Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: C33C12 .10
 63,145 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The mechanism of the periportal (p.p.) toxicity of allyl alcohol (AlOH) was investigated in p.p. and perivenous (p.v.) hepatocytes isolated by digitonin-collagenase perfusion. The distinct origin of the cell preparations was confirmed by the p.p./p.v. ratios of alanine aminotransferase (p.p./p.v. = 1.8), lactate dehydrogenase (1.3) and glutamine synthetase (0.10). The activity of alcohol dehydrogenase (ADH) was not markedly different in p.p. and p.v. cells. Both types of cells oxidized AlOH at a high but equal rate of about 3 mumol/(min.g cells). Concomitantly with rapid oxidation of 0.7 mM AlOH, glutathione (GSH) was depleted by about 95% and its secretion was completely inhibited in both cell types. Although the GSH content was partially restored during a subsequent 3-h incubation, cellular ATP and K+ content gradually decreased and the leakage of lactate dehydrogenase increased in both types of cells. However, the p.p. cells tended to resist AlOH in vitro better, probably due to their 26% higher GSH content after preincubation with L-methionine. Altering the partial pressure of oxygen in physiological range had no effect on the toxicity of AlOH. The results are contrary to the suggestions that the p.p. location of AlOH liver injury is caused by higher ADH activity or higher oxygen tension in the p.p. zone. Rather, the regiospecificity of the injury may be due to rapid uptake and oxidation of AlOH in the p.p. region.
 ...
PMID:Allyl alcohol cytotoxicity and glutathione depletion in isolated periportal and perivenous rat hepatocytes. 283 85

The effect of selective vs. nonselective beta-blockade on fast-twitch [extensor digitorum longus (EDL)] and slow-twitch [soleus (SOL)] muscle enzyme activities following endurance training were characterized. Citrate synthase (CS), lactate dehydrogenase (LDH), and beta-hydroxyacyl-CoA dehydrogenase (HAD) activities were compared in SOL and EDL muscles of trained (T), metoprolol-trained (MT), propranolol-trained (PT), and sedentary (C) rats. Following 8 wk of treadmill running (1 h/day, 5 days/wk at approximately 30 m/min), LDH activity was depressed approximately 20% (P less than 0.05) in both SOL and EDL in only the PT rats, indicating inhibition of beta 2-mediated anaerobic glycolysis. EDL CS activity was similarly elevated in all three trained groups compared with sedentary controls. In SOL muscle, however, a drug attenuation effect was observed so that CS activity was increased only in the T (P less than 0.01) and MT (P less than 0.05) groups. HAD enzyme activity was increased somewhat (P less than 0.10) in SOL muscle in only the T group, but more so (P less than 0.05) in EDL in all three trained groups. The above findings suggest a training-induced selectivity effect not only with respect to beta 1-vs. beta 1-beta 2-blockers, but also with respect to muscle fiber type.
 ...
PMID:Effects of beta 1- vs. beta 1- beta 2-blockade on training adaptations in rat skeletal muscle. 287 98

Because of reported synergism between 5-fluorouracil (5-FU) and cisplatin (CDDP) in L1210 leukemic mice and activity of this combination in clinical studies, a trial was initiated in previously untreated patients with advanced colorectal carcinoma. Cisplatin at 20 mg/m2 and 5-FU as a continuous infusion at 1000 mg/m2 were both administered for 5 consecutive days every 4 weeks. Forty-one patients were treated at Memorial Sloan-Kettering Cancer Center (MSKCC) and 46 were treated by the Community Clinical Oncology Program (CCOP) physicians. A 50% reduction in measurable disease was seen in 12 of 35 (34%) MSKCC patients and in nine of 41 (22%) of the CCOP patients with 95% confidence intervals of 0.18 to 0.50 and 0.10 to 0.35 in the two groups, respectively. The predominant toxicities were as follows: nausea and vomiting, 32%; mucositis, 26%; leukocyte counts less than 2000 cells/mm3, 17%; platelet counts less than 25,000 cells/mm3, 8%; and severe neurotoxicity, 5%. Dose attenuation was similar in the two groups. The median survival was 16.4 months for the MSKCC group and 9.6 months for the CCOP group (P = 0.0003). Although the baseline characteristics (age, sex, performance status, and baseline lactic dehydrogenase [LDH] and alkaline phosphatase) were similar, on further examination differences between the two groups were evident. In the MSKCC group, 14% of patients with liver metastases had greater than 50% of their liver involved with tumor whereas this occurred in 41% of the CCOP group (P = 0.03). The LDH values greater than 500 U/l were observed in 10% of patients in the MSKCC group and in 37% of the patients in the CCOP group (P = 0.007). Characteristics which reflect the bulk of disease, such as the percent of liver involvement, need to be analyzed in order to evaluate purported survival differences in randomized and nonrandomized trials of colorectal carcinoma.
 ...
PMID:Cisplatin and 5-fluorouracil infusion for metastatic colorectal carcinoma. Differences in survival in two patient groups with similar response rates. 291 9

