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Obstructive Sleep Apnea and Inflammation
McNicholas WT. Sleep Research Laboratory, St. Vincent's University Hospital, Dublin, Ireland. [email protected]

The pathogenesis of cardiovascular complications in obstructive sleep apnea syndrome (OSAS) is not fully understood but is likely multifactorial in origin. Inflammatory processes play an important role in the pathogenesis of atherosclerosis, and circulating levels of several markers of inflammation have been associated with future cardiovascular risk. These include cell adhesion molecules such as intercellular adhesion molecule-1 and selectins, cytokines such as tumour necrosis factor alpha and interleukin 6, chemokines such as interleukin 8, and C-reactive protein. There is also increasing evidence that inflammatory processes play an important role in the cardiovascular pathophysiology of OSAS and many of the inflammatory markers associated with cardiovascular risk have been reported as elevated in patients with OSAS. Furthermore, animal and cell culture studies have demonstrated preferential activation of inflammatory pathways by intermittent hypoxia, which is an integral feature of OSAS. The precise role of inflammation in the development of cardiovascular disease in OSAS requires further study, particularly the relationship with oxidative stress, metabolic dysfunction, and obesity.

PMID: 19249445 [PubMed - indexed for MEDLINE]

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Review Inflammatory cardiovascular risk markers in obstructive sleep apnoea syndrome.
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[Cardiovasc Hematol Agents Med Chem. 2009] ReviewIntermittent hypoxia and activation of inflammatory molecular pathways in OSAS.

Arch Physiol Biochem. 2008 Oct; 114(4):261-6.

[Arch Physiol Biochem. 2008]

ReviewObstructive sleep apnea and atherosclerosis.
Prog Cardiovasc Dis. 2009 Mar-Apr; 51(5):400-10.

[Prog Cardiovasc Dis. 2009] ReviewInflammation and obstructive sleep apnea syndrome pathogenesis: a working hypothesis.

Respiration. 2003 Nov-Dec; 70(6):665-71.

[Respiration. 2003] Elevated C-reactive protein levels and increased cardiovascular risk in patients with obstructive sleep apnea syndrome.

Int Heart J. 2005 Sep; 46(5):801-9.

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1: Acta Physiol Hung. 2009 Mar;96(1):37-44. Links
The alteration of glutathione peroxidase activity in rat organs after lead exposure.
Sobeková A, Holovská K, Lenártová V, Legáth J, Javorsk? P.
Department of Chemistry, Biochemistry and Biophysics, University of Veterinary Medicine, Kosice, Slovak Republic. [email protected]

The activity response of the antioxidant enzymes glutathione peroxidase (GPx), glutathione reductase (GR) and the contents of thiobarbituric reactive substances (TBARS) were investigated in rats exposed to lead. The enzyme activities were determined in the liver, kidney and heart of male and female rats which were received 100 mg and 1000 mg of lead acetate per liter water for 18 weeks. The statistical analyses indicated the differences related to the organs and to the sex of animals. Administration of lead evoked decrease of GPx activity in the kidney of both male and female rats. On the contrary, GPx activity increased in the heart of female rats, while in the male rats the higher dose of lead evoked a decrease in activity. In the kidneys of male rats and in the heart of female rats thiobarbituric acid reactive substances (TBARS), an indicators of oxidative stress, significantly increased in rats which were given the high lead dose. Most likely the observed changes could be a compensatory response to different lead accumulation in the male and female organs and also the possible distinct mechanisms in ROS elimination.

PMID: 19264041 [PubMed - indexed for MEDLINE]

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1: Toxicol Sci. 2009 Mar 6. [Epub ahead of print] Links
Pulmonary Nanoparticle Exposure Disrupts Systemic Microvascular Nitric Oxide Signaling.
Nurkiewicz TR, Porter DW, Hubbs AF, Stone S, Chen BT, Frazer DG, Boegehold MA, Castranova V.
Center for Cardiovascular and Respiratory Sciences, West Virginia University School of Medicine, Morgantown, WV, USA.

