Environmental and familial risk factors of Parkinsons disease: case-control study.

BACKGROUND: While the cause of Parkinson's disease (PD) remains unknown, evidence suggests certain environmental factors, such as well water drinking, herbicides, pesticides exposure and neurotoxins, may trigger the chain of oxidative reactions culminating in the death of dopaminergic neurons in substantia nigra to cause Parkinsonism. To investigate the possible impact of environmental risk factors for idiopathic PD, a case-control study was performed in the Eastern India. METHODS: During the period from January 1st, 2006 and December 10th, 2009, 175 PD patients (140 men, 35 women) and 350 non-Parkinson age-sex matched controls were included in the study. Subjects were given a structured neurological examination and completed an administered questionnaire which elicited detailed information on demographic data, pesticides, herbicides family history, occupation, dietary and smoking habits. RESULTS: The multivariate analysis revealed that family history of PD, pesticide exposure, exposure to toxins other than pesticides and herbicides, rural living and previous history of depression were associated with increased risk of PD, whereas, smoking appeared to be a protective factor. Well water drinking for at least five years, though a significant risk factor on univariate analysis (OR = 4.5, 95% CI = 2.1-9.9), could not be proved significant in multivariate analysis. Head trauma, vegetarian dietary habit, occupation involving physical exertion and exposure to domestic pets were not as significant risk factors. CONCLUSION: Results of our study support the hypothesis of multifactorial etiology of PD with environmental factors acting on a genetically susceptible host.

Arsenic contamination of groundwater and its induced health effects in Shahpur block, Bhojpur district, Bihar state, India: risk evaluation.

The objective of this study was to determine the magnitude of groundwater arsenic contamination in Shahpur block of Bhojpur district, Bihar state, India and its health effects such as dermal, neurological, obstetric effects, and cancer risk. The School of Environmental Studies (SOES) collected 4704 tube-well water samples from all 88 villages of Shahpur, which were analyzed for arsenic. We found 40.3 and 21.1 % of the tube-wells had arsenic above 10 and 50 µg/l, respectively, with maximum concentration of 1805 µg/l. The study shows that 75,000, 39,000, and 10,000 people could be exposed to arsenic-contaminated water greater than 10, 50, and 300 µg/l, respectively. Our medical team examined 1422 villagers from Shahpur and registered 161 (prevalence rate, 11.3 %) with arsenical skin lesions. Arsenical skin lesions were also observed in 29 children of 525 screened. We analyzed 579 biological samples (hair, nail, and urine) from Shahpur and found that 82, 89, and 91 % of hair, nail, and urine, respectively, had arsenic above the normal levels, indicating many people in the study area are sub-clinically affected. Arsenical neuropathy was observed in 48 % of 102 arsenicosis patients. The study also found that arsenic exposed women with severe skin lesions had adversely affected their pregnancies. The carcinogenic and non-carcinogenic risks were also estimated based on the generated data. Safe drinking water supply is urgently required to combat arsenic situation in affected villages of Shahpur.

Arsenic groundwater contamination and its health effects in Patna district (capital of Bihar) in the middle Ganga plain, India.

We investigated the extent and severity of groundwater arsenic (As) contamination in five blocks in Patna district, Bihar, India along with As in biological samples and its health effects such as dermatological, neurological and obstetric outcome in some villages. We collected 1365 hand tube-well water samples and analyzed for As by the flow injection hydride generation atomic absorption spectrometer (FI-HG-AAS). We found 61% and 44% of the tube-wells had As above 10 and 50 µg/l, respectively, with maximum concentration of 1466 µg/l. Our medical team examined 712 villagers and registered 69 (9.7%) with arsenical skin lesions. Arsenical skin lesions were also observed in 9 children of 312 screened. We analyzed 176 biological samples (hair, nail and urine). Out of these, 69 people had arsenical skin lesions and rest without skin lesions. We found 100% of the biological samples had As above the normal levels (concentrations of As in hair, nail and urine of unexposed individuals usually ranges from 20 to 200 µg/kg, 20-500 µg/kg and <100 µg/l, respectively), indicating many people are sub-clinically affected. Arsenical neuropathy was observed in 40.5% of 37 arsenicosis patients with 73.3% prevalence for predominant sensory neuropathy and 26.7% for sensor-motor. Among patients, different clinical and electrophysiological neurological features and abnormal quantitative sensory perception thresholds were also noted. The study also found that As exposed women with severe skin lesions had adversely affected their pregnancies. People including children in the affected areas are in danger. To combat As situation in affected areas, villagers urgently need (a) provision of As-safe water for drinking and cooking, (b) awareness about the danger of As toxicity, and (c) nutritious food.

