Mast cell degranulation during abdominal surgery initiates postoperative ileus in mice

BACKGROUND & AIMS: Inflammation of the intestinal muscularis following manipulation during surgery plays a crucial role in the pathogenesis of postoperative ileus. Here, we evaluate the role of mast cell activation in the recruitment of infiltrates in a murine model. METHODS: Twenty-four hours after control laparotomy or intestinal manipulation, gastric emptying was determined. Mast cell degranulation was determined by measurement of mast cell protease-I in peritoneal fluid. Intestinal inflammation was assessed by determination of tissue myeloperoxidase activity and histochemical staining. RESULTS: Intestinal manipulation elicited a significant increase in mast cell protease-I levels in peritoneal fluid and resulted in recruitment of inflammatory infiltrates to the intestinal muscularis. This infiltrate was associated with a delay in gastric emptying 24 hours after surgery. Pretreatment with mast cell stabilizers ketotifen (1 mg/kg, p.o.) or doxantrazole (5 mg/kg, i.p.) prevented both manipulation-induced inflammation and gastroparesis. Reciprocally, in vivo exposure of an ileal loop to the mast cell secretagogue compound 48/80 (0.2 mg/mL for 1 minute) induced muscular inflammation and delayed gastric emptying. The manipulation-induced inflammation was dependent on the presence of mast cells because intestinal manipulation in mast cell-deficient Kit/Kitv mice did not elicit significant leukocyte recruitment. Reconstitution of Kit/Kitv mice with cultured bone marrow-derived mast cells from congenic wild types restored the manipulation-induced inflammation. CONCLUSIONS: Our results show that degranulation of connective tissue mast cells is a key event for the establishment of the intestinal infiltrate that mediates postoperative ileus following abdominal surgery.     

Fundamentals of neurogastroenterology: basic science

The focus of neurogastroenterology in Rome II was the enteric nervous system (ENS). To avoid duplication with Rome II, only advances in ENS neurobiology after Rome II are reviewed together with stronger emphasis on interactions of the brain, spinal cord, and the gut in terms of relevance for abdominal pain and disordered gastrointestinal function. A committee with expertise in selective aspects of neurogastroenterology was invited to evaluate the literature and provide a consensus overview of the Fundamentals of Neurogastroenterology textbook as they relate to functional gastrointestinal disorders (FGIDs). This review is an abbreviated version of a fuller account that appears in the forthcoming book, Rome III. This report reviews current basic science understanding of visceral sensation and its modulation by inflammation and stress and advances in the neurophysiology of the ENS. Many of the concepts are derived from animal studies in which the physiologic mechanisms underlying visceral sensitivity and neural control of motility, secretion, and blood flow are examined. Impact of inflammation and stress in experimental models relative to FGIDs is reviewed as is human brain imaging, which provides a means for translating basic science to understanding FGID symptoms. Investigative evidence and emerging concepts implicate dysfunction in the nervous system as a significant factor underlying patient symptoms in FGIDs. Continued focus on neurogastroenterologic factors that underlie the development of symptoms will lead to mechanistic understanding that is expected to directly benefit the large contingent of patients and care-givers who deal with FGIDs.     

低剂量化疗药物诱导的荷瘤小鼠放、化疗时细胞遗传学适应性反应

目的 探讨低剂量化疗药物预先刺激对荷瘤小鼠放、化疗时细胞遗传学的影响，方法 以正常及接种瘤细胞的昆明种小白鼠为实验模型，用低剂量环磷酰胺或低剂量丝裂霉素C（简称为D1）预先刺激，检测皮下种植S180肉瘤细胞的荷瘤小鼠放、化疗后骨髓细胞染色体畸变（CA）。结果 虽然放、化疗导致荷瘤小鼠的CA升高，但D1可以使这种升高的程度降低。结论 低剂量化疗药物可以诱导细胞遗传学适应性反应。     

HPLC法测定丝裂霉素C聚氰基丙烯酸正丁酯纳米粒中丝裂霉素C的含量

目的:建立高效液相色谱法测定丝裂霉素 C 聚氰基丙烯酸正丁酯纳米粒(MMC-PBCA-NP)中药物含量。方法:采用C_(18)柱(4.6 mm×150 mm,5 μm),以混合磷酸盐缓冲液-乙腈(85:15)为流动相,流速为1 mL·min~(-1),紫外检测器,检测波长为365 nm。结果:丝裂霉素 C(MMC)浓度在5～250 μg·mL~(-1)范围内与峰面积呈良好的线性关系,r=0.9998;平均回收率(n=6)为98.15%。结论:本法专属性强,操作简便,结果准确。适用于 MMC-PBCA-NP 的质量控制。     

应用复合小梁切除术治疗具有手术失败高危因素青光眼的临床观察

个月的术后观察及随访,39眼眼压<21mmHg,成功率为70 %.9眼+药物治疗眼压<30mmHg,总有效率为84%.8例手术失败,其中1例为发育型青光眼,7例为新生血管性青光眼.并发症持续性低眼压发生率7.1 %,低眼压性黄斑变性1.7%.结论 对具有手术失败高危因素青光眼的复合小梁切除术与传统小梁切除术相比可明显提高好手术成功率.如药物浓度及作用时间适当,其抗增殖药物副作用的并发症与传统小梁切除术并发症闭角无明显提高.     

