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Biomedical subjects

S Skrede

Publications and source records attributed to S Skrede.

At least 55 records · Page 3Linked to original sources
PubMed1984

Incorporation of precursors into sterols and proteins in liver biopsies from patients with liver disorders.

Incorporation of 14C-acetate into 3-beta-OH sterols and of 3H-leucine into proteins was examined in liver biopsies from patients with liver disorders. Biopsies obtained from patients in whom no liver disease was found served as controls. Reduced 14C-acetate incorporation into sterols was found in biopsies from patients with chronic active hepatitis and primary biliary cirrhosis. Stimulated incorporation of 3H-leucine into proteins was demonstrated in patients with alcoholic liver cirrhosis and in patients with ulcerative colitis associated with liver disease. No correlation could be established between serum proteins and lipids, respectively, on the one hand, and between incorporation of precursors into proteins and sterols, on the other. 'Incorporation parameters' were also inferior to conventional liver tests when used in the differential diagnosis between different liver disorders by discriminant analysis. Our findings may suggest, however, that hepatic sterol synthesis is frequently decreased in patients with chronic active hepatitis and primary biliary cirrhosis.

Adult↗
PubMed1984

Nordic surveys of analytical quality in clinical chemistry laboratories.

The design of the 1979 revision of the Nordic interlaboratory survey of analytical quality is described. Two Nordic surveys have been run with the new scheme (in 1979 and 1980). State of the art data (intralaboratory imprecision and total variation) is presented and compared with previous Nordic survey results and with analytical goals (Aspen). The analytical bias of sodium, potassium, chloride, creatinine, urea, glucose, and cholesterol was estimated by comparison with highly accurate reference methods (neutron activation, isotope dilution mass spectrometry).

Analysis of Variance↗
PubMed1983

Isolation of 5 alpha-cholestane-3 beta, 7 alpha-diol from bile of patients with cerebrotendinous xanthomatosis. Inefficiency of this steroid as a precursor to cholestanol.

Cerebrotendinous xanthomatosis is a rare, inherited disease characterized by defective bile acid biosynthesis as well as by accumulation of cholesterol and cholestanol. The mechanism behind the accumulation of cholestanol is unknown. Using combined gas chromatography-mass spectrometry, 5 alpha-cholestane-3 beta, 7 alpha-diol could be identified as a minor component in bile from two such patients. There were no significant amounts of this steroid in bile from control subjects. Most probably, the 5 alpha-cholestan-3 beta, 7 alpha-diol found is formed from 7 alpha-hydroxy-4-cholesten-3-one in the liver. 7 alpha-Hydroxy-1-cholesten-3-one, being a normal intermediate in bile acid biosynthesis, is known to accumulate in the liver and bile of patients with cerebrotendinous xanthomatosis, due to a defect of the mitochondrial 26-hydroxylase. The possibility was tested that (7 beta-3H)-labeled 5 alpha-cholestane-3 beta, 7 alpha-diol could be converted into cholestanol by a direct 7 alpha-dehydroxylation in the intestine. This conversion did not occur in rabbits, however, regardless of whether the labelled steroid was administered orally or intracoecally. It is concluded that 5 alpha-cholestane-3 beta, 7 alpha-diol is of little or no importance as a precursor to cholestanol in rabbits. Most probably, this is also the case in patients with cerebrotendinous xanthomatosis.

Animals↗
PubMed1983

Coenzyme A in dog kidneys during hypothermic perfusion.

In kidneys perfused hypothermically for 48 hr, both major intracellular pools of CoA (present in cytosol and mitochondria) decreased when solutions with intracellular or extracellular electrolyte composition without CoA precursors were used. The presence of substrates such as glucose or caprylic acid in the perfusate did not counteract the depletion of CoA. The addition of the CoA precursors pantethine and adenosine together with respiratory substrates to the perfusion medium counteracted the loss of CoA. The best solution in this respect among 16 different perfusates tested contained palmitic acid and L-carnitine together with CoA precursors and dibutyryl cyclic AMP. With this solution, we obtained good preservation of the cytosolic and the mitochondrial pool of CoA.

