Changes in Gelatinase Activity in the Gastrointestinal Tract After Anastomotic Construction in the Ileum or Colon

PURPOSE The strength of the uninjured and anastomosed intestinal wall is determined by its submucosal connective tissue. Matrix degradation by matrix metalloproteinases may result in loss of strength. It is known that anastomotic construction leads to up-regulation of matrix metalloproteinase activity in the wound area, but no quantitative data are available as to the extent of this effect throughout the intestinal wall. This study was designed to quantitate changes in gelatinolytic activity in the intestine after anastomotic construction in the ileum or colon. METHODS An anastomosis was constructed in the distal ileum or distal colon of rats, and animals were killed after one or three days. Tissue samples (5 mm) were collected containing the suture line, its adjacent segments (2- × 5-mm in both directions) and at nine other, more distant, sites throughout the gastrointestinal tract. Similar samples were collected from nonoperated control rats. All samples were analyzed by quantitative gelatin zymography. RESULTS In control rats, the most prominent gelatinolytic activities were found at 80 kDa, thought to represent a nonspecific proteolytic activity, 60 kDa and 50 kDa, representing the proform and active form of matrix metalloproteinase-2, respectively. Activities were higher in the small bowel than in the large bowel. Anastomotic construction led to massive up-regulation of an activity at 105 kDa, and its dimer, believed to represent promatrix metalloproteinase-9. Matrix metalloproteinase-2 remained unaffected, whereas the activity of the 80 kDa protein was significantly (P < 0.05) reduced. Significantly increased matrix metalloproteinase-9 activity was found in the actual anastomotic segments and in the immediately adjacent tissue. Matrix metalloproteinase-9 activities in the anastomotic segments were highest at Day 1 in the ileum and at Day 3 in the colon. Anastomotic construction in the ileum or colon did not lead to any significant changes of any gelatinolytic activity at the more distant sites in the bowel wall. CONCLUSIONS Up-regulation of gelatinase activity after anastomotic construction in the intestine is caused by matrix metalloproteinase-9. Because the effect is local and not systemic, unwanted matrix degradation at distant sites seems unlikely. Supported by the Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. Reprints are not available.     

Pseudoreduction of intussusception: Is ileal reflux the end point?

Two cases of unsuccessful hydrostatic reduction of intussusception are reported. Both were associated with barium filling multiple loops of distal ileum, despite lack of complete reduction of the intussusception. The presence of free ileal reflux does not guarantee successful reduction. Careful examination of the cecum for residual intussus-ceptum and of non-contrast-filled small-bowel loops for evidence of remaining small-bowel obstruction is essential to recognize unsuccessful reduction.     

Poliovirus mutants excreted by a chronically infected hypogammaglobulinemic patient establish persistent infections in human intestinal cells

Immunodeficient patients whose gut is chronically infected by vaccine-derived poliovirus (VDPV) may excrete large amounts of virus for years. To investigate how poliovirus (PV) establishes chronic infections in the gut, we tested whether it is possible to establish persistent VDPV infections in human intestinal Caco-2 cells. Four type 3 VDPV mutants, representative of the viral evolution in the gut of a hypogammaglobulinemic patient over almost 2 years [J. Virol. 74 (2000) 3001], were used to infect both undifferentiated, dividing cells, and differentiated, polarized enterocytes. A VDPV mutant excreted 36 days postvaccination by the patient was lytic in both types of intestinal cell cultures, like the parental Sabin 3 (S3) strain. In contrast, three VDPVs excreted 136, 442, and 637 days postvaccination, established persistent infections both in undifferentiated cells and in enterocytes. Thus, viral determinants selected between day 36 and 136 conferred on VDPV mutants the capacity to infect intestinal cells persistently. The percentage of persistently VDPV-infected cultures was higher in enterocytes than in undifferentiated cells, implicating cellular determinants involved in the differentiation of enterocytes in persistent VDPV infections. The establishment of persistent infections in enterocytes was not due to poor replication of VDPVs in these cells, but was associated with reduced viral adsorption to the cell surface.     

