Efficacy of uremic pruritus treatment in patients undergoing hemodialysis, a network meta-analysis for randomized clinical trials.

INTRODUCTION: Uremic pruritus is very common in hemodialysis or renal failure patients, there were lots of available treatments such as gabapentin, pregabalin, ondansetron, etc. However, there is no quantified study comparing these treatments together, it is impossible to conduct a clinical trial involving so many treatments, so we conduct a network meta-analysis to compare them. METHOD: We collected mean difference and standard error of visual analogue scale data as outcome. In total we collected 15 articles, 15 articles, 1180 subjects and 6 treatments included to this study. RESULTS: In these comparisons, gabapentin showed the largest effect MD: 5.19, 95%CI [3.77, 6.61], anti-histamine MD: 4.65, 95%CI [2.22, 7.07] and pregabalin MD: 4.62, 95%CI [2.71, 6.62] showed a similar effect. Opioid pathway related treatment also showed a significant but not so large effect MD: 2.45, 95%CI [0.41, 4.49]. Ondansetron and Doxepin didn't show a significant improvement among placebo, the overall quantifying heterogeneity I2=43.1%. There is no statically difference between gabapentin, pregabalin and anti-histamine treatments. CONCLUSIONS: So we conclude that gabapentin, pregabalin and anti-histamine has a similar efficacy on pruritus control.

Reciprocal Substitution Between Methamphetamine and Heroin in Terms of Reinforcement Effects in Rats.

Heroin and methamphetamine are both popular illicit drugs in China. Previous clinical data showed that habitual users of either heroin or methamphetamine abuse the other drug for substitution in case of unavailability of their preferred drug. The present study aimed to observe whether heroin can substitute the methamphetamine reinforcement effect in rats, and vice versa. Rats were trained to self-administer heroin or methamphetamine (both 50 µg/kg/infusion) under an FR1 reinforcing schedule for 10 days. After having extracted the dose-effect curve of the two drugs, we administered methamphetamine at different doses (12.5-200 µg/kg/infusion) to replace heroin during the period of self-administration, and vice versa. The heroin dose-effect curve showed an inverted U-shaped trend, and the total intake dose of heroin significantly increased when the training dose increased from 50 to 100 or 200 µg/kg/infusion. Following replacement with methamphetamine, the total dose-effect curve shifted leftwards and upwards. By contrast, although the dose-effect curve of methamphetamine also showed an inverted U-shaped trend, the total dose of methamphetamine significantly decreased when the training dose decreased from 50 to 25 µg/kg/infusion; conversely, when the methamphetamine training dose increased, the total dose did not change significantly. The total dose-effect curve shifted rightwards after heroin was substituted with methamphetamine. Although heroin and methamphetamine had their own independent reward effects, low doses of methamphetamine can replace the heroin reward effect, while high doses of heroin can replace the methamphetamine reward effect. These results demonstrated that heroin and methamphetamine can substitute each other in terms of reinforcement effects in rats.

[COX-2 mediates U50488H-induced delayed cardioprotection in isolated rat heart].

OBJECTIVE: To determine whether U50488H, a selective agonist of kappa-opioid receptor, could induce biphasic (early and late) cardioprotection against myocardial ischemia/reperfusion injury and to explore the underlying mechanisms. METHODS: Isolated perfused rat hearts were subjected to 30 min of ischemia followed by 120 min reperfusion and the cardiac function was evaluated. RESULT: Left ventricular end-diastolic pressure (LVEDP), left ventricular developed pressure (LVDP) and maximal velocity of contraction and relaxation (+/-dP/dtmax) were improved when U50488H was administered 1 or 24 h before ischemia (P<0.05). Myocardial infarct size, activities of creatine kinase (CK) and lactate dehydrogenase (LDH) in the coronary effluent were lower in the U50488H pretreatment group than those in the control group. Administration of a selective cyclooxygenase-2 (COX-2) inhibitor, celecoxib abolished the late phase of cardioprotection produced by administration of U50488H 24 h before ischemia. Activities of CK and LDH in the coronary effluent were higher in U50488H and celecoxib co-pretreatment group than those in U50488H group. However, administration of celecoxib did not block the early phase of cardioprotection by 1 h treatment of U50488H before ischemia. CONCLUSION: The late (but not the early) phase of cardioprotection induced by kappa-opioid receptor agonist might be mediated by COX-2.