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Biomedical subjects

M Bugge

Publications and source records attributed to M Bugge.

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

The effect of ammonia infusion on brain monoamine metabolism in portacaval-shunted rats.

The effect of ammonia infusion on monoamine metabolism was studied in the rat brain. Seven days after portocaval shunt (PCS) or sham operation animals were infused with ammonia or saline. Brain metabolism of serotonin and norepinephrine was studied after injection of a decarboxylase inhibitor (m-hydroxybenzylhydrazine, NSD 1015) which blocks the conversion of 5-hydroxytryptophan to serotonin and dihydroxyphenylalanine to dopamine. Neurologic testing was conducted before killing. Plasma and brain amino acids were measured. PCS animals infused with ammonia were in deep coma after 6 h infusion, whereas sham-operated animals were virtually unaffected. Brain amino acid analyses demonstrated increased concentrations of the aromatic amino acids and a tenfold increase in glutamine. Serotonin metabolism was diminished after 6 h. Dopamine synthesis was normal, but norepinephrine levels were low after 6h. The study suggests that hyperammonemia in PCS rats results in a depression of the serotonin synthesis rate in accordance with two previous studies but in contrast to previous hypotheses on the regulation of serotonin metabolism.

5-Hydroxytryptophan↗
PubMed1989

Brain 5-HT1 and 5-HT2 binding sites following portacaval shunt in the rat.

Brain serotonin 5-HT1 and 5-HT2 binding properties were investigated in experimental chronic portal-systemic encephalopathy (PSE). End-to-side portacaval shunted (PCS) rats were subjected to open field behavioral testing (spontaneous activity and exploration) 3 weeks after the shunt procedure. Each individual animal was then assayed for 5-HT1 and 5-HT2 binding properties (Bmax and KD) in the cortex + hippocampus by the use of radioligand binding and rapid filtration technique. (3H)serotonin was used to label 5-HT1 binding sites and (3H)ketanserin to label 5-HT2 binding sites. Results revealed that the PCS rats exhibited significant behavioral changes with decreased spontaneous activity and exploratory behavior as compared with sham-operated controls (sham). The affinity for, and the number of, 5-HT1 and 5-HT2 binding sites, respectively, were not different between PCS and sham rats. The brain 5-HT1 and 5-HT2 binding properties were within the range of Bmax and KD previously reported for normal rats when similar techniques are used. This first report in PCS rats on the subject of brain 5-HT1 and 5-HT2 binding properties demonstrates that no major alterations are likely to occur. This contrasts the knowledge of a markedly increased brain serotonin synthesis rate in the PCS rat, suggesting minor functional relevance of the perturbed brain serotonin metabolism associated with chronic PSE.

Animals↗
PubMed1988

The impact of time after portacaval shunt in the rat on behavior, brain serotonin, and brain and muscle histology.

We investigated open field behavior, cellular fluorescence of brain serotonin and serotonin metabolism in different regions of the central nervous system (CNS), and brain and muscle histology in rats 3 weeks or 6 months after surgical end-to-side portacaval shunt (PCS). The results revealed a similar disturbance of the CNS serotonin at 3 weeks and 6 months after PCS in the rat. Progressive neurohistological changes were present between 3 weeks and 6 months after PCS. The open field behavioral impairment appeared, however, to diminish with time. There was no evidence from muscle biopsies that lesions in the muscles or in the peripheral nerves contributed to the motor disturbance.

5-Hydroxytryptophan↗
PubMed1988

The effect of porta-caval shunt, ammonia infusion and alcohol administration on rat plasma beta-hexosaminidase.

The activity of the lysosomal enzyme, beta-hexosaminidase, is increased in plasma of patients with various forms of liver disease as well as in plasma from rats with experimental cholestasis or cirrhosis. In this experimental study in the rat, the effect of porta-caval shunt, ammonia infusion and ethanol feeding on plasma beta-hexosaminidase activity was studied. Porta-caval shunted animals had significantly increased plasma beta-hexosaminidase activity compared to sham-operated animals. Ammonia infusion in porta-caval shunted rats resulted in a further increase of plasma enzyme activity. Ethanol feeding for different periods of time (1 day to 4 weeks) did not have any influence on plasma beta-hexosaminidase activity.

Ammonia↗
PubMed1987

The effect of liver ischaemia on brain monoamine synthesis in the rat.

