Evaluation of low-dose endotoxin administration during pregnancy as a model of preeclampsia

BACKGROUND: Recent evidence implicates nitric oxide (*NO) in the pathogenesis of preeclampsia. The authors tested the hypothesis that administration of low-dose endotoxin to pregnant rats mimics the signs of preeclampsia in humans and that *NO and *NO-derived species play a role in that animal model. METHODS: Endotoxin was infused at doses of 1, 2 and 10 microg/kg over 1 h to rats on day 14 of pregnancy. Mean arterial pressure, urinary protein, urinary and plasma nitrite plus nitrate (NO2- + NO3-) concentrations, and platelet count were measured before and after the endotoxin infusion. In another group of pregnant rats, the nitric oxide synthase inhibitor L-nitroarginine methyl ester (L-NAME) was administered in drinking water at a dose of 3 mg x kg(-1) x d(-1) starting on day 7 of pregnancy. Endotoxin was then infused at 10 microg/kg on day 14 of pregnancy. Kidneys and uteroplacental units were examined histologically and analyzed immunohistochemically for 3-nitrotyrosine. RESULTS: Endotoxin administration at doses of 2 and 10 microg/kg caused proteinuria and thrombocytopenia in pregnant rats, but did not result in hypertension. Urinary NO2- + NO3- concentration, reflective of tissue *NO production rates, was significantly elevated in pregnant rats that received endotoxin at 10 microg/kg. Ingestion of L-NAME caused hypertension. Tissues from pregnant rats treated with L-NAME, endotoxin at 10 microg/kg, and a combination of L-NAME and endotoxin had increased 3-nitrotyrosine immunoreactivity. CONCLUSION: Nitric oxide either directly or through secondary species plays a significant role in the biochemical and physiologic changes that occur in a rodent model of endotoxin-induced injury.     

Is the p53 gene mutation of prognostic value in hepatocellular carcinoma after resection?

HYPOTHESIS: Mutant p53 gene has lost its tumor suppression function and is considered to be a very important step in hepatocellular carcinoma development. We propose that the mutant p53 gene plays a role in its invasiveness and prognosis after resection. DESIGN: A case-controlled study. SETTING: A referral center. PATIENTS: Seventy-nine consecutive patients who underwent surgical resection for hepatocellular carcinoma entered this study. INTERVENTION: Tissue sections of resected hepatocellular carcinoma (deparaffinized and rehydrated from formalin-fixed and paraffin-embedded sections) were incubated with antihuman p53 monoclonal antibody and immunostained. The p53 result was scored without prior knowledge of the patients' status. A 10% immunopositivity was regarded as the threshold value. MAIN OUTCOME MEASURE: The immunopositive rate of p53 was 69.6% (55 of 79 patients). The clinical variables (age, sex, associated liver cirrhosis, hepatitis B virus infection, hepatitis C virus infection, serum alpha-fetoprotein, and Child-Pugh class); the histological variables (size, capsule, vascular permeation; grade of differentiation, and multinodularity); and postoperative course (recurrence, tumor-free interval, death, and survival period) were correlated with p53 immunopositivity. RESULTS: From univariate analysis, more patients with p53 positivity were male (92.7 vs 0%) (P<.001); had vascular permeation (80% vs 50%) (P =.007) (odds ratio [OR], 4.0); no complete capsule (83.6% vs 62.5%) (P =.04) (OR, 3.1); and daughter nodules (90.9% vs 70.8%) (P =.04) (OR, 4.1) than patients with negative p53 staining. From multivariate analysis, only sex and vascular permeation remained significant (P =.001 and P =.008, respectively). Although more patients with p53 positivity had tumor recurrence (78% vs 50%) (P =.01) and death (64% vs 33%) (P =. 01), the Cox proportional hazards model showed that p53 overexpression had only weak correlations with tumor-free interval and survival time (P =.09 and P =.08, respectively). CONCLUSIONS: Our results show that the biological behavior of the mutant p53 gene is strongly related to the invasiveness of hepatocellular carcinoma and may also influence the postoperative course. We suggest that the immunopositivity of the mutant p53 gene has a predictive role in the prognosis of patients with resected hepatocellular carcinoma.     

彩色多普勒超声检查在原发性肝癌经伽玛刀治疗32例的效果评价

目的:探讨彩色多普勒超声检查肝癌经伽玛刀(-γ刀)治疗效果的价值。方法:32例原发性肝癌患者37个肿块,-γ刀治疗前及治疗后1周、1个月、3个月、6个月运用彩色多普勒超声进行随访。结果:-γ刀治疗后1周～1个月,肝癌病灶表现为稳定,3～6个月,病灶表现为显效,且肿块越小,治疗效果越好。结论:-γ刀治疗肝癌,是一种体外无创性的放疗方法,近期疗效满意。彩超的检查结果与临床随访相符。彩超可望成为肝癌-γ刀治疗后的观测疗效及指导治疗的有效方法。     

细菌对MLS类和糖肽类抗生素产生耐药性的作用机制

MLS类和糖肽类抗生素在人类与细菌感染性疾病的对抗中发挥着重要作用.与其他抗生素一样,随着这些抗生素的临床使用,细菌耐药性的出现和不断发展给人们带来新的挑战.本综述对这两类抗生素的细菌耐药性产生机制进行了剖析,并就已开发的若干个新型MLS类和糖肽类抗生素作了介绍.     