Animals↗
PubMed1983

Role of the 26-hydroxylase in the biosynthesis of bile acids in the normal state and in cerebrotendinous xanthomatosis. An in vivo study.

On the basis of different in vitro studies, we have previously suggested that the basic metabolic defect in the rare inherited disease cerebrotendinous xanthomatosis (CTX) is a lack of a hepatic mitochondrial C27-steroid 26-hydroxylase, involved in the normal biosynthesis of bile acids (1980. J. Clin. Invest. 65: 1418-1430; 1981. J. Lipid Res. 22: 191-200; 22: 632-640). In the present work, this hypothesis was tested in vivo. One patient with CTX and two control subjects received intravenously a mixture of [4-14C]7 alpha-hydroxy-4-cholesten-3-one and [6 beta-3H]7 alpha,26-dihydroxy-4-cholesten-3-one, steroids believed to be important precursors of chenodeoxycholic acid. The ratio between 14C and 3H in cholic acid and chenodeoxycholic acid isolated from bile of the CTX-patient was approximately 1/40 and 1/60 of those of the control subjects, respectively. Another patient with CTX and one control subject received a mixture of [4-14C]5 beta-cholestane-3 alpha,7 alpha-diol and [1,2-3H]5 beta-cholestane-3 alpha,7 alpha,26-triol, both possible precursors to chenodeoxycholic acid. In this case the 14C/3H ratio in cholic acid and chenodeoxycholic acid from the patient with CTX was 1/10 and 1/15, respectively, compared with that of the control subject. The most likely explanation for these findings is that very little of the 14C-precursors, i.e. without a 26-hydroxyl group, can be converted into cholic acid and chenodeoxycholic acid because of a defect of the 26-hydroxylase step. The results obtained are in accord with our previous findings in vitro. The results further underline the importance of the 26-hydroxylase pathway in the normal biosynthesis of cholic acid and chenodeoxycholic acid in man.

Adult↗
PubMed1983

Pulmonary hydrogen and methane and plasma ammonia after the administration of lactulose or sorbitol.

The gut microfloral metabolism of sorbitol and lactulose was investigated in 10 healthy control subjects and 10 patients with cirrhosis of the liver, by measuring the pulmonary excretion of the fermentational gases hydrogen and methane during 3 h. A possible acute effect on venous plasma ammonia after a single dose of sorbitol or lactulose was also investigated. No significant difference in fermentation gas excretion was found after ingestion of sorbitol compared with lactulose in healthy controls or cirrhotic patients (p greater than 0.05). Neither sorbitol nor lactulose had significant effect on plasma ammonia concentrations during the first 3 h after ingestion. These findings indicate that both sorbitol and lactulose are extensively fermented by the colonic flora and that the possibility of replacing lactulose with the much cheaper sorbitol in the treatment of portal-systemic encephalopathy ought to be investigated. The suggested acute gut-ammonia trapping effect of lactulose caused by acidification of the gut lumen from fermentative end-products was not supported by the present findings.

Adult↗
PubMed1983

Improvement of physical capacity after long-term training in patients with chronic active hepatitis.

A training program was started in nine patients with chronic active hepatitis in clinical remission while receiving immunosuppressive therapy. The patients were examined before and after a training period of 4-5 weeks and 10-12 weeks, respectively. The calculated oxygen consumption increased by 19% and 29%, and the estimated work load capacity improved. No change occurred in alanine aminotransferase, aspartate aminotransferase, alkaline phosphatases, gamma-glutamyl-transpeptidase, serum bilirubin, or prealbumin, whereas creatine kinase and lactate dehydrogenase increased significantly. The clinical condition did not worsen in any patient, and most of the patients felt that their physical performance capacity had improved. We conclude that long-term regular physical training is well tolerated by patients with chronic active hepatitis in clinical remission and that training leads to improvement in the oxygen consumption and the estimated work load capacity in such patients.

