Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: HUMANGGP:025734 (ANOVA)
 22,580 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Intestinal ischemia was induced and maintained for 60 minutes in male Sprague-Dawley rats weighing 175 to 225 g. Prior to reperfusion, the following drugs were administered via the caudal vena cava: 0.9% NaCl (0.5 ml), superoxide dismutase (SOD; 1,000 IU/kg of body weight), polyethylene glycol-conjugated SOD (PEG-SOD; 1,000 IU/kg), or the 21-aminosteroids, U74006F (3 mg/kg) or U78715G (3 mg/kg). A sham-operated control group was included. Animals from each group were euthanatized at 5 periods of reperfusion: 5 minutes, 30 minutes, 18 hours, 3 days, and 7 days after reperfusion. Fixed tissues were embedded in paraffin, sectioned at 5 microns, and stained with H&E. Villi profiled in cross section were measured from the crypt villus junction to the tip of the villus. The mean villus height for each rat was calculated and compared by two-way ANOVA to determine the effects of time and treatment. Villus height was maintained after 30 minutes of reperfusion in rats of the sham- and U74006F-treated groups; U78715G and SOD treatment attenuated the loss in villus height, and villus height was not maintained in the PEG-SOD- and 0.9% NaCl-treated rats. In all rats, villus height was comparable to, or was greater than villus height in sham-operated controls by 18 hours after reperfusion in all animals and remained constant through 7 days. Administration of the 21-aminosteroids maintained villus height after ischemia and reperfusion. Treatment with PEG-SOD did not maintain villus height to the degree observed in rats treated with SOD.
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PMID:Evaluation of intestinal villus height in rats after ischemia and reperfusion by administration of superoxide dismutase, polyethylene glycol-conjugated superoxide dismutase, and two 21-aminosteroids. 146 14

The aim of this study was to determine whether oxidative stress occurs in unstable angina. Thirty patients with unstable angina class B (Braunwald classification) were prospectively studied. Control groups consisted of 23 patients presenting with stable angina and of 21 age-matched healthy volunteers. Upon admission and every 8 h for 24 h, blood samples were drawn for the determination of plasma malondialdehyde (MDA) levels, Se-glutathione peroxidase (GPX) activity, erythrocyte reduced glutathione (GSH) concentrations, erythrocyte GPX and superoxide dismutase (SOD) activities. Coronary angiograms were performed within 4 days of admission in 26 out of the 30 patients included in the study. Nine of these 30 patients were subsequently identified as presenting a non-Q wave myocardial infarction and were separately examined. On admission, only plasma MDA levels and erythrocyte GSH concentrations differed among groups. Plasma MDA levels of patients presenting with unstable angina (P < 0.01) and acute myocardial infarction (P < 0.05) were higher than those of patients with stable angina and of normal volunteers, whereas there was no difference in these parameters between unstable angina and non-Q wave myocardial infarction groups. Erythrocyte GSH concentration was lower in all patient groups as compared to normal subjects. ANOVA for repeated measures showed no difference between admission and subsequent levels for all parameters. Finally, no difference was observed for any of the parameters when anti-ischaemic or anti-aggregant treatment before admission, or the number of affected vessels on coronary angiograms, were considered. We conclude that an oxidative stress can be evidenced in patients with unstable angina or acute myocardial infarction.
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PMID:Oxidative stress in patients with unstable angina. 800 17

