选择性κ阿片激动剂K-Ⅱ与U-50488的药理作用比较

K-Ⅱ系k阿片激动剂U-50488的同类物。通过部分离体和整体实验比较了K-Ⅱ与U-50488的药理作用。实验发现,K-Ⅱ抑制电刺激兔输精管收缩的IC₅₀值为0.42 nmol/L,U-50488为26.5 nmol/L;K-Ⅱ抑制小鼠运动功能(横筛法)的ED₅₀值为1.7 mg/g,U-50488为15.3 mg/kg;K-Ⅱ的小鼠LD₅₀值为152.5 mg/kg,U-50488为118.4 mg/g;K-Ⅱ明显降低小鼠自发活动的作用比U-50488强5倍。结果表明,K-Ⅱ是一个药理作用较U-50488强的k受体激动剂。     

The use of nutritional status as a second outcome measure in case-control studies of environmental risk factors for diarrhoeal diseases

Case-control studies are typically used to study the effect of several factors on the risk/incidence rate of a single disease. This paper describes a particular situation in which it is of interest to study the effect of a factor--improved sanitation facilities--on the risk/incidence rate of two 'diseases'--the incidence rate of diarrhoea and the risk of undernutrition. The conditions under which it is valid to perform an analysis of the association between the risk factor (unimproved sanitation) and a second outcome variable (undernutrition) are examined. If the effect of exposure status (improved/unimproved sanitation facilities) on the propensity to report an episode of diarrhoea is independent of the effect of nutritional status it appears that such an analysis may be valid. There must also be no interaction between the risk factor (unimproved sanitation) and the second outcome (undernutrition) with respect to their effects as risk factors for the first outcome variable (diarrhoea incidence rate).     

A RANDOMISED,DOUBLE-BLIND,PARALLEL-GROUP COMPARISON OF VENLAFAXINE AND DOTHIEPIN IN GERIATRIC PATIENTS WITH MAJOR DEPRESSION

This randomised, double-blind study conducted at nine sites in the UK and the Netherlands compared the safety and antidepressant efficacy of venlafaxine and dothiepin. Ninety-two geriatric patients (aged 64-87 years) with major depression were randomly assigned to receive either venlafaxine or dothiepin for up to 43 days. The dose of venlafaxine or dothiepin was titrated up to a maximum of 150 mg per day for the first 15 days, and thereafter could range from 50 to 150 mg per day. Adjusted mean scores on the MADRS and the HAM-D decreased significantly (p 0.05) from baseline to the end of the study in both groups. A response to therapy was observed in 60% of patients in the venlafaxine group and 53% of patients in the dothiepin group on the MADRS, and in 60% of patients in both groups on the HAM-D. Suicidal ideation scores on the MADRS were significantly (p=0.042) lower in the venlafaxine group at week 6. Treatment-emergent study events were the primary reason for withdrawal in only 7% of venlafaxine-treated patients and 8% of dothiepin-treated patients. The results confirm the efficacy and tolerability of venlafaxine for treating major depression in the elderly.     

Infusible platelet membrane microvesicles: a potential transfusion substitute for platelets

BACKGROUND: Several substitutes for intact, viable platelets have been used for transfusion, both to people and in animal models, with varied success. Infusible platelet membrane (IPM) is prepared from human platelets. IPM retains the glycoprotein (GP)lb receptor and has platelet factor 3 activity (procoagulant activity). However, factor V, serotonin, a cytoplasmic marker enzyme (purine nucleotide phosphorylase), GPIIb/IIIa complex, and HLA class I and II antigens are all absent in IPM. STUDY DESIGN AND METHODS: IPM is prepared from outdated platelets. The platelets were disrupted by freezing and thawing; they were washed and heated to inactivate possible viral contaminants, and then the sonicated membrane microvesicle fraction was separated and lyophilized. The hemostatic activity of IPM was measured by its ability to reduce the prolonged bleeding time in thrombocytopenic rabbits. RESULTS: Administration of IPM at a dose of 2 mg per kg results in a substantial reduction in the bleeding time. In a series of 23 experiments, a median preinjection bleeding time of 15 minutes was reduced to 6 minutes within 4 hours after IPM administration. Administration of IPM did show a mild enhancement in the thrombogenicity index, as measured in the Wessler rabbit model. This enhancement is, however, not significant, as a thrombogenicity index value of up to 0.6 is clinically acceptable. CONCLUSION: IPM may have clinical potential as a substitute for platelets in the treatment of bleeding due to thrombocytopenia.     

A comparison of the pharmacokinetics,clinical efficacy,and tolerability of once-daily tramadol tablets with normal release tramadol capsules

This report describes a pharmacokinetic study and a clinical study of three different formulations of oral tramadol: once-daily tramadol tablets 150 and 200 mg, and normal release tramadol capsules 50 mg 8-hourly. The randomized, open-label, crossover pharmacokinetic study included 22 subjects. The three treatments showed equivalent mean systemic availability of tramadol. The mean relative systemic availabilities (90% confidence intervals) for the once-daily tablets 150 mg and the once-daily tablets 200 mg versus the normal release capsules were 89.6 (83.3-95.8)% and 90.5 (84.6-96.8)%, respectively. The values for the once-daily tablet 150 mg versus the once-daily tablet 200 mg were 99.0 (92.6-105.9)%. The randomized, double-blind, double-dummy, crossover clinical study included 134 patients with moderate osteoarthritic pain. The three treatments showed similar efficacy; they all reduced patients' pain scores from baseline and there were no significant treatment differences in pain scores during treatment. The three treatments were also well tolerated.     

Adjuvant therapy for locally advanced renal cell cancer: A systematic review with meta-analysis

Background  

Many adjuvant trials have been undertaken in an attempt to reduce the risk of recurrence among patients who undergo surgical resection for locally advanced renal cancer. However, no clear benefit has been identified to date. This systematic review was conducted to examine the exact role of adjuvant therapy in renal cancer setting.     

Effects of L-histidine depletion and L-tyrosine/L-phenylalanine depletion on sensory and motor processes in healthy volunteers

Background and purpose:

Animal studies show that histamine plays a role in cognitive functioning and that histamine H₃-receptor antagonists, which increase histaminergic function through presynaptic receptors, improve cognitive performance in models of clinical cognitive deficits. In order to test such new drugs in humans, a model for cognitive impairments induced by low histaminergic functions would be useful. Studies with histamine H₁-receptor antagonists have shown limitations as a model. Here we evaluated whether depletion of L-histidine, the precursor of histamine, was effective in altering measures associated with histamine in humans and the behavioural and electrophysiological (event-related-potentials) effects.

Experimental approach:

Seventeen healthy volunteers completed a three-way, double-blind, crossover study with L-histidine depletion, L-tyrosine/L-phenylalanine depletion (active control) and placebo as treatments. Interactions with task manipulations in a choice reaction time task were studied. Task demands were increased using visual stimulus degradation and increased response complexity. In addition, subjective and objective measures of sedation and critical tracking task performance were assessed.

Key results:

Measures of sedation and critical tracking task performance were not affected by treatment. L-histidine depletion was effective and enlarged the effect of response complexity as measured with the response-locked lateralized readiness potential onset latency.

Conclusions and implications:

L-histidine depletion affected response- but not stimulus-related processes, in contrast to the effects of H₁-receptor antagonists which were previously found to affect primarily stimulus-related processes. L-histidine depletion is promising as a model for histamine-based cognitive impairment. However, these effects need to be confirmed by further studies.