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Objective To explore the variation trend of natural killer (NK) cell subsets in the recipients infected with cytomegalovirus (CMV) after renal transplantation. Methods Clinical data of 92 renal transplant recipients were retrospectively analyzed. All recipients were divided into the CMV infection group (n=43), CMV infection recovery group (n=13), stable renal function group (n=15), rejection group (n=11) and other infection group (n=10). In addition, healthy adult volunteers were enrolled in the healthy control group (n=15). The proportion of NK cells in peripheral blood, the expression proportion and the mean fluorescence intensity (MFI) of CD226 and CD16 in NK cells were observed and statistically compared among different groups. Results The proportion of NK cells was 4.9% (2.2%, 11.5%) in the CMV infection group and 3.7% (2.3%, 6.5%) in the CMV infection recovery group, which were significantly lower than those in the other groups (all P < 0.05). The expression proportion of CD226 and CD16 in NK cells in the CMV infection group was significantly lower compared with those in the healthy control group and stable renal function group(all P < 0.05). The expression proportion of CD226 and CD16 in NK cells in the CMV infection recovery group was remarkably higher than those in the CMV infection group (both P < 0.05). The MFI of CD226 and CD16 in the CMV infection group was significantly lower than those in the healthy control group (both P < 0.05). The MFI of CD226 and CD16 in the CMV infection recovery group was significantly higher than those in the CMV infection group (both P < 0.05). Conclusions The expression proportion and MFI of CD226 and CD16 in NK cells are down-regulated in CMV infection period, whereas up-regulated during the CMV infection recovery period, prompting that CD226 and CD16 expressed by NK cells are intimately correlated with the course of CMV infection.
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Objective To investigate the effect and mechanism of interleukin (IL)-17C in mice undergoing kidney transplantation. Methods The life-supporting kidney transplantation mice models were established using Balb/c (H-2Kd) mice as the donors, IL-17C gene knock out (IL-17CKO) mice (knockout group) and C57BL/6J(H-2Kb) mice (wild group) were chosen as the recipients. The postoperative body mass and survival time of mice were statistically compared between two groups. Pathological examination of the kidney graft was performed by using hematoxylin-eosin (HE) staining and periodic acid-Schiff (PAS) staining. The expression levels of granzyme B, interferon (IFN)-γ, tumor necrosis factor (TNF)-α, IL-6 and IL-1β messenger ribonucleic acid (mRNA) in the kidney graft tissue were quantitatively measured by reverse transcription polymerase chain reaction (RT-PCR). The proportion of inflammatory cell infiltration in the kidney graft tissue was detected by flow cytometry. Results In the knockout group, the survival time of mice after kidney transplantation was significantly shorter than that of the wild mice (P=0.031). The body mass was more evidently decreased in the knockout group with no statistical significance from that in the wild group. Pathological examination demonstrated that the kidney graft injury in the knockout group was significantly worse than that in the wild group. The mRNA expression levels of granzyme B, IFN-γ, TNF-α, IL-6 mRNA in the knockout group were significantly up-regulated compared with those in the wild group (all P < 0.01). The mRNA expression level of IL-1β showed a decreasing trend with no statistical significance (P=0.16). Flow cytometry analysis revealed that the infiltration of CD45+CD11b+Ly6G+ neutrophil and CD45+CD11b+Ly6Chi monocyte in the kidney graft of knockout mice was significantly higher compared with that of the wild mice (P < 0.05, P < 0.01), whereas the infiltration of CD45+Ly6ChiF4/80+ macrophage did not significantly differ between two groups (P > 0.05). Conclusions IL-17C participates in the regulation of inflammatory response after kidney transplantation. It can alleviate acute rejection and improve the survival of kidney graft by down-regulating the expression of pro-inflammatory cytokines and infiltration of inflammatory cells.
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As d-amino acids play important roles in the physiological metabolism of bacteria, combination of d-amino acids with antibiotics may provide synergistic antibacterial activity. The aim of the study was to evaluate and activity of d-serine alone and in combination with -lactams against methicillin-resistant (MRSA) strains, and to explore the possible sensitization mechanisms. The activity of d-serine, -lactams alone and in combinations was evaluated both by standard MICs, time-kill curves and checkerboard assays, and by murine systemic infection model as well as neutropenic thigh infection model. An synergistic effect was demonstrated with the combination of d-serine and -lactams against MRSA standard and clinical strains. Importantly, the combinations enhanced the therapeutic efficacy in the animal models as compared to -lactam alone groups. Initial mechanism study suggested possible revision of d-alanine-d-alanine residue to d-alanine-d-serine in peptidoglycan by adding of d-alanine in the medium, which may cause decreased affinity to PBPs during transpeptidation. In conclusion, d-serine had synergistic activity in combination with -lactams against MRSA strains both and . Considering the relatively good safety of d-serine alone or in combination with -lactams, d-serine is worth following up as new anti-MRSA infection strategies.