1. Previous studies have shown that endothelium-dependent relaxation in the aorta of spontaneously diabetic bio bred rats (BB) is impaired. 2. We have investigated noradrenaline (NA) contractility, endothelium-dependent acetylcholine (ACh) and bradykinin (BK) relaxation, and endothelium-independent sodium nitroprusside (SNP) relaxation in mesenteric resistance arteries of recent onset BB rats and established insulin treated BB rats, compared to their age-matched non diabetic controls. 3. There was no significant difference in the maximum contractile response or sensitivity to noradrenaline in either of the diabetic groups compared to their age-matched controls. 4. Incubation with the nitric oxide synthetase inhibitor NG-nitro-L-arginine (L-NOARG) resulted in a significant increase in maximum contractile response to noradrenaline in the recent onset age-matched control group (P < 0.05). Analysis of the whole dose-response curve (using ANOVA for repeated measures with paired t test) showed a significant left-ward shift following the addition of L-NOARG (P < 0.001). A similar but less marked shift (P < 0.01) was evident in vessels from recent onset diabetics. An overall shift in both sensitivity and maximum response was also evident in the age-matched non diabetic controls of the insulin-treated group (P < 0.05). However, by contrast, there was no significant change in sensitivity in the insulin-treated diabetic rats. 5. ACh-induced endothelium-dependent relaxation was significantly impaired in the recent onset diabetic rats compared to their age-matched controls (47 +/- 11% versus 92 +/- 2%, P < 0.05, n = 6), and in the insulin treated diabetic rats (34 +/- 5% versus 75 +/- 6%, P < 0.05, n = 6). The relaxation responses to BK also were significantly impaired in the diabetic rats compared to their age-matched controls (recent onset: 20 +/- 3% versus 72 +/- 7%, P < 0.05, n = 6; insulin treated: 12 +/- 9% versus 68 +/- 7%, P < 0.05, n = 7). 6. Incubation with either the nitric oxide synthetase substrate, U-arginine, or the free radical scavenging enzyme superoxide dismutase (150 mu ml-1) failed to improve the attenuated response of acetylcholine-induced relaxation in the diabetic vessels. 7. Endothelium-dependent relaxation mediated by ACh and BK was significantly attenuated in both the diabetic and control vessels after incubation with L-NOARG. 8. Pretreatment with a cyclo-oxygenase inhibitor, indomethacin, significantly enhanced the relaxation to ACh in both the recent onset and insulin treated diabetic rats (42 +/- 10%, n = 7 versus 64 +/- 7%, n = 7, P < 0.05, and 40 +/- 5%, n = 7 versus 65 +/- 9%, n = 6, P < 0.05). 9. Following endothelium removal, there was a marked impairment in endothelium-dependent relaxation responses to ACh and BK in both the diabetic and control vessels. 10. Incubation with the thromboxane A2 receptor antagonist SQ29548, did not significantly improve the ACh endothelium-dependent relaxation response in the diabetic vessels. 11. Endothelium-independent relaxation to sodium nitroprusside was significantly impaired in the first group of diabetic vessels studied; however, subsequent studies showed no impairment of the sodium nitroprusside response in the diabetic vessels. 12. In conclusion, the ability of the endothelium to regulate vascular contractility is reduced in recent onset diabetic vessels, and significantly impaired in established insulin treated diabetics. Relaxation to the endothelium-dependent vasodilators ACh and BK was impaired in both the recent onset and the established insulin treated diabetics, and the ACh response was significantly improved following pretreatment with indomethacin, suggesting a role for a cyclo-oxygenase-derived vasoconstrictor. Preliminary studies with a thromboxane A2, receptor antagonist, SQ29548 did not significantly improve the impaired relaxation to ACh, indicating that the vasoconstrictor prostanoid is not thromboxane A2.
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PMID:Impaired endothelium-dependent relaxation in isolated resistance arteries of spontaneously diabetic rats. 871 4

Plasma, erythrocyte and leukocyte lipid peroxidation, erythrocyte superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and plasma gamma-glutamyl transferase (GGT) levels were investigated in 36 healthy non-drinkers aged between 18-55 years (mean 38.7) and 72 alcohol drinkers aged between 20-48 years (mean 35.3) in order to determine the oxidative effect of alcohol. Erythrocyte lipid peroxidation of the drinkers (measured in terms of MDA) was found to be significantly (P < 0.05) reduced compared to that of controls. However, when Tukey-HSD and F test with ANOVA were performed, that significance disappears in those who consume less than 140 g of alcohol per day and persists in those who consume more than 140 g of alcohol per day (P < 0.05). Plasma GGT level was significantly increased compared to that of controls (P < 0.001). Also, there was a significant (P = 0.01) correlation between serum GGT level and the amount of alcohol. There were no significant differences between all the other parameters of both groups. Reduced lipid peroxidation of erythrocytes without any accompanying increase in the activities of antioxidant enzymes shows that another mechanism might be responsible for this finding. This mechanism was thought to be an alteration in lipid composition of erythrocyte membranes.
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PMID:Effect of moderate alcohol intake on lipid peroxidation in plasma, erythrocyte and leukocyte and on some antioxidant enzymes. 943 42

