UMLS:C0016382 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0016382 (flushing)
6,387 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Vertical concentration profiles of diclofenac were measured in Lake Greifensee (Switzerland) under mixed (February/December) and stratified (July) lake conditions. The concentrations ranged from 1 to 12 ng/L and were lower in summer than in winter, especially near the lake surface, pointing to an efficient elimination of diclofenac by photodegradation in the lake. Laboratory experiments confirmed the rapid photodegradation of diclofenac in water when exposed to sunlight. First-order reaction rates varied seasonally according to actual solar radiation (half-lives, tau = 0.2-1.7 h). The initial photoproduct was 8-chlorocarbazole-1-acetic acid, which photodegraded even faster than the parent compound. Carbazole-1-acetic acid, previously reported as the main photoproduct, was only formed in the presence of a H-source, such as methanol. In the absence of a H-source and of air, hydroxycarbazole-1-acetic acid was formed. However, hydroxycarbazole-1-acetic acid was not observed in the presence of air and, thus, under conditions similar to those in a lake, likely because of its rapid further photooxidation. Computer simulations using a one-dimensional lake model taking actual solar radiation and flushing data of the lake into account confirmed that photolysis is the predominant elimination pathway for diclofenac in Lake Greifensee. These calculations further showed that the expected concentrations of the photoproduct 8-chlorocarbazole-1-acetic acid are less than the current detection limits of approximately 3 ng/L.
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PMID:Photodegradation of the pharmaceutical drug diclofenac in a lake: pathway, field measurements, and mathematical modeling. 1135 24

Multiple forms and gene loci of human alcohol dehydrogenase (ADH EC: 1.2.1.3) and aldehyde dehydrogenase (ALDH, EC: 1.2.1.3) in the major pathway of alcohol metabolism have been found and characterized in the last two decades. With the coenzyme NAD, these enzymes catalyze the reversible conversion of organic alcohols to ketones or aldehydes, and aldehyde to acetic acid. The ADH genes are mapped to chromosome 4p21-25, but the ALDH genes are localized at different chromosomes. The cytochrome P450 2E1 (CYP2E1) gene, which is mapped to chromosome 10q24.3-qter contributes also the conversion of ethanol to acetaldehyde. Genetic polymorphisms have been reported in these alcohol metabolizing enzymes. The metabolisms of alcohol and acetaldehyde in liver and blood after drinking alcohol are thought to be influenced by the interactive action of these enzymes. Amongst the five major classes of the ADH subunits (alpha, beta, gamma, pi, chi, sigma), beta and gamma subunits show genetic polymorphisms. Recently a new nomenclature for ALDH genes has been recommend based on divergent evolution and chromosomal mapping. Two major isoforms designated as cytosolic ALDH1 and mitochondrial ALDH2 can be distinguished by their electrophoretic and kinetic properties as well as by their subcellular localization. Mitochondrial ALDH2 is a major enzyme in the oxidation of acetaldehyde derived from ethanol metabolism. The catalytic deficiency of ALDH2 isozyme is responsible for flushing and other vasomotor symptoms caused by higher acetaldehyde levels after alcohol intake. So far, frequencies of the two alleles of ALDH2 in Mongoloid have been reported in the different population groups. The catalytic deficiency of ALDH2 is caused by a structural point mutation at amino acid position 487, where a substitution of Glu to Lys resulting from a transition of G (C) to A (T) at 1510 nucleotide from the initiation codon has occurred. Individuals deficient in ALDH2 activity refrain from excessive drinking of alcohol due to the aversive reactions, leading to protection against alcoholism. Prevalence of the ALDH2*1 allele is associated with alcoholism, and subsequent studies have confirmed the allelic association with alcoholism in different ethnic groups. The effects of polymorphisms of ADH2 and CYP2E1 remained controversial, even in the same ethnic group. Investigation of mutations for the transacting cis-element in promoter region of the ALDH2 gene will provide important information with respect to regulation of this gene. Transfection assays using the first 600 bp of the upstream nucleotide sequences indicated that a region from -75 to -120 was necessary for the ALDH2 gene expression, and especially NF-Y/CP1 binding site from -92 to -96 (CCAAT box) is important in the expression of the gene. A novel polymorphism due to the nucleotide replacement at -357 G to A was found in all the population groups. Alcoholism is thought to be a multifactorial disease with complex mode of inheritance in addition to psychological and social factors, and many studies of family, adoption and twins concerning alcoholism have revealed that hereditary factor is an important determinant for developing alcoholism. Genetic association studies have contributed to the identification of a number of genetic risk factors for the chronic diseases influenced by genetic disorders and environmental factors.
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PMID:[Classification of alcohol metabolizing enzymes and polymorphisms--specificity in Japanese]. 1139 42