Murshidabad--one of the nine groundwater arsenic-affected districts of West Bengal, India. Part I: magnitude of contamination and population at risk.

INTRODUCTION: To understand the severity of the arsenic crisis in West Bengal, India, a detailed, 3-year study was undertaken in Murshidabad, one of the nine arsenic-affected districts in West Bengal. The district covers an area of 5324 km2 with a population of 5.3 million. METHODS: Hand tubewell water samples and biologic samples were collected from Murshidabad and analyzed for arsenic by FI-HG-AAS method. Inter laboratory analysis and analyses of standards were undertaken for quality assurance. RESULTS: During our survey we analyzed 29,612 hand tubewell water samples for arsenic from both contaminated and non-contaminated areas, and 26% of the tubewells were found to have arsenic above 50 microg/L while 53.8% had arsenic above 10 microg/L. Of the 26 blocks in Murshidabad, 24 were found to have arsenic above 50 microg/L. Based on our generated data we estimated that approximately 0.2 million hand tubewells are installed in all 26 blocks of Murshidabad and 1.8 million in nine arsenic-affected districts of West Bengal. It was estimated on the basis of our data that about 2.5 million and 1.2 million people were drinking arsenic-contaminated water with concentrations above 10 and 50 microg/L levels respectively in this district. The analysis of total 3800 biologic (nail, urine, and hair) samples from arsenic-affected villages revealed that 95% of the nail and 94% of the urine samples contained arsenic above the normal levels and 75% of the hair samples were found to have arsenic above the toxic level. Thus, many villagers in the affected areas of Murshidabad might be subclinically affected. DISCUSSION AND CONCLUSION: Comparing our extrapolated data with international dose response results, we estimated how many people may suffer from arsenical skin lesions and cancer. Finally, if the exposed population is provided safe water, better nutrition, and proper awareness about the arsenic problem, lives can be saved and countless suffering of the affected population can be avoided.

Murshidabad--one of the nine groundwater arsenic-affected districts of West Bengal, India. Part II: dermatological, neurological, and obstetric findings.

INTRODUCTION: To understand the severity of related health effects of chronic arsenic exposure in West Bengal, a detailed 3-year study was carried out in Murshidabad, one of the nine arsenic-affected districts in West Bengal. METHODS: We screened 25,274 people from 139 arsenic-affected villages in Murshidabad to identify patients suffering from chronic arsenic toxicity for evidence of multisystemic features and collected biological samples such as head hair, nail, and spot urine from the patients along with the tubewell water they were consuming. RESULTS: Out of 25,274 people screened, 4813 (19%) were registered with arsenical skin lesions. A case series involving arsenical skin lesions resulting in cancer and gangrene were noted during this study. Representative histopathological pictures of skin biopsy of different types of lesions were also presented. Out of 2595 children we examined for arsenical skin lesions, 122 (4%) were registered with arsenical skin lesions, melanosis with or without keratosis. Different clinical and electrophysiological neurological features were noticed among the arsenic-affected villagers. Both the arsenic content in the drinking water and duration of exposure may be responsible in increasing the susceptibility of pregnant women to spontaneous abortions, stillbirths, preterm births, low birth weights, and neonatal deaths. Some additional multisystemic features such as weakness and lethargy, chronic respiratory problems, gastrointestinal symptoms, and anemia were also recorded in the affected population. DISCUSSION: The findings from this survey on different health effects of arsenic exposure were compared to those from previous studies carried out on arsenic-affected populations in India and Bangladesh as well as other affected countries. CONCLUSION: Multisystemic disorders, including dermal effects, neurological complications, and adverse obstetric outcomes, were observed to be associated with chronic arsenic exposure in the study population in Murshidabad, West Bengal. The magnitude of severity was related to the concentration of arsenic in water as well as duration of the exposure.

