ABSTRACT
Objective To explore the effects of ziprasidone and clozapine on serum cholinesterase (CHE) concentration in schizophrenia patients. Methods 126 schizophrenia patients were randomly divided into the observation group and the control group. The observation group was treated with ziprasidone. The control group received clozapine. The serum CHE concentration was assayed at 7, 14 and 28 days after treatment. Results ① The PANSS scores in both groups were significantly reduced after treatment, while the control group was lower than the observation group (PANSS score for positive symptoms: 15.3±4.7 vs 22.4±4.8, P<0.01; negative symptoms: 14.6±4.5 vs 21.8±5.2, P<0.01; general psychiatric symptoms: 13.3±3.4 vs 19.2±3.9, P<0.01). ② CHE levels were decreased in both groups after treatment. The control group exhibited greater decrease than the observation group. ③ The observation group had lower adverse reaction rate (34.9%) compared to control group (71.4%). Conclusion ziprasidone has weaker inhibitory effect on CHE activity compared to clozapine. This may explain that ziprasidone has lower therapeutic efficacy and better safety profile.
ABSTRACT
To observe the protective effect of alpha-mangostin (α-MG) on focal segmental glomurular sclerosis (FSGS) induced by adriamycin. Methods: Adriamycin nephropathy (AN) model was induced by adriamycin (10 mg/kg) via a tail vein. Then the mice were treated with α-MG (12.5 mg/kg) or normal salin once daily for 6 weeks. At the end of 6 weeks, the mice were sacrificed, and the kidneys and blood samples were collected. Histopathology of the kidneys were analyzed under the optical microscope. The serum levels of biochemical indicators, such as serum creatinine (SCr), blood urea nitrogen (BUN) and cholesterol were determined. The levels of superoxide anion, malondialdehyde (MDA), and glutathione (GSH), the activity of superoxide dismutase (SOD) and catalase (CAT) in kidney tissues were determined. Serum levels of IL-1β, IL-18, IL-10 and adiponectin were determined. The levels of TGF-β1, collagen I (Col I), α-SMA, silent information regulator 1 (Sirt1) and the nucleotide-binding domain (NOD)-like receptor protein 3 (NLRP3) in kidney tissues were determined using immunohistochemical staining, Western blot, and RT-PCR. Results: The levels of SCr, proteinuria, urine protein to creatinine ratio and serum cholesterol were attenuated in AN mice after α-MG treatment, while creatinine clearance rate and serum albumin were upregulated (P<0.05). α-MG treatment alleviated the glomerular and interstitial fibrosis, downregulated the expression of fibrosis markers, such as Col I and α-SMA (P<0.05). α-MG treatment reduced the production of superoxide anion, the levels of MDA and GSH, and increased the activity of CAT and SOD (P<0.05). α-MG treatment inhibitd the generation of pro-inflammatory cytokines, such as IL-1β and IL-18 and promoted the production of anti-inflammatory cytokines, such as the IL-10 and adiponectin (P<0.05); α-MG treatment promoted the expression of Sirt1, inhibitd the expression of NLRP3 in kidney tissues (P<0.05). Conclusion: α-MG could attenuates FSGS of mice induced by adriamycin ameliorate and improve renal function. α-MG exerts its anti-inflammatory and anti-oxidative effects by up-regulation the expression of Sirt1 and suppression of NLRP3.
Subject(s)
Animals , Mice , Disease Models, Animal , Doxorubicin , Glomerulosclerosis, Focal Segmental , Kidney , Mice, Inbred NOD , Protein Kinase Inhibitors , Pharmacology , Therapeutic Uses , Xanthones , Pharmacology , Therapeutic UsesABSTRACT
Objective To investigate the phenotypic and functional properties of in vitro-induced He-lios+regulatory T cells(Helios+iTreg) and to analyze the differences between Helios+iTreg and Helios+thymic-derived natural Treg (Helios+nTreg). Methods CD4+CD25- effector T cells (CD4+CD25- Teff) that were separated from healthy subjects were cultured with anti-CD3 and anti-CD28 antibodies and stimulated with IL-2 and TGF-β to induce the generation of Helios+iTreg. Flow cytometry and real-time PCR were respectively used to analyze the differences in phenotype and CpG methylation in Treg-specific demethylated region (TSDR) be-tween Helios+iTreg and Helios+nTreg derived from the same donor. Results CD45RA was highly expressed on Helios+iTreg, but not on Helios+nTreg. Additionally, Helios+iTreg expressed significantly higher levels of CD127,ICOS and PD-1,but lower levels of CXCR3,CCR4 and CD25 than Helios+nTreg did. IFN-γ and IL-2 that expressed by Helios+iTreg were more than those by Helios+nTreg. It was also found that the level of CpG methylation in TSDR was much higher in Helios+iTreg than in Helios+nTreg. Conclusion Both nTreg and iTreg expressed Helios,but the phenotypic and functional properties of the two Treg subsets were different. It was suggested that Helios+iTreg and Helios+nTreg might play different roles in the immune system.