Objective:To assess and characterize antibiotic resistance in Acinetobacter baumannii strains recovered from 5 health-care facilities in Algiers.Methods:Antibiotic susceptibility testing was performed by agar diffusio...Objective:To assess and characterize antibiotic resistance in Acinetobacter baumannii strains recovered from 5 health-care facilities in Algiers.Methods:Antibiotic susceptibility testing was performed by agar diffusion and agar dilution methods,resistance genes were identified by PCR and sequencing,and molecular typing of isolates was carried out by enterobacterial repetitive intergenic consensus-PCR(ERIC-PCR).Results:Among 125 tested isolates,117(93.6% ) were multidrug-resistant.of which 94(75.2% ) were imipenem resistant.The bla_(ADC)and bla_(OXA-51-like) genes were detected in all isolates,in association with ISAba I sequence in 84% and 8% (imipenem resistant) of isolates,respectively.The bla_(OXA-23-like) and bla_(OXA-24-like)carbapenemase genes were delected in 67.02% and 20.21% of imipenem-resistant isolates,respectively.The bla_(OXA-23-like) gene is linked to ISAba1 or ISAba4 elements.The metallo-β-lactamase NDM-1 gene was found in 10(10.6% ) imipenem-resisianl strains from three hospitals,it is linked to ISAba125 clement in nine strains.Extended spectrum β-lactamases production was not detected.Imipenem and cefotaxime resistance phenolypes could not be transferred to Escherichia coli by conjugation.Outer membrane protein CarO gene was not delected in four imipenem-resisianl isolates.The aac(6')-1b.sul1,sul2,tetA and tetB genes were present in 5.31% .36.17% .77.65% .1.06% and 65.92% of strains,respectively.Class 1 integrons were detected in 23.4% strains.KRIC-PCR typing showed a genetic diversity among bla_(OXA-23-like) and bla_(OXA-24-like) positive strains,while clonality was observed among bla_(NDM-1)positives.Conclusions:This study highlighted the high prevalence of imipenem resistance in Acinetobacter baumannii in Algiers hospitals mediated mainly by bla_(OXA-23-like),bla_(OXA-24-like),and bla_(NDM-1) genes.展开更多
AIM: To reveal the expression of multidrug-resistance associated proteins: glutathione-S-transferase π(GSTπ), P-glycoprotein(P-gp) and vault protein lung resistance protein(LRP) in retinoblastoma(RB) witho...AIM: To reveal the expression of multidrug-resistance associated proteins: glutathione-S-transferase π(GSTπ), P-glycoprotein(P-gp) and vault protein lung resistance protein(LRP) in retinoblastoma(RB) without any conservative treatment before primary enucleation and to correlate this expression with histopathological tumor features. METHODS: A total of 42 specimens of RB undergone primary enucleation were selected for the research. Sections from the formalin-fixed, paraffin-embedded specimens were stained with HE and immunohistochemistry to detect the expression of GSTπ, P-gp and LRP.RESULTS: GSTπ was expressed in 39/42(92.86%) RBs and in 9/9(100%) well-differentiated RBs. P-gp/GSTπ was found in 30(71.42%) of 42 RBs. Totally 9(21.43%) tumors were well differentiated and 33(78.57%) were poorly differentiated. Totally 15(35.71%) eyes had optic nerve(ON) tumor invasion, 36(85.71%) had choroidal tumor invasion, and 14(33.33%) had simultaneous choroidal and ON invasion. There was no statistically significant relationship between P-gp, GSTπ, LRP positivity and the degree of ocular layer tumor invasion and ON tumor invasion(P〉0.05). CONCLUSION: RB intrinsically expresses GSTπ, P-gp and LRP. GSTπ expression is positive in 100% welldifferentiation ones, so in which way it is correlated with differentiation. But the other two proteins expressions are not related to tumor differentiation and to the degree of tumor invasion. GSTπ may be a new target of chemotherapy in RB.展开更多
