Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: UMLS:C0011570 (depression)
172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It has been shown that alcohol administration causes baroreceptor reflex inhibition. The site of action of alcohol could reside anywhere within the baroreceptor reflex arc. Therefore, the goal of this study was to determine the effects of acute administration of alcohol on carotid sinus baroreceptor discharge characteristics. In pentobarbital-anesthetized dogs, the carotid sinus was isolated and perfused. Single unit baroreceptor discharge was recorded from the carotid sinus nerve along with carotid sinus diameter using sonomicrometry. Carotid sinus pressure-baroreceptor discharge and carotid sinus pressure-diameter curves were constructed. Perfusion of the carotid sinus with alcohol (100 mmol/L) significantly decreased the pressure threshold from 91.1 +/- 2.8 to 86.4 +/- 2.9 mm Hg (p < 0.05) and increased the peak discharge rate from 45.8 +/- 3.4 to 52.8 +/- 3.6 spikes per second (p < 0.01). The same phenomenon was seen during perfusion of the carotid sinus with acetaldehyde (2.5 mmol/L) but was not seen during perfusion with acetate (2.5 mmol/L). During perfusion of the carotid sinus with alcohol, the carotid sinus pressure-carotid sinus diameter relation did not change. The baroreceptor sensitization induced by alcohol is not an endothelium-dependent mechanism, because endothelial denudation did not block this alcohol-induced effect. Measurement of the duration of postexcitatory depression of carotid sinus baroreceptors, which is related to Na+,K(+)-ATPase activity, showed that perfusion of the carotid sinus with alcohol or acetaldehyde significantly reduced the duration of postexcitatory depression, indicating that the alcohol- and acetaldehyde-induced effect on baroreceptor discharge is most likely mediated by an inhibition of Na+,K(+)-ATPase.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Acute alcohol administration stimulates baroreceptor discharge in the dog. 849 3

Acrolein is a highly toxic, reactive, and irritating aldehyde that occurs as a product of organic pyrolysis, as a metabolite of a number of compounds, and as a residue in water when used for the control of aquatic organisms. It is an intermediate in the production of acrylic acid, DL-methionine, and numerous other agents. Its major direct use is as a biocide for the control of aquatic flora and fauna. It is introduced to the environment from a variety of sources, including organic combustion such as automobile exhaust, cigarette smoke, and manufacturing and cooking emissions, as well as direct biocidal applications. Organic combustion from both fixed and mobile sources is the significant source of acrolein in the atmosphere; it represents up to 8% of the total aldehydes generated from vehicles and residential fireplaces and 13% of total atmospheric aldehydes. This reactive aldehyde also occurs in organisms as a metabolite of allyl alcohol, allylamine, spermine, spermidine, and the anticancer drug cyclophosphamide, and as a product of UV radiation of the skin lipid triolein. Furthermore, small amounts are found in foods; when animal or vegetable fats are overheated, however, large amounts are produced. Most human contact occurs during exposure to smoke from cigarettes, automobiles, industrial processes, and structural and vegetation fires. Besides cigarette smoke, occupational exposures are a common mode of human contact, particularly in industries that involve combustion of organic compounds. Firefighters, in particular, are exposed to extremely high levels during the extinguishment and overhaul phases of their work. Water may contain significant levels of the herbicide. It has been found in paper mill and municipal effluents at 20-200 micrograms/L, and at 30 micrograms/L as far as 64 km downstream from the point of application. The USEPA-recommended water quality criteria for freshwater are only 1.2 micrograms/L (24-hr avg) and 2.7 micrograms/L (maximum ceiling). Acrolein is highly reactive, and intercompartmental transport is limited. However, it is eliminated from aqueous environments by volatilization and hydration to beta-hydroxypropanal, after which biotransformation occurs, with a half-life of 7-10 d. The Koc for acrolein is 24, and it is not likely to be retained in soil; activated carbon adsorbs only 30% from solution. Thus, the aldehyde is either leached extensively in moist soil or volatilizes quickly from dry soil. It is eliminated from air by reaction with .OH (half-life, 0.5-1.2 d), NOx (half-life, 16 d), and O3 (half-life, 59 d), as well as by photolysis and wet deposition. As expected from its high water solubility, bioaccumulation is low. Acrolein is highly toxic by all routes of exposure. The respiratory system is the most common target: exposure causes localized irritation, respiratory distress, pulmonary edema, cellular necrosis, and increased susceptibility to microbial diseases. Additionally, acute inhalation studies verify that it is a severe respiratory irritant that affects respiratory rates. Respiratory rate depression may have a protective effect by minimizing vapor inhalation, thereby explaining the subadditive effect of acrolein when combined with the other toxic combustion by-products CO and HCHO. Liquid contact with the skin and eyes causes severe irritation, opaque or cloudy corneas, and localized epidermal necrosis, but no allergic contact dermatitis. The cardiovascular system is affected, resulting in increased blood pressure, platelet aggregation, and quick cessation of beating in perfused rat hearts. It may also inhibit mitochondrial oxidative phosphorylation in the myocardium. Acute LD50s and LC50s are low. Levels are 7-46 mg/kg and 18-750 mg/m3, respectively, in rats; aquatic organisms are affected above 11.4 micrograms/L.(ABSTRACT TRUNCATED)
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PMID:Fate and effects of acrolein. 859 34

