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)

Graft pancreatitis is an inflammatory disease leading to autodigestion of the gland. The failure of the pancreatic graft can be attributed to immunological or nonimmunological causes. It consists of a premature activation of pancreatic proenzymes. When complications such as bleeding or leaks have already occurred, surgical correction should be considered. The aim of this review is to draw the attention of surgeons to the complications that can easily be avoided.
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PMID:Graft pancreatitis: literature review. 1677 82

SPINK1 can inhibit up to 20% of trypsin activity, and may constitute one major mechanism to protect the pancreas from autodigestion. In 2000, Witt et al. first recognized the association between mutations in the SPINK1 gene and chronic pancreatitis (CP), but the significance of SPINK1 gene mutation in pancreatitis and its relation to alcohol consumption remains unclear in Japan. The aim of the present paper was to clarify the incidence of SPINK1 mutations in CP patients with various etiologies in Japan and, in addition, to examine the relationship between alcohol metabolism and the polymorphisms in the key enzymes, alcohol dehydrogenase (ADH) and aldehyde dehydrogenase-2 (ALDH2). A total of 156 patients with CP, and 165 healthy volunteers, all Japanese, were examined for the SPINK1 mutations by polymerase chain reaction-restriction fragment length polymorphism and direct sequencing. In Japan, the prevalence of [N34S; IVS1-37T > C] and [-215G > A; IVS3 + 2T > C] was significantly higher in patients with idiopathic CP (10.6% and 12.8%, respectively) than normal subjects (0.6% and 0%). The frequency of the [-215G > A; IVS3 + 2T > C] mutation in Japan was significantly higher than that reported in other populations. Concerning alcoholic CP, the [-215G > A; IVS3 + 2T > C] mutation was found in only a small number of patients (3.9%). On analysis of ADH2 and ALDH2 gene polymorphisms an association was found between ADH2*2 allele and alcoholic CP, and the ADH2*2/2*2 genotype had a tendency to increase the risk of developing pancreatic pseudocyst. In conclusion, in Japan the [-215G > A; IVS3 + 2T > C] mutation in the SPINK1 gene may form a unique genetic background for pancreatitis.
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PMID:SPINK1 gene mutations and pancreatitis in Japan. 1695 72

Fibrocalculous pancreatitis diabetes (FCPD), a late stage of tropical chronic pancreatitis (TCP), is classified as a secondary cause of diabetes mellitus resulting from pancreatic exocrine dysfunction. The distinctive features of FCPD and TCP are young age at onset, presence of large intraductal pancreatic calculi, and reported mainly in tropical developing countries. Their etiology is still obscure, but the autodigestion due to aberrant intraductal activation of zymogens by trypsin is thought to be a primary common event. Recently, mutations in SPINKI gene encoding a pancreatic secretory trypsin inhibitor have been reported in association with an increased risk of pancreatitis. We describe a heterozygous mutation, IVS3+2 T>C, of SPINK1 gene in a young Thai female patient with typical presentation of FCPD. To our knowledge, this is the first report of the SPINK1 gene mutation in a FCPD patient in Southeast Asia.
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PMID:A SPINK1 gene mutation in a Thai patient with fibrocalculous pancreatic diabetes. 1712 Sep 80

Acute pancreatitis (AP) is characterized by edema, acinar cell necrosis, hemorrhage, and severe inflammation of the pancreas. Patients with AP present with elevated blood and urine levels of pancreatic digestive enzymes, such as amylase and lipase. Severe AP may lead to systemic inflammatory response syndrome and multiorgan dysfunction syndrome, which account for the high mortality rate of AP. Although most (>80%) cases of AP are associated with gallstones and alcoholism, some are idiopathic. Although the pathogenesis of AP has not yet been elucidated, a common feature is the premature activation of trypsinogen within pancreatic tissues, which triggers autodigestion of the gland. Recent advances in basic research suggest that etiologic factors including cyclooxygenase-2, substance P, and angiotensin II may have novel roles in this disease. Basic research data obtained thus far have been based on animal models of AP ranging from mild edematous pancreatitis to severe necrotizing pancreatitis. In view of this, an adequate selection of experimental animal models is of paramount importance. Notwithstanding these animal models, it should be emphasized that none of these models mimic the clinical situation where varying degrees of severity usually occur. In this review, commonly used animal models of AP will be critically evaluated. A discussion of recent advances in our knowledge about AP risk factors is also included.
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PMID:Acute pancreatitis: animal models and recent advances in basic research. 1719 79