Staphylococcus aureus is major human pathogen causing large variety of infections worldwide. This study carried out to isolate S. aureus from different clinical cases, also detection of MRSA prevalence and VRSA emerge...Staphylococcus aureus is major human pathogen causing large variety of infections worldwide. This study carried out to isolate S. aureus from different clinical cases, also detection of MRSA prevalence and VRSA emergence, in addition to shedding light on strains that have to be multidrug resistance against various antibiotics, The clinical samples were collected from AI-Jumhuory Teaching Hospital patients in Mosul, isolates identification were achieved by conventional procedures including biochemical and physiological tests, and the specific latex agglutination test. The sensitivity pattern achieved by using disk diffusion technique, for MRSA and VRSA detection oxacillin-disk (1 μg) and vancomycin-disk (30 μg) were used respectively. Results revealed, among 17 S. aureus isolates, 7 (41%) were mostly isolated from patients with wound and burn infections. Isolates had high resistance rate against ampicillin (100%) and cefotaxime (81%), and lower resistance rate against several antibiotics. MRSA was 88% of total isolates, 93.3% of MRSA were multidrug resistance to 3-9 of antibiotics. Six isolates (40%) of MRSA were VRSA. It is concluded that antibiotics other than vancomycin can be used as anti-MRSA agents after a sensitivity test to prevent the prevalence of VRSA, the major cause of this chemotherapy problems maybe irrational and indiscriminate use of broad-spectrum antibiotics.展开更多
Objective: To study the effect of adenovirus- mediated transfer of anti-MDR1 ribozyme on the reversal of multidrug resistant (MDR) phenotype of P-glycoprotein (P-gp)-positive Daudi human Burkitt lymphoma both in vitro...Objective: To study the effect of adenovirus- mediated transfer of anti-MDR1 ribozyme on the reversal of multidrug resistant (MDR) phenotype of P-glycoprotein (P-gp)-positive Daudi human Burkitt lymphoma both in vitro and in vivo. Methods: A recombinant adenovirus expressing 196Rz (Adv-196Rz) was developed and functionally evaluated. SCID mice inoculated subcutaneously (s.c.) with 5?06 Daudi/MDR20 cells were locally treated with Adv-196Rz or mock virus (Adv-Mock) at the multiplicity of infection (MOI) of 400 PFU once a day for 3 consecutive days. Then the mice were intraperitoneally (i.p.) administrated with vincristine (VCR) 450ng/g for 5 consecutive days. Results: In vitro employment of Adv-196Rz was able to interrupt MDR1 transcription, to inhibit P-gp expression and to restore drug sensitivity to VCR of Daudi/MDR20 cells. In vivo, 87.5% (7/8) of Daudi/MDR20-inoculated mice treated with Adv-Mock+ VCR developed palpable tumor by the 6th week and died or were sacrificed (because of tumor weight > 10% of body weight) by the 11th week. In contrast, among 9 Daudi/MDR20-inoculated mice treated with Adv-196Rz + VCR, only 3 developed tumor by the 11th, 13th and 14th week, respectively. 66.7% of mice survived >120 days in tumor-free. The survival difference between the two groups was very significant (P<0.01). Conclusion: Adenovirus- mediated Transfer of 196Rz can revert drug resistance of MDR tumor cells both in vitro and in vivo. Adv-196Rz may prove useful as an adjuvant in the chemotherapy of P-gp mediated MDR human tumors.展开更多
Purpose: The drug resistance pattern in tuberculosis (TB) is still under investigated. We analyzed the clinical data from the patients with smear positive TB and applied the model to predict the patients with smear-po...Purpose: The drug resistance pattern in tuberculosis (TB) is still under investigated. We analyzed the clinical data from the patients with smear positive TB and applied the model to predict the patients with smear-positive TB. Materials and Methods: Medical records information of 6977 cases was included from 11,950 inpatients from January 2009 to November 2013. The cases data were divided into a training set, test set and prediction set. Logistic regression analysis was applied to the training set data to establish a prediction classification model, the effect of which was then evaluated using the test set by receiver operating characteristic (ROC) analysis. The model was then applied to the prediction set to identify incidence of snMDR-TB. Results: Sixteen factors which correlate with MDR-TB-including frequency of hospitalization, province of origin, anti-TB drugs, and complications, were identified from the comparison between SP-TB and spMDR-TB. The area under the ROC curve (AUC) of the prediction model was 0.752 (sensitivity = 61.3%, specificity = 83.3%). The percentage of all inpatients with snMDR-TB (snMDR-TB/Total) was 28.7% ± 0.02%, while that of all SN-PTB with snMDR-TB (snMDR-TB/SN-PTB) was 26.5% ± 0.03%. The ratio of snMDR-TB to MDR-TB (snMDR-TB/MDR-TB) was 2.09 ± 0.33. Conclusion: snMDR-TB as an important source of MDR-TB is a significant hidden problem for MDR-TB control and can be identified by the prediction model. A kind of vicious circle with a certain delay effect exists between snMDR-TB and MDR-TB. To better control MDR-TB, it is necessary to pay greater attention to snMDR-TB, conduct further research and develop targeted therapeutic strategies.展开更多
