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Biomedical subjects

M Farstad

Publications and source records attributed to M Farstad.

At least 55 records · Page 3Linked to original sources
PubMed1989

Sixty minutes of normothermic ischemia in the rat liver: correlation between adenine nucleotides and bile excretion.

The effect of 60 min of normothermic liver ischemia on cellular levels of adenine nucleotides (ATP, ADP, and AMP), energy charge (EC), and bile excretion was studied. Following ischemia the concentration of ATP was reduced to 12% of preischemic and control values within the first 10 min and remained low during the remaining ischemic period. EC values were also low. During 120 min of reperfusion, ATP increased to 34% of the ATP level found in the control group. EC values increased immediately to reach values not significantly different from those of control animals. Bile flow was nonexistent during ischemia and increased during reperfusion. The increase paralleled those of ATP and EC. Bile flow seems to reflect the degree of liver ischemia and may be used as a functional parameter.

Adenine Nucleotides↗
PubMed1988

Ethionine-induced alterations of enzymes involved in lipid metabolism and their possible relationship to induction of fatty liver.

Changes of enzymes involved in the hepatic metabolism of long-chain fatty acids (palmitoyl-CoA synthetase (EC 6.2.1.3), carnitine palmitoyltransferase (EC 6.2.1.3), glycerophosphate acyltransferase (EC 2.3.1.15)) in the liver of male rats were examined after ethionine exposure. Ethionine administration resulted in a dose- and time-dependent enhancement of the palmitoyl-CoA synthetase activity both in the mitochondrial, peroxisomal and microsomal fractions. The total carnitine palmitoyltransferase activity in the mitochondrial fraction was enhanced. Ethionine administration was also associated with dose- and time-dependent changes of the microsomal glycerophosphate acyltransferase activity, whereas the mitochondrial enzyme activity was marginally affected. The hepatic triacylglycerol content of the ethionine-treated animals was increased. Hepatic lipids were accumulated in large droplets. Serum triacylglycerol and cholesterol were decreased. In particular, the serum HDL-cholesterol level was lowered. The concentration of ATP in the liver decreased. Accumulation of the metabolic product S-adenosylethionine (AdoEth) was observed for the first 2 days of exposure followed by a fall in S-adenosylmethionine (Ado-Met) during the next 10 days. Linear regression analysis of ATP content versus AdoEth and AdoMet showed highly significant correlations. A significant correlation between the hepatic triacylglycerol and AdoEth content was also observed upon ethionine treatment. The data show that ethionine perturbs the hepatic lipid metabolism. Enhanced esterification of long-chain fatty acids, but not a simple reduction of their oxidation, might contribute to ethionine-induced fatty liver in addition to a block in secretion of lipoproteins and decreased protein synthesis.

Acyltransferases↗
PubMed1987

Effect of volume depletion on the afferent arterioles in the avian kidney.

Nine white leghorn chickens were injected i.m. with furosemide (10 to 60 mg/kg body weight) twice daily for 18 days. The birds were then anesthetized with a combination of equithesin and diazepam and the kidneys perfused via the heart. Kidney tissue was sectioned serially and the granular epithelioid cells were counted in the juxtaglomerular apparatuses of the furosemide treated birds and in 3 normal chickens. Hyperplasia and hypergranulation of the epithelioid cells was found to occur in the juxtaglomerular apparatuses of both mammalian and reptilian type nephrons (with and without Henles loop) in the furosemide treated group. This finding was interpreted as an effect of hypovolaemia on the juxtaglomerular apparatuses. Furosemide caused an immediate stop in weight gain, an increase in the erythrocyte volume fraction and a sudden drop in blood pressure. The blood pressure later rose to subnormal levels. The heart rate was not altered. Plasma sodium and chloride fell significantly one day after furosemide administration and remained low throughout the experiment. Potassium fell during the second part of the experimental period. Captopril was injected after 18 days of furosemide treatment and lowered the blood pressure significantly. This was interpreted as indirect evidence for the presence of renin in the granular epithelioid cells and indicates the importance of the renin angiotensin system in maintaining the blood pressure in hypovolaemic conditions.

