Archive for January, 2009

« Older Entries

Weight gain associated with chronic exposure to chlorpyrifos in rats.

Wednesday, January 28th, 2009

J Med Toxicol. 2007 Sep;3(3):89-93

Weight gain associated with chronic exposure to chlorpyrifos in rats.
Meggs WJ, Brewer KL.

Department of Emergency Medicine, Brody School of Medicine at East Carolina University, Greenville, NC 27858, USA. meggsw@ecu.edu

OBJECTIVE: This work exposed rats to low levels of the organophosphate insecticide chlorpyrifos and monitored for toxic effects, including weight gain. METHODS: Rats received either a subcutaneous injection of chlorpyrifos, 5 mg/kg/day, or an equal volume of vehicle daily for 4 months. Subjects were observed for 30 minutes after injection for signs of acute toxicity. Body weights were recorded at baseline, 2 months, 3 months, and 4 months. At the end of the experiment, the weights of hearts, medial lobe of the livers, peri-nephric fat pads, and gastrocnemius muscles were recorded. Effects of chlorpyrifos on adipocyte differentiation in culture were studied. Results were compared using RMANOVA. RESULTS: No signs of acute cholinergic toxicity were observed after injections in any subject. Rats in the 5 mg/kg group were significantly heavier than those in the control group by 2 months (335.7 +/- 16.7 g vs. 318.6 +/- 15.8 g; p = 0.034). This difference increased at 3 months (350.1 +/- 16.4 g vs. 322.3 +/- 21.3 g p = 0.006) and 4 months (374.4 +/- 22.2 g vs. 340.2 +/- 25.2 g p = 0.006). At 4 months, the weights of the perinephric fat pads were significantly increased in the chlorpyrifos group relative to controls (2.867 + 0.516 vs. 1.130 + 0.171, p = 0.0039). The two groups showed no weight differences between hearts, livers, and gastrocnemius muscles. Chlorpyrifos did not affect adipocyte differentiation in tissue culture. CONCLUSIONS: Chronic exposure to chlorpyrifos at 5 mg/kg/day caused an increase in rat body weight when compared to controls. This increase was in adipose tissue. Chlorpyrifos did not induce differentiation of adipocytes in culture.

PMID: 18072142 [PubMed - indexed for MEDLINE]

Tags:
Posted in Obesity | No Comments »

The relationship between serum trace element levels and clinical parameters in patients with fibromyalgia.

Wednesday, January 28th, 2009

The relationship between serum trace element levels and clinical parameters in patients with fibromyalgia.

Rheumatol Int. 2008 May 22. [Epub ahead of print]

Sendur OF, Tastaban E, Turan Y, Ulman C.

Department of Physical Medicine and Rehabilitation, Adnan Menderes University Medicine School Hospital, Aydin, Turkey.

PMID: 18496697

We examined the association between serum trace elements and clinical findings such as number of sensitive tender points, severity of fatigue and functional status in patients with fibromyalgia (FM).

Thirty-two patients diagnosed as having FM according to the ACR 1990 criteria and 32 normal healthy controls (NHC) were included in this study. The demographic data, disease duration, number of tender
points and accompanying symptoms (fatigue, sleep disorders, headache, paresthesia, irritable bowel syndrome, sicca symptoms, Raynaud’s phenomena) of the patients were noted. Visual analog scale (10 cm) was implemented to estimate daily severity of pain and fatigue. Fibromyalgia impact questionnaire was used for functional assessment. Serum selenium (mug/dL) and serum zinc (mug/dL) levels were measured by atomic absorption spectrometer. Serum magnesium (mmol/L) level was measured by the original kits of Abbott Aeroset auto-analyzer.

The mean age of patients in FM group and NHC were calculated as 42.9 (SD = 7.7) years and 41.3 (SD = 9.7) years, respectively. Serum levels of zinc (P = 0.001) and magnesium (P = 0.002) were
significantly decreased by FM groups, whereas there was no
considerable difference with selenium levels of both groups (P > 0.05). Association between serum zinc level and number of tender points (P = 0.008) and that between fatigue and magnesium level (P =
0.003) was found as meaningful.