Objective: To explore the roles of intracellular pH value (pHi) and sodium-hydrogen exchanger isoform-1 (NHE-1) in the mechanism of multidrug resistance of leukemia cells. Methods: Multidrug resistant cell line HL-60 ...Objective: To explore the roles of intracellular pH value (pHi) and sodium-hydrogen exchanger isoform-1 (NHE-1) in the mechanism of multidrug resistance of leukemia cells. Methods: Multidrug resistant cell line HL-60 induced by doxorubicin(DOX) (called as HL-60/DOX cells) and their parent cell line HL-60 were employed as experiment group and control group. The proliferation and chemosensitivity of the cells were studied by MTT assay, and the expression of multidrug resistance protein (MRP) was detected by immol/Lunocytochemistry. Meanwhile, pHi was measured by spectrofluorometery with a fluorescence dye BCECF-AM. Based on the pHi recovery curve after intracellular acid loading, the activity of NHE-1 was analyzed. The expression of NHE-1 mRNA and MRP mRNA were determined by semi-quantitative RT-PCR. Cell apoptosis was observed with terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL), and apoptotic DNA was extracted and electrophoresed. Results: ① The IC 50 values for DOX, MTZ, VCR and homoharringtonine(HT), in HL-60/DOX cells were significantly higher than those in HL-60 cells (P<0.01). HL-60/DOX cells expressed abundant MRP, but HL-60 cells did not. ② pHi of HL-60/DOX cells were significantly higher than that of HL-60 cells(P<0.001). The expression and activity of NHE-1 in HL-60/DOX cells were significantly stronger than those of HL-60 cells. ③After administration of the specific NHE-1 inhibitor dimethyl amiloride (DMA) at a certain range of concentrations, compared with HL-60 cells, the rate of growth inhibition of HL-60/DOX cells increased significantly (P<0.05), the drug-sensitivity of HL-60/DOX cells was significantly sensitive (P<0.01), the expression of MRP and MRP mRNA decreased significantly (P<0.01), the apoptosis rate increased significantly (P<0.01). Conclusion: NHE-1 is involved in the drug-resistant mechanisms of multidrug-resistant HL-60 cells induced by DOX. The specific NHE-1 inhibitor DMA can partly reverse the multidrug resistance of HL-60 cells induced by DOX.展开更多
Objective:To observe the reversion of multi-drug resistance by proteasome inhibitor bortezomib in K562/DNR cell line and to analyze the possible mechanism of reversion of multidrug-resistance.Methods:MTT method was ...Objective:To observe the reversion of multi-drug resistance by proteasome inhibitor bortezomib in K562/DNR cell line and to analyze the possible mechanism of reversion of multidrug-resistance.Methods:MTT method was used to determine the drug resistance of K562/DNR cells and the cellular toxicity of bortezomib.K562/DNR cells were cultured for 12 hours,24 hours and 36 hours with 100 μg/ml DNR only or plus 4 μg/L bortezomib.The expressions of NF-κB,IκB and P-gp of K562/DNR were detected with Western blot method,the activity of NF-κB was tested by ELISA method and the apoptosis rate was observed in each group respectively.Results:The IC50 of DNR on cells of K562/S and K562/DNR groups were 1.16 μg/ml and 50.43 μg/mL,respectively.The drug-resistant fold was 43.47.The IC10 of PS-341 on Cell strain K562/DNR was 4 μg/L.Therefore,4 μg/L was selected as the concentration for PS-341 to reverse drug-resistance in this study.DNR induced down-regulation of IκB expression,up-regulation of NF-κB and P-gp expression.After treatment with PS-341,a proteasome inhibitor,the IκB degradation was inhibited,IκB expression increased,NF-κB and P-gp expression decreased in a time dependent manner.Compared to DNR group,the NF-κB p65 activity of DNR+PS-341 group was decreased.Compared to corresponding DNR group,DNR induced apoptosis rate increases after addition of PS-341 in a time dependent manner.Conclusion:Proteasome inhibitor bortezomib can convert the leukemia cell drug resistance.The mechanism may be that bortezomib decreases the degradation of IκB and the expression of NF-κB and P-gp,therefore induces the apoptosis of multi-drug resistant cells.展开更多
