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Biomedical subjects

E R Trimble

Publications and source records attributed to E R Trimble.

At least 55 records · Page 3Linked to original sources
PubMed1993

Lipid peroxidation and antioxidant status following thrombolytic therapy for acute myocardial infarction.

We have investigated the timescale of increased lipid peroxidation following successful early thrombolytic therapy for acute myocardial infarction and report for the first time reciprocal changes in plasma chain-breaking antioxidants. Sixty-seven patients were recruited following a first acute myocardial infarction within 6 h of the onset of symptoms and received 70 or 100 mg of recombinant tissue plasminogen activator (Actilyse) as two intravenous bolus injections 30 min apart. Serial blood samples were taken before administration of thrombolytic therapy and after 30 min, 60 min, 90 min, 6 h and 24 h. Coronary artery patency was assessed at 90 min by coronary angiography. Malondialdehyde (MDA), a marker of lipid peroxidation, and the chain-breaking antioxidants alpha-tocopherol, retinol and ascorbate were measured by high performance liquid chromatography. When the coronary artery was patent there was an early rise in plasma MDA (time 0 0.91 +/- 0.05 mumol.l-1) with levels peaking at 90 min (1.02 +/- 0.06, P < 0.05) and returning to baseline by 6 h (0.85 +/- 0.06), accompanied by reciprocal decreases in alpha-tocopherol (time 0 7.13 +/- 0.34 mumol.mmol-1 cholesterol, 90 min 6.64 +/- 0.33, P < 0.05) and retinol (time 0 1.99 +/- 0.10 mumol.l-1, 90 min 1.81 +/- 0.08, P < 0.05). Ascorbate levels did not change significantly until 24 h (time 0 29.5 +/- 4.9 mumol.l-1, 24 h 22.6 +/- 4.4, P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Altered cardiac oxygen extraction, lactate production and coronary blood flow after large dose transthoracic DC countershocks.

Although problems such as hypotension and pulmonary edema complicate the use of transthoracic DC countershocks, the mechanisms are not clear. In anesthetized dogs at 1 minute after only two defibrillator shocks there was a brief rise in coronary sinus lactate, exceeding arterial concentrations. Larger rises in lactate were seen after five shocks, indicating myocardial production of lactate. By contrast in eight animals given dummy shocks the heart always extracted lactate. At 2 minutes after five shocks mean myocardial oxygen extraction (6.5 +/- 0.6 mL/100 mL/100 mL blood; n = 4; P < 0.001), and remained so until 3 minutes after shocks, without significant increase in the lipid peroxidation product malondialdehyde in coronary sinus or arterial blood. Great cardiac venous blood flow, measured by thermodilution, rose after five shocks, and the heart rate pressure product also increased at 1-2 minutes. This transient failure of oxygen extraction, in the presence of arterial normoxia, hyperemia, and increased cardiac work, is best accounted for by a central effect of countershocks on myocardial cellular respiration.

Animals↗
PubMed1993

The effect of cortisol on glucose/glucose-6-phosphate cycle activity and insulin action.

Increased glucose/glucose-6-phosphate (G/G6P) substrate cycle activity may be an early marker of disordered hepatic glucose metabolism. To investigate the effects of glucocorticoids on G/G6P cycle activity and insulin resistance, we studied eight normal subjects using the euglycemic glucose clamp technique with high pressure liquid chromatography-purified [2(3)H]- and [6-3H]glucose tracers at insulin infusion rates of 0.4 and 2.0 mU/kg.min after 24-h cortisol (2 micrograms/kg.min) and saline infusions. Endogenous glucose production ([6-3H]glucose) was greater after cortisol than saline in the postabsorptive state (13.3 +/- 0.5 vs. 12.2 +/- 0.5 mumol/kg.min; P < 0.05) and during 0.4-mU insulin infusion (10.5 +/- 0.7 vs. 5.0 +/- 0.8 mumol/kg.min; P < 0.005). During 2.0-mU insulin infusion, endogenous glucose production was suppressed similarly (5.1 +/- 0.4 vs. 4.1 +/- 0.5 mumol/kg.min), but glucose disappearance was less after cortisol than saline (38.7 +/- 3.5 vs. 64.6 +/- 4.3 mumol/kg.min; P < 0.001). G/G6P cycle activity after cortisol and saline was similar in the postabsorptive state and during 0.4 mU insulin. During 2.0 mU insulin, cycle activity was greater after cortisol than saline (3.6 +/- 0.9 vs. 0.8 +/- 0.5 mumol/kg.min; P < 0.005). In conclusion, cortisol induces hepatic insulin resistance without significantly changing G/G6P cycle activity. At high glucose turnover rates, G/G6P cycle activity is increased by cortisol; however, reduced glucose disappearance is the main cause of impaired insulin action.

