Current Issue : January - March Volume : 2014 Issue Number : 1 Articles : 8 Articles
Cystic fibrosis is caused by more than 1000 mutations, the most common being the DF508 mutation. These mutations have\r\nbeen divided into five classes [1], with DF508 CFTR in class II. Here we have studied the class V mutation A455E. We report\r\nthat the mature and immature bands of A455E are rapidly degraded primarily by proteasomes; the short protein half-life of\r\nthis mutant therefore resembles that of DF508 CFTR. A455E could be rescued by treatment of the cells with proteasome\r\ninhibitors. Furthermore, co-transfection of A455E with the truncation mutant D264 CFTR also rescued the mature C band,\r\nindicating that A455E can be rescued by transcomplementation. We found that D264 CFTR bound to A455E, forming a\r\nbimolecular complex. Treatment with the compound correctors C3 and C4 also rescued A455E. These results are significant\r\nbecause they show that although DF508 belongs to a different class than A455E, it can be rescued by the same strategies,\r\noffering therapeutic promise to patients with Class V mutations....
Due to the increasing cases of neurodegenerative diseases in recent years, the eventual goal of nerve repair is very important.\r\nOne approach for achieving a neuronal cell induction is by regenerative pharmacology. Nerve growth factor (NGF) and brain\r\nderived neurotrophic factor (BDNF) are neurotrophins that play roles in neuronal development, differentiation, and protection.\r\nOn the other hand, dehydroepiandrosterone (DHEA) is a neurosteroid which has multiple actions in the nervous system. DHEA\r\ncould be an important agent in regenerative pharmacology for neuronal differentiation during tissue regeneration. In this study,\r\nwe investigated the possible role of DHEA to modulate NGF and BDNF production. The in vivo level of neurotrophins expression\r\nwas demonstrated by ELISA in rat harvested brain cortex. Also neurotrophins expression after DHEA treatment was revealed by\r\nthe increased neurite extension, immunostaining, and BrdU labeling in rats. Anti-NGF and anti-BDNF antibodies were used as\r\nsuppressive agents on neurogenesis. The results showed that NGF and BDNF are overproduced after DHEA treatment but there is\r\nnot any overexpression for NT-3 and NT-4. Also DHEA increased neurite extension and neural cell proliferation significantly.\r\nOverall, DHEA might induce NGF and BDNF neurotrophins overproduction in cortical neurons which promotes neural cell\r\nprotection, survival, and proliferation....
Background: Dipyrithione (PTS2) is widely used as a bactericide and fungicide. Here, we investigated whether PTS2\r\nhas broad-spectrum antitumor activity by studying its cytotoxicity and proapoptotic effects in four cancer cell lines.\r\nMethods: We used MTT assays and trypan blue staining to test the viability of cancer cell lines. Hoechst 33258 and\r\nDAPI staining were used to observe cell apoptosis. Cell-cycle percentages were analyzed by flow cytometry.\r\nApoptosis was assayed using caspase-3 and poly (ADP-ribose) polymerase (PARP) combined with Western blotting.\r\nStudent�s t-test was used for statistical analysis.\r\nResults: PTS2 inhibited proliferation in four cancer cell lines in a dose-dependent manner. Treated cells showed\r\nshrinkage, irregular fragments, condensed and dispersed blue fluorescent particles compared with control cells.\r\nPTS2 induced cycle-arrest and death. Cleavage of caspase-9, caspase-3, and PARP were detected in PTS2-treated\r\ncells. Antitumor activity of PTS2 was more effective against widely used cancer drugs and its precursor.\r\nConclusions: PTS2 appears to have novel cytotoxicity and potent broad-spectrum antitumor activity, which\r\nsuggests its potential as the basis of an anticancer drug....
This study was conducted to investigate effect of Bifenthrin on gravimetric parameters in Wistar rats. This study was conducted in eight week old Wistar rats. Twenty four male and twenty four female wistar rats were randomly divided into four different groups, Group I, II, III and IV comprising six male and six female rats. Group I served as vehicle control and treated with corn oil only. Group II, III and IV served as treatment group and treated with Bifenthrin at dose rates of 2.5, 10 and 20 mg/kg body weight respectively for 28 days daily in corn oil. Body weight was recorded on day 0, 7, 14, 21 and 28. Body weight change and feed consumption was calculated on weekly basis. After completion of 28 days of exposure period liver, kidney, heart, spleen, lungs, thymus and adrenals absolute and relative organ weight estimation was performed. Significant decrease in body weight and body weight gain was observed in treated group of animals in both male and female rats. Significant decrease in feed consumption was observed during treatment in treated group of animals in both male and female rats. Absolute and relative organ weight estimation revealed, significant increase in absolute liver and kidney weight in treatment group in both male and female rats. On the other hand significant decrease in absolute adrenal weight was observed in treatment group. There was significant increase in relative liver, kidney and heart weight observed in treatment group of male rats. Similarly significant increase in relative liver and kidney weight was observed in female treatment group of animals. Based on these study findings, it was concluded that Bifenthrin significantly altered the body weight, feed consumption, absolute and relative organ weight in wistar rats at the dose level tested....
