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)

Administration of total parenteral nutrition (TPN) solutions high in branched chain amino acids (BCAA) is thought to improve metabolic support during stress. This prospective, randomized, double blind study compared 45 per cent BCAA with 25 per cent BCAA in 12 patients. Seven patients had multiple trauma; two, gastrointestinal surgery; one, pancreatitis; and two, cirrhosis. The TPN regimen was 1.0-1.5 gm/kg/day amino acids and 30-45 glucose kcal/kg/day. The BCAA formula used was high in isoleucine and valine, but not leucine. Amino acid plasma levels, blood chemistries, 3-methylhistidine excretion, and nitrogen balance were studied. Control studies showed negative nitrogen balance (-7.1 +/- 2.9 gm) (mean +/- SEM), elevated insulin (61 +/- 21 microunit/ml), and elevated 3-methylhistidine (3MH) excretion (688 +/- 309 micromol); plasma leucine (93 +/- 11 nmol/ml) and isoleucine (37 +/- 23) were low, and valine (155 +/- 20) was elevated. Plasma methionine (40 +/- 9) and tyrosine (70 +/- 12) were high normal. Phenylalanine (85 +/- 5) was elevated. Both groups showed increased nitrogen excretion and positive nitrogen balance during the study (25 per cent, 2.0 +/- 1.4 gm/day; 45 per cent, 1.2 +/- 2.6 gm/day). Three-methylhistidine excretion changed little in either group (557 +/- 149, 414 +/- 91), insulin rose (135 +/- 27, 65 +/- 19), and plasma leucine (82 +/- 4, 71 +/- 9) changed little. Plasma isoleucine (51 +/- 3, 155 +/- 16) and valine (173 +/- 11, 691 +/- 23) both rose, more in the 45 per cent group. Methionine (67 +/- 12, 37 +/- 4) and tyrosine (51 +/- 6, 50 +/- 10) changed little.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Comparison of total parenteral nutrition with 25 per cent and 45 per cent branched chain amino acids in stressed patients. 393 93

The effects of growth hormone treatment and dietary alanine supplementation, individually and in combination, were studied in five patients with organic acidemias. Three patients had propionic acidemia, one had 3-hydroxyisobutyric acidemia, and one had a defect in isoleucine metabolism. Two patients with propionic acidemia had decreased growth hormone secretion in response to provocative stimuli (intravenous L-arginine and oral levodopa or clonidine); the remaining subjects had sufficient growth hormone secretion. Three of four subjects in whom IGF1 was measured showed subnormal concentrations at baseline (including two with normal growth hormone secretory responses). All patients showed an increase in linear growth with growth hormone. In the four patients studied, all had a significant increase in nitrogen retention over baseline with alanine or growth hormone alone, or with the combination of growth hormone and alanine, with a much greater effect of growth hormone. Lean body mass and body fat composition tended to become normal with treatment. Protein tolerance increased, and when the patients' dietary protein intakes were increased between 20 and 60% they maintained positive nitrogen balance, without a significant increase in metabolite excretion. One patient with propionic acidemia expired during the time of the study, following a course of recurrent pancreatitis and an episode of acute basal ganglia infarction. All of the other subjects showed clinical improvement (decreased incidence of ketoacidotic episodes and decreased frequency of hospital admission and school absence) during treatment, and even the patient who expired remained metabolically stable up to and through the terminal event. We conclude that growth hormone may be of value in the management of patients with organic acidemia.
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PMID:Anabolic effect of human growth hormone: management of inherited disorders of catabolic pathways. 799 63

The innervation of the sphincter of Oddi (SO) has been extensively studied experimentally, but human studies have not been published, which is why this study was undertaken. Biopsies, taken by gastroscopy-biopsy forceps from duodenal epithelium of the papilla of Vater and from ampullary epithelium after sphincterotomy, did not demonstrate nerves and could not be used for studying SO innervation. Therefore SO specimens were obtained from brain-dead organ donors (N = 5) and from autopsies (N = 14). By staining with a myelin marker S-100, a rich network of nerves was demonstrated in SO. The occurrence of vasoactive intestinal polypeptide (VIP), peptide histidine-isoleucine (PHI) (or its immunologically similar human equivalent peptide histidine methioninamide, PHM), neuropeptide Y, calcitonin gene-related peptide (CGRP), galanin, substance P, enkephalin, bombesin, and somatostatin were studied by immunohistochemical technique. SO demonstrated immunoreactivity for VIP, PHI (PHM), neuropeptide Y, CGRP, galanin, somatostatin, substance P, and enkephalin, but no immunoreactivity was observed for bombesin. The SO immunoreactivity was similar in specimens from organ donors and from autopsies of victims of violence without pancreatobiliary diseases (N = 3) when the specimens were taken within 48 hr of death. Autopsy specimens of SO from subjects with gallstone disease (N = 5), recurrent pancreatitis (N = 3) or periampullary carcinoma (N = 3) also demonstrated similar immunoreactivity. We conclude that VIP-, PHI- (PHM-), neuropeptide Y-, CGRP-, galanin-, substance P-, somatostatin-, and enkephalin-like immunoreactivity occur in human SO. These neuropeptides may have role in the neural control of human SO function.
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PMID:Peptidergic innervation of human sphincter of Oddi. 831 11