Absorption↗
PubMed1992

Insulin action and hepatic glucose cycling in essential hypertension.

Peripheral insulin resistance is a feature of essential hypertension, but there is little information about hepatic insulin sensitivity. To investigate peripheral and hepatic insulin sensitivity and activity of the hepatic glucose/glucose 6-phosphate (G/G6P) substrate cycle in essential hypertension, euglycemic glucose clamps were performed in eight untreated patients and eight matched controls at insulin infusion rates of 0.2 and 1.0 mU.kg-1.min-1. A simultaneous infusion of (2(3)H)- and (6(3)H)glucose, combined with a selective detritiation procedure, was used to determine glucose turnover, the difference being G/G6P cycle activity. Endogenous hepatic glucose production (EGP) determined with (6(3)H)glucose was similar in hypertensive and control groups in the postabsorptive state (11.0 +/- 0.3 v 10.9 +/- 0.3 mumol.kg-1.min-1) and with the 0.2 mU insulin infusion (4.9 +/- 0.5 v 4.0 +/- 0.8 mumol.kg-1.min-1). With the 1.0 mU insulin infusion, glucose disappearance determined with (6(3)H)glucose was lower in the hypertensive group (21.8 +/- 2.4 v 29.9 +/- 2.4 mumol.kg-1.min-1, P less than .001). G/G6P cycle activity was similar both in the postabsorptive state (2.2 +/- 0.4 v 2.7 +/- 0.4 mumol.kg-1.min-1) and during insulin infusion (0.2 mU, 2.5 +/- 0.3 v 2.9 +/- 0.4; 1.0 mU, 4.7 +/- 0.3 v 5.3 +/- 1.1 mumol.kg-1.min-1 for hypertensive and control groups, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

3-Hydroxybutyric Acid↗
PubMed1992

The effect of endothelin 1 on the retinal microvascular pericyte.

The effect of the highly vasoactive peptide endothelin 1 (ET1) was tested on bovine retinal microvascular pericytes propagated in vitro. Specific binding of 125I-ET1 to retinal pericytes was documented by autoradiography. ET1 caused contraction of pericytes at a concentration of 0.1 nM which was accompanied by increases in inositol phosphates. Exposure of pericytes to 10 nM ET1 resulted in the aggregation and realignment of muscle-specific actins into bundles which were oriented parallel to the long axis of the cell, and ET1 was also mitogenic to pericytes in the presence of low levels of fetal calf serum. These observations suggest that ET1 may play an important role in endothelial cell-pericyte interactions within the microvasculature of the retina and that it may be involved in the autoregulation of retinal blood flow.

Actins↗
PubMed1992

The effect of ascorbate supplementation on oxidative stress in the streptozotocin diabetic rat.

An increase in oxidative stress may contribute to the development of diabetic complications. The key aqueous-phase chain-breaking antioxidant ascorbate is known to be deficient in diabetes, and we have therefore investigated the effects of ascorbate supplementation on oxidative stress in the streptozotocin diabetic rat. Markers of lipid peroxidation (malondialdehyde [MDA] and diene conjugates) were increased in plasma and erythrocytes of untreated diabetic animals, and levels of the antioxidants ascorbate and retinol were reduced. Plasma tocopherol was unchanged. Insulin treatment normalized MDA and ascorbate levels, although ascorbate metabolism remained disturbed, as indicated by increased levels of dehydroascorbate. High-dose ascorbate supplementation in the absence of insulin treatment restored plasma ascorbate to normal and increased plasma retinol and tocopherol levels. However, MDA and diene conjugate levels remained unchanged, possibly as a result of increased iron availability. High-dose ascorbate supplementation should be approached with caution in diabetes, as ascorbate may exert both antioxidant and prooxidant effects in vivo.

Animals↗
PubMed1992

A comparison of acipimox and nicotinic acid in type 2b hyperlipidaemia.

The side effect profiles and lipid lowering efficacy of nicotinic acid (1 g three times daily) and its analogue acipimox (250 mg three times daily) in type 2b hyperlipidaemia were compared in a double-blind placebo controlled study. In the nicotinic acid group (n = 7) at 12 weeks there were significant reductions (P less than 0.05) with respect to placebo (n = 9) in total cholesterol (median and range) 6.6 mmol l-1 (4.8-8.4) vs 8.8 mmol l-1 (7.5-9.5), triglyceride 1.4 mmol l-1 (0.5-4.6) vs 2.8 mmol l-1 (1.5-9.5) and apoprotein B 88.6 mg dl-1 (62.1-114) vs 121.9 mg dl-1 (88.0-170.7). In contrast there was no significant alteration in lipids in the acipimox group (n = 12). Nicotinic acid was associated with a high incidence of side effects, principally cutaneous flushing, while acipimox was well tolerated by all patients.

