Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030305 (pancreatitis)
 16,014 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We investigated the effects of nafamostat mesilate, a synthetic protease inhibitor clinically used for patients with pancreatitis or disseminated intravascular coagulopathy, on NO synthesis and apoptosis in lipopolysaccharide (LPS)-treated human trophoblasts. Nafamostat mesilate or aminoguanidine, an inhibitor of NO synthase, suppressed NO synthesis and apoptosis in trophoblasts induced by LPS. Both agents also suppressed matrix metalloproteinase-2 activity induced by LPS. LPS also stimulated secretion of IL-6 and IL-8 in cultured trophoblasts, which was suppressed by nafamostat mesilate. Protease inhibitors including nafamostat mesilate may be therapeutic agents for chorioamnionitis and various diseases including septic shock, ischemia-reperfusion injury in brain and heart, graft rejection, and acute phase inflammatory diseases, in which overproduction of NO or peroxynitrite is involved in tissue injury.
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PMID:Nafamostat mesilate, a serine protease inhibitor, suppresses lipopolysaccharide-induced nitric oxide synthesis and apoptosis in cultured human trophoblasts. 1095 57

Alcohol induces pancreatic ischemia, but the mechanisms promoting pancreatic inflammation are unclear. We investigated whether cigarette smoke inhalation is a cofactor in the development of ethanol-induced pancreatic injury. Cigarette smoke was administered to anesthetized rats alone or in combination with intravenous ethanol infusion. Control animals received either saline or ethanol alone. Pancreatic capillary blood flow and leukocyte-endothelium interaction in postcapillary venules were evaluated by intravital microscopy. Leukocyte sequestration was assessed by measurement of myeloperoxidase activity in pancreatic tissue, and pancreatic injury evaluated by histology. Ethanol decreased pancreatic blood flow progressively over 90 minutes (p < 0.001 vs. baseline), but neither leukocyte-endothelium interaction nor leukocyte sequestration was altered. Cigarette smoke alone reduced pancreatic blood flow temporarily (p < 0.01 vs. baseline) and increased leukocyte-endothelium interaction (roller p < 0.001, sticker p < 0.01 vs. baseline). Cigarette smoke potentiated the impairment of pancreatic capillary perfusion caused by ethanol, and both the number of rolling leukocytes and myeloperoxidase activity levels were increased compared to ethanol or nicotine administration alone (p < or = 0.05 and p < or = 0.01, respectively). This study demonstrates that ethanol induces pancreatic ischemia and that cigarette smoke leads to both temporary pancreatic ischemia and minimal leukocyte sequestration. Cigarette smoke potentiates the amount of pancreatic injury generated by ethanol alone. Smoking therefore seems to be a contributing factor in the development of alcohol-induced pancreatitis in the rat model.
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PMID:Cigarette smoke enhances ethanol-induced pancreatic injury. 1103 72

An ischemic origin of acute pancreatitis has been considered for a long time, at least as an aiding factor: ischemia has a fundamental role in the development of necrotizing pancreatitis from an oedematous one. Shock, heart condition and celiac-mesenteric ischemia can determine the onset of an acute pancreatitis through local ischemic lesions. Personal experience with a case of acute pancreatitis following an intestinal ischemic failure is reported. The duration of ischemia and, in particular, the free radicals formation during the organ reperfusion have been considered as the main pathogenetic factors. In the observed case, the ischemic hypothesis seems to be supported from the lack of other known factors and from the intestinal ischemic failure episode.
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PMID:[Ischemic pathogenesis of acute pancreatitis. A case report]. 1105 41

A 72-year-old man underwent resection of an infrarenal aortic aneurysm; during postoperative recovery, multiorgan failure developed secondary to cholesterol emboli in several arteries. The initial sign consisted of patches of livedo in the lower limbs with pedal pulses, hematuria and hyperdynamic shock with high cardiac output and reduced vascular resistance. The clinical picture progressed to multiple organ failure with non-cardiogenic pulmonary edema, oliguric kidney failure, coagulopathy, necrotizing pancreatitis and colic ischemia. The patient died 15 days after surgery. The formation of multiple cholesterol emboli is a rare complication after aortic surgery, vascular catheterization or anticoagulant treatment. It is caused by cholesterol crystals measuring 100 to 200 mu that embolize and block small arteries. Diagnosis is difficult because the organs involved can be many and various. No specific treatment is available and the rates of morbidity and mortality are high.
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PMID:[Multiple cholesterol athero-embolisms after resection of an abdominal aortic aneurysm]. 1117 70

