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

The involvement of active oxygen has been suggested in the development of cerulein-induced acute pancreatitis in rats. Previously, we directly detected pancreatic active oxygen (O2-) production in rats with cerulein-induced pancreatitis by using a supersensitive photon counter and a cypridina luciferin analogue (MCLA) that reacts specifically with O2- by emitting luminescence. In the present study, with the specific aim of determining the source of O2-, we prepared two groups of animals with cerulein-induced pancreatitis: those treated with allopurinol, a xanthine oxidase inhibitor; and those treated with nitrogen mustard, a leukopenia-inducing substance. In each of these two groups, pancreatic O2- production and the severity of pancreatic injuries were comparatively studied. In the leukopenic animal group, decreases in O2- dependent chemiluminescence and improvement in the pancreatic condition coincided. This suggests that neutrophils might be involved in experimentally induced pancreatitis as a source of active oxygen.
 ...
PMID:The involvement and sources of active oxygen in experimentally induced acute pancreatitis. 872 Jun 65

The effect of verapamil administration on the changes of prostanoid synthesis, and on free radical production associated with acute pancreatitis, has been evaluated. A necrohemorrhagic model of pancreatitis was induced in Wistar rats by intraductal administration of sodium taurocholate (3.5%). This model is associated with initial increases in prostanoid synthesis and peroxidative damage. Verapamil, administered before pancreatitis induction, prevented initial increases in 6-keto prostaglandin F1alpha (PGF1alpha) and thromboxane B2 (TXB2) but had no effect on PGF2alpha or PGE2 or on lipoperoxidative damage. These results indicate that verapamil administration prevents the increases in pancreatic vasoactive prostanoids (TXB2 and 6-keto PGF1alpha) without affecting the increased levels of PGE2 and PGF2alpha and has no effect on oxygen free radical production in the initial stages of experimental acute pancreatitis.
 ...
PMID:Calcium channel blockers in experimental acute pancreatitis: effect on tissue prostanoids and oxygen free radicals. 872 Jun 66

The inhibitive effects of anti-CD11a/CD18 (LFA-1) and anti-CD54 (ICAM-1) antibodies on the generation of superoxide anion (O2-) by polymorphonuclear leukocytes (PMNs) was elucidated in rats induced with experimental acute pancreatitis. We investigated the generation of O2- by PMNs in two protocols: in the first, we measured the active oxygen-producing ability of PMNs isolated from blood in normal rats; in the second, we measured it from blood, peritoneal cavity, and bronchial alveolar lavage fluid in rats 3 h after the induction of pancreatitis. In normal rats, although LFA-1 antibody attenuated the generation of O2-, ICAM-1 antibody did not. However, in pancreatitis rats, both LFA-1 and ICAM-1 antibodies reduced the generation of O2- by PMNs isolated from blood and the peritoneal cavity. These results showed not only that both LFA-1 and ICAM-1 antibodies have a protective effect on the generation of O2-, but also that LFA-1 has a direct inhibitive effect on the generation of O2- by PMNs in this model. Furthermore, histological studies showed there to be less neutrophil accumulation in the lungs of LFA-1- and ICAM-1-treated animals compared to control animals.
 ...
PMID:LFA-1 (CD11a/CD18) and ICAM-1 (CD54) antibodies attenuate superoxide anion release from polymorphonuclear leukocytes in rats with experimental acute pancreatitis. 872 Jun 67