Subtotal or total liver ischaemia was induced in the rat by dividing the hepatic artery (Expt. I) or by total dearterialisation of the liver (Expt. II) 2 days after porta-caval shunt (PCS). The animals received i.v. a 10% glucose infusion for 5 h after the last operation and were killed by decapitation. At the end of the experiment all animals with liver ischaemia were in Grade III coma. In different regions of the CNS 5-hydroxytryptophan (5-HTP), 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA), were analysed by HPLC-technique with electrochemical detection, while dihydroxyphenylalanine (DOPA), dopamine (DA) and norepinephrine (NE) were analysed with a radio enzymatic method after blocking the decarboxylation of 5-HTP to 5-HT and DOPA to DA by inhibition of the aromatic amino acid decarboxylase enzyme with m-hydroxybenzylhydrazine (NSD 1015) in order to estimate the synthesis rate of 5-hydroxyindoles and catecholamines. In Expt. I concentrations of 5-HTP in animals with PCS were increased as compared to sham operation. In animals with liver ischaemia, 5-HTP concentrations were increased as compared to sham operation but similar to those in animals with PCS alone. These results suggest that ligation of the hepatic artery for 5 h in PCS animals does not further accelerate the rate of brain indole synthesis. In Expt. II, the 5-HTP concentrations were increased in PCS animals as compared to sham operation. Animals with total liver dearterialisation exhibited decreased 5-HTP levels as compared to PCS, suggesting a decreased brain indole synthesis after severe liver ischaemia. In Expt. II, CNS concentrations of DOPA following PCS were unaltered as compared with sham-operated animals. In animals with total liver dearterialisation, DOPA levels were increased, suggesting an augmented catecholamine synthesis. The NE levels were lower than in PCS and in sham-operated animals.

5-Hydroxytryptophan↗
PubMed1987

Brain serotonin metabolism and behavior in rats with carbon tetrachloride-induced liver cirrhosis.

Increased brain serotonin metabolism has been suggested as an etiologic factor in the development of portal-systemic encephalopathy (PSE) in connection with liver disease. We therefore investigated brain serotonin metabolism and open-field behavior (spontaneous activity and exploration) in rats with carbon tetrachloride (CCl4)-induced liver cirrhosis. Brain serotonin metabolism was evaluated in rats pretreated with an amino acid decarboxylase inhibitor. The 5-hydroxyindoles were analyzed by high-performance liquid chromatography (HPLC) with electrochemical detection. The results revealed an increased serotonin synthesis rate in all investigated brain regions in rats with histologically verified diffuse micronodular cirrhosis of the liver. Slightly impaired open-field behavior (i.e., decreased spontaneous activity) in the cirrhotic rats could not be excluded. However, the elevated brain serotonin synthesis rate could not be correlated to any abnormalities in open-field behavior.

Animals↗
PubMed1987

The effect of blood ingestion on brain serotonin synthesis in portacaval-shunted rats.

In rats with a portacaval shunt (PCS), the effect on the serotonin metabolism in the brain after oral administration of blood, a mixed amino acid solution (Vamin 14; KabiVitrum, Sweden) or a 10% glucose solution was studied. One week after PCS, the animals were fed with a gastric tube for 8 h and thereafter tested for behavioral abnormalities before decapitation at 12 h. The concentration of 5-hydroxytryptophan (5-HTP), serotonin (5-HT), and 5-hydroxyindoleacetic acid (5-HIAA) were analyzed chromatographically (HPLC technique with electrochemical detection) in different regions of the brain. Estimation of synthetic rates of 5-hydroxyindoles was facilitated by aromatic aminoacid decarboxylase inhibition (m-hydroxybenzyl-hydrazine; NSD 1015). The brain concentrations of 5-HTP, 5-HT, and 5-HIAA were increased in all shunted rats as compared with sham-operated animals. Whether animals received blood, glucose, or aminoacid solution made no differences in the brain concentrations of 5-HTP and 5-HT. Concentrations of 5-HIAA were lower in those animals receiving blood as compared with the other shunted groups. No reproducible differences in the behavior of the animals were observed. These results suggest that massive blood administration 1 week after PCS in rats has no influence on the rate of brain indole synthesis. While alterations in serotonin metabolism may play a role in some forms of encephalopathy, this study implies that the behavioral and neurologic disorders which follow gastrointestinal tract hemorrhage in patients with liver failure may have other etiologies.

5-Hydroxytryptophan↗
PubMed1987

Serotonin metabolism in the central nervous system following sepsis or portacaval shunt in the rat.

