A Prospective Study of Arsenic Exposure,Arsenic Methylation Capacity,and Risk of Cardiovascular Disease in Bangladesh

Background: Few prospective studies have evaluated the influence of arsenic methylation capacity on cardiovascular disease (CVD) risk.Objective: We evaluated the association of arsenic exposure from drinking water and arsenic methylation capacity with CVD risk.Method: We conducted a case–cohort study of 369 incident fatal and nonfatal cases of CVD, including 211 cases of heart disease and 148 cases of stroke, and a subcohort of 1,109 subjects randomly selected from the 11,224 participants in the Health Effects of Arsenic Longitudinal Study (HEALS).Results: The adjusted hazard ratios (aHRs) for all CVD, heart disease, and stroke in association with a 1-SD increase in baseline well-water arsenic (112 µg/L) were 1.15 (95% CI: 1.01, 1.30), 1.20 (95% CI: 1.04, 1.38), and 1.08 (95% CI: 0.90, 1.30), respectively. aHRs for the second and third tertiles of percentage urinary monomethylarsonic acid (MMA%) relative to the lowest tertile, respectively, were 1.27 (95% CI: 0.85, 1.90) and 1.55 (95% CI: 1.08, 2.23) for all CVD, and 1.65 (95% CI: 1.05, 2.60) and 1.61 (95% CI: 1.04, 2.49) for heart disease specifically. The highest versus lowest ratio of urinary dimethylarsinic acid (DMA) to MMA was associated with a significantly decreased risk of CVD (aHR = 0.54; 95% CI: 0.34, 0.85) and heart disease (aHR = 0.54; 95% CI: 0.33, 0.88). There was no significant association between arsenic metabolite indices and stroke risk. The effects of incomplete arsenic methylation capacity—indicated by higher urinary MMA% or lower urinary DMA%—with higher levels of well-water arsenic on heart disease risk were additive. There was some evidence of a synergy of incomplete methylation capacity with older age and cigarette smoking.Conclusions: Arsenic exposure from drinking water and the incomplete methylation capacity of arsenic were adversely associated with heart disease risk.     

Study on ascitic fluid complement 3 level in cirrhotic patients with spontaneous bacterial peritonitis and without spontaneous bacterial peritonitis

BACKGROUND/AIMS: Ascitic fluid Complement 3 (C3) concentration is the most important factor to offer local defense against infection of ascitic fluid. Hepatic synthesis of Complement 3 and its concentration in ascitic fluid is significantly reduced in patients with advanced cirrhosis. The aim of the study was to assess the level of Complement 3 in ascitic fluid in cirrhotic patients with and without spontaneous bacterial peritonitis (SBP) and to identify the group of cirrhotic ascites at risk of developing METHODOLOGY: A prospective case control study was carried out to compare the level of ascitic fluid Complement 3 concentration in patients with SBP (case-group) and without SBP (control-group). Ascitic fluid Complement 3 level was estimated in 15 patients with SBP (case) and another 15 patients without SBP (control). RESULTS: In the study, ascitic fluid Complement 3 concentration was 7.3+/-4.3 mg/dL in patients with SBP and 16.4+/-11.3 mg/dL in patients who did not develop SBP. CONCLUSIONS: Ascitic fluid Complement 3 level is significantly (P=0.009) reduced in cirrhotic patients who develop SBP.     

Association of arsenic exposure during pregnancy with fetal loss and infant death: a cohort study in Bangladesh

The authors evaluated the effect of arsenic exposure on fetal and infant survival in a cohort of 29,134 pregnancies identified by the health and demographic surveillance system in Matlab, Bangladesh, in 1991-2000. Arsenic exposure, reflected by drinking water history and analysis of arsenic concentrations in tube-well water used by women during pregnancy, was assessed in a separate survey conducted in 2002-2003. Data on vital events, including pregnancy outcome and infant mortality, were collected by monthly surveillance at the household level. The risk of fetal loss and infant death in relation to arsenic exposure was estimated by a Cox proportional hazards model. Drinking tube-well water with more than 50 microg of arsenic per liter during pregnancy significantly increased the risks of fetal loss (relative risk = 1.14, 95% confidence interval: 1.04, 1.25) and infant death (relative risk = 1.17, 95% confidence interval: 1.03, 1.32). There was a significant dose response of arsenic exposure to risk of infant death (p = 0.02). Women of reproductive age should urgently be prioritized for mitigation activities where drinking water is contaminated by arsenic.     

Protein kinase C stabilizes X‐linked inhibitor of apoptosis protein (XIAP) through phosphorylation at Ser87 to suppress apoptotic cell death