We have found that pretreatment of human neutrophils with ibuprofen (0.10-1.0 mg/ml) results in an irreversible, concentration-dependent inhibition of superoxide anion generation and release of lysosomal enzymes (myeloperoxidase, lysozyme) stimulated by the synthetic peptide, N-formyl-methionyl-leucyl-phenylalanine (FMLP), the complement fragment C5a, and to a lesser extent by serum opsonized zymosan. Inhibition of granule exocytosis and oxygen radical generation at ibuprofen concentrations less than 5 mg/ml was not due to drug cytotoxicity since release of the cytoplasmic enzyme lactate dehydrogenase was not affected by ibuprofen. In contrast to neutrophil responses mediated by C5a or FMLP, ibuprofen did not inhibit either enzyme release or superoxide anion generation by neutrophils stimulated with phorbol myristate acetate. Ibuprofen did not function as an oxygen radical scavenger in a cell-free system in which superoxide anion was generated by the aerobic action of xanthine oxidase on hypoxanthine. Ibuprofen also inhibited in a concentration-dependent fashion both directed migration (chemotaxis) and stimulated random migration (chemokinesis) of neutrophils exposed to either FMLP or C5a. Inhibition of neutrophil adherence to plastic surfaces and bovine pulmonary artery endothelial cells was equally effective when the neutrophils were treated with ibuprofen before stimulation with FMLP or phorbol myristate acetate. The inhibitory effects of ibuprofen pretreatment of neutrophils could not be overcome by addition of prostaglandins E1 or E2 (0.3-300 nM). These results demonstrate that ibuprofen is capable of suppressing many functions thought to be important in neutrophil-mediated acute pulmonary inflammatory processes. Results of these experiments further suggest that ibuprofen may inhibit neutrophil functions by acting on cellular components separate from membrane receptors or by blockade of cyclo-oxygenase products which may be involved in these neutrophil functions.
 ...
PMID:Inhibition of human polymorphonuclear leukocyte functions by ibuprofen. 303 52

The effect of early coronary artery reperfusion on ECG and enzymatic parameters was examined in 240 patients with acute myocardial infarction. These patients had participated in a randomized trial comparing intravenous anisoylated plasminogen streptokinase activator complex (APSAC) (n = 123) and intracoronary streptokinase (n = 117) therapy. Reperfusion occurred in 59 of 115 (51%) patients receiving APSAC and 67 of 111 (60%) patients receiving streptokinase (p = NS). There was greater early resolution of ST segment elevation in the reperfused than in the nonreperfused patients (p less than or equal to 0.003) and more rapid Q wave evolution (p less than or equal to 0.03). Sigma Q was lower in reperfused than in nonreperfused patients at 8 hours (1.41 +/- 1.18 versus 2.11 +/- 2.10 mV; p less than or equal to 0.05) and at 24 hours (1.43 +/- 1.25 mV versus 2.08 +/- 1.88 mV; p less than or equal to 0.02). Time to peak level was shorter in the reperfused patients for creatine kinase (CK) (10.7 +/- 5.5 hours versus 14.9 +/- 5.9 hours; p less than 0.0001) and lactic acid dehydrogenase (LDH) (29.6 +/- 13.6 hours versus 34.4 +/- 10.5 hours; less than or equal to 0.03) enzymes. Peak LDH-1 was lower in the reperfused group (274 +/- 149 U/L versus 341 +/- 173 U/L; p less than or equal to 0.04). Reperfusion at a mean of 3.9 hours after the onset of infarction was associated with more rapid resolution of ST segment elevation, faster Q wave evolution, smaller ECG infarct size, earlier cardiac enzyme release, and smaller enzymatic infarct size than later or no reperfusion.
 ...
PMID:Effect of reperfusion on electrocardiographic and enzymatic infarct size: results of a randomized multicenter study of intravenous anisoylated plasminogen streptokinase activator complex (APSAC) versus intracoronary streptokinase in acute myocardial infarction. 305 85

