Effect of groundwater flow on forming arsenic contaminated groundwater in Sonargaon, Bangladesh

Three-dimensional groundwater flow in Sonargaon, Bangladesh is numerically simulated in order to evaluate the flow paths of As-contaminated drinking groundwater in the Holocene aquifer of the Ganges-Blamaptra-Meghna delta plain over a recent 30-year period. The model indicates that vertical infiltration of surface groundwater into the shallow Holocene aquifer occurs frequently in the Ganges-Blamaptra-Meghna delta plain. It predicts that the water recharged from ground surface moves approximately 10-20 m vertically downward beneath the flood plain, with a gradually increasing horizontal flow, toward the underlying Pleistocene middle mud layer (aquitard). The model also predicts that groundwaters containing highest As concentrations (>700 mu g/L) are formed on the vertical groundwater flow paths where surface water recharges the Holocene aquifer and not on the horizontal flow paths. Combining with the groundwater chemistry, reducing groundwater condition is not essential for the As-contaminated groundwater of the studied area in the Ganges delta plain.ArticleJOURNAL OF HYDROLOGY. 409(3-4):724-736 (2011)journal articl

Nateglinide with glibenclamide examination using the respiratory quotient (RQ)

Purpose: The respiratory quotient (RQ) is useful for evaluating glucose and lipid metabolism in vivo. We previously reported that the RQ value, even after fasting, was high in diabetics being treated with sulphonylurea (SU), which might explain the accumulation of fat, leading to weight gain in such individuals. In the present study, wemeasured the RQ in type II diabetic patients who were being treated with a rapid-onset/short-duration insulinotropic agent, nateglinide, and compared it with those being treated with SU. Methods: A glucose tolerance test was performed in 20 patients with type II diabetes mellitus treated with nateglinide and in 14 patients treated with SU, and the RQ was simultaneously measured. Results : The RQ values in the patients treated with nateglinide, were similar to those in healthy adults, but was lower than in those treated with SU. No weight gain was observed in patients treated with nateglinide. Conclusion : A significant weight gain was reported in subjects treated with SU, accompanied by an increase in RQ. However, weight gain was less frequent in diabetics treated with nateglinide

Evaluation of recharge areas of Arusha Aquifer, Northern Tanzania: application of water isotope tracers

This research article published by IWA Publishing, 2020In Arusha urban, northern Tanzania, groundwater contributes about 80% of the water supply. However, elevated fluoride levels and evidence of anthropogenic pollution have been reported in the groundwater around Mount Meru which is a water source for Arusha urban. This study aims at understanding the recharge areas and flow pathways of groundwater in what has been a poorly monitored area. The study uses the isotopic ratio of oxygen and hydrogen to estimate the groundwater recharge area and flow pathway. The results show the recharge elevation of groundwater is between 1,800 and 3,500 m above mean sea level on the slopes of Mount Meru. The average fluoride contents in the study area are 5.3 ± 0.4 mg/L greater than the limits of 1.5 mg/L set by the World Health Organization (WHO) and Tanzania. The nitrate concentration of 83.9 mg/L at the lower elevation areas (<1,400 m above mean sea level) exceeds the 50 mg/L WHO limit. The relationship of F− with δ18O and NO3− suggests the leaching of fluoride in high altitudes and dilution in lower altitudes

Propofol-induced vasodilation and aging

Background : Propofol causes vasodilation via endothelium-dependent and -independent mechanisms. Because endothelial function is impaired with aging, the effects of propofol on endothelium-dependent vasodilation might be altered by aging. The aim of this study was thus to determine the effects of aging on vascular responses to propofol. Methods : Young (4-6 weeks old) or adult (16-25 weeks old) rats were anesthetized with sevoflurane. The thoracic aorta was dissected and cut into pieces 3-4mm in length. In some rings, the endothelium was deliberately removed. The ring segment of the aorta was mounted for isometric force recording at a resting tension of 0.5-1.0 g in a 2 ml organ bath, containing Krebs-Ringer bicarbonate buffer. Arteries were precontracted with phenylephrine, and the function of endothelium was confirmed with acetylcholine. Then, we studied the concentration-dependent effects of propofol in endothelium-intact (control group) and -denuded aortic rings (denuded group), as well as those treated with N[ω]-nitro-L-arginine methylester (L-NAME group). Results : Relaxation due to propofol was observed in the control groups of both young and adult rats in a concentration-dependent manner, but the magnitude of relaxation was significantly greater in young rats. In addition, in young rats, relaxation due to propofol was significantly and equally reduced in both L-NAME and denuded groups at all propofol concentrations that we studied (10[-6]-10[-3] M). In adult rats, relaxation due to propofol was quite similar between control and L-NAME groups at all propofol concentrations, whereas it was significantly reduced in the denuded group. Conclusion : These results suggest that endothelium-derived nitric oxide plays an important role in propofol-induced vasodilation in young rats, but not in adult rats

