Cortical Synaptic Reorganization Under Chronic Arsenic Exposure.

There is solid epidemiological evidence that arsenic exposure leads to cognitive impairment, while experimental work supports the hypothesis that it also contributes to neurodegeneration. Energy deficit, oxidative stress, demyelination, and defective neurotransmission are demonstrated arsenic effects, but it remains unclear whether synaptic structure is also affected. Employing both a triple-transgenic Alzheimer's disease model and Wistar rats, the cortical microstructure and synapses were analyzed under chronic arsenic exposure. Male animals were studied at 2 and 4 months of age, after exposure to 3 ppm sodium arsenite in drinking water during gestation, lactation, and postnatal development. Through nuclear magnetic resonance, diffusion-weighted images were acquired and anisotropy (integrity; FA) and apparent diffusion coefficient (dispersion degree; ADC) metrics were derived. Postsynaptic density protein and synaptophysin were analyzed by means of immunoblot and immunohistochemistry, while dendritic spine density and morphology of cortical pyramidal neurons were quantified after Golgi staining. A structural reorganization of the cortex was evidenced through high-ADC and low-FA values in the exposed group. Similar changes in synaptic protein levels in the 2 models suggest a decreased synaptic connectivity at 4 months of age. An abnormal dendritic arborization was observed at 4 months of age, after increased spine density at 2 months. These findings demonstrate alterations of cortical synaptic connectivity and microstructure associated to arsenic exposure appearing in young rodents and adults, and these subtle and non-adaptive plastic changes in dendritic spines and in synaptic markers may further progress to the degeneration observed at older ages.

Skeletal pathology and bone mineral density changes in wild muskrats (Ondatra zibethicus) and red squirrels (Tamiasciurus hudsonicus) inhabiting arsenic polluted areas of Yellowknife, Northwest Territories (Canada): A radiographic densitometry study.

The City of Yellowknife is a known hotspot of arsenic contamination and there is a growing body of evidence suggesting that local wildlife in the vicinity of the abandoned Giant Mine site may be at risk of decreased bone mineralization and various bone disorders. The purpose of this study was to preliminarily measure bone mineral density (BMD) changes and investigate the incidence, pattern, and severity of bone lesions in wild muskrats and red squirrels breeding in three (3) catchment areas at different distances from the Giant Mine Site in Yellowknife, Northwest Territories (Canada): ~2 km (location 1), ~18 km (location 2), and ~40-100 km (location 3). Full femoral bones of 15 muskrats and 15 red squirrels were collected from the three sampling locations (5 from each location) and subjected to radiographic analysis and densitometric measurements. The patterns and severities of bone lesions, including changes in bone mineral density, were evaluated and compared between groups. As levels were significantly higher in the bones of muskrats caught from location 1 and 2, relative to location 3. Further, As and Cd levels were significantly higher in the bones of squirrels caught from locations 1 and 2 relative to squirrels caught from location 3. The preliminary results from bones revealed that radiographic abnormalities such as bone rarefaction, osteopenia, and thinning of the femoral shafts with significant ossific cystic lesions and bowing were the most common skeletal pathologies found in bones of red squirrels from the three locations. Radiographic appearances of massive sclerosis and dysplasia, including severe osteocondensation and osteopathia striata-like abnormalities, were found in the bones of muskrats from all the sampling locations. Densitometric evaluation showed no significant differences between the three locations in the bone parameters measured. However, there was a statistically significant correlation between As content in the bones of muskrats and percent fat content in the femur samples, which suggests that accumulation of As could have been a causal factor for a change in percent fat in femurs of muskrats.

Demyelination associated with chronic arsenic exposure in Wistar rats.

