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 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We examined the role of reactive oxygen metabolites in the degradation of human glomerular basement membrane (GBM) by stimulated human neutrophils. Neutrophils stimulated with phorbol myristate acetate (PMA) caused a significant degradation of GBM over 3 h resulting in 11.4 +/- 0.9% (SEM), n = 11 release of hydroxyproline compared with 0.3 +/- 0.09%, n = 11 release by unstimulated neutrophils. Superoxide dismutase, a scavenger of superoxide, did not inhibit the GBM degradation, whereas catalase, a scavenger of hydrogen peroxide, caused a marked inhibition (-60 +/- 7%, n = 4, P less than 0.001) of hydroxyproline release. Neither alpha-1 proteinase inhibitor, an inhibitor of elastase, nor soya bean trypsin inhibitor, an inhibitor of cathepsin G, caused any significant inhibition of GBM degradation. GBM degradation by cell-free supernatants obtained from stimulated neutrophils was markedly impaired in the presence of metal chelators EDTA (-72 +/- 7, n = 6, P less than 0.001) and 1,10,phenanthroline (-85 +/- 5%, n = 3, P less than 0.001). Considering these results, we postulated that reactive oxygen metabolites generated by the stimulated neutrophils activate a latent GBM degrading metalloproteinase(s). GBM degradation by supernatants obtained from incubations with catalase, azide, an inhibitor of myeloperoxidase, and methionine and taurine, scavengers of hypochlorous acid, was markedly reduced. Our data thus indicate that degradation of the GBM by PMA-stimulated neutrophils is due to activation of a latent metalloproteinase by hypochlorous acid or a similar oxidant generated by the myeloperoxidase-hydrogen peroxide-halide system.
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PMID:Degradation of human glomerular basement membrane by stimulated neutrophils. Activation of a metalloproteinase(s) by reactive oxygen metabolites. 302 61

1. Somatostatin analogues, such as SMS 201-995 (sandostatin), have been suggested as treatment for a variety of disease states including acromegaly, secretory gastrointestinal tumours and diabetes mellitus. 2. Somatostatin-14 has actions to prolong gastro-intestinal transit time and inhibit intestinal absorption, and we have therefore studied the effects of SMS 201-995 on these processes. Five male subjects received a test meal having been given either saline or 50 micrograms of SMS 201-995 subcutaneously 30 min before ingestion. 3. SMS 201-995 caused a delay in mouth-to-caecum transit time for lactulose assessed by breath hydrogen analysis (316 +/- 17 vs 192 +/- 14 min, mean +/- SEM, P less than 0.01), a delay (234 vs 120 min, P less than 0.05) in the plasma peak of the non-metabolizable glucose analogue 3-O-methylglucose and conversion of the expected postprandial rise in serum triglycerides (with saline 1.02 +/- 0.20 to 1.51 +/- 0.28 mmol/l, P less than 0.05) to a decrease below basal values (with SMS 201-995 0.97 +/- 0.80 to 0.79 +/- 0.11 mmol/l, P less than 0.05). 4. After SMS 201-995, an enhancement of the increase in blood glucose (8.2 +/- 0.7 vs 4.7 +/- 0.2 mmol/l, P less than 0.01) and inhibition and postponement of the postprandial rise in insulin (27.6 +/- 6.7 vs 9.9 +/- 2.1 m-units/l, P less than 0.05) occurred. Furthermore, a rise in non-esterified fatty acids, glycerol and 3-hydroxybutyrate, compared with the decline in concentrations of these metabolites after saline, was observed.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of the somatostatin analogue SMS 201-995 (sandostatin) on mouth-to-caecum transit time and absorption of fat and carbohydrates in normal man. 305 74

The mechanism for the prolonged contractile dysfunction observed in myocardium reperfused after reversible regional ischemia ("stunned" myocardium) is unclear. Recent studies suggest that myocardial stunning may be mediated by oxygen-derived free radicals, but the precise molecular species involved remain unknown. Thus we explored the role of the highly cytotoxic hydroxyl radical in regional postischemic dysfunction by using dimethylthiourea (DMTU), an effective and highly permeable hydroxyl radical scavenger. Open-chest dogs undergoing a 15 min occlusion of the left anterior descending coronary artery followed by 4 hr of reperfusion received either DMTU (0.5 g/kg iv over 45 min starting 30 min before occlusion, n = 14) or saline (n = 15). Control and treated dogs were comparable with respect to variables that may affect postischemic dysfunction, including heart rate, aortic pressure, left atrial pressure, arterial blood gases and hemoglobin concentration, size of the occluded bed (determined by postmortem perfusion), and collateral blood flow (determined by radioactive microspheres). Regional myocardial function was assessed by measuring wall thickening with an epicardial Doppler probe. The two groups exhibited comparable systolic thickening under baseline conditions and similar degrees of dyskinesis during ischemia. After reperfusion, however, wall thickening (expressed as percent of baseline) was considerably greater in treated as compared with control dogs: 53 +/- 9% (mean +/- SEM) vs 9 +/- 14% (p less than .03) at 1 hr, 55 +/- 9% vs 23 +/- 13% (p less than .05) at 2 hr, 60 +/- 9% vs 28 +/- 14% (p less than .05) at 3 hr, and 67 +/- 5% vs 36 +/- 13% (p less than .05) at 4 hr. Thus DMTU produced a significant and sustained improvement in recovery of contractile function. In concentrations greater than the plasma levels attained in vivo, DMTU did not scavenge either hydrogen peroxide or superoxide anion in vitro. These results suggest that the myocardial dysfunction occurring after a brief episode of regional ischemia is mediated in part by the hydroxyl radical.
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PMID:Attenuation of dysfunction in the postischemic 'stunned' myocardium by dimethylthiourea. 311 44

