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 microcirculatory changes in sodium taurocholate (ST)-induced pancreatitis. Groups of rats received as tracer either fluorescein isothiocyanate-dextran or acridine orange intravenously. The microcirculation of the exposed pancreas was observed by use of a video camera attached to an epi-illumination microscope. Vessel diameters and plaques of adherent leukocytes were measured with a digital image-analyzing system. In contrast to 0.4 ml of saline, intraductal infusion of ST (4%, 0.4 ml) induced a constriction of interlobular pancreatic arteries of 79 +/- 2% (P < 0.01) within 2 min. This constriction could not be antagonized by the leukotriene antagonist CGP-35949B. The radical scavengers superoxide dismutase (SOD) and N-(2-mercaptopropionyl)glycine (MPG) prevented the arterial constriction. Constriction of pancreatic arteries was accompanied by a decrease of erythrocyte velocity in the pancreatic capillaries. Flux in the head of the pancreas measured by laser-Doppler velocimetry decreased from 300 +/- 69 to 74 +/- 23 perfusion units (P < 0.01) after 446 +/- 159 s. Subsequently an increase of perfusion values was observed indicating reperfusion phenomena. ST induced leukocyte adherence to the walls of interlobular veins forming plaques constituting 39% of the observed venular cross section within 6 min. The leukotriene antagonist, SOD, or MPG prevented leukocyte adherence. Arterial constriction followed by ischemia-reperfusion and leukocyte adherence to venular endothelium during the reperfusion period represented the sequence of microcirculatory changes in ST-induced pancreatitis. The radical scavengers SOD and MPG prevented arterial constriction and leukocyte adherence to venular endothelium, indicating the involvement of free radicals in the pathogenesis of ST-induced pancreatitis in the rat.
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PMID:Arterial constriction, ischemia-reperfusion, and leukocyte adherence in acute pancreatitis. 833 66

Rats develop acute pancreatitis when infused iv for 3 h with cerulein (10 micrograms/kg/h). Autopsies of the pancreas seen by light microscope show interstitial edema, acinar cells vacuolization, and leukocyte margination in pancreatic capillaries; under electron microscope, severe damage concerning mitochondrial and zymogen granules structures are apparent. Particularly, swelling of the mitochondria and disruption of mitochondrial cristae was observed as well as formation of large vacuoles arising from zymogen granules and liposome fusion. A significant increase of lipid hydroperoxide level in the pancreatic tissue was observed. The purpose of this study was to evaluate the effect of 4-hydroxy-TEMPO--a low-mol-wt superoxide dismutase mimic--in a rat cerulein model of acute pancreatitis, with the expectation that free radical mediated hydroperoxide formation and tissue damage may be reduced significantly. Twenty-one male Wistar rats were divided into three groups: Group 1 (n = 5) served as a control and was infused iv for 3 h with physiologic saline; Group 2 (n = 8) was infused i.v. for 3 h with cerulein 10 micrograms/kg/h; and Group 3 (n = 8) infused i.v. both with cerulein and 4-hydroxy-TEMPO 22.6 mg/kg/h. Pancreatic tissue damage was quantified by measuring lipid hydroperoxide (LOOH) level, the weight of the organ, and by light and electron microscopic examination. 4-hydroxy-TEMPO penetration across cellular membrane barriers was quantified by ESR spectrometric measurements of 4-hydroxy-TEMPO concentration in pancreatic tissue samples and pancreatic juice as well. Administering 4-hydroxy-TEMPO to rats resulted in preventing both lipid hydroperoxide formation and severe morphological damage. 4-hydroxy-TEMPO crossed cellular membrane barriers and was excreted to pancreatic juice. Infusion of 4-hydroxy-TEMPO appears to prevent pancreatic injury caused by free radicals in experimental cerulein pancreatitis.
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PMID:Protective effect of 4-hydroxy-TEMPO, a low molecular weight superoxide dismutase mimic, on free radical toxicity in experimental pancreatitis. 853 Aug 31

