Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent reports have described increased levels of a fast-moving hemoglobin (Hb) fraction in alcoholic patients and formation in vitro of stable adducts between acetaldehyde and Hb as well as between acetaldehyde and albumin. In the present study, we have found that factors other than acetaldehyde concentration can influence the rate of stable adduct formation. HbAo was purified and its 2,3-diPglycerate removed by dialysis. Under anaerobic condition and at 37 degrees, acetaldehyde (5 microM) reacted with deoxyHbAo to form 0.26 +/- 0.02 (+/- SEM) nmol of stable adduct/149 nmol Hb in 2 hr. By comparison, acetaldehyde reacted more slowly with oxyHbAo and carbonylHbAo; the rates were 0.21 +/- 0.01 (p less than 0.001) and 0.18 +/- nmol/149 nmol Hb/2 hr (p less than 0.001), respectively. Pyridoxal 5'-phosphate (50-500 microM), under anaerobic condition, inhibited by 36-56 percent the irreversible binding of acetaldehyde to deoxyHbAo. Ascorbic acid (2.5-10 mM) increased by 31-46 percent (p less than 0.001) the irreversible binding of acetaldehyde to human serum albumin and by 8-10 percent (p less than 0.05) the irreversible reaction of acetaldehyde with serum proteins. We conclude that the nonenzymatic binding of acetaldehyde to Hb, human serum albumin and serum proteins is influenced by factors other than acetaldehyde concentration. These factors include oxygen tension, pyridoxal 5'-phosphate and ascorbic acid. Among these factors, oxygen tension may be the most important in vivo.
 ...
PMID:Regulation of the formation of stable adducts between acetaldehyde and blood proteins. 402 57

Because ethanol consumption is associated with increased susceptibility to infection, we examined the effects of ethanol and its metabolite acetaldehyde on human T-lymphocyte migration, an important functional component of cellular inflammatory responses. With a modified Boyden chamber system, ethanol at 0.25% and 0.50% (vol/vol) inhibited spontaneous motility of human T-lymphocytes, in a noncytotoxic manner, to 65% +/- 7% (mean +/- SEM) and 62% +/- 7% of control values of migration, respectively. When T-lymphocyte migration was stimulated by colchicine (10(-5) mol/L), incubation with ethanol (0.25% and 0.50%, vol/vol) decreased migration to 80% +/- 4% and 66% +/- 8% of control values, respectively. Similar degrees of inhibition of migration were obtained with acetaldehyde at concentrations five to 10 times less than ethanol. Ethanol was similarly capable of inhibiting T cell migration induced by dibutyryl cyclic guanosine monophosphate, but it had no effect on stimulated migration induced by a human chemokinetic lymphokine. Our study demonstrates that ethanol, at concentrations achievable in vivo, is capable of depressing T-lymphocyte migration. This effect might contribute to the immunosuppression associated with ethanol consumption.
 ...
PMID:Influence of ethanol on human T-lymphocyte migration. 609

A three-way crossover study was undertaken in 10 healthy subjects to characterize the reported disulfiram-like activity of moxalactam and to assess its influence on ethanol and acetaldehyde metabolism. On different occasions separated by at least 2 wk subjects were given in random order: 0.5 gm/kg ethanol orally, 0.5 gm/kg ethanol followed in 1 hr by 1.0 gm IV moxalactam, and 1.0 gm IV moxalactam every 8 hr for four doses followed by 0.5 gm/kg ethanol. Mean ethanol elimination rates of 13.1 +/- 0.76, 10.1 +/- 1.11, and 10.9 +/- 1.06 mg/dl/hr (mean +/- SEM) were observed in the three protocols, respectively. Corresponding mean estimated acetaldehyde clearance rates were 103.7 +/- 15.55, 92.8 +/- 13.79, and 97.3 +/- 10.41 l/min (mean +/- SEM). While no consistent moxalactam effect on ethanol or acetaldehyde elimination was observed, two subjects experienced mild disulfiram-like reactions to ethanol after moxalactam pretreatment. In one subject this reaction was associated with markedly elevated blood acetaldehyde concentrations. We conclude that moxalactam pretreatment may induce a disulfiram-like reaction after ethanol ingestion in some, probably due to inhibition of aldehyde dehydrogenase, and that alcoholic beverages are contraindicated in patients receiving moxalactam. We suggest, however, that such reactions will not occur when moxalactam is given after ethanol ingestion.
 ...
PMID:On the disulfiram-like activity of moxalactam. 621 49