Acute pancreatitis is an autodigestive disease, in which the pancreatic tissue is damaged by the digestive enzymes produced by the acinar cells. Among the tissues in the mammalian body, pancreas has the highest concentration of the natural polyamine, spermidine. We have found that pancreas is very sensitive to acute decreases in the concentrations of the higher polyamines, spermidine and spermine. Activation of polyamine catabolism in transgenic rats overexpressing SSAT (spermidine/spermine-N(1)-acetyltransferase) in the pancreas leads to rapid depletion of these polyamines and to acute necrotizing pancreatitis. Replacement of the natural polyamines with methylated polyamine analogues before the induction of acute pancreatitis prevents the development of the disease. As premature trypsinogen activation is a common, early event leading to tissue injury in acute pancreatitis in human and in experimental animal models, we studied its role in polyamine catabolism-induced pancreatitis. Cathepsin B, a lysosomal hydrolase mediating trypsinogen activation, was activated just 2 h after induction of SSAT. Pre-treatment of the rats with bismethylspermine prevented pancreatic cathepsin B activation. Analysis of tissue ultrastructure by transmission electron microscopy revealed early dilatation of rough endoplasmic reticulum, probable disturbance of zymogen packaging, appearance of autophagosomes and later disruption of intracellular membranes and organelles. Based on these results, we suggest that rapid eradication of polyamines from cellular structures leads to premature zymogen activation and autodigestion of acinar cells.
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PMID:Mechanisms of polyamine catabolism-induced acute pancreatitis. 1737 Dec 71

Premature activation of digestive enzymes within the pancreas which leads to autodigestion of the gland is an early step in the pathogenesis of pancreatitis. Pancreatic injury is followed by other manifestations of inflammation including plasma extravasation, edema, and neutrophil infiltration which constitute the features of pancreatitis. Recent studies indicate that neural innervation of the pancreas may play an important role in the initiation and maintenance of the inflammatory response to injury. The pancreas is innervated by vagal, sympathetic and parasympathetic neurons, as well as sensory neurons. Activation of pancreatic primary sensory neurons causes the release of inflammatory neuropeptides both in the spinal cord to signal pain and in the pancreas itself where they produce plasma extravasation and neutrophil infiltration. Recent studies indicate that primary sensory neurons of the pancreas express transient receptor potential V1 (TRPV1) channels whose activation induces pancreatic inflammation. Moreover, blockade of these TRP channels significantly ameliorates experimental pancreatitis. This review describes our current understanding of the role of TRPV1 channels in pancreatitis and illustrates how this mechanism might be used to direct future treatments of pancreatic diseases.
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PMID:The role of Transient Receptor Potential Vanilloid 1 (TRPV1) channels in pancreatitis. 1742 42

Alcohol abuse is a major cause of pancreatitis, a condition that can manifest as both acute necroinflammation and chronic damage (acinar atrophy and fibrosis). It is generally accepted that alcohol-induced pancreatic injury is a consequence of the metabolism of alcohol by the pancreas (via the oxidative and non-oxidative pathways) producing the toxic metabolites acetaldehyde and fatty acid ethyl esters (FAEEs) respectively. Ethanol oxidation within the pancreas also leads to oxidant stress within the gland. Acetaldehyde, oxidant stress and FAEEs cause numerous molecular changes in pancreatic acinar cells which predispose the gland to autodigestion and necroinflammation. An important recent development relates to the identification of pancreatic stellate cells (PSCs) as the key mediators of alcohol-induced pancreatic fibrosis, when activated by ethanol, acetaldehyde or oxidant stress. Recent studies implicate the mitogen activated protein kinase (MAPK) pathway, a major signalling pathway in mammalian cells, as a critical regulator of the effects of ethanol and acetaldehyde on acinar cells as well as PSCs. Particularly important are the modulatory effects of ethanol and its metabolites on downstream transcription factors NF-kappaB and AP-1 (which regulate inflammatory responses via cytokine production) in acinar cells. In PSCs, additional signalling molecules identified as important to the process of ethanol and acetaldehyde-induced PSC activation include protein kinase C (PKC), phosphatidylinositol-3-kinase (PI3K) and peroxisome proliferator-activated receptor gamma (PPARgamma). Interestingly, cross-talk has been demonstrated between PI3K and MAPK in acetaldehyde-treated PSCs. The above advances in the identification of relevant signalling molecules may enable therapeutic targeting of these pathways so as to prevent/reduce alcohol-induced acute as well as chronic injury of the pancreas.
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PMID:Pancreatic MAP kinase pathways and acetaldehyde. 1759 Sep 96