According to the results of this study, it was asserted that serum magnesium and zinc levels may play an important role in the pathophysiology of FM.

http://www.ncbi.nlm.nih.gov/pubmed/18496697?dopt=AbstractPlus

Tags:
Posted in Fibromyalgia | No Comments »

On the relation between capsaicin sensitivity and responsiveness to CO(2): detection sensitivity and event-related brain potentials

Wednesday, January 28th, 2009

On the relation between capsaicin sensitivity and responsiveness to CO(2): detection sensitivity and event-related brain potentials

Andersson L, Nordin S, Millqvist E, Bende M.

Department of Psychology, Umeå University, 901 87, Umeå, Sweden.

Int Arch Occup Environ Health. 2008 May 14

OBJECTIVE: Sensory hyperreactivity (SHR) with predominantly airway symptoms is a subgroup of chemical intolerance to various environmental substances with pungent/odorous properties. The
hallmark of SHR is sensitivity to capsaicin inhalation, resulting in extensive coughing likely to be mediated by a C-fiber hyperreactivity of the airway sensory neurons. However, it is not clear whether
capsaicin sensitivity implies a greater sensitivity to chemosomatosensory substances in general. Therefore, the present study tested the hypothesis of an association between capsaicin cough
sensitivity and sensitivity to CO(2) with respect to detection sensitivity and electrophysiological brain response.

METHODS: A correlational study was employed to investigate the relation between capsaicin cough sensitivity and detection thresholds and chemosomatosensory event-related potentials (ERPs) for CO(2) presented in the nasal cavity in 35 persons varying in capsaicin cough sensitivity.

RESULTS: Number of coughs were found to correlate negatively with CO(2) threshold and tended to correlate negatively also with N1 and P2 latencies of the chemosomatosensory ERP for CO(2). No tendencies of correlations were found between number of coughs and latencies for olfactory and auditory ERPs, recorded for comparison, but, unexpectedly, were found between number of coughs and auditory N1 amplitude.

CONCLUSIONS: The results imply that capsaicin cough sensitivity, such as in SHR, is related to higher detection sensitivity, and tends to be related to faster cortical processing of other chemosomatosensory substances, at least of CO(2).

http://www.ncbi.nlm.nih.gov/pubmed/18478250?dopt=AbstractPlus

PMID: 18478250 [PubMed - as supplied by publisher]

Tags:
Posted in Chemical Intolerance | No Comments »

The herbicide atrazine activates endocrine gene networks via non-steroidal NR5A nuclear receptors in fish and mammalian cells.

Wednesday, January 28th, 2009

PLoS ONE. 2008 May 7;3(5):e2117.

The herbicide atrazine activates endocrine gene networks via non-steroidal NR5A nuclear receptors in fish and mammalian cells.
Suzawa M, Ingraham HA.

Department of Cellular and Molecular Pharmacology, University of California San Francisco, San Francisco, California, United States of America.

Atrazine (ATR) remains a widely used broadleaf herbicide in the United States despite the fact that this s-chlorotriazine has been linked to reproductive abnormalities in fish and amphibians. Here, using zebrafish we report that environmentally relevant ATR concentrations elevated zcyp19a1 expression encoding aromatase (2.2 microg/L), and increased the ratio of female to male fish (22 microg/L). ATR selectively increased zcyp19a1, a known gene target of the nuclear receptor SF-1 (NR5A1), whereas zcyp19a2, which is estrogen responsive, remained unchanged. Remarkably, in mammalian cells ATR functions in a cell-specific manner to upregulate SF-1 targets and other genes critical for steroid synthesis and reproduction, including Cyp19A1, StAR, Cyp11A1, hCG, FSTL3, LHss, INHalpha, alphaGSU, and 11ss-HSD2. Our data appear to eliminate the possibility that ATR directly affects SF-1 DNA- or ligand-binding. Instead, we suggest that the stimulatory effects of ATR on the NR5A receptor subfamily (SF-1, LRH-1, and zff1d) are likely mediated by receptor phosphorylation, amplification of cAMP and PI3K signaling, and possibly an increase in the cAMP-responsive cellular kinase SGK-1, which is known to be upregulated in infertile women. Taken together, we propose that this pervasive and persistent environmental chemical alters hormone networks via convergence of NR5A activity and cAMP signaling, to potentially disrupt normal endocrine development and function in lower and higher vertebrates.

