Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0406810 (NAME)
 13,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Organ Weight, hematologic and blood chemistry values were determined to establish reference values in the female ferret. Organ weight per kg body weight was calculated for various organs. Body surface area (BSA) was also determined by the direct method, and K values (constant) were calculated. The K value was 3.48 in the Dubois and Dubois equation, and 9.69 in the Meeh-Rubner equation. Blood samples were used to record 10 hematologic and 57 serum (plasma) chemistry values, and 7 immunological parameters. Among hematologic values, values whose coefficient of variation (cv) exceeded 30% were RBC, WBC and PLT. In blood chemistry, the CV of gamma-G, UA, ZTT, GPT, gamma-GTP, MAO, ALD and IgG exceeded 30%. In the total amino acid analysis, only the CV of TAU exceeded 30%. Electrophoretograms of amylase and CPK isozyme were quite different from those of humans. Although 1-MEHIS, 3-MEHIS and CAR have not been detected or are present in trace amounts in human plasma, concrete values were detected in female ferret plasma. Hematologic and serum chemistry values were in general agreement with normal values seen in cats and dogs. However, the alpha 1-G percentage, and ALP and amylase activities were lower than the corresponding values in cats and dogs. The RBC count, RET-C percentage and LDH activities were higher than in cats and dogs. Since there have been no comprehensive articles on reference values for the female ferret, the present report contributes to studies that involve this animal as an experimental model.
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PMID:Reference values for organ weight, hematology and serum chemistry in the female ferret (Mustela putrius furo). 851 87

The purpose of this study was to gain direct insights into mechanisms by which myoglobin induces proximal tubular cell death. To avoid confounding systemic and hemodynamic influences, an in vitro model of myoglobin cytotoxicity was employed. Human proximal tubular (HK-2) cells were incubated with 10 mg/ml myoglobin, and after 24 hours the lethal cell injury was assessed (vital dye uptake; LDH release). The roles played by heme oxygenase (HO), cytochrome p450, free iron, intracellular Ca2+, nitric oxide, H2O2, hydroxyl radical (-OH), and mitochondrial electron transport were assessed. HO inhibition (Sn protoporphyrin) conferred almost complete protection against myoglobin cytotoxicity (92% vs. 22% cell viability). This benefit was fully reproduced by iron chelation therapy (deferoxamine). Conversely, divergent cytochrome p450 inhibitors (cimetidine, aminobenzotriazole, troleandomycin) were without effect Catalase induced dose dependent cytoprotection, virtually complete, at a 5000 U/ml dose. Conversely, -OH scavengers (benzoate, DMTU, mannitol), xanthine oxidase inhibition (oxypurinol), superoxide dismutase, and manipulators of nitric oxide expression (L-NAME, L-arginine) were without effect. Intracellular (but not extracellular) calcium chelation (BAPTA-AM) caused approximately 50% reductions in myoglobin-induced cell death. The ability of Ca2+ (plus iron) to drive H2O2 production (phenol red assay) suggests one potential mechanism. Blockade of site 2 (antimycin) and site 3 (azide), but not site 1 (rotenone), mitochondrial electron transport significantly reduced myoglobin cytotoxicity. Inhibition of Na, K-ATPase driven respiration (ouabain) produced a similar protective effect. We conclude that: (1) HO-generated iron release initiates myoglobin toxicity in HK-2 cells; (2) myoglobin, rather than cytochrome p450, appears to be the more likely source of toxic iron release; (3) H2O2 generation, perhaps facilitated by intracellular Ca2+/iron, appears to play a critical role; and (4) cellular respiration/terminal mitochondrial electron transport ultimately helps mediate myoglobin's cytotoxic effect. Formation of poorly characterized toxic iron/H2O2-based reactive intermediates at this site seems likely to be involved.
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PMID:Myoglobin toxicity in proximal human kidney cells: roles of Fe, Ca2+, H2O2, and terminal mitochondrial electron transport. 906 5