We have shown that pulmonary nanoparticle exposure impairs endothelium dependent dilation in systemic arterioles. However, the mechanism(s) through which this effect occurs is/are unclear. The purpose of this study was to identify alterations in the production of reactive species and endogenous nitric oxide (NO) after nanoparticle exposure, and determine the relative contribution of hemoproteins and oxidative enzymes in this process. Sprague Dawley rats were exposed to fine TiO(2) (primary particle diameter approximately 1 mum) and TiO(2) nanoparticles (primary particle diameter approximately 21 nm) via aerosol inhalation at depositions of 4-90 mug/rat. As in previous intravital experiments in the spinotrapezius muscle, dose-dependent arteriolar dilations were produced by intraluminal infusions of the calcium ionophore A23187. Nanoparticle exposure robustly attenuated these endothelium-dependent responses. However, this attenuation was not due to altered microvascular smooth muscle NO sensitivity because nanoparticle exposure did not alter arteriolar dilations in response to local sodium nitroprusside iontophoresis. Nanoparticle exposure significantly increased microvascular oxidative stress by approximately 60%, and also elevated nitrosative stress four-fold. These reactive stresses coincided with a decreased NO production in a particle deposition dose-dependent manner. Radical scavenging, or inhibition of either myeloperoxidase (MPO) or NADPH oxidase partially restored NO production as well as normal microvascular function. These results indicate that in conjunction with microvascular dysfunction, nanoparticle exposure also decreases NO bioavailability through at least two functionally distinct mechanisms that may mutually increase local reactive species.

PMID: 19270016 [PubMed - as supplied by publisher]

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Environ Health Perspect. 2004 Sep; 112(13):1299-306.

[Environ Health Perspect. 2004] Nanoparticle inhalation augments particle-dependent systemic microvascular dysfunction.

Part Fibre Toxicol. 2008 Feb 12; 5:1. Epub 2008 Feb 12.

[Part Fibre Toxicol. 2008] C-reactive protein inhibits endothelium-dependent nitric oxide-mediated dilation of retinal arterioles via enhanced superoxide production.

Invest Ophthalmol Vis Sci. 2008 May; 49(5):2053-60.

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Physiol Rev. 2008 Jul; 88(3):1009-86.

1: Toxicology. 2009 Apr 5;258(1):1-9. Epub 2008 Dec 31. Links
Different pattern of brain pro-/anti-oxidant activity between depleted and enriched uranium in chronically exposed rats.

Finally, DU exposure increased significantly the transporters (Divalent-Metal-Transporter1; DMT1), the storage molecule (ferritin) and the ferroxidase enzyme (ceruloplasmin), but not EU. These results illustrate that oxidative stress plays a key role in the mechanism of uranium neurotoxicity. They showed that chronic exposure to DU, but not EU, seems to induce an increase of several antioxidant agents in order to counteract the oxidative stress. Finally, these results demonstrate the importance of the double toxicity, chemical and radiological, of uranium.
Lestaevel P, Romero E, Dhieux B, Ben Soussan H, Berradi H, Dublineau I, Voisin P, Gourmelon P.

Institut de Radioprotection et de Sûreté Nucléaire, Direction de la RadioProtection de l'Homme, Service de Radiobiologie et d'Epidémiologie, Laboratoire de RadioToxicologie Expérimentale. IRSN, B.P. n degrees 17, F 92262 Fontenay-aux-Roses Cedex, France.