This paper presents an evaluation of different extracting solutions for the removal of phenanthrene, lead and zinc from a contaminated soil obtained from a former manufactured gas plant site. The field soil contained 50%-88% sand, 11%-35% fines, 2.7%-3.7% organic matter and high concentrations of phenanthrene (260 mg/kg), lead (50.6 mg/kg) and zinc (84.4 mg/kg). A series of batch extraction experiments were conducted using the field soil with different extracting solutions at various concentrations to investigate the removal efficiency and to optimize the concentration of each extractant. The results showed that removal efficiencies of different flushing systems were significantly influenced by their affinity and selectivity for the contaminants in the soil matrix. Non-ionic surfactants (Igepal CA720 and Tween 80) were found to be effective in removing phenanthrene, but they were ineffective in removing lead and zinc. Chelating agents (ethylenediamine tetra acetic acid, EDTA and diethylene triamine penta acetic acid, DTPA) and selected acids were effective in removing lead and zinc, but they were ineffective for the phenanthrene removal. Co-solvents and cyclodextrins were not effective for removal of any of the contaminants. A sequential use of the 0.2 M EDTA followed by 5% Tween 80 or 5% Tween 80 followed by 1 M citric acid was found to be effective for the removal of lead, zinc, and phenanthrene. Overall, it can be concluded that sequential use of different extracting solutions is required for the removal of both heavy metals and organics from field contaminated silty sand soils.
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PMID:Effect of different extraction agents on metal and organic contaminant removal from a field soil. 1562 49

Ulcerative colitis is associated with altered contractile activity and transit time of colon. On the other hand, cholecystokinin (CCK) has been shown to play an important role in regulation of gastrointestinal motor function including colonic contraction and transit. In the present study, an attempt was made to study the effect of proglumide, a CCK receptor antagonist on experimental colitis in rats. Experimental colitis was induced in male Sprague-Dawley rats by instilling 1 ml of 4% acetic acid followed by flushing with 0.5 ml air. The rats were kept in a head-down position for 30s. Finally, each rat received 1.5 ml colonic wash with 1.5 ml saline. Four groups of rats received proglumide orally (0, 250, 500 and 1000mg/kg). The first dose of proglumide was given 1 h before acetic acid challenge, whereas the second dose of proglumide was given 25 h after the first dose. Sham control rats received an equal volume of saline instead of acetic acid. Forty-eight hours after the acetic acid challenge, the colon was removed, weighed and split longitudinally and scored for injury. Part of the colon was used for histopathological study as well as analysis of myeloperoxidase (MPO) activity (as a marker of neutrophil activity). Acetic acid produced severe diarrhea and exfoliation of the colonic epithelium accompanied by extensive destruction of the mucosal interstitium. Proglumide dose dependently protected rats against acetic acid-induced increase in colon weight, diarrhea, MPO activity and colonic injury. Inhibition of CCK exerts a beneficial effect in experimental colitis. Further studies are warranted to determine the mechanism of protection and the therapeutic potential of CCK inhibitors.
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PMID:Proglumide attenuates experimental colitis in rats. 1581 62