Adult↗
PubMed1992

Influence of growth hormone on glucose-glucose 6-phosphate cycle and insulin action in normal humans.

Increased activity of the hepatic glucose-glucose 6-phosphate (G/G-6-P) cycle is associated with hepatic and peripheral insulin resistance in acromegaly. To determine whether a similar association occurs after short-term growth hormone (GH) elevation within the physiological range, two-step euglycemic hyperinsulinemic clamps were performed in normal human males after 12-h GH (2.2 ng.kg-1 x h-1) and control infusions. G/G-6-P cycle activity and endogenous glucose production (EGP) were determined by [2-3H]- and [6-3H]-glucose using labeled exogenous glucose infusions and selective enzymatic detritiation. GH increased levels of circulating lipid intermediates despite a twofold increase in basal insulin (P < 0.005), but plasma glucose, EGP, and G/G-6-P cycle activity were unchanged. GH impaired insulin suppression of EGP and lipid intermediates and impaired insulin stimulation of glucose disposal, but G/G-6-P cycle activity was unchanged. We conclude that increased activity of the G/G-6-P cycle does not contribute to the hepatic insulin resistance induced by GH under these conditions but that changes in fatty acid metabolism may be partly responsible for the impairment in hepatic and peripheral insulin action.

Adult↗
PubMed1992

Pre-beta high-density lipoprotein determined by immunoblotting with chemiluminescent detection.

We describe a novel assay of pre-beta high-density lipoprotein (HDL), a unique apolipoprotein A-I (apo A-I)-containing lipoprotein particle. The pre-beta and alpha lipoproteins are separated by electrophoresis in agarose and transferred onto a membrane by capillary blotting. The membrane blot is sequentially incubated with sheep anti-human apo A-I antiserum and then with a conjugate of rabbit anti-sheep immunoglobulin and horseradish peroxidase. Chemiluminescence formed by the peroxidase-catalyzed oxidation of luminol in the presence of an enhancer is captured on photographic film, and the pre-beta HDL band is quantified by transmission densitometry. The assay is calibrated with standards prepared from a reference serum diluted in 9 mol/L urea. Within-batch precision (CV) at pre-beta HDL concentrations of 22.1 and 44.3 mg/L was 7% and 4.9% respectively. Pre-beta HDL contained 1.6% (0.65-2.6%, mean and range) of total serum apo A-I in 30 normolipidemic subjects.

Adult↗
PubMed1991

Comparison of histamine release from peritoneal mast cells derived from diabetic and control rats.

Clinical and experimental diabetes are associated with an increased number of mast cells and elevated tissue histamine concentrations. This study compared histamine release from peritoneal mast cells derived from diabetic and control rats. Experimental diabetes was induced by a single i.v. injection of streptozotocin (50 mg/kg body weight). Measurement of plasma glucose levels confirmed the diabetic state. Peritoneal mast cells were stimulated for 10 min with the lectin concanavalin A (0.5-100 micrograms/ml) in the presence or absence of phosphatidylserine, clinical dextran (0.6-1200 micrograms/ml) in the presence of phosphatidylserine, the calcium ionophore A23187 (0.1-1 microM) or the basic releasing agent compound 48/80 (0.1-10 micrograms/ml). Histamine release induced by these agents was similar in both populations. Further studies will compare the differences in histamine release from mast cells isolated from different tissues, e.g. heart and lung. In addition, physiological stimuli which are altered in the diabetic state (e.g. hyperosmolalar solutions and free radical generating systems) are under investigation.

Animals↗
PubMed1991

Pathogenesis of suxamethonium-induced muscle damage in the biventer cervicis muscle in the chick.

Muscle damage induced by suxamethonium, and the influence of halothane on it, has been examined by measuring the efflux of creatine kinase (CK) in the biventer cervicis muscle of the chick. Whereas halothane and suxamethonium alone did not increase the enzyme efflux significantly, the combination of the two was associated with significant increase in the concentration of CK in the bathing medium by 59-157%. The increase in CK was prevented by adding chlorpromazine 100 mumol litre-1 to the medium, suggesting the involvement of phospholipases in the pathogenesis of suxamethonium-induced muscle damage.

Animals↗
PubMed1991

Serum keratan sulphate level following chemonucleolysis.

