The influence of organophosphate and carbamate on sperm chromatin and reproductive hormones among pesticide sprayers.

This study is aimed at evaluating the association between occupational exposure to organophosphate (OP) and carbamate (CB) pesticides and semen quality as well as levels of reproductive and thyroid hormones of pesticide sprayers in Malihabad, Lucknow, Uttar Pradesh, India. Thirty-five healthy men (unexposed group) and 64 male pesticide sprayers (exposed group) were recruited for clinical evaluation of fertility status. Fresh semen samples were evaluated for sperm quality and analyzed for DNA fragmentation index (DFI) by flow cytometry. Pesticide exposure was assessed by measuring erythrocyte acetylcholinesterase and plasma butyrylcholinesterase (BuChE) with a Test-mate ChE field kit. Serum levels of total testosterone (Tt), prolactin (PRL), follicle-stimulating hormone (FSH), luteinizing hormone (LH), thyroid-stimulating hormone (TSH), and free thyroxine (FT4) were analyzed using enzyme immunoassay kits. Evidence of pesticide exposure was found in 88.5% of sprayers and significant increments were observed in sperm DFI with significant decrease in some semen parameters. DFI was negatively correlated with BuChE, sperm concentration, morphology, and vitality in these pesticide sprayers. The levels of Tt, PRL, FT4, and TSH appeared to be normal; however, there was a tendency for increased LH and FSH levels in exposed workers. The results confirm the potential impact of chronic occupational exposure to OP and CB pesticides on male reproductive function, which may cause damage to sperm chromatin, decrease semen quality, and produce alterations in reproductive hormones, leading to adverse reproductive health outcomes.

Conformational Dynamics of o-Fluoro-Substituted Z-Azobenzene.

A conformational analysis of o-fluoro Z-azobenzene reveals a slight preference for aromatic C-F/π interaction. Density functional theory (DFT) indicates that the conformation with a C-F/π interaction is preferred by approximately 0.3-0.5 kcal/mol. Ground-state conformations were corroborated with X-ray crystallography. (Z)-Azobenzene (Z-AB) with at least one o-fluoro per ring displays (19)F-(19)F through-space (TS) coupling. 2D J-resolved NMR was used to distinguish through-bond from TS coupling ((TS)JFF). (TS)JFF decreases as the temperature is lowered and the multiplets coalesce into broad singlets. We hypothesize that the coalescence temperature (Tc) corresponds to the barrier for phenyl rotation. The experimentally determined barrier of 8-10 kcal/mol has been qualitatively verified by DFT where transition states with a bisected geometry were identified with zero-point energies of 6-9 kcal/mol relative to ground state. These values are significantly higher that values estimated from previous theoretical studies but lie within a reasonable range for phenyl rotation in hydrocarbon systems.

Caput medusae in alcoholic liver disease.

Caput medusae and palmar erythema are cardinal signs in cirrhosis of liver with portal hypertension. Palmar erythema is described more often as a marker for alcoholic etiology of chronic liver disease. The peripheral stigmata of chronic liver disease are not routinely seen now a days due to early diagnosis and better therapy. We recently encountered an interesting patient of alcoholic liver disease with two classical signs of the disease and report the same for this unusual presentation.

A study of neurologic symptoms on exposure to organophosphate pesticides in the children of agricultural workers.

