Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q16637 (SMA)
 8,107 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ischemia of the intestines damages the permeability of the intestinal wall, allowing lipopolysaccharide (LPS) (endotoxin) to leak from the gut lumen into the blood circulation, causing shock and death. We measured LPS levels associated with corticosteroid treatment vs. no treatment in cats whose superior mesenteric artery had been occluded for 60 min. In untreated cats, the preocclusion mean plasma LPS concentration remained stable at 0.069 +/- 0.015 ng/ml. Toward the end of the occlusion period, mean plasma LPS rose to 0.239 +/- 0.032 ng/ml (p less than .01). Release of the clamp and reperfusion with oxygenated blood was followed within 20 min by a large rise in plasma LPS concentration to 0.825 +/- 0.11 ng/ml (p less than .01), which had returned to preocclusion levels about 80 min later. Methylprednisolone (30 mg/kg) was infused into a second group of cats 1.5 h before SMA occlusion. In these cats there was a complete inhibition of the LPS rise both during and after occlusion. These data suggest that the reported beneficial effect of corticosteroids in the treatment of septic shock may be mediated, in part, by reducing LPS leakage from the gut.
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PMID:Effect of corticosteroid prophylaxis on lipopolysaccharide levels associated with intestinal ischemia in cats. 375 30

The isolated small bowel from duodenojejunal junction to ileocecal junction with intact SMA and SMV was perfused with Krebs-Ringer solution intraluminally in rat. After all the branches from aorta and portal vein other than SMA and SMV were ligated, aorta and portal vein were cannulated and perfused with Krebs-Dextran solution. The isolated perfused bowel was transferred immediately to the chamber equipped with constant temperature and humidity. For the purpose of studying the direct toxicity to the bowel tissue, B4 endotoxin (Difco) was added to intravascular perfusate. Significant physiological and chemical changes listed below were observed as compared with those of the control group which was perfused with endotoxin free perfusate. Active transport of D-glucose was decreased. Net entry of water into the gut lumen was decreased. pH in intravascular fluid was significantly decreased. Lactic acid level in intravascular fluid was significantly high, which was well correlated with pH change. O2 consumption change was not marked, but CO2 accumulation in intravascular perfusate was significant. These were the results of the toxic effects of endotoxin on the rat bowel.
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PMID:[Toxic effects of endotoxin perfusion on isolated rat bowel]. 643 Dec 58

The expression of tenascin (Tn) and alpha-smooth muscle actin (alpha-SMA) was analyzed in the developing and adult human small intestine by means of double immunofluorescent staining with specific antibodies. By 7 weeks of gestation, the gut anlage has a simple tubular shape and is formed of a stratified undifferentiated epithelium surrounded by a poorly organized mesenchyme. Both Tn and alpha-SMA were found exclusively at the periphery of the tissue, corresponding to the presumptive muscularis propria. By 9 weeks, villus rudiments had formed but Tn and alpha-SMA remained restricted to the muscularis propria. Tn was first detected in the mesenchyme at 11 weeks. By 13 weeks, a preferential distribution of Tn in the subepithelial region of the mesenchyme was readily observed while alpha-SMA was still absent. From this stage to 20 weeks, Tn gradually concentrated in this region that, as determined by alpha-SMA detection, corresponded to the future muscularis mucosa area. As shown by double staining of Tn and alpha-SMA, deposition of Tn also preceded the appearance of the other alpha-SMA-expressing cells in the mucosa. These observations suggest that Tn could have a role in the differentiation of intestinal contractile cells.
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PMID:Relationship between tenascin and alpha-smooth muscle actin expression in the developing human small intestinal mucosa. 769 66