In this study inflammatory responses were determined in rat lungs 0, 1, 3, and 8 days following single 2- and 4-hr exposures to 1.8 ppm ozone. Analysis of lavage fluid immediately following exposure demonstrated enhanced lactate dehydrogenase activity and decreased numbers of lavageable macrophages but no alterations in albumin content. Similar analyses at one day postexposure demonstrated 282% and 456% increases in albumin content and enhanced numbers of lavageable neutrophils from a control value of 0.01 +/- 0.01 to 0.27 +/- 0.10 and 0.78 +/- 0.11 million cells per lung for 2-hr and 4-hr exposures, respectively. The observed increased levels of albumin were also present at 3 days, at which time the number of lavageable neutrophils was not significantly different than control. At both one and 3 days postexposure, lavageable lymphocytes were significantly increased 10-fold from a control value of 0.03 +/- 0.01 million cells per lung. However, the number of lavageable macrophages was unaltered on day 1, but enhanced on day 3, giving values of 0.67 +/- 0.05 (control), 2.25 +/- 0.46 (2 hr), and 2.70 +/- 1.05 (4 hr) million cells per lung. By 8 days both inflammatory cell numbers and albumin levels had returned to control values. Since these data demonstrated different time courses for each inflammatory cell type, this reversible model of acute lung injury should be useful for establishing possible involvement of these cells in processes of lung injury.
 ...
PMID:A reversible model of acute lung injury based on ozone exposure. 314 94

The effect of thrombolytic therapy on ECG and enzymatic indices, including estimates of relative infarct size, was studied in 93 patients with acute myocardial infarction randomised to intracoronary streptokinase or intravenous anisoylated plasminogen streptokinase activator complex (APSAC) therapy within 6 hours of the onset of symptoms. 90 minutes after treatment, 49% (19/39) of the evaluable streptokinase patients and 44% (19/43) of the APSAC patients had reperfused (p = NS). The time from treatment to reperfusion was less in the streptokinase patients (30 +/- 18 minutes for streptokinase and 42 +/- 22 minutes for APSAC, p less than or equal to 0.02). Resolution of ST segment elevation, 90 minutes after treatment, was greater in the streptokinase patients (residual ST segment elevation 47 +/- 36% of initial value for streptokinase and 70 +/- 49% for APSAC, p less than or equal to 0.06) and in the patients reperfused by either agent (residual ST segment elevation 46 +/- 34% for reperfused and 68 +/- 52% for non-reperfused, p less than or equal to 0.10). ECG infarct size at discharge, determined by sum of Q waves and a 29-point QRS score, relative to the degree of initial ST segment elevation was similar in the streptokinase and APSAC patients, but smaller in reperfused than non-reperfused patients (p less than or equal to 0.01 for sigma Q). Peak serum creatine kinase and MB isoenzyme of creatine kinase levels were similar in the streptokinase and APSAC, and in reperfused and non-reperfused patients. Lower peak lactic acid dehydrogenase and especially lactic acid dehydrogenase isoenzyme values (by 16% and 22%, respectively) were observed in reperfused patients, but differences did not achieve significance. However, the time to peak enzyme levels was significantly shorter in the reperfused patients. Early intracoronary streptokinase and intravenous APSAC therapy have similar effects on ECG and enzymatic infarct size. Reperfusion by either agent, given at a mean of 3 hours 25 minutes, may reduce estimates of infarct size modestly.
 ...
PMID:Electrocardiographic and enzymatic infarct size in a randomised study of intracoronary streptokinase and intravenous anisoylated plasminogen streptokinase activator complex in acute myocardial infarction. 331 92

The major surfactant-associated protein is a potent inhibitor of surfactant phospholipid secretion from isolated type II cells. Since the major surfactant-associated protein contains a carboxy terminal polypeptide domain which is homologous to the lectin-like liver mannose-binding protein, we tested whether lectins inhibit surfactant phospholipid secretion from rat alveolar type II cells. Concanavalin A, wheat germ agglutinin and Maclura pomifera agglutinin were potent inhibitors of surfactant phospholipid secretion. When adenosine 5'-triphosphate (ATP) was utilized as a secretagogue, the IC50 values for inhibition of surfactant phospholipid secretion were 5.10(-7) (wheat germ agglutinin), 1.10(-6) (concanavalin A) and 2.5.10(-5) M (M. pomifera agglutinin). Similar results were obtained when 12-O-tetradecanoylphorbol 13-acetate was utilized as a secretagogue: IC50 values of 1.10(-6) M for concanavalin A and wheat germ agglutinin and 2.5.10(-5) M for M. pomifera agglutinin. Hapten sugars were utilized to antagonize the inhibitory effect of the lectins. N-Acetyl-D-glucosamine significantly reversed inhibition of phospholipid secretion by wheat germ agglutinin in a dose-dependent fashion and methyl alpha-D-mannoside significantly reversed inhibition of phospholipid secretion by concanavalin A. N-Acetyl-D-galactosamine had no significant effect on inhibition of secretion produced by any of the lectins. The inhibitory effect of the lectins did not appear to be due to cytotoxicity since lactate dehydrogenase was not released above control levels and the inhibition of the surfactant phospholipid secretion by wheat germ agglutinin could be reversed after treatment of cells with wheat germ agglutinin by washing the lectin from the cells followed by treatment of the cells with ATP. These studies demonstrate a direct inhibitory effect of plant lectins on phospholipid secretion from type II cells in vitro.
 ...
PMID:Regulation of surfactant phospholipid secretion from isolated rat alveolar type II cells by lectins. 333 35