Pesticides are used extensively throughout the world in agriculture and in pest control as well as for community health purposes. Organophosphate (OP) pesticide self-poisoning is an important clinical problem in rural regions of the developing world that kills an estimated 200,000 people every year. Unintentional poisoning kills far fewer people but is an apparent problem in places where highly toxic OP pesticides are available. Neurologic dysfunction is the best documented health effect of pesticide exposure. High-level exposure has both acute and long-term neurologic signs and symptoms, and adverse effects have been reported in most type of pesticides, including organophosphate (OP), carbamate, organochlorine, and pyrethroid insecticides, herbicides, fungicides, and fumigants. Acute OP pesticide exposure can involve in wide range of both central and peripheral neurologic symptoms. Increased neurologic symptom prevalence may provide early evidence of neurologic dysfunctions, before clinically measurable signs are evident.In this study, we analyzed the cross-sectional data on neurologic signs and symptoms from 225 rural children, both males (n = 132) and females (n = 93) who were occupationally and paraoccupationally exposed to methyl OPs (dichlorvos, fenthion, malathion, methyl parathion) and ethyl OPs (chlorpyrifos, diazinon, ethyl parathion) as they belonged to agricultural families handling, mixing, and spraying the OP pesticides. The children completed a specially designed questionnaire (Q16) on neurologic symptoms associated with pesticide exposure with their parental help. A suitable reference group consisting of rural children (n = 50) never involved in pesticide handling (neither outdoor nor indoor) belonging to similar socioeconomic strata included in the study to compare the prevalence of various neurologic symptoms between the two groups.Among all the neurologic self-reported symptoms, headache, watering in eyes, and burning sensation in eye/face were the most important clinical manifestations attributed to OP pesticide exposure. These symptoms could probably be the consequence of chronic effects of most pesticides on the central nervous system. The muscarinic symptoms reported the maximum prevalence of salivation (18.22%), whereas lacrimation was observed in 17.33% cases, followed by diarrhea in 9.33% cases. The nicotinic clinical manifestations of acute OP poisoning revealed excessive sweating in 13.78% cases and tremors in 9.3% cases followed by mydriasis in 8.4% exposed children. The characteristic cholinergic symptoms, such as insomnia, headache, muscle cramps, weakness, and anorexia were also reported by both male and female exposed children. The high frequency of neurologic symptoms observed in the study may be due to parasympathetic hyperactivity due to the accumulated ACh resulting from AChE inhibition.

A study on oxidative stress and antioxidant status of agricultural workers exposed to organophosphorus insecticides during spraying.

Oxidative stress status and Acetylcholinesterase (AChE) activity were studied in blood samples obtained from 61 agricultural workers engaged in spraying organophosphorus (OP) insecticides in the mango plantation, with a minimum work history of one year, in the age range of 12-55 years. Controls were age-matched, unexposed workers, who never had any exposure to OP pesticides. They were evaluated for oxidative stress markers MDA (end product of lipid peroxidation), reduced glutathione (GSH), and Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) levels in blood. The results showed a marked inhibition of the AChE and BChE activities in the sprayers as compared to the controls. The malondialdehyde(MDA), the last product of lipid peroxidation was found to be increased significantly in sprayers(p<0.05), while depletion in the concentration of antioxidant glutathione(GSH) was also observed in the sprayers but the difference was statistically not significant. It was concluded on the basis of biochemical analysis that pesticides sprayers are exposed to more oxidative stress as evidenced by the changes in antioxidant status. The measurement of the AChE and BChE activities in agricultural workers who spray OPs could be a good biomonitoring factor and is recommended to be performed on a regular basis.

Monitoring of plasma butyrylcholinesterase activity and hematological parameters in pesticide sprayers.

To evaluate the health impact of spraying organophosphorus insecticides (OPs), 34 male sprayers in the mango belt of Malihabad, a small town located 27 km from Lucknow in North India was selected. Plasma butyryl cholinesterase (PBChE) and complete blood count were assessed among sprayers after spraying pesticides and the findings obtained were compared with those determined in a reference group (n = 18). The most common symptoms observed were burning sensation in the eyes (8.82%), itching/skin irritation (23.52%) and chest symptoms (32.35%) in the exposed workers. Plasma butyrylcholinesterase (PBChE) was significantly decreased in workers. The results indicated significant decrease in the mean value of hemoglobin, hematocrit and platelets count; however, significantly higher count of leukocytes was also observed in the exposed group (sprayers) compared to that observed in the control group (P < 0.05). Monitoring of PBChE in pesticide sprayers could be useful to predict and prevent health hazards of OPs.

