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Objective: To observe the changes in metabolites and metabolic pathways in SD rats after olanzapine treatment. Methods : Twenty female SD rats were randomly assigned to two groups, control group and olanzapine treatment group, respectively. During the treatment period, body weight and food intake of two groups were monitored. At the end of treatment, the liver tissues were collected and LC/MS technique was applied to detect metabolites in liver tissue. Subsequently, the raw data were converted for further analysis on the MetaboAnalysis platform. Results : Short-term olanzapine administration resulted in significant increases in body mass, food intake, and impaired glucose tolerance. Metabonomics results indicated rats from olanzapine treatment group had a significantly higher level of primary bile acid and 9-OxoODE (9-oxo-octadecadienoic acid) in liver tissue than those from control group. Conclusion:Primary bile acid biosynthesis process is significantly enhanced after short-time olanzapine treatment.
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Objective: To investigate association of cytochrome P450 1A2 (CYP1A2) gene polymorphisms and serum olanzapine concentration. Methods:Key words including “cytochrome P450 CYP1A2”, “genetic polymorphism”, “antipsychotic”, “olanzapine”, “schizophrenia”, and “serum concentration” were used to search in databases, including SinoMed, Wanfang, Weipu, CNKI, PubMed, Embase and Cochrane Library. The search period was limited from the establishment of the database to February 27th, 2018. STATA/SE 12.0 package was applied to conduct statistical analyses. Results: Four studies with a total of 330 schizophrenic patients were included. In the recessive model of CYP1A2 gene -163C>A SNP, patients with A/A genotype had significantly lower olanzapine concentration/dosage ratio (C/D) than patients with C/C or C/A genotype. Conclusion: A/A homozygote of CYP1A2 gene -163C>A SNP is significantly associated with the decreased olanzapine serum concentration.
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With an increasing number of reports on side effects including antipsychotic induced weight gain and cardiovascular risks, interest of the researchers has been transferred to a new target for the treatment of schizophrenia-serotonin 2C receptor (5-HT2C receptor). On one hand, activation on 5-HT2C receptors can lead to decrease of dopamine in the nigrostriatum, which presents its potential antipsychotic effect; on the other hand, the secondgeneration of antipsychotics’ antagonism on the 5-HT2C receptors is an important factor of patients' weight gain. Conversely, agonism on the 5-HT2C receptors may result in weight loss efficacy. This paper introduced the potential therapeutical effect of 5-HT2C receptor on schizophrenia and the relation between the receptor and correlated weight gain.
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Objective To explore the application of asymmetric kinetics of physiological inert gases in diving decompression algorithm.Methods Considering that the actual desaturation in the human body was slower than the saturation process,the kinetic equations of different saturation and desaturation rate of inert gases were constructed with piecewise functions on the basis of the original single exponential kinetic equation.The results were compared other adjustment methods.Results With the application of asymmetric kinetics, the time at each decompression stop was prolonged for an approximately equal proportion, remained unchanged at some deeper and shorter stops.Conclusion Asymmetric kinetics can more closely simulate the gas movement in the body to effectively control the conservativeness of decompression,and adapt to different decompression requirements by adjusting the half-saturation time ratio.
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OBJECTIVE@#To investigate the correlation between JNK signal and the apoptosis of VSMC as well as the expression of Cathepsin B and to explore the role of JNK signal in the development of cerebral aneurysm.@*METHODS@#Rat models of cerebral aneurysm were established and histopathologic changes of cerebral aneurysm and the apoptosis of VSMC were analyzed. Rat models were respectively subject to subcutaneous injection of Cathepsin B siRNA and JNK inhibitor SP600125. Western blot technique was used to detect the expression of proteins like Cathepsin B, Caspase-3, and p-JNK. Spearman's rho was used to examine the correlation between p-JNK and Cathepsin B, as well as the expression of relevant proteins.@*RESULTS@#The success rate of modeling rats with cerebral aneurysm was 88.75%. After the respective injection of Cathepsin B siRNA, SP600125 and their combination, the cell densities of VSMC of rats with cerebral aneurysm all increased significantly (P < 0.05 or P < 0.01), but the apoptosis rate of VSMC decreased significantly (P < 0.01). Compared with normal rats, the expression of Cathepsin B, Caspase-3 and p-JNK in Cerebral aneurysm models increased significantly. Effectively intervening Cathepsin B genes with Cathepsin B siRNA could significantly inhibit the expression of Cathepsin B and Caspase-3, but hardly influence the expression of p-JNK. JNK inhibitor SP600125 had no influence on the expression of Cathepsin B and Caspase-3, but effectively inhibited the expression of p-JNK. In cerebral aneurysm tissues, positive correlation was observed between the expression of p-JNK and Cathepsin B, the correlation coefficient was r = 0.640.@*CONCLUSION@#After the attack of cerebral aneurysm, proteins like Cathepsin B, Caspase-3 and p-JNK are all involved in the apoptosis of VSMCs. This process may be realized by Cathepsin B which activates the apoptosis mechanism of Caspase-3 and mediate the apoptosis of VSMC through the JNK signaling pathway. Therefore, silencing Cathepsin B gene or inhibiting the conduction through JNK signaling pathway can mitigate the apoptosis of vascular smooth muscle cells in cerebral aneurysm.
