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Query: UMLS:C0030305 (pancreatitis)
 16,014 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Little is known about the changes in pancreatic enzyme storage in acute pancreatitis. We have performed flow cytometric studies of zymogen granules from rats with acute pancreatitis induced by hyperstimulation with caerulein. A comparison was made with rats treated with hydrocortisone (10 mg/kg/day) over 7 days before inducing pancreatitis in order to find out whether the amount of enzymes stored in the pancreas plays a key role in the development of pancreatitis. The potentially therapeutic effect of L-364,718 (0.1 mg/kg/day, for 7 days), a CCK receptor antagonist, was assayed in the rats with caerulein-induced pancreatitis which had previously received the hydrocortisone treatment. A significant increase in the intragranular enzyme content was observed 5 h after hyperstimulation with caerulein. The highest values were reached in the rats previously treated with hydrocortisone. The greatest pancreatic enzyme load was parallel to the highest values in plasma amylase, edema and haematocrit observed. Acute pancreatitis was reversed seven days later. At this stage smaller granules appeared in the pancreas whose enzyme content was similar to that of controls when no treatment was applied after pancreatitis. In contrast, L-364,718 administration prevented the favourable evolution of pancreatitis since the antagonism exerted on CCK receptors induced a blockade of secretion of the large amounts of enzymes stored in the pancreas. Moreover, the enzyme content in zymogen granules was below normal values since the stimulatory CCK action on enzyme synthesis can be inhibited by L-364,718. Our results suggest that the efficiency of CCK antagonists, as potential therapy, would also depend on the load of enzymes in the pancreas when acute pancreatitis is produced.
Mol Cell Biochem 1999 Oct
PMID:The recovery of acute pancreatitis depends on the enzyme amount stored in zymogen granules at early stages. 1056 81

Programmed cell death (apoptosis), a form of cell death, described by Kerr and Wyllie some 20 years ago, has generated considerable interest in recent years. The mechanisms by which this mode of cell death (seen both in animal and plant cells), takes place have been examined in detail. Extracellular signals and intracellular events have been elaborated. Of interest to the clinician, is the concentrated effort to study pharmacological modulation of programmed cell death. The attempt to influence the natural phenomenon of programmed cell death stems from the fact that it is reduced (like in cancer) or increased (like in neurodegenerative diseases) in several clinical situations. Thus, chemicals that can modify programmed cell death are likely to be potentially useful drugs. From foxglove, which gave digitalis to the Pacific Yew from which came taxol, plants have been a source of research material for useful drugs. Recently, a variety of plant extracts have been investigated for their ability to influence the apoptotic process. This article discusses some of the interesting data. The ability of plants to influence programmed cell death in cancerous cells in an attempt to arrest their proliferation has been the topic of much research. Various cell-lines like HL60, human hepatocellular carcinoma cell line (KIM-1), a cholangiocarcinoma cell-line (KMC-1), B-cell hybridomas, U937 a monocytic cell-line, HeLa cells, human lymphoid leukemia (MOLT-4B) cells and K562 cells have been studied. The agents found to induce programmed cell death (measured either morphologically or flow cytometrically) included extracts of plants like mistletoe and Semicarpus anacardium. Isolated compounds like bryonolic acid (from Trichosanthes kirilowii var. Japonica, crocin (from saffron) and allicin (from Allium sativum) have also been found to induce programmed cell death and therefore arrest proliferation. Even Chinese herbal medicine "Sho-saiko-to" induces programmed cell death in selected cancerous cell lines. Of considerable interest is the finding that Panax ginseng prevents irradiation-induced programmed cell death in hair follicles, suggesting important therapeutic implications. Nutraceuticals (dietary plants) like soya bean, garlic, ginger, green tea, etc. which have been suggested, in epidemiological studies, to reduce the incidence of cancer may do so by inducing programmed cell death. Soy bean extracts have been shown to prevent development of diseases like polycystic kidneys, while Artemisia asiatica attenuates cerulein-induced pancreatitis in rats. Interestingly enough, a number of food items as well as herbal medicines have been reported to produce toxic effects by inducing programmed cell death. For example, programmed cell death in isolated rat hepatocytes has been implicated in the hepatitis induced by a herbal medicine containing diterpinoids from germander. Other studies suggest that rapid progression of the betel- and tobacco-related oral squamous cell carcinomas may be associated with a simultaneous involvement of p53 and c-myc leading to inhibition of programmed cell death. Several mechanisms have been identified to underlie the modulation of programmed cell death by plants including endonuclease activation, induction of p53, activation of caspase 3 protease via a Bcl-2-insensitive pathway, potentiate free-radical formation and accumulation of sphinganine. Programmed cell death is a highly conserved mechanism of self-defense, also found to occur in plants. Hence, it is natural to assume that chemicals must exist in them to regulate programmed cell death in them. Thus, plants are likely to prove to be important sources of agents that will modulate programmed cell death.
Cell Mol Biol (Noisy-le-grand) 2000 Feb
PMID:Modulation of programmed cell death by medicinal plants. 1072 85