Groundwater arsenic contamination in Bangladesh-21 Years of research.

Department of Public Health Engineering (DPHE), Bangladesh first identified their groundwater arsenic contamination in 1993. But before the international arsenic conference in Dhaka in February 1998, the problem was not widely accepted. Even in the international arsenic conference in West-Bengal, India in February, 1995, representatives of international agencies in Bangladesh and Bangladesh government attended the conference but they denied the groundwater arsenic contamination in Bangladesh. School of Environmental Studies (SOES), Jadavpur University, Kolkata, India first identified arsenic patient in Bangladesh in 1992 and informed WHO, UNICEF of Bangladesh and Govt. of Bangladesh from April 1994 to August 1995. British Geological Survey (BGS) dug hand tube-wells in Bangladesh in 1980s and early 1990s but they did not test the water for arsenic. Again BGS came back to Bangladesh in 1992 to assess the quality of the water of the tube-wells they installed but they still did not test for arsenic when groundwater arsenic contamination and its health effects in West Bengal in Bengal delta was already published in WHO Bulletin in 1988. From December 1996, SOES in collaboration with Dhaka Community Hospital (DCH), Bangladesh started analyzing hand tube-wells for arsenic from all 64 districts in four geomorphologic regions of Bangladesh. So far over 54,000 tube-well water samples had been analyzed by flow injection hydride generation atomic absorption spectrometry (FI-HG-AAS). From SOES water analysis data at present we could assess status of arsenic groundwater contamination in four geo-morphological regions of Bangladesh and location of possible arsenic safe groundwater. SOES and DCH also made some preliminary work with their medical team to identify patients suffering from arsenic related diseases. SOES further analyzed few thousands biological samples (hair, nail, urine and skin scales) and foodstuffs for arsenic to know arsenic body burden and people sub-clinically affected. SOES and DCH made a few follow-up studies in some districts to know their overall situations after 9 to 18 years of their first exposure. The overall conclusion from these follow-up studies is (a) villagers are now more aware about the danger of drinking arsenic contaminated water (b) villagers are currently drinking less arsenic contaminated water (c) many villagers in affected village died of cancer (d) arsenic contaminated water is in use for agricultural irrigation and arsenic exposure from food chain could be future danger. Since at present more information is coming about health effects from low arsenic exposure, Bangladesh Government should immediately focus on their huge surface water management and reduce their permissible limit of arsenic in drinking water.

Evaluating intra-genetic variants of DJ-1 among Parkinson's disease patients of eastern India.

OBJECTIVES: Mutations in the DJ-1 gene have been described in autosomal recessive Parkinson's disease (PD) of European ancestry, Ashkenazi Jews, and Afro-Caribbean patients. Up to date, there is a lack of information about the prevalence of DJ-1 mutations among Indian PD patients. MATERIALS AND METHODS: In this study, we examined for DJ-1 mutations in Eastern Indian PD patients. Exons (no. 2-7) and intron boundaries of the DJ-1 gene were screened in 300 individuals (PD, 150; controls, 150) by direct sequencing. RESULTS: A total of six intronic variants (IVS4+30T>G, IVS4+45G>A, IVS4+46G>A, IVS4-98G>A, IVS5+31G>A and IVS5+69G>C) were detected including one novel intronic change (IVS5+69G>C). Clinical features of the two patients exhibiting IVS5+69G>C (novel change) were compared and both were found to have early onset PD. IVS4+30T>G, IVS4+45G>A, and IVS4+46G>A were found to be present equally both in the patient and control cohorts. We did not find any DJ-1 mutations in our study. CONCLUSION: Our results suggest that, unlike Parkin, pathogenic DJ-1 mutations seem to be restricted in certain populations and are unlikely to be of clinical importance in the eastern part of India.

Deletional mutations of dystrophin gene and carrier detection in eastern India.