Several related substances were detected at trace level in (2R)-2,3-dihydro-2-methyl-6-nitro-2-[[4-[4-[4-(trifluoromethoxy)phenoxy]-1-piperidinyl] phenoxy] methyl]imidazo[2, 1-b]oxazole drug substance by a newly devel...Several related substances were detected at trace level in (2R)-2,3-dihydro-2-methyl-6-nitro-2-[[4-[4-[4-(trifluoromethoxy)phenoxy]-1-piperidinyl] phenoxy] methyl]imidazo[2, 1-b]oxazole drug substance by a newly developed high-performance liquid chromatography method. All related substances were characterized rapidly but some impurities were found to be intermediates. Proposed structures were further confirmed by characterization using NMR, FT-IR, and HRMS techniques. Based on the spectroscopic data;unknown related sub-stances were characterized as 1-(Methylsulfonyl)-4-[4-(trifluoromethoxy) phenoxy]piperidine;4-{4-[4-(Tri-fluoromethoxy)-phenoxy]piperidin-1-yl}phenol and 4-{4-[4-(trifluoromethoxy)phenoxy]piperidin-1-yl}phenyl methane sulfonate;4-Bromophenyl methane sulfonate, Ethyl 3,6-dihydro-1(2H)-pyridine carboxylate, (2S)-3-(4-Bromophenoxy)-2-hydroxy-2-methylpropyl methane sulfonate, (2S)-3-(4-Bromophenoxy)-2-methylpropane-1,2-diyldimethane-sulfonate, (2S)-2-Methyl-3-(4-{4-[4-(trifluoromethoxy) phenoxy]-piperidin-1-yl} phenoxy)-propane-1,2-diyldimethane sulfonate, (S)-3-(4-Bromophenoxy)-2-methyl-propane-1,2-diol and corresponding Enantiomer, (2R)-2-[(4-Bromo-phenoxy)methyl]-2-methyloxirane and (2R)-2-[(4-bromophenoxy)methyl]-2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b][1,3]oxazole. A possible mechanism for the formation of these related substances is also proposed.展开更多
Resistant bacteria can be transmitted to humans through feces or contaminated meat from local chickens. Bacterial strains were isolated from the intestinal contents of 400 local chicken samples from various sales site...Resistant bacteria can be transmitted to humans through feces or contaminated meat from local chickens. Bacterial strains were isolated from the intestinal contents of 400 local chicken samples from various sales sites. These strains were then characterized using bacteriological and biochemical methods to identify resistant strains. In a study conducted in Ouagadougou, we systematically collected chicken fecal samples from 20 locations across the city, followed by isolation and identification of Salmonella spp. using specific enrichment and culture methods, as well as Escherichia coli. Bacterial strains were characterized using antibiotic resistance profiles were determined through agar diffusion tests, revealing sensitivity or resistance to a range of antibiotics based on established scientific criteria. The results showed that out of the 400 samples collected, 81.25% and 63.5% were contaminated by Escherichia coli and Salmonella spp., respectively. Among these, 86.15% of identified Escherichia coli and 50.78% of Salmonella spp. displayed resistance to at least one tested antibiotic. Among 280 Escherichia coli isolates identified resistant to at least one antibiotic, 31.07% were resistant to cefotaxime (CTX), 20.35% to ceftazidime (CAZ), 21.07% to ceftriaxone (CTR), 75% to amoxicillin clavulanic acid (AMC), 23.57% aztreoname (ATM) and 27.14% were resistant to imipenem (IMP). In the case of the 129 Salmonella spp. isolates resistant to at least one tested antibiotic, 34.88% were resistant to CTX;41.08% to CAZ;35.65% to CTR, 92% to AMC, 39.53% to ATM and finally 47.28% were resistant to IMP. Our study revealed high prevalence of resistance in bacterial strains isolated from local chickens sold outdoors in Ouagadougou. These findings raise significant public health concerns, due to the possible transmission of these resistant strains to humans through the consumption of contaminated meat, thus complicating the treatment of bacterial infections.展开更多
Objective:To study the clinical efficacy and safety of tigecycline in the treatment of acute exacerbation of chronic obstructive pulmonary disease(COPD)combined with multidrug-resistant Acinetobacter baumannii infecti...Objective:To study the clinical efficacy and safety of tigecycline in the treatment of acute exacerbation of chronic obstructive pulmonary disease(COPD)combined with multidrug-resistant Acinetobacter baumannii infection.Methods:113 patients with acute exacerbation of COPD combined with multidrug-resistant Acinetobacter baumannii infection were recruited between January 2021 and January 2023,and given tigecycline treatment.The total effective rate,lung function