Attenuation of ethanol abstinence-induced anxiety- and depressive-like behavior by the phosphodiesterase-4 inhibitor rolipram in rodents.

RATIONALE: Withdrawal symptoms stand as a core feature of alcohol dependence. Our previous results have shown that inhibition of phosphodiesterase-4 (PDE4) decreased ethanol seeking and drinking in alcohol-preferring rodents. However, little is known about whether PDE4 is involved in ethanol abstinence-related behavior. OBJECTIVE: The objective of this study was to characterize the role of PDE4 in the development of anxiety- and depressive-like behavior induced by abstinence from ethanol exposure in different animal models. METHODS: Using three rodent models of ethanol abstinence, we examined the effects of rolipram, a prototypical, selective PDE4 inhibitor, on (1) anxiety-like behavior induced by repeated ethanol abstinence in the elevated plus maze test in fawn-hooded (FH/Wjd) rats, (2) anxiety-like behavior in the open-field test and light-dark transition test following acute ethanol abstinence in C57BL/6J mice, and (3) anxiety- and depressive-like behavior induced by protracted ethanol abstinence in the elevated plus maze, forced-swim, and tail-suspension tests in C57BL/6J mice. RESULTS: Pretreatment with rolipram (0.1 or 0.2 mg/kg) significantly increased entries and time spent in the open arms of the elevated plus maze test in rats with repeated ethanol abstinence. Similarly, in mice with acute ethanol abstinence, administration of rolipram (0.25 or 0.5 mg/kg) dose-dependently increased the crossings in the central zone of the open-field test and duration and transitions on the light side of the light-dark transition test, suggesting anxiolytic-like effects of rolipram. Consistent with these, chronic treatment with rolipram (0.1, 0.3, or 1.0 mg/kg) increased entries in the open arms of the elevated plus maze test; it also reduced the increased duration of immobility in both the forced-swim and tail-suspension tests in mice after protracted ethanol abstinence, suggesting antidepressant-like effects of rolipram. CONCLUSIONS: These results provide the first demonstration for that PDE4 plays a role in modulating the development of negative emotional reactions associated with ethanol abstinence, including anxiety and depression. PDE4 inhibitors may be a novel class of drugs for treatment of alcoholism.

Effectiveness of silver-impregnated central venous catheters for preventing catheter-related blood stream infections: a meta-analysis.

OBJECTIVES: The purpose of this meta-analysis was to examine the effectiveness of silver-impregnated central venous catheters (CVCs) in preventing catheter bacterial colonization and catheter-related blood stream infections (CRBSIs). METHODS: PubMed, Cochrane, and Embase databases were searched up to April 30, 2014. Studies in which other antiseptic reagents were used (e.g., chlorhexidine, octenidine dihydrochloride, urokinase rinses, benzalkonium chloride, rifampin-minocycline) were excluded. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Tests of heterogeneity and publication bias were performed. RESULTS: Twelve studies were included in the meta-analysis. The studies enrolled a total of 2854 patients; 1440 received a standard CVC and 1414 received a silver-impregnated CVC. No significant difference in catheter bacterial colonization rates was found between silver-impregnated and standard CVCs (OR 0.907, 95% CI 0.758-1.087, p=0.290). No significant difference in CRBSI rates was found between silver-impregnated and standard CVCs (pooled OR 0.721, 95% CI 0.476-1.094, p=0.124). No significant heterogeneity or publication bias was noted. CONCLUSIONS: Silver-impregnated CVCs are not associated with reduced rates of bacterial colonization or CRBSI.

Chlorbipram: a novel PDE4 inhibitor with improved safety as a potential antidepressant and cognitive enhancer.

Major depressive disorder is a common, but serious, psychiatric dysfunction that affects 21% of the population worldwide. Rolipram, a first-generation phosphodiesterase-4 (PDE4) inhibitor, has been shown to have significant antidepressant and cognitive enhancement effects; however, it was unsuccessful in clinic trials because of PDE4-dependent side effects such as nausea and emesis. In this study, we investigated the neuropharmacology of the novel PDE4 inhibitor chlorbipram and the classical PDE4 inhibitor rolipram. Using antidepressant-sensitive behavioral tests, we demonstrated that the acute single administration of chlorbipram (0.075-0.6 mg/kg) produced antidepressant-like effects, as evidenced by decreases in the duration of immobility in Kunming mice in the forced swim and tail suspension tests, and no significant changes in locomotor activity. Scopolamine-induced cognitive dysfunction was also significantly attenuated in the Morris water maze test after the treatment of Sprague Dawley rats with different doses of chlorbipram (0.5-1.5mg/kg). Furthermore, we evaluated the emetic potential of chlorbipram in beagle dogs. After oral administration, 0.5mg/kg rolipram showed emetic profiles in all dogs within 20 minutes, whereas chlorbipram did not induce any emesis during the 120-min observation period, even at the 1.0mg/kg dose. Together, our data suggest that chlorbipram is a novel antidepressant and cognitive enhancer with little or no emetic potency.

[Effect of Cordyceps sinensis sporocarp on learning-memory in mice].

OBJECTIVE: To study the effect of extracts of Cordyceps sinensis sporocarp on learning-memory in scopolamine treated mice and the possible mechanism. METHODS: ICR mice were randomly divided into five groups: sham control, model, piracetam and CSE 0.5, 1 g/kg. Lotomotor activity was assessed. Morris water maze was used to evaluate the memory ability of mice 30 min later after ip scopolamine 1.0 mg/kg BW. Then acitivity of AchE was measured after behavioral test. RESULTS: CSE had no influence on lotomotor activity. However, CSE 0.5, 1 g/kg both shortened escape latency and increased times of come-crossing platform in Morris water maze, meanwhile activity of AchE in the brain was decreased by CSE. CONCLUSION: CSE can significantly improve the learning and memory impairment in mice induced by scopolamine, which may be correlated with the inhibition of activity of AchE.

Clinical effect and action mechanism of Weicao Capsule in treating gout.

OBJECTIVE: To study the therapeutic effect of Weicao Capsule (WCC) on gout. METHODS: Two hundred gout patients were assigned to two groups. The treated group was treated with WCC and the control group was treated with Tongfengding Capsule. Both groups were given the respective treatments orally 3 times a day, 2 capsules each time with 2 weeks as one course and all patients received 2 successive courses of treatment. Changes of blood beta(2)-microglobulin (beta(2)-M), hemoglobin (Hb), 24 h urinary protein (24 h UP), pH value of urine and blood uric acid (BUA) as well as kidney function were observed. RESULTS: After treatment, level of beta(2)-M got lowered significantly, Hb and 24 h UP, blood urea nitrogen, serum creatinine and the clearance rate of creatinine, as well as blood lipids all improved obviously in the treated group (all P<0.01), while these parameters remained unchanged in the control group (P>0.05). The pH value of urine was improved in both groups showing an insignificant difference between them (P>0.05). BUA was decreased in both groups with a decrease to a larger extent in the treated group (P<0.01). The total effective rate was 87% in the treated group, which was superior to that in the control group (62%, P<0.05). CONCLUSION: WCC has a favorable therapeutic effect on gout and its mechanism of action for improving renal function and reducing urinary protein could be related with the lowering of blood beta(2)-M, BUA and lipids.