PMID: 18461179 [PubMed - in process]

PMCID: PMC2362696

Tags:
Posted in Uncategorized | No Comments »

Anandamide and neutrophil function in patients with fibromyalgia.

Wednesday, January 28th, 2009

1: Psychoneuroendocrinology. 2008 Jun;33(5):676-685. Epub 2008 Apr 18. Links

Anandamide and neutrophil function in patients with fibromyalgia.
Kaufmann I, Schelling G, Eisner C, Richter HP, Krauseneck T, Vogeser M, Hauer D, Campolongo P, Chouker A, Beyer A, Thiel M.

Clinic of Anaesthesiology, Klinikum Großhadern, Ludwig-Maximilians-University, Marchioninistrasse 15, 81366 Munich, Germany.

Fibromyalgia (FM) is a common stress-related painful disorder. There is considerable evidence of neuroimmunologic alterations in FM which may be the consequence of chronic stress and pain or causally involved in the development of this disorder. The endocannabinoid system has been shown to play a pivotal role in mammalian nociception, is activated under stressful conditions and can be an important signaling pathway for immune modulation. The endocannabinoid system could therefore be involved in the complex pathophysiology of FM. We tested this hypothesis by evaluating the effects of stress hormones and the endocannabinoid anandamide on neutrophil function in patients with FM. We determined plasma levels of catecholamines, cortisol and anandamide in 22 patients with primary FM and 22 age- and sex-matched healthy controls. Neutrophil function was characterized by measuring the hydrogen peroxide (H(2)O(2)) release (oxidative stress) and the ingestion capabilities of neutrophils (microbicidal function). FM patients had significantly higher norepinephrine and anandamide plasma levels. Neutrophils of FM patients showed an elevated spontaneous H(2)O(2) production. The ability of neutrophils to adhere was negatively correlated with serum cortisol levels. Adhesion and phagocytosis capabilities of neutrophils correlated positively with anandamide plasma levels. In conclusion, patients with FM might benefit from pharmacologic manipulation of endocannabinoid signaling which should be tested in controlled studies.

PMID: 18395993 [PubMed - as supplied by publisher]

http://www.ncbi.nlm.nih.gov/pubmed/18395993?dopt=AbstractPlus

Tags:
Posted in Fibromyalgia | No Comments »

Enhanced muscle fatigue occurs in male but not female ASIC3-/- mice.

Wednesday, January 28th, 2009

Am J Physiol Regul Integr Comp Physiol. 2008 Apr;294(4):R1347-55. Epub 2008 Feb 27.Links

Enhanced muscle fatigue occurs in male but not female ASIC3-/- mice.
Burnes LA, Kolker SJ, Danielson JF, Walder RY, Sluka KA.

Graduate Program in Physical Therapy and Rehabilitation Science, Pain Research Program, Neuroscience Graduate Program, University of Iowa, Iowa City, IA 52242, USA.

