ABSTRACT
Background & objectives: Biapenem is a newly developed carbapenem to treat moderate and severe bacterial infections. This multicenter, randomized, parallel-controlled clinical trial was conducted to compare the clinical efficacy, bacterial eradication rates and safety of biapenem and meropenem in the treatment of bacterial lower respiratory tract infections and urinary tract infections (UTIs) at nine centres in China. Methods: Patients diagnosed with bacterial lower respiratory tract infections or UTIs were randomly assigned to receive either biapenem (300 mg every 12 h) or meropenem (500 mg every 8 h) by intravenous infusion for 7 to 14 days according to their disease severity. The overall clinical efficacy, bacterial eradication rates and drug-related adverse reactions of biapenem and meropenem were analyzed. Results: A total of 272 enrolled cases were included in the intent-to-treat (ITT) analysis and safety analysis. There were no differences in demographics and baseline medical characteristics between biapenem group and meropenem group. The overall clinical efficacies of biapenem and meropenem were not significantly different, 94.70 per cent (125/132) vs. 93.94 per cent (124/132). The overall bacterial eradication rates of biapenem and meropenem showed no significant difference, 96.39 per cent (80/83) vs. 93.75 per cent (75/80). Drug-related adverse reactions were comparable in biapenem and meropenem groups with the incidence of 11.76 per cent (16/136) and 15.44 per cent (21/136), respectively. The most common symptoms of biapenem-related adverse reactions were rash (2.2%) and gastrointestinal distress (1.5%). Interpretation & conclusions: Biapenem was non-inferior to meropenem and was well-tolerated in the treatment of moderate and severe lower respiratory tract infections and UTIs.
ABSTRACT
The expression of CDs+CD25+FoxP3+ regulatory T cells (CDs+Tregs) in the peripheral blood of patients with stable chronic obstructive pulmonary disease (COPD),and the effect of muscarinic cholinergic receptor antagonist tiotropium bromide on the expression of CD8+Tregs were investigated.Twenty-three patients with moderate to severe stable COPD were enrolled in this study.All patients inhaled tiotropium bromide (18 μg daily) for 3 months.Before and after inhalation of tiotropium bromide,peripheral blood samples were collected from the patients,and T cells were labeled by three-color labeled monoelonal antibodies.Flow cytometry was used to detect the quantity and percentage of CD8+T cells,CD8+CD25+T cells,CD8+Tregs,CD4+T cells,CD4+CD25+T cells and CD4+CD25+FoxP3+ regulatory T cells (CD4+Tregs) respectively.The percentage of CD4+T cells was increased from (27.82±2.18)％ to (35.53±1.3)％ (t=3.20,P=0.004) in the peripheral blood of patients with stable COPD after inhalation of tiotropium bromide for 3 months,that of CD4+CD25+T cells was decreased from (10.03 ±1.42)％ to (4.21± 0.65)％ (t=3.78,P=0.001),and that of CD8+Tregs was increased from (8.41 ±1.68)％ to (21.34±4.20)％ (t=2.72,P=0.013).At baseline,CD8+T cells,CD8+CD25+T cells and CD4+Tregs were detectable in the peripheral blood,but no significant changes were observed after treatment.Linear correlation analysis revealed that the difference before and after treatment in CD4+T cells and CD4+CD25+T cells was negatively correlated with the ratio of change in CD8+Tregs before and after treatment (r=-0.61,P=0.013; r=-0.72,P=0.001 respectively).In the peripheral blood of patients with stable COPD,there was the expression of CD8+Tregs and CD4+Tregs.Muscarinic receptor antagonist,tiotropium bromide,can promote the amplification of CD4+T cells,inhibit the expression of CD25+T cells,and enhance the expression of CD8+Tregs.CD8+Tregs and CD4+Tregs can be used as new indicators to understand the immune status of patients.They are helpful in judging the treatment efficacy and disease immunophenotype.
ABSTRACT
To compare the difference in tumor immunity and autoimmunity elicited by adenovirus (Ad) encoding human or murine tyrosinase-related protein 2 (AdhTRP2 or AdmTRP2), and to find the most effective way to induce immunity by AdhTRP2 or AdmTRP2, C57BL/6 mice were im-munized with AdhTRP2 or AdmTRP2 intramuscularly at different doses of 105, 106, 107 and 108 separately (10 mice for each dose). Two weeks after the immunization, in vivo CTL assay and in- tracellular staining (ICS) of IFN-γ were carried out to analyze the dose-effect relationship. Tumor growth and vitiligo (as an sign of autoimmunity) were observed until 3 months after challenge with 105 B I6F10 tumor cells. The results showed that Ad encoding AdmTrp2 induced weak tumor im- mune response. Similar immunization with AdhTrp-2 elicited stronger protective immunity. CTL activity and IFN-γ-produced CD8+T cells were directly proportional to dose of AdhTrp2 or AdmTrp2. Moreover, AdhTrp2 group showed tumor rejection in 100% of challenged mice till the end of 3rd month while 60% of mice immunized with AdmTrp2 were protected against tumor. In the whole process of this experiment, no vitiligo was observed in mice immunized either with AdhTrp2 or AdmTrp2. It is concluded that anti-melanoma responses induced by genetic vaccina- tion expressing xenoantigens breaks immune tolerance effectively and is able to elicit strong anti-gen-specific cytotoxic T cell response without vitiligo.