Dietary calorie restriction extends both mean and maximum life span and retards age-related diseases, including eye lens cataract in Emory mice. The beneficial effects of calorie restriction have been hypothesized to reflect enhanced tissue antioxidant capacity. As a test of this hypothesis, we reared male and female Emory mice on control (C) or 40% calorie-restricted (R) diets. We then determined activities of total superoxide dismutase (T-SOD), Cu/Zn-SOD, Mn-SOD, glutathione peroxidase (GPx), glutathione reductase (GR) and catalase (CAT) in eye lens, liver and kidney of young (4.5 or 6 months), mature (11 or 12 months) and old (22 months) animals. Effects of diet, age and sex were evaluated by multi-factor ANOVA. Only kidney GR activities (mean +/- S.E.M.) were significantly enhanced with the R diet (R, 61 +/- 2 vs. C, 54 +/- 3 U/mg protein; P = 0.03). More frequently, we noted reduced antioxidant enzyme activity in R as compared with C animals, including reduced activities of T-SOD in lens, liver and kidney, Cu/Zn-SOD in liver and kidney, liver Mn-SOD and liver CAT (P < 0.05). Effects of age on antioxidant enzyme activity in C mice included age-dependent decreases in lens and kidney CAT and in liver Mn-SOD. There was also an age-dependent increases in liver and kidney Cu/Zn-SOD and liver GR. None of these age-dependent alterations in antioxidant enzyme function were attenuated in tissues of mice fed the R diet. Values for liver CAT were significantly lower in females than in males (P = 0.05). These results indicate that antioxidant enzyme activities in Emory mouse tissues are influenced by diet, age and sex. However, it is unlikely that increased lifespan and attenuation of cataract (and perhaps other age-dependent debilities), which are associated with the R diet in the Emory mouse, are due to enhanced antioxidant enzyme capabilities.
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PMID:Antioxidant enzyme activities in lens, liver and kidney of calorie restricted Emory mice. 948 91

Inhaled nitric oxide (NO) is an important new therapeutic agent used to treat pulmonary arterial hypertension in a variety of disease states. However, the effects of NO on cells in the lung are uncertain. Previously, we have shown that NO gas depresses neutrophil oxidative cell function and increases neutrophil cell death. The purpose of this in vitro study was to determine the mechanism of neutrophil death. We hypothesized that NO hastened cell death by inducing apoptosis. To mimic the clinical environment of patients with respiratory failure, we also studied the effects of hyperoxia on neutrophil cell viability and apoptosis. Isolated human neutrophils were exposed to 80% O2 (O2), NO at 20 ppm in room air (NO/RA), 20 ppm NO blended with 80% O2 (NO/O2), or RA alone (control) for 2 to 24 h. Experiments were repeated with NO concentrations of 5 and 50 ppm and with 20 ppm in the presence of superoxide dismutase (SOD). Neutrophils were also incubated in the absence or presence of neutrophil stimulant fMLP (10 nM). Neutrophil cell viability was measured by fluorescence viability/cytotoxicity assay. Neutrophil apoptosis was assessed by cell death detection ELISA for histone-associated DNA fragments, TdT transferase-mediated fluorescence-labeled dUTP nick end labeling (TUNEL) assay, and DNA fragmentation gel electrophoresis. NO/O2-exposed neutrophils showed decreased viability at 2 h (31.7 +/- 3.7%, mean % viability +/- SD) compared with control (94.7 +/- 4.7%), O2 (75.6 +/- 9.3%), and NO/RA (62.8 +/- 14.9%; P < 0.05 by ANOVA; n = 9). Although control neutrophils demonstrated marked apoptosis at 24 h, there was no significant apoptosis at 2, 4, or 6 h (P < 0.001 by Kruskal-Wallis, n = 20) as assessed by ELISA and TUNEL assays. When compared with RA controls at 2 h, neutrophils exposed to NO/O2 showed significantly more apoptosis (292% of control, range: 106 to 2,488%, P < 0.001 by ANOVA and Kruskal-Wallis) but not with exposure to NO/RA or O2 alone. These findings were confirmed by TUNEL assay (n = 4, P < 0.05). NO/ RA and NO/O2-exposed neutrophils demonstrated both evidence of necrosis and enhanced DNA fragmentation at 2 h by gel electrophoresis (n = 2). Fifty parts per million NO produced similar findings, but exposure to 5 ppm NO did not induce significant DNA fragmentation. Coincubation with SOD inhibited NO/ O2-associated apoptosis, suggesting peroxynitrite contributed to cell death. Stimulation with fMLP did not alter apoptosis induced in neutrophils exposed to NO/RA or NO/O2. We conclude that exogenous NO gas, at clinically relevant concentrations under hyperoxic conditions, induces cell death in neutrophils in part by enhancing DNA fragmentation.
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PMID:Exogenous nitric oxide enhances neutrophil cell death and DNA fragmentation. 949 Jun 60