Occupational cancers in leather tanning industries: A short review.

Work in leather tanning involves exposure to a wide range of chemicals. Some of these are carcinogens or suspected carcinogens. Increased risks for a number of cancers have been reported among the tannery workers. In the present review, a detailed account of lung cancer, testicular cancer, soft tissue sarcoma, pancreatic cancer, bladder cancer among tannery workers is mentioned.

Environmental health survey in asbestos cement sheets manufacturing industry.

About 673 small-scale asbestos mining and milling facilities and 33 large - scale asbestos manufacturing plants, (17 asbestos-cement product manufacturing plants and 16 other than asbestos-cement product plants) are situated in India. The present study reveals the exposure of commercial asbestos (chrysotile) in the occupational as well as ambient air environment of the asbestos-cement (AC) sheets industry using membrane filter method of Bureau of Indian Standards (BIS). The fibre concentrations in 15 samples collected in the occupational environment at ingredient feeding site, sheet-producing site, fibre godown were 0.079, 0.057 and 0.078 f/cc, respectively and in five samples from surrounding ambient air at factory gate resulted fibre concentration of 0.071 f/cc. All the samples have shown fibre concentration lower than the threshold limit values (TLVs) prescribed by BIS. Morphological analysis of samples, further under phase contrast and polarized microscopy indicates the presence of chrysotile asbestos, which acts as carcinogen as well as co-carcinogen. A clinical examination of exposed subjects reveals that there was no case of clubbing, crepitation, ronchi and dyspnea on exertion; however, obstruction and restriction were 10.9 per cent and 25 per cent in exposed subjects, respectively while in control there were 12 per cent and 28 per cent, respectively. The study revealed that chrysotile asbestos is emitted in the occupational as well as ambient environment that may cause adverse health impact.

Respiratory effects due to occupational exposure to formaldehyde: Systematic review with meta-analysis.

Subjects exposed to organic solvents frequently complain of respiratory symptoms. Epidemiological studies conducted in these exposed subjects with special reference to respiratory effects are very few and that too are on very small number of subjects. This paper critically reviews most of the epidemiological studies in formaldehyde induced respiratory effects and combines them through meta analysis to get global precise estimates of the respiratory risks.A computerized bibliographic search revealed 16 epidemiological studies out of which 12 studies were considered for meta analysis. The symptoms of upper respiratory tract were more prevalent as the combined odds of exposed was 5.04 compared to controls. The pooled odds ratio for acute lower respiratory symptoms ranged between 1.85 and 2.91. The mean fall of FVC, FEV1 and FEV1/FVC was only 3.4%, 3.6% and 0.6% respectively, which was not statistically or physiologically considered significant.

Biomonitoring of organochlorines, glutathione, lipid peroxidation and cholinesterase activity among pesticide sprayers in mango orchards.

BACKGROUND: Pesticide sprayers in mango orchards of Malihabad, Lucknow (India) are generally exposed to organophosphate (OP) and pyrethroid pesticides. We determined the pesticide exposure levels along with their biochemical and clinical effects in 31 sprayers, compared with 18 controls. METHODS: Assay of acetyl and butyrylcholinesterases (AChE, BChE respectively) as an indirect measurement of OP exposure and levels of malondialdehyde (MDA) and glutathione (GSH) were estimated in blood samples to determine their impact on redox potential. Organochlorines were estimated by GLC-ECD. RESULTS: Significantly inhibited AChE, BChE activities and higher MDA level were found among sprayers compared to controls (p<0.05). Mean of total organochlorines were surprisingly higher (97.65+/-13.38 ppb) in sprayers than in those of controls (20.42+/-3.56 ppb) (p<0.05). Respiratory morbidity (32.4%), ocular problems (8.8%), gastrointestinal (17.6%) and skin problems (23.5%) were found in sprayers. There was significant correlation between AChE and GSH (r=0.29, p<0.05) and AChE with MDA (r=-0.34, p<0.05). CONCLUSION: Results indicated the significantly enhanced lipid peroxidation in sprayers correlated with cholinesterases inhibition. A small sample size limits the significance of this study. However, it paves the way for a larger Indian study with extended practical significance.

