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Acta Pharmaceutica Sinica ; (12): 1721-1725, 2018.
Article in Chinese | WPRIM | ID: wpr-780052


In this study, the change of intestinal microflora in rat fecal samples after amoxicillin administration was observed. In vitro incubation experiments combined with LC-MS/MS assay were used to test the role of intestinal flora in the metabolism of nifedipine. The effect of changes of intestinal flora was determined after amoxicillin administration on the metabolism of nifedipine. We found that the number and types of intestinal flora decreased after taking amoxicillin. After incubation for 12 h, the results showed that the remaining amounts of nifedipine in the N1 group (nifedipine) and N2 group (amoxicillin + nifedipine) were 0.057 6 and 0.064 8 μmol·L-1, respectively, while the remaining amounts of nifedipine after 24 h of incubation were 0.039 6 and 0.050 4 μmol·L-1, respectively. These results show that the intestinal flora is involved in the metabolism of nifedipine. After administration of amoxicillin, the metabolism of nifedipine was slowed down, the AUC0-t was increased by 39.10%, tmax was advanced by 0.45 h, and the CL was reduced 34.71%. The data suggest that the combination may enhance the therapeutic effect of nifedipine. Therefore, drug-drug interactions mediated by gut microbiota cannot be ignored when combined with antibiotics and nifedipine, one of the important factors affecting drug efficacy.

Acta Pharmaceutica Sinica ; (12): 1533-1540, 2017.
Article in Chinese | WPRIM | ID: wpr-779757


The study is designed to evaluate the protective effect of xanthan gum (XG) injection on cartilage injury in the rabbit osteoarthritis (OA) model induced by anterior cruciate ligament transection (ACLT), and to explore the effect of XG on the expression of caspase-3 and Bax protein in OA cartilage. Sixty male New Zealand white rabbits were randomly divided into 6 groups (n=10) according to random number table method, and one group was selected randomly as the normal control group (control) while the other 5 groups of right knee were used to establish the OA model with ACLT, which were then divided into model group (model), XG-0.6 mg·kg-1, XG-1.2 mg·kg-1, XG-2.4 mg·kg-1 treatment group and sodium hyaluronate (SH-1.2 mg·kg-1) treatment group according to drug intervention. The knee joint temperature and knee joint width of each group were measured in the course of treatment. After treatment, the macroscopic morphology of rabbit joints in each group was observed. The pathological morphology of articular cartilage of rabbits in each group was observed using HE staining. The expression of Bax and cleaved caspase-3 in the cartilage of rabbits were detected by Western blot. The result shows that XG inhibited the increase in knee joint temperature and knee width caused by OA in a dose-dependent manner. XG improved the morphological abnormalities and tissue injuries of the femoral condyle and tibial plateau caused by OA. Western blot result shows that, compared with the control group, the levels of Bax and cleaved caspase-3 in knee cartilage cells of model group and XG-0.6 mg·kg-1 group were significantly increased (P-1 group (P>0.05). These two groups are significantly higher than those of XG-1.2 mg·kg-1 and XG-2.4 mg·kg-1 (P-1 and XG-1.2 mg·kg-1 group (P>0.05). The level of Bax in knee cartilage in XG-2.4 mg·kg-1 group was lower than that of XG-1.2 mg·kg-1 group (P<0.05). In conclusion, XG effectively protected cartilage damage in OA, and inhibited the expression of Bax and caspase-3 protein in OA cartilage.

Article in Chinese | WPRIM | ID: wpr-325105


<p><b>OBJECTIVE</b>To study the inhibitory effect of dexamethasone (DEX) on myeloid differentiation factor 88 (MyD88) and tumor necrosis factor-alpha (TNF-alpha) expression in mouse peritoneal macrophages in innate immune response to Penicillium marneffei (PM).</p><p><b>METHODS</b>Mouse peritoneal macrophages were cultured in the presence of heat-inactivated yeast-phase PM with or without DEX, and the protein and mRNA expressions of MyD88 in the macrophages were detected using Western blotting and real-time PCR, respectively. TNF-alpha in the cell culture supernatant was measured with enzyme-linked immunosorbent assay.</p><p><b>RESULTS</b>DEX suppressed TNF-alpha production by the macrophages co-cultured with PM. The expressions of MyD88 were up-regulated by PM stimulation, whose effect was inhibited by the application of DEX.</p><p><b>CONCLUSION</b>The inhibitory effect of DEX on PM-induced proinflammatory responses of the macrophage is directly associated with the inhibition of MyD88 expression.</p>