indexes,related biochemical index levels,and the incidence rate of adverse reactions were observed after the treatment.Results:After the treatment,100 patients were cured,1 case with apparent effect,2 cases were effective,10 cases were ineffective,and the total effective rate was 91.15%.The post-treatment CRP(21.22±3.35 mg/L),PCT(3.18±1.11 ng/L),CRE(76.36±9.24μmol/L),and ALT(37.76±6.99 U/L)were significantly improved as compared to the pre-treatment(P<0.05).After treatment,10 cases of vomiting(8.85%),13 cases of nausea(11.50%),4 cases of diarrhea(3.53%),1 case of abdominal pain(0.88%),and 2 cases of allergy(1.77%)were observed in 113 patients.Conclusion:Tigecycline therapy for patients with acute exacerbation of COPD combined with multidrug-resistant Acinetobacter baumannii infection not only has significant therapeutic efficacy but also has a high degree of safety.展开更多
基金supported by grants from National Fund for the Research and National Agency for the Development of Research in Health(Algeria)
文摘Objective:To assess and characterize antibiotic resistance in Acinetobacter baumannii strains recovered from 5 health-care facilities in Algiers.Methods:Antibiotic susceptibility testing was performed by agar diffusion and agar dilution methods,resistance genes were identified by PCR and sequencing,and molecular typing of isolates was carried out by enterobacterial repetitive intergenic consensus-PCR(ERIC-PCR).Results:Among 125 tested isolates,117(93.6% ) were multidrug-resistant.of which 94(75.2% ) were imipenem resistant.The bla_(ADC)and bla_(OXA-51-like) genes were detected in all isolates,in association with ISAba I sequence in 84% and 8% (imipenem resistant) of isolates,respectively.The bla_(OXA-23-like) and bla_(OXA-24-like)carbapenemase genes were delected in 67.02% and 20.21% of imipenem-resistant isolates,respectively.The bla_(OXA-23-like) gene is linked to ISAba1 or ISAba4 elements.The metallo-β-lactamase NDM-1 gene was found in 10(10.6% ) imipenem-resisianl strains from three hospitals,it is linked to ISAba125 clement in nine strains.Extended spectrum β-lactamases production was not detected.Imipenem and cefotaxime resistance phenolypes could not be transferred to Escherichia coli by conjugation.Outer membrane protein CarO gene was not delected in four imipenem-resisianl isolates.The aac(6')-1b.sul1,sul2,tetA and tetB genes were present in 5.31% .36.17% .77.65% .1.06% and 65.92% of strains,respectively.Class 1 integrons were detected in 23.4% strains.KRIC-PCR typing showed a genetic diversity among bla_(OXA-23-like) and bla_(OXA-24-like) positive strains,while clonality was observed among bla_(NDM-1)positives.Conclusions:This study highlighted the high prevalence of imipenem resistance in Acinetobacter baumannii in Algiers hospitals mediated mainly by bla_(OXA-23-like),bla_(OXA-24-like),and bla_(NDM-1) genes.
基金Supported by the National Natural Science Foundation of China(No.30371515)
文摘AIM: To reveal the expression of multidrug-resistance associated proteins: glutathione-S-transferase π(GSTπ), P-glycoprotein(P-gp) and vault protein lung resistance protein(LRP) in retinoblastoma(RB) without any conservative treatment before primary enucleation and to correlate this expression with histopathological tumor features. METHODS: A total of 42 specimens of RB undergone primary enucleation were selected for the research. Sections from the formalin-fixed, paraffin-embedded specimens were stained with HE and immunohistochemistry to detect the expression of GSTπ, P-gp and LRP.RESULTS: GSTπ was expressed in 39/42(92.86%) RBs and in 9/9(100%) well-differentiated RBs. P-gp/GSTπ was found in 30(71.42%) of 42 RBs. Totally 9(21.43%) tumors were well differentiated and 33(78.57%) were poorly differentiated. Totally 15(35.71%) eyes had optic nerve(ON) tumor invasion, 36(85.71%) had choroidal tumor invasion, and 14(33.33%) had simultaneous choroidal and ON invasion. There was no statistically significant relationship between P-gp, GSTπ, LRP positivity and the degree of ocular layer tumor invasion and ON tumor invasion(P〉0.05). CONCLUSION: RB intrinsically expresses GSTπ, P-gp and LRP. GSTπ expression is positive in 100% welldifferentiation ones, so in which way it is correlated with differentiation. But the other two proteins expressions are not related to tumor differentiation and to the degree of tumor invasion. GSTπ may be a new target of chemotherapy in RB.