Uranium is not only a heavy metal but also an alpha particle emitter. The main toxicity of uranium is expected to be due to chemiotoxicity rather than to radiotoxicity. Some studies have demonstrated that uranium induced some neurological disturbances, but without clear explanations. A possible mechanism of this neurotoxicity could be the oxidative stress induced by reactive oxygen species imbalance. The aim of the present study was to determine whether a chronic ingestion of uranium induced anti-oxidative defence mechanisms in the brain of rats. Rats received depleted (DU) or 4% enriched (EU) uranyl nitrate in the drinking water at 2mg(-1)kg(-1)day(-1) for 9 months. Cerebral cortex analyses were made by measuring mRNA and protein levels and enzymatic activities. Lipid peroxidation, an oxidative stress marker, was significantly enhanced after EU exposure, but not after DU. The gene expression or activity of the main antioxidant enzymes, i.e. superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx), increased significantly after chronic exposure to DU. On the contrary, oral EU administration induced a decrease of these antioxidant enzymes. The NO-ergic pathway was almost not perturbed by DU or EU exposure. Finally, DU exposure increased significantly the transporters (Divalent-Metal-Transporter1; DMT1), the storage molecule (ferritin) and the ferroxidase enzyme (ceruloplasmin), but not EU. These results illustrate that oxidative stress plays a key role in the mechanism of uranium neurotoxicity. They showed that chronic exposure to DU, but not EU, seems to induce an increase of several antioxidant agents in order to counteract the oxidative stress. Finally, these results demonstrate the importance of the double toxicity, chemical and radiological, of uranium.

PMID: 19154773 [PubMed - in process]

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Arch Environ Contam Toxicol. 2007 Jan; 52(1):145-51. Epub 2006 Oct 9.

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Encephale. 2006 Mar-Apr; 32(2 Pt 1):244-52.

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1: Life Sci. 2009 Mar 13;84(11-12):328-36. Epub 2008 Dec 31. Links

N-acetylcysteine prevents glucose/glucose oxidase-induced oxidative stress, mitochondrial damage and apoptosis in H9c2 cells.
Kumar S, Sitasawad SL. National Centre for Cell Science, NCCS Complex, Ganeshkhind, Pune 411007, India.

AIMS: High blood glucose may auto-oxidize and generate free radicals, which are proposed to induce apoptosis in cardiac cells. The aim of the present study was to investigate the cell damage induced by glucose/glucose oxidase-dependent oxidative stress and the protective effect of N-acetylcysteine (NAC) on H9c2 cardiac muscle cells. MAIN METHODS: H9c2 cells were exposed to 33 mM glucose (G)+1.6 milliunits (mU) of glucose oxidase (GO) and termed G/GO. Cell apoptosis, generation of reactive oxygen species (ROS-super oxide anion and hydrogen peroxide) and reactive nitrogen species (RNS-peroxinitrite), and the change in mitochondrial membrane potential (DeltaPsim) was studied using flow cytometry and confocal microscopy, and cytochrome c release was measured using confocal microscopy. The expression of Bcl-2, Bax and the activation of procaspase-9 was studied by western blot. KEY FINDINGS: Exposure of H9c2 cells to G/GO resulted in a significant increase in cellular apoptosis (P<0.05) and the generation of ROS and RNS (P<0.001). Further, G/GO treatment led to a decrease in DeltaPsim, release of cytochrome c, decrease in Bcl-2, increase in Bax expression and the activation of procaspase-9. Treatment with NAC significantly decreased apoptosis (P<0.05) and reduced the levels of ROS and RNS (P<0.001). NAC was also able to normalize DeltaPsim, inhibit cytochrome c release, increase Bcl-2 and decrease Bax expression and procaspase-9 activation. SIGNIFICANCE: Our studies suggest that NAC has antioxidative and antiapoptotic activity against G/GO-induced oxidative stress through the inhibition of mitochondrial damage in H9c2 cells.

PMID: 19159629 [PubMed - in process]

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J Biol Chem. 2003 Sep 19; 278(38):36676-87. Epub 2003 Jul 16.

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1: Biochem Pharmacol. 2009 Apr 1;77(7):1291-301. Epub 2008 Dec 31. Links

The NF kappa B-mediated control of RS and JNK signaling in vitamin A-treated cells: duration of JNK-AP-1 pathway activation may determine cell death or proliferation.