Animal experiments suggest that endogenous substances that could result from the interaction between neurotransmitters (dopamine and indoleamines) and ethanol and its metabolite acetaldehyde might be involved in the pathogenesis and maintenance of alcohol dependence. Therefore, aromatic beta-carbolines (norharman and harman) were investigated repeatedly in 24-hr urine of 13 male severe alcoholics without any psychiatric comorbidity during a controlled inpatient abstention program of up to 8 weeks. Harman excretion was approximately 2-fold above levels in control subjects, with a steady decline after 3 weeks of abstinence and lower levels in patients with a longer duration of alcohol dependence. Severity of withdrawal symptoms and actual feelings of anxiety/depression were negatively associated with urinary harman excretion. Positive associations could be established with daily ethanol consumption the month before admission and the score on the scale "reward dependence" according to Cloninger's Tridimensional Personality Questionnaire. Moreover, patients without alcohol-dependent first-degree relatives and higher "reward dependence" exhibited an increased excretion of harman. Therefore, harman levels might characterize a distinct subgroup of alcoholic patients, who in part resemble the so-called type l alcoholics of Cloninger. However, this awaits further study in a larger number of individuals. In contrast, norharman excretion was elevated up to 6-fold, compared with nonalcoholics over 6 to 8 weeks of controlled abstention. No correlations to demographic or clinical variables could be observed. Therefore, increased norharman levels might be proposed as a "residual marker" or a trait variable. Whether the observed changes are specific markers of at least certain aspects of alcoholism or dependence remain to be elucidated.
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PMID:Excretion of beta-carbolines harman and norharman in 24-hour urine of chronic alcoholics during withdrawal and controlled abstinence. 880 Mar 88

Acetaldehyde (ACA), an ethanol metabolite, exerts both stimulatory and depressive effects on isolated myocardial tissue, but its impact on individual cardiac myocytes is unknown. The purpose of this study was to determine whether ACA-induced myocardial depression is due to an intrinsic alteration of the contractile properties of heart at the cellular level. Mechanical properties of adult rat ventricular myocytes were evaluated using a video edge-detection system. Myocytes were electrically stimulated to contract at 0.5 Hz under isotonic conditions in a physiological buffer containing 1 mM CaCl2. Contractile properties analyzed include: peak twitch amplitude (PTA), time-to-PTA (TPT), time-to-relengthening (TR90) and maximal velocities of shortening and relengthening (+/-dL/dt). Ca2+ transients were measured as fura-2 fluorescence intensity (FFI) changes. ACA (1-30 mM) disproportionately depressed PTA and FFI in a dose-dependent manner, with maximal inhibitions of 57 and 19%, respectively. Neither the durations nor maximal velocities of shortening and relengthening were affected by ACA. The depression of cell shortening by ACA was either attenuated or blocked by BayK 8644 or elevated extracellular Ca2+ (2.7 mM). In addition, ACA also reduced caffeine-induced FFI changes. These results suggest that ACA-induced myocardial depression in multicellular preparations is due to an intrinsic action on individual myocytes. The mechanism underlying ACA-induced myocardial depression may be due, in part, to either reduced Ca2+ entry through voltage-dependent Ca2+ channels and/or depression of sarcoplasmic reticular Ca2+ release.
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PMID:Acetaldehyde depresses shortening and intracellular Ca2+ transients in adult rat ventricular myocytes. 935 29

