Arsenic, Familicide, and Female Physiology in Nineteenth-Century America.

Sarah Jane Whiteling was accused of fatally poisoning her husband and two children in Philadelphia in 1888. The case prompted public outrage over the appearance that Ms. Whiteling's motive was to collect life insurance. It was evident, however, that she was disturbed, raising a question of culpability. Dr. Alice Bennett, the first female physician in charge of an asylum, provided the defense with expert testimony on the defendant's mental state. Dr. Bennett, who had little forensic but much clinical experience, proposed a physiological theory of insanity among women with reproduction-related derangements. At that time, cultural ideas about "female poisoners" colored popular and journalistic perceptions of Ms. Whiteling. Familicide was considered unconscionable because a mother's duty was to nurture and protect her family. When Ms. Whiteling was convicted and sentenced to death, Dr. Bennett undertook a campaign for commutation. Her unsuccessful efforts to reduce culpability were followed by Ms. Whiteling's hanging in 1889, the first execution of a woman in Philadelphia since colonial times. This article recounts the Whiteling case, Dr. Bennett's involvement in it, and how it relates to what is known about familicide. It is argued here that Dr. Bennett was a pioneer in applying medical expert testimony to effect individualized mitigation.

Influence of age on arsenic-induced behavioral and cholinergic perturbations: Amelioration with zinc and α-tocopherol.

This study was planned to determine arsenic (As) (10 mg/kg body weight given through oral gavage) induced behavioral and cholinergic perturbations in three different age groups of rats; young (postnatal day 21), adult (3 months), and aged (18 months) at 7 days post-acute exposure ( n = 6 for each of the four groups of all three age points). Further, we also evaluated the ameliorative effect of essential metal zinc (Zn; 0.02% through drinking water) and an antioxidant, α-tocopherol (vitamin E; 125 mg/kg body weight through oral gavage) against As-induced neurotoxicity. As exposure showed significant alterations in behavioral functions (open-field behavior, total locomotor activity, grip strength, exploratory behavior, and water maze learning). Cholinergic studies in three brain regions (cerebral cortex, cerebellum, and hippocampus) of different age groups also showed significant increase in acetylcholine levels and a decrease in acetylcholinesterase activity. These effects were more pronounced in hippocampus followed by cerebral cortex and cerebellum. Among the three different age points, aged animals were found to be more vulnerable to the As-induced toxicity as compared to young and adult animals suggesting that As neurotoxicity is age dependent. These As-induced alterations were significantly reversed following supplementation with Zn or vitamin E. However, vitamin E was found to elicit greater protection as compared to Zn in restoring the altered behavioral and cholinergic perturbations, providing evidence for As-induced oxidative damage.

Low-level arsenic exposure during pregnancy and its association with postpartum depression: A cohort study of women from Arica, Chile.

BACKGROUND: While the relationship between inorganic arsenic exposure and psychological impairment has been studied previously, the association between low-level arsenic exposure during pregnancy and postpartum depression has not yet been examined. The objective is to estimate the association between low-level arsenic exposure during pregnancy and the Edinburgh score. METHODS: A sample of 223 women was collected from five public health services in Arica, Chile. Participation was voluntary and written consent was mandatory. Sociodemographic data related to arsenic exposure and urine samples for total inorganic arsenic assessments were collected during the second trimester. Postpartum depression symptoms were estimated by the Edinburgh Postpartum Depression scale. We examined descriptive statistics and ran multiple linear regressions. The modifying effect of age and depression history was evaluated separately. RESULTS: The median for total urinary inorganic arsenic was 14.6µg/L (range: 2-69.2µg/L), the median for postpartum depression score was 8 points (range: 0-27 points) and 20.6% of women were considered as postpartum depressed. For women older than 25years old without depression history, the adjusted coefficient for the total urinary natural logarithm of inorganic arsenic in multiple linear regressions was -2.51 (95% CI: -4.54, -0.48; P-value=0.02). For women older than 25years old with a depression history, this value was 2.09 (95% CI: -0.90, 5.08; P-value=0.16). CONCLUSIONS: In this cohort, the number of children, physical perception, depression history, stressful maternity, and age were associated with postpartum depression score. The Edinburgh score was associated with inorganic arsenic in women older than 25years without depression history.

Family-based association study of the arsenite methyltransferase gene (AS3MT, rs11191454) in Korean children with attention-deficit hyperactivity disorder.