免眼实验性小梁切除术后应用曲尼斯特的组织病理学和免疫组化的研究

目的探讨曲尼斯特在青光眼滤过术后抑制纤维瘢痕形成的价值。方法27只兔子分为对照组、MMC组及曲尼斯特组,双眼均行标准小梁切除术。MMC组术中应用丝裂霉素C（MMC）,曲尼斯特组术后应用曲尼斯特眼水。术后7d、14d、28d各组分别处死兔子3只,眼球组织固定,用HE、Masson三色染色和PCNA和TGF-1免疫组化染色。结果HE染色,对照组术后7d滤过道成纤维组织在滤过道大量增生。Masson三色法染色,对照组的新生胶原纤维排列致密。术后7d、14d对照组PCNA阳性细胞明显多于MMC组和曲尼斯特组（〈0.05）。对照组TGF-1染色阳性面积和平均光密度值明显大于曲尼斯特组和MMC组,差异均有显著性（〈0.05）;曲尼斯特组和MMC组比较差异无显著性（〉0.05）。结论曲尼斯特能抑制青光眼滤过术后成纤维细胞的增殖,其作用机制可能包括减少TGF-分泌从而抑制成纤维细胞增值。     

Inhibitory effects of water extract of propolis on doxorubicin-induced somatic mutation and recombination in Drosophila melanogaster.

Propolis is a substance produced by honeybees (Apis mellifera L.). Its components are strong antioxidants and free radical scavengers. The aim of this study was to evaluate the protective effects of a water extract of Brazilian green propolis (WEP) combined with the antitumor agent doxorubicin (DXR) on Drosophila melanogaster wing cells through the somatic mutation and recombination test (SMART). Two different crosses were used: The standard (ST) cross and the high bioactivation (HB) cross. The HB cross is characterized by a constitutively enhanced level of cytochrome P450 which leads to an increased sensitivity to a number of promutagens and procarcinogens. Larvae obtained from these two crosses were chronically treated with different concentrations of WEP (12.5,25.0 and 50.0 mg/mL) alone or combined with DXR (0.125 mg/mL). The results obtained with the two different crosses were rather similar. Neither toxicity nor genotoxicity were observed in WEP treated series. Simultaneous treatment with different concentrations of WEP and DXR led to a reduction in the frequency of recombination compared to the treatment with DXR alone. This anti-recombinogenic effect was proportional to the concentrations applied, indicating a dose-response correlation and can be attributed to the powerful scavenger ability of WEP.     

Plasma-derived mannose-binding lectin shows a direct interaction with C1-inhibitor

MBL-deficiency has been associated with an increased frequency and severity of infection, in particular in children and under immunocompromized conditions. In an open uncontrolled safety and pharmacokinetic MBL-substitution study using plasma-derived MBL (pdMBL) in MBL-deficient pediatric oncology patients, we found that despite MBL trough levels above 1.0 μg/ml MBL functionality was not efficiently restored upon ex vivo testing.     

胃动素对消化间期胃动脉血流影响的在体机制研究

目的此研究目的在于试图揭示胃动素对消化间期意识清醒狗胃动脉血流影响的调节机制。方法 5条意识清醒狗的胃左动脉（LGA）血流通过超声波传输时间血流仪（ultrasound transit-time blood flow meters）进行了测定。在有或无GM-109（Phe-cyclo[Lys-Tyr（3-tBu）-βAla.trifluoroacetate,胃动素受体拮抗剂）,granisetron（5HT3受体拮抗剂）,at-ropine（M胆碱能受体阻滞剂）,hexamethonium（N胆碱能受体阻滞剂）,phenoxybenzamine（α-肾上腺素能受体阻滞剂）和propranolol（β-肾上腺素能受体阻滞剂）分别静脉内持续性滴注的前提下,反复静点胃动素进行实验。结果消化间期,胃动素（100 pmol/kg/h）诱导了LGA血流的增加。GM-109完全抑制了由胃动素引起的LGA血流增加和胃肠运动。At-ropine、C6、granisetron抑制了胃动素诱导的胃运动,但未能影响LGA血流的持续性增加。α-肾上腺素能受体阻滞剂和β-肾上腺素能受体阻滞剂对胃动素诱导的LGA血流和胃机械性收缩无影响。结论胃动素是一个有效的胃血管舒张剂,胃动素通过胃动脉壁上胃动素受体调节消化间期胃动脉血流。胃动素在消化间期胃血流的调节中起着一个非常重要的作用。