Animals , Cells, Cultured , Dexamethasone , Pharmacology , Macrophages, Peritoneal , Cell Biology , Metabolism , Male , Mice , Mice, Inbred BALB C , Myeloid Differentiation Factor 88 , Genetics , Metabolism , Penicillium , Tumor Necrosis Factor-alpha , Genetics , Metabolism
Article in Chinese | WPRIM | ID: wpr-268062


<p><b>OBJECTIVE</b>To investigate the differential expression of isocitrate lyase in Penicillium marneffei phagocytized by nonstimulated and stimulated murine macrophages, and explore the role of glyoxylate pathway in pathogenesis of Penicilliosis marneffei.</p><p><b>METHODS</b>Penicillium marneffei conidia and Raw264.7 cells were incubated in 16 cultures, which were divided to 4 groups for treatment with N-monomethyl-L-arginine (LNMMA, CI group), murine interferon-gamma (IFN-gamma) plus lipopolysaccharide (LPS) (T group), IFN-gamma plus LPS and LNMMA (TI group), or the same volume of culture medium (C group). The transcriptional levels of isocitrate lyase were detected using real-time RT-PCR, and its expression levels detected biochemically.</p><p><b>RESULTS</b>The transcriptional levels of isocitrate lyase in C, CI, T, TI groups were 1.00, 1.42, 33.09, and 74.88 (P<0.05), while the expression levels were 0.06, 0.07, 0.18, and 0.93, respectively (P<0.05). The content of nitric oxide in T group was significantly higher than that in the other groups (P<0.01), but the CFU of T group was the lowest (P<0.01).</p><p><b>CONCLUSION</b>Reactive nitrogen intermediates induced by stimulated murine macrophages restrain the expression of isocitrate lyase of Penicillium marneffei and development of Penicillium marneffei, in which process the glyoxylate pathway may play an important role.</p>

Animals , Cell Line , Fungal Proteins , Genetics , Gene Expression Profiling , Gene Expression Regulation, Enzymologic , Gene Expression Regulation, Fungal , Host-Pathogen Interactions , Interferon-gamma , Pharmacology , Isocitrate Lyase , Genetics , Lipopolysaccharides , Pharmacology , Macrophages , Allergy and Immunology , Microbiology , Mice , Nitric Oxide , Allergy and Immunology , Penicillium , Genetics , Allergy and Immunology , Physiology , Phagocytosis , Allergy and Immunology , Reverse Transcriptase Polymerase Chain Reaction , omega-N-Methylarginine , Pharmacology
Article in Chinese | WPRIM | ID: wpr-685252


Objective To investigate the dynamic distribution changes of fungi responsible for the deep infection and antifungal susceptibility to provide a basis for the empirical antifungal treatment.Methods Medical records were reviewed from cases suspectedof deep fungal infection at our hospital from January 1998 to December 2004.3122 isolates of 13 species were analyzed with SPSSll.0.Etest was used for the antifungal susceptibility test.Results Candida albicans was the most commonly isolated organism,while the prevalence of Candida albicans decreased(76.3% vs 66.8%,x~2=34.33,P

Microbiology ; (12)1992.
Article in Chinese | WPRIM | ID: wpr-685832


To assay the influence of dendritic cells(DCs)on the function of anti-infective immunity to Penicillium marneffei.DCs were generated from peripheral blood mononuclear cells(PBMC)and pulsed with Penicillium marneffei yeasts.DCs morphology was observed by the inverted microscope and cell surface markers of DCs were analyzed by flow cytometry.The concentrations of IL-12p70 were detected by ELISA. Mixed lymphocyte reaction was performed to assay the proliferation of T cells.The mRNA of CCR7 and CXCR4 were detected by the Real-time PCR quantifications.The acquired DCs exhibited irregular appearance and numerous long dendrites under light microscope.DCs and Penicillium marneffei yeasts were co-cultured for 24 h,numerous yeasts were observed inside the cells;an enhanced expression of the cell sur-face markers CD86、CD83、HLA-DR and CD40 were demonstrated;the expression of CCR7 and CXCR4 mRNA were also increased;the improved proliferation of T cells were observed in the mixed lymphocyte reaction.Yeasts-pulsed DCs secreted more IL-12p70 than that of non-pulsed,but less than that of LPS-pulsed DCs.DCs can engulf the Penicillium marneffei yeasts.When pulsed with Penicillium marneffei yeasts,DCs improved their expression of the co-stimulatory molecules and chemokine receptor CCR7、CXCR4,enhanced their capacity to process antigen.DCs play an important role in host defense against Penicillium marneffei infection.But the low level of the IL-12p70 production may lead to deficiency in the cell-mediated immunity against Penicillium marneffei.