The pharmacokinetic parameters controlling paraldehyde elimination were determined in nine infants infused with paraldehyde at the rate of 150 mg/kg/hr in a 5% solution in 5% dextrose for the treatment of status epilepticus. The mean +/- SEM values for the observed parameters were as follows: rate constant for the disposition of paraldehyde 0.0680 +/- 0.0071 hr,-1 half-life 10.2 +/- 1.0 hr; volume of distribution 1.73 +/- 0.20 L/kg; clearance 0.121 +/- 0.023 L/hr/kg. Phenobarbital administration prior to or within 24 hours of the cessation of paraldehyde infusion decreased both paraldehyde clearance and volume of distribution in a manner linearly related to the logarithm of the phenobarbital dose. The rate constant for paraldehyde elimination was decreased as a linear function of the logarithm of the combined dose of administered phenobarbital and phenytoin. No acetaldehyde was detected in any blood samples. Paraldehyde administration was not correlated with any adverse reactions or toxicities.
 ...
PMID:Pharmacokinetics of paraldehyde disposition in the neonate. 669 30

Female mice were injected intravenously with acetaldehyde on single (seventh, eighth or ninth), or on multiple (sixth to eighth, seventh to ninth) days, and examined on the tenth or twelfth day of gestation. Exposure to acetaldehyde on multiple days resulted in high incidence of embryonic resorptions. However, when females were injected on single days and examined on the tenth day, a high incidence of neural tube defects was encountered in surviving embryos. The neural tube anomalies were located at a number of sites along the neuraxis. When examined by scanning electron microscopy, the individual neuroepithelial cells in acetaldehyde-treated embryos exhibited a characteristic rounded-up appearance with small surface blebs and spiny processes. These characteristic cell surface features were seen in acetaldehyde-treated embryos at all stages of development examined. When additional females were examined on the twelfth day, a much lower incidence of open neural tube defects was observed. When embryos at this stage of development were examined in more detail by SEM, many had numerous subectodermal blebs along the dorsal mid-line, which were not initially apparent on gross inspection. The neuroepithelial morphology was also found to bae abnormal in embryos with no obvious external anomalies. The results confirm and elaborate on previous observations on the teratogenicity of acetaldehyde, stressing the ultrastructural changes that are induced in the cells of the neuroepithelium, and the possible relationship between the damage induced by this agent and certain features of the fetal alcohol syndrome.
 ...
PMID:Effect of acetaldehyde on the neuroepithelium of early mouse embryos. 727 85

The aim was to study the effect of the type of polymer solvent on characteristics of microspheres produced by spray drying. The water-soluble model protein, bovine serum albumin (BSA) was microencapsulated into biodegradable poly(D,L-lactic acid) using the following 10 different polymer solvents: acetaldehyde dimethyl acetal, acetone, dichloromethane, dioxane, ethyl acetate, ethyl vinyl ether, nitromethane, tetrahydrofuran, 1,1,1-trichloroethane, and 1,1,2-trichloroethylene. These solvents having similar toxicity levels differ greatly in their physico-chemical characteristics such as boiling point, vapour pressure, miscibility and interfacial tension with an aqueous phase, and solubility parameter. The effect of these solvents on microsphere morphology was studied by SEM-micrographs. Regular particle morphology was obtained when dichloromethane, ethyl acetate, or nitromethane was used as the polymer solvent, whereas the trichlorinated solvents, tetrahydrofuran, and dioxane produced a substantial number of coalesced particles. The results are interpreted in terms of boiling point, vapour pressure, and polymer-solvent affinity. Further, BSA-loading and -integrity in the microspheres, and burst release were analysed. The theoretical loading of 2.9% was attained with dichloromethane, ethyl acetate and nitromethane, in agreement with observations of particle morphology. HPLC- and SDS-PAGE analysis of the microencapsulated BSA did not show any protein degradation or dimerization, whereas solid-phase ELISA clearly revealed that the in vitro protein antigenicity was substantially reduced (50%), particularly by water miscible solvents. Dichloromethane and ethyl acetate did not show any detrimental effect on protein antigenicity. Finally, burst release could be related again to particle morphology, with dichloromethane and nitromethane giving a burst release of only 5%. In conclusion, dichloromethane, ethyl acetate and nitromethane proved to be the most suitable solvents for the polymer-protein system studied.
 ...
PMID:Quality improvement of spray-dried, protein-loaded D,L-PLA microspheres by appropriate polymer solvent selection. 773 Sep 60

The actions of ethanol and its primary oxidative metabolite, acetaldehyde, on plasma membrane and mitochondrial transmembrane potentials were examined in rat brain using fluorescence techniques. Subchronic treatment of adult rats with ethanol resulted in a significant depolarization of both the plasma and mitochondrial membranes when the mean blood ethanol level of the rats was 59 +/- 11 mM (mean +/- SEM, n = 6). Acute dosing of animals (4.5 g/kg, i.p.) failed to show any significant alterations. Various concentrations of ethanol, added in vitro to a crude synaptosomal preparation isolated from the rat cerebrocortex (P2) from untreated animals, depolarized both the plasma and mitochondrial transmembrane potentials in a dose-related manner. Addition of acetaldehyde in vitro did not reveal any significant effects on plasma or mitochondrial transmembrane potential.
 ...
PMID:Inhibition of plasma membrane and mitochondrial transmembrane potentials by ethanol. 778 41