Muscle fatigue is associated with a number of clinical diseases, including chronic pain conditions. Decreases in extracellular pH activates acid-sensing ion channel 3 (ASIC3), depolarizes muscle, protects against fatigue, and produces pain. We examined whether ASIC3-/- mice were more fatigable than ASIC3+/+ mice in a task-dependent manner. We developed two exercise protocols to measure exercise-induced muscle fatigue: (fatigue task 1, three 1-h runs; fatigue task 2, three 30-min runs). In fatigue task 1, male ASIC3+/+ mice muscle showed less fatigue than male ASIC3-/- mice and female ASIC3+/+ mice. No differences in fatigue were observed in fatigue task 2. We then tested whether the development of muscle fatigue was dependent on sex and modulated by testosterone. Female ASIC3+/+ mice that were ovariectomized and administered testosterone developed less muscle fatigue than female ASIC3+/+ mice and behaved similarly to male ASIC3+/+ mice. However, testosterone was unable to rescue the muscle fatigue responses in ovariectomized ASIC3-/- mice. Plasma levels of testosterone from male ASIC3-/- mice were significantly lower than in male ASIC3+/+ mice and were similar to female ASIC3+/+ mice. Muscle fiber types, measured by counting ATPase-stained whole muscle sections, were similar in calf muscles from male and female ASIC3+/+ mice. These data suggest that both ASIC3 and testosterone are necessary to protect against muscle fatigue in a task-dependent manner. Also, differences in expression of ASIC3 and the development of exercise-induced fatigue could explain the female predominance in clinical syndromes of pain that include muscle fatigue.

PMID: 18305024 [PubMed - in process]

Tags:
Posted in Uncategorized | No Comments »

A mathematical model of glutathione metabolism.

Wednesday, January 28th, 2009

Theor Biol Med Model. 2008 Apr 28;5(1):8 [Epub ahead of print] Links

A mathematical model of glutathione metabolism.
Reed MC, Thomas RL, Pavisic J, James SJ, Ulrich CM, Nijhout HF.

ABSTRACT: BACKGROUND: Glutathione (GSH) plays an important role in anti-oxidant defense and detoxification reactions. It is primarily synthesized in the liver by the transulfuration pathway and exported to provide precursors for in situ GSH synthesis by other tissues. Deficits in glutathione have been implicated in aging and a host of diseases including Alzheimeras disease, Parkinsonas disease, cardiovascular disease, cancer, Down syndrome and autism. Approach: We explore the properties of glutathione metabolism in the liver by experimenting with a mathematical model of one-carbon metabolism, the transsulfuration pathway, and glutathione synthesis, transport, and breakdown. The model is based on known properties of the enzymes and the regulation of those enzymes by oxidative stress. We explore the regulation of glutathione synthesis and its sensitivity to fluctuations in amino acid input. We use the model to simulate the metabolic profiles previously observed in Down syndrome and autism and compare the model results to clinical data. CONCLUSIONS: We show that the glutathione pools in hepatic cells and in the blood are quite insensitive to fluctuations in amino acid input and offer an explanation based on model predictions. In contrast, we show that hepatic glutathione pools are highly sensitive to the level of oxidative stress. The model shows that trisomy 21, an increase in oxidative stress, and subsequent increased transport of GSH precursors by peripheral cells can explain the metabolic profile of Down syndrome. The model also correctly simulates the metabolic profile of autism when oxidative stress is substantially increased, the adenosine concentration is raised, and the uptake of GSH precursors by peripheral tissues is increased. Finally, we discuss how individual variation arises and its consequences for one-carbon and glutathione metabolism.

PMID: 18442411 [PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/18442411?ordinalpos=22&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum

Tags:
Posted in Glutathione | No Comments »

Systemic inflammation, endothelial dysfunction, and activation in clinically healthy children exposed to air pollutants.

Wednesday, January 28th, 2009

Inhal Toxicol. 2008 Mar;20(5):499-506.

Systemic inflammation, endothelial dysfunction, and activation in clinically healthy children exposed to air pollutants.
Calderón-Garcidueñas L, Villarreal-Calderon R, Valencia-Salazar G, Henríquez-Roldán C, Gutiérrez-Castrellón P, Torres-Jardón R, Osnaya-Brizuela N, Romero L, Torres-Jardón R, Solt A, Reed W.

Instituto Nacional de Pediatría, Mexico City, Mexico.

