This study investigated the therapeutic effects of interleukin （IL）-2 and granulocyte-macrophage colony-stimulating factor （GM-CSF） co-administrated with antibacterial agents isoniazid （INH） and rifampin （RIF）...This study investigated the therapeutic effects of interleukin （IL）-2 and granulocyte-macrophage colony-stimulating factor （GM-CSF） co-administrated with antibacterial agents isoniazid （INH） and rifampin （RIF） to treat a mouse model of tuberculo- sis （TB） infection. A drug-susceptible TB strain, H37Rv was used to infect mice and the effectiveness of IL-2 and GM-CSF was initially evaluated based on survival rate, bacterial counts in lungs and spleens and the pathological condition of the lungs. Next, the therapeutic effect of the immunotherapy regimen was assessed in multidrug-resistant strain OB35-infected mice. In the H37Rv infection model, 1L-2 and GM-CSF monotherapies reduced bacterial numbers in the lungs by 0.82 （P〈0.01） and 0.58 （P〈0.05） lg colony-forming units （CFU）, respectively, and in the spleens by 1.42 （P〈0.01） and 1.22 （P〈0.01） lg CFU, re- spectively, compared with the untreated group. Mice receiving immunotherapy developed fewer lesions in the lungs compared with mice receiving antibacterial therapy alone. In the OB35 infection model, immunotherapy with either cytokine resulted in a significant reduction of bacterial load in the lungs and spleens and less severe lesions in the lungs compared with the untreated or antibacterial therapy treated mice. Notably, mice receiving immunotherapy with both cytokines had a 30% survival rate which was higher than that in other treated groups, and had significantly less CFUs in the lungs and spleens （1.02 and 1.34 lg CFU） compared with antibacterial therapy alone （P〈0.01）. This study demonstrated that immunotherapy with both IL-2 and GM-CSF may be useful to treat multidrug resistant tuberculosis （MDR-TB）.展开更多
The anti-fungus mechanisms and curative effects of cinnamon oil and pogostemon oil complexes to wards intestinal Candida infections were investigat ed.We measured the minimal inhibitory concentra tion(MIC) values of t...The anti-fungus mechanisms and curative effects of cinnamon oil and pogostemon oil complexes to wards intestinal Candida infections were investigat ed.We measured the minimal inhibitory concentra tion(MIC) values of the complexes against Candida using proportionally-diluted test-tube medium and examined the evolution of the morphology and structures of Candida albicans using scanning electronic microscopy(SEM) and transmission elec tronic microscopy(TEM).We found that the aver age MIC values of the complexes against the fung were 0.064 mg/mL(cinnamon oil),0.032 mg/mL(pogostemon oil) for Candida albicans,0.129 mg/mL(cinnamon oil),0.064 mg/mL(pogostemon oil for Candida tropicalis,and 0.129 mg/mL(cinnamon oil),0.064 mg/mL(pogostemon oil),for Candida krusei.SEM examination over a 24-48 h period showed that the morphology of Candida albicans cells changed significantly.Irregular hollows ap peared on the surfaces,inside organelles were destroyed and the cells burst after treatment.TEM examination over a 48-72 h period indicated that the cell walls were damaged,organelles were destroyed and most cytoplasms became empty bubbles.Sixty intestinal Candida-infected patients were treated with a capsule containing cinnamon and pogostemon oil.The curative ratio was 71.67%(43/60),and the improvement ratio was 28.33%(17/60),giving a to talratio of 100%.Thus,the cinnamonoil and pogostemon oil complexes had strong anti-funguseffectsag ainst Candida albicans,Candidatropicalis,and Candidakrusei.They impacted the morphology and sub-micro structures of the fungus within48-72h,and eventually denatured and killed the cells.The complexes have also shown considerable curative effects to intestinal Candida infections.展开更多
In the present study,we optimized the ceftriaxone dosing regimens based on pharmacokinetic/pharmacodynamic(PK/PD)principles using Monte Carlo simulation(MCS).Based on PK/PD theory,MCS was performed using Crystal Ball ...In the present study,we optimized the ceftriaxone dosing regimens based on pharmacokinetic/pharmacodynamic(PK/PD)principles using Monte Carlo simulation(MCS).Based on PK/PD theory,MCS was performed using Crystal Ball software combining PK and PD parameters with 10000 simulation runs to calculate the probability of target attainment(PTA)and cumulative fraction of response(CFR)for the seven clinically common dosing regimens of ceftriaxone(1 g qd,1.5 g qd,1 g bid,2 g qd,1 g tid,1.5 g bid,and 2 g bid).A%fT≥50 as the target value expected to achieve satisfactory clinical efficacy and a dosing regimen with an obtained CFR≥90%or the ability to achieve the highest PTA was used as a reasonable choice for empirical antimicrobial therapy,i.e.the clinically optimal regimen.All eight pathogenic bacteria had a CFR>90%when the dosing regimen was 2 g bid and 1 g tid,seven pathogenic bacteria had a CFR>90%when the dosing regimen was 1 g bid and 1.5 g bid,except for Pseudomonas aeruginosa,and all pathogenic bacteria had a CFR<90%when the dosing regimen was 1 g qd and 1.5 g qd.The dosing regimens of 2 g bid and 1 g tid were effective against all eight pathogenic bacteria infections,and 1 g bid and 1.5 g bid dosing regimens were effective against the other seven pathogenic bacteria except for Pseudomonas aeruginosa.展开更多