Antioxidants blocked the persistent JNK-AP-1 activation, cell oxidative damage, and the decreases in cell viability induced by NFkappaB inhibition. Finally, our data point superoxide dismutase (SOD)2 as a potential antioxidant factor involved in NFkappaB protective effects against ROH-induced oxidative stress. Taken together, data presented here show that NFkappaB mediates cellular resistance to the pro-oxidant effects of vitamin A by inhibiting RS accumulation and the persistent and redox-dependent activation of JNK-AP-1 cascade.
Zanotto-Filho A, Gelain DP, Schröder R, Souza LF, Pasquali MA, Klamt F, Moreira JC.

Centro de Estudos em Estresse Oxidativo, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil. [email protected]

Nuclear factor kappa B (NFkappaB) has emerged as a crucial regulator of cell survival, playing important functions in cellular resistance to oxidants and chemotherapeutic agents. Recent studies showed that NFkappaB mediates cell survival through suppression of the accumulation of reactive species (RS) and a control of sustained activation of the Jun-N-terminal kinase (JNK) cascade. This work was undertaken in order to evaluate the role of NFkappaB in modulating the pro-oxidant effects of supplementation with vitamin A (retinol, ROH) in Sertoli cells, a major ROH physiological target. In this work, we reported that ROH treatment increases mitochondrial RS formation leading to a redox-dependent activation of NFkappaB. NFkappaB activation played a pivotal role in counteract RS accumulation in ROH-treated cells, since NFkappaB inhibition with DNA decoy oligonucleotides or pharmacological inhibitors (BAY-117082) potentiated ROH-induced RS accumulation and oxidative damage. In the presence of NFkappaB inhibition, ROH-induced oxidative stress promoted a prolonged activation of the JNK-activator protein 1 (AP-1) pathway and induced significant decreases in cell viability. Inhibition of JNK-AP-1 with decoy oligonucleotides to AP-1 or JNK inhibitor SP600125 prevented the decreases in cell viability. Antioxidants blocked the persistent JNK-AP-1 activation, cell oxidative damage, and the decreases in cell viability induced by NFkappaB inhibition. Finally, our data point superoxide dismutase (SOD)2 as a potential antioxidant factor involved in NFkappaB protective effects against ROH-induced oxidative stress. Taken together, data presented here show that NFkappaB mediates cellular resistance to the pro-oxidant effects of vitamin A by inhibiting RS accumulation and the persistent and redox-dependent activation of JNK-AP-1 cascade.

PMID: 19161988 [PubMed - indexed for MEDLINE]

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Histol Histopathol. 2006 Jan; 21(1):69-80.

[Histol Histopathol. 2006] ReviewSignal transduction during liver regeneration.

J Gastroenterol Hepatol. 1998 Sep; 13 Suppl:S93-5.

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Biol Chem. 2009 Jan 23. [Epub ahead of print] Links

Glutathione dysregulation and the etiology and progression of human diseases.
The present report highlights and integrates the growing connections between imbalances in GSH homeostasis and a multitude of human diseases.
Ballatori N, Krance SM, Notenboom S, Shi S, Tieu K, Hammond CL.
1Department of Environmental Medicine, University of Rochester School of Medicine, Rochester, NY 14642, USA.

