Association of Arsenic Exposure With Cardiac Geometry and Left Ventricular Function in Young Adults.

BACKGROUND: Arsenic exposure has been related to numerous adverse cardiovascular outcomes. The aim of this study was to investigate the cross-sectional and prospective association between arsenic exposure with echocardiographic measures of left ventricular (LV) geometry and functioning. METHODS: A total of 1337 young adult participants free of diabetes mellitus and cardiovascular disease were recruited from the SHFS (Strong Heart Family Study). The sum of inorganic and methylated arsenic concentrations in urine (ΣAs) at baseline was used as a biomarker of arsenic exposure. LV geometry and functioning were assessed using transthoracic echocardiography at baseline and follow-up. RESULTS: Mean follow-up was 5.6 years, and median (interquartile range) of ΣAs was 4.2 (2.8-6.9) µg/g creatinine. Increased arsenic exposure was associated with prevalent LV hypertrophy, with an odds ratio (95% CI) per a 2-fold increase in ΣAs of 1.47 (1.05-2.08) in all participants and of 1.58 (1.04-2.41) among prehypertensive or hypertensive individuals. Measures of LV geometry, including LV mass index, left atrial systolic diameter, interventricular septum, and LV posterior wall thickness, were positively and significantly related to arsenic exposure. Among measures of LV functioning, stroke volume, and ejection fraction were associated with arsenic exposure. CONCLUSIONS: Arsenic exposure was related to an increase in LV wall thickness and LV hypertrophy in young American Indians with a low burden of cardiovascular risk factors. The relationship was stronger in participants with prehypertension or hypertension, suggesting that potential cardiotoxic effects of arsenic might be more pronounced in individuals already undergoing cardiovascular adaptive mechanisms following elevated systemic blood pressure.

Poisoned blood, ghaa, and the infected body: lay understandings of arsenicosis in rural Bangladesh.

This article draws on ethnographic data from rural Bangladesh to examine how community members affected by arsenicosis understand, explain, and experience this deadly illness. Biomedically, arsenicosis has been described as a disease caused by drinking arsenic-contaminated water, and it is manifested through physiological complications such as symmetric hyperkeratosis of the palms and soles, cancer of the skin, kidney and lungs, and diseases of the blood vessels. This article goes beyond such biomedical discourse and illustrates how arsenicosis has been vernacularized as ghaa in practice. It focuses on lay world views, logic, local knowledge systems, and sociocultural factors that shape popular understandings of the disease. This article is thus a contribution to our understanding of how arsenicosis, apart from its biomedical and clinical manifestations, is understood and experienced by affected individuals living within the particular sociocultural and ecological constraints of rural Bangladesh.

Arsenic exposure and cancer mortality in a US-based prospective cohort: the strong heart study.

BACKGROUND: Inorganic arsenic, a carcinogen at high exposure levels, is a major global health problem. Prospective studies on carcinogenic effects at low-moderate arsenic levels are lacking. METHODS: We evaluated the association between baseline arsenic exposure and cancer mortality in 3,932 American Indians, 45 to 74 years of age, from Arizona, Oklahoma, and North/South Dakota who participated in the Strong Heart Study from 1989 to 1991 and were followed through 2008. We estimated inorganic arsenic exposure as the sum of inorganic and methylated species in urine. Cancer deaths (386 overall, 78 lung, 34 liver, 18 prostate, 26 kidney, 24 esophagus/stomach, 25 pancreas, 32 colon/rectal, 26 breast, and 40 lymphatic/hematopoietic) were assessed by mortality surveillance reviews. We hypothesized an association with lung, liver, prostate, and kidney cancers. RESULTS: Median (interquartile range) urine concentration for inorganic plus methylated arsenic species was 9.7 (5.8-15.6) µg/g creatinine. The adjusted HRs [95% confidence interval (CI)] comparing the 80th versus 20th percentiles of arsenic were 1.14 (0.92-1.41) for overall cancer, 1.56 (1.02-2.39) for lung cancer, 1.34 (0.66, 2.72) for liver cancer, 3.30 (1.28-8.48) for prostate cancer, and 0.44 (0.14, 1.14) for kidney cancer. The corresponding hazard ratios were 2.46 (1.09-5.58) for pancreatic cancer, and 0.46 (0.22-0.96) for lymphatic and hematopoietic cancers. Arsenic was not associated with cancers of the esophagus and stomach, colon and rectum, and breast. CONCLUSIONS: Low to moderate exposure to inorganic arsenic was prospectively associated with increased mortality for cancers of the lung, prostate, and pancreas. IMPACT: These findings support the role of low-moderate arsenic exposure in development of lung, prostate, and pancreas cancer and can inform arsenic risk assessment.