Alcohol consumption is a risk factor for esophageal cancer. Acetaldehyde, a highly toxic intermediate produced from ethanol, is converted to acetic acid mainly by aldehyde dehydrogenase 2 (ALDH2) in the metabolic pathway of ethanol. Fifty percent of Japanese have inactive ALDH2 due to genetic polymorphism, which is considered to be a risk factor associated with esophageal cancer. In our previous study, we have demonstrated that ALDH2 is expressed in the esophagus with a considerable variation among individuals. In this study, we further investigated the expression of ALDH2 in esophagus and its relationship with risk factors of esophageal cancer. Tissue specimens resected from 51 patients with esophageal cancer were analyzed by immunohistochemistry using ALDH2-antibody. The immuno-staining of ALDH2 in the esophageal epithelium was compared with both the drinking habit and the occurrence of flushing that is closely associated with the ALDH2 deficiency. ALDH2 was not detectable in 8 (16%) among 51 specimens. All of the 8 patients were non- or light-drinkers but not heavy-drinkers. Among 18 patients showing the high level ALDH2 expression in the esophagus, 15 patients (83%) were heavy-drinkers. Although the relationship between the ALDH2 deficiency and drinking habit is not clear, the patients with ALDH2 deficiency tend to be non- or light drinkers while heavy-drinkers tend to have the active form of ALDH2. These results suggest that both inactive and active forms of ALDH2 are induced in the esophagus by heavy drinking and also support a hypothesis that ALDH2 deficiency might be a high-risk factor of esophageal cancer for the individuals having a heavy-drinking habit. To our knowledge, this is the first study demonstrating the induction of ALDH2 in the esophagus by ethanol consumption.
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PMID:Expression of aldehyde dehydrogenase 2 in the normal esophageal epithelium and alcohol consumption in patients with esophageal cancer. 1597 Apr 97

Gastro-intestinal carcinoids are slow growing tumors arising from enterochromaffin or Kulchitsky cells. Their clinical presentation depends on what combination of bioactive substances is secreted. Midgut carcinoid can present with the carcinoid syndrome in the presence of liver metastases. Its most typical clinical manifestations include cutaneous flushing and diarrhea. A nonspecific biochemical tumor marker for carcinoid tumors is serum chromogranin A and a specific marker for the carcinoid syndrome is the increased urinary excretion of 5-hydroxy indole acetic acid (5-HIAA). Localizing studies in carcinoid tumors/syndrome are: transabdominal ultrasonography (US), endoscopy, endoscopic US, videocapsule endoscopy, computerized tomography, magnetic resonance imaging, selective abdominal angiography, 111In-pentetreotide scintigraphy (and intraoperative radionuclide probe), 123I (131I)-metaiodobenzylguanidine (MIBG) scintigraphy, bone scintigraphy and 11C-5-HT positron emission tomography (PET). Therapies for carcinoid tumors/syndrome are: surgery, somatostatin analogs, interferon-alpha, radiotherapy, liver dearterialization, liver (chemo, or radio)-embolization, alcohol sclerotherapy of liver metastases, radiofrequency ablation of liver metastases, cryosurgery of liver metastases, occasionally liver transplantation, radiotherapy-coupled somatostatin analogs, 131I-MIBG and occasionally chemotherapy.
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PMID:Carcinoid syndrome: diagnosis and medical management. 1644 70

Spring-flushing, over-wintered buds of Douglas-fir (Pseudotsuga menziesii (Mirb.) Franco) produce new buds that may follow various developmental pathways. These include second flushing in early summer or dormancy before flushing during the following spring. Second flushing usually entails an initial release of apical dominance as some of the current-season upper lateral buds grow out. Four hypotheses concerning control of current bud outgrowth in spring-flushing shoots were tested: (1) apically derived auxin in the terminal spring-flushing shoot suppresses lateral bud outgrowth (second flushing); (2) cytokinin (0.5 mM benzyladenine) spray treatments given midway through the spring flush period induce bud formation; (3) similar cytokinin spray treatments induce the outgrowth of existing current lateral buds; and (4) defoliation of the terminal spring-flushing shoot promotes second flushing. Hypothesis 1 was supported by data demonstrating that decapitation-released apical dominance was completely restored by treatment with exogenous auxin (22.5 or 45 mM naphthalene acetic acid) (Thimann-Skoog test). Hypothesis 2 was marginally supported by a small, but significant increase in bud number; and Hypothesis 3 was strongly supported by a large increase in the number of outgrowing buds following cytokinin applications. Defoliation produced similar results to cytokinin application. We conclude that auxin and cytokinin play important repressive and promotive roles, respectively, in the control of second flushing in the terminal spring-flushing Douglas-fir shoot.
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PMID:Hormonal control of second flushing in Douglas-fir shoots. 1681 39