Adolescent↗
PubMed1983

The pattern of lysosomal, cytosolic and plasma membrane enzymes in epidermis, dermis and suction blister fluid after ultraviolet radiation.

Slightly lower lysosomal enzyme activities were found in epidermis 18 h after irradiation with middle wave ultraviolet light while the values were invariably higher in the dermis of inflamed skin. The activities of the plasma membrane and the cytosol marker enzymes were higher in normal epidermis and dermis than in inflamed skin. Higher values were also found in suction blisters raised on inflamed skin, suggesting labilization/destruction of the plasma membrane during the inflammatory process.

Aged↗
PubMed1982

Biosynthesis of cholestanol from intestinal 7 alpha-hydroxy-4-cholesten-3-one.

Using isotope dilution-mass spectrometry, it was shown that human bile contains significant amount of 7 alpha-hydroxy-4-cholesten-3-one, an intermediate in the major pathway for bile acid biosynthesis. In bile from 14 healthy subjects, the concentration was 0.14 +/- 0.01 micrograms/ml (mean +/- S.E.). Four bile samples collected from two patients with cerebrotendinous xanthomatosis contained considerably higher amounts of this steroid, 0.47-1.32 micrograms/ml. After oral administration of [4-14C]7 alpha-hydroxy-4-cholesten-3-one to rabbits, 14C-labeled cholestanol could be isolated from the intestinal wall, liver, and blood after 24 h. The label incorporated into the intestinal wall was about 10% of that obtained with [4-14C]cholesta-4,6-dien-3-one or [4-14C]4-cholesten-3-one as precursors. Labeled cholesta-4,6-dien-3-one and 4-cholesten-3-one could be isolated from the intestinal contents 12 h after feeding [4-14C]7 alpha-hydroxy-4-cholesten-3-one to rabbits. It is proposed that cholesta-4,6-dien-3-one and 4-cholesten-3-one are formed from 7 alpha-hydroxy-4-cholesten-3-one by the same mechanism as that involved in 7 alpha-dehydroxylation of primary bile acids. We suggest that biliary 7 alpha-hydroxy-4-cholesten-3-one may be a physiological precursor to cholestanol. The possibility is discussed that part of the increased formation of cholestanol in patients with cerebrotendinous xanthomatosis is due to excess biliary 7 alpha-hydroxy-4-cholesten-3-one or some metabolite of this steroid.

Animals↗
PubMed1982

Serum selenium levels in liver diseases.

A possible pathogenetic role of selenium deficiency in alcoholic cirrhosis of the liver has previously been discussed. In the present study serum selenium was analyzed in 5 groups of liver diseases. The method used for selenium determination was electrothermal atomic absorption, after thermal stabilization of selenium compounds by addition of nickel nitrate. The selenium level of a reference group of healthy Norwegian adults (n = 40) was 1.53 +/- 0.25 mumol/l. The serum concentrations of selenium in patients suffering from alcoholic cirrhosis, chronic active hepatitis and chronic persistent hepatitis were lowered to 40-80 per cent of those of the reference group. In alcoholic cirrhosis and chronic active hepatitis the decreased serum selenium concentrations were significantly correlated to decreased levels of albumin and prealbumin.

Hepatitis, Chronic↗
PubMed1982

A possible model for accuracy control of determination of serum cholesterol with use of reference methods. A NORDKEM project.