The etiology of acute pancreatitis, apart from alcohol abuse and cholelithiasis may also include a vascular component responsible for pancreatic ischemia. It is now acknowledged that chronic pancreatitis may be a consequence of the acute variant, but it remains unclear what factors influence this sequence of morphological changes. In order to clarify this issue we proposed a model of experimental acute pancreatitis in rats induced by a 30 min reduction of blood flow in inferior splenic artery followed by reperfusion. Rats were sacrificed at 1 h, 12 h, 24 h, and 2, 3, 5, 7, 14, 21, 28 days after cessation of ischemia. We performed histopathological examination of pancreatic tissue and measured pancreatic blood flow, plasma amylase activity and interleukin-1 beta concentration. The present findings indicate that transient pancreatic ischemia leads to the development of acute necro-haemorrhagic pancreatitis. The morphological features of acute inflammation are correlated positively with functional disorders. In some cases the features of chronic pancreatitis may appear transiently after the acute phase, whereas the repair of postinflammatory injury involves the regeneration of acinar cells.
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PMID:Morphological changes and morphological-functional correlations in acute experimental ischemia/reperfusion pancreatitis in rats. 1124 88

Fifty-nine consecutive patients underwent live donor nephrectomy for transplantation. Twenty-nine patients (Group I) had open kidney procurement, and 30 patients (Group II) had laparoscopic procurement. The mean operative time in Group I was 2:30 hours (range 1:55-2:59), whereas in Group II it was 3:01 hours (1:54-5:21). All kidneys functioned immediately after transplantation. The average warm ischemia time was not calculated in Group I; it was 3.9 minutes (2-15) in Group II. Intraoperative complications occurred in two patients in Group II. One patient had bleeding from an accessory renal artery. The second patient had a tear in the splenic capsule. No ureteral complications occurred in either group. Postoperatively one patient in Group I developed incisional hernia, one developed pneumothorax, and two developed atelectasis. In Group II one patient developed pancreatitis, one developed flank ecchymosis, and two had suprapubic wound hematomas. Using the laparoscopic approach the hospital stay decreased from 4.1 to 1.27 days (69%) (P < 0.001) and return to work decreased from 28.4 to 14.8 days (49%) (P < 0.01). Live donation increased by 67 per cent. We conclude that the laparoscopic procurement of kidneys for transplantation compares well with the open method. It offers several advantages that may increase the living donor pool.
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PMID:Laparoscopic versus conventional live donor nephrectomy: experience in a community transplant program. 1130

The mesenteric hemodynamic response to circulatory shock is characteristic and profound; this vasoconstrictive response disproportionately affects both the mesenteric organs and the organism as a whole. Vasoconstriction of post-capillary mesenteric venules and veins, mediated largely by the alpha-adrenergic receptors of the sympathetic nervous system, can effect an "autotransfusion" of up to 30% of the total circulating blood volume, supporting cardiac filling pressures ("preload"), and thereby sustaining cardiac output at virtually no cost in nutrient flow to the mesenteric organs. Under conditions of decreased cardiac output caused by cardiogenic or hypovolemic shock, selective vasoconstriction of the afferent mesenteric arterioles serves to sustain total systemic vascular resistance ("afterload"), thereby maintaining systemic arterial pressure and sustaining the perfusion of non-mesenteric organs at the expense of mesenteric organ perfusion (Cannon's "flight or fight" response). This markedly disproportionate response of the mesenteric resistance vessels is largely independent of the sympathetic nervous system and variably related to vasopressin, but mediated primarily by the renin-angiotensin axis. The extreme of this response can lead to gastric stress erosions, nonocclusive mesenteric ischemia, ischemic colitis, ischemic hepatitis, ischemic cholecystitis, and/or ischemic pancreatitis. Septic shock can produce decreased or increased mesenteric perfusion, but is characterized by an increased oxygen consumption that exceeds the capacity of mesenteric oxygen delivery, resulting in net ischemia and consequent tissue injury. Mesenteric organ injury from ischemia/reperfusion due to any form of shock can lead to a triggering of systemic inflammatory response syndrome, and ultimately to multiple organ dysfunction syndrome. The mesenteric vasculature is therefore a major target and a primary determinant of the systemic response to circulatory shock.
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PMID:The mesenteric hemodynamic response to circulatory shock: an overview. 1133 91

The objective of this study was to assess the biochemical and histological signs of pancreatic damage development and pancreatic recovery in the course of ischemia-reperfusion induced pancreatitis. Acute pancreatitis was induced in rats by limitation of pancreatic blood flow (PBF) in inferior splenic artery for 30 min using microvascular clips, followed by reperfusion. Rats were sacrificed at the time: 1 h, 12 h, 24 h, and 2, 3, 5, 7, 10, 14, 21 and 28 days after ischemia. PBF was measured using laser Doppler flowmeter. Plasma amylase, interleukin 1beta (IL-1beta) and interleukin 10 (IL-10) concentration, pancreatic DNA synthesis, as well as, morphological features of pancreatic damage were examined. Ischemia with reperfusion caused acute necrotizing pancreatitis followed by pancreatic regeneration. After removal of microvascular clips, PBF was reduced and the maximal fall of PBF was observed 24 h after ischemia, then PBF grew reaching the control value at 28th day. Plasma amylase activity was increased between 12th h and 3rd day with maximum at 24 h after ischemia. Also plasma IL-1beta and IL-10 were elevated with maximal value at the first and second day after ischemia, respectively. DNA synthesis was maximally reduced at the first day (by 70%) and from second day the reversion of this tendency was observed with full restoration of pancreatic DNA synthesis within four weeks. Morphological features of pancreatic tissue showed necrosis, strongly pronounced edema and leukocyte infiltration. Maximal intensity of morphological signs of pancreatic damage was observed between first and second day of reperfusion. During pancreatic regeneration between second and tenth day after ischemia the temporary appearance of chronic pancreatitis-like features such as fibrosis, acinar cell loss, formation of tubular complexes and dilatation of ducts was observed. The regeneration was completed within four weeks after pancreatitis development. We conclude that partial and temporary pancreatic ischemia followed by reperfusion causes acute necrotizing pancreatitis with subsequent regeneration within four weeks. Pancreatic repair after necrotizing pancreatitis is connected with the increase in plasma IL-10 concentration and transitory formation of tubular complexes.
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PMID:Pancreatic damage and regeneration in the course of ischemia-reperfusion induced pancreatitis in rats. 1145 2