Possible mechanism of pesticide toxicity-related oxidative stress leading to airway narrowing.

The study was conducted to assess the magnitude of oxidative stress and lung function abnormalities in 34 male pesticide sprayers on exposure to pesticides in mango plantations. Biochemical studies on blood antioxidant enzymes revealed an unchanged glutathione level and increased level of malondialdehyde (P < 0.001), which indicates that pesticide sprayers may have suffered from oxidative stress. Decreased acetyl-cholinesterase levels (P < 0.001) in sprayers compared to the controls suggest inhibition of cholinesterase activity. The present study shows that pesticide toxicity might lead to oxidative stress and airway narrowing resulting in decreased peak expiratory flow rate.

Working conditions and health among employees at information technology--enabled services: a review of current evidence.

Workers in information technology (IT)-enabled services like business process outsourcing and call centers working with visual display units are reported to have various health and psycho-social disorders. Evidence from previously published studies in peer- reviewed journals and internet sources were examined to explore health disorders and psycho-social problems among personnel employed in IT-based services, for a systematic review on the topic. In addition, authors executed a questionnaire- based pilot study. The available literature and the pilot study, both suggest health disorders and psychosocial problems among workers of business process outsourcing. The details are discussed in the review.

An environmental profile of brick kilns in Lucknow.

Twenty two kilns in Lucknow were studied to identify the environmental hazards posed by the brick kilns and to quantify the environmental degradation which could be attributed to this industry. Study variables comprised SPM and RSPM levels, metal concentrations and total silica content in soil, temperature, humidity and noise levels in the work environment. Information's about the nature and type of kiln, fuel and water sources was also collected. 18.18 per cent of the kilns had moving steel chimneys with less than prescribed height. Approximately 1.89 + 0.87 acre of fertile agricultural land was used for manufacturing of clay brick per kiln, resulting in land degradation decrease in herb density and nutrient disorders in plants/trees in immediate vicinity. SPM level (93.3 mg/m3) was found to be much higher than the prescribed limit. The workers engaged in these kilns were at risk from dust and heat related diseases.

Identification of novel alpha-glucosidase inhibitors by screening libraries based on N- [4-(benzyloxy) benzoyl] alanine derivatives.

A library of 72 compounds related to N- [4-(benzyloxy) benzoyl]alanine (I) was synthesized, prepared and screened for alpha-glucosidase inhibitory activity. Four compounds showed potent inhibition, six compounds moderate inhibition, and 16 were weak inhibitors. One compound, N- [4-(benzyloxy) benzoyl] serine, was found to be a potent inhibitor of alpha-glucosidase with 100% inhibition at 1 micro M. This inhibitor was at least five times more potent than the lead compound I.

Combinatorial synthesis and biological evaluation of isoxazole-based libraries as antithrombotic agents.

The 3-substituted phenyl-5-isoxazolecarboxaldehydes have been identified as activated aldehydes for the generation of isoxazole-based combinatorial libraries on solid phase through automation. Three highly functionalized isoxazole-based libraries comprising of 32, 96 and 45 compounds each have been synthesized in parallel format using Baylis Hillman reaction, Michael addition, reductive amination and alkylation reactions. With an objective of lead generation all the three libraries were evaluated for their antithrombin activity in vivo.

Identification of enzyme inhibitors using combinatorial libraries.