When protamine (2 mg/kg) was injected intravenously into awake sheep 5 minutes after infusing heparin (200 units/kg), there was transient diffuse pulmonary vasoconstriction with mean pulmonary arterial pressure increasing from 18.0 +/- 0.7 to 43.8 +/- 2.7 mm Hg at 1 minute (x +/- SEM; n = 10). In addition, there was profound leukopenia (36.9 +/- 7.7% of baseline values at 2 minutes) with transpulmonary leukocyte sequestration and transiently elevated plasma concentrations of C3a (from 420 +/- 146 to 1,599 +/- 249 ng/ml; n = 3, p less than 0.01) and thromboxane B2 (from 0.30 +/- 0.05 to 6.3 +/- 2.8 ng/ml; n = 10, p less than 0.0001), without significant increases of plasma 6-keto-prostaglandin F1 alpha, prostaglandin F2 alpha, leukotrienes, or histamine. Intravenous injection of protamine alone produced no hemodynamic effects and did not increase plasma levels of vasoconstrictor eicosanoids. Intravenous pretreatment with either a cyclooxygenase inhibitor or a hydrogen peroxide scavenger (dimethylthiourea) blocked both the increases of thromboxane levels and the pulmonary vasoconstriction.
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PMID:Acute pulmonary vasoconstriction and thromboxane release during protamine reversal of heparin anticoagulation in awake sheep. Evidence for the role of reactive oxygen metabolites following nonimmunological complement activation. 312 8

Orocecal transit time was measured simultaneously by the hydrogen breath test and a barium meal study in 12 hospitalized patients, the objective being to determine whether the former test accurately represents the orocecal transit time, and to establish an adequate criterion for the transit time, based on the former test. Two definitions of orocecal transit time by the hydrogen breath test were evaluated: the time from lactulose ingestion to a sustained increase of over 5 ppm above fasting levels in the end-expiratory hydrogen concentration (definition A) and the interval to that of over 10 ppm (definition B). The orocecal transit time measured by the radiologic method was 63 +/- 9 min (mean +/- SEM), whereas that using definition A of the hydrogen breath test was 74 +/- 9 min, and that using definition B was 87 +/- 10 min. Transit times determined by both definitions closely correlated with that obtained by the radiologic method (A, r = 0.86, p less than 0.01; B, r = 0.81, p less than 0.01). Therefore, elevation of end-expiratory hydrogen concentrations seemed to coincide with cecal appearance of the head of the lactulose load. When the mean transit times were compared with findings in case of the radiologic method, definition A rather than B appeared to be more appropriate to determine orocecal transit time.
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PMID:Hydrogen breath test assessment of orocecal transit time: comparison with barium meal study. 319 40

Cylinders of microfil and small-particle light-cured composite resin were bonded to the flattened labial enamel surface of young bovine incisor teeth which had previously been subjected to four different treatments: (1) teeth immersed in 35% hydrogen peroxide (HP) for 60 min and etched (E) with 37% phosphoric acid gel for 60 sec; (2) teeth immersed in saline (S) for 60 min and E for 60 sec; (3) teeth E for 60 sec and immersed in HP for 60 min; and (4) teeth E for 60 sec, immersed in S for 60 min. Specimens were stored in water at 37 degrees for one and seven days prior to tension- and shear-testing. A total of 256 teeth was tested--eight teeth in each group for each day, for each resin, and for each test. Statistical analysis of the results indicated that there was a highly significant reduction in adhesive bond strength of the resins when the enamel was exposed to HP as compared with S. SEM examination of randomly selected fractured test specimens indicated that this reduction in adhesive bond strength occurred primarily at the bonding resin-enamel interface. Less significant differences in bond strength were noted in the control specimens, with regard to resin type, time of storage, and the etching order.
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PMID:Adhesion of composite resin to bleached and unbleached bovine enamel. 319 53