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Objective To investigate the phenotypic and genetic characteristics of the lysostaphin‐resistant Staphylococcus aureus variants induced by recombinant lysostaphin in vitro .Methods Three clinical isolates of S . aureus ,including two resistant to methicillin (MRSA ) and one susceptible to methicillin (MSSA ) were induced by treatment with sub‐MIC of recombinant lysostaphin via one‐step selection in vitro .Susceptibility of the variants to antibiotics were determined and compared with their parental strains .The full length of femABX genes was amplified by polymerase chain reaction and sequenced to identify the potential mutation sites in these genes .The growth‐curve in liquid medium and virulence in a mouse systemic infection model of both parental and variant strains were observed . Results The frequency of lysostaphin resistance in S . aureus was between 10-4 to 10-8 following induction by lysostaphin . Resistance to lysostaphin was associated with a significant decrease in growth rate in vitro and virulence in vivo ,as well as increased susceptibility toβ‐lactams evidenced by the M IC of β‐lactams against the variants as low as 1/4 000 to 1/2 of the M IC against their parental strains . Sequencing of f emA BX genes showed mutation in femA gene in both variants ,which resulted in a premature termination codon .Conclusions Resistance of S . aureus to lysostaphin may develop following induction by recombinant lysostaphin in vitro . The lysostaphin‐resistant S . aureus variants are characteristic of lower growth rate , decreased virulence ,and higher susceptibility to β‐lactams .
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(E)-Methyl-4-aryl-4-oxabut-2-enoate (YH-8) is a novel PKnB protein kinase inhibitor with good anti-tuberculosis activity. To evaluate its pharmacokinetics in rats, a sensitive and selective high performance liquid chromatography-tandem mass spectrometric (LC--MS/MS) method has been developed and validated for the quantification of YH-8 in rat plasma for the first time. Samples were pre-treated using a liquid--liquid extraction with ethyl acetate and the chromatographic separation was performed on a C18 column by gradient elution with methanol--water as the mobile phase. YH-8 was detected using a tandem mass spectrometer in positive selected reaction monitoring (SRM) mode. Method validation revealed good linearity over the range of 1-500 ng/mL for YH-8 with a lower limit of quantification (LLOQ) of 1 ng/mL. Intra- and inter-day precision of YH-8 assay in rat plasma samples were 2.0%-6.8%, with accuracy of the method being 100.69%-106.18%. Stability test showed that when spiked into rat plasma, YH-8 was stable for 12 h at room temperature, for up to 15 days at -70 °C, and after three freeze-thaw cycles. Extracted samples were found to be stable over 12 h in an auto-sampler. The method was successfully applied to the pharmacokinetic study of YH-8 in rats after oral administration at 100 mg/kg and 200 mg/kg.
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The objective of this study was to investigate the genetic basis of high level aminoglycoside resistance in Acinetobacter baumannii clinical isolates from Beijing, China. 173 A. baumannii clinical isolates from hospitals in Beijing from 2006 to 2009 were first subjected to high level aminoglycoside resistance (HLAR, MIC to gentamicin and amikacin>512 µg/mL) phenotype selection by broth microdilution method. The strains were then subjected to genetic basis analysis by PCR detection of the aminoglycoside modifying enzyme genes (aac(3)-I, aac(3)-IIc, aac(6')-Ib, aac(6')-II, aph(4)-Ia, aph(3')-I, aph(3')-IIb, aph(3')-IIIa, aph(3')-VIa, aph(2″)-Ib, aph(2″)-Ic, aph(2″)-Id, ant(2″)-Ia, ant(3″)-I and ant(4')-Ia) and the 16S rRNA methylase genes (armA, rmtB and rmtC). Correlation analysis between the presence of aminoglycoside resistance gene and HLAR phenotype were performed by SPSS. Totally 102 (58.96%) HLAR isolates were selected. The HLAR rates for year 2006, 2007, 2008 and 2009 were 52.63%, 65.22%, 51.11% and 70.83%, respectively. Five modifying enzyme genes (aac(3)-I, detection rate of 65.69%; aac(6')-Ib, detection rate of 45.10%; aph(3')-I, detection rate of 47.06%; aph(3')-IIb, detection rate of 0.98%; ant(3″)-I, detection rate of 95.10%) and one methylase gene (armA, detection rate of 98.04%) were detected in the 102 A. baumannii with aac(3)-I+aac(6')-Ib+ant(3″)-I+armA (detection rate of 25.49%), aac(3)-I+aph(3')-I+ant(3″)-I+armA (detection rate of 21.57%) and ant(3″)-I+armA (detection rate of 12.75%) being the most prevalent gene profiles. The values of chi-square tests showed correlation of armA, ant(3″)-I, aac(3)-I, aph(3')-I and aac(6')-Ib with HLAR. armA had significant correlation (contingency coefficient 0.685) and good contingency with HLAR (kappa 0.940). The high rates of HLAR may cause a serious problem for combination therapy of aminoglycoside with β-lactams against A. baumannii infections. As armA was reported to be able to cause high level aminoglycoside resistance to most of the clinical important aminoglycosides (gentamicin, amikacin, tobramycin, etc), the function of aminoglycoside modifying enzyme gene(s) in A. baumannii carrying armA deserves further investigation.