Background: Multiple protein kinases have been shown to be involved in the apoptotic neuronal loss of Alzheimer's disease (AD). Although some studies support the role of protein kinase C (PKC) in amyloid precursor protein processing as well as in tau phosphorylation, a direct role for PKC in apoptotic neuronal death remains to be clarified. In the present study, we report on the possible role of PKC in cell survival during conditions of stress through phosphorylation of the X‐linked inhibitor of apoptosis protein (XIAP). Methods: Phosphorylation of XIAP at Ser87 was confirmed by western blot analysis employing phosphorylation dependent anti‐XIAP antibody after incubation of recombinant XIAP with active PKC in vitro. And increased phosphorylation of XIAP at the site was also confirmed in SH‐SY5Y cells treated with PKC activator, phorbol 12‐myristate 13‐acetate (PMA). A mutant XIAP construct in which Ser87 was substituted by Ala, was prepared, and transfected to cells. After the transfection of wild or mutant XIAP, cells viability was evaluated by counting living and dead cells treated with PMA during etoposide‐induced apoptosis. Results: Recombinant XIAP was phosphorylated at Ser⁸⁷ by PKC in vitro and treatment of XIAP‐transfected SH‐SY5Y cells with a PKC activator, phorbol 12‐myristate 13‐acetate (PMA) induced phosphorylation of XIAP at Ser⁸⁷. Pulse chase experiments revealed that, when phosphorylated at Ser⁸⁷, wild‐type XIAP is more stable than XIAP with a Ser87Ala substitution, which is degraded faster. Importantly, the phosphorylation of XIAP at the site by PKC significantly increased cell survival up to approximately 2.5 times under the condition of apoptosis induced by 25 µg/ml etoposide. Conclusion: The findings of the present study indicate a role for PKC, through phosphorylation of XIAP at Ser⁸⁷ and its stabilization, in cell survival under conditions of stress and lend strength to the idea that PKC is crucial in regulating neuronal homeostasis, which may be impaired in AD.     

In Vivo Study of Salsolinol Produced by a High Concentration of Acetaldehyde in the Striatum and Nucleus Accumbens of Free-Moving Rats

Background: Salsolinol, a neuropharmacologically active compound, is formed by the condensation of acetaldehyde (AcH) with dopamine (DA) in the brain. The aim of our study was to examine the effect of a high concentration of AcH on salsolinol formation and to compare the release of DA, serotonin (5-HT), and salsolinol in the striatum and nucleus accumbens (NAc) in free-moving rats.
Methods: After the insertion of a microdialysis probe, male Wistar rats (250–300 g) were treated with cyanamide (CY, a potent aldehyde dehydrogenase inhibitor) + ethanol (EtOH), CY + 4-methylpyrazole (4-MP, a strong alcohol dehydrogenase inhibitor) + EtOH, 4-MP + EtOH, CY, and 4-MP. Simultaneous quantitation of DA, 5-HT, and salsolinol in dialysates was performed by using in vivo microdialysis coupled with high-performance liquid chromatography with an electrochemical detector and blood EtOH and AcH by using a head-space gas chromatographic method.
Results: Salsolinol was detected only in the CY + EtOH groups in both the striatum and NAc, and we also detected a high AcH concentration in the blood in those groups. A correlation was found between the dialysate levels of salsolinol and blood concentrations of AcH. The striatal levels of DA and 5-HT were approximately two times higher, whereas salsolinol levels were approximately three times higher compared with the usual level in the NAc. No significant difference of DA and 5-HT levels in the dialysates was observed in either the control or the other study groups.
Conclusion: Our observation suggested that the brain salsolinol formation may depend on the concentrations of DA and AcH in freely moving rats, and there is no effect of a high concentration of AcH on DA and 5-HT levels in the striatum and NAc.     

Calculated 11B–13C NMR chemical shift relationship in hypercoordinate methonium and boronium ions

The boronium-carbonium continuum was extended to include hypercoordinated protonated methanes and their boron analogs. The ¹¹B NMR chemical shifts of the hypercoordinated hydriodo boron compounds and the ¹³C NMR chemical shifts of the corresponding isoelectronic and isostructural carbocations were calculated by using the GIAO-MP2 method. The data show good linear correlation between ¹¹B and ¹³C NMR chemical shifts, which indicates that the same factors that determine the chemical shifts of the boron nuclei also govern the chemical shifts of carbon nuclei of these hypercoordinated hydriodo compounds.     

Anti-inflammatory effects of Dendrobium nobile derived phenanthrenes in LPS-stimulated murine macrophages

Archives of Pharmacal Research - Dendrobium nobile belongs to the Orchidaceae family and is one of the medicinal herbs used in traditional Chinese medicine as a therapeutic agent for...     

Association between arsenic exposure from drinking water and hematuria: Results from the Health Effects of Arsenic Longitudinal Study

Arsenic (As) exposure has been associated with both urologic malignancy and renal dysfunction; however, its association with hematuria is unknown. We evaluated the association between drinking water As exposure and hematuria in 7843 men enrolled in the Health Effects of Arsenic Longitudinal Study (HEALS). Cross-sectional analysis of baseline data was conducted with As exposure assessed in both well water and urinary As measurements, while hematuria was measured using urine dipstick. Prospective analyses with Cox proportional regression models were based on urinary As and dipstick measurements obtained biannually since baseline up to six years. At baseline, urinary As was significantly related to prevalence of hematuria (P-trend < 0.01), with increasing quintiles of exposure corresponding with respective prevalence odds ratios of 1.00 (reference), 1.29 (95% CI: 1.04–1.59), 1.41 (95% CI: 1.15–1.74), 1.46 (95% CI: 1.19–1.79), and 1.56 (95% CI: 1.27–1.91). Compared to those with relatively little absolute urinary As change during follow-up (− 10.40 to 41.17 μg/l), hazard ratios for hematuria were 0.99 (95% CI: 0.80–1.22) and 0.80 (95% CI: 0.65–0.99) for those whose urinary As decreased by > 47.49 μg/l and 10.87 to 47.49 μg/l since last visit, respectively, and 1.17 (95% CI: 0.94–1.45) and 1.36 (95% CI: 1.10–1.66) for those with between-visit increases of 10.40 to 41.17 μg/l and > 41.17 μg/l, respectively. These data indicate a positive association of As exposure with both prevalence and incidence of dipstick hematuria. This exposure effect appears modifiable by relatively short-term changes in drinking water As.