Our previous study has reported that ethanol (ETOH) partially inhibited the endotoxin (LPS)-induced tissue factor (TF)-activation in monocytes including blood peripheral monocytes as well as cultured leukemic U937 and THP-1 cells. The present study shows a strong correlation (r = 0.92; p < 0.01) between TF-activation and depression in LPS binding blocked by ETOH in U937 cells. The antagonism by ETOH of LPS binding was not due to a direct extracellular blockade, since ETOH did not affect the affinity of fluorescein isothiocyanate (FITC)-LPS or -anti CD14 mAb on U937 cells. After U937 cells were treated with 2 per cent (v/v) ETOH for 3 h, LPS binding was however drastically inhibited as shown by immunostaining with FITC-LPS which was viewed on a confocal laser scanning microscope. The results imply that cellular events of the ETOH effect mediate this inhibition of LPS binding. Anti-CD14 mAb (UCHM-1) inhibited LPS binding in a dose-dependent fashion, revealing a competitive specific binding to the LPS receptor. The results suggest that CD14 plays an important role in the recognition of LPS. FITC-UCHM-1 binding was significantly reduced in the cells pretreated with 2 per cent (v/v) ETOH for 3 h, indicating that ETOH modulates the ability to express CD14. CD14 expression was upregulated by priming with LPS which was offset by ETOH. Acetaldehyde, a possible metabolite of ETOH, was tested with no effect on CD14 expression. Taken together, our results show that ETOH downregulates the recognition of LPS, and suggest that the inhibitory action is likely to be mediated by the depression in CD14 expression which was also accompanied by a significantly altered membrane fluidity. Thus, the antagonism by ETOH of the binding of LPS results in a depression in the LPS-induced TF-activation.
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PMID:Antagonism by ethanol of endotoxin-induced tissue factor activation in relation to the depressed endotoxin binding to monocyte-like U937 cells. 941 74

Acetaldehyde (ACA), the major metabolite of ethanol, exerts both stimulatory and depressive actions on myocardial tissue. We have recently shown that ACA depresses myocardial contraction, cardiac myocyte shortening and intracellular Ca2+ transients in normal rat heart. The purpose of the present study was to determine the influence of hypertension on ACA-induced myocardial actions. Mechanical properties of left ventricular papillary muscles and ventricular myocytes isolated from both 25-week-old normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) were evaluated using force-transducer and video edge-detection, respectively. Papillary muscles and cardiac myocytes were electrically stimulated to contract at 0.5 Hz. Contractile properties analyzed include: peak tension development (PTD), peak twitch amplitude (PTA), time-to-PTD/PTA (TPT/TPS), time-to-90% relaxation/relengthening (RT90/TR90) and maximal velocities of contraction/shortening and relaxation/relengthening (+/-VT/+/-dL/dt). Intracellular Ca2+ transients were measured as fura-2 fluorescence intensity (FFI) changes. ACA (1-30 mM) depressed PTD without affecting other mechanical indices in both WKY and SHR myocardium, with maximal inhibition of 64 and 69%, respectively. SHR myocytes exhibited increased cell dimension, baseline PTA and resting intracellular Ca2+ levels, compared to WKY counterparts. ACA (0.03-30 mM) depressed PTA without affecting TPT, TR90 and +/-dL/dt. The maximal inhibitions were 31 and 36% in WKY and SHR groups, respectively. Interestingly, ACA exerted a biphasic effect on FFI, displaying potentiation at lower doses (<3 mM) and inhibition at higher doses (>3 mM). The maximal increase in FFI changes were 19 and 22% at 0.3 mM and the maximal decreases were 37 and 29% at 30 mM ACA, in WKY and SHR myocytes, respectively. Neither resting intracellular Ca2+ levels (FFI) nor fluorescence decay time (FDT) were affected by ACA. The increase in FFI was attenuated by propranolol (1 microM), whereas the decrease in FFI was reversed by BayK 8644 (1 microM). These results suggest that hypertension does not appear to alter ACA-induced myocardial depression. The mechanism underlying ACA-induced myocardial actions may involve increased beta-adrenergic activity at low doses and reduced Ca2+ entry and/or release at high doses.
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PMID:Acetaldehyde depresses myocardial contraction and cardiac myocyte shortening in spontaneously hypertensive rats: role of intracellular Ca2+. 1043 92

It is well established that cardiomyopathy is a consistent feature of diabetes and that alcohol consumption increases the risk of cardiovascular disease among diabetic subjects. Acetaldehyde (ACA), the main ethanol metabolite, is considered to play a role in the ethanol-induced cardiac dysfunction. It has been reported recently that the negative inotropic effect of ACA was more potent in the diabetic myocardium. To determine whether the disparate ACA-induced myocardial depression in diabetes is due to intrinsic alterations at the cellular level, mechanical properties in response to ACA were evaluated in ventricular myocytes from both normal and streptozotocin-induced diabetic rat hearts. Myocytes were electrically stimulated to contract at 0.5 Hz and contractile properties analyzed included peak shortening (PS), time-to-PS (TPS), time-to-90% relengthening (TR(90)) and maximal velocities of shortening and relengthening (+/-dL/dt). Ca(2+) transients were measured as fura-2 fluorescence intensity (DeltaFFI) changes. ACA (0. 1-30 mM) disproportionately depressed PS in a dose-dependent manner, in myocytes from diabetic hearts compared to normal hearts. Interestingly, the degree of inhibition in DeltaFFI was similar in both groups. Neither the duration nor maximal velocities of shortening and relengthening were affected by ACA in either group. These results are the first to suggest that enhanced ACA-induced myocardial depression in diabetes is due to disparate intrinsic actions on individual myocytes. The mechanism underlying the alteration of ACA-induced myocardial depression may be due, in part, to depressed Ca(2+) responsiveness in diabetic hearts.
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PMID:Diabetes enhances acetaldehyde-induced depression of cardiac myocyte contraction. 1072 Apr 79

