Experimental down-regulation of the NMDA channel associated with synapse pruning

The N-methyl-D-aspartate (NMDA) receptor has been implicated in activity-dependent synapse stabilization, but its role as a detector of correlated activity during development is debated. In the amphibian retinotectal system, synaptic sorting and stabilization occur throughout larval life, and map refinement is dependent on continuous NMDA receptor function. Moreover, tadpole tecta chronically treated with NMDA selectively fail to maintain retinal synapses wherever their activity correlations are lowest. To determine whether this synapse elimination is associated with a specific down-regulation of NMDA receptor function, whole cell voltage-clamp recordings were made from single neurons in tectal slices. After chronic NMDA treatment, decreases in the magnitude of NMDA currents were detected in glutamatergic synaptic currents, in agonist-evoked currents, and in single-channel currents activated by NMDA. The results suggest that the efficacy of NMDA receptors on tectal neurons determines the amount of correlation required to stabilize sets of tectal inputs during formation of the retinotectal projection.     

Drug interactions with the nonsedating antihistamines

The nonsedating antihistamines are frequently prescribed agents. Well-documented drug-drug interactions with two of these agents, terfenadine and astemizole, may result in serious adverse effects, including death, when they are prescribed along with macrolide antibiotics and/or the antifungal agents itraconazole or ketoconazole. Fexofenadine and loratadine appear to be the least likely nonsedating antihistamines to interact with other medications and to result in a life-threatening interaction. This article reviews the known drug-drug interactions involving nonsedating antihistamines and provides a basis from which the clinician can predict potential interactions.     

(D)-penicillamine increases hepatic oxalate production resulting in hyperoxaluria

PURPOSE: To determine whether (D)-penicillamine is effective in reducing hepatic oxalate production and urinary oxalate excretion. MATERIALS AND METHODS: (D)-Penicillamine was administered orally to rats to determine its effect on urinary oxalate excretion and used in isolated rat hepatocytes to investigate the effect of (D)-penicillamine on oxalate production from glycolate. Studies involving hepatic aminotransferases and hepatocytes isolated from (D)-penicillamine treated rats were used to clarify the discrepancy between the in vitro and in vivo results. RESULTS: In hepatocytes (D)-penicillamine lead to a significant reduction in oxalate production from glycolate. In vivo however. (D)-penicillamine led to a significant increase in urinary oxalate excretion and a decrease in plasma aminotransferase activity. Hepatic aminotransferases are involved in diverting oxalate precursors from oxalate production. In vitro, (D)-penicillamine was shown to inhibit hepatic aminotransferases. Hepatocytes isolated from (D)-penicillamine-treated rats produced significantly more oxalate than controls. CONCLUSIONS: These results indicate that (D)-penicillamine increases hepatic oxalate production and urinary oxalate excretion. (D)-penicillamine therefore has no therapeutic potential for reducing endogenous oxalate production and urinary oxalate excretion. Moreover, in conditions such as Wilson's Disease which is often associated with hypercalcuria, its use may be contraindicated.     

Improved osseointeraction of calcium phosphate-coated external fixation pins. Studies in calves

The analysis of health state of drivers sent for an extra health examination for the estimation of driving capability for the driving of motor vehicle in alcoholic state was presented. The study included 380 drivers who were found driving drunk by traffic police (studied group) and 180 drivers of control group sent for an extra health examination for some other reason. The disorders in psychomotor sphere were noticed in the drivers of studied group and it was determined that they had caused significantly larger number of traffic accidents in last five-year period compared to the drivers of control group. The alcohol consumption in driving population represents significant medical, social, economic and traffic problem. The control of driver's alcoholism, the sending of alcoholic drivers to an extra health examination for the repeated estimation of driving capability and including in therapeutic and health-educational program can present significant measure of the primary prevention of road traffic traumatism which is on the constant increase.