Current Issue : January - March Volume : 2016 Issue Number : 1 Articles : 6 Articles
The research work was carried out to investigate the combination effect of dexamethasone with glipizide for a period of two weeks on blood glucose and triglyceride levels in wistar rats by oral route. Healthy young adult wistar rats of six to eight weeks old were randomly divided in to five groups. Out of five groups (6 rats/sex/group), one group was kept as control received vehicle alone and other three groups were treated with dexamethasone alone at different dose levels (2.5, 6.25 and 12.5 mg/kg) and another one group of rats received a combination of dexamethasone and glipizide at 12.5 and 2.0 mg/kg, respectively. At the end of treatment period, blood sample was collected from each animal for the estimation of glucose and triglyceride levels. A significant (p<0.01) increase in blood glucose and triglyceride level was noticed on 15th day following administration of dexamethasone at all dose levels in both the sexes. On the other hand, animals treated with combination of dexamethasone and glipizide showed significant (p<0.01, p<0.001) decrease in blood glucose and triglyceride levels in both male and female rats at the end of study period. This effect of combination therapy reveals an ameliorative effect of glipizide on dexamethasone induced hyperglycemia and increased triglyceride level in the blood. Based on the findings, it may be concluded that oral administration of glipizide along with dexamethasone has an ameliorative effect on blood glucose and triglyceride levels in rats indicate this combination therapy may be explored further in the treatment of diabetic arthropathy....
Physiological levels of estrogen appear to enhance angiotensin type 2 receptor- (AT2R-) mediated vasodilatation. However,\nthe effects of supraphysiological levels of estrogen, analogous to those achieved with high-dose estrogen replacement therapy\nin postmenopausal women, remain unknown. Therefore, we pretreated ovariectomized rats with a relatively high dose of\nestrogen (0.5mg/kg/week) for two weeks. Subsequently, renal hemodynamic responses to intravenous angiotensin II (Ang II, 30ââ?¬â??\n300 ng/kg/min) were tested under anesthesia, while renal perfusion pressure was held constant. The role of AT2R was examined\nby pretreating groups of rats with PD123319 or its vehicle. Renal blood flow (RBF) decreased in a dose-related manner in response\nto Ang II. Responses to Ang II were enhanced by pretreatment with estradiol. For example, at 300 ng kgâË?â??1 minâË?â??1, Ang II reduced\nRBF by 45.7 Ã?± 1.9% in estradiol-treated rats but only by 27.3 Ã?± 5.1% in vehicle-treated rats. Pretreatment with PD123319 blunted\nthe response of RBF to Ang II in estradiol-treated rats, so that reductions in RBF were similar to those in rats not treated with\nestradiol.We conclude that supraphysiological levels of estrogen promote AT2R-mediated renal vasoconstriction. This mechanism\ncould potentially contribute to the increased risk of cardiovascular disease associated with hormone replacement therapy using\nhigh-dose estrogen....
A key process in the regulation of protein activities and thus cellular signaling\npathways is the modification of proteins by post-translational mechanisms. Knowledge\nabout the enzymes (writers and erasers) that attach and remove post-translational\nmodifications, the targets that are modified and the functional consequences elicited by\nspecific modifications, is crucial for understanding cell biological processes. Moreover\ndetailed knowledge about these mechanisms and pathways helps to elucidate the molecular\ncauses of various diseases and in defining potential targets for therapeutic approaches.\nIntracellular adenosine diphosphate (ADP)-ribosylation refers to the nicotinamide adenine\ndinucleotide (NAD+)-dependent modification of proteins with ADP-ribose and is catalyzed\nby enzymes of the ARTD (ADP-ribosyltransferase diphtheria toxin like, also known as\nPARP) family as well as some members of the Sirtuin family. Poly-ADP-ribosylation is\nrelatively well understood with inhibitors being used as anti-cancer agents. However, the\nmajority of ARTD enzymes and the ADP-ribosylating Sirtuins are restricted to catalyzing\nmono-ADP-ribosylation. Although writers, readers and erasers of intracellular mono-ADPribosylation\nhave been identified only recently, it is becoming more and more evident that this\nreversible post-translational modification is capable of modulating key intracellular processes\nand signaling pathways. These include signal transduction mechanisms, stress pathways\nassociated with the endoplasmic reticulum and stress granules, and chromatin-associated\nprocesses such as transcription and DNA repair. We hypothesize that mono-ADP-ribosylation\ncontrols, through these different pathways, the development of cancer and infectious diseases....
Signalling proteins are key regulators of basic cell physiology and tissues\nmorphogenesis. Whilst signalling proteins are paramount for the cell to function optimally,\ntheir down regulation or inhibition is also central to tune the cell and its environment. One\nprocess involved in this tuning mechanism is membrane budding, otherwise known as\nendocytosis. The origin of the physical force driving the budding process and endocytosis\nhas been the subject of much controversy. After two decades the budding process is now\nwell described and it is acknowledged that fundamental principles from soft matter physics\nare at play. This opens a new window for understanding gene regulations, pharmacokinetic\nand multi drug resistance in cancer. This review recalls the first steps that have led to a better\nunderstanding of cell biology through the use of physics and; how the use of physics has\nshed light in areas of cell biology, cancer and pharmacology. It is, therefore, not a review of\nthe many enzymes involved in membrane vesiculation and membrane curvature; it is more\nof an historical account....
Background.The accompanied role of Mas receptor (MasR), bradykinin (BK), and female sex hormone on renal blood flow (RBF)\nresponse to angiotensin 1-7 is not well defined.We investigated the role ofMasR antagonist (A779) and BK on RBF response to Ang\n1-7 infusion in ovariectomized estradiol-treated rats. Methods.Ovariectomized Wistar rats received estradiol (OVE) or vehicle (OV)\nfor two weeks. Catheterized animals were subjected to BK and A799 infusion and mean arterial pressure (MAP), RBF, and renal\nvascular resistance (RVR) responses to Ang 1-7 (0, 100, and 300 ng kgâË?â??1 minâË?â??1) were determined. Results. Percentage change of RBF\n(%RBF) in response to Ang1-7 infusion increased in a dose-dependentmanner. In the presence of BK, when MasR was not blocked,\n%RBF response to Ang 1-7 in OVE group was greater than OV group significantly (...
Diabetes is a chronic endocrine disorder associated with several complications as hypertension, advanced brain aging, and\ncognitive decline. Accumulation of advanced glycation end products (AGEs) is an important mechanism that mediates diabetic\ncomplications. Upon binding to their receptor (RAGE), AGEs mediate oxidative stress and/or cause cross-linking with proteins\nin blood vessels and brain tissues. The current investigation was designed to investigate the effect of agents that decrease AGEs\nsignaling, perindopril which increases soluble RAGE (sRAGE) and alagebrium which cleaves AGEs cross-links, compared to the\nstandard antidiabetic drug, gliclazide, on the vascular and central nervous system (CNS) complications in STZ-induced (50mg/kg,\nIP) diabetes in rats. Perindopril ameliorated the elevation in blood pressure seen in diabetic animals. In addition, both perindopril\nand alagebrium significantly inhibited memory decline (performance in theY-maze), neuronal degeneration (Fluoro-Jade staining),\nAGEs accumulation in serum and brain, and brain oxidative stress (level of reduced glutathione and activities of catalase and\nmalondialdehyde). These results suggest that blockade of AGEs signaling after diabetes induction in rats is effective in reducing\ndiabetic CNS complications....
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