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)

Two separate experiments evaluated ID-1 (a commercial bovine whey product containing 5200 pg of thymosin alpha 1/ml) as an immunotherapeutic agent in lactating cows. In the first experiment, cows without mastitis were evaluated for blood leukogram, milk production, total and differential milk cell counts, lymphocyte (Lc) blastogenesis, and neutrophil (PMN) functions (random and directed migration under agarose, chemiluminescence, ingestion of bacteria, iodination, cytochrome C reduction, antibody-independent neutrophil-mediated cytotoxicity, and antibody-dependent cell-mediated cytotoxicity) before and after ID-1 therapy. ID-1 treatment resulted in a significant treatment group by time period interaction for the relative proportion of mononuclear cells (MNC) in milk (P less than 0.009) and for PMN random migration (P less than 0.01). Based on these interactions, ID-1 treatment appeared to slightly increase the proportion of small MNC in milk and to increase random migration from pretreatment levels by 73% more than increases observed in controls. No significant effect of ID-1 treatment on milk production, total milk somatic cell counts, Lc blastogenesis, or other PMN functions was observed. In cows with experimental Staphylococcus aureus intramammary infections, ID-1 treatment resulted in a significant decline in blood leukocyte count (P less than 0.001) and blood PMN count (P less than 0.02), and maintained PMN random migration (P less than 0.01) while controls declined and abrogated a depression in the ability of Lc to respond to mitogens (P less than 0.05) that developed in controls as a result of S. aureus mastitis. Injection of ID-1 into cows had no adverse effect on their overall health or level of milk production, but did cause subtle and potentially favorable changes in several in vitro immune parameters. In spite of these subtle changes which might indicate increased resistance to mastitis, cows actually developed a more severe S. aureus intramammary infection based on a 9% increase in log 10 bacterial shedding in milk.
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PMID:In vivo effects of a thymosin alpha 1-containing colostral whey product on neutrophils and lymphocytes from lactating cows without and with experimentally induced Staphylococcus aureus mastitis. 270 95

The function of renal cortical mitochondria isolated from rats with cyclosporine nephrotoxicity was studied. Renal cortical mitochondria were isolated from 5 male Fischer rats after 14 days of daily intraperitoneal administration of CsA, 25 mg/kg body wt. Compared with the mitochondrial function of 5 pair-fed control rats receiving vehicle alone, state 3 respiration (ADP-dependent) using several substrates was mildly depressed only with pyruvate-malate supported respiration (27 +/- 3 vs. 36 +/- 2 nmol O2/min/mg protein; P less than 0.05). The Ca2+ accumulation rate was slightly reduced (354 +/- 14 vs. 416 +/- 18 nmol/min/mg protein; P less than 0.025) while the cytochrome enzyme concentrations were not different from controls. Respiratory control ratios were not affected (CsA group: 9.5 +/- 2.8, control group: 8.9 +/- 2.3; glutamate-malate as substrates). These minor alterations in mitochondrial function occurred in the presence of severe depression in the glomerular filtration rate and renal morphologic changes commonly seen with CsA administration. Moreover, there was no increase in enzymuria. These results indicate that CsA has minor effects on the respiratory function of renal cortical mitochondria. The severe depression in the glomerular filtration rate is out of proportion to these minor alterations in mitochondrial function. These findings argue against a prominent role for a direct toxic action of CsA on tubular cells in the pathogenesis of acute cyclosporine-induced renal dysfunction.
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PMID:Renal cortical mitochondrial integrity in experimental cyclosporine nephrotoxicity. 274 85

Oral therapy with nizoral and griseofulvin influences the system of cytochrome P = 450-dependent monoxygenases of the liver, this resulting in the depression of antipyrine microsomal oxidation. Recommendations are given on how to regard the data of antipyrine test over the course of therapy with oral antimycotic drugs.
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PMID:[Detoxifying function of the liver in patients with rubromycosis during treatment with antimycotics]. 276 9

The influence of dietary 2-acetylaminofluorene (AAF) on the cytochrome P-450 content of rat liver microsomal and nuclear fractions was immunochemically probed with monoclonal and polyclonal antibodies to cytochromes P-450c and P-450d. Cytochrome P-450d but not P-450c was immunodetected in microsomes, nuclear envelopes, and nuclei from untreated rats. The levels of both cytochromes P-450c and P-450d were elevated after a diet of either 0.1% AAF for 1 week or 0.05% AAF for 3 weeks. However, the level of cytochrome P-450c relative to P-450d was lower after the more prolonged AAF feeding. Supplementation of AAF-containing diets with 0.3% butylated hydroxytoluene (BHT), which affords protection against AAF hepatocarcinogenesis in high-fat fed rats, protected and/or induced total (spectral) nuclear envelope cytochrome P-450 content. Immunochemical studies of liver fractions showed that BHT enhanced the AAF-dependent induction of cytochrome P-450c, but not of P-450d. This was a concerted effect of AAF + BHT since dietary BHT by itself did not affect the levels of cytochrome P-450c or P-450d as compared to control rats. Since 1- to 3-week dietary AAF had little effect on total (spectral analyses) microsomal cytochrome P-450 but markedly reduced total P-450 in nuclear envelopes, the coordinated induction of specific cytochrome P-450s in the different fractions suggests selective induction and depression of different forms of cytochrome P-450 and provides additional evidence for independent regulation of the drug-metabolizing system in nuclear envelope and microsomes. In addition, these results suggest that regulation of cytochrome P-450 may play a crucial role in the nutritional modulation of AAF hepatocarcinogenesis.
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PMID:Induction of rat liver microsomal and nuclear cytochrome P-450 by dietary 2-acetylaminofluorene and butylated hydroxytoluene. 278 62

