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)

Post-tetanic potentiation (PTP) of monosynaptic reflex was estimated in spinal cords in the drug-free state after the administration of a convulsant dose of penicillin and after the administration of phenytoin. There was no apparent correlation between the degree of depression of PTP and the efficacy of controlling seizure activity by phenytoin. Extracellular potassium levels were measured with ion-selective microelectrodes. The post-stimulation clearing of [K+]0 was not accelerated by phenytoin, and frequently it was slowed. Post-stimulus undershooting of [K+]0 was diminished. Oxidation of NADH in cortex and of cytochrome a, a3 in spinal cord were measured by optical methods. Stimulus-evoked transient oxidation responses evoked by electrical stimulation were depressed by phenytoin. It is concluded that systemic administration of phenytoin in therapeutic doses does not stimulate Na+-K+-activated membrane ATPase in cortex and spinal cord. Unlike other depressants, phenytoin did not cause a reduction of "resting" redox levels of respiratory enzymes. The local regulation of blood flow remained unaltered after phenytoin administration. Phenytoin caused a moderate but consistent depression of the stimulus-evoked responses of potassium activity, electric potential, and oxidative enzymes, consistent with diminished outflow of potassium from cells, owing either to lesser activation of cells or to a lesser exchange of ions.
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PMID:Phenytoin, electric, ionic, and metabolic responses in cortex and spinal cord. 19 41

Non-invasive optical techniques were used to monitor the effects of increasing cerebral energy demand on metabolic capabilities and vascular reactivity in young and aged brain. Low level of electrical stimulation of the cortex, in both young (4--7 months) and aged (24--28 months) rat brain, were accompanied by transient oxidations of NADH and cytochrome oxidase (a,a3) as measured by microfluorometry and reflection spectrophotometry respectively. Stimulation sufficient to produce spreading cortical depression was accompanied by an oxidation of both NADH and cytochrome a,a3 in young brain together with an increase in local blood volume. There was either no change or a slight disoxygenation of hemoglobin. In aged brain, however, spreading depression was associated with an oxidation of NADH and a reduction of cytochrome a,a3 together with an increase in local blood volume and an oxygenation of hemoglobin. The present results indicate that the relationship between microcirculation and the terminal oxidase step of the respiratory chain is altered in aged brain when energy demand is high.
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PMID:Effects of age on brain oxidative metabolism in vivo. 21 92

Gene differences may alter an individual's response to foreign compounds by affecting their absorption, binding, distribution, excretion, biotransformation, or drug-drug interactions. Genetic differences in the metabolism of xenobiotics among inbred strains of various laboratory animals and model systems are reviewed. The inbred mouse has been studied most extensively. Genetic differences in toxicity are shown to be caused by various environmental pollutants in several inbred strains of mice and in siblings of the (C57BL/6N)(DBA/2N)F1 X DBA/2N backcross, in which the phenotypes "aromatic hydrocarbon responsiveness" or "nonresponsiveness" had been predetermined. This trait of "responsiveness"--which refers to the capacity for induction of cytochrome P1450 and numerous monooxygenase activities by certain aromatic compounds--segregates almost exclusively as a single gene among offspring of this backcross. All nonresponsive mice ingesting benzo/a/pyrene (about 125 mg/kg per day) die within 4 weeks, whereas the survival of responsive mice receiving the chemical orally is not significantly different from that of control mice; the apparent cause of early death in these experiments in toxic depression of the bone marrow. The life span of animals exposed to certain environmental pollutants can therefore be markedly influenced by a single gene or a very small number of genes. The same genetic trait can be either beneficial or detrimental to the animal, depending on whether detoxification or metabolic potentiation occurs. There also may exist genetic differences in man's susceptibility to toxicity or cancer caused by the numerous foreign compounds in his environment.
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PMID:Importance of genetic factors influencing the metabolism of foreign compounds. 81 76