We examined the association between the selected polymorphisms in two candidate genes, the arsenite methyltransferase gene (AS3MT, rs11191454) and the inter-α-trypsin inhibitors heavy chain-3 gene (ITIH3, rs2535629), and attention-deficit hyperactivity disorder (ADHD) in a Korean population. A total of 238 patients with ADHD, along with both of their biological parents, were recruited. The children were administered intelligence quotient tests, whereas their parents completed the Child Behavior Checklist. In the transmission disequilibrium test on 181 trios, we found overtransmission of the A allele at the AS3MT rs11191454 polymorphism in children with ADHD (χ²=8.81, P=0.003). However, there was no preferential transmission at the ITIH3 rs52535629 polymorphism (χ²=0.14, P=0.707). Our results provide preliminary evidence for the overtransmission of the A allele at the AS3MT rs11191454 polymorphism in ADHD.

Arsenic downregulates gene expression at the postsynaptic density in mouse cerebellum, including genes responsible for long-term potentiation and depression.

Arsenic (As) is a neurotoxin induces dysfunction of learning and memory. Research has indicated that cerebellum may be involved in arsenic-induced impairment of learning and memory. However, the molecular mechanisms that underlie these effects remain unclear. This study screened for the differentially expressed genes related to the long-term potentiation and long-term depression (LTP and LTD) at the cerebellar postsynaptic density (PSD) of mice following exposure to arsenic, and we provide evidence of the mechanism by which arsenic adversely affects the functions of learning and memory. Here, SPF mice were exposed to 1ppm, 2ppm and 4ppm As2O3 for 60 days. The ultrastructure of the synapses in cerebella of these mice was observed via transmission electron microscopy. The cerebellum global gene expression of mice exposed to 4ppm As2O3 was determined through GeneChip analysis. We used the web tool DAVID to analyze the Gene Ontology (GO) and KEGG pathways that were significantly enriched among the differentially expressed genes. Our observations of synaptic ultrastructure showed that the thickness of the cerebellar PSD was reduced in mice exposed to arsenic. Go analysis revealed the PSD as a significantly altered cellular component. KEGG pathway analysis showed that LTP and LTD were affected by arsenic with highest statistical significance, and 20 differentially expressed genes were associated with them. Among these differentially expressed genes, significant decreases in the mRNA expressions of CaMKII, Gria1, Gria2, Grin1, Itpr1, Grm1 and PLCß4 related to the LTP and LTD were found at the PSD of mouse cerebellum exposed to arsenic. The downregulation of these genes was further confirmed via real-time reverse transcription PCR or Western blot at 1ppm, 2ppm and 4ppm As2O3. Our results indicate that the 7 genes with in cerebellar PSDs may be involved in arsenic-induced neurotoxicity, including impairment of learning and memory.

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.

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.

Neuroprotective efficacy of curcumin in arsenic induced cholinergic dysfunctions in rats.

Our recent studies have shown that curcumin protects arsenic induced neurotoxicity by modulating oxidative stress, neurotransmitter levels and dopaminergic system in rats. As chronic exposure to arsenic has been associated with cognitive deficits in humans, the present study has been carried out to implore the neuroprotective potential of curcumin in arsenic induced cholinergic dysfunctions in rats. Rats treated with arsenic (sodium arsenite, 20mg/kg body weight, p.o., 28 days) exhibited a significant decrease in the learning activity, assessed by passive avoidance response associated with decreased binding of (3)H-QNB, known to label muscarinic-cholinergic receptors in hippocampus (54%) and frontal cortex (27%) as compared to controls. Decrease in the activity of acetylcholinesterase in hippocampus (46%) and frontal cortex (33%), staining of Nissl body, immunoreactivity of choline acetyltransferase (ChAT) and expression of ChAT protein in hippocampal region was also observed in arsenic treated rats as compared to controls. Simultaneous treatment with arsenic and curcumin (100mg/kg body weight, p.o., 28 days) increased learning and memory performance associated with increased binding of (3)H-QNB in hippocampus (54%), frontal cortex (25%) and activity of acetylcholinesterase in hippocampus (41%) and frontal cortex (29%) as compared to arsenic treated rats. Increase in the expression of ChAT protein, immunoreactivity of ChAT and staining of Nissl body in hippocampal region was also observed in rats simultaneously treated with arsenic and curcumin as compared to those treated with arsenic alone. The results of the present study suggest that curcumin significantly modulates arsenic induced cholinergic dysfunctions in brain and also exhibits neuroprotective efficacy of curcumin.