OBJECTIVE: To determine the pattern of deletions of the dystrophin gene, the major class of mutations among the Duchenne and Becker muscular dystrophy patients of eastern India and to analyze the carrier frequency of the female members of the proband's family. METHODS: Deletional mutations occurring in patients have been characterized by multiplex polymerase chain reaction. Carrier state of mothers and sisters of probands were analyzed by either of two methods: 1) typing polymorphic short tandem repeat markers in or around the regions of deletion, by radioactive polymerase chain reaction and 2) quantitative real time amplification of the region of deletion. RESULTS: Deletions were detected in 67 (62.04%) out of 108 male patients, about 76.12% of these being localized in the central hot spot region of the gene, i.e., between exon 42 to exon 53 and 17.91% at the proximal hot spot i.e., between exon 1 to exon 20. In the present study were found 43 types of deletions, out of which 25 (58%) were new deletions, which were not described earlier among the Indian patients. Distribution pattern of deletions in different hot spot regions has been compared with that of other countries and statistical analysis reveals significant difference between countries (p<0.001). Correlation of the pattern of deletion with clinical phenotype of patients has been discussed. Interesting case of germline mosaicism and its implications in counseling has also been discussed. CONCLUSION: About half the mothers of affected probands were not carriers of the deletion, underscoring the need to use real time techniques for carrier detection.

Effect of multiple injections of beta-glucan on non-specific immune response and disease resistance in Labeo rohita fingerlings.

The purpose of this study was to determine if multiple injections of different dosages of beta-glucan derived from barley would enhance the immune response and disease resistance against infections due to opportunistic pathogens Aeromonas hydrophila and Edwardsiella tarda in Labeo rohita fingerlings. Hence, four different dosages of beta-glucan suspension in phosphate-buffered saline at the rate of 0, 5, 10, 15 mg kg(-1) body weight of fish were injected intraperitoneally to the fingerlings of Labeo rohita at two-week intervals for four times. After every two-week interval different serum biochemical, haematological and immunological parameters of fish were evaluated. At the end of immunostimulation trial of 56 days, fish were divided into four subgroups under each major treatment group for challenge through i.p injection and bath immersion with two pathogens, A. hydrophila and E. tarda. The mortality (%) and agglutinating antibody titre was recoded on 28th day post challenge. Most of the immune parameters such as leucocyte count, phagocytic ratio, phagocytic index, lysozyme activity, complement activity, serum bactericidal activity were significantly (P < 0.05) enhanced on 42 days after three i.p injections of 10 mg of beta-glucan kg(-1) body wt. Challenge study indicated least mortality in the group of fishes injected with medium dose of 10 mg of beta-glucan kg(-1) body wt. four times. Multiple injections of beta-glucan might have maintained the activation of phagocytic cells for a long period which in turn would lead to long-term protection in fishes. Thus, injections of 10 mg of beta-glucan kg(-1) body wt. for three times can be advocated to enhance the immune response of fish species under aquaculture.

Arsenic toxicity from homeopathic treatment.

UNLABELLED: Homeopathic medicine is commonly believed to be relatively harmless. However, treatment with improperly used homeopathic preparations may be dangerous. CASE REPORTS: Case 1 presented with melanosis and keratosis following short-term use of Arsenic Bromide 1-X followed by long-term use of other arsenic-containing homeopathic preparations. Case 2 developed melanotic arsenical skin lesions after taking Arsenicum Sulfuratum Flavum-1-X (Arsenic S.F. 1-X) in an effort to treat his white skin patches. Case 3 consumed Arsenic Bromide 1-X for 6 days in an effort to treat his diabetes and developed an acute gastrointestinal illness followed by leukopenia, thrombocytopenia, and diffuse dermal melanosis with patchy desquamation. Within approximately 2 weeks, he developed a toxic polyneuropathy resulting in quadriparesis. Arsenic concentrations in all three patients were significantly elevated in integument tissue samples. In all three cases, arsenic concentrations in drinking water were normal but arsenic concentrations in samples of the homeopathic medications were elevated. CONCLUSION: Arsenic used therapeutically in homeopathic medicines can cause clinical toxicity if the medications are improperly used.

Neuropathy in arsenic toxicity from groundwater arsenic contamination in West Bengal, India.

