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)

Oral contraceptive (OC) use is discussed as a factor in various diseases and disorders of internal medicine. Studies show a significant increase in the risk of developing thromboembolism, pulmonary embolism, cerebrovascular incidents, and coronary infarction among OC users. These problems are caused by changes in blood coagulation, hemodynamics, fibrinolysis, and the damaging of vascular walls, all of which are attributable to OC use. OC use leads to a minor hypertension in 1% of users during the first year of use and in 2.5% by the fifth year. This is initially caused by increased angiotensinogen production in the liver; later, sodium retention caused by the gestagen OC component, mineralocorticoid activity and vascular damage play a part in causing this hypertension. Glucose tolerance is reduced by OCs; lipid metabolism is affected in many ways: e.g. elevation of plasma triglyceride levels. OC users run an increased risk of developing hepatic tumors. Jaundice, Budd Chiari syndrome, gall stones, and pancreatitis have all been observed among OC users. Contraindications to OC use are listed.
 ...
PMID:[Internal medicine problems regarding contraception. Part I]. 744 16

Our previous studies have provided evidence for the existence of an intrinsic renin-angiotensin system (RAS) in the rat pancreas, which may play a role in the regulation of pancreatic microcirculation and ductal secretion. Such a pancreatic RAS has recently shown to be activated by chronic hypoxia. The activation of a local RAS in the pancreas by chronic hypoxia and its significance of changes may be important for the physiological and pathophysiological aspects of the pancreas. In the present study, the regulation of experimentally induced acute pancreatitis on the expression of local RAS in the pancreas was investigated using Western blot, semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemical approaches. Results from Western blot demonstrated that experimentally induced pancreatitis caused significantly increased expression of the pancreatic RAS component proteins. In keeping with the protein level, RT-PCR analysis also revealed the enhanced expression of pancreatic RAS genes, notably the angiotensinogen in experimental pancreatitis. Immunohistochemical results further demonstrated that increased immunoreactivity for RAS in experimental pancreatitis was predominantly localized to the endothelia and epithelia of pancreatic vasculature and ductal system respectively. The data indicate that experimental pancreatitis may elicit activation of a local RAS in the pancreas. Such an activation of pancreatic RAS and its significance of differential changes in individual RAS components could play a role in the pathophysiology of acute pancreatitis
 ...
PMID:Regulated expression of pancreatic renin-angiotensin system in experimental pancreatitis. 1099 30

The circulating renin-angiotensin system (RAS) plays an important role in the maintenance of blood pressure and fluid homeostasis. Recently, there has been a shift of emphasis from the circulating RAS to the local RAS in the regulation of individual tissue functions via a paracrine and/or autocrine mechanism. In fact, a local RAS has been proposed to be present in an array of tissues including the brain, heart, kidney and gonads. Our previous studies have provided solid evidence that several key elements of the RAS, notably angiotensinogen and renin, are present in the rat pancreas. The data support the existence of an intrinsic RAS in the pancreas and this local RAS may be important for the exocrine/endocrine functions of the pancreas. Interestingly, such a pancreatic RAS has been demonstrated to be markedly activated by experimental rat models of chronic hypoxia and acute pancreatitis. The activation of the pancreatic RAS by chronic hypoxia and experimental pancreatitis could play a role in the physiology and pathophysiology of the pancreas. The significant changes of pancreatic RAS may have clinical relevance to acute pancreatitis and hypoxia-induced injury in the pancreas.
 ...
PMID:Local renin-angiotensin system in the pancreas: the significance of changes by chronic hypoxia and acute pancreatitis. 1186 15

The pancreas contains a local renin-angiotensin system (RAS), which is subject to activation by experimental pancreatitis. In the exocrine pancreas, angiotensin II receptor subtypes AT1 and AT2 have been localized in the pancreatic ducts, blood vessels and acinar cells. We hypothesize that local RAS activities may have a potential role in regulating pancreatic acinar digestive enzyme secretion. The present study was designed to elucidate firstly the existence of RAS components in pancreatic acinar cells and their regulation by acute pancreatitis. Secondly, the differential roles of AT1 and AT2 receptors in controlling digestive enzyme secretion from dispersed functional pancreatic acini were also investigated. The mRNA levels of RAS components were assessed by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR). Acinar secretions were assayed by the measurement of alpha-amylase and lipase activities. Induction of acute pancreatitis was achieved by hyperstimulation of two intraperitoneal (i.p.) injections of cerulein (50 microg/kg/h). Results from RT-PCR showed that the mRNA levels of the major RAS components (angiotensinogen, AT1 and AT2 receptors) were expressed in isolated rat pancreatic acinar cells, and they were upregulated during pancreatitis. Exogenous addition of angiotensin II could stimulate a dose-dependent release of digestive enzymes from the acinar cells. Administration of the selective AT1 receptor antagonist losartan significantly inhibited the acinar digestion enzyme secretion in both normal and pancreatitis-induced acini. However, a specific AT2 receptor blocker PD123319 did not exhibit such a suppressive effect. These data indicate the existence of an acinar RAS in the pancreas of potential importance in the physiological regulation of digestive enzyme secretion. The differential actions of AT1 and AT2 receptors and their upregulation may have clinical relevance to the pathogenesis and management of acute pancreatitis.
 ...
PMID:The role of the pancreatic renin-angiotensin system in acinar digestive enzyme secretion and in acute pancreatitis. 1512 Apr 83

Angiotensin II is a key mediator of inflammation, and nuclear factor-kappaB (NF-kappaB) plays a critical role in various inflammatory diseases, including acute pancreatitis (AP). This study sought to elucidate the mechanism mediating angiotensin II involvement in angiotensin II type 1 (AT1) receptor-mediated NF-kappaB activation, and ultimately in proinflammatory actions of AP pathogenesis. A rat model of obstructive pancreatitis was induced by ligation of the common biliopancreatic duct. Pancreatic injury was determined by assessing pancreatic histology, myeloperoxidase activity, and serum interleukin-6. Protein levels of pancreatic angiotensinogen and AT1 receptor as well as NF-kappaB inhibitory subunits (IkappaBalpha and IkappaBbeta) and phospho-NF-kappaB p65, kappaB-related proteins (intercellular adhesion molecule-1, cyclooxygenase-2, and interleukin-1), and NADPH oxidase isoforms p67 and p22 were examined by Western blot. Nuclear kappaB binding activity and degree of oxidative stress were determined by electrophoretic mobility shift assay and glutathione/nitrotyrosine examination, respectively. The effects of losartan, an AT1 receptor antagonist, on NF-kappaB-mediated proinflammatory actions were also assessed. Induction of AP was associated with a time-dependent increase in pancreatic angiotensinogen levels. AT1 receptor blockade with losartan improved the pancreatic histological damage, myeloperoxidase activity, and serum interleukin-6. Losartan treatment also reduced AP-associated depletion of IkappaBbeta and elevation of phospho-NF-kappaB p65 protein expression as well as the enhanced nuclear kappaB binding activity and elevated levels of kappaB-related proteins. In addition, losartan treatment suppressed pancreatic glutathione and nitrotyrosine levels, which were consistent with decreased NADPH oxidase expression. These data provide substantial evidence that angiotensin II is involved in AT1 receptor-mediated NADPH oxidase-dependent NF-kappaB activation; thus, it might ultimately promote proinflammatory actions during AP pathogenesis.
 ...
PMID:Angiotensin II type 1 receptor-dependent nuclear factor-kappaB activation-mediated proinflammatory actions in a rat model of obstructive acute pancreatitis. 1761 60