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)

The aim of this study was to measure vascular reactivity in the isolated middle cerebral artery (MCA) after brain injury. Segments of MCA were prepared from control, sham-operated, and cold-lesioned rats. Cold lesion was induced by application of a precooled (-78 degrees C) copper cylinder (diameter 5 mm) for 60 sec to the intact dura over the parietal cortex. Endothelin-1 (ET-1) (10(-12) to 3 x 10(-7) M) induced a dose-dependent contraction with a pD2 (-log10 EC50) of 8.36+/-0.12 (mean+/-SEM) and an Emax (maximal response) of 2.41+/-0.15 mN (millinewton) at 10(-7) M in sham-operated animals under resting conditions. This maximum contraction induced by 10(-7) M ET-1 was significantly (p < 0.05) reduced 24 and 48 h after cold lesion by 41% and 30%, respectively. After precontraction with 10(-5) M prostaglandin (PG) F2alpha, ET-3 (10(-12) to 10(-8) M) relaxed the MCA with an Emax of 0.42+/-0.07 mN at 10(-8) M and a pD2 of 9.20+/-0.19 in sham-operated animals. This relaxation was reduced 24 and 48 h after cold lesion by 19% and 62% at 10(-8) M, respectively. Concentration-effect curves for bradykinin (BK, 10(-8) to 10(-5) M) in uridine triphosphate (UTP, 10(-4) M)-precontracted MCA segments revealed relaxation with a pD2 of 7.08+/-0.10 and an Emax of 0.65+/-0.06 mN at 10(-6) M in sham-treated animals. This effect of BK was reduced by 35% and 20% at 10(-6) M 24 and 48 h after cold lesion, respectively. In addition, the contractile responses to 124 mM K+, 10(-5) M PGF2alpha and the dilation induced by 10(-3) sodium nitroprusside (SNP) were reduced in MCA segments taken 24 and 48 h after lesion compared with shams. We conclude that attenuation of ET effects can be explained, at least in part, by tachyphylaxis to ETs. The unspecific reduction of vascular reactivity may result from spreading depression.
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PMID:Reduced reactivity of the middle cerebral artery and its large branches after cold lesion. 987 63

Inhalation of zinc fumes may lead to the acute respiratory distress syndrome. The mechanisms of pulmonary zinc toxicity are not yet understood. Therefore we investigated zinc-dependent depression of protein and RNA synthesis in rat and human lung cell lines. 1. After exposure to 120 or 150 micromol/l zinc, RNA synthesis as assessed by uridine incorporation decreased by 60-70% between 0 and 2 h exposition in rat alveolar type II cells (L2 cells) and human fibroblast-like cells (11Lu and 16Lu cells), and by 90% between 0 and 4 h in carcinoma-derived cells (A549 cells). 2. After 2 h exposure, L2, 11Lu, and 16Lu cells were half-maximally inhibited by 50 micromol/l zinc, whereas A549 cells were more resistant with half-maximal inhibition at 100 micromol/zinc. 3. Protein and RNA synthesis was inhibited in parallel in L2, 11Lu, and A549 cells as indicated by simultaneous determination of uridine and amino acid incorporation. In 16Lu cells, the decline in protein synthesis preceded RNA synthesis inhibition. Pretreatment with RNA synthesis inhibitors (amanitin or actinomycin D) had no effect on time curve and intensity of RNA synthesis inhibition. Taken together, our results indicate that the suppression of RNA and protein synthesis likely are independent phenomena, due to direct zinc effects on these biosynthetic pathways.
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PMID:Inhibition of protein synthesis by zinc: comparison between protein synthesis and RNA synthesis. 998 70

In previous work, mouse lines were selected for eight generations for resistance (R) or susceptibility (S) to endophyte-infected fescue toxicosis using depression in postweaning gain caused by a toxin-containing diet as the selection criterion. Characterizing biological changes associated with resistance or susceptibility in those mice might suggest genetic or therapeutic approaches to alleviate fescue toxicosis in cattle. The first objective of the current experiment was to determine whether the toxin-containing diet depressed reproduction and mature size more severely in S than in R mice. The second was to investigate line and diet effects on hepatic glutathione-S-epoxytransferase (GST) and uridine diphosphate glucuronosyl-transferase (UDPGT) activities and to relate enzyme activities to reproduction within line by diet groups. Twenty-eight pairs per line (S or R) x diet (toxin-containing [+] or toxin-absent [-]) group cohabitated for 36 wk. The + diet depressed the number of pups born and weaned and litter weight weaned (P < .01) within the first two litters produced. Diet effects were greatest early in the experiment. Percentage changes in reproduction caused by the + diet for R and S pairs, respectively, were -13 and -28 for total pups born, -10 and -25 for total pups weaned, -13 and -14 for total litters produced, and -30 and -42 for total litter weight weaned. The S line mice were heavier than R line mice on both diets, but the + diet had a larger depressing effect on mature size of S line than of R line males (line x diet interaction, P = .09) and females (interaction not significant). Averaged across diets, GST activity was higher in R than in S dams (P = .05) at 44 wk of age but was not affected by diet or line x diet. Activity of GST was correlated with number of pups born (-.50), number of litters produced (-.44), and survival percentage (.40) within the R- group; in the R+ group, GST activity was correlated only with survival percentage (.37). In the S- and S+ groups, GST activity was not correlated with any reproductive trait. Line, diet, and their interaction did not affect UDPGT activity, and UDPGT activity was not correlated with any reproductive trait in any line x diet group. Selected lines differed in response to a toxin-containing diet as measured by its effect on reproduction and mature size. The R and S mice also differed in GST activity, but GST activity was correlated with reproductive traits only in R-line mice.
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PMID:Impacts of an endophyte-infected fescue seed diet on traits of mouse lines divergently selected for response to that same diet. 1083 71

