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)

This study compared symptom reports and cardiovascular reactivity of a group of 24 individuals recruited from the community who reported a cognitive or emotional symptom caused by at least one food (food-sensitivity reporters, FSR) vs those of 15 controls (C) without a history of food, chemical, drug, or inhalant sensitivities. The main findings were: 1) FSR indicated sensitivities not only to foods, but also to environmental chemicals, drugs, and natural inhalants, as well as significantly more symptoms than C in multiple systems; 2) more FSR than C noted recent state depression and anxiety, as well as higher trait anxiety on the Bendig form of the Taylor Manifest Anxiety Scale; 3) however, on multiple regression analysis, not only depression, but also the number of sensitivities (foods, chemicals, drugs, inhalants), accounted for part of the variance in total number of symptoms (38 and 17%, respectively), whereas none of the affective measures accounted for any of the variance in total number of sensitivities over all subjects; 4) after controlling for depression and anxiety, FSR still showed a trend toward poorer performance on a timed mental arithmetic task (p = 0.16); and 5) FSR and C showed opposite patterns of heart rate change to two different stressful tasks (mental arithmetic and isometric exercise) (group by task interaction, p < 0.05). The data are discussed in terms of a time-dependent sensitization (TDS) process that predicts a cross-sensitizing and cross-reactive role for xenobiotic agents (e.g., foods, chemicals, drugs, and inhalants) and for salient psychological stress in the expression of psychophysiological dysfunctions of FSR. As in other chronically ill populations, negative affect in food-sensitive individuals may explain greater symptom reporting, but not necessarily account for the illness itself. For either a food or a psychological stimulus to begin to elicit sensitized responses, e.g., marked physiological differences from C, FSR may require multiple, intermittent exposures spaced over 5-28 days rather than on only 1 day.
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PMID:Polysymptomatic syndromes and autonomic reactivity to nonfood stressors in individuals with self-reported adverse food reactions. 840 77

Monoamine oxidase (MAO) plays an essential role in the regulation of various neurotransmitter and xenobiotic amines. Inhibitors of MAO have been employed in the treatment of depression and as adjuncts in Parkinson's disease therapy. X-Band and Q-band electron paramagnetic resonance (EPR) and electron nuclear double resonance (ENDOR) spectroscopic techniques are employed to characterize a signal assigned as a stable red anionic semiquinone radical in the resting state of MAO B. It is shown that the radical signal is not affected during substrate (either benzylamine or phenylethylamine) turnover, by anaerobic incubation with substrate, or by covalent modification of the active site flavin cofactor in the catalytically active dimer. Upon denaturation, however, the semiquinone absorbances and EPR signals are lost. Photoreduction of the native enzyme in the presence of ethylenediaminetetraacetate generates an EPR signal that is not the same as that obtained in the resting state and shows different proton ENDOR signals. These results suggest that the two flavin prosthetic groups that exist in catalytically active monoamine oxidase B are physically distinct.
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PMID:Observation of a flavin semiquinone in the resting state of monoamine oxidase B by electron paramagnetic resonance and electron nuclear double resonance spectroscopy. 878 May 11

1. The metabolism of 1-ethylphenoxathiin-10,10-dioxide (BW1370U87), an experimental compound designed as an inhibitor of monoamine oxidase-A for use as a possible anti-depression agent, has been studied in a human liver microsome preparation. 2. The identities of the metabolites have been determined using directly coupled hplc-1H nmr at 600 MHz in the stop-flow mode in this first study of in vitro xenobiotic metabolism using hplc-nmr. 3. The xenobiotic substances that were identified comprised the parent compound BW1370U87 (with -CH2CH3 at C1) together with sidechain-oxidized metabolites with C1 substituents of -CHOH.CH3, -CH2.CH2OH, -CHOH.CH2OH and -CH2.COOH, plus the unsubstituted phenoxathiin-10,10-dioxide.
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PMID:Characterization of in vitro metabolites from human liver microsomes using directly coupled hplc-nmr: application to a phenoxathiin monoamine oxidase-A inhibitor. 885 20