The present study was conducted in eight week old male and female Wistar rats. Twenty four male and twenty four female wistar rats were randomly divided into four different groups, Group I, II, III and IV comprising six male and six female rats. Group I served as vehicle control and treated with corn oil. Group II, III and IV served as treatment group and treated with Bifenthrin at dose rates of 2.5, 10 and 20 mg/kg body weight respectively for 28 days daily in corn oil. After 28 days continuous exposure period blood sample was collected on day 29 to study effect on various hematological and biochemical parameters. Bifenthrin, a synthetic pyrethroid insecticide significantly altered hematological parameters (MCV and MCH) in male treated rats. Similarly there was significant increase in serum aminotransferases (ALT, AST), alkalne phosphatase (ALP), creatinine (CRT), urea and glucose levels in treated group of rats as compared to concurrent control group of rats in both sexes. Serum potassium electrolyte level was significantly decreased in male treated rats. Based on these study findings, it was concluded that Bifenthrin significantly altered the hematological and biochemical parameters in wistar rats after four weeks repeated oral exposure....
Anemia is one of the many complications of chronic kidney disease (CKD). However, the current prevalence of anemia in\r\nCKD patients in the United States is not known. Data from the National Health and Nutrition Examination Survey (NHANES)\r\nin 2007ââ?¬â??2008 and 2009ââ?¬â??2010 were used to determine the prevalence of anemia in subjects with CKD. The analysis was\r\nlimited to adults aged .18 who participated in both the interview and exam components of the survey. Three outcomes\r\nwere assessed: the prevalence of CKD, the prevalence of anemia in subjects with CKD, and the self-reported treatment of\r\nanemia. CKD was classified into 5 stages based on the glomerular filtration rate and evidence of kidney damage, in\r\naccordance with the guidelines of the National Kidney Foundation. Anemia was defined as serum hemoglobin levels #12 g/\r\ndL in women and #13 g/dL in men. We found that an estimated 14.0% of the US adult population had CKD in 2007ââ?¬â??2010.\r\nAnemia was twice as prevalent in people with CKD (15.4%) as in the general population (7.6%). The prevalence of anemia\r\nincreased with stage of CKD, from 8.4% at stage 1 to 53.4% at stage 5. A total of 22.8% of CKD patients with anemia\r\nreported being treated for anemia within the previous 3 monthsââ?¬â??14.6% of patients at CKD stages 1ââ?¬â??2 and 26.4% of patients\r\nat stages 3ââ?¬â??4. These results update our knowledge of the prevalence and treatment of anemia in CKD in the United States....
PTEN is a tumor suppressor and multi-functional growth regulator gene that encodes the protein phosphatase and\r\ntensin homolog. The phosphatase and tensin homolog and exerts its action by dephosphorylating PIP3 (phosphotidyl inositol\r\ntriphosphate), the lipid second messenger which activates the mTOR intracellular signaling pathway thereby regulating cell\r\ncycle and apoptosis. PTEN gene mutations are common in human cancer cell lines. In addition, PTEN gene has been found to be\r\nmutated in patients with autism and certain macrocephaly associated inherited disorders such as hamartomatous syndromes.\r\nThe role of PTEN gene and mTOR has been reported in a diverse spectrum of neurological disorders. The objective of the review\r\nis to focus on PTEN gene mutation, its impact on neurological disorders and the need for vital research in the area so as to\r\ndevelop novel targets for therapy....
Background: Given that toxicology studies the potential adverse effects of environmental exposures on various\r\nforms of life and that clinical toxicology typically focuses on human health effects, what can and should the\r\nrelatively new term of ââ?¬Å?translational toxicologyââ?¬Â be taken to mean?\r\nDiscussion: Our assertion is that the core concept of translational toxicology must incorporate existing principles\r\nof toxicology and epidemiology, but be driven by the aim of developing safe and effective interventions beyond\r\nsimple reduction or avoidance of exposure to prevent, mitigate or reverse adverse human health effects of\r\nexposures.\r\nThe field of toxicology has now reached a point where advances in multiple areas of biomedical research and\r\ninformation technologies empower us to make fundamental transitions in directly impacting human health.\r\nTranslational toxicology must encompass four action elements as follows:\r\n1) Assessing human exposures in critical windows across the lifespan\r\n2) Defining modes of action and relevance of data from animal models\r\n3) Use of mathematical models to develop plausible predictions as the basis for\r\n4) Protective and restorative human health interventions.\r\nThe discussion focuses on the critical window of in-utero development.\r\nSummary: Exposure assessment, basic toxicology and development of certain categories of mathematical models\r\nare not new areas of research; however overtly integrating these in order to conceive, assess and validate effective\r\ninterventions to mitigate or reverse adverse effects of environmental exposures is our novel opportunity. This is\r\nwhat we should do in translational toxicology so that we have a portfolio of interventional options to improve\r\nhuman health that include both minimizing exposures and specific preventative/restorative/mitigative therapeutics....
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