Quality of life and mental health status of arsenic-affected patients in a Bangladeshi population.

Contamination of groundwater by inorganic arsenic is one of the major public-health problems in Bangladesh. This cross-sectional study was conducted (a) to evaluate the quality of life (QOL) and mental health status of arsenic-affected patients and (b) to identify the factors associated with the QOL. Of 1,456 individuals, 521 (35.78%) were selected as case and control participants, using a systematic random-sampling method. The selection criteria for cases (n=259) included presence of at least one of the following: melanosis, leucomelanosis on at least 10% of the body, or keratosis on the hands or feet. Control (nonpatient) participants (n=262) were selected from the same villages by matching age (±5 years) and gender. The Bangladeshi version of the WHOQOL-BREF was used for assessing the QOL, and the self-reporting questionnaire (SRQ) was used for assessing the general mental health status. Data were analyzed using Student's t-test and analysis of covariance (ANCOVA), and the WHOQOL-BREF and SRQ scores between the patients and the non-patients were compared. The mean scores of QOL were significantly lower in the patients than those in the non-patients of both the sexes. Moreover, the mental health status of the arsenic-affected patients (mean score for males=8.4 and females=10.3) showed greater disturbances than those of the non-patients (mean score for males=5.2 and females=6.1) of both the sexes. The results of multiple regression analysis revealed that the factors potentially contributing to the lower QOL scores included: being an arsenic-affected patient, having lower age, and having lower annual income. Based on the findings, it is concluded that the QOL and mental health status of the arsenic-affected patients were significantly lower than those of the non-patients in Bangladesh. Appropriate interventions are necessary to improve the well-being of the patients.

A cultural practice of drinking realgar wine leading to elevated urinary arsenic and its potential health risk.

Toasting friends and family with realgar wines and painting children's foreheads and limbs with the leftover realgar/alcohol slurries is an important customary ritual during the Dragon Boat Festival (DBF); a Chinese national holiday and ancient feast day celebrated throughout Asia. Realgar is an arsenic sulfide mineral, and source of highly toxic inorganic arsenic. Despite the long history of realgar use during the DBF, associated risk to human health by arsenic ingestion or percutaneous adsorption is unknown. To address this urine samples were collected from a cohort of volunteers who were partaking in the DBF festivities. The total concentration of arsenic in the wine consumed was 70 mg L⁻¹ with all the arsenic found to be inorganic. Total arsenic concentrations in adult urine reached a maximum of ca. 550 µg L⁻¹ (mean 220.2 µg L⁻¹) after 16 h post-ingestion of realgar wine, while face painting caused arsenic levels in children's urine to soar to 100 µg L⁻¹ (mean 85.3 µg L⁻¹) 40 h after the initial paint application. The average concentration of inorganic arsenic in the urine of realgar wine drinkers on average doubled 16 h after drinking, although this was not permanent and levels subsided after 28 h. As would be expected in young children, the proportions of organic arsenic in the urine remained high throughout the 88-h monitoring period. However, even when arsenic concentrations in the urine peaked at 40 h after paint application, concentrations in the urine only declined slightly thereafter, suggesting pronounced longer term dermal accumulation and penetration of arsenic. Drinking wines blended with realgar or using realgar based paints on children does result in the significant absorption of arsenic and therefore presents a potentially serious and currently unquantified health risk.

Association between GSTO2 polymorphism and the urinary arsenic profile in copper industry workers.

Two members of the recently identified Omega class glutathione S-transferase enzymes (GSTO1 and GSTO2) have been proposed to play a role in the response to arsenic exposure. Therefore, polymorphisms in these genes could be related with variations in the arsenic excretion profile and, consequently, with the individual response to chronic exposure. Exons and flanking regions of GSTO2 gene have been screened in two different ethnic groups (20 Europeans and 20 Chilean Indians), and the urinary arsenic patterns and the GSTO2 Asn142Asp polymorphism have been investigated in 207 copper mine workers occupationally exposed to arsenic. Three polymorphisms of GSTO2 already described were detected in Europeans and Chilean Indians, although with significant different allele frequencies. The genotyping for the Asn142Asp polymorphism revealed that almost no significant association exists between this change and the arsenic excretion profile. However, 142Asp change seems to be correlated with an increase in DMA excretion after age and total urinary arsenic adjustment (OR=3.61; P=0.05). Altogether, our findings indicate that ethnical differences should be taken into account for correlation studies between GST Omega polymorphisms and arsenic susceptibility, and that the 142Asp allozyme could modulate arsenic biotransformation and thereby arsenic toxicity.