In a patient with pituitary ACTH-dependent adrenal hyperplasia (AH), the standard oral metyrapone test resulted in a decrease in "apparent 11beta-hydroxylase activity" (-48%) accompanied by an increase in "apparent cholesterol cleavage activity" (+318%). When incubated adrenal mitochondria from this patient were studied, metyrapone inhibited both 11beta-hydroxylation of labeled 11-deoxycorticosterone and cleavage of labeled cholesterol, although at 0.1 and 1.0 mM metyrapone concentrations, depression of cholesterol cleavage (23 and 54%, respectively) was less than that of 11beta-hydroxylation (62 and 84%, respectively). The inhibition of cholesterol cleavage by metyrapone (26 and 62%, at 0.1 and 1.0 mM concentrations, respectively) was also demonstrable in adrenal mitochondria from a patient with hypercorticism resulting from an ACTH-independent adrenal adenoman (AA). Metyrapone administration to AA resulted in a significant depression of both 11beta-hydroxylase (-62%) and cholesterol cleavage (-36%) "apparent activities"; when metyrapone and ACTH were given together to this patient, however, only 11beta-hydroxylase "apparent activity" diminished (-26%), while cholesterol cleavage "apparent activity" was greatly augmented (+231%), thereby simulating the results of the standard metyrapone test in AH. These data demonstrate that metyrapone inhibits both mitochondrial reactions involved in cortisol synthesis--initial cholesterol cleavage and final 11beta-hydroxylation; these effects probably result from interference by this agent with the interaction between substrate and related cytochrome P - 450. Since ACTH has a major stimulatory effect on cholesterol cleavage but not on 11beta-hydroxylation, the outcome of metyrapone administration is thus determined by whether a change in ACTH level ensues: while 11beta-hydroxylation is inhibited by metyrapone under any circumstances, total steroid output rises when a compensatory ACTH increase overcomes metyrapone inhibition of cholesterol conversion into pregnenolone and falls when metyrapone inhibition of this reaction is unopposed.
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PMID:Dual sites of inhibition by metyrapone of human adrenal steroidogenesis: correlation of in vivo and in vitro studies. 126 43

Salmonella typhimurium infection in swine causes an enterocolitis followed by a persistent carrier state, but little is known about the mechanisms that allow this organism to colonize and persist in host tissues. Neutrophils provide a first line of defense against invading pathogens such as Salmonella typhimurium. The purpose of this study was to evaluate porcine neutrophil function after in vivo exposure to Salmonella and to determine if the immunomodulator, bacillus Calmette Guerin (BCG), exerts any effect on neutrophil function or on the colonization and persistence of S. typhimurium in the pig. Compared to negative controls, neutrophils from pigs exposed to S. typhimurium exhibited significantly decreased iodination, cytochrome-C reduction, antibody-dependent cell-mediated cytotoxicity, random migration, and chemotaxis (P less than or equal to 0.05). Neutrophil bactericidal activity against S. typhimurium was significantly enhanced. Most of the significant differences were noted in the first two days after exposure to Salmonella. Often the functional alterations were biphasic, peaking again 7-10 days after exposure. BCG alone significantly depressed random migration and cytochrome-C reduction in unstimulated neutrophils. The clinical course, colonization pattern, and persistence of Salmonella were similar between pigs receiving BCG and untreated pigs. These data suggest that S. typhimurium infection causes a depression in oxidative metabolism and motility, yet an increase in overall bactericidal activity against S. typhimurium in circulating porcine neutrophils. It also appears that BCG treatment, as reported here, does not enhance resistance of pigs to S. typhimurium colonization or reduce the number of persistent organisms in the porcine ileum.
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PMID:Alteration of neutrophil function in BCG-treated and non-treated swine after exposure to Salmonella typhimurium. 132 31

In 26 hospitalized patients with depression, a combined pharmacogenetic test with dextromethorphan, a substrate of cytochrome P450IID6, and mephenytoin, the S-form of which is hydroxylated by a P450IIC isozyme, was carried out before amitriptyline therapy. Metabolites were determined in 24-hour urine samples collected on treatment day 8, and the contributions of individual compounds, including the four isomers of 10-hydroxyamitriptyline and 10-hydroxynortriptyline to total excretion were calculated. Formation of (-)-E-10-hydroxyamitriptyline and (-)-E-10-hydroxynortriptyline apparently depends on the activity of cytochrome P450IID6 because negative correlations existed between the log metabolic ratio of dextromethorphan and the relative quantities of these enantiomers. In contrast, correlations were positive for nortriptyline, (+)-E-10-hydroxynortriptyline, (-)-Z-10-hydroxynortriptyline, and (+)-Z-10-hydroxynortriptyline. The mephenytoin hydroxylase seems to participate in side-chain demethylation to the secondary and primary amines, because the log metabolic ratio of mephenytoin correlated negatively with the relative quantity of E-10-hydroxydidesmethylamitriptyline and positively with that of amitriptyline and its N-glucuronide.
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PMID:Enantioselective amitriptyline metabolism in patients phenotyped for two cytochrome P450 isozymes. 142 8