模拟生物矿化制备多糖铁的新方法

目的建立模拟生物矿化制备多糖铁的新方法.方法选用壳聚糖,与FeCl3制成复合膜,模拟铁矿化过程,制备多糖铁.结果多糖铁为β-FeOOH晶形,且为纳米级.结论为开发补铁药提供了新途径,丰富和发展了纳米药学理论.     

Expression of cytochrome p450 and other biotransformation genes in fetal and adult human nasal mucosa.

Despite recent progress in the identification and characterization of numerous nasal biotransformation enzymes in laboratory animals, the expression of biotransformation genes in human nasal mucosa remains difficult to study. Given the potential role of nasal biotransformation enzymes in the metabolism of airborne chemicals, including fragrance compounds and therapeutic agents, as well as the potential interspecies differences between laboratory animals and humans, it would be highly desirable to identify those biotransformation genes that are expressed in human nasal mucosa. In this study, a global gene expression analysis was performed to compare biotransformation enzymes expressed in human fetal and adult nasal mucosa to those expressed in liver. The identities of a list of biotransformation genes with apparently nasal mucosa-selective expression were subsequently confirmed by RNA-polymerase chain reaction (PCR) and DNA sequencing of the PCR products. Further quantitative RNA-PCR experiments indicated that, in the fetus, aldehyde dehydrogenase 6 (ALDH6), CYP1B1, CYP2F1, CYP4B1, and UDP glucuronosyltransferase 2A1 are expressed preferentially in the nasal mucosa and that ALDH7, flavin-containing monooxygenase 1, and glutathione S-transferase P1 are at least as abundant in the nasal mucosa as in the liver. The nasal mucosal expression of CYP2E1 was also detected. These findings provide a basis for further explorations of the metabolic capacity of the human nasal mucosa for xenobiotic compounds.     

脊柱结核的影像学诊断及临床病理分析

研究脊柱结核的影像学诊断价值,并探讨各型脊柱结核的临床病理特点.对156例经临床及病理证实且影像学资料完整的脊柱结核进行回顾性分析,比较其X线(或CR)、CT及MRI的影像学特点及符合率.结果显示①X线(或CR)、CT及MRI对脊柱结核诊断符合率分别为90.5%、96.2%及99.5%.②X线(或CR)、CT及MRI对椎体骨质破坏、椎间隙狭窄的敏感性分别为74.5%、89.9%及96.87%.③对椎旁软组织肿块和腰大肌脓肿、附件破坏及骨性椎管受累的显示,CT优于X线(和CR)片;对早期病变的显示及脊髓受累情况,MRI优于X线(或CR)及CT,有显著差异性(P＜0.01).④对死骨及钙化的显示CT优于X线(或CR)及MRI.认为X线(或CR)检查为诊断脊柱结核的基本方法,但对早期病变的显示有限度;CT显示早期微小的骨质破坏、死骨、脓肿、钙化及脓肿对椎管脊髓压迫明显优于X线;MRI可清晰显示硬膜外脓肿及脊柱后突畸形对脊髓的压迫和脊髓变性情况,尤其是对早期病变的诊断,有较高的敏感性和特异性,但对死骨及钙化不敏感.     

养阴清热煎剂对系统性红斑狼疮患者黏附分子表达及狼疮损伤指数的影响

目的:研究中医药对系统性红斑狼疮(SLE)的治疗作用机制及其对SLE器官损害的远期疗效.方法:1999～2003年住院及门诊的SLE患者51例,随机分为以中药养阴清热煎剂为主的中西医结合治疗组(简称治疗组)和单纯西药治疗的对照组(简称对照组),进行了治疗前后血清细胞黏附分子1(ICAM-1)、黏附分子3(ICAM-3)、P-选择素以及SLE损伤指数(SLICC/ACRDI)的研究.结果:SLE患者的ICAM-1、ICAM-3、P-选择素均较正常人明显增高;治疗组治疗后ICAM-1、P-选择素比对照组明显下降;而SLE损伤指数积分显示,治疗组比较稳定,对照组较治疗前有明显增加.结论:提示以中药养阴清热煎剂为主的治疗组对SLE患者的血清黏附分子高表达有明显的抑制作用,并对SLE的器官损害有明显的保护与修复作用.