It was previously shown that K+ secretion by vestibular dark cell epithelium is under control of G protein-coupled receptors of the P2Y family in the apical membrane that are activated by both purine and uridine nucleotides (P2Y2, P2Y4, or P2Y6). The present study was conducted to determine the subtype of purinergic receptor and to test whether these receptors undergo desensitization. The transepithelial short-circuit current represents electrogenic K+ secretion and was found to be reduced by UTP, ATP, and diadenosine tetraphosphate, but not UDP. Neither pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid (PPADS, 30 microM) nor suramin (100 microM) inhibited the effect of UTP. The potencies of the agonists were consistent with rodent P2Y4 and P2Y2, but not P2Y6, receptors. The ineffectiveness of suramin was consistent with P2Y4, but not P2Y2. Transcripts for both P2Y2 and P2Y4 were found in vestibular labyrinth. Sustained exposure to ATP or UTP for 15 min caused a constant depression of short-circuit current with no apparent desensitization. The results support the conclusion that regulation of K+ secretion across vestibular dark cell epithelium occurs by P2Y4 receptors without desensitization of the response.
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PMID:Apical P2Y4 purinergic receptor controls K+ secretion by vestibular dark cell epithelium. 1140 51

Isolated testes of the locust Schistocerca gregaria were immersed in solutions of tritiated thymidine, cytidine, uridine, or arginine for short periods to study nucleic acid and protein synthesis during spermatogenesis. DNA synthesis in this tissue is completed prior to initiation of meiosis. Protein synthesis continues throughout the whole meiotic cycle as well as during spermatid development. Meiotic cells, except those in metaphase through early telophase, and early spermatids are also actively synthesizing RNA. The heteropycnotic X-chromosome does not produce RNA at any stage of spermatogenesis. The rates of protein and particularly RNA synthesis decrease as chromosome condensation progresses. Depression of RNA synthesis, however, is not always accompanied by cytologically detectable condensation of chromatin, since very little or no RNA is synthesized in spermatids in which chromatin condensation has barely begun.
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PMID:SYNTHETIC ACTIVITIES DURING SPERMATOGENESIS IN THE LOCUST. 1428 88

The control of de novo pyrimidine biosynthesis in the industrially important patent strain "Pseudomonas alkanolytica" ATCC 21034 was investigated. Uracil supplementation of succinate-grown "P. alkanolytica" cells produced the greatest depression of the de novo pyrimidine biosynthetic pathway enzyme activities. After the pyrimidine limitation of a "P. alkanolytica" orotate phosphoribosyltransferase mutant strain grown on succinate, the pyrimidine biosynthetic pathway enzyme activities were derepressed. The pyrimidine biosynthetic pathway enzyme aspartate transcarbamoylase in "P. alkanolytica" was inhibited by pyrophosphate, cytidine 5'-triphosphate (CTP), uridine 5'-triphosphate (UTP), and guanosine 5'-triphosphate (GTP).
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PMID:Control of pyrimidine biosynthesis in "Pseudomonas alkanolytica" ATCC 21034. 1516 99

The Orca Basin is a hypersaline depression in the northern Gulf of Mexico with anoxic conditions observed in the lower 200 m of the water column. Measurements of adenosine 5'-triphosphate, heterotrophic potential, and uridine uptake made above and across the interface into the anoxic zone revealed the presence of an active microbial population approximately 100 m above the interface. Biomass and activity decreased at and just below the interface but increased near the bottom, consistent with similar observations made in the Cariaco Trench. The maximum adenosine 5'-triphosphate concentration above the interface of 5.9 ng/liter (2,173 m) is about eight times greater than the value found in oxygenated waters of corresponding depth in the absence of an anoxic zone. The maximum adenosine 5'-triphosphate concentration in the anoxic zone is approximately 15 times greater than that found in oxygenated water of similar depth, suggesting anoxia will support the development of a larger bacterial population. Our findings suggest that autotrophic bacteria may be the dominant physiological group in the region just above the interface.
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PMID:Microbial biomass and activity distribution in an anoxic, hypersaline basin. 1634 55