Animals↗
PubMed1986

A method for production of N2 microbubbles in platelet-rich plasma in an aggregometer-like apparatus, and effect on the platelet density in vitro.

The mechanisms involved in the interactions between microgasbubbles and platelets are not clear. The platelet aggregatory response to agonist-induced, receptor-mediated stimuli has been studied extensively. As a direct in vitro approach to elucidate the interaction between gas bubbles and platelets, N2 microbubbles were used as a platelet agonist in an experimental apparatus similar to an ordinary aggregometer. N2 microbubbles of varying number and size were produced in platelet-rich plasma (PRP) and incubated at 37 degrees C. The gas-liquid interface of the gas bubbles consists of plasma proteins and lipids. In stirred PRP a considerable decrease occurred in the platelet density, which could not be attributed to formation of citrate complexes with calcium and/or the corresponding reduction in the concentration of free calcium. Gas bubbles with a diameter in the range of 40-120 micron caused the greatest reduction in the platelet density. The platelet movements in PRP and the curvature of the N2 microbubble surface seemed more important for the interaction than the total gas bubble surface available for contact.

Analysis of Variance↗
PubMed1985

Liquid chromatography of serotonin and adenine nucleotides in blood platelets, illustrated by evaluation of functional integrity of platelet preparations.

In this relatively rapid liquid-chromatographic procedure the endogenous serotonin in blood platelets is quantified by fluorometry. We used this experimental procedure to estimate the platelet-release reaction as an indicator of the functional integrity of stored platelets. a decrease in the platelet-release reaction more sensitively indicates platelet changes during storage than do alterations in total ATP concentration or adenylate energy charge. The described method for quantifying serotonin is convenient enough for routine use in blood banks.

Adenine Nucleotides↗
PubMed1984

Enzymatic changes in rat liver associated with low and high doses of a peroxisome proliferator.

The activities of a number of lipid-metabolizing and subcellular marker enzymes were measured in total homogenates and subcellular fractions prepared from the livers of male rats fed diets containing 0.05, 0.1, 0.3, and 0.5% of the hypolipidemic drug tiadenol, resulting in mean drug intake of 45, 90, 330, and 530 mg/day/kg body wt, respectively. In the total homogenates, a massive induction of palmitoyl-CoA hydrolase and peroxisomal palmitoyl-CoA oxidation accompanied by increased free CoASH and long-chain acyl-CoA content was observed at the highest dose levels whereas little change occurred up to 90 mg/day/kg/body wt. The palmitoyl-CoA synthetase activity increased slightly up to 90 mg/day/kg body wt, but higher doses resulted in decreased enzyme activity. Catalase activity increased with the dose to be elevated by a factor of approximately 1.6 at 330 mg/day/kg, whereas the activities of urate oxidase decreased. The specific activities of palmitoyl-CoA hydrolase and peroxisomal palmitoyl-CoA oxidation increased in all fractions, but most markedly in the cytosol. The changes in the activities and the distribution of subcellular marker enzymes and the increase of the peroxisome-associated polypeptide (PPA-80) are in keeping with a peroxisome proliferating effect resulting in formation of premature organelles with altered properties. Since high doses of many hypolipidemic drugs produce hepatic tumors and peroxisomal proliferation in rodents and since no increase in peroxisomes is found in human liver after therapeutic use of lower doses, the dose-response relationship is of interest for the evaluation of the toxicology of this class of agents.

Animals↗
PubMed1984

Effects of timolol on adenine nucleotide catabolism in cat hearts with acute regional ischaemia.