Hereditary, chronic pancreatitis is an autosomal dominant genetic disorder, frequently associated with two point mutations in the cationic trypsinogen gene. The mutations result in characteristic changes in the amino-acid sequence of trypsinogen: an arginine residue at position 117 is changed to histidine (Arg117-->His) or an asparagine residue at position 21 is replaced by isoleucine (Asn21-->Ile). Current opinion on the pathogenesis of hereditary pancreatitis suggests that the mutations lead to increased trypsin activity in the pancreatic tissue as a result of enhanced autoactivation of trypsinogen or decreased autocatalytic degradation (autolysis) of trypsin. To investigate the relationship between the altered properties of mutant trypsinogens and the pathomechanism of pancreatitis, wild-type and two mutant forms of recombinant human cationic trypsinogen were produced and autoactivation of trypsinogens and autolysis of trypsins were studied. The results indicate that trypsin stabilization (i.e. decreased autolysis) caused by the Arg117-->His mutation may contribute to the development of pancreatitis, however, the Asn21-->Ile mutation has no such effect. In contrast, enhanced autoactivation of mutant trypsinogens may contribute to the pathogenesis of both forms of hereditary pancreatitis. This notion is strongly supported by the clear correlation between the autoactivation rates of mutant trypsinogens and the severity of clinical symptoms.
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PMID:[Significance of trypsinogen gene mutations in the etiology of hereditary pancreatitis]. 1132 17

A patient with severe hypertriglyceridemia and recurrent pancreatitis was found to have significantly decreased lipoprotein lipase (LPL) activity and normal apolipoprotein C-II concentration in post-heparin plasma. DNA analysis of the LPL gene revealed two mutations, one of which was a novel homozygous G-->C substitution, resulting in the conversion of a translation initiation codon methionine to isoleucine (LPL-1). The second was the previously reported heterozygous substitution of glutamic acid at residue 242 with lysine (LPL-242). In vitro expression of both mutations separately or in combination demonstrated that LPL-1 had approximately 3% protein mass and 2% activity, whereas LPL-242 had undetectable activity but normal mass. The combined mutation LPL-1-242 exhibited similar changes as for LPL-1, with markedly reduced mass, and for LPL-242, with undetectable activity. These results suggest that the homozygous initiator codon mutation rather than the heterozygous LPL-242 alteration was mainly responsible for the patient phenotypes.
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PMID:A novel substitution at the translation initiator codon (ATG-->ATC) of the lipoprotein lipase gene is mainly responsible for lipoprotein lipase deficiency in a patient with severe hypertriglyceridemia and recurrent pancreatitis. 1643 Dec 16

The etiology and pathogenesis of pancreatitis remains unclear. In the presence of pancreatic inflammation, metabolite abnormalities appear before transformation of tissue structure and changes in functions occur. Detection of abnormalities in metabolite levels facilitates a greater understanding of the pathophysiological events and aids in the early diagnosis of the disease. In this study, metabolic profiles from the pancreas of Wistar rats were examined using high-resolution proton magic angle spinning nuclear magnetic resonance (MAS NMR) spectroscopy to investigate the metabolite indicator(s) of acute necrotizing pancreatitis (ANP) and chronic pancreatitis (CP). The animals were divided into three groups: those with histologically confirmed ANP (n = 7), those with CP (n = 6) and a control group (n = 9). The processed NMR spectra were analyzed using principal component analysis (PCA) to extract characteristic metabolites of ANP and CP. Levels of leucine, isoleucine and valine were increased in the ANP group, whereas an opposite trend was observed in the CP group. Increases in phosphocholine, glycerophosphocholine and choline levels, and decreases in fatty acids, lactate, betaine and glycine levels were observed in both the ANP and CP groups. Additionally, the lipid content in the CP group was higher than that observed in the ANP group. An increase in taurine levels was observed only in the CP group. In conclusion, pancreatitis causes a disruption of the metabolism in the pancreas at a molecular level, with increased taurine levels being a potential metabolite indicator for those with CP.
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PMID:Metabolic characteristics of acute necrotizing pancreatitis and chronic pancreatitis. 2257 38