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OBJECTIVE：To establish a method for de termining stiripentol （STP）concentration in plasma and brain of rats ， and to compare the concentrations of STP and its self-nanoemulsifying drug delivery system （STP-SNEDDS）in plasma and brain. METHODS：Using xanthone as internal standard ，HPLC-fluorescence（HPLC-FLR）method was adopted. The determination was performed on Diamonsil C 18 column with mobile phase consisted of acetonitrile- 25 mmol/L KH 2PO4 solution [ 44 ∶ 56（V/V），pH 2.6] at a flow rate of 1.5 mL/min；the excitation and emission wavelengths were 210 nm and 400 nm，respectively；the column temperature was 30 ℃；the sample size was 10 μL. Totally 36 rats were randomly divided into 2 groups，with 18 rats in each group. They were given STP-SNEDDS and STP suspension （40 mg/kg，by STP ）intragastrically. Blood and brain tissue samples were collected at 0.5，1，2 h after administration （6 rats in each group at different time point ）. After the protein was precipitated by acetonitrile （brain tissue should be homogenized ），the concentrations of STP were determined by the above chromatographic conditions. RESULTS ：The linear ranges of STP concentration in plasma and brain tissue were 0.02-8.00 μg/mL（r were 0.999 6， 0.999 4，respectively）. The limits of quantitation were both 0.02 μg/mL. The inter-day and intra-day RSDs were all less than 5％. The extraction recovery and method recovery were all no less than 90％. Compared with STP suspension group ，the plasma concentration（except for 1 h after administration ）and cerebral concentration （except for 2 h after administration ）of STP in STP-SNEDDS group were all significantly increased （P＜0.05），showing significant linear relationship between them （for STP-SNEDDS）. CONCLUSIONS ：Established HPLC-FLR method presents high accuracy and precision ，and can be used for the distribution of STP and STP-SNEDDS in plasma and brain.The concentration of STP in plasma and brain tissue isincreased after STP is made into SNEDDS.
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han that in the control one (t=3.94, P<0.01).Conclusion Social skills training can effectively improve subjective satisfactions of the long-terra hospitalized patients with chronic schizophrenia.
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Objective To investigate the prevalence, characteristics and correlates of depressive symptoms in first episode schizophrenic patients. Methods To examine 164 first episode schizophrenic patients at the time of admission and at 3,6,9, and 12 months after starting treatment using the HAMD, BPRS, the Chinese version of SANS, CGI and GAF. Results 71% of the patients had depressive symptoms (mild or more) at damission, but the prevalence of depressive symptoms dropped to a mean of 12% during the recovery period. The most prominent depressive symptoms during the acute phase of schizophrenia were ‘cognitive disturbance’ and ‘retardation’ (the respective subscales constituted 35% and 29% of the total HAMD score on admission). Depressive symptoms improved in parallel with the schizophrenic illness. The severity of depressive symptoms was not related to gender, age of onset, educational level, duration of prodromal period or duration of illness. At admission the severity of depressive symptoms was only related to the BPRS anxiety and depression subscale score, but during the recovery period the HAMD total score was significantly correlated with all of the other clinical scales. The level of depressive symptoms at admission and at three months after starting treatment was not related to the subsequent course of positive or negative symptoms. Conclusions Depressive symptoms appeared to be a separate symptom cluster during the acute phase of first episode schizophrenia. The severity of depressive symptoms did not predict the clinical outcome of first episode schizophrenic patients.
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It was found that the proliferation of mice L7712 leukemic cells in vitro was markedly inhibited by 5 mg/L GP1 and VP10 The inhib itory rate increased with the incubation time. At a concentration of 0 .04-20mg/L, the mitotic index ( MI ) of GP1 group increased, but the MI of VP16 group decreased. After L7712 cells were treated with GP, 5 mg/L for 12 h the MI reached the highest point which was 8 times as high as that of the control, at the same time, the MI of VP16 ( 5 mg/L) group was about one-third of that of the control. The result of the combination of GP1 with VP16 showed that VP16 could antagonize the effect of GP on MI of L7712 cells. After being treated by GP1 and VP18 for 24 h, serious damage of L7712 cells could be observed. Both drugs inhibited the incorporation of (3H) TdR into DNA of S180, ascitic hepatoma (AH), L1210 and L7712 cells incubated for 24 h. It was further observed that S180 and L7712 cells were more sensitive than other cells to both drugs.
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The antiumor activity of a new podophyllotoxin spin-labeled derivative, 4 -C 4 "-( 2 ", 2", C", 6"-tetramethyl- 1 "-piperidinyoxy ) amino]-4'-demethylepipodophyllotoxin ( GP-7 ) was studied. It was found that the growth of transplanted mouse tumors S180, HePS and Lewis lung cancer was markedly inhibited by GP-7. At a dose of 7.5-20 mg/kg, the inhibition rates of it against Sl80, HePS and Lewis lung cancer were 36.0-58.4, 29.6-60.0, and 27.2-46.5 % respectively. The toxicity of GP-7 was low, as indicated by the LD50 value of 231.2 mg/kg which was 3.3 times higher than that of etoposide ( VP-16 ) . On the other hand, the effects of GP-7 on spleen index and thymus index of mice bearing S180 tumor were remarkably lower than that of VP-16. In vitro GP-7 exhibited marked inhibition effects against L1210 and SGC-7901 cells. After exposure of L1210 cells to GP-7 and VP-16 5 mg/L for 24 h, the. inhibition rates were 75.5 and 73.6 %. after exposure of SGC-7901 cells to GP-7 and VP-16 5 mg/L for 72 h, the inhibition rates were 81.4 and 84.2 %. The new podophyllotoxin derivative GP-7 was similar to its structure analogues, clinical drug VP-16, in antitumor activity, while the toxicity of it was much lower than that of VP-16.