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Biomedical subjects

O Almersjö

Publications and source records attributed to O Almersjö.

At least 19 recordsLinked to original sources
PubMed1988

Inhibition of thymidylate synthase after administration of doxifluridine in a transplantable colon carcinoma in the rat.

Parameters for inhibition of thymidylate synthase (TS) in a DMH-induced transplantable rat colon carcinoma were studied after intraperitoneal administration of bolus doxifluridine (5'-dFUR) 200 mg/kg. Levels of 5'-dFUR, 5-fluorouracil (5-FU), fluorouridinediphosphate (FUDP), and fluorouridinetriphosphate (FUTP) were determined by use of high-performance liquid chromatography. Micromethods for analysis of 5-fluoro-2'-deoxyuridylate (FdUMP) and TS were used to study the in vivo intracellular pharmacokinetics of TS inhibition. Peak values of 5'-dFUR and 5-FU were found at 30 min and showed exponential declines with values close to zero at 5 hr. Substantial levels of FUDP and FUTP were found throughout the 24 h observation time. Peak FdUMP levels were modest compared to those observed after equimolar administration of 5-FU, but FdUMP persisted in amounts well above available binding sites on TS for the 24 h observation time. Reduction of free TS enzyme to undetectable levels (less than 0.05 pmol/g) lasted for 4 h, and at 24 h, there was still almost 70% enzyme inhibition. The total amount of TS (TStot) defined as free [3H]FdUMP-titrable enzyme (TSf) plus TS bound to FdUMP in a ternary complex (TSb) increased as a result of 5'-dFUR bolus injection from 15 to 50 pmol/g during the 24 hr observation time. We conclude from these data that 5'-dFUR is converted to 5-FU and subsequently to FdUMP, and the results suggest that 5'-dFUR exerts its cytotoxic effects through inhibition of TS and incorporation into RNA.

Animals↗
PubMed1987

Concurrent allopurinol and 5-fluorouracil: 5-fluoro-2'-deoxyuridylate formation and thymidylate synthase inhibition in rat colon carcinoma and in regenerating rat liver.

The formation of FdUMP and the inhibition of TS were studied in a subcutaneously growing transplantable rat colon carcinoma and in regenerating rat liver following bolus administration of 5-FU, with or without HPP pretreatment. In tumor, peak levels of FdUMP at 30 min following bolus 5-FU, 100 mg/kg, averaged 4931 +/- 587 pmol/g. Pretreatment with HPP, 50 mg/kg, 24 h and 1 h before 5-FU, reduced the peak FdUMP level to 2085 +/- 387 pmol/g. The inhibition of TS by 5-FU treatment was greater than 95% by 30 min, and after 48 h residual enzyme inhibition averaged 40%. No effect on TS inhibition by 5-FU treatment could be observed as a result of HPP pretreatment. The levels of TStot increased linearly after 5-FU treatment and doubled within 48 h. In regenerating rat liver, neither FdUMP levels nor TS inhibition, studied at 1 h after bolus 5-FU, were affected by HPP pretreatment.

Adenocarcinoma↗
PubMed1986

Sequential methotrexate/5-FU: FdUMP formation and TS inhibition in a transplantable rodent colon adenocarcinoma.