The potent endothelial-derived vasodilator nitric oxide (NO) has been identified as a protective agent in acute renal failure. However, some recent studies have suggested a detrimental effect of NO on rat proximal tubules exposed to hypoxia and reoxygenation. We determined whether NO metabolites cause intracellular oxidation during hypoxia and reoxygenation and whether this oxidative stress is linked to irreversible cell injury. Primary cultures of rat proximal tubular epithelial cells were studied in a subconfluent stage and subjected to 60 min hypoxia and 30 min reoxygenation. Intracellular oxidation was assessed by monitoring the conversion of nonfluorescent dihydrorhodamine 123 (DHR) to fluorescent rhodamine 123 as a probe for the long-lived oxidant peroxynitrite. Hypoxia and reoxygenation produced a marked increase in cellular generation of oxidant species. Intracellular oxidation of DHR was reduced by approximately 40% when cells were also exposed to the NO synthase inhibitor L-NAME. Oxidation of DHR following hypoxia and reoxygenation was not affected by SOD or DMTU. A combination of SOD and L-NAME was no more effective than L-NAME alone. Hypoxia and reoxygenation produced substantial injury (as LDH release). There was a 40% reduction in LDH release when cells were pretreated with a NO synthase inhibitor. In summary, increased generation of NO capable of inducing intracellular oxidizing reactions and cell death occurred during renal hypoxia and reoxygenation.
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PMID:Nitric oxide-mediated renal epithelial cell injury during hypoxia and reoxygenation. 960 34

Nitric oxide (NO) has been shown to be a mediator of hypoxic injury in rat renal proximal tubules (PT). However, the role of NO in hypoxic injury to mouse. PT has not been examined. The aim of the present study was to determine the effect of knockout of nitric oxide synthase (NOS) isoforms on hypoxic injury in mouse PT. Mouse PTs were isolated by collagenase digestion and Percoll centrifugation. The nonselective NOS inhibitor, N-nitro-L-arginine methyl ester (L-NAME, 10 mM), but not its inactive stereoisomer D-NAME, protected against hypoxic injury as assessed by LDH release. Carboxy-imidazolineoxyl N-oxide (carboxy-PTIO, 100 microM), a stable NO scavenger, also afforded cytoprotection against hypoxic injury. To determine the role of the different NOS isoforms in the hypoxic injury, we examined the effect of hypoxia on PT isolated from knockout mice in which either the inducible NOS (iNOS) endothelial NOS (eNOS) or neuronal NOS (nNOS) gene was lacking. PT isolated from iNOS knockout mice were resistant to hypoxic injury compared to wild-type controls. In contrast, PT isolated from both nNOS and eNOS knockout mice were not protected against hypoxic injury. In conclusion, the present study demonstrates that NO is a mediator of hypoxic PT injury in the mouse and that knockout of the iNOS gene is cytoprotective against this hypoxic PT injury.
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PMID:Effect of hypoxia on proximal tubules isolated from nitric oxide synthase knockout mice. 960 95

This study was performed to determine whether ischemia/reperfusion (I/R) injury in rat liver results in alterations in endothelin receptor expression. Hepatic ischemia was produced in rats for 60 min followed by 6 or 24 h reperfusion. Portal inflow pressure was increased (7.38+/-0.60 mmHg) at 24 hours after reperfusion. Serum ALT increased significantly at both 6 and 24 h (6 h; 258.3+/-74.3, 24 h; 243.1+/-74.8 IU/L). Portal vascular response to an endothelin-B receptor agonist (IRL 1620) was significantly increased in the I/R livers compared to control and this was potentiated by L-NAME. IRL 1620 also caused LDH release from I/R livers but not controls. LDH release after IRL 1620 in I/R livers correlated with increased portal pressure response. To determine whether the altered response might be the result of altered endothelin receptor expression, livers were harvested after reperfusion and total endothelin binding sites were determined by competitive binding with ET-1. Proportion of endothelin receptor subtypes (ET(A)/ET(B)) was determined using the ET(A) antagonist BQ-610 (1 microM) and ET(B) agonist IRL-1620 (100 nM). There were no significant changes in Kd but Bmax for endothelin-1 was decreased in I/R group especially non-ischemic lobe at 24 h. ET(A) receptors were significantly decreased whereas ET(B) receptors were increased. These changes were more pronounced at 24 h after reperfusion than at 6 h. Interestingly, the changes in ET receptors was observed identically both in ischemic and non-ischemic lobes (ischemic lobe ET(A) 41.9%, ET(B) 51%; non-ischemic lobe ET(A) 38.8%, ET(B) 49.5%). These results indicate that the major functional endothelin receptor subtype upregulated in I/R is the ET(B) receptor and that this upregulation may contribute to microvascular dysregulation and hepatic injury.
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PMID:Altered endothelin receptor subtype expression in hepatic injury after ischemia/reperfusion. 1063 73