The effects of the beta-adrenergic blocking agent timolol on cardiac function and adenine nucleotide metabolism were investigated in cats with 45 min of acute ischaemia following coronary occlusion. Regional myocardial blood flow was measured by 15 micron radiolabelled microspheres, and adenine nucleotides and their degradation products were measured by high performance liquid chromatography in 16 tissue regions in each cat. During ischaemia, cats treated with timolol exerted a reduced cardiac performance as judged from reduced heart rate and cardiac contractility; consequently preocclusion tissue blood flow was reduced compared with a control group of cats. The ATP concentration was less severely depleted in ischaemic regions of the left ventricle in cats treated with timolol. The energy charge was reduced to a lesser extent in ischaemic regions, and in intermediate flow ranges the contents of the inosine and hypoxanthine/xanthine were reduced compared with untreated cats. These results indicate that the beta-adrenergic blocking agent timolol might protect the myocardium within a 45 min ischaemic period. The mechanism for this effect is most probably related to the reduction in overall cardiac performance.

Acute Disease↗
PubMed1984

Relationship between myocardial adenine nucleotide catabolism and tissue blood flow rate in experimental ischaemia.

A method was developed for tissue preservation and evaluation of the adenine nucleotide metabolism in small samples of myocardium after 45 min of ischaemia. Ischaemia was produced by coronary artery occlusion in anaesthetized cats. Adenine nucleotides and their metabolites were measured by isocratic liquid chromatographic systems which allow quantitative analysis of the nucleotides and their metabolites inosine, hypoxanthine and xanthine in biopsies of 5-20 mg tissue. Regional myocardial blood flow was measured in the tissue surrounding the biopsies by the distribution of 15 micron radiolabelled microspheres. In central ischaemic regions the ATP level was approximately 1 mumol/g wet weight, whereas in normally perfused myocardium the ATP level was approximately 5 mumol/g tissue. In tissue with intermediate flow values, intermediate ATP levels were found. Energy charge, which summarizes all adenine nucleotide concentrations, was reduced from 0.88 to 0.50, and the molar concentrations of inosine, hypoxanthine and xanthine increased in ischaemic tissue. We conclude that this method provides reliable characterization of the local cellular energy status in cat hearts with ischaemic regions.

Adenine Nucleotides↗
PubMed1983

Hepatic enzymes, CoASH and long-chain acyl-CoA in subcellular fractions as affected by drugs inducing peroxisomes and smooth endoplasmic reticulum.

1. The activities of acyl-CoA hydrolase, catalase, urate oxidase and peroxisomal palmitoyl-CoA oxidation as well as the protein content and the level of CoASH and long-chain acyl-CoA were measured in subcellular fractions of liver from rats fed diets containing phenobarbital (0.1% w/w) or clofibrate (0.3% w/w). 2. Whereas phenobarbital administration resulted in increased microsomal protein, the clofibrate-induced increase was almost entirely attributed to the mitochondrial fraction with minor contribution from the light mitochondrial fraction. 3. The specific activity of palmitoyl-CoA hydrolase in the microsomal fraction was only slightly affected while the mitochondrial enzyme was increased to a marked extent (3-4-fold) by clofibrate. 4. Phenobarbital administration mainly enhanced the microsomal palmitoyl-CoA hydrolase. 5. The increased long-chain acyl-CoA and CoASH level observed after clofibrate treatment was mainly associated with the mitochondrial, light mitochondrial and cytosolic fractions, while the slight increase in the levels of these compounds found after phenobarbital feeding was largely of microsomal origin. 6. The findings suggest that there is an intraperoxisomal CoASH and long-chain acyl-CoA pool. 7. The specific activity of palmitoyl-CoA hydrolase, catalase and peroxisomal palmitoyl-CoA oxidation was increased in the lipid-rich floating layer of the cytosol-fraction. 8. The changes distribution of the peroxisomal marker enzymes and microsomal palmitoyl-CoA hydrolase after treatment with hypolipidemic drugs may be related to the origin of peroxisomes.