Parameters for inhibition of thymidylate synthetase were studied after sequential methotrexate/5-fluorouracil (5-FU) administration in a dimethylhydrazine (DMH)-induced transplantable rat colon carcinoma. Tumor-bearing rats were treated with methotrexate (MTX) 40 mg/kg IP Bolus 5-FU, 100 mg/kg IP, was injected after 24 h. Micromethods for assay of 5-fluoro-2'-deoxyuridylate (FdUMP) and thymidylate synthetase (TS) were used to study the in vivo intracellular pharmacokinetics of 5-FU. Formation of FdUMP was equally rapid in tumors regardless of MTX pretreatment, with peak values found at 30 min. Although MTX pretreatment did not increase peak FdUMP levels, it appeared to result in increased persistence of FdUMP, well in excess of available TS-binding sites, at 24 and 48 h. The combination therapy was less effective in terms of TS inhibition over the first 8 h after 5-FU administration, but may have been associated with improved TS inhibition at later time points. Total levels of TS (TStot) steadily increased from a pre-5-FU treatment level of 18.8 pmol to more than 40 pmol/g at 24 h. MTX per se had no apparent effect on baseline TStot levels or on the 5-FU-mediated increases in TStot. We conclude that MTX and 5-FU were antagonistic in terms of TS inhibition over the first 8 h after 5-FU in this DMH-induced rat colon carcinoma, but were possibly synergistic in increasing persistent levels of FdUMP and TS inhibition at later time points. The observation that 5-FU treatment can result in progressive increases in TS levels in some tumors suggests that this may be an important mechanism of 5-FU resistance.

Adenocarcinoma↗
PubMed1984

Effects of hydralazine on liver blood flow in normovolemic dogs.

The effects on liver blood flow caused by hydralazine were studied in 14 dogs. Hepatic artery and femoral artery blood flow were estimated with an electromagnetic flow meter. Total hepatic blood flow (THBF) was measured by 133Xenon clearance. Cardiac output (CO) was determined by intravenous injection of Cardio-Green. After 0.2 mg/kg of hydralazine total hepatic blood flow increased by 57%. The hepatic artery blood flow increased by 82% and portal blood flow by 58%. Cardiac output increased by about 50%, while total peripheral vascular resistance decreased. The results further suggest that hydralazine increases portal blood flow. Also the ratio THBF : CO increased. These findings together indicate a hydralazine-induced redistribution of cardiac output with a relatively increased proportion provided to the liver.

Animals↗
PubMed1981

Ultrasound in the differential diagnosis of jaundice.

Ultrasound examination was performed in 53 jaundiced patients; successful examination was accomplished in 48. Ultrasonography revealed mechanical biliary obstruction in 34 of 35 patients with obstructive jaundice. Dilatation of the intrahepatic or extrahepatic biliary ducts or the gallbladder was not present in any patient with non-obstructive jaundice. The value of ultrasound examination in the differential diagnosis of jaundice is emphasized.

Aged↗
PubMed1981

Trauma to the liver during a ten-year period. With special reference to morbidity and mortality after blunt trauma and stab wounds.

The records of 58 patients with hepatic injuries treated between 1969 and 1978 were analyzed in retrospect. The hepatic injury was caused by blunt trauma in 30 cases (52%), stab wounds in 26 cases (45%) and gun shot wounds (GSW) in 2 cases (3%). In 45 patients (78%) the injury could be managed by simple methods such as laparotomy alone or suture and/or drainage. Hepatic lobectomy was performed in 5 patients (9%). When compared with stab wounds, hepatic injuries after blunt trauma were associated with higher frequency of shock, more blood transfusions, more associated injuries, more severe liver injuries and longer hospital stay. Overall mortality rate was 19%. True hepatic injury mortality rate was 5%. After blunt trauma mortality rate was 30% and after stab wounds 4%. The mortality rate was higher in patients with multiple associated injuries and after more severe hepatic injuries.

Adolescent↗
PubMed1980

Structural and functional changes in ribosomes from ischemic liver in the dog: effects of short-term hepatic artery ligation and hemorrhagic shock.

Structure and function of isolated liver ribosomes from 10 dogs subjected to 1 h of hepatic artery ligation (HAL) or hemorrhagic shock were studied. A shift of polyribosomes to monoribosomes and a decreased capacity to incorporate amino acids into proteins were seen in both experimental conditions. The effects were more pronounced in hemorrhagic shock. Both structural and functional changes were reversible after HAL. In the shock experiments a slight increase of the ribosomal activity was seen after reinfusion but the initial values were not reached during the 2 h after the shock period. Some of the underlying mechanism of altered ribosomal structure and function in liver ischemia are discussed.

