related immune response directed against neopitopes formed by oxidative or nitrosative damage to lipids and proteins.

• Maes M,
• Mihaylova I,
• Leunis JC.

MCare4U Outpatient Clinics, Belgium.

There is now some evidence that chronic fatigue syndrome (CFS) is accompanied by signs of oxidative stress and by a decreased antioxidant status. The aim of the present study was to examine whether CFS is accompanied by an immune response to neoepitopes of a variety of modified lipids and proteins indicating damage caused by oxidative and nitrosative stress. Toward this end we examined serum antibodies to fatty acids (oleic, palmitic and myristic acid), by-products of lipid peroxidation, i.e. azelaic acid and malondialdehyde (MDA), acetylcholine, S-farnesyl-L-cysteine, and N-oxide modified amino-acids in 14 patients with CFS, 14 subjects with partial CFS and 11 normal controls. We found that the prevalences and mean values for the serum IgM levels directed against oleic, palmitic and myristic acid, MDA, azelaic acid, S-farnesyl-L-cysteine, and the N-oxide derivates, nitro-tyrosine, nitro-phenylalanine, nitro-arginine, nitro-tryptophan, and nitro-cysteinyl were significantly greater in CFS patients than in normal controls, whereas patients with partial CFS took up an intermediate position. There were significant and positive correlations between the serum IgM levels directed against fatty acids, MDA and azelaic acid and the above N-oxide-derivates and the severity of illness (as measured by the FibroFatigue scale) and symptoms, such as aches and pain, muscular tension and fatigue. The results show that CFS is characterized by an IgM-related immune response directed against disrupted lipid membrane components, by-products of lipid peroxidation, S-farnesyl-L-cysteine, and NO-modified amino-acids, which are normally not detected by the immune system but due to oxidative and nitrosative damage have become immunogenic.

PMID: 17159817 [PubMed - in process]

Erythrocyte oxidative damage in chronic fatigue syndrome.

• Richards RS,
• Wang L,
• Jelinek H.

School of Community Health, Faculty of Health Sciences, Charles Sturt University, NSW, Australia.

BACKGROUND: It has been hypothesized that a link exists between erythrocyte metabolism (particularly redox metabolism) and erythrocyte shape and that both are related to erythrocyte deformability. The aim of this research is to confirm the results of earlier studies and to investigate a correlation between erythrocyte morphology and erythrocyte oxidative damage in chronic fatigue syndrome (CFS). METHODS: Reduced glutathione (GSH), malondialdehyde (MDA), methemoglobin (metHb) and 2,3-diphosphoglyceric acid (2,3-DPG) were measured in 31 patients suffering from CFS and 41 healthy control subjects. Scanning electron microscopic studies of the erythrocytes from both groups were also carried out. RESULTS: There was evidence of oxidative damage in CFS with statistically significant increases in 2,3-DPG (p <0.05), metHb (p <0.005) and MDA (p <0.01). The CFS patients in this study also had significantly more stomatocytes in their blood than the normal subjects (p <0.005). CONCLUSIONS: There is a strong likelihood that the increase in erythrocyte antioxidant activity is associated with the presence of stomatocytes. The results of this study provide further evidence for the role of free radicals in the pathogenesis of CFS and a link between erythrocyte metabolism and erythrocyte shape.

PMID: 17174731 [PubMed - in process]

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Effects of sarin and cyclosarin exposure during the 1991 Gulf War on neurobehavioral functioning in US army veterans.

• Proctor SP,
• Heaton KJ,
• Heeren T,
• White RF.

Boston Environmental Hazards Center, VA Boston Healthcare System, Boston, MA, United States; Boston University School of Public Health (Environmental Health), Boston, MA, United States; National Center for PTSD, VA Boston Healthcare System, Boston, MA, United States; Military Performance Division, US Army Research Institute of Environmental Medicine, Natick, MA, United States.

BACKGROUND: During the Gulf War (GW), in early March 1991, a munitions dump at Khamisiyah, Iraq, was destroyed. Later, in 1996, the dump was found to have contained the organophosphate chemical warfare agents, sarin and cyclosarin. METHODS: Data collected in a study conducted between 1994 and 1996, before the Khamisiyah incident was publicly disclosed, were used to examine neurobehavioral task performances of GW veterans (n=140) categorized as having received high, moderate, or low-to-no exposure dose levels to sarin and cyclosarin at Khamisiyah, Iraq. Exposure levels were based on modeled estimates of the exposure plume and on troop location information at the time of the Khamisiyah event. Based on recent findings observed in follow-up studies of persons exposed to sarin during the 1995 terrorist attacks in Japan, we hypothesized that exposure to sarin and cyclosarin would be associated with poorer performances on objective neurobehavioral tasks in specific functional domains (particularly in visuospatial abilities and psychomotor functioning) in a dose-dependent manner. RESULTS: Sarin and cyclosarin exposure was significantly associated with less proficient neurobehavioral functioning on tasks involving fine psychomotor dexterity and visuospatial abilities 4-5 years after exposure. CONCLUSIONS: Findings suggest a dose-response association between low-level exposure to sarin and cyclosarin and specific functional central nervous system effects 4-5 years after exposure.