Ischemia/reperfusion injury plays an important role in the development of graft pancreatitis and thrombosis after pancreas transplantation. Up to now there are few therapeutic options for this severe complication because very little is known about pancreatic ischemia/reperfusion injury. The same pathomechanisms may also be involved in the induction and determination of the course of acute pancreatitis. We observed the effect of 2 h of warm in situ ischemia on the postischemic tissue oxygenation, histological organ damage, and pancreatic enzymes. Experiments were performed in 21 male Wistar rats. In sham-operated animals without ischemia, the pancreas was not dissected. In the ischemia/reperfusion group a pancreatic tail-segment was carefully separated from the head, and ischemia was induced by clamping the splenic vessels for 2 h, after flushing the pancreatic tail-segment with heparinized saline. Animals treated similarly, but with opening of the clamps some seconds after induction of ischemia, served as controls. The animals were observed for 2 h after reperfusion. Tissue oxygenation was monitored by a PO2-sensitive probe (LICOX, GMS, Kiel, Germany) which was implanted into the pancreatic tissue. Blood samples were taken before, 5 min, 60 min, and 120 min after reperfusion. At the end of the experiment the pancreatic tail was excised for histological examination; biopsies froin the non-ischemic pancreatic head served as intraindividual control to exclude side effects on the nonischemic pancreatic head. In the ischemia/reperfusion group, PO2ti was significantly lower 1 h (18.0+/-1.7 mmHg) and 2 h (16.4+/-1.6 mmHg) after reperfusion compared with baseline conditions (32.8+/-5.2 mmHg) and the control group (1 h 30.6+/-1.9 mmHg, 2 h 32.4+/-2.4 mmHg). Histological injury score and plasma lipase activity were significantly higher in the ischemia/reperfusion group compared with the control group. Thus we describe a new experimental model of complete normothermic in situ ischemia of a pancreatic tail-segment with the possibility of flushing the pancreatic tail-segment and selective local application of drugs to the pancreas.
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PMID:Ischemia/reperfusion-induced pancreatitis in rats: a new model of complete normothermic in situ ischemia of a pancreatic tail-segment. 1146 2

Although alcohol is well recognized as a systemic toxin, the enteric manifestations of alcohol abuse have only recently begun to be elucidated at the cellular and microvascular levels. Since the microvascular mechanism of the toxicity of alcohol has progressively been revealed, clinical applications of this research field should increase the availability of therapeutic options for alcohol-induced injuries of liver, pancreas and gastrointestinal (GI) tract. A high concentration of ethanol reduces GI and pancreas blood flow. Ethanol-induced GI hemorrhage, GI ulcer, and pancreatitis are initiated by the microcirculatory disturbance of GI mucosa and pancreas. Ethanol administration induces an increase in vasoactive agents such as endothelin and nitric oxide and oxidative stress. They appear to be involved in ethanol-induced GI and pancreatic injury. Regarding the effects of ethanol on the liver, small amount of ethanol increases hepatic blood flow, and prevents gut ischemia/reperfusion (I/R)-induced hepatic microvascular dysfunction and subsequent liver injury. While large amount of ethanol itself causes hepatic microvascular dysfunction, and aggravates the gut I/R-induced hepatic microvascular dysfunction and subsequent liver injury. Vasoactive agents and oxidative stress also appear to be involved in the liver injury. In endotoxemic animals, even small amount of ethanol causes hepatic microvascular dysfunction. Chronic ethanol consumption aggravates endotoxin-induced hepatic microvascular dysfunction. Chronic ethanol consumption aggravates gut I/R-induced leukostasis in the liver and hepatocellular injury associated with an enhanced expression of adhesion molecules, while it prevents the gut I/R-induced sinusoidal perfusion injury. Thus, effects of chronic ethanol consumption on the I/R injury are still controversial.
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PMID:[Effect of alcohol on organ microcirculation: its relation to hepatic, pancreatic and gastrointestinal diseases due to alcohol]. 1172 32


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