In chemonucleolysis, accuracy of injection can be in doubt if the patient fails to respond. Discography preceding chemonucleolysis is associated with increased neurologic complications. Biplane fluoroscopy may fail to provide a clear picture on many occasions. The serum keratan sulphate levels were estimated in patients undergoing chemonucleolysis to ascertain if this could be used as a biochemical indicator to confirm accurate needle placement and to predict outcome. Serum keratan sulphate levels rose significantly following chemonucleolysis during the first 3 days (P less than 0.01). The rise was not significantly different, however, in patients who had improvement in their leg pain from those who did not improve (P = 0.35). Serum keratan sulphate level estimation before chemonucleolysis and at 24 or 48 hours following the procedure can be used to confirm accuracy of needle placement, but the rise in keratan sulphate is not predictive of the clinical outcome of the procedure.

Adult↗
PubMed1991

Simvastatin in severe hypercholesterolaemia: a placebo controlled trial.

The effect of simvastatin in 27 patients with severe primary hypercholesterolaemia was assessed by a double-blind placebo controlled parallel group trial. Total serum cholesterol, LDL-cholesterol and apoprotein B (ApoB) were significantly reduced by simvastatin 40 mg daily. Reductions in triglyceride and VLDL-cholesterol and an increase in HDL-cholesterol levels were only significant when calculated as a percentage of baseline, because of wide inter-individual variability. No changes in apoprotein A1, lipoprotein (a), fibrinogen, viscosity or blood pressure were observed. Leucocyte HMG-CoA reductase activity was unchanged after 4 weeks of active treatment but increased by 87% after 3 months (n = 21, P less than 0.05). No severe adverse effects or changes in CK or AST levels were noted. We conclude that simvastatin is effective in the treatment of severe and resistant hypercholesterolaemia, and well tolerated in the short term.

Adult↗
PubMed1991

Measurement of malondialdehyde in plasma by high performance liquid chromatography with fluorimetric detection.

The thiobarbituric acid test for malondialdehyde is widely used as an indicator of lipid peroxidation and free radical activity. We describe a simple and sensitive high performance liquid chromatographic (HPLC) method for measuring the malondialdehyde-thiobarbituric acid adduct using fluorimetric detection. Extraction into organic solvent or other complex sample preparation is not required and the assay is sensitive to less than 0.05 mumol/L. This method could easily be applied to any setting where a measure of lipid peroxidation is required.

Blood Preservation↗
PubMed1991

Magnesium status and digoxin toxicity.

1. Eighty-one hospital patients receiving digoxin were separated into groups with and without digoxin toxicity using clinical criteria. Serum digoxin, sodium, potassium, calcium, creatinine, magnesium and monocyte magnesium concentrations were compared. 2. Subjects with digoxin toxicity had impaired colour vision (P less than 0.0001, Farnsworth-Munsell 100 hue test) and increased digoxin levels (1.89 (1.56-2.21) vs 1.34 (1.20-1.47) nmol l-1, P less than 0.01) (mean (95% confidence limits], though there was considerable overlap between two groups. 3. Subjects with digoxin toxicity had lower levels of serum magnesium (0.80 (0.76-0.84) vs 0.88 (0.85-0.91) mmol l-1, P less than 0.01) and monocyte magnesium (6.40 (5.65-7.16) vs 8.76 (7.81-9.71) mg g-1 DNA, P less than 0.01), but there were no significant differences in other biochemical parameters. A greater proportion of toxic subjects were receiving concomitant diuretic therapy (20/21 vs 37/60, P less than 0.05). 4. Magnesium deficiency was the most frequently identified significant electrolyte disturbance in relation to digoxin toxicity. In the presence of magnesium deficiency digoxin toxicity developed at relatively low serum digoxin concentrations.

Adult↗
PubMed1990

Transient release of lipid peroxides after coronary artery balloon angioplasty.

Free radical production may cause myocardial damage during reperfusion of ischaemic myocardial tissue; when free radicals interact with polyunsaturated fatty acids or their esters, lipid peroxides are produced. A product of lipid peroxidation, malondialdehyde, was measured in 10 subjects with stable angina who underwent angioplasty of a proximal high-grade stenosis (over 90%) of the left anterior descending coronary artery. In all subjects the duration of balloon occlusion was 60 s. Blood was withdrawn from the great cardiac vein immediately before balloon inflation (T0), immediately after balloon deflation (T60), 15 s after balloon deflation (T75), and 1 min after balloon deflation (T120). There was a significant increase in malondialdehyde at T60 compared with T0 for the first balloon inflation (mean increase 0.3 mumol/l [95% confidence limits 0.1, 0.5]), and at both T60 (0.31 mumol/l [0.15, 0.47]) and T75 (0.22 mumol/l [0.04, 0.40]) for the second balloon inflation. This model could be used to assess antioxidant effects of drugs.

Adult↗