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
Mol Cell Endocrinol 2000 Aug 30
PMID:Regulated expression of pancreatic renin-angiotensin system in experimental pancreatitis. 1099 30

Over the past decade, gene conversion has been shown increasingly to be a cause of human disease. Through this process, a functional gene is converted into a mutant by a homologous, nonfunctional one. In this article, we demonstrate that gene conversion is a likely cause of the mutations of the human cationic trypsinogen (PRSS1) gene that are associated with hereditary or sporadic pancreatitis, including the R122H (CGC>CAT: c.365-366 GC>AT), N29I (AAC>ATC: c.86A>T), and A16V (GCC>GTC: c.47C>T) missense mutations. This hypothesis is strongly supported by four lines of observation. First, human group I trypsinogen genes are tandemly repeated and share a high sequence homology between them. Secondly, a possible donor sequence for each variant is present in the PRSS1 gene's paralog(s). Thirdly, there exist uninterrupted sequence tracts ranging from 30 to 114 bp in the putatively converted regions. Finally, Chi-like and palindromic sequences are found in the vicinity of these missense mutations. This theory, if correct, will make the pancreatitis-associated PRSS1 mutations a unique example, as it shows that a functional gene may be converted by several paralogs, and that such an event may even occur between two functional genes (i.e., the N29I mutation), resulting in disease. This adds further to the diversity of genetic mechanisms underlying human disease. In addition, this genetic finding provides, for the first time, concrete evidence of the contribution made by gene conversion to the molecular evolution of the human trypsinogen family.
Mol Genet Metab 2000 Nov
PMID:Gene conversion-like missense mutations in the human cationic trypsinogen gene and insights into the molecular evolution of the human trypsinogen family. 1107 13

We have used a microarray-based strategy to characterize, at the molecular level, the pancreatic emergency program set up by the pancreatic cells in response to pancreatitis. In this strategy, the phenotype of the pancreatitis-affected pancreas is established by characterization of a large number of its transcripts using a high-density mouse cDNA microarray. This method allows identification of transcripts differentially expressed during pancreatitis. We describe here the cloning, sequencing, and expression analysis of a new gene, named PIP49 (Pancreatitis Induced Protein 49). Its very strong expression is specific of acinar cells and occurs rapidly after initiation of the acute phase of pancreatitis. Analysis of its primary and secondary structures strongly suggests that PIP49 encodes a putative transmembrane protein.
Mol Cell Biol Res Commun 2000 Sep
PMID:Cloning and expression of the mouse PIP49 (Pancreatitis Induced Protein 49) mRNA which encodes a new putative transmembrane protein activated in the pancreas with acute pancreatitis. 1128 35

Over the past 5 years, several gain-of-function missense mutations in the human cationic trypsinogen gene (PRSS1, OMIM 276000) have been associated with hereditary and/or sporadic pancreatitis. This study reports a new pancreatitis-associated mutation--R116C (CGT > TGT: c.346C > T)--in the gene.
Mol Genet Metab 2001 Nov
PMID:Identification of a novel pancreatitis-associated missense mutation, R116C, in the human cationic trypsinogen gene (PRSS1). 1170 64

Syncollin is a small protein that is abundantly expressed in pancreatic acinar cells and that is tightly associated with the lumenal side of the zymogen granule membrane. To shed light on the hitherto unknown function of syncollin, we have generated syncollin-deficient mice. The mice are viable and show a normal pancreatic morphology as well as normal release kinetics in response to secretagogue stimulation. Although syncollin is highly enriched in zymogen granules, no change was found in the overall protein content and in the levels of chymotrypsin, trypsin, and amylase. However, syncollin-deficient mice reacted to caerulein hyperstimulation with a more severe pancreatitis. Furthermore, the rates of both protein synthesis and intracellular transport of secretory proteins were reduced. We conclude that syncollin plays a role in maturation and/or concentration of zymogens in zymogen granules.
Mol Cell Biol 2002 Mar
PMID:Loss of the zymogen granule protein syncollin affects pancreatic protein synthesis and transport but not secretion. 1183 20

