Bilateral vagotomy attenuates the severity of secretagogue-induced acute pancreatitis in the rat

PurposeWe assessed the effect of bilateral vagotomy (BV) on the course of acute caerulein-induced pancreatitis (AP) in the rat.Material/methodsThe study was performed on Wistar rats surgically prepared by subdiaphragmatic BV. Control group underwent sham operation. Four days later, AP was induced by subcutaneous injection of caerulein (25 μg/kg/5 h) to the conscious animals with or without BV. After administration of caerulein the blood samples were taken for determination of serum lipase activity and interleukin-10 (IL-10) concentration. Pancreatic tissue samples were subjected to histological examinations and to the measurement of lipid peroxidation products (MDA + 4-HNE) concentration and the activity of an antioxidant enzyme – glutathione peroxidase (GPx). After application of caerulein pancreatic blood flow was measured by laser Doppler flowmetry.ResultsAP was manifested by oedema and neutrophil infiltration of the pancreatic tissue and accompanied by significant increases of serum lipase activity, serum concentration of IL-10 and pancreatic concentration of MDA + 4HNE (ca. 50×, 2× and 4× respectively p ≥ 0.05). Pancreatic activity of GPx and pancreatic blood flow were decreased (both by 60%). In vagotomised rats with AP serum lipase activity and pancreatic concentration of MDA + 4-HNE were lower whereas Il-10 concentration and pancreatic activity of GPx, as well as pancreatic blood flow were significantly higher as compared to AP rats with intact vagal nerves. In AP rats with vagotomy all histological signs of pancreatitis were significantly reduced.ConclusionsBilateral vagotomy resulted in the significant attenuation of caerulein-induced pancreatitis in the rat.     

Predictability of IL-28B-polymorphism on protease-inhibitor-based triple-therapy in chronic HCV-genotype-1 patients: A meta-analysis

AIM: To investigate the predictability of interleukin-28 B single nucleotide polymorphism rs12979860 with respect to sustained virological response(SVR) in chronically hepatitis C virus(HCV) genotype-1 patients treated with a protease-inhibitor and pegylated interferon-α(Peg-INF-α) based triple-therapy. METHODS: We searched PubMed, the Cochrane Library and Web of Knowledge for studies regarding the interleukin 28B(IL-28B)-genotype and protease-inhibitor based triple-therapy. Ten studies with 2707 patients were included into this meta-analysis. We used regression methods in order to investigate determinants of SVR.RESULTS: IL-28B-CC-genotype patients achieved higher SVR rates(odds 5.34, 95%CI: 3.81-7.49) than IL-28B-non-CC-genotype patients(1.88, 95%CI: 1.43-2.48) receiving triple-therapy. The line of therapy(treatment-nave or-experienced for Peg-INF-α) did not affect the predictive value of IL-28B(P = 0.1). IL-28BCC-genotype patients treated with protease inhibitorbased triple-therapy consisting of Boceprevir, Simeprevir, Telaprevir or Vaniprevir showed odds of 3.38, 14.66, 7.84 and 2.91, respectively. The odds for CC genotype patients treated with Faldaprevir cannot be quantified, as only a single study with a 100% SVR rate was available.CONCLUSION: IL-28B-SNP predicts the outcome for chronic HCV genotype-1 patients receiving protease inhibitor-based triple-therapy. The predictive value varies between the different protease inhibitors.     

Hepatic apoptosis and proliferation in male and female rats fed alcohol: role of cytokines

Background: The female liver is more sensitive to the toxic effect of chronic alcohol intake than the male liver. The aim of the study was to compare the influence of gender and sex hormonal status on apoptosis and cell proliferation following chronic ethanol intake.
Methods: Male and female rats were pair fed for 8 weeks a liquid diet containing 36% of their total daily calories as ethanol (ETOH group) or sucrose (control group). Liver samples were analyzed for apoptosis and hepatocyte proliferation by immunohistochemistry. The hepatic production of factors able to influence cell death and proliferation, such as tumor necrosis factor alpha (TNFα) and interleukin 6 (IL-6) were determined.
Results: In both male and female rats, ethanol intake promoted apoptosis in the liver. This effect of ethanol was more evident in female than male rat livers. Hepatic TNFα levels, which promote apoptosis, are significantly more elevated in female than in male livers. Hepatic IL-6 production, which promotes hepatocyte proliferation, was induced by ethanol only in males, but not female animals.
Conclusion: This observed difference in cytokine responses may contribute to the enhanced sensitivity of female liver to EtOH-induced injury.     