文摘Staphylococcus aureus is major human pathogen causing large variety of infections worldwide. This study carried out to isolate S. aureus from different clinical cases, also detection of MRSA prevalence and VRSA emergence, in addition to shedding light on strains that have to be multidrug resistance against various antibiotics, The clinical samples were collected from AI-Jumhuory Teaching Hospital patients in Mosul, isolates identification were achieved by conventional procedures including biochemical and physiological tests, and the specific latex agglutination test. The sensitivity pattern achieved by using disk diffusion technique, for MRSA and VRSA detection oxacillin-disk (1 μg) and vancomycin-disk (30 μg) were used respectively. Results revealed, among 17 S. aureus isolates, 7 (41%) were mostly isolated from patients with wound and burn infections. Isolates had high resistance rate against ampicillin (100%) and cefotaxime (81%), and lower resistance rate against several antibiotics. MRSA was 88% of total isolates, 93.3% of MRSA were multidrug resistance to 3-9 of antibiotics. Six isolates (40%) of MRSA were VRSA. It is concluded that antibiotics other than vancomycin can be used as anti-MRSA agents after a sensitivity test to prevent the prevalence of VRSA, the major cause of this chemotherapy problems maybe irrational and indiscriminate use of broad-spectrum antibiotics.
基金This work was supported in part by theNational Natural Science Foundation of China (No. 39970831).
文摘Objective: To study the effect of adenovirus- mediated transfer of anti-MDR1 ribozyme on the reversal of multidrug resistant (MDR) phenotype of P-glycoprotein (P-gp)-positive Daudi human Burkitt lymphoma both in vitro and in vivo. Methods: A recombinant adenovirus expressing 196Rz (Adv-196Rz) was developed and functionally evaluated. SCID mice inoculated subcutaneously (s.c.) with 5?06 Daudi/MDR20 cells were locally treated with Adv-196Rz or mock virus (Adv-Mock) at the multiplicity of infection (MOI) of 400 PFU once a day for 3 consecutive days. Then the mice were intraperitoneally (i.p.) administrated with vincristine (VCR) 450ng/g for 5 consecutive days. Results: In vitro employment of Adv-196Rz was able to interrupt MDR1 transcription, to inhibit P-gp expression and to restore drug sensitivity to VCR of Daudi/MDR20 cells. In vivo, 87.5% (7/8) of Daudi/MDR20-inoculated mice treated with Adv-Mock+ VCR developed palpable tumor by the 6th week and died or were sacrificed (because of tumor weight > 10% of body weight) by the 11th week. In contrast, among 9 Daudi/MDR20-inoculated mice treated with Adv-196Rz + VCR, only 3 developed tumor by the 11th, 13th and 14th week, respectively. 66.7% of mice survived >120 days in tumor-free. The survival difference between the two groups was very significant (P<0.01). Conclusion: Adenovirus- mediated Transfer of 196Rz can revert drug resistance of MDR tumor cells both in vitro and in vivo. Adv-196Rz may prove useful as an adjuvant in the chemotherapy of P-gp mediated MDR human tumors.
文摘Purpose: The drug resistance pattern in tuberculosis (TB) is still under investigated. We analyzed the clinical data from the patients with smear positive TB and applied the model to predict the patients with smear-positive TB. Materials and Methods: Medical records information of 6977 cases was included from 11,950 inpatients from January 2009 to November 2013. The cases data were divided into a training set, test set and prediction set. Logistic regression analysis was applied to the training set data to establish a prediction classification model, the effect of which was then evaluated using the test set by receiver operating characteristic (ROC) analysis. The model was then applied to the prediction set to identify incidence of snMDR-TB. Results: Sixteen factors which correlate with MDR-TB-including frequency of hospitalization, province of origin, anti-TB drugs, and complications, were identified from the comparison between SP-TB and spMDR-TB. The area under the ROC curve (AUC) of the prediction model was 0.752 (sensitivity = 61.3%, specificity = 83.3%). The percentage of all inpatients with snMDR-TB (snMDR-TB/Total) was 28.7% ± 0.02%, while that of all SN-PTB with snMDR-TB (snMDR-TB/SN-PTB) was 26.5% ± 0.03%. The ratio of snMDR-TB to MDR-TB (snMDR-TB/MDR-TB) was 2.09 ± 0.33. Conclusion: snMDR-TB as an important source of MDR-TB is a significant hidden problem for MDR-TB control and can be identified by the prediction model. A kind of vicious circle with a certain delay effect exists between snMDR-TB and MDR-TB. To better control MDR-TB, it is necessary to pay greater attention to snMDR-TB, conduct further research and develop targeted therapeutic strategies.