Our in vivo model of mesenteric ischemia/reperfusion (I/R) has shown that the gut serves as a priming bed for neutrophils (PMN). Activation of phospholipase A2 (PLA2) during ischemia temporally precedes PMN sequestration in the gut and the appearance of primed PMN in the portal circulation. Therefore, we hypothesized that reperfused gut secretes platelet activating factor (PAF) via PLA2 activation that is responsible for increased PMN chemotaxis and priming for superoxide (O2-) generation. Sprague-Dawley rats underwent gut ischemia/reperfusion (45 min SMA occlusion/2 hr reperfusion) or sham laparotomy. Distal ileum was harvested, rinsed with bacteriostatic saline/neomycin, and incubated for 1 hr at 37 degrees C in RPMI 1640 and the cell-free supernatant was collected. Normal human PMNs, isolated by plasma-Percoll gradients, were pretreated with or without a PAF receptor antagonist (WEB 2170). Chemotaxis toward gut supernatant was then measured by the agarose method. Additionally, PMNs were preincubated with or without WEB 2170 and their O2- release in response to 1 microM FMLP was measured by the Vmax of SOD-inhibitable cytochrome c reduction. Reperfused gut produced a chemotactic index of 2.1 +/- 0.1 compared to 0.2 +/- 0.9 following sham laparotomy (P < 0.05); this was reduced to 0.4 +/- 0.9 with PAF receptor blockade. Similarly, gut I/R supernatant primed PMNs for O2- (P < 0.05) compared to laparotomy, and this effect was abrogated by a PAF antagonist. These data suggest that reperfused gut can elaborate PAF which chemoattracts and primes PMNs for O2- generation.
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PMID:Reperfused gut elaborates PAF that chemoattracts and primes neutrophils. 779 40

Currently there exists no reliable serum marker for the early diagnosis of acute mesenteric ischemia. We investigated D(-)-lactate as a marker of acute mesenteric ischemia in a rat model. D(-)-Lactate is a byproduct of bacterial metabolism; it is neither produced nor metabolized by mammalian cells. In an ischemic segment of bowel the resident microflora rapidly proliferate and soon overgrow the affected intestinal segment. Additionally, the mucosal barrier of the gut begins to break down. Under these conditions we hypothesize that D(-)-lactate should cross the mucosal barrier in large quantities. To determine if this rapid bacterial proliferation and mucosal leakage produces D(-)-lactate concentrations in quantities sufficient to elevate peripheral blood levels, two models of acute intestinal ischemia and one model of simple obstruction were developed in rats. The three models included: strangulation obstruction of terminal ileum, superior mesenteric artery ligation, and simple intestinal obstruction of the ileum. Controls were divided into two groups: sham-operated controls and unoperated controls. Serum samples were collected via an internal jugular catheter at 5 min, 2 hr, and 4 hr after surgery. These samples were then assayed for D(-)-lactate using an enzymatic-spectrophotometric assay. Data was analyzed by repeated measures analysis of variance and where applicable the Student t test was used to determine statistical significance. We found statistically significant elevations in D(-)-lactate concentrations as early as t = 5 min in the strangulation obstruction model and SMA ligation model compared to unoperated controls.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Serum D(-)-lactate levels as a predictor of acute intestinal ischemia in a rat model. 836 Nov 76

To determine whether critical splanchnic artery hypoperfusion can provoke systemic shock and to identify the roles of the peripheral opioid and nitric oxide (NO) systems in this process, various degrees of superior mesenteric artery hypoperfusion (SMA-H) were produced in anesthetized adult rabbits (n=40), and hemodynamic and metabolic indices were measured. Metabolic acidosis and irreversible hypodynamic shock occurred with SMA-H at levels representing 25-20% of mean baseline SMA blood flow. In 112 other rabbits subjected to SMA-H at 20% (SMA-H20%), we studied plasma NO and enkephalin (ENK) levels, cardiovascular reactivity to selected physiological agonists, effects of ENKs on plasma NO levels, and effects of peripheral opioid receptor blockade and inducible NO synthase (iNOS) inhibition. SMA-H20% progressively increased systemic blood levels of NO and ENKs. Exogenous ENK administration accentuated SMA-H20%-induced increases in plasma NO levels, and their cardiovascular depressing effects were significantly greater when they were administered during SMA-H20% (vs. administration under baseline conditions). Selective blockade of cardiovascular delta-opioid receptors improved hemodynamics, prevented shock irreversibility and reduced plasma NO levels; similar effects were obtained by selective iNOS inhibition. These findings demonstrate that critical arterial hypoperfusion of the gut can induce hypodynamic systemic shock through ENK-induced hyperactivation of cardiovascular delta-opioid receptors, which leads to increased plasma levels of NO related in part to increased iNOS activity. Since pronounced splanchnic artery hypoperfusion occurs in all advanced systemic shock states, selective delta-opioid receptor antagonists and/or iNOS inhibitors may prove to be useful in improving shock hemodynamics and metabolic derangements and/or preventing progression toward irreversibility.
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PMID:Shock induction by arterial hypoperfusion of the gut involves synergistic interactions between the peripheral enkephalin and nitric oxide systems. 1569 9