Conjugation of xenobiotic alcohols with endogenous fatty acids is considered one of the mechanisms of their retention in the target organs. A number of fatty acid esters of alcohol's detected in the human tissues were found to be toxic in vivo and in vitro. Non-oxidative metabolism of ethanol resulting in the formation of fatty acid ethyl esters (FAEEs) appears to be one of the major pathways of ethanol disposition in the pancreas during chronic alcohol abuse, and could be associated with pancreatitis. In most cases, pancreatic damage occurs in alcoholics preceding the onset of clinical pancreatitis. Early markers of ethanol-induced pancreatitis could be important for early prevention of such injury. Although FAEEs have been implicated in the ethanol-induced pancreatitis, mechanism(s) of such injury is not well understood. Studies by others and by our own group have shown that plasma levels of FAEEs correlate well with plasma/blood alcohol concentration. FAEE synthase is known to catalyze the formation of FAEEs. The activity of FAEE synthase was found highest in the pancreas. Excessive synthesis of FAEEs during chronic alcohol abuse in the pancreas may be associated with pancreatic injury as supported by in vivo and cell culture studies. Human studies correlating plasma FAEE levels with that of markers of pancreatic injury could be important in developing markers of ethanol-induced toxicity. Although toxicity of exogenously administered FAEEs is shown in vivo and in vitro, the toxicity associated with endogenously formed FAEEs has not been studied. Therefore, studies regarding the role of endogenously formed FAEEs could be important in understanding the mechanism of ethanol-induced pancreatitis.
Cell Mol Biol (Noisy-le-grand) 2001
PMID:Fatty acid ethyl esters and ethanol-induced pancreatitis. 1193 65

There is growing evidence that immunocompetent cells are involved in the pathogenesis of chronic pancreatitis. Using a model of chronic pancreatitis induced by dibutyltin dichloride (DBTC) in rats, we have immunohistochemically phenotyped the infiltrating T lymphocytes, CD45RC+ cells, macrophages, as well as the IL-2 receptor as an activation marker during a time course of two months. In addition, the expression of CD44, of the integrin component CD18, and of MHC class II was determined. Furthermore, the isoforms of CD45 which are generated by alternative mRNA splicing were analysed using reverse transcription followed by the polymerase chain reaction-technique (RT-PCR). The pattern of the local leukocytes in the DBTC pancreatitis suggests that the acute unspecific inflammation is followed by an activation of T lymphocytes resulting in the chronic course of the disease.
Cell Mol Biol (Noisy-le-grand) 2002 May
PMID:Persistence of memory type lymphocytes in an experimental model of chronic pancreatitis in rats. 1203 Apr 36

Severe pancreatitis is frequently associated with acute lung injury (ALI) and the respiratory distress syndrome. The role of granulocyte-macrophage colony-stimulating factor (GM-CSF) in mediating the ALI associated with secretagogue-induced experimental pancreatitis was evaluated with GM-CSF knockout mice (GM-CSF -/-). Pancreatitis was induced by hourly (12x) intraperitoneal injection of a supramaximally stimulating dose of the cholecystokinin analog caerulein. The resulting pancreatitis was similar in GM-CSF-sufficient (GM-CSF +/+) control animals and GM-CSF -/- mice. Lung injury, quantitated by measuring lung myeloperoxidase activity (an indicator of neutrophil sequestration), alveolar-capillary permeability, and alveolar membrane thickness was less severe in GM-CSF -/- than in GM-CSF +/+ mice. In GM-CSF +/+ mice, pancreas, lung and serum GM-CSF levels increase during pancreatitis. Lung levels of macrophage inflammatory protein (MIP)-2 are also increased during pancreatitis, but, in this case, the rise is less profound in GM-CSF -/- mice than in GM-CSF +/+ controls. Administration of anti-MIP-2 antibodies was found to reduce the severity of pancreatitis-associated ALI. Our findings indicate that GM-CSF plays a critical role in coupling pancreatitis to ALI and suggest that GM-CSF may act indirectly by regulating the release of other proinflammatory factors including MIP-2.
Am J Physiol Lung Cell Mol Physiol 2002 Sep
PMID:In vivo evidence for the role of GM-CSF as a mediator in acute pancreatitis-associated lung injury. 1216 73


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