文摘Objective: To explore the roles of intracellular pH value (pHi) and sodium-hydrogen exchanger isoform-1 (NHE-1) in the mechanism of multidrug resistance of leukemia cells. Methods: Multidrug resistant cell line HL-60 induced by doxorubicin(DOX) (called as HL-60/DOX cells) and their parent cell line HL-60 were employed as experiment group and control group. The proliferation and chemosensitivity of the cells were studied by MTT assay, and the expression of multidrug resistance protein (MRP) was detected by immol/Lunocytochemistry. Meanwhile, pHi was measured by spectrofluorometery with a fluorescence dye BCECF-AM. Based on the pHi recovery curve after intracellular acid loading, the activity of NHE-1 was analyzed. The expression of NHE-1 mRNA and MRP mRNA were determined by semi-quantitative RT-PCR. Cell apoptosis was observed with terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL), and apoptotic DNA was extracted and electrophoresed. Results: ① The IC 50 values for DOX, MTZ, VCR and homoharringtonine(HT), in HL-60/DOX cells were significantly higher than those in HL-60 cells (P<0.01). HL-60/DOX cells expressed abundant MRP, but HL-60 cells did not. ② pHi of HL-60/DOX cells were significantly higher than that of HL-60 cells(P<0.001). The expression and activity of NHE-1 in HL-60/DOX cells were significantly stronger than those of HL-60 cells. ③After administration of the specific NHE-1 inhibitor dimethyl amiloride (DMA) at a certain range of concentrations, compared with HL-60 cells, the rate of growth inhibition of HL-60/DOX cells increased significantly (P<0.05), the drug-sensitivity of HL-60/DOX cells was significantly sensitive (P<0.01), the expression of MRP and MRP mRNA decreased significantly (P<0.01), the apoptosis rate increased significantly (P<0.01). Conclusion: NHE-1 is involved in the drug-resistant mechanisms of multidrug-resistant HL-60 cells induced by DOX. The specific NHE-1 inhibitor DMA can partly reverse the multidrug resistance of HL-60 cells induced by DOX.
基金supported by Educational Commission of Liaoning Province, China (No. 20060985)
文摘Objective:To observe the reversion of multi-drug resistance by proteasome inhibitor bortezomib in K562/DNR cell line and to analyze the possible mechanism of reversion of multidrug-resistance.Methods:MTT method was used to determine the drug resistance of K562/DNR cells and the cellular toxicity of bortezomib.K562/DNR cells were cultured for 12 hours,24 hours and 36 hours with 100 μg/ml DNR only or plus 4 μg/L bortezomib.The expressions of NF-κB,IκB and P-gp of K562/DNR were detected with Western blot method,the activity of NF-κB was tested by ELISA method and the apoptosis rate was observed in each group respectively.Results:The IC50 of DNR on cells of K562/S and K562/DNR groups were 1.16 μg/ml and 50.43 μg/mL,respectively.The drug-resistant fold was 43.47.The IC10 of PS-341 on Cell strain K562/DNR was 4 μg/L.Therefore,4 μg/L was selected as the concentration for PS-341 to reverse drug-resistance in this study.DNR induced down-regulation of IκB expression,up-regulation of NF-κB and P-gp expression.After treatment with PS-341,a proteasome inhibitor,the IκB degradation was inhibited,IκB expression increased,NF-κB and P-gp expression decreased in a time dependent manner.Compared to DNR group,the NF-κB p65 activity of DNR+PS-341 group was decreased.Compared to corresponding DNR group,DNR induced apoptosis rate increases after addition of PS-341 in a time dependent manner.Conclusion:Proteasome inhibitor bortezomib can convert the leukemia cell drug resistance.The mechanism may be that bortezomib decreases the degradation of IκB and the expression of NF-κB and P-gp,therefore induces the apoptosis of multi-drug resistant cells.