The effects of the neurotoxic compound, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on the hepatic cytochrome P-450 monooxygenase system were assessed using C57 BL/6J mice. Treatment with MPTP caused a marked depression of hepatic cytochrome P-450 content, ethoxyresorufin O-dealkylase and NADPH cytochrome C reductase activities. This effect was maximal 3 to 6 hours after treatment and was dependent on the dose of MPTP administered. Depression of spectrophotometrically measured cytochrome P-450 content was associated with increase in cytochrome P-420 content and lipid peroxidation. In vitro studies showed the formation of a metabolic-intermediate complex with cytochrome P-450 which may partially explain the depression of cytochrome P-450 content and activity by MPTP.
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PMID:Depression of the hepatic cytochrome P-450 monooxygenase system by the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). 278 11

A previously validated small mammal trauma model, hindlimb ischemia secondary to infrarenal aortic ligation in the rat, was utilized to investigate the effects of traumatic injury on two of the major hepatic enzymes of detoxification, glutathione S-transferase and epoxide hydrolase. Hepatic cytosolic glutathione S-transferase activity toward a variety of substrates showed a 26-34% decrease at 24 hr after model injury. Hepatic microsomal epoxide hydrolase activity toward 1,2-epoxy-3-(p-nitrophenoxy)propane was diminished by 53% after model trauma. Both enzymatic activities toward styrene oxide were similarly depressed. The toxicological sequelae of these derangements were illustrated by administering a dose of styrene oxide (300 mg/kg, ip) which was below the threshold dose (350 mg/kg, ip) necessary to produce hepatotoxicity in control animals. Model trauma dramatically enhanced the hepatotoxic effects of the subthreshold dose, as well as the covalent binding of labeled styrene oxide to liver proteins. These findings indicate that traumatic injury renders the animal more susceptible to agents which are detoxified by glutathione S-transferase and epoxide hydrolase. Conversely, model trauma provided almost complete protection from the hepatotoxic effects of a standard dose (200 mg/kg, ip) of bromobenzene. This protection appeared to derive from a post-traumatic alteration of cytochrome P-450 subpopulations that decreased the formation of the potentially toxic 3,4-epoxide metabolite, despite an increase in the cytochrome P-448-mediated generation of the nontoxic 2,3-epoxide. For bromobenzene, the change in cytochrome P-450-mediated activation appeared quantitatively more significant in overall toxicity than the post-traumatic depression of detoxification pathways described above, leading to decreased toxicity in vivo. For other compounds, the combination of post-traumatic influences on cytochrome P-450/P-448 activity and epoxide hydrolase/glutathione S-transferase activities could lead to markedly enhanced toxicity.
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PMID:Effects of model traumatic injury on hepatic drug metabolism in the rat. VI. Major detoxification/toxification pathways. 289 98

A novel analogue of human alpha-interferon (IFN-alpha CON1) was tested for its ability to modify the hepatic cytochrome P-450-dependent mixed-function oxidase system in the hamster. This cloned interferon was derived by selecting the most frequently observed amino acid sequences at each position in the known human alpha-interferon subtypes. IFN-alpha CON1 had a biphasic effect on cytochrome P-450 and related drug biotransformation in the hamster causing an initial increase followed by a significant depression. IFN-alpha CON1 also had a biphasic effect on cytochrome P-450 in the lung, adrenal and spleen but only a depressant effect in the kidney. This effect was not due to morphological damage and followed the species specificity for this type of interferon. Both the increase and the decrease in cytochrome P-450 could be prevented by the administration of the protein synthesis inhibitor puromycin. Various isozymes of cytochrome P-450 induced by phenobarbital, beta-napthaflavone and clofibrate were also depressed by this interferon. The results presented in this report suggest that IFN-alpha CON1 interferon will likely depress drug biotransformation in humans because the antiviral effects and the "anti-cytochrome P-450" effect of interferons cannot be separated, and this interferon has antiviral properties in both hamster and human cells. Clinically relevant drug interactions may be common during the concomitant use of this interferon and other drugs that are metabolized by cytochrome P-450.
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PMID:Induction and depression of cytochrome P-450-dependent mixed-function oxidase by a cloned consensus alpha-interferon (IFN-alpha CON1) in the hamster. 291 6