Large number of people from 9 out of 18 districts of West Bengal, India are endemically exposed to arsenic contaminated groundwater due to drinking of tubewell water containing arsenic level above World Health Organization's maximum permissible limit of 50 microg/L. From our ongoing studies on neurological involvement in patients of arsenicosis from different districts of West Bengal, we report our findings in a total of 451 patients of three districts (Murshidabad, Nadia, and Burdwan), comprising 267 males and 184 females with age ranging from 11 to 79 years. They all had arsenical skin lesions, positive biomarkers and identified source of arsenic contaminated water drinking. Peripheral neuropathy was the predominant neurological complication in these patients affecting 154 (37.3%) of 413 patients of Group 1 and 33 (86.8%) of 38 patients of Group 2. Other possible causes and alternative explanations of neuropathy were excluded. The temporal profile in most of the cases (154 of Group 1) were of chronic affection while the 33 patients of Group 2 developed both neuropathy and dermopathy subacutely. Subacutely affected Group 2 patients had much higher incidence of neuropathy. Paresthesias and pains in the distal parts of extremities were much higher in incidence in Group 2 (73.7% and 23.7% respectively) than in Group 1 (18.4% and 11.1%). Distal limb weakness or atrophy was evident in 7.3% in Group 1 and 10.5% in Group 2. Overall, sensory features were more common than motor features in patients of neuropathy and sensory neuropathy was diagnosed in 30% and 76.3% and sensorimotor in 7.3% and 10.5% respectively in Group 1 and Group 2 subjects. Nerve conduction and electromyographic studies performed in 88 cases revealed dysfunction of sensory nerve in 45% and 27% and of motor nerve in 20% and 16.7% of patients with moderate degree and mild degree of clinical neuropathies respectively. Evoked potential studies performed in 20 patients were largely normal except for two instances each of abnormal visual evoked potential and brainstem auditory evoked potential findings. Prognosis was favorable in mild and early diagnosed cases of neuropathy whereas most of the other more severe and late diagnosed cases showed slow and partial recovery or even deterioration. Outcome in neuropathic patients of arsenicosis and long term toxic neurologic effects yet unexplored and unknown remain as matters of future concern requiring close monitoring.

Arsenic groundwater contamination and sufferings of people in North 24-Parganas, one of the nine arsenic affected districts of West Bengal, India.

To understand the magnitude of the arsenic calamity in West Bengal, a detailed study spanning 7 years was made in North 24-Parganas, one of the nine arsenic affected districts. Area and population of North 24-Parganas district are 4093.82 sq. km and 7.3 million, respectively. Fourty eight thousand and thirty water samples were analyzed from hand tubewells of North 24-Parganas in use for drinking, cooking and 29.2% of the tubewells were found to have arsenic above 50 microg/L, the maximum permissible limit of World Health Organization (WHO) and 52.8% have arsenic above 10 microg/L, WHO recommended value of arsenic in drinking water. Out of the 22 blocks of North 24-Parganas, in 20 blocks arsenic has been found above the maximum permissible limit and so far in 16 blocks people have been identified as suffering from arsenical skin lesions. From the generated data, it is estimated that about 2.0 million and 1.0 million people are drinking arsenic contaminated water above 10 microg/L and 50 microg/L level, respectively in North 24-Parganas alone. So far, in our preliminary study 33,000 people have been examined at random from arsenic affected villages in North 24-Parganas and 2274 people have been registered with arsenical skin lesions. Extrapolation of the available data indicates about 0.1 million people may be suffering from arsenical skin lesions from North 24-Parganas alone. A sum of 21,000 hair, nail, and urine samples analyses from arsenic affected villages show 56%, 80%, and 87% people have arsenic in biological specimen more than normal/toxic (hair) level, respectively. Thus, many may be subclinically affected. Due to use of arsenic contaminated groundwater for agricultural irrigation, rice and vegetable are getting arsenic contaminated. Hence there is an additional arsenic burden from food chain. People from arsenic affected villages are also suffering from arsenical neuropathy. A followup study indicates that many of the victims suffering from severe arsenical skin lesions for several years are now suffering from cancer or have already died of cancer.