Carcinoid tumors are rare, often insidious neoplasms arising from neuroendocrine cells. The majority arise in the gastrointestinal system, and are often incidentally found during investigation, although some may present as an emergency bleed or perforation. The prosaic symptoms of flushing, diarrhea, and sweating are often overlooked; thus, the diagnosis is usually much delayed and the tumor is advanced at presentation. This diagnostic delay renders effective management difficult and adversely affects outcome. This overview provides a current assessment of the evolution of the diagnostic techniques available to establish an accurate biochemical (5-hydroxyindole-3-acetic acid and chromogranin A) and topographic diagnosis (octreoscan, radio-labeled metaidobenzylguanidine, computerized tomography, magnetic resonance imaging, positron emission tomography, enteroclysis, endoscopic ultrasound, enteroscopy, capsule endoscopy, and angiography) of carcinoid tumors. The utility and shortcomings of the respective modalities available are evaluated. Although considerable advances have been made in establishing the diagnosis of carcinoid tumors and in defining the topography of metastatic disease, the major limitation is the inability to establish an early and timely diagnosis before the advent of metastatic disease.
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PMID:Gastrointestinal carcinoids: the evolution of diagnostic strategies. 1691 96

A sequential injection-capillary electrophoresis (SI-CE) system for the fast and automated quantitative analysis of anions and cations is described. Because of the low sample load in capillary electrophoresis a split injection approach had to be used to achieve reliable hydrodynamic injection. The use of a capillary of 8 cm effective length allowed for the separation of five inorganic cations within 11 s. One common electrolyte solution containing 12 mM l-histidine and 2 mM 18-crown-6 whose pH value was adjusted to 4.0 with 10% v/v acetic acid was used for anions and cations, thus the analysis of both groups of analytes could be carried out in rapid sequence simply by switching the polarity of the high voltage supply. The system also allows automated flushing of the capillary. Detection limits between about 2 and 5 micromol l(-1) could be achieved with the contactless conductivity detector employed.
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PMID:Rapid electrophoretic separations in short capillaries using contactless conductivity detection and a sequential injection analysis manifold for hydrodynamic sample loading. 1702 29

(3R)-4-(4-Chlorobenzyl)-7-fluoro-5-(methylsulfonyl)-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl acetic acid (MK-0524) is a potent orally active human prostaglandin D(2) receptor 1 antagonist that is currently under development for the prevention of niacin-induced flushing. The major in vitro and in vivo metabolite of MK-0524 is the acyl glucuronic acid conjugate of the parent compound, M2. To compare metabolism of MK-0524 across preclinical species and humans, studies were undertaken to determine the in vitro kinetic parameters (K(m) and V(max)) for the glucuronidation of MK-0524 in Sprague-Dawley rat, beagle dog, cynomolgus monkey, and human liver microsomes, human intestinal microsomes, and in recombinant human UDP glucuronosyltransferases (UGT). A comparison of K(m) values indicated that UGT1A9 has the potential to catalyze the glucuronidation of MK-0524 in the liver, whereas UGT1A3 and UGT2B7 have the potential to catalyze the glucuronidation in the intestine. MK-0524 also was subject to phase I oxidative metabolism; however, the rate was significantly lower than that of glucuronidation. The rate of phase I metabolism was ranked as follows: rat approximately monkey > human intestine > dog > human liver with qualitatively similar metabolite profiles across species. In all the cases, the major metabolites were the monohydroxylated epimers (M1 and M4) and the keto-metabolite, M3. Use of inhibitory monoclonal antibodies and recombinant human cytochromes P450 suggested that CYP3A4 was the major isozyme involved in the oxidative metabolism of MK-0524, with a minor contribution from CYP2C9. The major metabolite in hepatocyte preparations was the acyl glucuronide, M2, with minor amounts of M1, M3, M4, and their corresponding glucuronides. Overall, the in vivo metabolism of MK-0524 is expected to proceed via glucuronidation, with minor contributions from oxidative pathways.
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PMID:Metabolism of MK-0524, a prostaglandin D2 receptor 1 antagonist, in microsomes and hepatocytes from preclinical species and humans. 1713 65

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