Vincristine-induced neuropathy in rats is mediated via NMDA excitotoxicity and impairment of CGRP: possible neuroprotective effect of erythropoietin

Vincristine [VCR] is a potent anticancer drug and neurotoxicity is one of its most important dose-limiting toxicities. In this study, we investigated the effect of VCR by neurophysiological recordings and the tail flick test. To elucidate the underlying mechanism of action of VCR, expression of both N-methyl-D-aspartate [NMDA] receptor, an index of glutamate excitotoxity and calcitonin gene-related peptide [CGRP], an important regulator of vascular tone, were measured in both spinal cord and sciatic nerves. The role of erythropoietin [EPO] in the protection against VCR-incluced neurotoxicity was also examined. Methods: Rats were divided into control group, VCR treated group and two groups given EPO in two different doses concomitant with VCR administration. VCR significantly decreased the amplitude of maximum compound action potential [MCAP] and prolonged the duration of action potential [AP] and relative refractory period [RRP], decreased chronaxie and the latency of tail flick test, but it had no effect on conduction velocity. VCR increased NMDA receptor expression and it decreased CGRP expression. The smaller dose of EPO improved all VCR induced changes. except chronaxie, while its higher dose reversed all parameters and its effect was more prominent on tail flick test latency and NMDA receptor expression. VCR resulted in axonal degeneration. It caused increased neuronal excitability and induced a state of glutamate excitotoxicity. Finally, VCR caused a decrease in blood flow in the nervous [issue resulting in vascular neurotoxicity. EPO had an obvious neuroprotective effect probably through decreasing NMDA receptor expression and increasing CORP expression both centrally and peripherally

Blood coagulation changes in response to dexamethasone in the normal rat

The effect of daily dexamethasone on blood coagulation was studied in normal male rats. Dexamethasone was injected daily [0.4 mg/kg body weight] for 3 weeks. Blood was collected retro-orbitally from the rats before and after 2 days, after 1 week and after 3 weeks of dexamethasone administration. Prothrombin time [PT], fibrinogen [FIB] and activated partial thromboplastin time [APTT] were determined in plasma. Results were compared with the values found in normal adult male rats before injections [controls]. It was found that dexamethasone significantly increased the FIB already after 2 days of administration, while it significantly decreased APTT starting after one week of dexamethasone injections. PT, however, remained unaffected by dexamethasone throughout the time of the study. From these results, it can be concluded that dexamethasone does not seem to affect the extrinsic coagulation cascade, but increases procoagulant activity via the intrinsic pathway. Also, decreased fibrinolysis was recorded, as witnessed by increased fibrinogen levels. Thus, glucocorticoids should be prescribed with caution in patients with hypercoagulable states

Fibrinolytic activity in patients with chronic low back pain

A group of sixteen patients with chronic low back pain [CLBP] of various aetiology was examined clinically and radiologically. Blood samples were withdrawn and fibrinolytic activity [FA] was examined by measuring the percentage of plasminogen and infinity-antiplasmin in the plasma of the patient group and of a control group consisting of twenty matched healthy individuals. Four patients [25%] showed defective fibrinolysis namely, significant reduction of plasminogen percentage below normal. In addition, mean plasminogen percentage in plasma in the patient group was significantly lower than in controls [P < 005], but there was no significant difference in the mean plasma percentage of infinity-antiplasmin. Furthermore, no association could be detected between defective fibrinolysis and the degree of the clinical and radiological manifestations of CLBP. Larger patient groups should be investigated to verify the importance of fibrinolytic defect in the aetiology of CLBP. In addition, enhancement of FA may be used as a trial to manage patients showing fibrinolytic defect