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OBJECTIVE: Tacrolimus is widely used in organ transplant. However, the long-term effects of tacrolimus on Asian, in particular in Chinese people, are few. The aim of this study is to evaluate the efficacy and safety of long-term curative effect of tacrolimus used in kidney transplantation patients in China.DATA SOURCES: Electronic and manual retrieve of Medline database, Chinese journal full-text database, Cochrane library, and CEBM/CCD, and relevant medical journals in China were applied.DATA SELECTION: Published randomized controlled trials on tacrolimus in kidney allograft recipient were retrieved, and the data were underwent Meta analysis. Odds ratio (OR) and its 95% confidence interval (CI) were used as the measurement parameter of efficacy comparison. The statistical analyses were performed using Stata software.MAIN OUTCOME MEASURES: ①The survival ratio of patient/kidney after 1 year. ②The survival ratio of patient/kidney after 3 years. ③Rejection ratio after 3 years. ④Infection rate after 3 years. ⑤Incidence of liver dysfunction after 3 years. ⑥Blood glucose disorder after 3 years.RESULTS: A total of 3 trials were eligible for the inclusion efficacy, including 3 Chinese trials and 0 foreign trials. Results of meta-analysis indicated that tacrolimus prevented the recipients of kidney transplantation from rejection effectively in three years [OR=0.40, 95%CI (0.27-0.61), P < 0.000 1]. Tacrolimus prevented the recipients of kidney transplantation from impaired liver function in three years [OR=0.28, 95%CI (0.15-0.52), P < 0.000 1]. No statistical difference of the 1-year and 3-year survival rate of patients/ kidney was found in the patients between group tacrolimus and group cyclosporine. Statistical difference of blood glucose disorder were found in the patients between group tacrolimus and group cyclosporine [OR=2.39, 95%CI (1.41-4.05), P=0.001].CONCLUSIONS: Tacrolimus prevented the recipients of kidney transplantation from rejection and impaired liver function effectively in three years in China. No statistical difference of the 1-year and 3-year survival rate of patients/kidney was found in the patients between two groups. In addition, the main side effect of tacrolimus is blood glucose elevation.
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OBJECTIVE To study the in virto interaction of allicin combined with cefoperazone against clinical isolates of Pseudomonas aeruginosa.METHODS The protocol was designed by checkerboard method and the MICs of allicin combined with cefoperazone against the 17 strains of sensitive and 14 strains of drug-resistant P.aeruginosa were determined by broth dilution method,the FIC index was calculated according to MIC results.The combined effects were confirmed by FIC index.RESULTS The percentage of the FIC index less than 0.5,from 0.5 to 1,from 1 to 2,and more than 2 was 41.2-64.3% 35.7-41.2% 0-17.6%,and 0%,respectively.CONCLUSIONS Synergism and additivity of allicin combined with cefoperazone against P.aeruginosa are their main action,there are little autonomy and no antagonism.Allicin can significantly improve the antibacterial activity of cefoperazone against drug-resistant P.aeruginosa.
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OBJECTIVE: To investigate the resistance phenotype of acinetobacter baumannii and the expression of ade efflux pump gene. METHODS: Non-repetitive 51 strains of Acinetobacter baumannii were collected in Peking Union Medical Hospital between Feb. 2004 and Feb. 2005. The active efflux system adeB structural gene and sequence were identified by PCR. RESULTS: The tested strains were not susceptible to common broad-spectrum antibiotics. Multidrug resistant Acinetobacter baumannii carried adeB active efflux pump gene. CONCLUSION: The multiple-drug resistance of Acinetobacter baumannii is independent of ?-lactamase. It maybe related to other drug resistance mechanism. The effect of active efflux system is possibly one of the major mechanisms of multidrug resistance of acinetobacter baumannii.
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Objective To study the effect of basiliximab,an anti-IL-2R monoclonal antibody,on the prevention of acute rejection and promoting graft survival in renal allograft recipients.Methods Published literature regarding the effects of basiliximab used for the prevention of acute rejection and promoting renal graft survival was reviewed,and Meta analysis was employed to analyze the results.Odds ratio(OR)and its 95% confidence interval(95%CI)were used as the parameters to evaluate the therapeutic effects.The statistical analyses were performed with RevMan 4.2 software.Results A total of 13 pertinent research articles were reviewed,including 2 papers written by Chinese authors and 11 by foreign authors.Meta-analysis of pooled results indicated that basiliximab prevented the recipients of kidney transplantation from acute rejection effectively with half-year prevention of OR 0.49 and 95%CI 0.28-0.87(P=0.01),and one-year prevention of OR 0.48,95%CI 0.35-0.65(P
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Objective: To study the protective effect of ginkgolide on rat's renal failure induced by adenine.Methods: The chronic renal functional failure model of rat was established with adenine. Its urea nitrogen (BUN), reatinine (Crea), Cholesterin (CH), total protein (TP), and albumin (ALP) in blood were determined. The pathologic changes were also observed. Results: Ginkgolide has effects on renal failure caused by adenine. Low and high dose groups decrease BUN. Crea, low dose group decrese CH, high dose group increase numbers of kindney glomerulus.Conclusion: Ginkgolide has protective effect on rat's renal failure induced by adenine.