Cerebral and extracerebral effects of moderate hypothermia (core temperature 32.5 degrees C-33.0 degrees C) were prospectively studied in 10 patients with severe closed head injury (Glasgow Coma Scale score < 7) in the intensive care unit of a university hospital. Hypothermia was induced by cooling the patient's body surface with water-circulating blankets. Before cooling, a conventional intracranial pressure (ICP) reduction therapy was applied, which remained unchanged throughout the study. Cerebral blood flow (CBF), cerebral metabolic rates for oxygen (CMRO2) and lactate (CMRL), and ICP were simultaneously measured prior to inducing hypothermia, after obtaining hypothermia, after 24 hours of hypothermia, and after rewarming. With respect to extracerebral effects, supplemental investigations were conducted 24 and 72 hours after rewarming. The median delay between injury and induction of hypothermia was 16 hours. Hypothermia reduced CMRO2 by 45% (p < 0.01), whereas CBF did not change significantly. Before cooling, six patients had elevated CMRL indicating cerebral ischemia. Cooling normalized CMRL in all patients (p < 0.01). The intracranial hypertension present prior to cooling declined markedly during hypothermia (p < 0.01) without significant rebound effects after rewarming. Cardiac index decreased by 18% after hypothermia was reached (p < 0.05), recovered at 24 hours of hypothermia, and surpassed baseline values after rewarming. Platelet counts dropped continuously up to 24 hours after rewarming (p < 0.01). Plasma coagulation tests did not show significant worsening. Creatinine clearance decreased during cooling (p < 0.01) and recovered by 24 hours after rewarming. Twenty-four hours after cooling had begun, eight patients had elevated serum lipase activity (p < 0.01) and four of them acquired pancreatitis. Rewarming normalized both pancreatic alterations. Seven patients made a good recovery; one survived severely disabled; and two patients died. Moderate hypothermia is effective in preventing secondary brain damage while reducing cerebral ischemia. However, there are potentially hazardous side effects that require additional monitoring.
 ...
PMID:Moderate hypothermia in patients with severe head injury: cerebral and extracerebral effects. 912 14

Despite the accumulation of large amounts of physiological and pathophysiological data on acute pancreatitis, our understanding of this disease remains still not clear. Among many etiological causes especial attention is focuse to the role of oxygen derived free radicals as mediators of inflammation. The significant oxidant-antioxidant imbalance found in acute experimental pancreatitis caused a new therapeutic approach eg.: the use of natural antioxidants in patients with pancreatitis.
 ...
PMID:Etiology and pathogenesis of acute pancreatitis--current view. 883 3

During the last 10 years, the role of oxidative stress in pancreatitis and the benefits or otherwise of antioxidants has been the subject of numerous research papers. There is general agreement that glutathione and other sulphydryl compounds are depleted while lipid peroxidation is increased in pancreatic tissue during the development of acute pancreatitis. Treatment with antioxidants has been shown to reduce acinar cell injury and oedema in various animal models of pancreatitis, suggesting that the sustained generation of reactive oxygen species depletes cellular antioxidant defences. Evidence for a role for bradykinin and nitric oxide in pancreatitis has been conflicting with some studies suggesting these agents might ameliorate pancreatic dysfunction by enhancing pancreatic blood flow and secretion in response to bradykinin-stimulated generation of nitric oxide from endothelium, while other studies suggest that nitric oxide potentiates pancreatic oxidative stress. Thus, there is clearly a need for well-designed clinical trials to evaluate the protective role of antioxidant therapy in acute pancreatitis.
 ...
PMID:Role of oxidative stress in the pathogenesis of acute pancreatitis. 886 64

Gastrointestinal tract failure may be involved in the development of systemic septic complications in acute pancreatitis. Systemic and intestinal circulation, intestinal permeability and absorptive function were evaluated in the early course of acute pancreatitis induced in rats by retrograde intraductal injection of 0.2 ml of 5 per cent sodium taurodeoxycholate and 0.4 nmol trypsin. A decrease in systemic arterial pressure and intestinal blood flow and an increase in intestinal permeability as measured by the leakage of 125I-labelled human serum albumin from blood to lumen were noted in the distal ileum and colon, reaching statistically significant differences 6 h after induction of pancreatitis. The transport of small molecular markers (sodium fluorescein and 51Cr-labelled ethylenediamine tetra-acetic acid) through the distal ileum and colon in vitro from the mucosal to the serosal site in Ussing chambers significantly increased in the early periodic (20-60 min) of incubation, while the passage of a macromolecular marker (ovalbumin) demonstrated a definite increase at 60-120 min of incubation. D-Xylose absorption from the gut lumen to the portal vein was significantly less in acute pancreatitis than after sham operation. Intravenous administration of the hydroxyl radical scavenger dimethylsulphoxide prevented the compromised intestinal permeability and gut absorptive capacity induced by acute pancreatitis, but did not affect the reduced arterial pressure and intestinal microcirculation. Cytotoxic oxygen-derived free radicals may contribute to the development of alterations in intestinal permeability and absorptive function found in the early stage of acute pancreatitis in the rat.
 ...
PMID:Alterations in intestinal function in acute pancreatitis in an experimental model. 902 31

