Differential effects of monoclonal antibodies to tumor necrosis factor alpha and gamma interferon on induction of hepatic nitric oxide synthase in experimental gram-negative sepsis.

To investigate the stimuli required for the induction of nitric oxide synthase (NOS) in sepsis, we have analyzed the levels of this enzyme in the livers of mice infected with a 90% lethal dose of Escherichia coli in a model of gram-negative sepsis. Hepatic NOS levels are markedly induced in this model, with peak values occurring 12 to 22 h following infection. Treatment with TN3-19.12, a neutralizing monoclonal antibody to tumor necrosis factor alpha (TNF-alpha), resulted in complete protection from death in this model of sepsis but had no significant effect on the level of induction of hepatic NOS. Treatment with H22, a monoclonal antibody to gamma interferon (IFN-gamma), also gave significant protection against death and, in addition, did lead to a decrease in the level of induction of the hepatic NOS. Treatment of mice with pure TNF-alpha (0.2 microgram), IFN-gamma (2,000 U), or a combination of the two did not induce the hepatic NOS, but treatment with the combination led to significant mortality (probability of survival at 22 h, 0.32). Thus, the level of induction of NOS within the liver either in sepsis or by the coadministration of TNF-alpha and IFN-gamma does not correlate with death.     

rhGM-CSF对小鼠口腔粘膜损伤的防治作用

目的：探讨rhGM-CSF促进口腔腔溃愈合的作用机制。方法：取体外培养的胎儿口腔粘膜成纤维细胞，用rhGM-CSF刺激成纤维细胞后第2、4、6天用细胞计数及^3H－胸腺嘧啶掺入法（^3H-TdR）测定其增殖情况，结果rhGM-CSF对胎儿口腔粘膜成纤维细胞增殖及DNA合成有刺激作用，在80－100ng/ml时，细胞生长达到最佳状态，过高浓度rhGM-CSF的刺激作用反而下降。结论：rhGM-CSF可以通过刺激成纤维细胞增殖及DNA合成促进口腔溃疡愈合。     

Modulation of trenimon-induced cytotoxicity by DT-diaphorase in isolated rat hepatocytes under aerobic versus hypoxic conditions.

Trenimon belongs to a class of aziridinylbenzoquinone anticancer drugs that cross the blood-brain barrier. In this study we have investigated the molecular mechanisms for trenimon-induced toxicity in aerobic versus hypoxic conditions with the use of freshly isolated rat hepatocytes. The following evidence suggests the mechanisms for trenimon detoxification involves reduction by DT-diaphorase, while the cytotoxic mechanism involves macromolecular alkylation under hypoxic conditions as well as oxidative stress under aerobic conditions. (a) Hepatocyte cytotoxicity induced by trenimon (250 microM) under aerobic conditions ensued following an initial induction of cyanide-resistant respiration and partial oxidation of glutathione to oxidized glutathione. Trenimon reduction to the hydroquinone by the hepatocytes was rapid. Inhibition of hepatocyte DT-diaphorase by dicumarol increased trenimon-induced cytotoxicity by approximately 10-fold, and markedly inhibited hydroquinone formation. Furthermore, both cyanide-resistant respiration and oxidized glutathione formation were markedly increased, resulting in depletion of oxygen in the media. Trenimon reduction to the hydroquinone then occurred. This suggests that DT-diaphorase in normal hepatocytes prevents the formation of the semiquinone that causes cytotoxic protein alkylation and oxidative stress. (b) Hepatocyte cytotoxicity induced by trenimon (350 microM) under hypoxic conditions ensued following glutathione depletion without oxidized glutathione formation. Inactivation of hepatocyte DT-diaphorase by dicumarol under hypoxic conditions increased trenimon-induced cytotoxicity by approximately 3.5-fold and increased semiquinone radical levels 2-fold without affecting its reduction rate. This suggests that the cytotoxic mechanism involves protein alkylation by semiquinone radicals formed by reductases catalyzing a one-electron reduction of trenimon.     

肺癌侵犯中央肺动脉继发肺低灌注的CT与DSA对照研究

目的　探讨肺癌侵犯中央肺动脉继发肺低灌注的CT特征及其诊断价值。方法　对2 0例手术及病理证实的肺癌侵犯中央肺动脉 (cancerousinvasionofcentralpulmonaryarteriesinlungcancer,CICPA)患者术前肺血管DSA及增强螺旋CT(含高分辨率CT ,即HRCT)征象行前瞻性对照研究。根据DSA和CT胸膜下末梢肺动脉分布和数量变化 ,即肺血管征、肺毛细血管充盈度和肺实质强化后密度及时间 密度曲线变化 (即肺实质征 ) ,行两者间的盲法对照 ,统计学分析CT与DSA征象及其一致性 ,评估CT对CICPA继发肺低灌注的诊断价值。结果　 2 0例手术病理证实的CICPA病例中 ,共3 0支肺叶动脉受累 ,DSA显示 90 % (2 7/3 0 )出现肺叶低灌注征象 ,CT诊断肺低灌注敏感度为 78%(2 1/2 7) ,特异度 10 0 % (3 /3 ) ,准确度 80 % (2 4/3 0 )。肺低灌注与CPA狭窄程度无明显相关性 (rs=0 40 ,P =0 0 73 )。CT与DSA的肺血管征一致性较好 (Kappa =0 69,P <0 0 0 1) ,而肺实质征一致性稍差 (Kappa =0 3 7,P =0 0 11)。结论　肺低灌注是肺癌侵犯中央肺动脉的常见表现 ,CT对其定性诊断具有重要价值 ,而定量判断有一定限度     