Milacemide or 2-n-pentylaminoacetamide hydrochloride, a new glycine derivative, was found to cause elevations of plasma transaminases in patients suffering from severe depression and Alzheimer's disease. However, no signs of liver toxicity were observed during the course of earlier conducted subchronic and chronic in vivo studies in rodents and cynomolgus monkeys. In this study an in vivo/in vitro approach has been proposed to detect early alterations in key metabolic and functional liver capacities. Milacemide was administered by continuous i.v. infusion for 7 days to male Sprague-Dawley rats using subcutaneously implanted osmotic pumps. Doses were given of 0, 250 and 500 mg/kg per day. Body weight and food intake were recorded and at day 7 of exposure, Milacemide concentration, glucose, urea, triglycerides and cholesterol levels and alanine (ALT) and aspartate aminotransferase (AST) activities were measured in plasma. Non-esterified fatty acids were determined in serum. On day 8, after overnight fasting, hepatocytes were isolated. A portion of the cells derived from untreated animals (no osmotic pumps) were cultured in a primary monolayer and exposed in vitro to different Milacemide concentrations. The xenobiotic biotransformation capacity of the isolated hepatocytes was studied by measuring the cytochrome P450 content, ethoxycoumarin-O-deethylase (ECOD), pentoxyresorufin-O-deethylase (PROD), ethoxyresorufin-O-deethylase (EROD), aldrin epoxidase (AE), epoxide hydrolase (EH) and glutathione S-transferase (GST) enzyme activities. Triglycerides, cholesterol and phospholipid contents were measured on the isolated cells. At plasma concentrations of 43 and 130 microM Milacemide, the ALT activity was unchanged or significantly decreased, whereas the AST activity was increased in both cases. Other clinical chemistry parameters remained unchanged. Weight gain was significantly lower in rats treated with the high Milacemide dose. In addition, decreased food consumption was observed in all treated animals leading to significantly lower food efficiency factors for the rats treated with the high dose. Milacemide had a specific inhibitory effect on xenobiotic biotransformation: ECOD activity decreased to 60% of the control value for both Milacemide doses, PROD activity remained unaffected whereas EROD activity decreased to 65% of the control value. A decrease was also observed at the highest drug concentration for AE (to 41%), EH (to 65%), cytochrome P450 content (to 80%) and GST (to 85%). At 500 mg Milacemide kg/day, hepatocyte triglycerides levels increased 3.1-fold while cholesterol and phospholipid levels remained unaffected. Electron and light microscopy on total liver and isolated hepatocytes indicated a concentration-dependent accumulation of lipid droplets, the occurrence of numerous vacuoles in the cytoplasm and other structural abnormalities. When the cultured hepatocytes of control animals (without osmotic pumps) were exposed to Milacemide, the appearance of vacuoles and myeloid bodies could be confirmed in vitro. The results of this study using an in vivo/in vitro approach clearly show potential hepatotoxic properties of Milacemide, an effect not observed in conventional toxicity studies.
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PMID:Observation of hepatotoxic effects of 2-n-pentylaminoacetamide (Milacemide) in rat liver by a combined in vivo/in vitro approach. 913 5

Rifampicin, an antibiotic widely used in tuberculosis therapy, is known to exert psychotropic side effects in some patients. Recently, rifampicin has been reported to activate the glucocorticoid receptor (GR) in human hepatocytes. Because there is evidence that increased levels of glucocorticoids may induce cognitive impairment, sometimes culminating in depression, the side effects of rifampicin may result from GR activation in central nerve cells. Therefore, we used reporter gene assays to determine whether rifampicin displays glucocorticoid-like effects in human neuroblastoma SK-N-MC cells or mouse hippocampal HT22 cells. Rifampicin was unable to elicit any detectable transactivation of GR in both cell types, whereas cortisol or dexamethasone led to a potent transcriptional response. Rifampicin was also inactive in the same HepG2 cell line that was originally used to demonstrate the effect of rifampicin on GR. Moreover, rifampicin was unable to compete with dexamethasone for binding to GR. Finally, by blocking the multidrug resistance P-glycoprotein transporter (a xenobiotic extrusion pump) with verapamil or cyclosporin A, we excluded the possibility that the lack of effect by rifampicin was due to its export from the cell. Our results establish that rifampicin does not activate GR, and rule out the hypothesis that the psychotropic side effects of rifampicin treatment are a consequence of GR activation.
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PMID:Rifampicin is not an activator of glucocorticoid receptor. 1072 19

Self-reported cacosmia (i.e. feeling ill from the odour of xenobiotic substances) was studied in 151 young, healthy workers, unexposed to unpleasant odours and working in food stores without air-conditioning. Almost half (46%) of the sample reported feeling ill from the smell of chemical materials. Chemical odour intolerance induced headache, itching eyes, irritated or congested nose, dry and/or sore throat, cough, dizziness, and itching or rash. Cacosmic subjects showed a slight prevalence of the female sex, and had significantly higher symptom scores, anxiety, and depression than non-cacosmic subjects. Cacosmia may be related to multiple chemical sensitivity, sick-building syndrome and psychopathology. Individual variability in odour tolerance may substantially bias epidemiological studies on indoor air quality and health.
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PMID:Cacosmia in healthy workers. 1131 99

Self-reported cacosmia (i.e. feeling ill from the odour of xenobiotic substances) was studied in 151 young, healthy workers, unexposed to unpleasant odours and working in food stores without air-conditioning. Almost half (46%) of the sample reported feeling ill from the smell of chemical materials. Chemical odour intolerance induced headache, itching eyes, irritated or congested nose, dry and/or sore throat, cough, dizziness, and itching or rash. Cacosmic subjects showed a slight prevalence of the female sex, and had significantly higher symptom scores, anxiety, and depression than non-cacosmic subjects. Cacosmia may be related to multiple chemical sensitivity, sick-building syndrome and psychopathology. Individual variability in odour tolerance may substantially bias epidemiological studies on indoor air quality and health.
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PMID:Cacosmia in healthy workers. 1180 31

