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Biomedical subjects

B Jeppsson

Publications and source records attributed to B Jeppsson.

At least 127 records · Page 7Linked to original sources
PubMed1988

RNA labelling with 3H-orotic acid and 3H-fluorouracil of rat liver tumour following transient hepatic arterial ischaemia.

Recent studies have demonstrated that transient (1 h) hepatic arterial ischaemia is followed by increased incorporation of labelled thymidine into tumour DNA 24 h later. The present study aimed at investigating if and when there is a corresponding increase in incorporation of labelled 5-fluorouracil (5-FU) or orotic acid into tumour tissue. Incorporation was studied at 0, 6, 24 and 48 h after discontinuation of transient hepatic arterial ischaemia in Wistar-Furth rats having liver tumour. The transient ischaemia was followed by increased RNA and RNA/DNA ratios in normal liver but not in tumour. Incorporation of orotic acid into RNA and DNA was unchanged in tumour but increased at 0 and 6 h in normal liver. Incorporation of 5-FU decreased with time in liver and tumour DNA and in tumour RNA. It is suggested that 5-FU has an optimal effect on tumour tissue when infused immediately after transient hepatic arterial ischaemia.

Animals↗
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

Control of traumatic liver hemorrhage in the cirrhotic rat by intraportal infusion of norepinephrine.

The effect of intraportal infusion of norepinephrine (NE) on primary hemostasis in the cirrhotic rat was investigated at standardized liver trauma. Cirrhosis was induced by simultaneous administration of increasing amounts of carbontetrachloride (CCl4) and phenobarbitone. Infusion of norepinephrine took place after cannulation of the gastroduodenal vein. Intraportal infusion of NE resulted in a significant increase in arterial blood pressure and portal pressure in all animals. No difference was observed between cirrhotic and control rats. Cirrhotic animals bled longer and more profusely as compared with the controls. Infusion of NE resulted in significant decrease in bleeding time and blood loss. NE did not affect hematocrit, hemoglobin, platelet, or white cell count. Platelet aggregation was not influenced by the compound. In conclusion, intraportal infusion of NE proved effective in decreasing hemorrhage at liver trauma in cirrhotic rats.

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↗
PubMed1987

Increased uptake of 5-FU in experimental liver tumours by simultaneous infusion of norepinephrine.

The effect of the simultaneous administration of norepinephrine and 5-fluorouracil (5-FU) on the uptake of radiolabelled 5-FU by liver tumours was studied in rats. Three different concentrations of 5-FU were used (15, 1.5 and 0.15 microgram/g body weight). The drugs were infused over a 30 min period via the hepatic artery, following cannulation of the gastroduodenal artery. The radioactivity in liver tumour, normal liver, lungs and intestines was estimated by liquid scintillation counting. At all concentrations tested, an increased uptake of radioactive 5-FU was found in the tumour when norepinephrine was infused. Tumour/liver ratios also increased significantly in all these cases. No significant differences were noted between norepinephrine infused and control animals in the radioactivity in normal liver, lungs and intestines. The effects noted were possibly due to changes in blood flow within the liver, but the possibility of a direct effect of norepinephrine on DNA metabolism is discussed.

Animals↗
PubMed1987

Early biochemical and histological changes in rats exposed to a single injection of thioacetamide.

Liver injury was induced by one subcutaneous administration of thioacetamide (200 mg/kg b.wt.) and studied 24 and 48 hrs later. Levels of aspartate aminotransferase (ASAT) and alanine aminotransferase (ALAT) increased after 24 and 48 hrs. The lysosomal enzymes beta-hexosaminidase (beta-NAG) and beta-glucuronidase (beta-GLU) increased significantly after 24 hrs, while the level of beta-GLU returned to normal after 48 hrs, but the activity of beta-NAG remained significantly high even after 48 hrs. Histopathological examination showed necrotic hepatocytes around the central vein with infiltration of macrophages, neutrophils and eosinophils. The plasma zinc level decreased after 24 hrs and returned to normal after 48 hrs. Liver zinc content increased simultaneously at 24 hrs, returning to normal after 48 hrs. No alterations of plasma copper were observed after 24 and 48 hrs. Copper content of the liver increased significantly after 24 and 48 hrs. The present study thus shows that one dose of thioacetamide results in profound liver injury and supplementation of zinc prior to and simultaneously with thioacetamide normalized plasma zinc, increased liver zinc content and reduced the increase of beta-NAG, but did not influence the histological changes.

Acetamides↗
PubMed1987

beta-Hexosaminidase in plasma and liver after partial hepatectomy in normal and cirrhotic rats.

The liver and plasma level of the lysosomal enzyme beta-hexosaminidase was analyzed in partially (about 70%) hepatectomized rats with normal liver or carbon tetrachloride (CCl4)-induced cirrhosis. The enzyme level of the liver did not show marked changes after partial hepatectomy in either normal or cirrhotic rats. In contrast, the plasma basal level was significantly higher in cirrhotic rats and increased to a peak at 6 h, followed by a decrease to a minimum level 24 h after operation. The enzyme returned to its high plasma basal level at 36 h after partial hepatectomy, when the liver had recovered to 70% of its initial weight. In rats with normal liver the plasma beta-hexosaminidase showed another pattern, with a rapid increase at 6 h and thereafter gradually reaching a peak at 36 h after hepatectomy. We conclude that the cells responsible for increased plasma beta-hexosaminidase in cirrhotic rats are situated in the liver.

Alanine Transaminase↗
PubMed1986

Determinants of survival after intraarterial infusion of 5-fluorouracil for liver metastases from colorectal cancer: a multivariate analysis.

A consecutive series of 73 patients treated with intraarterial infusion of 5-fluorouracil (5-FU) for liver metastases from colorectal primary was studied retrospectively using multivariate analysis in order to find determinants of survival. Nontreatment factors had a great impact on variation in survival with liver tumor volume and metastases to lymph glands in the liver hilum as major prognostic determinants. In addition, survival from onset of treatment varied with the interval between the primary operation and the diagnosis of liver metastases. Treatment with intraarterial 5-FU was more effective when administered at long-term (3 months every 6 months) than at short-term (5 days every 6 weeks). Single temporary dearterialization, used as an adjunct to infusion of 5-FU, had a negative impact on length of survival and was followed by a high frequency of complications. The occurrence of hepatic arterial thrombosis was associated with comparatively good prognosis.

Adult↗
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

Portacaval shunt in the rat: selective alterations in behavior and brain serotonin.

Portacaval shunted (PCS) rats and sham-operated controls were investigated for spontaneous activity, exploration, somatosensory reactivity, swim latencies in a water maze, motor coordination, and passive avoidance 2 to 3 weeks after operation. The rats were subsequently decapitated and indole metabolism was investigated in different brain regions. The results showed that shunted rats were impaired in both open field tests (spontaneous activity and exploration) and in somatosensory reactivity (latency to respond, maximal response and integrated response). Results from motor coordination tasks and learning and memory tests (water maze and passive avoidance) did not demonstrate differences between the groups. There was an increased brain indolamine metabolism in PCS compared to sham-operated rats. No correlation between the behavioral impairment and the altered indolamine metabolism could be demonstrated with multiple correlation analysis.

5-Hydroxytryptophan↗