The protective effects of l-3-n-butylphthalide (l-NBP) and d-3-n-butylphthalide (d-NBP) on KCl (20 mmol.L-1)- or NMDA (N-methyl-D-aspartate, 30 mumol.L-1)-induced cytotoxicity in primary cultured rat cortical neurons were studied. Intracellular LDH release, percentage of cell death and cellular morphological changes were used to evaluate the effect of drugs. l-NBP (1-100 mumol.L-1) and d-NBP (1-100 mumol.L-1), but not nimodipine (1-100 mumol.L-1), were shown to dose-dependently inhibit LDH release induced by NMDA (30 mumol.L-1) in cultured rat cortical neurons with IC50 values of 4.89 mumol.L-1 and 13.52 mumol.L-1, respectively. The percent cell death was reduced with IC50 values of 44.37 and 49.78 mumol.L-1, and the cellular morphology improved. The effect seemed to be the same as that of equal concentration of NAME(NG-nitro-L-arginine methyl ester). In addition, l-NBP(10 mumol.L-1), d-NBP (10 mumol.L-1) and nimodipine(10 mumol.L-1) also produced significant inhibition on intracellular LDH release and decrease in percent cell death induced by KCl(20 mmol.L-1) in cultured neurons. The potencies of l-NBP and d-NBP were similar to that of equal dose of nimodipine. These data suggest that l-NBP and d-NBP can remarkably protect cultured neurons against the damage induced by KCl and NMDA.
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PMID:[Protective effects of D-3-N-butylphthalide and L-3-N-butylphthalide on neuronal damage induced by KCl and NMDA in cultured rat cortical neurons]. 1149 68

The antioxidant effect of the non-specific nitric oxide synthase inhibitor, N omega-nitro-L-arginine methyl ester (CAS 50903-99-6, L-NAME), was studied in a rat model of global cerebral ischemia. In addition, the influence of low doses of L-NAME on nitric oxide production, measured as nitrate/nitrite end products, was investigated in the ischemic rats. Ischemia was induced by bilateral clamping of the common carotid arteries for 60 min followed by a reperfusion period for 60 min. L-NAME was administered intraperitoneally in the doses of 1 and 3 mg kg-1, twice, immediately after ischemia and 15 min before termination of the experiment. The drug decreased the elevated activity of lactate dehydrogenase (LDH, 1.1.1.27) as well as the increased level of lipid peroxide in the rat brain. L-NAME was also capable to normalize the reduced activity of superoxide dismutase (SOD, 1.15.1.1) that was observed after ischemia. Improvement of these parameters in L-NAME-treated rats was parallel to normalization of nitric oxide production in the treated animals. These results indicate that inhibition of nitric oxide synthase, induced by L-NAME, could improve the oxidative status of the rat brain after ischemia.
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PMID:Antioxidant effect of N omega-nitro-L-arginine methyl ester (L-NAME) on global cerebral ischemia in a rat model. 1155 22

During intestinal ischemia, CO2 accumulates in tissue as a result of bicarbonate buffering of anaerobic acid generation. Previous studies have shown that nitric oxide (NO) generated during ischemic preconditioning acts as a glycolytic modulator, thus decreasing tissue lactate production. We studied if ischemic preconditioning induces NO-dependent changes in static mesenteric venous blood Pco2 values and CO2 accumulation during intestinal ischemia. Superior mesenteric venous (smv) acid base variables were studied in 4 groups of rats: a control group (C), an ischemic (90-min period of flow arrest) group (I), an ischemic group subjected to previous ischemic preconditioning (P), and an ischemic group subjected to previous ischemic preconditioning in which nitric oxide synthase (NOS) was inhibited by N-nitro-L-arginine methyl ester (L-NAME) administration (P+N). Preconditioning induced acidosis in smv blood during reperfusion before ischemia, but this effect was counteracted by L-NAME. Group P showed the lowest values of end-ischemic tissue lactate, smv blood CO2 accumulation, and LDH in perfusate, whereas group P+N showed the highest level of LDH in perfusate but the lowest end-ischemic smv blood Pco2 and acidity. We conclude that lower ischemic CO2 accumulation in static smv blood, but not lower end-ischemic Pco2, was related with the protective effect of ischemic preconditioning in our rat model. Thus, the use of stagnant smv blood Pco2 as an indicative of intestinal dysoxia can lead to misinterpretations if a broader acid-base picture is not considered.
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PMID:CO2 in static mesenteric venous blood during intestinal ischemia and ischemic preconditioning in rats. 1169 82