New insight in the field of chronic pancreatitis was provided by the discovery of protease serine 1 (PRSS1) mutation, inherited by autosomal dominant trait in hereditary pancreatitis. Serine protease inhibitor, Kazal type 1 (SPINK1) is a potent protease inhibitor which prevents premature intrapancreatic activation of trypsin and pancreatic autodigestion. Strong associations of SPINK1 mutation and different forms of pancreatitis were suggested. However, it is unlikely that SPINK1 mutation alone can cause chronic pancreatitis. This mutation acts as a disease-modifier or plays a role within polygenic or multifactorial models. A 23 year-old young woman with chronic pancreatitis was recently discovered to have SPINK1 N34S heterozygous mutation cosegregated with two intronic mutations, IVS1-37TC and IVS3-69insTTTT, during the evaluation for potential cause of chronic idiopathic pancreatitis. The same mutation was identified in her mother. This is the first report in Korea suggesting that SPINK1 mutation would be a possible cause of chronic pancreatitis in a patient with familial background.
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PMID:[SPINK1 N34S mutation as a possible cause of chronic pancreatitis in a patient with familial background]. 1764 57

Autophagy is an evolutionarily preserved degradation process of cytoplasmic cellular constituents, which has been known for its role in protecting cells against stresses such as starvation and in eliminating defective subcellular structures. It is essentially a form of self-cannibalism - hence the name that means 'self-eating' - in which the cell breaks down its own components. By mostly morphological studies, autophagy has been linked to a variety of pathological processes such as neurodegenerative diseases and tumorigenesis, which highlights its biological and medical importance. However, whether autophagy protects from or causes disease is unclear. Autophagic morphology was described in human pancreatitis by Helin et al. in 1980. Actually, acute pancreatitis is one of the earlier pathological processes where autophagy has been described in a human tissue. Autophagy, autodigestion and cell death are early cellular events in acute pancreatitis. The aim of this review is to introduce a description of the autophagic process and to discuss the possible role of autophagy in acute pancreatitis.
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PMID:Autophagy and pancreas disease. 1871 76

Pancreatitis, a potentially fatal disease in which the pancreas digests itself as well as its surroundings, is a well recognized complication of hyperlipidemia. Fatty acids have toxic effects on pancreatic acinar cells and these are mediated by large sustained elevations of the cytosolic Ca(2+) concentration. An important component of the effect of fatty acids is due to inhibition of mitochondrial function and subsequent ATP depletion, which reduces the operation of Ca(2+)-activated ATPases in both the endoplasmic reticulum and the plasma membrane. One of the main causes of pancreatitis is alcohol abuse. Whereas the effects of even high alcohol concentrations on isolated pancreatic acinar cells are variable and often small, fatty acid ethyl esters--synthesized by combination of alcohol and fatty acids--consistently evoke major Ca(2+) release from intracellular stores, subsequently opening Ca(2+) entry channels in the plasma membrane. The crucial trigger for pancreatic autodigestion is intracellular trypsin activation. Although there is still uncertainty about the exact molecular mechanism by which this Ca(2+)-dependent process occurs, progress has been made in identifying a subcellular compartment--namely acid post-exocytotic endocytic vacuoles--in which this activation takes place.
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PMID:Fatty acids, alcohol and fatty acid ethyl esters: toxic Ca2+ signal generation and pancreatitis. 1932 25


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