Factors impacting on the excess arseniasis prevalence due to indoor combustion of high arsenic coal in a hyperendemic village.

BACKGROUND: A few villages in Southwest Guizhou, China represented a unique case of arseniasis due to indoor combustion of high arsenic-content coal. The present study is aimed to analyze the contribution of possible factors or of their combination to excess prevalence of arseniasis in the exposed population. METHODS: An epidemiological investigation was conducted in all the members of three large ethnic, patrilineal clans in one of the hyperendemic villages (702 residents in 178 families, including 408 Han and 294 Hmong) where farmers of different ethnic origin have been living together in the same village for generations. A multilevel model logistic regression analysis was performed. RESULTS: The arseniasis prevalence was found to associate with the duration of As indoor exposure (years of high As coal burning and of poorly ventilated traditional stove using) and is largely dependent on the subject's ethnicity and clan consanguinity, too. The prevalence of arseniasis in ethnic Han residents was significantly higher than that in their Hmong neighbors (35.0 vs 4.8% OR = 15.18, 95% CI = 3.45-67.35). Notable variances of arseniasis prevalence were observed not only between the ethnic Han clans (G1, G3, and B) and Hmong clan P, but also between different lineages (G1 and G2) inside the ethnic Han clan. Smokers suffered more frequently from arseniasis than non-smokers (47.3 vs 15.7% OR = 5.42, 95% CI = 2.25-12.93). CONCLUSIONS: Arseniasis prevalence in this unique exposure case was impacted by an array of multiple factors. Besides a long-term indoor exposure to As, the ethnicity or the clan consanguinity of exposed subjects may play an important role, too.

Arsenic: a beneficial therapeutic poison - a historical overview.

Arsenicals have been used since ancient Greek and Roman civilizations and in the Far East as part of traditional Chinese medicine. In Western countries, they became a therapeutic mainstay for various ailments and malignancies in the 19th and early 20th centuries. Fowler's potassium bicarbonate-based solution of arsenic trioxide (As2O3)solution was the main treatment of chronic myeloid leukaemia until the 1930s. After a decline in the use of arsenic during the mid-20th century, arsenic trioxide was reintroduced as an anticancer agent after reports emerged from China of the success of an arsenic trioxide-containing herbal mixture for the treatment of acute promyelocytic leukaemia. Arsenic trioxide was first purified and used in controlled studies in China in the 1970s.Subsequently, randomised clinical trials performed in the United States led to FDA approval of arsenic trioxide in the treatment of patients with relapsed or refractory acute promyelocytic leukaemia.

Arseniasis prevalence and mortality in a multiethnic, endemic township in Guizhou, China.

OBJECTIVE: Farmers in Southwest Guizhou Autonomous Prefecture, China, represent a unique case of arseniasis, which is related to indoor combustion of high arsenic-containing coal instead of to arsenic-contaminated drinking water. A significant difference in the prevalence of arseniasis was observed in two neighboring ethnic clans in one village. The question arose whether the ethnicity-dependent difference observed in this village was more widely spread throughout the whole township. An epidemiologic investigation was designed to explore arseniasis distribution and mortality among all four ethnic groups in a multiethnic township. METHODS: The cohort of arseniasis patients, diagnosed and registered in the overall field survey of 1991 as well as all the asymptomatic residents of the township, were enrolled in the present investigation. Indirect standardization was used for calculating the age-adjusted standardized incidence ratio (SIR) of arseniasis, the standardized mortality ratio (SMR) of various death causes (including some cancers), and their corresponding intervals of 95% confidence in both genders and in each local ethnic group. RESULTS: The descending rank of arseniasis SIRs among local ethnic groups was found as: Hui>Han>Bouyei>Hmong. The descending rank of SMRs of malignancies was displayed as: Han>Hui>Bouyei>Hmong in males and both genders together as well. Concerning deaths of non-malignant causes the rank was observed as: Hui>Han>Bouyei>Hmong in males. The arseniasis SIR for ethnic Hmong residents (both genders combined) was found to be significantly less profound than the overall level in the township. No death cases in diagnosed ethnic Hmong patients and no cases of death from malignant causes in asymptomatic Hmong residents were recorded. The significant increase of arseniasis prevalence was observed in all males, compared with the overall prevalence of all residents. However, a significantly lower prevalence was seen in all females. CONCLUSION: Significant ethnicity-dependent difference in arseniasis prevalence and mortality from all causes was found in a multiethnic rural township where farmers have been exposed to the indoor combustion of high arsenic coal for decades. The ethnic Hmong residents seemed to be the least susceptible to arseniasis among the four local ethnic groups.