The relationship between nitric oxide (NO) and intracellular Ca2+ in hypoxic-ischemic brain damage is not known in detail. Here we used rat striatal slices perfused under low-oxygen and Ca2+-free conditions and cultured human astrocytoma cells incubated under similar conditions as models to study the dynamics of intracellular NO and Ca2+ in hypoxia-induced tissue damage. Exposure of rat striatal slices for 70 min to low oxygen tension elicited a delayed and sustained increase in the release of 45Ca2+. This was potentiated by the NO donors sodium nitroprusside (SNP) and spermine-NO and inhibited by N-omega-nitro-L-arginine methyl ester (L-NAME) or by the NO scavenger 2-phenyl-4,4,5,5 tetramethylimidazoline-1-oxyl-3-oxide (PTIO). A membrane-permeant form of heparin in combination with either ruthenium red (RR) or ryanodine (RY) also inhibited 45Ca2+ release. In human astrocytoma U-373 MG cells, hypoxia increased intracellular Ca2+ concentration ([Ca2+]i) by 67.2 +/- 13.1% compared to normoxic controls and this effect was inhibited by L-NAME, PTIO or heparin plus RR. In striatal tissue, hypoxia increased NO production and LDH release and both effects were antagonized by L-NAME. Although heparin plus RR or RY antagonized hypoxia-induced increase in LDH release they failed to counteract increased NO production. These data therefore indicate that NO contributes to hypoxic damage through increased intracellular Ca2+ mobilization from endoplasmic reticulum and suggest that the NO-Ca2+ signalling might be a potential therapeutic target in hypoxia-induced neuronal degeneration.
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PMID:Potentiation of intracellular Ca2+ mobilization by hypoxia-induced NO generation in rat brain striatal slices and human astrocytoma U-373 MG cells and its involvement in tissue damage. 1260 59

The role of nitric oxide (NO) in ischemia/reperfusion injury is controversial. We tested the role of inducible NOS (iNOS) in the ischemia/reperfusion injury in isolated rat hearts using the selective iNOS inhibitor S-methylisothiourea sulfate (SMT) and the non-selective NOS inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME). After 15 min of stabilization in Langendorff mode, hearts were perfused either with normal Krebs-Henseleit buffer, buffer containing 100 microM L-NAME, 0.5 microM SMT or 50 microM SMT for 5 min and were subjected to 25 min of ischemia followed by 30 min of reperfusion. Left ventricular developed pressure (LVDP) and total coronary flow (CF) were recorded continuously. After ischemia/reperfusion, a marked expression of iNOS protein was demonstrated by Western blotting, while virtually no iNOS protein was present in hearts without ischemia/reperfusion. Regional myocardial blood flow (RMBF) was measured with colored microspheres. Coronary vasoactive concentration of L-NAME and SMT depressed myocardial function as shown by decreased LVDP, dP/dt(max) and coronary.ow before ischemia. After ischemia the recovery of the total CF was impaired in L-NAME and 50 microM SMT pretreated hearts which was related to homogenous RMBF decrease in the right and left ventricle compared to that in control group. Low concentration SMT (0.5 microM) showed no coronary vasoactive effects before ischemia and attenuated ischemia/reperfusion injury indicated by lower ischemic contracture at 25 min of ischemia and reduced CK and LDH release during reperfusion. Thus, NOS inhibition did not affect blood flow distribution in rat hearts either in the pre-ischemic or reperfusion period. Selective iNOS inhibition reduced ischemic injury by reducing ischemic contracture and CK as well as LDH release during reperfusion.
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PMID:Selective modulation of endogenous nitric oxide formation in ischemia/reperfusion injury in isolated rat hearts--effects on regional myocardial flow and enzyme release. 1288 34


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