Long-standing ethanol consumption acts as a chronic cardiac stress and often leads to alcoholic cardiomyopathy. We have recently shown that the acute ethanol-induced depression in myocardial contraction was substantiated by chronic ethanol ingestion. Acetaldehyde (ACA), the main ethanol metabolite, has been considered to play a role in ethanol-induced cardiac dysfunction. To evaluate the ACA-induced cardiac contractile response following chronic ethanol ingestion, mechanical properties were examined using left ventricular papillary muscles and myocytes from rats fed with control or ethanol-enriched diet. Muscles and myocytes were electrically stimulated at 0.5 Hz and contractile properties analysed included peak tension development (PTD) and peak shortening (PS). Intracellular Ca(2+) transients were measured as fura-2 fluorescence intensity changes (DeltaFFI). Papillary muscles from ethanol-consuming animals exhibited reduced baseline PTD and attenuated responsiveness to increase of extracellular Ca(2+). Acute ACA (0.3-10 mM) addition elicited a dose-dependent depression of PTD. However, the inhibition magnitude was significantly reduced in ethanol-treated rats. Myocytes from both control and ethanol-treated rats exhibited comparable ACA-induced depression in both PS and DeltaFFI. Collectively, these data suggest that the ACA-induced depression of myocardial contraction is reduced at the multicellular level, but unchanged at the single cell level, following chronic ethanol ingestion.
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PMID:Influence of chronic alcohol ingestion on acetaldehyde-induced depression of rat cardiac contractile function. 1109 61

The mitochondrion is the subcellular organelle affected earliest during the development of alcoholic liver disease. As a result of chronic ethanol consumption mitochondrial protein synthesis is decreased significantly due to a depression in the functioning of the mitochondrial ribosome. This causes a significant decrease in the concentrations of the thirteen mitochondria gene products, all of which are components of the oxidative phosphorylation system. Consequently, there is a depression in the rate at which ATP is synthesized in hepatic mitochondria. In addition to this loss in function, hepatic mitochondria either acutely or chronically exposed to ethanol generate increased levels of reactive oxygen species (ROS). This elevation in ROS has been demonstrated in both isolated mitochondria and hepatocytes. The increase in mitochondrial ROS production accompanying acute ethanol exposure is due to mitochondrial associated reoxidation of NADH produced during ethanol and acetaldehyde metabolism. The elevation in ROS generation observed in mitochondria from chronic ethanol consumers is likely due to decreases in mitochondrial-derived electron transport components, which in turn results in higher levels of the semiquinone forms of flavin mononucleotide and ubiquinone. Both these semiquinones readily donate electrons to molecular oxygen to form superoxide.
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PMID:Ethanol consumption and liver mitochondria function. 1135 Nov 33

Alcoholic cardiomyopathy is characterized by impaired ventricular function although its toxic mechanism is unclear. This study examined the impact of cardiac overexpression of alcohol dehydrogenase (ADH), which oxidizes ethanol into acetaldehyde (ACA), on ethanol-induced cardiac contractile defect. Mechanical and intracellular Ca(2+) properties were evaluated in ventricular myocytes from ADH transgenic and wild-type (FVB) mice. ACA production was assessed by gas chromatography. ADH myocytes exhibited similar mechanical properties but a higher efficiency to convert ACA compared with FVB myocytes. Acute exposure to ethanol depressed cell shortening and intracellular Ca(2+) in the FVB group with maximal inhibitions of 23.3% and 23.4%, respectively. Strikingly, the ethanol-induced depression on cell shortening and intracellular Ca(2+) was significantly augmented in the ADH group, with maximal inhibitions of 43.7% and 40.6%, respectively. Pretreatment with the ADH inhibitor 4-methylpyrazole (4-MP) or the aldehyde dehydrogenase inhibitor cyanamide prevented or augmented the ethanol-induced inhibition, respectively, in the ADH but not the FVB group. The ADH transgene also substantiated the ethanol-induced inhibition of maximal velocity of shortening/relengthening and unmasked an ethanol-induced prolongation of the duration of shortening/relengthening, which was abolished by 4-MP. These data suggest that elevated cardiac ACA exposure due to enhanced ADH expression may play an important role in the development of alcoholic cardiomyopathy.
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PMID:Overexpression of alcohol dehydrogenase exacerbates ethanol-induced contractile defect in cardiac myocytes. 1189 54


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