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Biomedical subjects

H Vilstrup

Publications and source records attributed to H Vilstrup.

143 records · Page 8Linked to original sources
PubMed1983

Insulin sensitivity in alcoholic cirrhosis.

The amount-of-substance rate of glucose metabolism and its sensitivity to the concentration of insulin was quantified in 10 non-diabetic patients with alcoholic cirrhosis of varying severity, using the 'glucose clamp technique'. Fasting glucose and insulin were 5.4 +/- 0.3 mmol/l and 187 +/- 50 pmol/l (mean +/- SEM), respectively. During the hyperglycaemic clamp (blood glucose at 12.5 mmol/l) the glucose metabolic rate (divided by body mass) was 27 +/- 4 mumol X min-1 X kg-1 at an insulin concentration of 998 +/- 158 pmol/l. Thus the insulin sensitivity of the tissue glucose metabolism was 22 +/- 7 m3 X min-1 X kg-1. During the euglycaemic clamp exogenous insulin was given to a concentration of 574 +/- 72 pmol/l. The resulting glucose metabolic rate was 20 +/- 4 mumol X min-1 X kg-1 and the insulin sensitivity the same as during hyperglycaemia. The calculated systemic delivery rate of insulin (divided by body surface area) was 783 +/- 172 pmol X min-1 X m-2. Fasting glucagon was 32 +/- 5 pmol/ and only partly depressed by glucose or insulin. In comparison with stated relevant control groups cirrhotics exhibit glucose intolerance characterized by decreased sensitivity to insulin, hyperinsulinaemia due to increased release, and hyperglucagonaemia with decreased suppressibility. There was no relation between clinical or biochemical data of the patients and the above results, suggesting that the abnormal glucose metabolism does not depend directly on the decreased liver function but on a disturbed pancreatic-hepatic-peripheral axis.

Aged↗
PubMed1983

Effects of acute carbon tetrachloride intoxication on kinetics of galactose elimination by perfused rat livers.

Seventeen livers of 200 g rats, of which seven had received 435 microliters of CCl4 (LD15) by gastric tube 36 h earlier, were isolated and perfused in a once-through system at 9 ml/min with a semi-śynthetic medium to which galactose was added to concentrations from 0.1 to 3.3 mmol/l. The relative liver weight was increased by 13% by CCl4. The portal pressure was 16 cmH2O and the oxygen consumption of the livers 20 mumol/min, both unchanged by CCl4. In each liver four to six sets of galactose elimination rate at different galactose concentrations were measured. The relation was examined by a model including modification of the simple Michaelis-Menten kinetics by allosterism. The resulting Vmax values were decreased by CCl4 from 1.20 +/- 0.18 in controls to 0.78 +/- 0.19 mumol X min-1 X 100 g-1 body weight (mean +/- SEM, P less than 0.001). The affinity constant was decreased from 0.18 +/- 0.06 to 0.11 +/- 0.02 mmol/l (mean +/- SEM, P less than 0.015) in CCl4-treated livers. The decrease in affinity constant may--if it also applies to other substances eliminated by the liver--have implications for the use of a clearance as a measure of functional capacity, since this presupposes that the affinity constant remains unchanged during liver disease.

Animals↗
PubMed1982

Elimination of infused amino acids from plasma of control subjects and of patients with cirrhosis of the liver.

In four control subjects and four patients with cirrhosis of the liver a multiple amino acid mixture was infused for 12 h at a constant rate of 68 and 56 mumol alpha-amino N/s, respectively. Before infusion the plasma amino N concentration was 2.4 +/- 0.2 (mean +/- SD) mmol/l in control subjects and 3.5 +/- 0.7 mmol/in patients (P less than 0.025). The concentration of alanine, proline, arginine, tyrosine, and citrulline was significantly increased in the cirrhosis group. 12 h after the infusion began approximately constant amino N concentrations of 11.4 +/- 1.8 mmol/l in controls and 13.7 +/- 3.9 mmol/l in patients were attained, and the urea N synthesis rate was 63 +/- 17 and 44 +/- 8 mumol/s, respectively (P less than 0.05). After correction for loss of amino acids in urine this means that on the average 94 per cent of the N load was recovered as urea. The plasma clearance of infused amino acids, calculated as the ratio between infusion rate and steady state concentration, was 6.0 +/- 1.2 and 4.1 +/- 0.9 ml/s for amino N in the control and cirrhosis group, respectively (P less than 0.025). The clearance of individual amino acids ranged between 2.5 and 28 ml/s. The clearance of most amino acids was decreased in the cirrhosis groups, and of glycine, proline, lysine, threonine, and arginine significantly so (P less than 0.05), reflecting accumulation of amino acids in patients. This indicates that a primary defect in the conversion of amino N in cirrhosis is the reduced urea synthesis.

Adult↗
PubMed1981

Number connection test and continuous reaction times in non-encephalopathic patients: a comparative study.