Mexico City children are chronically exposed to significant concentrations of air pollutants and exhibit chronic respiratory-tract inflammation. Epidemiological, controlled human exposures, laboratory-based animal models, and in vitro/in vivo studies have shown that inflammatory, endothelial dysfunction, and endothelial damage mediators are upregulated upon exposure to particulate matter (PM). Endothelial dysfunction is a critical event in cardiovascular disease. The focus of this work was to investigate whether exposure to ambient air pollution including PM(2.5) produces systemic inflammation and endothelial injury in healthy children. We measured markers of endothelial activation, and inflammatory mediators in 52 children age 8.6+/-0.1 yr, residents of Mexico City (n: 28) or of Polotitlán (n: 24), a city with low levels of pollutants. Mexico City children had significant increases in inflammatory mediators and vasoconstrictors, including tumor necrosis factor (TNF)alpha, prostaglandin (PG) E2, C-reactive protein, interleukin-1beta, and endothelin-1. There was a significant anti-inflammatory response, and a downregulation of vascular adhesion molecule-1, intercellular adhesion molecule-1 and -2, and selectins sE and sL. Results from linear regression found TNF a positively associated with 24- and 48-h cumulative levels of PM(2.5), while the 7-d PM(2.5) value was negatively associated with the numbers of white blood cells in peripheral blood in highly exposed children. Systemic subclinical inflammation, increased endothelin- 1, and significant downregulation of soluble adhesion molecules are seen in Mexico City children. Children chronically exposed to fine PM above the standard could be at risk of developing cardiovascular diseases, atherosclerosis, stroke, and other systemic effects later in life.

PMID: 18368620 [PubMed - in process]

Tags:
Posted in Air Pollutants, Children | No Comments »

Gain Access to Proceedings from the First International Conference on Biocides in Plastics: from Preservation to Hygiene Control

Wednesday, January 28th, 2009

Gain Access to Proceedings from the First International Conference on Biocides in Plastics: from Preservation to Hygiene Control

DUBLIN, Ireland–(BUSINESS WIRE)–Research and Markets

( http://www.researchandmarkets.com/reports/c90744) has announced the addition of Biocides in Plastics – From Preservation to Hygiene Control to their offering.

Conference Proceedings, 2008

Proceedings from our New International Conference!

Brussels, Belgium, 26-27 February 2008

Current consumer demand for bacterial-resistant products, global concern over hospital acquired infections such as MRSA, and conditions such as the so-called “sick building syndrome” have done
much to promote the rise in biocides in plastics in recent years. As such biocides are now being increasingly used in materials such as PVC, PU, PE and WPC and in low -VOC water-based paints and coatings to prevent fungal and bacterial growth.

However impending environmental regulations both in Europe and abroad present major challenges for suppliers of biocides. The EU’s Biocidal Products Directive (BPD) and the flagship REACH chemicals policy – will force the rationalisation of many product lines, removing a large number of active ingredients from the market and requiring manufacturers to source replacement “green” actives.

It is critical now – perhaps more than ever – to formulate new biocidal blends. With this in mind Smithers Rapra developed the first international conference on Biocides in Plastics: From Preservation
to Hygiene Control.

The conference featured case studies from the likes of Arch Chemicals, PolyChem Alloy, Ciba Specialty Chemicals, Sanitised and Thor Specialities as well as a regulatory update from the US EPA. Papers provided insight into many key developments and solutions to the key issues of the biocides sector.

These include:

Test methods for plastics: antifungal and antibacterial testing
The harmonization of regulation for biocides for treated articles
How to implement an antimicrobial hygiene concept for appliances
Modelling the end-use of plastic treated articles to support label claims

For more information visit
http://www.researchandmarkets.com/reports/c90744

http://www.businesswire.com/portal/site/google/ ?
ndmViewId=news_view&newsId=20080505005093&newsLang=en

Tags:
Posted in Biocides, Plastics | No Comments »

Bone mineral density, osteoporosis, and osteoporotic fractures: a genome-wide association study

Wednesday, January 28th, 2009

The Lancet

Early Online Publication, 1 May 2008

The Lancet DOI:10.1016/S0140-6736(08)60599-1

Bone mineral density, osteoporosis, and osteoporotic fractures: a genome-wide association study