Laser Doppler flowmetry (LDF) was tested in an experimental ischaemic model on rat limbs to evaluate the degree of ischaemia and to find a possible correlation with values obtained with this device and prognosis. Under general anaesthesia, 40 Wistar rats were submitted to 4 h and 30 min of ischaemia of the left hind limb. Ten rats formed the control group (group 1). Two enzymes, native superoxide dismutase (SOD) and SOD modified with polyethylene glycol, were employed in 15 rats each (groups 2 and 3). Data were collected by means of LDF both in the sole and muscles before ischaemia (steady state), during ischaemia and at the beginning of reperfusion, and only in the sole after 1 h of reperfusion. A range of predictive (95%) perfusion values (PU) for limb healing or necrosis was identified at the beginning of reperfusion. During ischaemia, PU changed from 0 to 10, both in the sole and in the muscle. A three-factor ANOVA (site, group, time) did not show interaction of these factors with PU (F = 1.655; p = 0.195), even if every single effect was significant (p < 0.0005). A two-factor ANOVA (group, time) showed a significant interaction of these factors with PU (F = 4.079; p = 0.019). The logistic regression between the reperfusion PU of each site and the survival of the limb was observed at the beginning and after 1 h of reperfusion in the sole only. Furthermore, a correlation between sole and muscle PU at the steady state and at the beginning of the reperfusion period was observed. The results showed the effectiveness of LDF, which can be considered a quite reliable tool to evaluate the degree of ischaemia and to have a good correlation with prognosis in this kind of experiments.
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PMID:Laser Doppler evaluation of microcirculation behaviour during an ischaemia-reperfusion injury. 956 44

Oxidative stress has been proposed as a possible pathogenic factor for diabetic complications. It is relevant in determining cell replicative capacity and life span, and in vitro antioxidant treatment is able to reverse the impaired proliferative activity of different cell types. It was recently demonstrated that cultured skin fibroblasts from insulin-dependent diabetic patients with nephropathy age prematurely and have a shorter life cell cycle. To test whether the growth phenotype of cells from patients with diabetic nephropathy was related to a lack of protection from oxidative stress, the effect of reduced glutathione (GSH) on cultured skin fibroblasts from 13 insulin-dependent diabetes mellitus (IDDM) patients with nephropathy (DN), 10 IDDM patients without kidney disease (D), and 10 nondiabetic control subjects (C), in normal (5 mM) glucose (NG) and high (22 mM) glucose (HG) medium was studied. After 6 to 8 passages, fibroblasts from DN showed impaired growth both in NG (mean +/- SD fold increase over baseline counts in DN 1.17 +/- 0.6 versus D 1.7 +/- 0.5 versus C 1.95 +/- 0.8; P = 0.04 by ANOVA) and in HG (mean +/- SD fold increase over baseline counts DN 1.16 +/- 0.41 versus D 1.89 +/- 0.66 versus C 2.24 +/- 0.9; P = 0.003 by ANOVA). GSH prevented the growth abnormalities of cells from DN restoring it to values similar to that of the other two groups (mean +/- SD fold increase over baseline counts NG +/- GSH: DN 1.68 +/- 0.9 versus D 1.78 +/- 0.49 versus C 1.99 +/- 0.7, P = 0.6; and in HG + GSH: DN 1.66 +/- 0.69 versus D 1.87 +/- 0.75 versus C 2.2 +/- 0.9, P = 0.3). Growth rates were not affected by the addition of GSH in fibroblasts from D and C. The treatment of fibroblasts from D and C with the inhibitor of the gamma-glutamylcysteine synthetase activity, L-buthionine-S,R-sulfoximine, resulted in growth impairment, and the addition to the culture medium of another antioxidant, superoxide dismutase, corrected the growth abnormalities in fibroblasts from DN. The impaired growth of cultured fibroblasts from IDDM patients with nephropathy is prevented by GSH and superoxide dismutase and is independent of prevailing glucose concentrations. This suggests that oxidative stress is an important mechanism of intrinsic cell dysfunction in these patients.
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PMID:Glutathione reverses the growth abnormalities of skin fibroblasts from insulin-dependent diabetic patients with nephropathy. 962 Dec 89

