MicroRNA Expression Profiling of Human Respiratory Epithelium Affected by Invasive Candida Infection

Invasive candidiasis is potentially life-threatening systemic fungal infection caused by Candida albicans (C. albicans). Candida enters the blood stream and disseminate throughout the body and it is often observed in hospitalized patients, immunocompromised individuals or those with chronic diseases. This infection is opportunistic and risk starts with the colonization of C. albicans on mucocutaneous surfaces and respiratory epithelium. MicroRNAs (miRNAs) are small non-coding RNAs which are involved in the regulation of virtually every cellular process. They regulate and control the levels of mRNA stability and post-transcriptional gene expression. Aberrant expression of miRNAs has been associated in many disease states, and miRNA-based therapies are in progress. In this study, we investigated possible variations of miRNA expression profiles of respiratory epithelial cells infected by invasive Candida species. For this purpose, respiratory epithelial tissues of infected individuals from hospital laboratory were accessed before their treatment. Invasive Candida infection was confirmed by isolation of Candia albicans from the blood cultures of the same infected individuals. The purity of epithelial tissues was assessed by flow cytometry (FACSCalibur cytometer; BD Biosciences, Heidelberg, Germany) using statin antibody (S-44). TaqMan quantitative real-time PCR (in a TaqMan Low Density Array format) was used for miRNA expression profiling. MiRNAs investigated, the levels of expression of 55 miRNA were significantly altered in infected tissues. Some miRNAs showed dramatic increase (miR-16-1) or decrease of expression (miR-17-3p) as compared to control. Gene ontology enrichment analysis of these miRNA-targeted genes suggests that Candidal infection affect many important biological pathways. In summary, disturbance in miRNA expression levels indicated the change in cascade of pathological processes and the regulation of respiratory epithelial functions following invasive Candidal infection. These findings contribute to our understanding of host cell response to Candidal systemic infections

Inotropic and chronotropic effects of methanol extract of Aquilaria agallocha on rabbit heart

Aquilaria agallocha Roxb. (Thymelaeceae) heartwood is used in cardiac failure; however, its cardiotonic properties are poorly understood at a pharmacological level. This study investigated methanol extract of A. agallochafor presence of glycosides and its effects on force of contraction, heart rate and coronary flow on rabbit isolated heart. Furthermore, contribution of β1-adrenoceptors and/or L-type Ca2+ channels in A. agallocha-induced cardiac effects was explored. A. agallocha extract, digoxin, verapamil and metoprolol were administered in a retrograde manner. Force of contraction and heart rate were recorded with a force transducer attached to the heart. Coronary flow was measured from collected effluent. The extract induced a significant increase in force of contraction (p<0.001), decrease in heart rate (p<0.05) and coronary flow (p<0.001). Metoprolol (p<0.01) and verapamil (p<0.01) significantly inhibited the plant extract-induced effects. Thus, A. agallocha exhibited cardiotonic effects, most likely via cardiac glycosides, involving ?1-adrenoceptors and L-type Ca2+ channels

Hepato- and nephro-protective as well as hypoglycemic effects of sea buckthorn berries (Hippophae rhamnoides L.) in rabbits and humans

The hepato- and nephro-protective effects of sea buckthorn berries (Hippophae rhamnoides L) were investigated in paracetamol-induced toxicity in animals and hypoglycemic effects in type II diabetic patients. Crude drug preparation and its methanol extract have shown a profound decrease in paracetamol-induced elevated serum levels of liver and kidney functions under investigation, which suggests a possible therapeutic role of its constituents in hepatic injury and altered kidney functions. Similarly, in human patients with raised glucose levels, sea buckthorn shows hypoglycemic effect which could likely make it a potential therapeutic agent to mange type II diabetes mellitus. However, further investigations are required to unveil the mechanism of action of sea buckthorn preparations in these ailments.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Iono- and chronotropic effects of aqueous extract of berberis lycium royle root bark and berberine on in situ frog-heart preparation

Berberis lycium Royle is used in folk medicines for treating various ailments however it has not been investigated in cardiac problems at pharmacological level. Here, iono- and chronotropic effects of B. lycium root bark’s aqueous extract and berberine were studied on frog-heart. Present data showed that aqueous extracts of B. lycium and berberine exhibited dose-dependent negative chronotropic and ionotropic effects and at higher doses both caused a heart block. Berberine also displayed a positive ionotropic effect but at very low doses. Diltiazem did not antagonize positive ionotropic effect of berberine indicating that this activity is independent of L-type calcium channels, while propranolol antagonized the positive ionotropic effect, suggesting involvement of β1 - adrenoceptors. It is concluded that ionotropic and chronotropic effects exerted by aqueous extract of B. lycium may be due to berberine while its negative ionotropic actions and heart block may attribute to other active principle(s) present in the extract.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Comparison of signalling mechanisms underlying UTP-evoked vasoconstriction of rat pulmonary and tail arteries