Incubation of human colonic contents with various ethanol concentrations (2.75-44 mM) in vitro at 37 degrees C resulted in significant accumulation of acetaldehyde--a toxic and highly reactive compound. At pH 9.6, all samples produced notable acetaldehyde concentrations (58 (13) microM; mean (SEM)) even from the lowest (2.75 mM) ethanol concentration, and the production of acetaldehyde increased lin-early with rising ethanol concentration (r = 0.97; p < 0.005), reaching a peak concentration of 238 (37) microM at 44 mM ethanol. The formation of acetaldehyde took place rapidly, as almost 50% of acetaldehyde formed during the total eight hour incubation was detectable after one hour, and 75% of the total after four hours. Maximal acetaldehyde production from 22 mM ethanol occurred at pH 9.6 (160 (35) microM) but appreciable concentrations were also seen at pH 7.4 (110 (38) microM) and pH 6.0 (63 (19) microM). At pH 4.0, by contrast, acetaldehyde formation was negligible (17 (5) microM). 4-Methylpyrazole, a potent inhibitor of alcohol dehydrogenase, showed a decreasing effect on acetaldehyde production in vitro but first at a concentration of 100 mM. Considerable acetaldehyde production by human colonic bacteria--if it occurs also in vivo--could constitute a risk factor for rectal cancer in heavy drinkers and also provide a pathogenetic mechanism for alcohol induced diarrhoea.
 ...
PMID:In vitro acetaldehyde formation by human colonic bacteria. 795 36

By virtue of possessing alcohol dehydrogenase activity, cytosol prepared from Helicobacter pylori produces toxic acetaldehyde from ethanol in vitro. To approach the in vivo situation in the stomach, we have now investigation whether intact H. pylori--without addition of exogenous nicotinamide adenine dinucleotide--also forms acetaldehyde. Furthermore, to assess the energy metabolism of H. pylori, we determined whether the alcohol dehydrogenase-catalyzed reaction can run in the opposite direction with ethanol as the end-product and thereby yield energy for the organism. Intact H. pylori formed acetaldehyde already at low ethanol concentrations (at 0.5% ethanol, acetaldehyde, 64 +/- 21 and 75 +/- 9 mumol/l (mean +/- SEM) for strains NCTC 11637 and NCTC 11638, respectively). H. pylori produced ethanol in concentrations that can be significant for the energy metabolism of the organism. Acetaldehyde production by H. pylori may be an important factor in the pathogenesis of gastroduodenal diseases associated with the organism. The primary function of H. pylori alcohol dehydrogenase may, however, be alcoholic fermentation and consequent energy production under microaerobic conditions.
 ...
PMID:Acetaldehyde and ethanol production by Helicobacter pylori. 804 4

Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) isoenzymes from surgical esophageal and gastric mucosa were compared by agarose isoelectric focusing. Two prominent ADH forms, designated mu 1 (equivalent to the recently reported mu-form) and mu 2, were expressed in all the 15 esophagus specimens studied, whereas only four of seven examined gastric specimens exhibited a weak to moderately strong mu 1-ADH activity band on the isoelectric focusing gels. pI values of the esophageal mu 1-ADH and mu 2-ADH, and the liver pi-ADH were determined to be 8.61, 8.13, and 8.90, respectively. mu-ADHs exhibited high Km for ethanol (12 mM) and low sensitivity to 4-methylpyrazole inhibition. ALDH3 (BB form) and ALDH1 were the major high- and low-Km aldehyde dehydrogenase in the esophagus, respectively. The ADH and ALDH activities were determined at pH 7.5 to be 751 +/- 78 and 29.9 +/- 3.0 nmol/min/g tissue, respectively (measured at 500 mM ethanol or at 200 microM acetaldehyde; mean +/- SEM; N = 15). The esophageal ADH activity was approximately 4-fold and the ALDH activity 20% that of the stomach enzyme. Because the presence of high activity and high Km mu-ADHs as well as low-activity ALDH1 were found in human esophageal mucosa, it is suggested that there may exist an accumulation of intracellular acetaldehyde during alcohol ingestion. This reactive and toxic metabolite may be involved in the pathogenesis of alcohol-induced esophageal disorders.
 ...
PMID:Alcohol and aldehyde dehydrogenases in human esophagus: comparison with the stomach enzyme activities. 848 82


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>