Chronic administration of enalapril in the aging mouse prevents myocardial fibrosis. To investigate the mechanisms involved, we studied 30 CF1 female mice that received enalapril (ENAL:20 mg/L) in their drinking water after weaning and 30 control (CONT) mice. Ten animals from each group were killed at 12, 18, and 24 months. Half of the samples were prepared for light microscopy (LM) and the other half for electron microscopy (EM). Cardiac histologic sections were studied by an image analyzer (Bioscan OPTIMAS 4.1). We performed the following measurements in cardiomyocytes: mitochondrial number, mitochondrial superoxide dismutase (SOD) using immunohistochemical methods with EM, the percentage of cell cyclin, and apoptosis. The results obtained for CONT and ENAL, respectively were as follows. For cyclin (percentage of positive) our results were: 12 months 17.1+/-0.1% and 18.2+/-0.8%, 18 months 2.4+/-1.6% (P < .001), and 11.4+/-0.1% (P < .001), 24 months 1.2+/-1.3% (P < .001), and 8.2+/-1.2% (P < .001) with significant differences at 18 and 24 months. For the Feulgen method (cell/mm2) we found: 12 months CONT 89.7+/-1.2, ENAL 84.6+/-1.2; 18 months CONT 62.8+/-1.2, ENAL 98.7+/-1.3, and 24 months CONT 81.2+/-1.3, ENAL 112.3+/-1.4. Apoptosis (percentage of positive) was found to be 12 months 3.7+/-0.4% and 1.9+/-0.1%, 18 months 7.1 +/-0.3% (P < .001), and 1.5+/-0.1% (P < .001), 24 months 10.9+/-0.5% (P < .001) and 2.1+/-1.8% (P < .001), for CONT and ENAL, respectively; there were significant differences at 18 and 24 months. The number of mitochondria per cardiomyocyte were: 12 months 85.9+/-1.8 and 87.3+/-1.5, 18 months 69.2+/-1.5t and 82.2+/-1.8 (P < .001), 24 months 54.6+/-1.1 (P < .001) and 81.4+/-1.6 (P < .001) for CONT and ENAL respectively, with significant differences at 18 and 24 months. Mitochondrial SOD was found to be: 12 months 13.6%+/-0.2% (P < .05) and 17.8%+/-1.3% (P < .05), 18 months 7.1%+/-1.0% (P < .001) and 16.7%+/-1.6% (P < .001), 24 months 4.1%+/-0.5% (P < .001), and 12.4%+/-0.9% (P .001) for CONT and ENAL respectively, with significant differences at 12 months and at 18 and 24 months (ANOVA and contrast Scheffe's test). We conclude that chronic administration of ENAL modifies mitochondrial SOD at 12 months, whereas at 18 and 24 months ENAL was associated with higher mitochondrial SOD and a higher mitochondrial number with a greater cyclin expression, and a lower percentage of apoptosis. Enalapril may prevent myocardial fibrosis, possibly by causing changes related to enzymatic-mitochondrial or cellular cycle modifications.
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PMID:Biomolecular changes in the aging myocardium: the effect of enalapril. 983 72

Endogenous superoxide anion (O(-)(2)) interferes with the bioactivity of nitric oxide (NO) in endothelium-dependent arterial relaxation (EDR). Using the lucigenin chemiluminescence assay, we measured O(-)(2) in the thoracic and abdominal aortas and the carotid artery of rabbits to determine whether ambient O(-)(2) varies among the three arteries and differentially diminishes the effect of NO. Basal levels of O(-)(2) were significantly higher in carotid arteries than in the thoracic aorta [23 +/- 6.1 vs. 3.9 +/- 1.4 chemiluminescence units (CU); P < 0.05], whereas EDR in response to ACh (10(-8)-10(-5) M) was not significantly different on ANOVA. After treatment with the superoxide dismutase (SOD) inhibitor diethyldithiocarbamate (DDC; 10 mM), O(-)(2) levels were significantly elevated, becoming greater in the carotid artery and abdominal aorta than in the thoracic aorta (185 +/- 31.2 and 202 +/- 40.3 vs. 89 +/- 18 CU; P < 0.05). DDC significantly reversed EDR in the thoracic aorta but not in the carotid artery; at 10(-6) M ACh, the decrease seen with DDC was 48 +/- 6.2 vs. 6.8 +/- 8.0% of maximal relaxation in the thoracic aorta and carotid artery, respectively. In the thoracic aorta, exogenous SOD reversed the inhibition of EDR caused by DDC. Moreover, DDC/O(-)(2)-resistant EDR in the carotid artery was ablated by the addition of nitro-L-arginine methyl ester (300 microM; P < 0.05), an NO synthase inhibitor, consistent with peroxynitrite or an O(-)(2)-resistant NO donor being involved in carotid relaxation. Indeed, exogenous peroxynitrite caused similar relaxation of the carotid artery and thoracic aorta, which was unaffected by DDC. Our studies show a greater production of nitrite and O(-)(2) per unit area by the carotid artery, suggesting a greater amount of their product peroxynitrite. These findings support the hypothesis that peroxynitrite is the relaxing agent that resists high O(-)(2) in the carotid artery.
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PMID:Resistance of endothelium-dependent relaxation to elevation of O(-)(2) levels in rabbit carotid artery. 1056 67


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