JB Richards MD a *, F Rivadeneira MD b c *, M Inouye MSc d *, TM Pastinen MD e, N Soranzo PhD d, SG Wilson PhD f g, T Andrew PhD a, M Falchi PhD a, R Gwilliam PhD d, KR Ahmadi PhD a, AM Valdes PhD a, P Arp BSc b, P Whittaker BSc d, DJ Verlaan PhD e h, M Jhamai BSc b, V Kumanduri MSc d, M Moorhouse PhD b, JB van Meurs PhD b, Prof A Hofman MD c, Prof HAP Pols MD b c, D Hart PhD a, G Zhai PhD a, BS Kato PhD a, BH Mullin BSc g, F Zhang PhD a, P Deloukas PhD d †, Prof AG Uitterlinden PhD b c † and Prof TD Spector MD a †
*†These authors contributed equally

Summary
Background
Osteoporosis is diagnosed by the measurement of bone mineral density, which is a highly heritable and multifactorial trait. We aimed to identify genetic loci that are associated with bone mineral density.

Methods
In this genome-wide association study, we identified the most promising of 314?075 single nucleotide polymorphisms (SNPs) in 2094 women in a UK study. We then tested these SNPs for replication in 6463 people from three other cohorts in western Europe. We also investigated allelic expression in lymphoblast cell lines. We tested the association between the replicated SNPs and osteoporotic fractures with data from two studies.

Findings
We identified genome-wide evidence for an association between bone mineral density and two SNPs (p<5×10-8). The SNPs were rs4355801, on chromosome 8, near to the TNFRSF11B (osteoprotegerin) gene, and rs3736228, on chromosome 11 in the LRP5 (lipoprotein-receptor-related protein) gene. A non-synonymous SNP in the LRP5 gene was associated with decreased bone mineral density (rs3736228, p=6·3×10-12 for lumbar spine and p=1·9×10-4 for femoral neck) and an increased risk of both osteoporotic fractures (odds ratio [OR] 1·3, 95% CI 1·09–1·52, p=0·002) and osteoporosis (OR 1·3, 1·08–1·63, p=0·008). Three SNPs near the TNFRSF11B gene were associated with decreased bone mineral density (top SNP, rs4355801: p=7·6×10-10 for lumbar spine and p=3·3×10-8 for femoral neck) and increased risk of osteoporosis (OR 1·2, 95% CI 1·01–1·42, p=0·038). For carriers of the risk allele at rs4355801, expression of TNFRSF11B in lymphoblast cell lines was halved (p=3·0×10-6). 1883 (22%) of 8557 people were at least heterozygous for these risk alleles, and these alleles had a cumulative association with bone mineral density (trend p=2·3×10-17). The presence of both risk alleles increased the risk of osteoporotic fractures (OR 1·3, 1·08–1·63, p=0·006) and this effect was independent of bone mineral density.

Interpretation
Two gene variants of key biological proteins increase the risk of osteoporosis and osteoporotic fracture. The combined effect of these risk alleles on fractures is similar to that of most well-replicated environmental risk factors, and they are present in more than one in five white people, suggesting a potential role in screening.

Funding
Wellcome Trust, European Commission, NWO Investments, Arthritis Research Campaign, Chronic Disease Research Foundation, Canadian Institutes of Health Research, European Society for Clinical and Economic Aspects of Osteoporosis, Genome Canada, Genome Quebéc, Canada Research Chairs, National Health and Medical Research Council of Australia, and European Union.

Affiliations

a. Department of Twin Research and Genetic Epidemiology, King’s College London, London, UK
b. Department of Internal Medicine, Erasmus MC, Rotterdam, Netherlands
c. Department of Epidemiology, Erasmus MC, Rotterdam, Netherlands
d. Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, UK
e. McGill University and Genome Québec Innovation Centre, Department of Human Genetics, McGill University, Montréal, Canada
f. School of Medicine and Pharmacology, University of Western Australia, Crawley, Western Australia
g. Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Nedlands, Western Australia
h. Hôpital Sainte-Justine, Université de Montréal, Montréal, Canada

Correspondence to: Prof T D Spector, Twin Research and Genetic Epidemiology Unit, St Thomas’ Hospital, London SE1 7EH, UK

Tags:
Posted in Osteoporosis | No Comments »

« Older Entries