Meltonkelley7072

CONCLUSION Fascinatingly Qrctn and N-GIuta combination was the most powerful regimen to frustrate ACMP reno-toxicity and may be deliberate as a hopeful applicant for renal therapy.BACKGROUND The regulation of the immune system by the sympathetic nervous system is allowing the design of novel treatments for inflammatory disorders such as arthritis. In this study, we have analyzed the effects of a- and p-adrenoceptor agonists injected subcutaneously, intrathecally, or intra-articularly in zymosan-induced arthritis. METHODS Murine arthritis was induced by intra-articular (knee joint) injection of zymosan. α1 (phenylephrine), α2 (clonidine), β1 (dobutamine), or β2 (salbutamol)-adrenoceptor agonists were injected subcutaneously (sc), intrathecally (it), or intra-articularly (id) to activate peripheral, spinal, or intra-articular adrenoceptors and to study their effects on articular edema formation and neutrophil migration into the synovial cavity. RESULTS Treatments with phenylephrine did not affect the edema formation, but it increased neutrophil migration when injected subcutaneously (155.3%) or intra-articularly (187.7%). Treatments with clonidine inhibited neutrophil migration (59.9% sc, 68.7% it, 42.8% ia) regardless of the route of administration, but it inhibited edema formation only when injected intrathecally (66.7%) or intra-articularly (36%) but not subcutaneously. Treatments with dobutamine inhibited both edema (42.0% sc, 69.5% it, 61.6% ia) and neutrophil migration (28.4% sc, 70.3% it, 82.4% ia) in a concentration dependent manner. Likewise, all the treatments with salbutamol also inhibited edema formation (89.9% sc, 62.4% it, 69.8% ia) and neutrophil migration (76.6% sc, 39.1% it, 71.7% ia). CONCLUSION Whereas the p-adrenoceptor agonists induced anti-inflammatory effects regardless of their route of administration, α1- and α2-adrenoceptor agonists induced either pro- and anti-inflammatory effects, respectively.BACKGROUND Alzheimer's disease (AD) constitutes a neural loss in histology of brain with involvement of complex genomic and environmental factors. Accumulation of amyloid beta (Aβ) peptide and phosphorylated tau are indicative of progression and cognitive decline. Hence an understanding of the underlying biological pathways and targets along with associated mechanisms would be useful for the development of improved therapeutics for treating AD. In the present work, we aim to identify concealed targets for developing first line therapeutics and repositioning of validated targets as well as FDA- approved drugs using a system biology approach. METHODS We have collated information pertaining to the biological targets as well as the approved drugs, from scientific literature and patents. RESULTS In all, the imbalance in the functioning of around 79 proteins and genes were identified to be involved in Alzheimer's cascade. Amongst them, around 21 targets were found to be under therapeutic consideration for AD. Of the remaining, around 17 targets were reported as potential targets for AD, although they are under researcher's attention for other physio-pathological conditions. The analysis further revealed that -41 therapeutic targets are pharmacologically concealed but structurally validated targets and may constitute as potential therapeutic candidate for future drug discovery for AD. CONCLUSION The biological pathway vs. drug mapping provides a complete overview about underlying biological pathways, therapeutic targets (explored and concealed), associated mechanisms, existing therapeutics and the information pertaining to molecules currently under active drug development for further drug discovery and drug re-positioning/repurposing approaches for AD management.BACKGROUND To compare pharmacologic effects of pirenzepine and AF-DX116, a selective competitive antagonist for M1 and M2 subtype muscarinic cholinergic receptors (mAChRs), respectively, with atropine, a non-selective competitive antagonist for mAChRs, on Lipopolysaccharide (LPS). METHODS Male C57BL/6 mice were used to establish models of LPS-induced experimental endotoxemia. Mice were intraperitoneally injected 10 min prior to LPS injection with control (saline), atropine, pirenzepine and AF-DX116, respectively. find more Overall survival time was estimated using Kaplan-Meier plots. Inflammatory cytokine tumor necrosis factor-α (TNF-α) was monitored at various intervals after LPS injection and individual reagent administration. Pathological alternations in lungs and liver were analyzed. RESULTS Pirenzepine and atropine pretreatment improved survival rate of LPS-induced septic shock; in contrast, AF-DX116 accelerated death from sepsis. Moreover, TNF-α plasma level was decreased in response to pirenzepine or atropine, whereas increased in response to AF-DX116. Pirenzepine and atropine relieved whereas AF-DX116 accelerated LPS-induced pulmonary and hepatic injury. Pirenzepine reduced proportion of M1 subtype of macrophages, while AF-DX116 promoted polarization of macrophages to M1 subtype. Pirenzepine pretreatment reduced while AF-DX116 enhanced expression of SOCS3 at mRNA level. CONCLUSIONS The administration of pirenzepine and atropine may have beneficial effects on septic shock.BACKGROUND Metformin, a widely used anti-diabetic drug has gained enormous attention as an anticancer agent. This study seeks to investigate the efficacy of metformin in ameliorating aqueous extract of betelnut (AEBN) and arecoline induced carcinogenesis in a murine model. METHODS Swiss albino mice were exposed to AEBN (2 mg ml 1) and arecoline (10 μg ml 1) in drinking water for 16 weeks followed by co-administration of metformin (75 mg kg 1 or 150 mg kg 1) for 4 or 8 weeks. Histological changes and oxidative stress were assessed by haematoxylin and eosin staining, TBARS assay and protein carbonylation assay respectively. Lipid profile was determined using an automated analyzer. Expression of total and phosphorylated AMPK, ACC and p53 were determined by immunoblotting. RESULTS AEBN and arecoline induced dyslipidemia by downregulating AMPK (Thr-172) and activating ACC (Ser-79); they also downregulated tumor suppressor p53 (Ser-15). Metformin treatment induced AMPK-dependent alleviation of dyslipidemia in a dose and time dependent manner, upregulated p53 (Ser-15), restored tissue architecture and reduced oxidative stress in tissues of AEBN and arecoline treated mice.