We assessed the prevention of hepatic fibrogenesis by water-extract of Panax notoginseng Buck F.H. Chen. (Arialiaceae) root (PNS) in Long-Evans rats with cinnamon coat color (LEC rats). LEC rats were divided into three groups A, fed on a basal diet (BD); B, fed on BD plus 1% PNS; and C), fed on BD plus 0.005% lycopene as a control. All rats were sacrificed at 26 weeks of age. The percentage of the total area involved by fibrosis was 1.46 +/- 0.47 in group A, 0.83 +/- 0.10 in B (P=0.0030, B vs A) and 0.91 +/- 0.45 in C (P=0.0035, C vs. A). The percentage of the total area that was stained for alpha-SMA was 0.56 +/- 0.34 in group A, 0.15 +/- 0.02 in B (P=0.0016, B vs. A and 0.11 +/- 0.01 in C (P=0.0025, C vs. A. In group B, malondialdehyde (MDA) in the liver was lower than in group C (P=0.007). In group C, the concentration of iron in the liver was lower than in group A (P=0.0053). Thus, PNS suppressed fibrogenesis through reduced generation of lipid peroxides. The mechanisms of this preventive effect of fibrogenesis with PNS were suggested to inhibit the stellate cell activity. Second objective of this study was to determine whether PNS affects hepatic microvascular dysfunction elicited by gut ischemia and reperfusion (I/R), since gut I/R causes hepatic microvascular dysfunction, and to investigate the role of nitric oxide (NO). Male Wistar rats were exposed to 30 min of gut ischemia followed by 60 min of reperfusion. Intravital microscopy was used to monitor the number of non-perfused sinusoids (NPS). In another set of experiments, PNS (1 g/kg per day intragastrically) was administered to rats for 7 days. In some experiments, dexamethasone (ST) (2 mg/kg per day intravenously) was administered. In control rats, gut I/R elicited increases in the number of NPS, and plasma TNF-alpha and ALT activities, and these changes were mitigated by the pretreatment with PNS. Pretreatment with an NO synthase inhibitor diminished the protective effects of PNS on the increase in NPS and plasma TNF-alpha levels, but not its effect on the increase in plasma ALT activities. Pretreatment with PNS increased plasma nitrite/nitrate levels. The responses caused by gut I/R were attenuated by the pretreatment with ST. Pretreatment with an NO synthase inhibitor did not affect the effect of ST. These results suggest that PNS attenuates the gut I/R-induced hepatic microvascular dysfunction and inflammatory responses such as TNF-alpha production in the early phase via enhancement of NO production, and sequential hepatocellular damage via its anti-inflammatory effect.
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PMID:A Korean herbal medicine, Panax notoginseng, prevents liver fibrosis and hepatic microvascular dysfunction in rats. 1569 47