Transforming growth factor-beta1 (TGF-beta1) is a multifunctional polypeptide that is related to the progression of chronic pancreatitis. However, the mechanism of beta-cell damage by TGF-beta1 is unknown. Treatment with TGF-beta1 enhanced internucleosomal DNA cleavage caused by exogenous hydrogen peroxide in a hamster pancreatic beta-cell line (HIT). TGF-beta1 also induced protein oxidation, assessed by measuring carbonyl groups in proteins, and was involved in reactions that lead to lipid peroxidation. This eventually destructs membrane lipids and forms malondialdehyde. We have investigated its effects on two major antioxidative enzymes, catalase and glutathione peroxidase (GPx). TGF-beta1 suppressed mRNA expression as well as reduced the activities of catalase and GPx. The decrease in the catalase and GPx activities in TGF-beta1-treated cells resulted in an increase in intracellular peroxides as judged by flow cytometric analysis using a peroxide-sensitive dye, 2',7'-dichlorofluorescin diacetate. These data suggest that the augmented production of reactive oxygen species by TGF-beta1 through suppression of antioxidative enzymes may cause cellular damage and consequent apoptosis and induce pancreatitis or diabetes.
 ...
PMID:TGF-beta1 triggers oxidative modifications and enhances apoptosis in HIT cells through accumulation of reactive oxygen species by suppression of catalase and glutathione peroxidase. 903 40

Oxygen-derived free radicals have been implicated in the pathogenesis of acute pancreatitis, yet adaptive responses in the pancreas in vivo to oxidative stress remain poorly defined. We have investigated expression of the stress protein heme oxygenase in the intact pancreas of rats with caerulein-induced pancreatitis and in cultured pancreatic acinar and islet cell lines. Expression of inducible heme oxygenase-1 (HO-1) in the pancreas in vivo was enhanced 12-24 h after induction of pancreatitis. In murine islet (betaTC3) and rat acinar (AR42J) pancreatic cells, H2O2, methyl viologen, cadmium chloride and diethylmaleate enhanced HO-1 expression in a dose- and time-dependent manner, without altering expression of constitutive HO-2. Enhanced expression of HO-1 in the pancreas in vivo and pancreatic islet and acinar cells may contribute to cellular defences against oxidative stress associated with acute pancreatitis.
 ...
PMID:Expression of stress proteins heme oxygenase-1 and -2 in acute pancreatitis and pancreatic islet betaTC3 and acinar AR42J cells. 908 94

Infectious complications are the leading cause of death in acute pancreatitis. Individual factors of immune defence could be of significance, whether or not a patient develops a severe course with infectious complications. In a prospective 5-year trial including 72 patients, we investigated 29 cellular and humoral markers of the body's defence system for their potential to indicate the severity and course of acute pancreatitis. Complement factors C3 and C4 as well as immunoglobulins IgG, IgM and IgA were normal, in general. Measurable levels of IL-1 alpha, IL-1 beta, IL-2 and sIL-2R could be detected only occasionally. Values of alpha 1-AT, TNF-alpha, TNF alpha-Rp75, neopterin, sICAM-1, IL-8, IL-1RA and sIL-6R did not correlate with a severe course. Due to the high magnitude of increase, CRP, IL-6 and granulocyte elastase were the best indicators of the inflammatory process. Delayed-type hypersensitivity response was the only early predictor of a severe course. It was superior over other cellular markers such as monocyte count or CD4+/CD8+ ratio. In vitro function of polymorphonuclear granulocytes (PMN) was not adequate to the severity of the disease already during the first week of illness. During further course, PMN motility and capacities to produce reactive oxygen species even worsened. The compromized PMN function could explain the frequent development of infectious complications in patients suffering from severe pancreatitis. These results should encourage new concepts of infection prophylaxis using stimulants of cellular defence.
 ...
PMID:[Cellular and humoral functions in acute pancreatitis]. 913


<< Previous 1 2 3 4 5 6 7 8 9 10