A candidate definitive method for determination of total serum cholesterol developed at the Center for Analytical Chemistry, National Bureau of Standards, USA, has recently been compared with a reference method based on isotope dilution-mass spectrometry, developed at Huddinge Hospital. There was no significant difference (0.2%) in results obtained with the two methods. The Huddinge method was used here for assessment of inaccuracy of a defined enzymatic method, set up and used at four laboratories, one in each of four Nordic countries. The results obtained in the analysis of 21 patient samples were not significantly different from those obtained with the isotope dilution method. In the analytical range 1.7-14.2 mmol/1, the regression equation for the defined enzymatic method (y) versus the isotope dilution method (x) was y = 0.994x - 0.06 and the correlation coefficient 0.9999. The mean between-laboratory variation for the defined enzymatic method was 2.3%. The possibility is discussed that the defined enzymatic method can be used as candidate secondary reference method for assessment of inaccuracy of field methods in national quality control activities. In such a control system, the accuracy can be traced back to the definitive methodology through the hierarchical system.

Cholesterol↗
PubMed1982

On the pathogenesis of acquired hypo-beta-lipoproteinemia. A case associated with sideroblastic anemia.

A 71-year-old previously hypercholesterolemic woman developed gradually severe hypocholesterolemia of 1.55 mmol/l. Simultaneously she developed progressive sideroblastic anemia, altered erythrocyte morphology and defective platelet function. Hypo-beta-lipoproteinemia was demonstrated with abnormal lipid composition of both very low density (VLDL), low density (LDL) and high density lipoprotein (HDL) fractions. Other plasma lipids, as well as erythrocyte lipids, were normal. The fractional catabolic rate of homologous 125I-LDL was increased to 4-5-fold, while its rate of synthesis was normal. The patient's serum contained autoantibodies directed against LDL. It is concluded that her hypo-beta-lipoproteinemia was due to autoantibodies towards LDL causing an increased catabolism without any concomitant effect on the rate of LDL synthesis. It is suggested that acquired hypo-beta-lipoproteinemia can be subdivided into two types, one in which the primary defect is an increased catabolism due to immunoelimination, and another in which the primary defect is a decreased rate of LDL synthesis.

Aged↗
PubMed1982

Regulation of the biosynthesis of CoA at the level of pantothenate kinase.

1. Pantothenate kinase, which is present in cytosol, was studied in preparations from livers of rats fed normal or clofibrate-enriched diets. Effects of CoA, dephospho-CoA and different acyl-CoA derivatives on this enzyme activity were examined in vitro. 2. With partially purified pantothenate kinase or crude particle-free supernatant from the liver of normal or clofibrate-treated rats, Km for pantothenic acid was 0.016 mmol/l at the pH optimum 6.1. 3. Acetyl-CoA, propionyl-CoA, malonyl-CoA and other short-chain acyl-CoA derivatives were strong inhibitors of pantothenate kinase, with Ki in the range 0.001-0.003 mmol/l. The mechanism of inhibition appeared to be of an uncompetitive type. 4. Free CoA has been held to be the main regulator of pantothenate kinase. We found, however, that free CoASH, dephospho-CoA and long-chain acyl-CoA (with Ki 0.003-0.08 mmol/l) were less efficient inhibitors than acetyl-CoA. 5. With pantothenate kinase from clofibrate-treated animals, all inhibitors were less potent. This was most pronounced when the enzyme was assayed in a crude supernatant fraction, possibly because the inhibitors were degraded and/or protein bound. Such a reduction of normal inhibition may contribute to the increased biosynthesis of CoA previously observed during clofibrate treatment. 6. Fasting or diabetes leads to an increase of long-chain acyl-CoA and total CoA in the liver. The increase of CoA has been explained by increased acylation of CoA, and thereby reduced feed-back inhibition by free CoASH at the pantothenate kinase level. We propose another explanation. In these metabolic states, the cytosolic pool of acetyl-CoA is decreased. Since pantothenate kinase is present only in the cytosol, its activity will be released and the biosynthesis of CoA will increase. 7. Acetyl-CoA is probably a more important physiological regulator of pantothenate kinase activity than is free CoASH.

Acetyl Coenzyme A↗