Skeletal muscle injury after revascularization (ischemia-reperfusion) continues to be a major clinical problem. Although heparinization has been recommended, its action in an experimental model of I-R has not been evaluated. We investigated the ability of heparinization to decrease I-R injury in 10 anesthetized dogs (nonheparinized, n = 5; heparinized, n = 5), subjecting one gracilis muscle to 6 hours of ischemia followed by 1 hour of reperfusion while the identically prepared contralateral muscle served as a nonischemic control. Skeletal muscle infarction was determined by Tc-PYP uptake. Endothelial permeability was quantified by measurement of skeletal muscle 125I-Alb activity after intravenous injection. Interstitial hydrogen ion (H+) accumulation was determined by a miniature pH electrode inserted into the gracilis muscle. Isotopic activities from the ischemic muscle were calculated as a percentage of the contralateral nonischemic muscle (mean +/- SEM). Nonheparinized ischemic muscles had an increase in the activities of Tc-PYP and 125I-Alb of 684% +/- 149% and 742% +/- 130%, which were reduced to 218% +/- 54% and 378% +/- 85% by heparinization, respectively (p less than 0.05). During ischemia, the nonheparinized muscles accumulated 1223 +/- 121 nmol of H+ compared with 785 +/- 95 nmol in the heparinized animals (p less than 0.01). This significant reduction in I-R injury may be causally related to diminished endothelial permeability and H+ accumulation.
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PMID:Heparinization reduces endothelial permeability and hydrogen ion accumulation in a canine skeletal muscle ischemia-reperfusion model. 335 77

Malabsorption after total gastrectomy and Roux-en-Y reconstruction was studied in 11 patients. Absorption of fat, xylose and lactose was tested and the orocaecal transit time was radiologically determined. Bacterial colonization of the small intestine was studied by culturing jejunal juice and indirectly with a hydrogen breath test. Ten patients lost weight postoperatively and six had diarrhoea. All 11 had steatorrhoea with mean faecal fat excretion 289 +/- 55 (SEM) mmol free and esterified fatty acids/72 h (upper reference limit 60 mmol/72 h). Low xylose absorption was found in only one patient and low lactose absorption in none. The median orocaecal transit time was only 110 minutes (less than or equal to 60 min in 4 cases). Postoperative weight loss showed significant inverse correlation with orocaecal transit time. Bacterial overgrowth of the small intestine was found in four patients. The cause of malabsorption was assumed to be rapid intestinal transit in four patients and bacterial overgrowth in four others, leaving three in whom pancreatic understimulation is suggested as the reason for steatorrhoea.
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PMID:Causes of malabsorption after total gastrectomy with Roux-en-Y reconstruction. 335 82

Dietary starch delivery to the colon and excretion in stools and the ability of unabsorbed carbohydrates to promote hydrogen and methane release in breath were evaluated in 6 volunteers during two 8-day periods on starch diets of 100 and 300 g, respectively. Significantly less starch was recovered from the terminal ileum by aspiration per 24 h during the low-starch period (4.1 +/- 0.3 vs. 9.5 +/- 1.1 g, mean +/- SEM, p less than 0.01). Unabsorbed glucose tended to rise during the high-starch period (2.7 +/- 0.8 vs. 1.1 +/- 0.3 g). Fecal outputs of starch, glucose, volatile fatty acids, and lactic acid were not significantly different during the two periods. Daily breath hydrogen excretion was unchanged (181.2 +/- 22.7 vs. 193.7 +/- 19.8 ml for the low- and high-starch periods, respectively), whereas breath methane excretion increased markedly in the three methane producers during the high-starch period (217.2 +/- 80.9 vs. 32.4 +/- 7.3 ml). Starch malabsorption in the healthy small intestine was moderate even with a high-starch diet and less than that previously estimated by indirect methods. Unabsorbed starch catabolism by the colonic flora does not seem to explain most of the breath hydrogen excretion.
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PMID:Starch malabsorption and breath gas excretion in healthy humans consuming low- and high-starch diets. 339 66

Platelet-activating factor has been implicated in a variety of disease processes including ischemic brain injury and endotoxic shock, but its effects on cerebral blood flow (CBF) and metabolism in normal brain have not been described. The effects of platelet-activating factor on global CBF (hydrogen clearance) and the global cerebral metabolic rate for oxygen (CMRO2) were studied in halothane-N2O anesthetized Wistar rats. Hexadecyl-platelet-activating factor infused into the right carotid artery (67 pmol/min) for 60 min decreased mean arterial pressure (MAP) from 122 +/- 4 (x +/- SEM) to 77 +/- 6 mm Hg and CBF from 159 +/- 12 to 116 +/- 14 ml/100 g/min (p less than 0.002). In contrast, CMRO2 increased from 9.7 +/- 0.9 to 11.7 +/- 1.1 ml/100 g/min after 15 min (p less than 0.05). In controls rendered similarly hypotensive by blood withdrawal and infused with the platelet-activating factor vehicle, CMRO2 was unchanged, whereas CBF transiently decreased then returned to baseline at 60 min. These cerebrovascular and cerebrometabolic effects of PAF are reminiscent of and may be relevant to hypoperfusion and hypermetabolism observed after global brain ischemia and in endotoxic shock.
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PMID:Cerebrovascular and cerebrometabolic effects of intracarotid infused platelet-activating factor in rats. 339 15


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