Inorganic arsenic is among the major contaminants of groundwater in the world. Worldwide population-based studies demonstrate that chronic arsenic exposure is associated with poor cognitive performance among children and adults, while research in animal models confirms learning and memory deficits after arsenic exposure. The aim of this study was to investigate the long-term effects of environmentally relevant arsenic exposure in the myelination process of the prefrontal cortex (PFC) and corpus callosum (CC). A longitudinal study with repeated follow-up assessments was performed in male Wistar rats exposed to 3 ppm sodium arsenite in drinking water. Animals received the treatment from gestation until 2, 4, 6, or 12 months of postnatal age. The levels of myelin basic protein (MBP) were evaluated by immunohistochemistry/histology and immunoblotting from the PFC and CC. As plausible alterations associated with demyelination, we considered mitochondrial mass (VDAC) and two axonal damage markers: amyloid precursor protein (APP) level and phosphorylated neurofilaments. To analyze the microstructure of the CC in vivo, we acquired diffusion-weighted images at the same ages, from which we derived metrics using the tensor model. Significantly decreased levels of MBP were found in both regions together with significant increases of mitochondrial mass and slight axonal damage at 12 months in the PFC. Ultrastructural imaging demonstrated arsenic-associated decreases of white matter volume, water diffusion anisotropy, and increases in radial diffusivity. This study indicates that arsenic exposure is associated with a significant and persistent negative impact on microstructural features of white matter tracts.

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.

An Unusual Case of Acute Psychosis With Obsessive-Compulsive Features Following Arsenic Poisoning.

Arsenic exposure, particularly the chronic type, can lead to poisoning with manifestations presenting in multiple organ systems. However, acute psychosis is not a commonly described manifestation of arsenic exposure. In this report, we present the case of a patient who developed acute psychosis with hallucinations, disorganized thinking, and obsessive-compulsive symptoms following chronic occupational arsenic exposure. The patient was treated with the combination of an antipsychotic and an antidepressant and he responded well with significant improvement in both the acute psychosis and obsessive-compulsive symptoms. The authors concluded that patients can develop atypical symptoms, including acute psychosis, following arsenic poisoning. In the case described in this report, the patient also presented with a new onset of obsessive-compulsive symptoms. Given this rare manifestation of arsenic poisoning for which there is no clearly defined treatment regimen, this case suggests that the use of a combination of an antipsychotic and an antidepressant may be considered in the rare event of psychosis with obsessive-compulsive features following arsenic poisoning.

Chronic lung disease and detection of pulmonary artery dilatation in high resolution computerized tomography of chest in chronic arsenic exposure.

Lung affection in chronic arsenicosis developing from chronic ingestion of arsenic contaminated groundwater has been known but little is known on its effect on pulmonary arterial system. A cross sectional study was carried out at two geographically similar areas and demographically similar populations with or without evidence of chronic arsenic exposure in West Bengal, India. The willing participants in both the groups with chronic respiratory symptoms were evaluated with High Resolution Computerized Tomography (HRCT) of Chest. Evaluation of High Resolution Computerized Tomography of chest followed clinical assessment of lung disease in194 and 196 subjects from the arsenic exposed and unexposed people; the former had a higher prevalence of cough OR(Odds Ratio) 3.23 (95% CI(Confidence Interval): 1.72-6.07) and shortness of breath OR1.76 (95% CI: 0.84-3.71), respectively. The arsenic exposed individuals showed higher score for bronchiectasis [mean ± SD(Standard Deviation)] as 2.41 ± 2.32 vs. 1.22 ± 1.48 (P <0.001), pulmonary artery branch dilatation (PAD) as 2.48 ± 2.33 vs. 0.78 ± 1.56, (P <0.001) and pulmonary trunk dilatation as 0.26 ± 0.45 vs. nil. Age-adjusted prevalence odds ratio (POR) for Pulmonary Artery Dilatation Found in HRCT comparing those exposed to arsenic (Group 1) to unexposed participants (Group 2) was found to be 6.98 (CI: 2.26-16.48). There was a strong dose-response relationship between the PAD (Pulmonary Artery Dilatation) and cumulative arsenic exposure. Pulmonary trunk and branch dilatation in chronic arsenicosis is a frequent abnormality seen in HRCT Chest of arsenicosis patients. The significance of such finding needs further investigation.

Arsenic-induced QT dispersion is associated with atherosclerotic diseases and predicts long-term cardiovascular mortality in subjects with previous exposure to arsenic: A 17-Year follow-up study.