Number Connection Test (NCT) and Continuous Reaction Times (CRT) were determined in 94 hospitalized patients with no previous or actual cerebral dysfunction. By NCT, 47 patients used more than 30 s which is the upper normal limit. Of these, 5 used more than 50 s. Two patients exhibited a CRT exceeding the upper normal limit of 240 ms. Thus, accepting the upper limits quoted, one-half of the patients were falsely classified as encephalopathic by NCT, but only 2% by CRT. This indicates that the NCT is too unspecific to exclude encephalopathy and suggests that the CRT is a more valid measure in this respect.

Adult↗
PubMed1981

Quantitative liver function and morphology after paracetamol administration to rats.

The functional status of the liver after paracetamol administration to rats was dissociated with regard to cytosolic and microsomal functions. The cytosolic function, measured as galactose elimination capacity, was unchanged even after high doses of paracetamol. The microsomal function, measured as the prothrombin time, was reversibly decreased to a minimum 12 h after paracetamol administration and showed dose dependence. The structural changes of the liver cells were centrilobular necroses and dilatation of the endoplasmic reticulum. They were most marked 36 h after paracetamol and were not correlated to the functional impairment. We conclude that during acute paracetamol induced liver damage to rats different functions of the liver are unequally influenced and that the structural changes occur later than the functional ones. The paracetamol intoxicated rat is a promising model for further investigation of dissociation of subcellular functions during acute liver damage.

Acetaminophen↗
PubMed1980

Synthesis of urea after stimulation with amino acids: relation to liver function.

Hepatic urea synthesis is the organism's main channel for the disposal of nitrogen and it may be an 'essential' liver function. In six control subjects and five patients with cirrhosis of the liver urea synthesis was studied during continuous infusion for six to 24 hours of about 3 mmol alpha-amino nitrogen/h X kg body weight. The urea synthesis rate was calculated in intervals of two hours as urinary excretion with correction for accumulation in the total body water and for hydrolysis of urea in the gut. The peripheral venous plasma alpha-amino nitrogen concentration increased from 3 to about 14 mmol/l and the urea nitrogen synthesis rate from 25 to about 215 mmol/h. In all cases the urea synthesis rate rose linearly with the alpha-amino concentration throughout the examined range. The slope of this linear relationship is an expression of the hepatic conversion of alpha-amino nitrogen to urea nitrogen ('functional hepatic nitrogen clearance'). The functional hepatic nitrogen clearance was 22.4 l/h in control subjects and 13.7 1/h (P < 0.025) in the patients with cirrhosis. It was correlated with quantitative measures of the liver function (the galactose elimination capacity, r = 0.84, and the clearance of antipyrine, 4 = 0.80). These observations, while confirming the abundant capacity of the urea synthesis system, imply that a given urea synthesis rate requires a higher alpha-amino level in patients with reduced liver function.

Adult↗
PubMed1980

Importance of flow and haematocrit for metabolic function of perfused rat liver.

The influence of flow rate and haematocrit on the metabolic function of once-through perfused rat liver, as assessed by galactose elimination and oxygen uptake, was studied. Rats weighting from 195 to 220 g were used. Each of eleven experiments consisted of four periods; the blood flow rate was 10 ml/min in the first and the last period, and it was varied at random from 0.6 to 18 ml/min in the second and the third period. Haematocrit values of either 0.40, 0.28 or 0.16 1/1 were constant in each experiment. The input concentration of galactose was 1.7 mmol/l. Both galactose elimination and oxygen uptake were independent of the flow rate between 6 and 18 ml/min. At flow rates below 6 ml/min (i.e. below 0.9 ml/min/g liver) both functions were reversibly decreased in parallel with the flow. The values were highly correlated. There was a trend towards a lower galactose elimination rate and oxygen uptake at lower haematocrit values. It is emphasized that flow rate and haematocrit must be kept above certain limits in metabolic studies with perfused rat liver.

Animals↗
PubMed1979

Relation between liver function and hepatocyte ultrastructure in a case of paracetamol intoxication.

In a case of reversible paracetamol intoxication ultrastructural changes were correlated to changes in tests of microsomal and cytosolic liver function: the prothrombin index (PP) and the galactose elimination capacity (GEC), respectively. The decrease in the PP was at maximum after 2 days and in the GEC after 5 days, when the PP was normalized. Liver biopsies were taken after 1 and 5 days. Electron microscopy of the early biopsy revealed midzonal increased vacuolization of the endoplasmic reticulum (ER), detachment of ribosomes, and centrilobular mitochondrial injury. The late biopsy exhibited midzonal organelle-depleted areas with pale glycogen rosettes, perinuclear proliferating granulated ER, and centrilobular frank necrosis. These observations are in accordance with the concept that paracetamol-induced hepatocellular injury is due to damage to the membranes of the ER and indicate that the chronological dissociation of the liver function tests reflects the time sequence of the structural changes.

Acetaminophen↗
PubMed1978

The galactose elimination capacity as a quantitative measure of liver function in acute carbon tetrachloride intoxication of rats.