文摘Several related substances were detected at trace level in (2R)-2,3-dihydro-2-methyl-6-nitro-2-[[4-[4-[4-(trifluoromethoxy)phenoxy]-1-piperidinyl] phenoxy] methyl]imidazo[2, 1-b]oxazole drug substance by a newly developed high-performance liquid chromatography method. All related substances were characterized rapidly but some impurities were found to be intermediates. Proposed structures were further confirmed by characterization using NMR, FT-IR, and HRMS techniques. Based on the spectroscopic data;unknown related sub-stances were characterized as 1-(Methylsulfonyl)-4-[4-(trifluoromethoxy) phenoxy]piperidine;4-{4-[4-(Tri-fluoromethoxy)-phenoxy]piperidin-1-yl}phenol and 4-{4-[4-(trifluoromethoxy)phenoxy]piperidin-1-yl}phenyl methane sulfonate;4-Bromophenyl methane sulfonate, Ethyl 3,6-dihydro-1(2H)-pyridine carboxylate, (2S)-3-(4-Bromophenoxy)-2-hydroxy-2-methylpropyl methane sulfonate, (2S)-3-(4-Bromophenoxy)-2-methylpropane-1,2-diyldimethane-sulfonate, (2S)-2-Methyl-3-(4-{4-[4-(trifluoromethoxy) phenoxy]-piperidin-1-yl} phenoxy)-propane-1,2-diyldimethane sulfonate, (S)-3-(4-Bromophenoxy)-2-methyl-propane-1,2-diol and corresponding Enantiomer, (2R)-2-[(4-Bromo-phenoxy)methyl]-2-methyloxirane and (2R)-2-[(4-bromophenoxy)methyl]-2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b][1,3]oxazole. A possible mechanism for the formation of these related substances is also proposed.
文摘Resistant bacteria can be transmitted to humans through feces or contaminated meat from local chickens. Bacterial strains were isolated from the intestinal contents of 400 local chicken samples from various sales sites. These strains were then characterized using bacteriological and biochemical methods to identify resistant strains. In a study conducted in Ouagadougou, we systematically collected chicken fecal samples from 20 locations across the city, followed by isolation and identification of Salmonella spp. using specific enrichment and culture methods, as well as Escherichia coli. Bacterial strains were characterized using antibiotic resistance profiles were determined through agar diffusion tests, revealing sensitivity or resistance to a range of antibiotics based on established scientific criteria. The results showed that out of the 400 samples collected, 81.25% and 63.5% were contaminated by Escherichia coli and Salmonella spp., respectively. Among these, 86.15% of identified Escherichia coli and 50.78% of Salmonella spp. displayed resistance to at least one tested antibiotic. Among 280 Escherichia coli isolates identified resistant to at least one antibiotic, 31.07% were resistant to cefotaxime (CTX), 20.35% to ceftazidime (CAZ), 21.07% to ceftriaxone (CTR), 75% to amoxicillin clavulanic acid (AMC), 23.57% aztreoname (ATM) and 27.14% were resistant to imipenem (IMP). In the case of the 129 Salmonella spp. isolates resistant to at least one tested antibiotic, 34.88% were resistant to CTX;41.08% to CAZ;35.65% to CTR, 92% to AMC, 39.53% to ATM and finally 47.28% were resistant to IMP. Our study revealed high prevalence of resistance in bacterial strains isolated from local chickens sold outdoors in Ouagadougou. These findings raise significant public health concerns, due to the possible transmission of these resistant strains to humans through the consumption of contaminated meat, thus complicating the treatment of bacterial infections.
文摘Objective:To study the clinical efficacy and safety of tigecycline in the treatment of acute exacerbation of chronic obstructive pulmonary disease(COPD)combined with multidrug-resistant Acinetobacter baumannii infection.Methods:113 patients with acute exacerbation of COPD combined with multidrug-resistant Acinetobacter baumannii infection were recruited between January 2021 and January 2023,and given tigecycline treatment.The total effective rate,lung function indexes,related biochemical index levels,and the incidence rate of adverse reactions were observed after the treatment.Results:After the treatment,100 patients were cured,1 case with apparent effect,2 cases were effective,10 cases were ineffective,and the total effective rate was 91.15%.The post-treatment CRP(21.22±3.35 mg/L),PCT(3.18±1.11 ng/L),CRE(76.36±9.24μmol/L),and ALT(37.76±6.99 U/L)were significantly improved as compared to the pre-treatment(P<0.05).After treatment,10 cases of vomiting(8.85%),13 cases of nausea(11.50%),4 cases of diarrhea(3.53%),1 case of abdominal pain(0.88%),and 2 cases of allergy(1.77%)were observed in 113 patients.Conclusion:Tigecycline therapy for patients with acute exacerbation of COPD combined with multidrug-resistant Acinetobacter baumannii infection not only has significant therapeutic efficacy but also has a high degree of safety.