Recent studies suggest that enhanced release of free oxygen radicals plays an important role in the pathogenesis of acute pancreatitis. Therefore, we studied the activity of the oxygen radical generating xanthine oxidase (XOD) in pancreatic tissue from rats treated with either dibutyltin dichloride/ethanol (DBTC/EtOH: 6 mg kg-1/13.7 mg kg-1, i.v.), ethanol alone (EtOH: 13.7 mmol kg-1, i.v.), or isotonic saline (NaCl) as control. We also investigated activities of the oxygen radical scavengers superoxide dismutase (SOD) and glutathione peroxidase (GPX). In addition, levels of the lipid peroxidation marker malondialdehyde (MDA) were determined. Enhanced activity of XOD was not detected. While SOD activity 1 and 6 h after treatment was significantly more reduced by DBTC/EtOH than by EtOH alone, no difference was found thereafter. Correspondingly, both regimens diminished GPX activity. Moreover, DBTC/EtOH and EtOH rapidly increased MDA levels within 1 h, indicating release of oxygen radicals early on after administration. After 16 h the MDA concentration was still elevated only in the DBTC/EtOH group. Although similar metabolic alterations were observed in both groups, only DBTC/EtOH induced acute interstitial pancreatitis within 24 h. We conclude that (a) a tissue imbalance between oxidants and antioxidants might be of importance in the pathogenesis of DBTC/EtOH-induced acute interstitial pancreatitis; (b) although EtOH increases oxygen radical levels, additional damage is required for development of acute pancreatitis; (c) XOD does not seem to be responsible for significant oxygen radical generation; and (d) the DBTC/EtOH model is a useful tool to study acute interstitial pancreatitis in rats.
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PMID:Oxygen radical generation and acute pancreatitis: effects of dibutyltin dichloride/ethanol and ethanol on rat pancreas. 853 55

Intraperitoneal injection of lipopolysaccharide (LPS) at a dose of 50 micrograms/kg increased the activity and the mRNA level of manganese superoxide dismutase (Mn-SOD) but did not change those of copper/zinc-SOD (Cu/Zn-SOD) in the rat pancreas. Both the formation of pancreatic edema and the elevation of serum amylase during caerulein pancreatitis were significantly relieved in the rats pretreated with LPS (50 micrograms/kg) compared with the rats without the pretreatment. These results support the view that superoxides play a key role in the pathogenesis of caerulein pancreatitis, and that Mn-SOD in the pancreas may work as a defense against the development of this disease.
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PMID:Lipopolysaccharide induces manganese superoxide dismutase in the rat pancreas: its role in caerulein pancreatitis. 855 79

The role of liver in the respiratory dysfunction associated with acute pancreatitis has been evaluated. For this purpose, an experimental necrohemorrhagic pancreatitis was induced in rats by intraductal administration of 3.5% sodium taurocholate. Additionally, a portocaval shunt was performed before induction of acute pancreatitis to prevent the initial passage through the liver of substances released by the pancreas. Twelve hours after the induction of pancreatitis, increases in lung prostacyclin and thromboxane B2 synthesis, decreased lung superoxide dismutase activity, and increases in plasma phospholipase A2 activity were found. In addition, inflammatory injury was evidenced in lung by histopathological analysis. The portocaval shunt was able to prevent the metabolic changes and ameliorate the inflammatory process in the lung, suggesting that the liver plays an active role in the systemic inflammatory response to acute pancreatitis.
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PMID:Hepatic involvement in pancreatitis-induced lung damage. 877 95

The role of oxidative stress in acute pancreatitis was investigated by comparing the pathological features of caerulein pancreatitis between transgenic mice that overexpress human Cu/Zn-superoxide dismutase (SOD) and nontransgenic littermates. Both the elevation of serum amylase and the formation of pancreatic edema during the pancreatitis were significantly reduced in the transgenic mice compared with the nontransgenic littermates. In the transgenic mice, the pancreatitis-associated reduction of Cu/Zn-SOD activity in the pancreatic tissues was significantly smaller than that in the nontransgenic mice. These results provide direct evidence that the elevation of intracellular oxygen radicals is an important factor for the progress of acute edematous pancreatitis.
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PMID:Transgenic copper/zinc-superoxide dismutase ameliorates caerulein-induced pancreatitis in mice. 914 18

The role of oxygen-derived free radicals in pancreatitis after pancreas transplantation was examined in a porcine pancreatic transplantation model. Trypsin activation, protease inhibitor consumption, kininogen consumption, and postoperative graft function were investigated in 24 pigs subjected to whole organ pancreaticoduodenal transplantation. The animals were divided into one control group and two groups treated with free radical scavengers. One group was given allopurinol, and one group was treated with superoxide dismutase in combination with catalase. In the early phase (within 1 hr) after reperfusion, no differences were seen between the groups as to protease activation. Neither trypsin-protease inhibitor imbalance nor any signs of kininogen consumption were seen. In a later phase (1-3 days after the transplantation), the trypsin activation, measured as high molecular weight immunoreactive cationic trypsin in plasma, was significantly less pronounced in allopurinol-treated animals. This finding indicates a less severe form of reperfusion pancreatitis in this group compared with the other groups. A tendency toward better function in the allopurinol-treated group was also seen. We conclude that oxygen-derived free radicals seem to be of importance in the development of reperfusion pancreatitis after pancreas transplantation in the pig. We also conclude that allopurinol, but not superoxide dismutase/catalase, possibly due to the administration regimens used in this series, is able to attenuate the trypsin activation and the development of pancreatitis in the later phase in this model.
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PMID:Role of oxygen-derived free radicals in protease activation after pancreas transplantation in the pig. 948 64

