In-vitro Toxicity Study of Cylindrospermopsin on Wistar Rats

Naturally derived cyanotoxin, Cylindrospermopsin (CYN) found in fresh water systems poses a threat to human health worldwide. Cylindrospermopsin (CYN) is most potent cyanotoxin which affects the functions of kidney and liver. The present study was carried out to determine the possible effects of Cylindrospermopsin on mammals using male Wistar rats as an animal model. All experimental protocols were approved by the ethics committee of Faculty of Medical Science, University of Sri Jayewardenepura (No. 17/18). Thirty-five Wistar rats were divided into five groups (n=7) and rats were orally treated with different concentrations of cyanotoxin; Cylindrospermopsin (2.5 μg/L, 2 μg/L, 1.5 μg/L) and control group was treated with distilled water for 90 days. Fifth group received environmental water sample contaminated with Cylindrospermopsin (2.3 μg/L) obtained from randomly selected well in Padaviya. Blood and urine samples from each individual were collected at 0, 7, 14, 28, 42, 60, 90 days intervals and the collected samples were subjected to serum creatinine and urine creatinine analysis using creatinine assay kits. Cylindrospermopsin in urine samples were quantified by the ELISA methods. Aspartate aminotransferase (AST), Aspartate alaninetransferase (ALT) and Full Blood Count (FBC) were analysed. The mean body weight of treated (200 to 310 g) and control groups (200-335 g) of the experiment gradually increased until fourteenth week. There was no significant difference of body weights between treated and control groups (p=0.08). The absolute and relative (% body weight) weights of liver and kidneys of the treated groups were less than control group. Cylindrospermopsin dose 2.5 μg/L, 2 μg/L , 1.5 μg/L, 2.3 μg/L and control showed increased serum creatinine levels from 0.62 to 0.87 mg/dL, 0.64 to 0.86 mg/dL, 0.64 to 0.86 mg/dL, 0.61 to 0.83 mg/dL and 0.6 to 0.79 mg/dL respectively after 90 days treatment. The control group did not show a significant cause. Rat treated with different concentrations of Cylindrospermopsin, 2.5 μg/L, 2 μg/L, 1.5 μg/L, 2.3 μg/L and control showed gradually decreased of urine creatinine level from 34 to 55 mg/dL, 40 to 54 mg/dL, 38 to 54 mg/dL, 32 to 53 mg/dL and 43 to 54 mg/dL respectively after 90 days treatment and statistically significant (p<0.05) difference was found between treated and control groups. The highest Aspartate Aminotransferase (AST) and Aspartate Alaninetransferase (ALT) levels were obtained from Cylindrospermopsin dose 2.5 μg/L at 90 days exposure. Cylindrospermopsin concentration in urine gradually increased from 1.5 to 2.32 μg/L, 0.9 to 1.7 μg/L, 0.8 to 1.1 μg/L and 0.4 to 1.5 μg/L when animal exposed to 2.5 μg/L, 2 μg/L, 1.5 μg/L and 2.3 μg/L concentrations of Cylindrospermopsin where control did not show. Thus, the result of present study show consumption of Cylindrospermopsin contaminated water may lead to liver and kidney injuries.Keywords: Cylindrospermopsin (CYN), Wistar rats, ELISA, AST, AL

The costs in provision of haemodialysis in a developing country: A multi-centered study

<p>Abstract</p> <p>Background</p> <p>Chronic Kidney Disease is a major public health problem worldwide with enormous cost burdens on health care systems in developing countries. We aimed to provide a detailed analysis of the processes and costs of haemodialysis in Sri Lanka and provide a framework for modeling similar financial audits.</p> <p>Methods</p> <p>This prospective study was conducted at haemodialysis units of three public and two private hospitals in Sri Lanka for two months in June and July 2010. Cost of drugs and consumables for the three public hospitals were obtained from the price list issued by the Medical Supplies Division of the Department of Health Services, while for the two private hospitals they were obtained from financial departments of the respective hospitals. Staff wages were obtained from the hospital chief accountant/chief financial officers. The cost of electricity and water per month was calculated directly with the assistance of expert engineers. An apportion was done from the total hospital costs of administration, cleaning services, security, waste disposal and, laundry and sterilization for each unit.</p> <p>Results</p> <p>The total number of dialysis sessions (hours) at the five hospitals for June and July were 3341 (12959) and 3386 (13301) respectively. Drug and consumables costs accounted for 70.4-84.9% of the total costs, followed by the wages of the nursing staff at each unit (7.8-19.7%). The mean cost of a dialysis session in Sri Lanka was LKR 6,377 (US$56). The annual cost of haemodialysis for a patient with chronic renal failure undergoing 2-3 dialysis session of four hours duration per week was LKR 663,208-994,812 (US$ 5,869-8,804). At one hospital where facilities are available for the re-use of dialyzers (although not done during study period) the cost of consumables would have come down from LKR 5,940,705 to LKR 3,368,785 (43% reduction) if the method was adopted, reducing costs of haemodialysis per hour from LKR 1,327 at present to LKR 892 (33% reduction).</p> <p>Conclusions</p> <p>This multi-centered study demonstrated that the costs of haemodialysis in a developing country remained significantly lower compared to developed countries. However, it still places a significant burden on the health care sector, whilst possibility of further cost reduction exists.</p

BAF complex-mediated chromatin relaxation is required for establishment of X chromosome inactivation

The process of epigenetic silencing, while fundamentally important, is not yet completely understood. Here we report a replenishable female mouse embryonic stem cell (mESC) system, Xmas, that allows rapid assessment of X chromosome inactivation (XCI), the epigenetic silencing mechanism of one of the two X chromosomes that enables dosage compensation in female mammals. Through a targeted genetic screen in differentiating Xmas mESCs, we reveal that the BAF complex is required to create nucleosome-depleted regions at promoters on the inactive X chromosome during the earliest stages of establishment of XCI. Without this action gene silencing fails. Xmas mESCs provide a tractable model for screen-based approaches that enable the discovery of unknown facets of the female-specific process of XCI and epigenetic silencing more broadly.Andrew Keniry ... Jose M. Polo ... et al

Smchd1 is a maternal effect gene required for genomic imprinting

Genomic imprinting establishes parental allele-biased expression of a suite of mammalian genes based on parent-of-origin specific epigenetic marks. These marks are under the control of maternal effect proteins supplied in the oocyte. Here we report epigenetic repressor Smchd1 as a novel maternal effect gene that regulates the imprinted expression of ten genes in mice. We also found zygotic SMCHD1 had a dose-dependent effect on the imprinted expression of seven genes. Together, zygotic and maternal SMCHD1 regulate three classic imprinted clusters and eight other genes, including non-canonical imprinted genes. Interestingly, the loss of maternal SMCHD1 does not alter germline DNA methylation imprints pre-implantation or later in gestation. Instead, what appears to unite most imprinted genes sensitive to SMCHD1 is their reliance on polycomb-mediated methylation as germline or secondary imprints, therefore we propose that SMCHD1 acts downstream of polycomb imprints to mediate its function