Similar neurological disturbances and metabolic alterations have been observed in liver insufficiency and in bacterial sepsis. In both liver failure and sepsis an altered neurotransmitter profile in the central nervous system (CNS) has been implicated in the pathogenesis of encephalopathic symptoms. It has been suggested that equivalent disturbances in brain neurotransmitters, especially serotonin, play a role in the encephalopathy accompanying sepsis and liver failure. The objective of this study was to compare the CNS serotonin metabolism in rats with an end-to-side portacaval shunt (PCS) with that found in rats with 12 or 24 hr of intraabdominal sepsis. The metabolism of CNS serotonin was estimated after inhibition of two enzymes acting in the 5-hydroxyindole synthetic pathway (decarboxylase and monoamine oxidase). The 5-hydroxyindoleacetic acid (5-HIAA) concentrations were determined in different regions of the CNS, thereby permitting evaluation of the synthetic activity of the serotonin neurotransmitter system. As previously reported, a marked increase in CNS serotonin synthetic rate was noted following PCS. In contrast, and in contradistinction to several recent reports, no major changes in the CNS serotonin synthesis rate were present following 12 or 24 hr of sepsis. CNS levels of the serotonin metabolite 5-HIAA were elevated in both sepsis and PCS rats. These data indicate that sepsis and liver failure have different effects upon serotonin metabolism in the CNS and suggest that differing pathogenetic mechanisms may underlie the encephalopathy clinically associated with these conditions.

5-Hydroxytryptophan↗
PubMed1986

Metabolism of monoamines in the brain after total hepatectomy in the rat.

Rats were subjected to total hepatectomy or a sham operation and infused 5 h with 10% glucose solution. The metabolism of indoleamines and catecholamines was studied in five regions of the brain and two regions of the spinal cord by using a decarboxylase inhibitor (NSD 1015) blocking the conversion of 5-hydroxytryptophan (5-HTP) to serotonin and DOPA to dopamine. In the brain the concentrations of 5-HTP, serotonin, and 5-hydroxyindoleacetic acid (5-HIAA) were elevated in all regions compared with controls except for serotonin in the mesencephalon-pons. In the spinal cord the concentrations of 5-HIAA were elevated whereas the concentrations of 5-HTP and serotonin were unchanged. The concentrations of DOPA were increased in the mesencephalon-pons whereas those of norepinephrine were decreased in cortex and mesencephalon-pons compared with controls. The results suggest an increased synthesis rate of the indoleamines in the brain and probably also of the catecholamines in the mesencephalon-pons at 5 h after hepatectomy.

5-Hydroxytryptophan↗
PubMed1986

The Third Whitbread Round the World Race.

A medical report from the Third Whitbread Round the World Race (1981-1982) is presented by the doctor on board the Swedish entry, who was also the contact doctor for the fleet. The race is the longest ocean race in the world at 27,000 nautical miles. It is divided into four legs with the yachts being offshore for 4-6 weeks on each leg. The medical preparation for the Swedish entry and the organization for the contact between the 28 participating boats are presented. The problems of medical interest during the race, as well as the possible dangers on board and their prevention, are listed and discussed. It is concluded that good medical preparation for the race is of great importance for the results.

Morbidity↗
PubMed1985

Arterial embolism of the legs. A follow-up study of 252 patients.

This retrospective study of 279 embolectomies in 252 patients shows a mortality of 27%, and an amputation rate of 15% within the first month after the embolectomy. The mortality as well as the rate of amputations decreased through the first year. After this period the mortality was comparable to that of a normal population and the rate of amputation was negligible. The mortality rate as well as the number of amputations increased with increasing time-lag of the embolectomy. In addition, the rate of amputation increased with preexisting intermittent claudication. There was no significant difference in amputation rate between limbs with and without palpable pulsations in the groin on admission, but 8 out of 103 limbs without groin pulsations had successful major vascular reconstruction performed after failing embolectomy in contrast to none in the group where pulsations were present. In 28 patients the embolectomy was followed by impairment of renal function and 14 of these died. It is concluded that embolectomy must be performed as early as possible, vascular reconstruction must be considered if the embolectomy fails to revascularize the limb, preventive measures should be taken against renal failure, i.e. the myonephropathic-metabolic syndrome.

Acute Kidney Injury↗
PubMed1983

Pregnancy-associated plasma protein A in the prediction of early pregnancy failure.

Maternal circulating pregnancy-associated plasma protein A (PAPP-A) was measured in 51 patients with vaginal bleeding in the first half of pregnancy. Concentrations of PAPP-A were consistently lower in pregnancies which failed. In the prediction of early pregnancy failure, the predictive value of depressed maternal PAPP-A levels was 58%, the sensitivity was 91.9%, and specificity was 95.1%. These results compared favorably with other biochemical tests of placental function. However, if fetal life was demonstrated ultrasonically, depressed levels of PAPP-A substantially differentiated between those pregnancies which continued normally and those which did not, suggesting that PAPP-A estimations would be of clinical value in cases previously beyond the reach of any diagnostic measure.

Abortion, Threatened↗