Intestinal Anastomoses from Diabetic Rats Contain Supranormal Levels of Gelatinase Activity

PURPOSE: Early postoperative strength in intestinal anastomoses is reduced in diabetic rats, whereas collagen deposition is essentially unchanged, suggesting that increased matrix degradation may be the cause of diminished wound strength. The aim of this study was to investigate whether (gelatin-degrading) matrix metalloproteinase activity is enhanced in intestinal anastomoses from diabetic rats. METHODS: Sixty male young adult Wistar rats underwent resection and anastomosis of both ileum and colon. In half the animals diabetes was induced seven days before operation by streptozotocin injection (50 mg/kg intravenously). Gelatinase activities in extracts from uninjured intestine and anastomoses at one, three, or seven days after surgery were measured by quantitative gelatin zymography. RESULTS: After surgery, profound changes were observed with time for gelatinase activities with molecular weights of 50 and 60 kDa, thought to represent matrix metalloproteinase-2, and of 66, 80, 105, 140, 220, and 260 kDa, thought to represent various forms of matrix metalloproteinase-9. In many cases, specific activities were significantly (P < 0.05) higher in the anastomotic extracts from diabetic rats. Total anastomotic activities present at Day 7 were strongly elevated for most matrix metalloproteinase forms in ileum and colon from diabetic animals. CONCLUSION: Experimental diabetes leads to a sustained and elevated presence of gelatinase activity in intestinal anastomoses. Increased local matrix degradation may contribute significantly to impaired anastomotic strength in the intestine observed under this condition.     

Human gastrointestinal sulfotransferases: identification and distribution

Sulfotransferases (STs) catalyze the sulfation of many structurally diverse molecules. Enzymatic assays and Western blots have been used to identify and characterize STs in the human gastrointestinal tract. Sulfation activities for 2-naphthol, dopamine, estradiol, and dehydroepiandrosterone (DHEA) from 23 donors were measured in cytosol prepared from stomach, duodenum, segments of small intestine, and colon and were compared to levels in human liver cytosol. Stomach and colon had low 2-naphthol and dopamine sulfation activities and almost no estradiol and DHEA sulfation activity. For all four substrates, small intestine has higher activities than both stomach and colon. Human small intestine 2-naphthol sulfation specific activity is approximately half that of human liver. Human small intestine dopamine sulfation activity is three times as high as that of human liver. While estrogen sulfation activity is about the same for both human intestine and human liver, human liver DHEA sulfation activity is about five times as high as that of human small intestine. The distribution of ST activities along the length of the small intestine was very different among different donors. Some donors had higher activity in the proximal segments of the small intestine, whereas other donors had higher activity in the distal segments of the small intestine. Our results also demonstrated high variation of small intestine sulfation activities compared with human liver activities among different donors. The Western blot results agreed with the enzymatic assay results. These results suggest that xenobiotics may regulate human small intestinal STs.     

21例原发性小肠肿瘤临床病理特点分析

目的：探讨原发性小肠肿瘤的临床病理特点。方法：对21例原发性小肠肿瘤临床病理资料进行回顾性分析。结果：21例原发性小肠肿瘤中，良性5例，恶性16例。肿瘤发病分布特点是从近端到远端良性肿瘤所占比例依次降低，恶性肿瘤所占比例依次增高。临床表现以消化道出血和腹痛不适为主。结论：小肠肿瘤以恶性为主，预后差：     