The effect of a single dose of 5 mg/kg body weight of aflatoxin B1 on rat liver mitochondrial enzymes, succinate dehydrogenase (SDH) and Mg++ adenosine triphosphatase (Mg++-ATPase) and on certain lipids were studies at various intervals of time from 3 to 24 hours. A significant decrease in the specific activity of SDH was observed after 6, 12, 18 and 24 hr treatment. The Mg++-ATPase activity remained unaffected up to 12 hr but appreciably decreased after, 18 and 24 hr of the treatment. The level of phospholipids and cholesterol were not altered after 3, 6 and 12 hr treatment, thereafter (18 and 24 hr) an increase was observed in both the lipids following the aflatoxin treatment. Medroxyprogesterone acetate (MPA) did not cause any alteration in the specific activities of these enzymes as well as levels of cholesterol and phospholipids. The treatment with MPA caused significant increase in contents of cytochromes P-450, b5 and activities of Arylhydrocarbon hydroxylase (AHH), UDP-glucuronyl transferase (UDP-GT) and NADPH-cytochrome C-reductase of hepatic microsomes. It was observed that pretreatment with medroxyprogesterone acetate (MPA) could significantly minimuze the depression caused in mitochondrial SDH and Mg++-ATPase activities by aflatoxin B1.
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PMID:Modification of aflatoxin B1-induced changes in certain mitochondrial enzymes and lipids by medroxyprogesterone acetate. 294 74

Nephrotoxicity is a serious side effect that limits the use of cyclosporine (CyA) as an immunosuppressive agent. The purpose of this study was to develop a model of CyA nephrotoxicity in the isolated perfused rat kidney and to evaluate the effects of adenosine triphosphate (ATP)-MgCl2 and verapamil treatment on this model. Kidneys were perfused for 90 minutes in a 7.5% albumin-Krebs-HCO3 solution containing 3H-inulin (glomerular marker) and 5.0 micrograms/ml 14C-cytochrome C (cyt) (marker of tubular protein absorption). After 10-minute equilibration, perfusate and urine samples were collected with 10-minute clearance periods. After two control clearance periods, 500 ng/ml CyA was added to the perfusate. In some experiments, 1 micrograms/ml of verapamil was added 10 minutes before CyA and in others 2 mmol/l ATP-MgCl2 was added with CyA. Cyt and inulin radioactivity, [Na+] and [K+], were measured in perfusate and urine. Tissue ATP levels were also determined. The results demonstrate that CyA treatment leads to a marked depression of glomerular filtration rate (GFR), tubular absorption of protein, urine output, and renal flow. ATP-MgCl2 cotreatment improved GFR, tubular absorption, and renal perfusate flow but the increase in urine output was not dramatic. Verapamil pretreatment markedly improved GFR and urine and renal perfusate flow but not tubular function. The combination of verapamil and ATP-MgCl2 treatment with CyA returned GFR to control values, significantly improved tubular absorption, urine and renal perfusate flow, and enhanced renal tissue ATP of isolated kidneys to levels seen in vivo. These data lead us to conclude that ATP-MgCl2 cotreatment with CyA after verapamil pretreatment greatly reduces the nephrotoxic potential of this immunosuppressive agent.
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PMID:Treatment with verapamil and adenosine triphosphate-MgCl2 reduces cyclosporine nephrotoxicity. 295 Jun 8

This study was directed at relating ion transport and mitochondrial redox activity during hypoxia, as a step toward definition of brain oxygen sufficiency. To accomplish this, extracellular potassium ion activity (K+o) was recorded by ion-selective microelectrodes while reduction/oxidation (redox) ratios of cytochrome oxidase (cytochrome a,a3) were monitored by reflection spectrophotometry in cerebral cortex of rats anesthetized with pentobarbital. In normoxia, neuronal activation by direct cortical stimulation produced transient oxidation of cytochrome a,a3 and elevation of K+o. Moderate hypoxia (PaO2 above 50 mm Hg) resulted in reduction of cytochrome a,a3 but only slight elevation of K+o. At this level of hypoxia, cytochrome a,a3 continued to respond to neuronal activation with transient shifts toward oxidation and rates of K+o reaccumulation were unchanged from control. When PaO2 was further decreased below a critical threshold, stimulus-provoked oxidative responses of mitochondrial reactants were replaced by shifts toward reduction, but rates of reaccumulation of K+, spilled into the extracellular space by neuronal activation, remained unchanged. Only during severe hypoxia (PaO2 less than 20 mm Hg) was it possible in some animals to record a slowing in the reaccumulation of K+o without provocation of spreading cortical depression. These data indicate that ion transport activity in cerebral cortex is more refractory to hypoxia than is mitochondrial redox functioning. They suggest an in vivo parallel to the "cushioning" effect of mitochondria in vitro, in which oxygen consumption remains constant despite fluctuations in oxygenation and redox ratios, and also that there may be a greater anaerobic capacity to provide energy for ion transport in mammalian brain than has previously been appreciated.
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PMID:Potassium ion homeostasis and mitochondrial redox activity in brain: relative changes as indicators of hypoxia. 334 90


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