Effect of Clozapine on DNA Methylation in Peripheral Leukocytes from Patients with Treatment-Resistant Schizophrenia

Clozapine is an atypical antipsychotic, that is established as the treatment of choice for treatment-resistant schizophrenia (SCZ). To date, no study investigating comprehensive DNA methylation changes in SCZ patients treated with chronic clozapine has been reported. The purpose of the present study is to reveal the effects of clozapine on DNA methylation in treatment-resistant SCZ. We conducted a genome-wide DNA methylation profiling in peripheral leukocytes (485,764 CpG dinucleotides) from treatment-resistant SCZ patients treated with clozapine (n = 21) in a longitudinal study. Significant changes in DNA methylation were observed at 29,134 sites after one year of treatment with clozapine, and these genes were enriched for “cell substrate adhesion” and “cell matrix adhesion” gene ontology (GO) terms. Furthermore, DNA methylation changes in the CREBBP (CREB binding protein) gene were significantly correlated with the clinical improvements. Our findings provide insights into the action of clozapine in treatment-resistant SCZ

Monkeys mutant for PKD1 recapitulate human autosomal dominant polycystic kidney disease.

Autosomal dominant polycystic kidney disease (ADPKD) caused by PKD1 mutations is one of the most common hereditary disorders. However, the key pathological processes underlying cyst development and exacerbation in pre-symptomatic stages remain unknown, because rodent models do not recapitulate critical disease phenotypes, including disease onset in heterozygotes. Here, using CRISPR/Cas9, we generate ADPKD models with PKD1 mutations in cynomolgus monkeys. As in humans and mice, near-complete PKD1 depletion induces severe cyst formation mainly in collecting ducts. Importantly, unlike in mice, PKD1 heterozygote monkeys exhibit cyst formation perinatally in distal tubules, possibly reflecting the initial pathology in humans. Many monkeys in these models survive after cyst formation, and cysts progress with age. Furthermore, we succeed in generating selective heterozygous mutations using allele-specific targeting. We propose that our models elucidate the onset and progression of ADPKD, which will serve as a critical basis for establishing new therapeutic strategies, including drug treatments

ガン カガク リョウホウ ニオケル ショウカカン ドクセイ ト ケッセイ Diamine Oxidase DAO カッセイ ニ カンスル ケントウ

There are so many patients with advanced gastric cancer who undergo systemic chemotherapy worldwide. The quality of life（QOL）of patients with gastric cancer who receive chemotherapy is often lowed by various gastrointestinal toxicities during the chemotherapy. Nutrition is also impaired by gastrointestinal toxicities. However, it is difficult to predict their occurrence in advance and further there is no good serum marker for nutrition in the patients treated with chemotherapy. Thus, it is important to objectively evaluate and predict the toxicity of the digestive tract during cancer chemotherapy. Diamine Oxidase（DAO）is an enzyme that is expressed in intestinal epithelial cells. Recently it has been reported that DAO activity may reflect damage or atrophy of the intestinal villi, and therefore it may be a sensitive serum marker for nutritional state. In this study, we measured serum DAO activity of patients with gastric cancer treated with systemic chemotherapy, and investigated the correlation between DAO activity and gastrointestinal toxicities. Six patients with gastric cancer, who were treated by docetaxel+cisplatin+S‐１combination chemotherapy, were enrolled. DAO activity was measured by sensitive colorimetric assay. DAO activities diminished after treatment in４patients with moderate to severe gastrointestinal toxicities. In contrast, they did not change in２patients with no gastrointestinal toxicities. Our results may suggest that DAO activity is a good serum marker for the gastrointestinal toxicities as well as nutrition state in patients who receive systemic chemotherapy. More large scale study is needed to warrant