多孔β-TCP/rhBMP-2人工骨在小鼠体内的诱导成骨和早期降解行为的研究

目的 将多孔β—磷酸三钙和重组人的骨形成蛋白—2复合物，植入小鼠肌肉内，观察复合物的骨诱导能力和早期降解行为。方法 将多孔β—磷酸三钙／人骨形成蛋白—2复合物植入25只小鼠右侧大腿后侧肌肉内，单纯多孔β—磷酸三钙植入左侧为对照，分别于72h、1、2、3、4周取材，进行组织学和扫描电镜观察。结果 72h可见幼稚软骨，1周见成熟软骨，2周见编织骨和少量板层骨，3周和4周成熟的板层骨生成，对照组则无骨或软骨生成。2周开始间充质细胞和纤维组织长入材料，3～4周将材料包裹分割，同时可见多核巨细胞反应及吞噬现象，这些是降解早期组织学改变。结论 多孔β—TCP／rhBMP—2复合人工骨显示了良好的生物相容性，有强大的骨诱导能力，有希望作为新型骨移植替代材料用于临床。     

Japanese encephalitis after a two-week holiday in Bali

Japanese encephalitis is described in a 10-year-old girl after a short holiday in Bali. Four days after returning to Australia the patient presented with a high fever, stupor and rapidly-developing focal neurological signs. Recovery occurred gradually over a period of three months and she has returned to school. Japanese encephalitis viral infection was confirmed by a marked rise in specific haemagglutination-inhibition antibodies and the presence of immunoglobulin M antibodies to the flavivirus group. It is important to be aware of the possibility of arboviral infection in patients with encephalitis. In view of the recent outbreaks of Japanese encephalitis in Asia, travellers to the region should be warned to protect themselves from mosquito-bites.     

Hepatotoxicity in HIV-infected children and adolescents on antiretroviral therapy.

CONTEXT AND OBJECTIVE: Adverse drug reactions are a significant problem in patients on antiretroviral therapy (ART). We determined liver enzyme elevation frequencies in HIV-infected children and adolescents receiving ART, and their association with risk factors. DESIGN AND SETTING: Cross-sectional study, at the Pediatrics Immunodeficiency Division, University Hospital, Universidade Estadual de Campinas. METHODS: Medical records of 152 children and adolescents (54.6% male; median age 7.48 years) were analyzed, with a mean of 2.6 liver enzyme determinations per patient. Clinically, patients were classified in categories N (6), A (29), B (78) and C (39). Serum levels of aspartate aminotransferase and alanine aminotransferase were evaluated. Hepatotoxicity was scored as grade 1 (1.1-4.9 times upper limit of normality, ULN), grade 2 (5.0-9.9 times ULN), grade 3 (10.0-15.0 times ULN) and grade 4 (> 15.0 times ULN). To assess hepatotoxicity risk factors, odds ratios (OR) and adjusted odds ratios (aOR) for age, gender, TCD4+ cell count, viral load and medication usage were calculated. RESULTS: We observed grade 1 hepatotoxicity in 19.7 % (30/152) patients. No cases of grade 2, 3 or 4 were detected. There was a significant association between hepatotoxicity and use of sulfonamides (OR, 3.61; 95% confidence interval (CI), 1.50-8.70; aOR, 3.58; 95% CI, 1.44-8.85) and antituberculous agents (OR, 9.23; 95% CI, 1.60-53.08; aOR, 9.05; 95% CI, 1.48-55.25). No toxicity was associated with ART. CONCLUSIONS: One fifth of patients experienced mild hepatotoxicity, attributed to antituberculous agents and sulfonamides. Our results suggest that ART was well tolerated.     

Nasal lavage leukotrienes in infants with RSV bronchiolitis

Respiratory syncytial virus (RSV) bronchiolitis is a very common infection in infants and, after the acute phase, a number of patients develop a reactive airway disease that lasts for years. Although the pathogenesis of the lung damage after RSV bronchiolitis is still largely unknown, previous studies suggest that leukotrienes may play an active part in it. The aim of this study was to measure leukotriene levels in the nasal lavage fluid (NLF) collected in infants during RSV bronchiolitis and 1 month later. Cysteinyl leukotrienes (Cys-LTs) and leukotriene B(4) (LTB(4)) were measured in the NLF of 22 infants with their first episode of RSV bronchiolitis and 16 healthy infants. A second NLF sample was collected to measure leukotriene levels 1 month after the acute disease. NLF Cys-LT levels were significantly higher in infants with RSV bronchiolitis than in healthy controls [950 pg/ml (285.5-2155.9) vs. 110.5 pg/ml (66.5-451.3), p = 0.01], and they remained so a month after the acute infection (p = 0.02). A subanalysis showed no difference in Cys-LTs concentrations, either between bronchiolitis infants with and without a family history of atopy, or between those with and without passive exposure to cigarette smoke. No significant difference was found between the LTB(4) levels measured in the bronchiolitis cases and the control children. Cys-LTs are significantly increased in the NLF of infants with acute RSV bronchiolitis, and remain so at 1-month follow-up, suggesting a possible role of these eicosanoids in the pathogenesis of the disease.