The objective of this study was to evaluate the polymorphonuclear leukocyte (PMN) function in a poorly controlled adult insulin-dependent diabetic patient (IDDM) with severe recurrent periodontitis, while describing the microbiological and clinical findings. Chemotaxis, superoxide production, and phagocytosis and killing of Porphyromonas (Bacteroides) gingivalis by the IDDM PMN were evaluated 1 week before treatment relative to a healthy, matched control. These analyses revealed a significant (P less than .05) depression in the number of IDDM PMNs migrating along an FMLP gradient (Boyden chamber assay). In addition, a significant (P less than .05) enhancement of IDDM PMN superoxide production in response to opsonized zymosan (cytochrome C reduction) was observed. Phagocytosis and killing (fluorochrome phagocytosis assay) by IDDM PMN of two P. gingivalis strains was also impaired significantly (P less than .05). The subgingival microflora contained significant levels of P. gingivalis, Actinobacillus actinomycetemcomitans, Eikenella corrodens, and Peptostreptococcus micros. Periodontal treatment consisted of extraction of hopeless teeth, scaling and root planing and 3 weeks of Augmentin therapy. The antibiotic therapy resulted in unrecoverable numbers of the putative pathogens and a reduction in both gingival inflammation and disease progression. The IDDM healing response to previous surgical treatment and extractions was poor, presumably due to a marked thrombocytopenia (91 x 10(3) platelets/mm3).
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PMID:Defective neutrophil function in an insulin-dependent diabetes mellitus patients. A case report. 165 89

Influence of fructose++-1,6-diphosphate, succinate, malate and cytochrome C on free lipid peroxidation (FLP), infarct sizes and metabolic acidosis was studied in experiments on rats. The good correlation between inhibition of FLP and cardioprotector activity was established for activators of glycolytic energy production only. Krebs' cycle metabolites limited the zone of myocardial necrosis after coronary occlusion without any significant depression of FLP. Succinate and malate were practically inactive under acute metabolic acidosis of isolated rat heart.
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PMID:[Relationship of antioxidant and anti-ischemic effects of various energy-yielding compounds]. 166 19

During episodes of infectious disease the mixed function oxidase system is depressed and the capacity of the liver to metabolize drugs can be compromised in both animals and humans. The depression that occurs during viral infections is mediated via the production of interferon. This action of interferon requires the synthesis of an intermediate protein(s) yet to be identified. Using an oligonucleotide probe for a unique sequence in cytochrome P-450LA omega we have now shown that the mRNA for this isozyme is depressed following the administration of interferon inducers. The magnitude in the loss of mRNA corresponds to the magnitude of the loss in the levels of this isozyme. This depression is observed within 6 h of interferon exposure. It is concluded that the decrease in drug metabolism during viral infections is caused by an interferon-mediated loss in mRNA and subsequent cytochrome P-450 synthesis in the liver.
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PMID:Regulation of hepatic cytochrome P-450 during infectious disease. 169 39

p-Cresol methylhydroxylase (PCMH) isolated from Pseudomonas putida is an alpha 2 beta 2 tetramer of approximate subunit Mr 49,000 and 9,000. It is a flavocytochrome c containing covalently bound FAD in the larger subunit and covalently bound heme in the smaller. Crystals in space group P2(1)2(1)2(1) with unit-cell parameters a = 140.3 A, b = 130.6 A, and c = 74.1 A contain one full molecule per asymmetric unit and diffract anisotropically to about 2.8-A resolution in two directions and to about 3.3-A resolution in the third. An electron density map has been computed at a nominal resolution of 3.0 A by use of area detector data from native crystals and from two derivatives. The phases were improved with the B.C. Wang solvent leveling procedure, and the map was averaged about the noncrystallographic 2-fold axis. The cytochrome subunit, whose amino acid sequence is known, has been fitted to the electron density on a graphics system. The course of the polypeptide chain of the flavoprotein subunit, whose sequence is mostly unknown, has been traced in a minimap and a model of polyalanine fitted to the electron density on the graphics system. The flavoprotein subunit consists of three domains in close contact. The N-terminal domain consists largely of beta-structure and contains most of the FAD binding site. The second domain contains a seven-stranded antiparallel beta-sheet of unusual topology connected by antiparallel alpha-helices on one side. The flavin ring lies at the juncture of the first two domains. The third domain lies against the first domain and helps cover the rest of the FAD chain. The cytochrome subunit resembles other small cytochromes such as c-551 and c5 and fits into a depression on the surface of the large flavoprotein subunit. The flavin and heme planes are nearly perpendicular, the normals to the planes being approximately 65 degrees apart. The two groups are separated by about 8 A, the distance from one of the vinyl methylene carbon atoms of the heme to the 8 alpha-methyl group of the flavin ring.
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PMID:Three-dimensional structure of p-cresol methylhydroxylase (flavocytochrome c) from Pseudomonas putida at 3.0-A resolution. 184 90


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