Acyl Coenzyme A↗
PubMed1983

The existence of separate peroxisomal pools of free coenzyme a and long-chain acyl-CoA in rat liver, demonstrated by a specific high performance liquid chromatography method.

1. Tiadenol administration of rats lead to an increased hepatic content of unesterified and esterified CoA. 2. Liver homogenates from normal tiadenol treated rats were fractionated by differential centrifugation and fractions enriched in peroxisomes were subfractionated by isopycnic density gradient centrifugation. 3. The analysis demonstrated that purified peroxisomes contained a separate pool of free CoASH and long-chain acyl-CoA. 4. The data also provides indications of the presence of palmitoyl-CoA synthetase in the peroxisomes.

Acyl Coenzyme A↗
PubMed1982

The content of coenzyme A, acetyl-CoA and long-chain acyl-CoA in human blood platelets.

The amounts of coenzyme A (CoASH) and acetyl-CoA in the acid-soluble extract of human blood platelets were quantitated by an isocratic reversed-phase liquid-chromatographic system. The analytical column was Supelcosil LC-18, and the solvent was 220 mmol/l potassium phosphate, pH 4.0, and 120 ml/l methanol. Long-chain acyl-CoA was estimated by the released coenzyme A after an alkaline hydrolysis of the acid-insoluble material of the blood platelets. The median values in platelets from fourteen healthy persons were 30 pmol CoASH/mg platelet protein, 45 pmol acetyl-CoA/mg platelet protein, and 34 pmol long-chain acyl-CoA/mg platelet protein.

Acetyl Coenzyme A↗
PubMed1982

Determination of adenine nucleotides and inosine in human myocard by ion-pair reversed-phase high-performance liquid chromatography.

An isocratic high-performance liquid chromatographic system for the quantitation of AMP, ADP and ATP is presented. The separations were achieved at room temperature by reversed-phase chromatography (Supelcosil LC-18). The standard solvent was 220 mM potassium phosphate, pH 6.9, 1% (v/v) methanol and 0.3 mM tetrabutylammonium hydrogen sulphate. A selective retention of the adenine nucleotides as a group relative to the mono-, di- and triphosphates of guanosine, uridine and cytidine was observed under these experimental conditions. The adopted procedure was applied to the separation of adenine nucleotides in biological extracts, i.e., human myocard. The adenine nucleotides in an extract of myocard were quantitated in less than 20 min. Only 5-10 mg (wet weight) of myocard were needed in order to determine the energy charge of a myocardial sample. Also inosine was easily quantitated in this liquid chromatographic system.

Adenine Nucleotides↗
PubMed1982

Uric acid determinations: reversed-phase liquid chromatography with ultraviolet detection compared with kinetic and equilibrium adaptations of the uricase method.

A reversed-phase liquid-chromatographic procedure is presented for quantitation or uric acid in human serum, with absorbance measured at 292 nm. The mobile phase was sodium acetate (35 mmol/L, pH 5.0)/acetonitrile (9/1 by vol). Complete precipitation of serum proteins was obtained by mixing serum (50-500 microL) with an equal volume of acetonitrile, and the precipitate was removed by centrifugation. Aliquots (20 microL) of the supernate were injected directly into the liquid chromatograph, which was adjusted so that the absorbance reading of the uric acid peak was as high as possible. Routinely, a full-scale deflection of 1.28 absorbance units was used. The within-run precision (CV) was 0.6% for a serum uric acid concentration of 227 mumol/L and day-to-day precision over a 15-day period was 0.8% for uric acid of 345 mumol/L. No interferences from related compounds were observed. We compared results by this method with those by kinetic (aca, Du Pont) and equilibrium adaptations (Ames kit; Nyco-test, Nyegaard; and Monotest, Boehringer Mannheim) of uricase methods. The method we report is simple, and can be used in a fully automatic liquid-chromatographic system.

Chromatography, High Pressure Liquid↗