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Objective To investigate the correlation between JNK signal and the apoptosis of VSMC as well as the expression of Cathepsin B and to explore the role of JNK signal in the development of cerebral aneurysm. Methods Rat models of cerebral aneurysm were established and histopathologic changes of cerebral aneurysm and the apoptosis of VSMC were analyzed. Rat models were respectively subject to subcutaneous injection of Cathepsin B siRNA and JNK inhibitor SP600125. Western blot technique was used to detect the expression of proteins like Cathepsin B, Caspase-3, and p-JNK. Spearman's rho was used to examine the correlation between p-JNK and Cathepsin B, as well as the expression of relevant proteins. Results The success rate of modeling rats with cerebral aneurysm was 88.75%. After the respective injection of Cathepsin B siRNA, SP600125 and their combination, the cell densities of VSMC of rats with cerebral aneurysm all increased significantly (P < 0.05 or P < 0.01), but the apoptosis rate of VSMC decreased significantly (P < 0.01). Compared with normal rats, the expression of Cathepsin B, Caspase-3 and p-JNK in Cerebral aneurysm models increased significantly. Effectively intervening Cathepsin B genes with Cathepsin B siRNA could significantly inhibit the expression of Cathepsin B and Caspase-3, but hardly influence the expression of p-JNK. JNK inhibitor SP600125 had no influence on the expression of Cathepsin B and Caspase-3, but effectively inhibited the expression of p-JNK. In cerebral aneurysm tissues, positive correlation was observed between the expression of p-JNK and Cathepsin B, the correlation coefficient was r = 0.640. Conclusion After the attack of cerebral aneurysm, proteins like Cathepsin B, Caspase-3 and p-JNK are all involved in the apoptosis of VSMCs. This process may be realized by Cathepsin B which activates the apoptosis mechanism of Caspase-3 and mediate the apoptosis of VSMC through the JNK signaling pathway. Therefore, silencing Cathepsin B gene or inhibiting the conduction through JNK signaling pathway can mitigate the apoptosis of vascular smooth muscle cells in cerebral aneurysm.
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<p><b>OBJECTIVES</b>To identify the nonmuscle myosin heavy chain 9 (MYH9) gene mutation site in a May-Hegglin anomaly(MHA) patient, and to analyze the genotype of her relatives to exclude the inherit correlation between the proband and her family members.</p><p><b>METHODS</b>Inclusion bodies in neutrophils of the proband were examined by transmission electron microscope, and giant platelets by scanning electron microscope. The mutation "hot spot" on the MYH9 gene of the proband and her family members was amplified with polymerase chain reaction(PCR), and then sequenced in both directions to identify the mutant site.</p><p><b>RESULTS</b>(1) The proband manifested with the typical MHA triad of giant platelet, thrombocytopenia and Dohle-like inclusion bodies in neutrophil. However, all of the proband's family members had no such anomaly. (2) Transmission electron microscope and scanning electron microscope confirmed that giant platelets and neutrophils inclusion bodies existed in the proband peripheral blood cells. (3) There was a missense mutation 5797 C-->T in the exon 40 of MYH9 gene which led to Arg changing into termination codon (Arg1933 stop). The proband also had a heterozygous mutation 4876A-->G in exon 33. There was no abnormal finding in the sites mentioned above in her mother, while her father carried the homozygous 4876A-->G mutation.</p><p><b>CONCLUSIONS</b>This MHA case is a sporadic one, in whose family a mode for autosomal dominant inheritance can not be established. The 5797C-->T substitution in MYH9 gene is a pathogenic mutation, however, 4876A-->G is simply a polymorphism.</p>