Abstract Glutathione (GSH) plays an important role in a multitude of cellular processes, including cell differentiation, proliferation, and apoptosis, and as a result, disturbances in GSH homeostasis are implicated in the etiology and/or progression of a number of human diseases, including cancer, diseases of aging, cystic fibrosis, and cardiovascular, inflammatory, immune, metabolic, and neurodegenerative diseases. Because of GSH's pleiotropic effects on cell functions, it has been quite difficult to define the role of GSH in the onset and/or the expression of human diseases, although significant progress is being made. GSH levels, turnover rates and/or oxidation state can be compromised by inherited or aquired defects in the enzymes, transporters, signaling molecules, or transcription factors that are involved in its homeostasis, or from exposure to reactive chemicals or metabolic intermediates. GSH deficiency or a decrease in the GSH/glutathione disulfide (GSSG) ratio manifests itself largely through an increased susceptibility to oxidative stress, and the resulting damage is thought to be involved in diseases such as cancer, Parkinson's disease, and Alzheimer's disease. In addition, imbalances in GSH levels affect immune system function, and are thought to play a role in the aging process. Just as low intracellular GSH levels decrease cellular antioxidant capacity, elevated GSH levels generally increase antioxidant capacity and resistance to oxidative stress, and this is observed in many cancer cells. The higher GSH levels in some tumor cells are also typically associated with higher levels of GSH-related enzymes and transporters. Although neither the mechanism nor the implications of these changes are well defined, the high GSH content makes cancer cells chemoresistant, which is a major factor that limits drug treatment. The present report highlights and integrates the growing connections between imbalances in GSH homeostasis and a multitude of human diseases.

PMID: 19166318 [PubMed - as supplied by publisher]

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J Nutr. 2004 Mar; 134(3):489-92.

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Exp Gerontol. 2001 Sep; 36(9):1539-50.

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1: Nutr Res. 2009 Jan;29(1):70-4. Links
Dietary supplementation with a combination of alpha-lipoic acid, acetyl-L-carnitine, glycerophosphocoline, docosahexaenoic acid, and phosphatidylserine reduces oxidative damage to murine brain and improves cognitive performance.
We further demonstrate that supplementation with these agents prevented the marked cognitive decline otherwise observed in normal mice maintained on this challenge diet. These findings add to the growing body of research indicating that key dietary supplementation may delay the progression of age-related cognitive decline.

Suchy J, Chan A, Shea TB.
Center for Cellular Neurobiology and Neurodegeneration Research, Department of Biological Sciences, University of Massachusetts Lowell, Lowell, MA 01854, USA.

Alzheimer disease has a complex etiology composed of nutritional and genetic risk factors and predispositions. Moreover, genetic risk factors for cognitive decline may remain latent pending age-related decline in nutrition, suggesting the potential importance of early nutritional intervention, including preventative approaches. We hypothesized that a combination of multiple nutritional additives may be able to provide neuroprotection. We demonstrate herein that dietary supplementation with a mixture of ALA, ALCAR, GPC, DHA, and PS reduced reactive oxygen species in normal mice by 57% and prevented the increase in reactive oxygen species normally observed in mice lacking murine ApoE when maintained on a vitamin-free, iron-enriched, oxidative-challenge diet. We further demonstrate that supplementation with these agents prevented the marked cognitive decline otherwise observed in normal mice maintained on this challenge diet. These findings add to the growing body of research indicating that key dietary supplementation may delay the progression of age-related cognitive decline.

PMID: 19185780 [PubMed - indexed for MEDLINE]

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J Alzheimers Dis. 2005 Dec; 8(3):283-7.

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J Nutr Health Aging. 2004; 8(6):492-6.

[J Nutr Health Aging. 2004] Folate and vitamin E deficiency impair cognitive performance in mice subjected to oxidative stress: differential impact on normal mice and mice lacking apolipoprotein E.

Neuromolecular Med. 2003; 4(3):197-202.

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Ann N Y Acad Sci. 2002 Apr; 959:491-507.

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1: Toxicol Appl Pharmacol. 2009 Feb 21. [Epub ahead of print] Links
Role of oxidative stress in cadmium toxicity and carcinogenesis.
In chronic Cd-transformed cells, less ROS signals are detected with fluorescence probes. Acquired apoptotic tolerance renders damaged cells to proliferate with inherent oxidative DNA lesions, potentially leading to tumorigenesis.

Liu J, Qu W, Kadiiska MB.
Inorganic Carcinogenesis Section, Laboratory of Comparative Carcinogenesis, NCI at NIEHS, 111 T.W. Alexander Drive, MD F0-09, Research Triangle Park, NC 27709, USA.