The aim of this study was to test the hypothesis that apoptosis can protect against experimental pancreatitis and induction of apoptosis by an extract of Artemisia asiatica (DA-9601) is beneficial in cerulein-induced pancreatis in rats. Pancreatitis was induced in 6-week-old male SPF Sprague-Dawley rats by two intravenous (i.v.) administrations of 40 microg/kg cerulein. To investigate the effects of DA-9601 on the severity of pancreatitis and extent of apoptosis, rats were treated with intragastric DA-9601, 30 mg/kg (D30), 100 mg/kg (D100), or 300 mg/kg (D300), intraperitoneal superoxide dismutase, 10,000 U/kg (SOD), and i.v. gabexate mesilate, 40 mg/kg (Foy), three times (30 min before cerulein injection, 30 and 90 min after cerulein injection). The control group was administered vehicle alone. Ten rats were included in each treatment group and control group. Rats were sacrificed 5 h after cerulein treatment. Serum amylase, histological activity index (HAI), pancreatic lipid peroxide levels, and apoptotic index [in situ hybridization by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL)] were determined. Gel electrophoresis was performed for the presence of DNA fragmentations. The results were as follows. Serum amylase was significantly increased in all cerulein-treated groups compared to normal controls (p < 0.001). The HAI was significantly decreased in only the D300 group compared to the controls (p < 0.05). The apoptotic index of the cerulein-alone group was 3.8 +/- 2.7, but the mean apoptotic indexes of the SOD and Foy groups were 16.4 +/- 4.6 and 13.3 +/- 1.8, respectively, a significant increase (p < 0.01). The apoptotic index was more significantly increased in the DA-9601-treated groups, dose dependently (8.4 +/- 3.4 in D30, 14.8 +/- 4.3 in D100, 24.2 +/- 4.7 in D300). A smearing pattern of DNA electrophoresis was noted in the DA-9601-treated groups. In conclusion, DA-9601, an extract of Artemisia, induced apoptosis of pancreatic acinar cells dose dependently and concomitantly attenuated the severity of pancreatitis.
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PMID:Induction of apoptosis with an extract of Artemisia asiatica attenuates the severity of cerulein-induced pancreatitis in rats. 970 Sep 46

We review here the oxygen insensitivity of the histochemical assay of glucose-6-phosphate dehydrogenase (G6PDH) activity to detect cancer cells. This inexpensive and rapid assay can be performed within half an hour. Discrimination between cancerous and noncancerous cells is based on a combination of elevated G6PDH activity, decreased superoxide dismutase (SOD) activity, and decreased lipid peroxidation in cancer cells. The test discriminates between adenomas and carcinomas of the colon with a certainty of >80% and has a high prognostic value for survival of colon cancer patients. Pancreatitis and pancreatic cancer are discriminated with a certainty of 100%. Therefore, the test can be applied by pathologists to provide additional information in difficult cases of diagnosis of cancer and for prognosis.
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PMID:Oxygen insensitivity of the histochemical assay of glucose-6-phosphate dehydrogenase activity for the discrimination between nonmalignant and malignant cells. 1021 51

Reactive oxygen species (ROS), generated by infiltrating neutrophils, are considered as an important regulator in the pathogenesis and deveolpment of pancreatitis. A hallmark of the inflammatory response is the induction of cytokine gene expression, which may be regulated by oxidant-sensitive transcription factor, nuclear factor-kappaB (NF-KB). Present study aims to investigate whether neutrophils primed by 4beta-phorbol 12beta-myristate 13alpha-acetate (PMA) affect the productions of H2O2 and lipid peroxide (LPO), NF-kappaB activation and cytokine production in pancreatic acinar cells, and whether these alterations were inhibited by N-acetylcysteine (NAC) and superoxide dismutase (SOD). ROS generation in neutrophils increased by PMA, which was inhibited by NAC and SOD. The productions of H2O2, LPO and TNF-alpha were increased with the amounts of PMA-primed neutrophils added to acinar cells while the productions of H2O2, LPO and cytokines increased with time. PMA-primed neutrophils resulted in the activation of two species of NF-kappaB dimers (a p50/p65 heterodimer and a p50 homodimer). Both NAC and SOD inhibited neutrophil-induced alterations in acinar cells. In conclusion, ROS, generated by neutrophils, activates NF-kappaB, resulting in upregulation of inflammatory cytokines in acinar cells. Antioxidants such as NAC might be clinically useful antiinflammatory agents by inhibiting oxidant-mediated activation of NF-KB and decreasing cytokine production.
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PMID:NF-kappaB and cytokines in pancreatic acinar cells. 1098 15


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