基金supported in part by the Key Technologies Research and Development Program for Infectious Diseases of China (Grant No. 2012ZX10003001)the Key Project of Science and Technology of Shanghai (Grant No.10411955000)the Shanghai Science and Technology Development Funds (Grant No. 10XD1400900)
文摘This study investigated the therapeutic effects of interleukin （IL）-2 and granulocyte-macrophage colony-stimulating factor （GM-CSF） co-administrated with antibacterial agents isoniazid （INH） and rifampin （RIF） to treat a mouse model of tuberculo- sis （TB） infection. A drug-susceptible TB strain, H37Rv was used to infect mice and the effectiveness of IL-2 and GM-CSF was initially evaluated based on survival rate, bacterial counts in lungs and spleens and the pathological condition of the lungs. Next, the therapeutic effect of the immunotherapy regimen was assessed in multidrug-resistant strain OB35-infected mice. In the H37Rv infection model, 1L-2 and GM-CSF monotherapies reduced bacterial numbers in the lungs by 0.82 （P〈0.01） and 0.58 （P〈0.05） lg colony-forming units （CFU）, respectively, and in the spleens by 1.42 （P〈0.01） and 1.22 （P〈0.01） lg CFU, re- spectively, compared with the untreated group. Mice receiving immunotherapy developed fewer lesions in the lungs compared with mice receiving antibacterial therapy alone. In the OB35 infection model, immunotherapy with either cytokine resulted in a significant reduction of bacterial load in the lungs and spleens and less severe lesions in the lungs compared with the untreated or antibacterial therapy treated mice. Notably, mice receiving immunotherapy with both cytokines had a 30% survival rate which was higher than that in other treated groups, and had significantly less CFUs in the lungs and spleens （1.02 and 1.34 lg CFU） compared with antibacterial therapy alone （P〈0.01）. This study demonstrated that immunotherapy with both IL-2 and GM-CSF may be useful to treat multidrug resistant tuberculosis （MDR-TB）.
文摘The anti-fungus mechanisms and curative effects of cinnamon oil and pogostemon oil complexes to wards intestinal Candida infections were investigat ed.We measured the minimal inhibitory concentra tion(MIC) values of the complexes against Candida using proportionally-diluted test-tube medium and examined the evolution of the morphology and structures of Candida albicans using scanning electronic microscopy(SEM) and transmission elec tronic microscopy(TEM).We found that the aver age MIC values of the complexes against the fung were 0.064 mg/mL(cinnamon oil),0.032 mg/mL(pogostemon oil) for Candida albicans,0.129 mg/mL(cinnamon oil),0.064 mg/mL(pogostemon oil for Candida tropicalis,and 0.129 mg/mL(cinnamon oil),0.064 mg/mL(pogostemon oil),for Candida krusei.SEM examination over a 24-48 h period showed that the morphology of Candida albicans cells changed significantly.Irregular hollows ap peared on the surfaces,inside organelles were destroyed and the cells burst after treatment.TEM examination over a 48-72 h period indicated that the cell walls were damaged,organelles were destroyed and most cytoplasms became empty bubbles.Sixty intestinal Candida-infected patients were treated with a capsule containing cinnamon and pogostemon oil.The curative ratio was 71.67%(43/60),and the improvement ratio was 28.33%(17/60),giving a to talratio of 100%.Thus,the cinnamonoil and pogostemon oil complexes had strong anti-funguseffectsag ainst Candida albicans,Candidatropicalis,and Candidakrusei.They impacted the morphology and sub-micro structures of the fungus within48-72h,and eventually denatured and killed the cells.The complexes have also shown considerable curative effects to intestinal Candida infections.
基金2019 Second Hospital of Hebei Medical University Pro ject(Grant No.2h2019042)。
文摘In the present study,we optimized the ceftriaxone dosing regimens based on pharmacokinetic/pharmacodynamic(PK/PD)principles using Monte Carlo simulation(MCS).Based on PK/PD theory,MCS was performed using Crystal Ball software combining PK and PD parameters with 10000 simulation runs to calculate the probability of target attainment(PTA)and cumulative fraction of response(CFR)for the seven clinically common dosing regimens of ceftriaxone(1 g qd,1.5 g qd,1 g bid,2 g qd,1 g tid,1.5 g bid,and 2 g bid).A%fT≥50 as the target value expected to achieve satisfactory clinical efficacy and a dosing regimen with an obtained CFR≥90%or the ability to achieve the highest PTA was used as a reasonable choice for empirical antimicrobial therapy,i.e.the clinically optimal regimen.All eight pathogenic bacteria had a CFR>90%when the dosing regimen was 2 g bid and 1 g tid,seven pathogenic bacteria had a CFR>90%when the dosing regimen was 1 g bid and 1.5 g bid,except for Pseudomonas aeruginosa,and all pathogenic bacteria had a CFR<90%when the dosing regimen was 1 g qd and 1.5 g qd.The dosing regimens of 2 g bid and 1 g tid were effective against all eight pathogenic bacteria infections,and 1 g bid and 1.5 g bid dosing regimens were effective against the other seven pathogenic bacteria except for Pseudomonas aeruginosa.