Mesenteric ischemia/reperfusion (IR) damages the gastrointestinal epithelia and impairs gut function. Ischemic preconditioning (IPC) has been shown to protect organs against IR injury. We hypothesized that IPC protects the gut from IR injury. Rats were randomized to a sham group, a sham early IPC + IR group (sham IPC + SMA occlusion for 30 min and 6 h of reperfusion), an early IPC + IR group (IPC, three cycles of SMA occlusion for 4 min and reperfusion for 10 min) followed immediately by SMA occlusion for 30 min and 6 h of reperfusion), a sham 24-h group, a sham late IPC + IR group (sham IPC followed by additional reperfusion for 24 h + SMA occlusion for 30 min and 6 h of reperfusion), and a late IPC + IR group (IPC protocol followed by additional reperfusion for 24 h, and then SMA occlusion for 30 min followed by 6 h of reperfusion). At 6 h, transit was determined and expressed as the mean geometric center. Ileum was harvested for assessment of mucosal injury and myeloperoxidase (MPO) activity. Tissue water was determined using the wet-to-dry weight ratio to assess gut edema. Early IPC + IR significantly improved transit (3.9 +/- 0.2), decreased MPO levels (3 +/- 2), and lessened mucosal injury (1.2 +/- 0.3) compared with animals subjected to sham early IPC + IR (transit, 2.9 +/- 0.2; MPO levels, 9 +/- 1; mucosal injury, 3.0 +/- 0.6). Late IPC + IR also improved transit (6.0 +/- 0.4) and decreased MPO levels (1 +/- 1) compared with sham late IPC + IR (transit, 4.4 +/- 0.2; MPO levels, 8 +/- 1), however, there was no difference in the mucosal protection between late IPC + IR (1 +/- 0.3) and sham late IPC + IR (1 +/- 1). Our results suggest that early and late IPC improves intestinal dysfunction, decreases inflammation, and provides mucosal protection in the intestine after IR. Our results show that IR-induced gut dysfunction can be improved by IPC. Both phases of IPC can potentially be useful in the clinical setting of surgical patient care.
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PMID:Ischemic preconditioning protects against gut dysfunction and mucosal injury after ischemia/reperfusion injury. 1571 25

Gastro-intestinal stromal tumours (GIST) are a biologically distinct heterogenous group of tumours of the gut. They are said to arise from interstitial cells of Cajal in gut wall. The turnour results from mutation of c-kit gene which codes for CD117 containing tyrosine kinase receptor of Cajal cells. Identification of this mutation by immunohistochemistry (IHC) is the key to the diagnosis of these tumours. CD117 negative GISTs develop from gene mutation through alternate pathway (PDGFRA). The accurate diagnosis is important as specific chemotherapeutic agents are now available for their management. We have studied 8 cases of GISTs during last 2 years in our institute. Half of the cases were female, six cases were in the age group between 35 to 50 years, the other two being of 19 and 70 years. On histology, 5 cases were categorized as high grade on the basis of their size and mitotic count. All cases were subjected to IHC. Only 4 cases were CDll7 positive, one case was positive for S100 and one case for SMA. Remaining 2 cases, negative for CD117, S100 and SMA, histologically resembled GISTs. CD117 positive cases are ideal candidates for treatment with molecularly targeted specific chemotherapeutic agents, e.g., imatinib as these tumours are non-responsive to conventional chemotherapy. Histologically diagnosed stromal tumours of the gut should be subjected to immunostain for CD117 so that specific medical management can be provided to prevent recurrence and metastasis as well as pre-operative debulking of the tumour.
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PMID:Gastro-intestinal stromal tumour--role of CD117 in diagnosis and management. 1788 45

The type of fluid used during resuscitation may have an important impact on tissue edema. We evaluated the impact of two different regimens of fluid resuscitation on hemodynamics and on lung and intestinal edema during splanchnic hypoperfusion in rabbits. The study included 16 female New Zealand rabbits (2.9 to 3.3 kg body weight, aged 8 to 12 months) with splanchnic ischemia induced by ligation of the superior mesenteric artery. The animals were randomized into two experimental groups: group I (N = 9) received 12 mL x kg-1 x h-1 lactated Ringer solution and 20 mL/kg 6% hydroxyethyl starch solution; group II (N = 7) received 36 mL x kg-1 x h-1 lactated Ringer solution and 20 mL/kg 0.9% saline. A segment from the ileum was isolated to be perfused. A tonometric catheter was placed in a second gut segment. Superior mesenteric artery (Q SMA) and aortic (Qaorta) flows were measured using ultrasonic flow probes. After 4 h of fluid resuscitation, tissue specimens were immediately removed for estimations of gut and lung edema. There were no differences in global and regional perfusion variables, lung wet-to-dry weight ratios and oxygenation indices between groups. Gut wet-to-dry weight ratio was significantly lower in the crystalloid/colloid-treated group (4.9 +/- 1.5) than in the crystalloid-treated group (7.3 +/- 2.4) (P < 0.05). In this model of intestinal ischemia, fluid resuscitation with crystalloids caused more gut edema than a combination of crystalloids and colloids.
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PMID:Comparison of the effects of lactated Ringer solution with and without hydroxyethyl starch fluid resuscitation on gut edema during severe splanchnic ischemia. 1871 46


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