Estrogen receptor (ER) activity can be modulated by the action of other nuclear receptors. To study whether ER activity is altered by orphan nuclear receptors that mediate the cellular response to xenobiotics, cross-talk between ER and constitutive androstane receptor (CAR), steroid and xenobiotic receptor, or peroxisome proliferator-activated receptor gamma was examined in HepG2 cells. Of these receptors, CAR substantially inhibited ER-mediated transcriptional activity of the vitellogenin B1 promoter as well as a synthetic estrogen responsive element (ERE)-containing promoter. Treatment with an agonist of CAR, 1,4-bis-(2-(3,5-dichloropyridoxyl))benzene, potentiated CAR-mediated transcriptional repression. In contrast, an antagonist of CAR, androstenol, alleviated the repression effect. Although CAR interacted with the ER in solution, CAR did not interact with the ER bound to the ERE. CAR/retinoid X receptor bound to the ERE but with much lower affinity than ER. Incremental amounts of CAR elicited a progressive reduction of the ER activity induced by the p160 coactivator glucocorticoid receptor interacting protein 1 (GRIP-1). In turn, increasing amounts of GRIP-1 progressively reversed the depression of ER activity by CAR. An agonist or antagonist of CAR potentiated or alleviated, respectively, the CAR-mediated repression of the GRIP-1-enhanced ER activity, which is consistent with the ability of theses ligands to increase or decrease, respectively, the interaction of CAR with GRIP-1. A CAR mutant that did not interact with GRIP-1 did not inhibit ER-mediated transactivation. Our data demonstrate that xenobiotic nuclear receptor CAR antagonizes ER-mediated transcriptional activity by squelching limiting amounts of p160 coactivator and imply that xenobiotics may influence ER function of female reproductive physiology, cell differentiation, tumorigenesis, and lipid metabolism.
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PMID:Inhibitory cross-talk between estrogen receptor (ER) and constitutively activated androstane receptor (CAR). CAR inhibits ER-mediated signaling pathway by squelching p160 coactivators. 1211 25

The presence of chemical contaminants in marine coastal waters is a major subject of concern since many molecules are potentially immunotoxic, even at low concentration. During the last decade, studies in sentinel species, such as the blue mussel, Mytilus edulis, or the Pacific oyster, Crassostrea gigas, have revealed that immunosuppressive responses can be related to xenobiotic exposure, in the laboratory and in the field. In the present study, European flat oysters were experimentally exposed to heavy metals, to investigate possible alterations of their immune function. Several hematological and functional parameters of hemocytes were measured by flow cytometry, a technique allowing rapid, sensitive, cell-by-cell measurements in large cell populations. Results reveal a depression of phagocytosis and several subcellular, physiological changes in oysters exposed to cadmium alone or to cadmium and copper, suggesting an overall alteration of the phagocytic function.
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PMID:Xenobiotic-induced immunomodulation in the European flat oyster, Ostrea edulis. 1240 22

When male rats were given a single dose of cadmium (Cd) (3.58 mg CdCl2 x H2O/kg, i.p.) 72 hr prior to sacrifice, the testicular 7-ethoxyresorufin O-deethylase (EROD) and glutathione S-transferase (GST) activities toward the substrates 1-chloro-2,4-dinitrobenzene (CDNB), 1,2-dichloro-4-nitrobenzene (DCNB), ethacrynic acid (EAA), 1,2-epoxy-3-(p-nitrophenoxy)-propane (EPNP), and cumene hydroperoxide (CHPx) decreased significantly as compared to controls. Cd also inhibited reduced glutathione (GSH) level while increasing the lipid peroxidation (LP) level significantly. When the animals were given a single dose of nickel (Ni) (59.5 mg NiCl2 x 6H2O/kg, i.p.) 16 hr prior to sacrifice, significant decreases were observed in EROD and GST activities toward CDNB, EAA, EPNP, and CHPx, and GSH level. No significant alterations were noted in DCNB GST activity and LP level by Ni. For the combined treatment, rats received the single dose of Ni 56 hr after the single dose of Cd and were killed 16 hr later. In these animals, lesser depressions were observed on EROD activity and LP level than those of Cd alone. The combination of metals significantly inhibited GST activities and GSH level but not to a greater degree than noted by Cd or Ni alone. Plasma testosterone levels of Cd-, Ni-, and combination-treated rats decreased significantly compared to controls. The strongest depression was achieved by Cd alone. Cd, both alone and in combination with Ni, increased the tissue Ni uptake significantly. Ni, however, did not produce such an effect on the tissue uptake of Cd in either case. Cd treatment caused interstitial edema and coagulation necrosis in seminiferous tubules and also caused fibrinoidal necrosis in vascular endothelium. Ni treatment did not produce any pathological testicular alterations compared to controls. Combined treatment produced fewer pathological alterations (i.e., only interstitial edema) than that of Cd treatment. These results reveal that the combination of Cd and Ni does nothave a synergistic effect on testicular xenobiotic metabolizing enzymes, and in contrast, Ni has an ameliorating effect on pathological disturbances caused by Cd alone in the rat testis.
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PMID:Combined effects of cadmium and nickel on testicular xenobiotic metabolizing enzymes in rats. 1244 41


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