For most drug-metabolizing enzymes (DMEs), the functional consequences of genetic polymorphisms have been examined. Variants leading to reduced or increased enzymatic activity as compared to the wild-type alleles have been identified. This review tries to define potential fields in the therapy of major medical conditions where genotyping (or phenotyping) of genetically polymorphic DMEs might be beneficial for drug safety or therapeutic outcome. The possible application of genotyping is discussed for depression, cardiovascular diseases and thromboembolic disorders, gastric ulcer, malignant diseases and tuberculosis. Some drugs used for relief of these ailments are metabolized with participation of genetically polymorphic DMEs including CYP2D6, CYP2C9, CYP2C19, thiopurine-S-methyltransferase, dihydropyrimidine dehydrogenase, uridine diphosphate glucuronosyltransferase and N-acetyltransferase type 2. Current evidence suggests that taking genetically determined metabolic capacities of DMEs into account has the potential to improve individual risk/benefit relationship. However, more prospective studies with clinical endpoints are needed before the paradigm of 'personalized medicine' based on DME variants can be established.
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PMID:The clinical role of genetic polymorphisms in drug-metabolizing enzymes. 1754 68

Eleven patients with bipolar depression were given doses of up to 18 g per day of triacetyluridine (TAU) over 6 weeks to test the effect of uridine on symptoms of depression via Montgomery-Asberg Depression Rating Scale (MADRS; Asberg, Montgomery, Perris, Schalling, & Sedvall, 1978) scores and on cellular bioenergetics using phosphorus magnetic resonance spectroscopic imaging (31P-MRSI). All patients and comparison participants (n = 9) completed baseline 31P-MRSI scans, and 9 patients completed posttherapy scans. The percentage changes for MADRS scores (Week 2, -23.8; Week 3, -34.9; Week 4, -42.5) and the time effects of TAU on MADRS scores (Week 2, z = -2.07, p = .039; Week 3, z = -4.28, p < .001; Week 4, z = -4.54, p < .001) may reflect TAU effects on early symptom improvement. TAU responders (patients who had a 50% or greater reduction in MADRS scores from baseline at any time) demonstrated a significant difference from nonresponders in pH changes from baseline (effect size = 150). These results suggest that TAU treatment may decrease symptoms of depression and improve mitochondrial functioning.
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PMID:Triacetyluridine (TAU) decreases depressive symptoms and increases brain pH in bipolar patients. 1854 Jul 79

Abstract Serum aminotransferase elevations are a commonly known adverse effect of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin) therapy. However, hepatotoxic events have not been widely published with ezetimibe or the combination agent simvastatin-ezetimibe. We describe a 70-year-old Hispanic woman who developed fulminant hepatic failure necessitating liver transplantation 10 weeks after conversion from simvastatin 40 mg/day to simvastatin 10 mg-ezetimibe 40 mg/day. The patient's lipid panel had been maintained with simvastatin for 18 months before the conversion without evidence of hepatotoxicity. A routine laboratory work-up 10 weeks after conversion revealed elevated serum aminotransferase levels. Simvastatinezetimibe and escitalopram (which she was taking for depression) were discontinued, and other potential causes of hepatotoxicity were excluded. A repeat work-up revealed further elevations in aminotransferase levels, and liver biopsy revealed evidence of moderate-to-severe drug toxicity. She underwent liver transplantation with an uneventful postoperative course. Her aminotransferase levels returned to normal by postoperative day 23, and her 2-year follow-up showed no adverse events. Ezetimibe undergoes extensive glucuronidation by uridine diphosphate glucoronosyltransferases (UGT) in the intestine and liver and may have inhibited the glucuronidation of simvastatin hydroxy acid, resulting in increased simvastatin exposure and subsequent hepatotoxicity. To our knowledge, this is the first case report of simvastatin-ezetimibe-induced liver failure that resulted in liver transplantation. We postulate that the mechanism of the simvastatinezetimibe-induced hepatotoxicity is the increased simvastatin exposure by ezetimibe inhibition of UGT enzymes. Clinicians should be aware of potential hepatotoxicity with simvastatin-ezetimibe especially in elderly patients and should carefully monitor serum aminotransferase levels when starting therapy and titrating the dosage.
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PMID:Simvastatin-ezetimibe-induced hepatic failure necessitating liver transplantation. 1875 89


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