Arsenic and manganese exposure and children's intellectual function.

Recently, epidemiologic studies of developmental neurotoxicology have been challenged to increase focus on co-exposure to multiple toxicants. Earlier reports, including our own work in Bangladesh, have demonstrated independent associations between neurobehavioral function and exposure to both arsenic (As) and manganese (Mn) in school-aged children. Our earlier studies, however, were not designed to examine possible interactive effects of exposure to both As and Mn. To allow investigation of possible synergistic impact of simultaneous exposures, we recruited a new sample of 299 8-11 year old children, stratified by design on As (above and below 10 µg/L) and Mn (above and below 500 µg/L) concentrations of household wells. When adjusted only for each other, both As and Mn in whole blood (BAs; BMn) were significantly negatively related to most WISC-IV subscale scores. With further adjustment for socio-demographic features and ferritin, BMn remained significantly associated with reduced Perceptual Reasoning and Working Memory scores; associations for BAs, and for other subscales, were expectably negative, significantly for Verbal Comprehension. Urinary As (per gram creatinine) was significantly negatively associated with Verbal Comprehension scores, even with adjustment for BMn and other contributors. Mn by As interactions were not significant in adjusted or unadjusted models (all p's>0.25). Findings are consistent with other reports documenting adverse impact of both As and Mn exposure on child developmental outcomes, although associations appear muted at these relatively low exposure levels.

Quality of life of arsenicosis patients in an arsenic-affected rural area in Bangladesh.

The objective of this cross-sectional comparative study was to assess quality of life (QOL) of arsenicosis patients. A total of 104 arsenicosis patients, 104 arsenic-exposed individuals without arsenicosis (nonpatients), and 104 individuals not exposed to arsenic (controls) were interviewed based on a questionnaire constructed based on the WHOQOL-BREF instrument. The facets of life considered for assessing QOL were physical health domain, psychological domain, social relationships domain, and environment domain. All the domain-wise QOL scores of the arsenicosis patients were significantly smaller than those of the controls as well as of the nonpatients. The findings of the study assessing QOL of arsenicosis patients might be helpful to understand the condition and justify for the policy makers to adopt adequate measures to alleviate the sufferings through prevention, treatment, and rehabilitation.

Applying the common sense model to measure representations of arsenic contaminated well water.

Theory-based research is needed to understand how people respond to environmental health risk information. Both the common sense model (CSM) of self-regulation and the mental models approach propose that information shapes individuals' personal understandings that, in turn, influence their decisions and actions. We compare these frameworks and explain how the CSM was applied to describe and measure mental representations of arsenic contaminated well water. Educational information, key informant interviews, and environmental risk literature were used to develop survey items to measure dimensions of cognitive representations (identity, cause, timeline, consequences, control) and emotional representations. Surveys mailed to 1,067 private well users with moderate and elevated arsenic levels yielded an 84 % response rate (n = 897). Exploratory and confirmatory factor analyses of data from the elevated arsenic group identified a factor structure that retained the CSM representational structure and was consistent across moderate and elevated arsenic groups. The CSM has utility for describing and measuring representations of environmental health risks, thus supporting its application to environmental health risk communication research.

"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.

Knowledge of arsenic in drinking-water: risks and avoidance in Matlab, Bangladesh.

Widespread contamination of arsenic in Bangladesh has been jeopardizing the health of millions of people. Residents of Matlab, Bangladesh, are among the millions at risk. Using bivariate models in the analysis of survey data, knowledge of health risks and avoidance of arsenic exposure in response to widespread contamination of arsenic for residents of Matlab were estimated. The models examined individuals' knowledge of an arsenic problem in the household and knowledge of specific illnesses caused by arsenic exposure. The likelihood of avoiding exposure to arsenic contamination was further examined. Results of the estimation showed that individual's knowledge of arsenic problems in the household was gathered through awareness campaigns and by word of mouth and that knowledge of illnesses was predicated on education, health, presence of children, elderly and young women. Adoption of avoidance measures was not affected by exposure to arsenic-information sources, but level of education had a statistically significant positive effect on the decision to avoid arsenic exposure. Lack of convenience of safe drinking-water practices lead people to persist in drinking arsenic-contaminated water.

Access to drinking-water and arsenicosis in Bangladesh.