Cadmium (Cd) is a toxic metal, targeting the lung, liver, kidney, and testes following acute intoxication, and causing nephrotoxicity, immunotoxicity, osteotoxicity and tumors after prolonged exposures. Reactive oxygen species (ROS) are often implicated in Cd toxicology. This minireview focused on direct evidence for the generation of free radicals in intact animals following acute Cd overload and discussed the association of ROS in chronic Cd toxicity and carcinogenesis. Cd-generated superoxide anion, hydrogen peroxide, and hydroxyl radicals in vivo have been detected by the electron spin resonance spectra, which are often accompanied by activation of redox sensitive transcription factors (e.g., NF-kappaB, AP-1 and Nrf2) and alteration of ROS-related gene expression. It is generally agreed upon that oxidative stress plays important roles in acute Cd poisoning. However, following long-term Cd exposure at environmentally-relevant low levels, direct evidence for oxidative stress is often obscure. Alterations in ROS-related gene expression during chronic exposures are also less significant compared to acute Cd poisoning. This is probably due to induced adaptation mechanisms (e.g., metallothionein and glutathione) following chronic Cd exposures, which in turn diminish Cd-induced oxidative stress. In chronic Cd-transformed cells, less ROS signals are detected with fluorescence probes. Acquired apoptotic tolerance renders damaged cells to proliferate with inherent oxidative DNA lesions, potentially leading to tumorigenesis. Thus, ROS are generated following acute Cd overload and play important roles in tissue damage. Adaptation to chronic Cd exposure reduces ROS production, but acquired Cd tolerance with aberrant gene expression plays important roles in chronic Cd toxicity and carcinogenesis.

PMID: 19236887 [PubMed - as supplied by publisher]

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Glutathione S-transferase pi localizes in mitochondria and protects against oxidative stress.
Goto S, Kawakatsu M, Izumi SI, Urata Y, Kageyama K, Ihara Y, Koji T, Kondo T.
Department of Biochemistry and Molecular Biology in Disease, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8523, Japan.

Glutathione S-transferases (GSTs) are multifunctional enzymes involved in the protection of cellular components against anti-cancer drugs or peroxidative stress. Previously we found that GST pi, an isoform of the GSTs, is transported into the nucleus. In the present study, we found that GST pi is present in mitochondria as well as in the cytosol and nucleus in mammalian cell lines. A construct comprising the 84 amino acid residues in the amino-terminal region of GST pi and green fluorescent protein was detected in the mitochondria. The mutation of arginine to alanine at positions 12, 14, 19, 71, and 75 in full-length GST pi completely abrogated the ability to distribute in the mitochondria, suggesting that arginine, a positively charged residue, is required for the mitochondrial transport of GST pi. Chemicals generating reactive oxygen species, such as rotenone and antimycin A, decreased cell viability and reduced mitochondrial membrane potential. The overexpression of GST pi diminished these changes. GST pi-targeting siRNA abolished the protective effect of GST pi on the mitochondria under oxidative stress. The findings indicate that the peptide signal is conducive to the mitochondrial localization of GST pi under steady-state conditions without alternative splicing or posttranslational modifications such as proteolysis, suggesting that GST pi protects mitochondria against oxidative stress.

PMID: 19269317 [PubMed - as supplied by publisher]

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Comparative immunopathogenesis of acute disseminated encephalomyelitis, neuromyelitis optica, and multiple sclerosis.
Wingerchuk DM, Lucchinetti CF.
Mayo Clinic College of Medicine, Scottsdale, Arizona 85259, USA. [email protected]