Time course of adaptation to low and high NaCl diets in the domestic fowl

Short circuit currents (I _sc), resting electrical potential differences (p.d.) and resistances were measured in vitro for stripped rectal (colonic) and coprodeal epithelia from fowls transferred to low from high NaCl diet for 1, 2, 4 or 8 days (NaCl depletion), and from birds adapted to low NaCl diet and sacrificed 8, 16 and 24 h after NaCl-loading (resalination). NaCl-depletion enhancedI _sc and p.d. fully by 4 days in rectum but took 8 days in coprodeum (half times 1.2 days and 4 days respectively); rectal amino acid-sensitiveI _sc was abolished and amiloride-sensitiveI _sc was established by 4 days (half-time 1 day). Resistance changes were transient and relatively small in rectum, but coprodeal resistance decreased. Resalination reversed these changes very rapidly in both tissues (within 25–50 h; half times 10–20 h). It is concluded that responses to NaCl-depletion are mediated by aldosterone (and possibly by some other unknown agonist); responses to resalination may be due in part to suppressed aldosterone secretion and possibly to the evocation of some other controller (perhaps prolactin or corticosterone) antagonising aldosterone.     

针刺对手阳明大肠经线下深部组织中氧分压的影响

目的:探讨与手阳明大肠经线相关组织的能量代谢特点。方法:31名健康志愿者,沿手阳明大肠经脉循行线上取5个测试点,测试深度为皮下1.5cm,其中3个为穴位(臂臑、手五里、手三里),2个为经上非穴位点(曲池-臂臑中点、曲池-阳溪中点);同时在各测试点内外1.5～2cm处各取1个非经对照点,形成5个横向测试水平。观察电针前、电针合谷穴时及电针后各测试点氧分压的变化情况,连续记录60min。结果:正常情况下沿手阳明大肠经循行线上测试点深部组织氧分压非常显著地高于两侧非经对照部位(P0.01)。电针合谷穴时,手阳明大肠经线上测试点氧分压降低,与电针前比较差异有统计学意义(P0.05)。电针后手阳明大肠经上氧分压与电针期间比较差异无统计学意义(P0.05),与电针前比较显著降低(P0.01,P0.05)。而两侧非经对照部位,电针时、电针后各测试点的氧分压与电针前比较均无明显变化(P0.05)。结论:常态下手阳明大肠经循行线下深部组织中的能量代谢较其两侧非经对照部位旺盛,电针可以使沿经组织的氧利用率提高,能量代谢进一步增强。提示经脉可能是与物质、能量和信息的转换和传递相关的某种通道。     

结直肠癌HLA-DR表达与树突细胞浸润及其临床意义

目的:分析结直肠癌HLA-DR表达及癌组织中树突细胞(DC)的密度,探讨两者对结直肠癌患者临床分期及预后的影响。方法:47例结直肠癌石蜡标本,应用免疫组织化学SP法检测癌组织HLA-DR表达和S100阳性树突细胞的浸润密度,并与患者的临床分期和预后进行统计学分析。结果:结直肠癌HLA-DR表达率27.7%(13/47),表达率随临床分期增加而逐渐下降(P<0.05),但对预后无明显影响。S-100阳性DC丰富(≥10/HPF)的病例为44.7%(21/47),DC浸润密度在患者的临床分期和预后方面均有显著差异性(P<0.05)。HLA-DR表达与DC浸润程度密切相关(r=0.522;P<0.01)。结论:HLA-DR表达与DC浸润密度可反映了结直肠癌患者的抗肿瘤免疫状况,可能成为判断临床分期和预后的重要指标。     

小肠良性肿瘤临床分析——附70例报告

目的：对手术病理证实的小肠良性肿瘤70例，就其主要临床表现和有关诊断方法价值进行分析。方法：采用血常规、X线检查和其他检查。结果：小肠良性肿瘤中以平滑肌瘤和血管瘤为多，占82．86％（58／70），病变部位以空肠居首，占57．14％（40／70），无明显慢性腹痛而又反复大出血者，19例急诊血管造影阳性，手术证实的病变部位与造影一致，病理诊断符合率89．47％（17/19）。结论：血管造影对小脑肿瘤出血有定性及定位的诊断价值．小肠钡灌亦有较高的诊断价值．剖腹探查应慎重，以期达到确诊及治疗的目的。