The discovery of arsenic contamination in groundwater has challenged efforts to provide safe drinking-water to households in rural Bangladesh. Two nationally-representative surveys in 2000 and 2002 investigated water-usage patterns, water-testing, knowledge of arsenic poisoning, and behavioural responses to arsenic contamination. Knowledge of arsenicosis rose between the two surveys among women from 42% to 64% but awareness of consequences of arsenic remained limited; only 13% knew that it could lead to death. Behavioural responses to arsenic have been limited, probably in part because of the lack of concern but also because households are uncertain of how best to respond and have a strong preference for tubewell water even when wells are known to be contaminated. Further work conducted by the survey team highlighted the difficulties in providing alternative sources of water, with many households switching back to their original sources of water.

Social implications of arsenic poisoning in Bangladesh.

Besides its toxicity, groundwater arsenic contamination creates widespread social problems for its victims and their families in Bangladesh. There is, for instance, a tendency to ostracise arsenic-affected people, arsenicosis being thought of as a contagious disease. Within the community, arsenic-affected people are barred from social activities and often face rejection, even by their immediate family members. Women with visible arsenicosis symptoms are unable to get married and some affected housewives are divorced by their husbands. Children with symptoms are not sent to school in an effort to hide the problem. This paper employs mainly qualitative methods to interpret people's understandings about the toxic impact of groundwater arsenic poisoning on their social lives. Arsenic-affected patients in southwest Bangladesh were asked to determine their 'own priorities' in measuring arsenic toxicity on their social activities and to explore their perceptions about their own survival strategies. We found that patients' experiences reveal severe negative social impacts, and a sharp difference of perceptions about arsenic and social issues between arsenicosis patients and unaffected people.

The effects of chronic arsenic exposure from drinking water on the neurobehavioral development in adolescence.

This cross-sectional study examined the possible influence on the development of cognitive function among adolescents due to long-term arsenic exposure. Forty-nine junior school students drinking arsenic-containing well water and 60 controls matched with age, sex, education, body height, body weight, body mass index, and socioeconomic status were compared. The former was divided into two groups: high and low exposure, with mean cumulative arsenic levels of 520629.0+/-605824.2 and 13782.2+/-12886.0 ppm, respectively. Four neurobehavioral tests including continuous performance test (CPT), symbol digit (SD), pattern memory (PM) and switching attention (SA) were applied. A strong correlation between age and education caused collinearity in the multiple regression model (r=0.84, P<0.0001). Only education and sex, excluding age, were entered into the model as covariates. Pattern memory and switching attention were significantly affected by long-term cumulative exposure to arsenic after adjusting for education and sex. It is suggested that the arsenic levels in the well water may be monitored extensively, but if there is no intervention, then neurobehavioral function will not be protected. Limitations of the current study require replication of this effect in other studies to confirm this conclusion.

Acute arsenic poisoning treated by intravenous dimercaptosuccinic acid (DMSA) and combined extrarenal epuration techniques.

Arsenic poisoning was diagnosed in a 26-year-old man who had been criminally intoxicated over the last two weeks preceding admission by the surreptitious oral administration of probably 10 g of arsenic trioxide (As2O3). The patient developed severe manifestations of toxic hepatitis and pancreatitis, and thereafter neurological disorders, respiratory distress, acute renal failure, and cardiovascular disturbances. In addition to supportive therapy, extrarenal elimination techniques and chelating agents were used. Dimercaprol (BAL) and dimercaptosuccinic acid (DMSA or succimer) were used simultaneously as arsenic chelating agents for two days, and thereafter DMSA was used alone. DMSA was administered by intravenous (20 mg/kg/d for five days, then 10 mg/kg/d for six days) and intraperitoneal route. Intravenous DMSA infusion was well tolerated and resulted in an increase in arsenic blood concentration immediately after the infusion. Continuous venovenous hemofiltration combined with hemodialysis, and peritoneal dialysis were proposed to enhance arsenic elimination. It was calculated that over an 11-day period 14.5 mg arsenic were eliminated by the urine, 26.7 mg by hemodialysis, 17.8 mg by peritoneal dialysis, and 7.8 mg by continuous venovenous hemofiltration. These amounts appeared negligible with regard to the probable ingested dose. The patient died on day 26 from the consequences of multiple organ failure, with subarachnoid hemorrhage and generalized infection caused by Aspergillus fumigatus.