Amino Acids↗
PubMed1980

Amino acid incorporation into liver and tumor proteins in patients with hepatic neoplasms-effects of liver dearterialization.

The effects of liver dearterialization on the rate of amino acid incorporation into liver and tumor proteins were studied with an in vitro method in seven patients with liver metastases. Before liver dearterialization the incorporation rate was 0.074 +/- 0.020 nmol leucine x mg prot-1 x h-1 in liver tissue and 0.234 +/- 0.049 nmol leucine x mg prot-1 x h-1 in tumor tissue. After dearterialization for 1 h the incorporation rate was reduced to about half of the initial values in both liver and tumor tissue. The vascularity of the tumors was evaluated from preoperative hepatic angiograms. The reduction of the incorporation rate was more pronounced in highly vascularized tumors than in poorly vascularized tumors and liver tissue. The clinical implications of a more pronounced metabolic effect of the dearterialization in high vascularized tumors are discussed.

Adult↗
PubMed1979

New assay of 5-fluorouracil in serum by isotachophoresis.

Blood levels of 5-fluorouracil are quantitatively determined by isotachophoresis. Serum is deproteinized, purified on an ion-exchange column and concentrated to 20 microliter, and the drug is measured isotachophoretically. Down to 50 pmol (6.5 ng) of the drug can be determined in serum with a methodological error of +/- 6%. The method can be used for routine control of patients undergoing therapy with the drug.

Chromatography, Ion Exchange↗
PubMed1979

Amino acid incorporation into liver proteins during hemorrhagic shock in the dog.

Liver protein synthesis was studied with an in vitro method during and after 1 h of hemorrhagic shock in the dog. Protein synthesis was significantly decreased already 15 min after induction of hypovolemia and was about 50% of the initial value at the end of the shock period. 2 h following retransfusion, protein synthesis was normalized. Some of the underlying mechanisms leading to decreased protein synthesis in hemorrhagic shock are discussed. Serum concentrations of liver enzymes were unchanged during the shock period indicating that the liver metabolism may be affected without changes in parameters often used to evaluated liver function.

Alanine Transaminase↗
PubMed1979

Liver circulation and oxygen metabolism during short time ligation and the hepatic artery in the dog.

The changes of liver circulation and liver oxygen metabolism during and after one hour hepatic artery ligation (HAL) were studied in eight mongrel dogs. At the end of the HAL period total hepatic blood flow (THBF) was reduced from 115.6 +/- 5.5 ml/min . 100 g liver tissue to 68.0 +/- 3.7 ml/min . 100 g or 59% of the initial value. The portal venous blood flow was reduced from 83.1 +/- 3.4 to 58.8 +/- 3.7 ml/min . 100 or 82% of the initial value and the liver oxygen consumption was reduced from 4.1 +/- 0.2 ml/min . 100 g to 3.1 +/- 0.3 ml/min . 100 g or 76% of the initial value. The changes in portal venous blood flow and liver oxygen consumption were reversible following reopening of the hepatic artery. The clinical importance of a reduced portal venous blood flow and liver oxygen consumption following HAL and the possibilities to increase the portal venous blood flow are discussed.

Animals↗
PubMed1977

Methodological aspects of an agar plate technique for determination of biologically active 5-fluorouracil in blood, urine and bile.

A microbiological agar plate technique for estimation of 5-fluorouracil concentrations in blood, urine and bile from man, dog and pig was evaluated. Different bacterial test strains, media modifications and techniques for inoculation were studied. The strain Streptococcus faecalis ATCC 8043, recommended previously by Clarkson et al., was found to be the most suitable. The influence of prediffusion, dilution, antibiotics and chemotherapeutic agents and their antagonists, as well as the effect of storage of samples containing 5-fluorouracil were examined. A detailed methodological description is presented. The method seems to be sufficiently sensitive and practical for routine determination of cytotoxic compounds from 5-fluorouracil in serum, plasma and urine.

Agar↗