To investigate some biochemical changes during bovine follicle development, ovaries were obtained from cyclic heifers (7 to 11 heifers/d on each day of the 21-d estrous cycle; N = 152). Follicular fluid from the two largest follicles from both ovaries and a pool from small follicles (N = 30/cow) were collected from each animal and analyzed for ionic, enzymatic and endocrine changes in relation to day of the estrous cycle, follicle size, rank and atretic or growing status. Follicular fluid alkaline phosphatase activity and ascorbate concentrations were highest in all follicular sizes during the earlier portion of the estrous cycle (d 1 to 12; P less than .05), then decreased to the lowest levels (d 13 to 21). As follicular size (diameter) increased lactate dehydrogenase (LDH), acid and alkaline phosphatase activity was reduced in follicular fluid (P less than .05). Alkaline phosphatase and LDH activity tended to be increased in atretic follicles (P less than .10), and was correlated with increased progesterone and androgen concentrations of follicular fluid (r = .4, P less than .05). Both albumin and total protein concentrations decreased as follicular diameter increased (P less than .05). Sodium concentrations in follicular fluid were greater in growing-antral than atretic follicles, and increased with follicular enlargement (P less than .05). Follicular potassium concentrations increased as the estrous cycle progressed (P less than .05), and tended to be elevated in atretic follicles (nonsignificant). Both Ca and Mg concentrations increased with follicular enlargement (P less than .05). Dehydroepiandrosterone and testosterone were the predominant androgens in follicular fluid (androstenedione, the lowest concentration); their concentration decreased with follicle development (P less than .05), but were quite variable. Estradiol was increased in growing follicles (P less than .01). Estrone and estradiol concentrations increased as ovulation approached, particularly in small follicles (less than or equal to 4 mm diameter). Changes of biochemical components found in follicular fluid that relate to the growth and atresia process may provide a more sensitive and accurate method to classify follicle status, and thus aid in understanding the complexity of events associated with maturation of the bovine follicle and oocyte.
 ...
PMID:Biochemical analysis of bovine follicular fluid: albumin, total protein, lysosomal enzymes, ions, steroids and ascorbic acid content in relation to follicular size, rank, atresia classification and day of estrous cycle. 357 Oct 24

The effects of isoprenaline administration (300 micrograms/kg for 5 weeks) on rat soleus muscle capillarity and glycolytic and oxidative capacities were evaluated. The treatment resulted in ventricular hypertrophy. The activities of lactic dehydrogenase, pyruvate kinase, citrate synthase, and cytochrome c oxidase in soleus muscle homogenates were not different between control and isoprenaline-injected animals. Capillaries were visualized in muscle cross sections treated to demonstrate ATPase activity after acid preincubation. Capillary density was higher in the experimental (873 +/- 38 capillaries/mm2) than in the control (713 +/- 33 capillaries/mm2) animals. Capillary to fiber ratio was also higher in the experimental (2.47 +/- 0.10) than in control (2.09 +/- 0.08) animals, but fiber cross-sectional area was not changed by the treatment (2836 +/- 87 microns2 in controls and 2951 +/- 136 microns2 in experimental). A plot of capillary to fiber ratio vs. fiber cross-sectional area showed that at a given fiber cross-sectional area the value of capillary to fiber ratio of the treated animals was higher than that of the controls. This indicates that treatment resulted in the proliferation of microvessels. The results suggest that prolonged beta-adrenergic stimulation results in the development of new capillaries but that this is not accompanied by increases in the oxidative capacity of the soleus muscle of the rat.
 ...
PMID:Long-term isoprenaline administration produces an increase in capillarity in the soleus muscle of the rat. 358 Sep 52


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>