细胞因子在肺结核病理生理过程及治疗随访中的临床意义

目的 探讨肺结核患者治疗前后血清细胞因子水平变化的临床意义.方法 采用酶联免疫吸附分析(ELISA)测定215例肺结核患者治疗前后和60例正常对照组血清细胞因子IL-2,IL-10,IL-17,IL-18水平,并进行对比性分析,测定了215例肺结核患者治疗后的痰菌转阴率和有效率,通过测定灵敏度、特异度和准确度等指标比较了单项和多项细胞因子在肺结核患者诊断中的变化.结果 215例肺结核患者治疗前血清IL-2和IL-10水平较之60例正常对照组明显降低(tIL-2=3.216,tIL.10=3.164,P均＜0.01),而IL-17和IL-18水平明显增高(tIL-17=2.942,P＜0.01,tIL-18 =2.175,P均＜0.05),治疗后血清IL-2和IL-10水平明显增高(tIL-2=2.237,tIL-1o=2.248,P均＜0.05),而血清IL-17的水平降低(tIL-17 =2.120,P＜0.05),血清IL-18恢复至正常水平(tIL-18=1.873,P＞0.05).215例肺结核治疗后的痰菌转阴率为87.00％,有效率为92.1％.结论 细胞因子参与肺结核的病理生理过程,并是治疗后随访的有价值指标.单项细胞因子测定在肺结核诊断中的价值较低,四项联合测定的灵敏度,特异度和准确度分别为69.8％,65.0％和72.0％.     

Helicobacter hepaticus infection in BALB/c mice abolishes subunit-vaccine-induced protection against M. tuberculosis

BCG, the only licensed vaccine against tuberculosis (TB), provides geographically variable protection, an effect ascribed to exposure to environmental mycobacteria (EM). Here we show that altering the intestinal microbiota of mice by early-life infection with the commensal bacterium Helicobacter hepaticus (Hh) increases their susceptibility to challenge with Mycobacterium tuberculosis (Mtb). Furthermore Hh-infected mice immunised parenterally with the recombinant subunit vaccine, human adenovirus type 5 expressing the immunodominant antigen 85A of Mtb (Ad85A), display a reduced lung immune response and protection against Mtb challenge is also reduced. Expression of interleukin 10 (IL10) messenger RNA is increased in the colon of Hh infected mice. Treatment of Hh-infected Ad85A-immunised mice with anti-IL10 receptor antibody, following challenge with Mtb, restores the protective effect of the vaccine. These data show for the first time that alteration of the intestinal microbiota by addition of a single commensal organism can profoundly influence protection induced by a TB subunit vaccine via an IL10-dependent mechanism, a result with implications for the deployment of such vaccines in the field.     

苦参注射液对肝硬化患者血清、腹水纤维化及白介素的影响

目的:观察苦参注射液治疗肝硬化的疗效及其对患者血清、腹水中纤维化指标和白介素水平的影响.方法:将180例肝硬化患者随机分为两组,对照组和观察组各90例.对照组采用西医基础治疗,观察组则加载苦参注射液治疗.比较治疗前后两组患者间Child pugh分级、肝功能差异及血清、腹水中纤维化指标和白介素的水平差异.结果:2个疗程结束后观察组Child pugh分级改善率显著高于对照组;治疗3、6个月后,观察组患者血清丙氨酸转氨酶(ALT)、谷草转氨酶(AST)、总胆红素(TBIL)水平显著低于对照组,血浆白蛋白水平高于对照组,凝血酶原时间(PT)则较对照组显著缩短(P＜0.05).治疗3、6个月后,观察组血清和腹水中纤维化指标透明质酸酶(HA)、Ⅲ型前胶原肽(PCⅢ)、Ⅳ型胶原(Ⅳ-C)水平以及白介素-8(IL-8)、白介素-10(IL-10)水平均显著低于对照组(P＜0.05).结论:苦参注射液能通过抑制肝纤维化和调节机体的免疫应激反应,发挥治疗肝硬化的疗效.     

Toxic trace elements at gastrointestinal level

Many trace elements are considered essential [iron (Fe), zinc (Zn), copper (Cu)], whereas others may be harmful [lead (Pb), cadmium (Cd), mercury (Hg), arsenic (As)], depending on their concentration and chemical form. In most cases, the diet is the main pathway by which they enter our organism. The presence of toxic trace elements in food has been known for a long time, and many of the food matrices that carry them have been identified. This has led to the appearance of legislation and recommendations concerning consumption. Given that the main route of exposure is oral, passage through the gastrointestinal tract plays a fundamental role in their entry into the organism, where they exert their toxic effect. Although the digestive system can be considered to be of crucial importance in their toxicity, in most cases we do not know the events that occur during the passage of these elements through the gastrointestinal tract and of ascertaining whether they may have some kind of toxic effect on it. The aim of this review is to summarize available information on this subject, concentrating on the toxic trace elements that are of greatest interest for organizations concerned with food safety and health: Pb, Cd, Hg and As.