Chronic arsenic poisoning is a major worldwide public health problem. Recently, we had reported chronic arsenic poisoning was dose-dependently associated with ventricular abnormalities quantified by electrocardiographic QT prolongation linking to atherosclerotic diseases. An association of chronic arsenic poisoning with ventricular repolarization inhomogeneity quantified by QT dispersion (QTD) is of particular interest from a theoretical and practical perspective. We aimed to further elucidate (1) the association of chronic arsenic exposure with ventricular abnormalities quantified by QTD, (2) the association of QTD with atherosclerotic diseases and (3) the predictability of QTD for long-term mortality in subjects with chronic arsenic poisoning. We followed up 280 men and 355 women living in arseniasis-endemic area in southwestern coast in Taiwan for 17 years. QTD in electrocardiogram and carotid intima-media thickness by ultrasonography were measured. Coronary artery disease was diagnosed by an abnormal electrocardiogram and a definite history. Cumulative arsenic exposure was significantly associated with QTD showing a dose-response relationship (P < 0.001). Significant associations of the QTD with coronary artery disease and carotid atherosclerosis existed after adjustment for potential confounders in the multiple linear regression analysis (all P values < 0.05). In the multivariate Cox regression analyses, the hazard ratios (95% confidence interval, P value) of cumulative cardiovascular and all-cause mortality were 3.9 (2.1-6.2, P = 0.002) and 1.4 (0.9-2.3, P = 0.10), respectively, for QTD > or = 65 ms compared with QTD < 65. QTD may be indicated as an early biomarker for atherosclerotic diseases and a significant and strong predictor of cardiovascular mortality in population with chronic arsenic exposure.

[Clinical manifestation and ultrasonic characteristics of five patients with acute arsenic poisoning].

OBJECTIVE: To study the clinical manifestation and ultrasonic characteristics of liver, kidney and heart of five patients with acute arsenic poisoning. METHODS: The activity of serum myocardial enzymes, function of liver and kidney, and urinary As concentrations were measured. HDI 3000 Enhanced, and Toshiba 38A two dimensional ultrasound was used to examine the ultrasonic echogram of heart, liver, kidney of the patients. RESULTS: (1) The arsenic concentrations in the urine (1.9 approximately 15.6 micromol/L) were higher than the normal value (1.17 micromol/L) in these patients (blood dialytic fluid of one patient with anuria was measured); (2) Four of them had increased WBC, or anemia, and abnormal urine routine to various degree; (3) The activities of serum myocardial enzymes (CK, AST, LDH and HBDH) in 4 patients were at least 2 items increased; (4) Serum bilirubin and urea nitrogen in all patients were increased; (5) The ultrasonic echogram of liver and kidney in these 5 patients showed abnormality to various degree, one of them had slight enlargements in left atrium and ventricle as well as a little pericardial fluid. CONCLUSION: The clinical manifestation and ultrasonic characteristics of liver, kidney, and heart were consistent with the pathologic changes in acute arsenic poisoning. Early blood dialysis may reduce visceral damage.

Repetitive endoscopy and continuous alkaline gastric irrigation in a case of arsenic poisoning.

BACKGROUND: The poor prognosis of patients with persistent gastrointestinal radio-opacities after oral arsenic poisoning supports efficient gastrointestinal decontamination as critical for survival. In a case of massive arsenic ingestion, we performed repetitive gastric endoscopy and a continuous alkaline irrigation of the stomach over several days. CASE REPORT: A 41-year-old woman was admitted 4 hours after intentional ingestion of trivalent arsenic powder 5 g. The admission abdominal X-ray confirmed the presence of multiple gastric opacities. Initial treatment was gastric lavage with normal saline, dimercaprol chelation, and supportive therapy. Since gastric opacities persisted on the abdominal X-ray at 34 hours despite repeated gastric lavage, a gastroscopy was performed showing nonremovable agglomerates. In an attempt to achieve further gastric decontamination, we performed a continuous gastric alkaline irrigation. After 3 days of alkaline irrigation, the abdomen was normal on X-ray but the gastroscopy still showed arsenic concretions. Alkaline irrigation was continued for another 3 days until total disappearance of arsenic agglomerates at the gastroscopy. Admission urinary arsenic was 3663 microg/L. A total of 46.2 mg of inorganic arsenic, or less than 1% the ingested dose, was extracted from the stomach by this technique. The patient was discharged from the intensive care unit 20 days after admission without sequelae.