The endogenous nucleotide, UTP, acts at smooth muscle P2Y receptors to constrict rat pulmonary and tail arteries, but the underlying signalling pathways are poorly understood. The aim was to characterise the contribution of Ca2+ release and influx, rho kinase and protein kinase C to these contractions. Isometric tension was recorded from endothelium-denuded rat intralobar pulmonary and tail artery rings mounted on a wire myograph. Contractions were evoked by UTP and peak amplitude measured. Thapsigargin (1 µM), but not ryanodine (10 µM), significantly depressed contractions in both by 30-40% (P<0.05). Nifedipine (1 µM) significantly reduced contractions in tail artery by ~60% (P<0.01). Y27632 (10 µM), a rho kinase inhibitor and GF109203X (10 µM), a protein kinase C inhibitor, each significantly reduced pulmonary vasoconstriction by ~20%, and tail artery contractions by ~80% and ~40%, respectively (P<0.01). In pulmonary artery, Y27632, GF109203X and thapsigargin, acted in an additive manner, but nifedipine less so. Adding all four together abolished the UTP response. In tail artery, Y27632 plus thapsigargin or GF109203X or nifedipine abolished contractions. Thapsigargin, GF109203X and nifedipine, coapplied pair-wise, acted additively and applying all three together abolished UTP-evoked contractions. So, Ca2+ release from the sarcoplasmic reticulum and influx through Cav1.2 channels, but not ryanodine receptors, play significant roles in UTP-evoked vasoconstriction of rat pulmonary and tail arteries. Rho kinase and protein kinase C are also involved, but more so in tail artery. Thus UTP activates multiple signalling mechanisms that lead to vasoconstriction, but their relative importance differs in pulmonary compared with systemic arteries

Hepatoprotective effect of aqeous methanolic extract of Rumex dentatus in paracetamol induced hepatotoxicity in mice

Rumex dentatus is well known plant of Polygonaceae family which is widely used in traditional medicine to treat gastrointestinal tract. R. dentatus at doses 250 and 500 mg/kg significance decreased (p<0.001) the elevated level of ALT, AST, ALP and bilirubin induced by paracetamol and results are comparable (p<0.001) with silymarin. The results were supported by histopathological investigations, phytochemical screening and detection of hepatoprotective active constituents e.g quercetin, kaempferol, myricetin by HPLC. So, it is concluded that R. dentatus has hepatoprotective effect against paracetamol liver damage in mice

GC-MS Analysis and Gastroprotective Evaluations of Crude Extracts, Isolated Saponins, and Essential Oil from Polygonum hydropiper L.

Peptic ulceration is among the most prevalent gastrointestinal disorders characterized by pepsin and gastric acid mediated mucosal damage, as result of imbalance between defensive and offensive processes. The main objective of the current study was to investigate the antiulcer potentials of Polygonum hydropiper crude methanolic ectract (Ph.Cr) in aspirin induced ulcerogenesis using pylorus ligated rat model. In-vitro urease and Proteus mirabilis inhibitory potentials were evaluated using standard protocols. All fractions were analyzed using GC-MS to identify major components. The aspirin induced ulcerogenesis in pylorus ligated rat model was associated with significant changes in the mean ulcer score [F(5, 30) = 7.141, P = 0.0002], gastric juice volume [F(5, 30) = 8.245, P &lt; 0.0001], gastric juice pH [F(5, 30) = 5.715, P = 0.0008], free acidity [F(5, 30) = 4.544, P = 0.0033], total acidity [F(5, 30) = 2.740, P = 0.0373], and pepsin concentration [F(5, 30) = 2.335, P = 0.0664]. Pre-treatment with Ph.Cr at 100, 200, and 400 mg/kg dose exhibited marked gastroprotective and anti-ulcerogenic effect in the aspirin induced pyloric ligation ulcerogenesis model at 100, 200, and 400 mg/kg as indicated by ulcerative biochemical parameters. In urease inhibition assay, leaves essential oil (Ph.Lo), saponins (Ph.Sp), and chloroform extract (Ph.Chf) exhibited highest activities with IC50 of 90, 98, and 520 μg/ml, respectively. Ph.Sp, Ph.Chf, ethyl acetate (Ph.EtAc), and Ph.Cr showed MICs of 25, 30, 32.25, and 40.50 μg/ml, respectively against P. mirabilis. Several compounds were identified in GC-MS analysis of samples. Significant in-vivo antiulcer, urease inhibitory as well as anti-proteus potentials of P. hydropiper solvent extracts, signify its potential use for the management of peptic ulcers and may provide scientific bases for the traditional uses of the plant

Expression of P2X receptors in rat pulmonary artery

The P2X receptors expressed in rat large (LPA) and small (SPA) pulmonary artery were characterised using pharmacological and molecular techniques and signalling pathways that mediate their contractile effects were investigated. The role of P2X receptors in sympathetic neurotransmission was also investigated.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Expression of P2X receptors in rat pulmonary artery

The P2X receptors expressed in rat large (LPA) and small (SPA) pulmonary artery were characterised using pharmacological and molecular techniques and signalling pathways that mediate their contractile effects were investigated. The role of P2X receptors in sympathetic neurotransmission was also investigated.EThOS - Electronic Theses Online ServiceGBUnited Kingdo