Potent enzyme inhibitors have long been recognized as powerful tools for assessing the physiological roles of enzymes and have led to the therapeutic drugs able to modulate their activities in vivo. However, to be valuable tools such inhibitors should be selective so that they do not interfere with other members of the particular enzyme family. Combinatorial chemistry has proven to be a novel approach for the identification of molecules with a desired selectivity profile from the libraries of several million compounds. In recent years it has been extensively used in conjunction with computational methods for the development of potent inhibitors of therapeutically interesting targets. This review describes the various structurally diverse enzyme inhibitors identified by screening combinatorial libraries of peptides and small organic molecules.

Lipid extraction and transport of hydrophilic solutes through porcine epidermis.

The purpose of this study was to investigate the effect of delipidization of the stratum corneum (SC) on the in vitro percutaneous absorption of hydrophilic solutes (i.e. water, urea, and inulin). Fourier transform infrared (FT-IR) spectroscopy was employed to study the extent of delipidization of porcine SC due to chloroform:methanol (2:1) (C:M (2:1)) treatments for various time periods. In vitro percutaneous absorption of [3H] water, [14C] urea, and [3H] inulin were studied through C:M (2:1) treated epidermis in Franz diffusion cells. There was a greater decrease in peak areas of the asymmetric and symmetric C-H stretching absorbances (i.e. increase in lipid extraction) with increasing exposure times of the SC with C:M (2:1). After 40-min treatment, asymmetric and symmetric C-H stretching peak area showed a decrease of 75.9 and 89.9%, respectively. The permeability coefficient of water, urea, and inulin increased with increasing lipid extraction. Enhancement in the permeability coefficient, through 40 min C:M (2:1) treated epidermis in comparison to the control, for water, urea, and inulin was 48.72, 215.65, and 3.90, respectively. Log (permeability coefficient) and log (mol. wt.) for test solutes and leuprolide acetate were found to be inversely related (R(2)=0.9974). In conclusion, this study implies that penetration enhancers that are safe and extract the SC lipids can be selected in order to enhance the percutaneous absorption of polar solutes through the skin.

Identification of inhibitors of DNA topoisomerase II from a synthetic library of glycoconjugates.

A library of 24 glycoconjugates related to glycosylated beta-amino acid derivative (I) was been prepared and screened against DNA topoisomerase-II of the filarial parasite S. cervi. Among these, compound 6 was found to be a potent inhibitor of DNA topoisomerase-II with 95% inhibition at 1.09 microM. Furthermore, compound 6 was at least three times more potent than the lead compound, glycosylated beta-amino acid derivative I.

Lipid extraction and iontophoretic transport of leuprolide acetate through porcine epidermis.

The purpose of this study was to explore the effect of lipid extraction by the simple alkyl acetates of increasing carbon chain lengths (e.g. methyl, ethyl, propyl, butyl, pentyl, hexyl, and octyl acetates) and iontophoresis on the in-vitro transport of leuprolide acetate through porcine epidermis. The extent of lipid extraction from the stratum corneum (SC) by alkyl acetates was studied by Fourier transform infrared (FT-IR) spectroscopy. Ethyl, propyl, pentyl, hexyl, and octyl acetates significantly increased (P < 0.05) the permeability of leuprolide acetate through the epidermis in comparison to the control (epidermis without alkyl acetate treatment). Iontophoresis further increased (P < 0.05) the permeability of leuprolide acetate for all the alkyl acetates studied, when compared to their corresponding passive permeability. Ethyl acetate produced the maximum passive (13.47 microg/cm(2)/h) and iontophoretic (89.79 microg/cm(2)/h) flux among all the alkyl acetates studied. The SC treated with alkyl acetates showed a decrease in peak heights and areas of asymmetric and symmetric C--H stretching absorbances in comparison to untreated SC. A greater percentage decrease in peak heights and areas was obtained by ethyl acetate. Chloroform:methanol(2:1) [C:M(2:1)] was used as a positive control for lipid extraction. Our findings provide evidence that alkyl acetates cause lipid extraction, which leads to an enhancement in the passive and iontophoretic permeability of leuprolide acetate.