Differences in neutrophil death among beta-lactam antibiotics after in vitro killing of bacteria

Antibiotic therapy is an essential treatment for gram-negative bacterial infections. Antibiotic-induced endotoxin release and subsequent production of inflammatory cytokines reportedly depend on the type of antibiotic action. This study examined the effects of various beta-lactam antibiotics on cell death of human polymorphonuclear neutrophils (PMNs) cocultured with Escherichia coli (E. coli) in vitro. E. coli morphology after antibiotic treatment was determined. PMNs and E. coli were cocultured with antibiotics for 0, 4, or 12 h. Levels of endotoxin and cytokines (TNF-alpha, IL-1beta, and IL-6) in the supernatants were measured. The filtrates of antibiotic-treated E. coli supernatants were cocultured with PMNs for 0, 4, or 12 h. In all experiments, ampicillin (ABPC), cefazolin sodium (CEZ), cefoperazone sodium (CPZ), latamoxef sodium (LMOX), imipenem (IPM), and polymyxin B sulfate (PLB) were used at 30 microg/mL. PMNs were isolated from healthy volunteers. PMN cell death was assessed by flow cytometry and light microscopy. ABPC, CEZ, CPZ, and LMOX, which induce bacterial filament formation with lysis, caused PMN necrosis when cocultured with E. coli. In contrast, IPM, which induces bacterial spheroplast formation with lysis, caused PMN apoptosis. Levels of endotoxin, TNF-alpha and IL-6 in the supernatants with IPM and PLB were significantly lower than in those with other beta-lactam antibiotics. The filtrates of IPM- and PLB-treated E. coli supernatants induced PMN apoptosis, whereas those treated with other beta-lactam antibiotics increased PMN necrosis. Beta-lactam antibiotics have different impacts on the types of PMN cell death after E. coli killing. Underlying mechanisms and the clinical relevance of IPM-induced PMN apoptosis in severe gram-negative infection warrant further investigation.     

PFI融资方式在我国公有制医院中的应用

英国政府在财政对卫生投入不足和公众对医疗保健需求增长很快,公众对此十分不满的情况下,把PFI引入了医院,取得了一定的效果。目前,我国公有制医院也陷入了类似的困境。因此,在我国的公共卫生改革中考虑引入PFI具有一定的可行性。     

Nucleotide excision repair gene polymorphisms and risk of advanced colorectal adenoma: XPC polymorphisms modify smoking-related risk.

OBJECTIVES: Nucleotide excision repair enzymes remove bulky damage caused by environmental agents, including carcinogenic polycyclic aromatic hydrocarbons found in cigarette smoke, a risk factor for colorectal adenoma. Among participants randomized to the screening arm of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, we studied the risk of advanced colorectal adenoma in relation to cigarette smoking and selected single nucleotide polymorphisms (SNP) in the nucleotide excision repair pathway.METHODS: Cases (n = 772) were subjects with left-sided advanced adenoma (>1 cm in size, high-grade dysplasia, or villous characteristics). Controls (n = 777) were screen-negative for left-sided polyps by sigmoidoscopy. DNA was extracted from blood samples and 15 common nonsynonymous SNPs in seven-nucleotide excision repair genes [XPC, RAD23B (hHR23B), CSB (ERCC6), XPD (ERCC2), CCNH, XPF (ERCC4), and XPG (ERCC5)] were genotyped.RESULTS: None of the studied SNPs were independently associated with advanced adenoma risk. Smoking was related to adenoma risk and XPC polymorphisms (R492H, A499V, K939Q) modified these effects (P(interaction) from 0.03-0.003). Although the three XPC variants were in linkage disequilibrium, a multivariate logistic regression tended to show independent protective effects for XPC 499V (P(trend) = 0.06), a finding supported by haplotype analysis (covariate-adjusted global permutation P = 0.03).CONCLUSIONS: Examining a spectrum of polymorphic variants in nucleotide excision repair genes, we found evidence that smoking-associated risks for advanced colorectal adenoma are modified by polymorphisms in XPC, particularly haplotypes containing XPC 499V.     

RNA Interference-Mediated Gene Silencing of Vascular Endothelial Growth Factor

A ngiogenesis is a well-known process that is essential for tumor growth beyond 2 mm.[1] Although numerous growth factors are involved, vascular endothelial growth factor (VEGF), in particular VEGF-A, has been shown to play an important role in tumor angi…     

榄香烯和姜黄素诱导晶状体上皮细胞凋亡的超微结构改变

目的观察榄香烯（Ele）、姜黄素（Cur）对体外培养的牛晶状体上皮细胞（LECs）凋亡的超微结构的影响。方法分别用160μg／mlEle，20μg／ml Cur与LECs共同孵育24、48、72h，采用透射电子显微镜观察LECs超微结构的变化。结果Ele和Cur作用不同时间的LECs均出现核染色质凝集、固缩、边集等典型的凋亡形态学改变，呈时一效依赖关系。超微结构研究显示，Cur诱导凋亡的同时，也诱导发生细胞胀亡。结论Ele和Cur具有明显诱导LECs凋亡或胀亡的作用。     

Changes in the gene expression associated with carbon tetrachloride-induced liver fibrosis persist after cessation of dosing in mice.

Recent studies have shown that gene expression profiles change in the livers of animals treated acutely with toxic chemicals such as carbon tetrachloride (CCl(4)). This study was undertaken to evaluate the changes in gene expression in mouse liver immediately after a long-term treatment with CCl(4) and possible effects of treatment cessation on these changes. Adult 129/Sv(pc)J mice were treated twice a week with CCl(4) at 1 ml/kg in olive oil for 4 weeks. Hepatic pathological changes observed in the CCl(4)-treated mice included necrosis, inflammation, and fibrosis, along with increased serum alanine aminotransferase activities. Consistent with these changes, expression of genes involved in cell death, cell proliferation, metabolism, DNA damage, and fibrogenesis were upregulated as detected by microarray analysis and confirmed by real-time RT-PCR. Four weeks after CCl(4) treatment cessation, the pathological changes were recovered, with the exception of fibrosis, which was not completely reversed. Most of the gene expression profiles also returned to the control level; however, the fibrogenetic genes remained at a high level of expression. These results demonstrate that changes in gene expression profile correlate with pathological alterations in the liver in response to CCl(4) intoxication. Most of these changes are recoverable upon withdrawal of the toxic insult. However, liver fibrosis is a prolonged change both in gene expression and histopathological alterations.