PMID: 16982099 [PubMed - as supplied by publisher]

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The next study comes out of Wright State of OHIO.

It is an important article for any of you gulf war veterans that have cardiac type symptoms!

Results show that a dose of sarin which had no peripheral cholinergic effects caused changes in autonomic modulation, a short-term enhancement followed by a delayed impairment in heart rate variability

Again this make me reflect back to what Dr Bill Baumzweiger demonstrated by just checking pulse differences re sitting vs standing vs after 5 minutes of exercise.  Also may answer the veterans that experienced the sudden palpitations.  Re increased heart rate that occurred enough to notice and make the veteran sit down to let it pass.

1: Exp Neurol. 2007 Jan;203(1):110-5. Epub 2006 Sep 25.  Links

Sarin produces delayed cardiac and central autonomic changes.

• Morris M,
• Key MP,
• Farah V.

Department of Pharmacology and Toxicology, Boonshoft School of Medicine, Wright State University, 3640 Colonel Glenn Highway, Dayton, OH 45435, USA.

The aim was to evaluate the acute and delayed effects of low dose sarin exposure on cardiac autonomic and brainstem catecholaminergic function in mice. The rationale was to expand our knowledge of the cardiovascular effects of this neurotoxic, acetylcholinesterase (AChE) inhibitor. C57BL/6 male mice with telemetric arterial catheters were injected with saline or sarin (8 mug/kg, 0.05x LD(50); sc, two injections) with blood pressure (BP) measurements made at 1 and 10 weeks after sarin exposure. BP and pulse interval variability (PI) and low and high frequency spectral oscillations were measured using autoregressive spectral analysis. In situ hybridization (ISH) was used to quantify tyrosine hydroxylase (TH) mRNA expression in brainstem cardiovascular centers. Sarin had no effect on blood AChE activity, heart rate (HR) or BP. There was a biphasic response in PI variance, an early increase (+140%) and a delayed decrease (-62%) at more than 2 months after sarin exposure. There were no changes in BP variance. Assuming that increased PI variance is a positive outcome, the short-term response to sarin should be protective. This is opposite for the delayed decrease in PI variance which is associated with adverse cardiovascular effects. There was an increase in TH mRNA in both locus coeruleus (0.18+/-0.05 vs. 1.4+/-0.2 muCi/g; control vs. sarin) and dorsal vagal complex (0.09+/-0.06 vs. 1.17+/-0.03 muCi/g; control vs. sarin). Results show that a dose of sarin which had no peripheral cholinergic effects caused changes in autonomic modulation, a short-term enhancement followed by a delayed impairment in heart rate variability. Sarin-induced cardiac effects suggest a controversial aspect to the use of pharmacological agents which target AChE for management of cardiovascular risk.

PMID: 16996499 [PubMed - in process]

___________________________________________________________________

The next paper originates from Japan!  It relates to the sarin sub way exposures.

They used T1-weighted and diffusion tensor magnetic resonance imaging (DTI) ---My question does the VA have this type diagnostic method readily available?  At which VA centers?

How does T1-weighted and diffusion tensor magnetic resonance imaging (DTI)

compare to the MRI-RS that Dr Hailey does?????

changes were found in in the insular cortex and neighboring white matter, as well as in the hippocampus in the victims.

How long will it take to add this as a standard diagnostic tool at the VA hospitals across the nation?

Ann Neurol. 2006 Dec 22; [Epub ahead of print]  Links

Human brain structural change related to acute single exposure to sarin.

• Yamasue H,
• Abe O,
• Kasai K,
• Suga M,
• Iwanami A,
• Yamada H,
• Tochigi M,
• Ohtani T,
• Rogers MA,
• Sasaki T,
• Aoki S,
• Kato T,
• Kato N.

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]

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Below is a list of other research studies that I found of interest....So I invite vets to click on the studies and then ask questions.....Yes there is a lot to digest.

I am pausing here because I need to hear number one from the VA or DRs answers to questions I have asked above.

I need to also ask the veterans for feed back comments----does it help anyone that I am doing these comments and reviews?

I could probably use a bit of help to translate the findings into useful information for the gulf war veterans that are not medical.

I truly believe we are making headway.  But the research findings must be translated into something that is applied by DRs, nurses, adjudicators to help the gulf war veterans directly!

WE must see the implementing of new diagnostic testing in the VA hospitals!

What is the timetable to see changes occur?

Email me by hitting reply to this message

Sincerely,

Denise Nichols