In rats given rising single doses of carbon tetrachloride (CCl4) intragastrically the relation between dose and mortality, between time after injection and the quantitative liver function measured by the galactose elimination capacity (GEC), and between the dose and the GEC, was examined. The change in hepatic contents of galactose metabolites after CCl4 was measured. There was a linear relation between the dose and mortality. No rat died later than 36 h after injection. Following injection of a dose lethal to 15% of rats the GEC fell to 40% of control after 36 h and was normalized after 72 h. There was a dose dependent decrease in the GEC with rising doses given 36 h earlier up to a dose lethal to 15%. Galactose metabolites other than UDP-galactose, which was decreased, were not affected by CCl4, suggesting a general enzyme depression. The results are compatible with the concept of proportionality between the GEC and 'the functioning liver mass' and indicate that the GEC presents prognostically valuable information during acute hepatic insufficiency.

Animals↗
PubMed1976

Effect of dietary protein depletion on the galactose elimination capacity in intact rats.

The galactose elimination capacity (GEC) of rats fed low protein liquid diets and libitum with 5% or 0.5% of the energy as protein was compared with that of a control group receiving a similar diet with 25% of the energy as protein. The daily dietary energy intake was almost identical in the three groups. The rats fed the 5% protein diet showed slightly higher GEC than the control group. In the rats receiving the 0.5% protein diet, GEC was significantly decreased to approximately half of the control values and the hepatic protein content was reduced to the same extent. Body weight and liver weight showed reductions to approximately 75% of control values. Triglyceride content in the livers was increased five times in the protein depleted rats. The results indicate that GEC in rats deprived of dietary protein is determined by the amount of hepatic protein.

Animals↗
PubMedDate not supplied

Xylitol normalizes the accelerated hepatic capacity for conversion of amino nitrogen to urea nitrogen in diabetic rats.

In diabetes, the capacity of urea nitrogen synthesis, ie, a substrate-independent measure of the hepatic conversion of amino nitrogen to urea nitrogen, is increased. Xylitol decreases urea synthesis in normal rats. Capacity of urea nitrogen synthesis and nitrogen balance were measured during intravenous alanine loading in control rats, rats with experimental diabetes (streptozocin 75 mg/kg), and rats with experimental diabetes infused with xylitol to 1 mmol/L. In control rats, capacity of urea nitrogen synthesis was 9.4 +/- 1.1 mumol/min per 100 g of body weight, and nitrogen balance -2.7 +/- 1.2 mumol/min per 100 g of body weight. In the diabetics, these values were markedly increased to 26.6 +/- 1.9 and -16.3 +/- 2.1 mumol/min per 100 g of body weight, respectively (p < 0.01). The infusion of xylitol normalized these values to 11.2 +/- 1.0 and -3.6 +/- 2.1 mumol/min per 100 g of body weight for capacity of urea nitrogen synthesis and nitrogen balance, respectively. Xylitol did not change glucagon or insulin. Xylitol improved the nitrogen economy of uncontrolled diabetic rats by decreasing urea synthesis. The mechanism is not settled, but it does not involve insulin or glucagon.

Amino Acids↗
PubMedDate not supplied

Effects of xylitol on urea synthesis in patients with cirrhosis of the liver.

BACKGROUND: In individuals with cirrhosis the normal inhibiting effect of glucose on urea synthesis is lost, probably because of very high concentrations of glucagon. In agreement, glucose does not prevent the inducing effect of glucagon on urea synthesis in normal humans. In contrast, the sugar alcohol, xylitol, prevents the increasing effect of glucagon in normal humans. We, therefore, examined the effect of xylitol on urea synthesis in individuals with cirrhosis and hyperglucagonemia. METHODS: Urea synthesis, calculated as urinary excretion rate corrected for accumulation in total body water and intestinal loss, was measured during infusion of alanine (2 mmol/[h x kg body wt]) and during infusion of alanine superimposed on infusion of xylitol (0.12 g/[h x kg body wt]) in 8 individuals with biopsy-proven alcoholic cirrhosis. The functional hepatic nitrogen clearance (FHNC), ie, urea synthesis expressed independent of changes in plasma amino acid concentration, was calculated as the slope of the linear relation between the urea synthesis rate and the plasma amino acid concentration. RESULTS: All individuals had elevated basal plasma glucagon concentration (261 +/- 61 ng/L; mean +/- SEM) and a markedly increased response to alanine infusion (1037 +/- 226 ng/L). This was not changed by xylitol. Neither the basal urea synthesis rate (13.2 +/- 2.5 mmol/h) nor the alanine-stimulated urea synthesis rate (76.8 +/- 3.64 mmol/h) was changed by xylitol. FHNC during the infusion of alanine alone was 10.5 +/- 0.9 L/h and did not change during the concomitant infusion of xylitol (10.1 +/- 1.1 L/h). CONCLUSIONS: Xylitol reduces neither urea synthesis nor FHNC. The data do not support an important role of xylitol as a nitrogen-sparing agent in cirrhosis.

Adult↗