PURPOSE OF REVIEW: Advanced immunopathological techniques hold promise for more precise diagnosis of idiopathic demyelinating diseases of the central nervous system. We review recent progress in differentiating and understanding the disease mechanisms of acute disseminated encephalomyelitis, neuromyelitis optica, and classical multiple sclerosis. RECENT FINDINGS: Four distinct immunopathological patterns have been described in multiple sclerosis patients, potentially implicating different inflammatory, demyelinating, and apoptotic mechanisms. A specific serum biomarker, neuromyelitis optica immunoglobulin G, is strongly associated with neuromyelitis optica and identifies patients with severe optic nerve and spinal cord lesions with specific pathological features such as eosinophilic and neutrophilic inflammatory infiltrates, necrosis, vascular hyalinization, and extensive vasculocentric immunoglobulin and complement deposition. This biomarker targets the water channel aquaporin-4, which is lost in neuromyelitis optica lesions. Acute disseminated encephalomyelitis still has no validated clinical diagnostic criteria but its perivenous pathological findings distinguish it from multiple sclerosis and neuromyelitis optica. SUMMARY: The clinically heterogeneous group of idiopathic inflammatory demyelinating diseases of the central nervous system is characterized by several immunopathological patterns that suggest the involvement of diverse pathogenic effector mechanisms. Future advances in experimental pathology, immunology, molecular genetics, and neuroimaging, as well as the discovery of specific biomarkers, will more precisely define these disorders and lead to better targeted therapies.

PMID: 17495631 [PubMed - indexed for MEDLINE]

Study Links Pesticides to Birth Defects

Tue Mar 31, 7:03 pm ET
TUESDAY, March 31 (HealthDay News) -- Pesticides may increase the risk of birth defects, say researchers who found that the highest rates of birth defects in U.S. babies occur among those conceived in the spring and summer, the same time that there are increased levels of pesticides in surface water.

Researchers analyzed all 30.1 million births in the United States between 1996 and 2002. They found a strong association between higher rates of birth defects among women whose last menstrual period was in April, May, June or July and elevated levels of nitrates, atrazine and other pesticides in surface water during those same months.

The data showed a statistically significant correlation between the last menstrual period and higher rates of birth defects for half of 22 categories of birth defects, including spina bifida, cleft lip, clubfoot and Down's syndrome.

"Elevated concentrations of pesticides and other agrochemicals in surface water during April through July coincided with significantly higher risk of birth defects in live births conceived by women whose last menstrual period began in the same months," study first author Dr. Paul Winchester, professor of clinical pediatrics at the Indiana University School of Medicine, said in a school news release. "While our study didn't prove a cause and effect link, the fact that birth defects and pesticides in surface water peak during the same four months makes us suspect that the two are related," he said.

It's long been believed that these chemicals pose a threat to developing embryos, but this is the first study to make the connection between birth defects and elevated levels of pesticides at the time of conception, the authors said. The study is in the April issue of the journal Acta Paediatrica.

"Birth defects, which affect about three out of 100 newborns in the U.S., are one of the leading causes of infant death. What we are most excited about is that if our suspicions are right, and pesticides are contributing to birth defect risk, we can reverse or modify the factors that are causing these lifelong and often very serious medical problems," Winchester said.

Known risk factors for birth defects include alcohol use, smoking, diabetes, and advanced age among pregnant women. But even mothers who didn't have these risk factors had higher overall birth defect rates for babies conceived from April to July, the study found.

"These observations by Dr. Winchester are extremely important, as they raise the question for the first time regarding the potential adverse effect of these commonly used chemicals on pregnancy outcome -- the health and well-being of our children," Dr. James Lemons, a professor of pediatrics at the IU School of Medicine, said in the news release.

More information
The March of Dimes has more about birth defects.

Gulf War Illness report shows cancers ignored by US government scientists
A US Congressional report on Gulf War illness has accused US Government scientists of ignoring key data on the impact of depleted uranium on veterans' health.

12 December 2008 - Dave Cullen
This is an updated version of a story first published on ICBUW's site on Dec 12th 2008. We have now added additional detail and a full review of the report. A PDF of this is available at the end of the article

In mid November, a committee set up by the US Congress released a landmark report on Gulf War Illness (GWI), an event widely reported by the media. It was considered a landmark study, as it stated categorically that the ill effects suffered by veterans of the 1990-1991 Gulf War were real, and amounted to a distinct medical condition.