Asian specific low mutation frequencies of the M287T polymorphism in the human arsenic (+3 oxidation state) methyltransferase (AS3MT) gene.

Groundwater pollution by arsenic is a serious worldwide problem, especially in Asian countries. Inter-individual variation in arsenic metabolism has been reported and recent studies demonstrate that 287T allele in human arsenic (+3 oxidation state) methyltransferase (AS3MT) increase the percentage of monomethylated arsenic in urine. The objectives of the present study was to evaluate the ethnic difference in M287T (T/C) polymorphism in AS3MT among Japanese (n=1074), Koreans (n=435), Chinese (n=154), Mongolians (n=246), Uygurs (n=56), Tibetans (n=180), Tamangs (n=53), Tamils (n=58), Sinhalese (n=54), Turks (n=243), Ovambos (n=185), Ghanaians (n=121), Xhosas (n=101), and other four populations from previous studies. Of 17 populations, Xhosas had the highest 287T frequency (0.233). Other African and Caucasian populations had similar287T frequencies above 0.100 with the exception of the Ghanaians (0.071). On the other hand, the Asian populations had relatively lower 287T allele frequencies ranging from 0.000 to 0.041 than the Africans and Caucasians. Our findings indicate that genetic susceptibility to arsenic toxicity in Asian is different from Africans and Caucasians.

"The horizon opened up very greatly": Leland O. Howard and the transition to chemical insecticides in the United States, 1894-1927.

The transition to synthetic chemicals as a popular method of insect control in the United States was one of the most critical developments in the history of American agriculture. Historians of agriculture have effectively identified the rise and charted the dominance of early chemical insecticides as they came to define commercial agriculture between the emergence of Paris green in the 1870s and the popularity of DDT in the 1940s and beyond. Less understood, however, are the underlying mechanics of this transition. this article thus takes up the basic question of how farmers and entomologists who were once dedicated to an impressively wide range of insect control options ultimately settled on the promise of a chemically driven approach to managing destructive insects. Central to this investigation is an emphasis on the bureaucratic maneuverings of Leland O. Howard, who headed the Bureau of Entomology from 1894 to 1927. Like most entomologists of his era, Howard was theoretically interested in pursuing a wide variety of control methods--biological, chemical, and cultural included. In the end, however, he employed several tactics to streamline the government's efforts to almost exclusively support arsenic and lead-based chemical insecticides as the most commercially viable form of insect control. While Howard in no way "caused" the national turn to chemicals, this article charts the pivotal role he played in fostering that outcome.

Population differences in the human arsenic (+3 oxidation state) methyltransferase (AS3MT) gene polymorphism detected by using genotyping method.

Arsenic poisoning from drinking groundwater is a serious problem, particularly in developing Asian countries. Human arsenic (+3 oxidation state) methyltransferase (AS3MT) is known to catalyze the methylation of arsenite. Recently, a single nucleotide polymorphism (SNPs; rs17885947, M287T (T860C)) in the AS3MT gene was shown to be related to enzyme activity and considered to be related to genetic susceptibility to arsenic. In the present study, a useful genotyping method for M287T was developed using the polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) technique. Applying this method, the genotype distribution of M287T in Ovambo (n=185), Turkish (n=191), Mongolian (n=233), Korean (n=200), and Japanese (n=370) populations were investigated. The mutation frequencies in Asian populations were relatively lower than those of African and Caucasian populations, including those from previous studies: the frequencies of mutation in the Mongolian, Korean, and Japanese populations were 0.040, 0.010, and 0.010, respectively. In the course of this study, a PCR-based genotyping method that is inexpensive and does not require specialized equipment was developed. This method could be applied to a large number of residents at risk for arsenic poisoning.