Objective To explore effects of long-term low-dose ketamine treatment on locomotor activity and apoptosis of the thalamus in cynomolgus monkeys.Methods 12 male cynomolgus monkeys [(46.25±5.40)months old] were randomly divided into the ketamine group(n=8) and the control group(n=4).Monkeys in the ketamine group were injected with 1 mg/mL of ketamine,1 mL/kg;while those in the control group were injected with an equal dose of normal saline(1 mL/kg).Locomotor activities of all monkeys were recorded at regular intervals.3 months later,monkeys were sacrificed.The apoptosis of thalamic cells was observed by TUNEL staining.Western blot was used to detect Caspase-3 and Bcl-2 expressions.Results There was no statistically significant difference in locomotor activity between the ketamine group and the control group.The ketamine group showed a statistically significant decrease in locomotor activity with prolongation of treatment time,while the control group had no statistically significant change.The ketamine group showed a statistically significant increase in apoptosis and the Caspase-3 level in the thalamus compared with the control group.There was no statistically significant difference in the Bcl-2 expression between the two groups.Conclusion Chronic repeated treatment of ketamine with recreational dosage decreases locomotor activities which may be caused by drug tolerance,and induces apoptosis of the thalamus which may be associated with up-regulation of Caspase-3.

Objective To explore effects of long-term low-dose ketamine on behavior and ultrastructures of the hippocam-pus and prefrontal cortex in Cynomolgus monkeys.Methods 12 male Cynomolgus monkeys were randomly divided into the ketamine group (n=8) and the control group (n=4) .The ketamine group was daily intravenously injected with ket-amine(1 mg/kg) ,while the control group injected with normal saline(1 mL/kg) .Observations on behavior were regularly made and ultrastructural changes of the hippocampus and prefrontal cortex were observed by a transmission electron micro-scope after 6 months.Results There was no statistically significant difference in locomotor activities between the two groups(P﹥0.05) .Ultrastructural changes in the ketamine group,including neuron necrosis,glial cell apoptosis and li-pofuscin accumulation,appeared in the hippocampus; a mass of autophagosomes,reduction of the rough endoplasmic reticulum,neuron necrosis,and glial cell apoptosis were observed in the prefrontal cortex in the ketamine group,while not observed in the control group.Conclusion Long-term low-dose ketamine induces ultra-structural changes in the hippo-campus and prefrontal cortex,including neuron degeneration,necrosis and apoptosis,which appear earlier than behavioral changes do.

Objective: To investigate the mechanism of immune escape through Fas/FasL pathway in hepatoma cells.Methods: Fas and FasL expressions of hepatoma cell line HepG2.2.15 were examined by flow cytometry.Resistance of hepatoma cells to Fas-mediated apoptosis was determined by using anti-Fas agonistic monoclonal antibody CH11.FasL function of inducing T-lymphocytes to apoptosis was assessed by coculture assays in vitro by using hepatoma cells HepG2.2.15 and Jurkat cells.Results: ①Fas expression of HepG2.2.15 was low,and CH11 could not induce the cells to apoptosis;②FasL expression rate of HepG2.2.15 was 18.03%,and FasL could induce Jurkat cells to apoptosis in coculture assays;③The apoptosis rate of Jurkat cells in coculture assays was decreased from 21.41% to 8.91% after FasL having been blocked with FasL-neutralizing antibody NOK-2. Conclusions: Hepatoma cells can resist to Fas-mediated apoptosis,and FasL expressed by the cells can inhibit the immune function of T-lymphocytes.Fas/FasL pathway is one of the mechanisms of immune escape in hepatoma cells and may be a new target point of immunological therapy.