The report identified two probable causes of this illness - pyridostigmine bromide (PB) pills which were given to troops to protect them from nerve agents, and pesticides which were liberally used to protect troops from insects.
However, amidst all the fuss, some damning information on the US government's response to the use of uranium weapons was completely ignored by the media. The section on DU supported ICBUW's finding that a touchstone study on US veterans affected by DU shrapnel ignored an incidence of cancer in the group.

McDiarmid Study
Melissa McDiarmid’s Baltimore study, which looks at the long-term health of friendly fire victims, many of whom have DU fragments in their bodies, drew particular criticism. This study is frequently referred to by the UK and US governments when they seek to defend DU, and has been repeatedly attacked by campaigners.

While the DoD has indicated that at least 900 veterans were involved in incidents that could cause higher-level DU exposure, only 70 were studied in total - and only 30 in any single follow up. The crude categories used for medical problems and the lack of a control group in all but one of the studies, mean that they are of little use for drawing meaningful conclusions. It is also suggested that the studies failed to follow up significant findings, including detectable levels of uranium in the sperm of several veterans in 1997.

Cancer Cover-up?
The RAC report found that McDiarmid apparently chose to ignore two veterans with tumours in her study group. That one veteran developed Hodgkin’s lymphoma is mentioned in passing in one write-up in 1999, but omitted from subsequent reports, and the occurrence of a non-malignant bone tumour in another is not mentioned at all.

This was first exposed by US veteran and DU researcher Dan Fahey, and was mentioned in his presentation during ICBUW’s workshop at the United Nations in April 2008, but the fact that the committee confirmed it is a huge vindication. The omission is described as ‘puzzling’, and the committee questioned the study director about it, who apparently replied that: “these cases were not included because they were not believed to be the result of DU exposure.”

McDiarmid’s team maintain that none of the veterans in their cohort are suffering from DU exposure, and are in good health, at least from this point of view. Most of these V.A. studies do not have an un-exposed control group, thereby lessening their value with regard to their results and their overall applicability to other veterans. These longitudinal studies, which the Pentagon has taken seriously, have retarded research on DU and any serious health effects in humans.

Knowledge gaps
In comparison to the evidence for PB and pesticides being a possible cause of Gulf War illness, the information on other possible causes is much less clear, and DU falls into this category. The report observes that there are huge gaps in our knowledge concerning the impact of the use of uranium munitions.

Unlike oil well fires and possible nerve agent exposure, the US government has not provided reports into the areas where DU was used, and the units most likely to be affected. Although a map exists, it appears the committee was not shown it. Instead they have to fall back on the estimates by Dan Fahey that several hundred thousand veterans may have been exposed to DU.

Other knowledge gaps highlighted by the committee are that most of the models used to estimate the dangers of DU are based around the scenario of friendly fire incidents, which are not typical of the majority of exposures, and that self-reporting - the main source of information for studies which track exposure to health problems - will be even less reliable as most soldiers knew nothing about DU during deployment.

Institute of Medicine
When considering Gulf War illness overall, the RAC report criticized Gulf War and Health, a series of reports put out by the Institute of Medicine, saying that they “provided little information that is directly relevant to health conditions that affect Gulf War veterans at excess rates or their association with Gulf War exposures.” The reports had failed to determine which health conditions: “occur(ed) at excess rates and had not drawn any conclusions from animal studies." They added: “The hundreds of findings provided in the IOM reports are largely inconclusive…” RAC stated that these reports had delayed research on Gulf War illness.

This led the committee to declare that the way the series was commissioned did not fulfil Congress's legal requirements, and it recommends that the government office that commissioned them should be stripped of responsibility for future research.

Potential dangers of DU
The committee raises concerns about the potential dangers from DU exposure, citing preli

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