Search

As a strategy to prevent the well-known immunosuppressant effects of cyclophosphamide (CY), the immunomodulatory activity of the polysaccharide isolated from Urtica macrorrhiza Hand.-Mazz. (UMHMPS) was investigated in the present study. The chemical properties of UMHMPS, including total carbohydrates, uronic acid, protein contents, monosaccharide compositions, molecular weight and structural confirmation, were investigated. The immunomodulatory activity of UMHMPS was evaluated using a CY-induced immunosuppression mouse model. The results revealed that UMHMPS, which is composed of rhamnose, gluconic acid, galactose acid, galactose and xylose, exhibited potent immunomodulatory activity and low toxicity in mice. It increased the secretions of secretory immunoglobulin A, interferon (IFN)-γ and interleukin (IL)-4, and maintained the balance of the ratios of IFN-γ/IL-4 and cluster of differentiation (CD)3+/CD19+ cells in Peyer's patches. Furthermore, it increased the expression of Toll-like receptor (TLR)-4, indicating that TLR4 may be one of the receptors of UMHMPS. Therefore, the present study provides evidence for the potential use of UMHMPS as an immune enhancement drug in chemotherapy. [ABSTRACT FROM AUTHOR]

Objective: Adenylyl cyclases (ACs) play important role in regulating pancreatic beta cell growth, survival and secretion through the synthesis of cyclic AMP (cAMP). MDL-12,330A and SQ 22536 are two AC inhibitors used widely to establish the role of ACs. The goal of this study was to examine the effects of MDL-12,330A and SQ 22536 on insulin secretion and underlying mechanisms. Methods: Patch-clamp recording, Ca2+ fluorescence imaging and radioimmunoassay were used to measure outward K+ currents, action potentials (APs), intracellular Ca2+ ([Ca2+]i) and insulin secretion from rat pancreatic beta cells. Results: MDL-12,330A (10 µmol/l) potentiated insulin secretion to 1.7 times of control in the presence of 8.3 mmol/l glucose, while SQ 22536 did not show significant effect on insulin secretion. MDL-12,330A prolonged AP durations (APDs) by inhibiting voltage-dependent K+ (KV) channels, leading to an increase in [Ca2+]i levels. It appeared that these effects induced by MDL-12,330A did not result from AC inhibition, since SQ 22536 did not show such effects. Furthermore, inhibition of the downstream effectors of AC/cAMP signaling by PKA inhibitor H89 and Epac inhibitor ESI-09, did not affect KV channels and insulin secretion. Conclusion: The putative AC inhibitor MDL-12,330A enhances [Ca2+]i and insulin secretion via inhibition of KV channels rather than AC antagonism in beta cells, suggesting that the non-specific effects is needed to be considered for the right interpretation of the experimental results using this agent in the analyses of the role of AC in cell function. [ABSTRACT FROM AUTHOR]

We monitored the therapeutic drug paclitaxel (Zisu) and studied its anticancer activity and side effects in 11 cancer patients. After intravenous infusion of 135 to 185 mg/m2 of paclitaxel, Cmax ranged from 2.17 to 9.17 mg/L and AUC ranged from 4.37 to 16.01 mg/h/L. A significant individual difference in pharmacokinetic parameters was found. Among the 11 patients, 6 achieved a partial remission and one patient had a mild response. The Cmax of the patients who achieved PR and MR was higher in comparison to the patients with no response. In 4 of the 6 PR patients, Cmax was above 4.38 mg/L. In four of the NR patients, Cmax was equal to or below 4.04 mg/L. These results suggested a relationship between Cmax and the cancer response rate. No significant relationship could be found between Cmax and the nadir of thewhite blood cells and platelets. [ABSTRACT FROM AUTHOR]

Objective: To investigate the vasorelaxant effect of taurine (Tau) in rat aortic rings and the mechanism., Method: The isolated thoracic aortic rings of male Wistar rats were mounted on the organ bath. The effect of Tau 10, 20, 40, 80 mmol x L(-1) on the rings with endothelium intact or endothelium denuded precontracted by the phenylephrine (1 micromol x L(-1)) or KCl (60 mmol x L(-1)), and the effect of Tau on the vessel reaction induced by various drugs were recorded with biological signal analytical system., Result: Taurine completely relaxed the contractions induced by KCl and phenylephrine in a concentration-dependent manner in endothelium-intact and endothelium-denuded rat aorta. Taurine attenuated the contraction to PE both in the absence and presence of calcium, but had no significant effect on the contraction induced by caffeine. The relaxant effect of taurine was significantly inhibited by pretreatment of endothelium-denuded aorta with potassium channel antagonists glibenclamide and tetraethylamine but not by BaCl2 or 4-aminopyridine., Conclusion: Taurine induces an endothelium-independent relaxation in rat aortic rings. The mechanisms may involve the reduction in Ca2+-influx and Ca2+-release and the participation of the potassium channels (KATP and KCa, but not Kir or KV).