Search PubMed⌕ Search

Biomedical subjects

L Ekman

Publications and source records attributed to L Ekman.

At least 37 records · Page 2Linked to original sources
PubMed1989

N-acetyl-L-tyrosine and N-acetyl-L-cysteine as tyrosine and cysteine precursors during intravenous infusion in humans.

The usefulness of N-acetyl-L-tyrosine (NAT) and N-acetyl-L-cysteine (NAC) as tyrosine and cysteine precursors during intravenous infusion was investigated in humans. Plasma levels and urinary excretion of NAT, tyrosine, NAC, and total cysteine were determined, and the site of deacetylation was examined by measuring the splanchnic and renal balances. Eleven healthy volunteers were given 5 g of either NAT or NAC as a 4-hour intravenous infusion. Plasma levels of NAT and NAC increased rapidly, accompanied by a 25% increase in tyrosine levels and a 35% decrease in total cysteine. Urinary excretion of NAT and NAC in 4 hours accounted for 56% and 11% of the infused amount, respectively. No net production of tyrosine or cysteine was found from the splanchnic area, but from the kidneys there was a small release of both tyrosine (10 +/- 3 mumol/min) and cysteine (64 +/- 3 mumol/min). We conclude that under these conditions the usefulness of NAT and NAC as precursors for the corresponding amino acids in humans is not apparent.

Acetylcysteine↗
PubMed1989

Utilization of intravenously administered N-acetyl-L-glutamine in humans.

L-glutamine is too unstable for inclusion in solutions for parenteral nutrition, but its acetylated analogue, N-acetyl-L-glutamine is not. The purpose of this three-part study was to investigate the utilization of intravenously (IV) administered acetylglutamine in humans. In study 1, nine healthy postabsorptive subjects were given 9.4 g acetylglutamine IV during four hours. In study 2, five healthy subjects were studied on two occasions following an overnight fast. They were given 9.4 g of acetylglutamine or an equivalent amount of glutamine as part of a total parenteral nutrition (TPN) regimen during 7.2 hours. A control group of five subjects was given the same TPN regimen, but without acetylglutamine or glutamine. The nutrient solution included glucose, amino acids, and a fat emulsion, supplying 9.4 g nitrogen and 6,300 kJ in a total volume of 1.8 L. In study 3, four patients were studied the day after major surgery. They were given the same TPN regimen as in study 2, containing 9.4 g acetylglutamine, during 7.2 hours. Plasma concentrations and urinary excretion of acetylglutamine and glutamine were measured in all three studies, and so were splanchnic and renal exchange of acetylglutamine and glutamine in study 1. In study 1, the plasma concentration of glutamine rose from 594 +/- 28 mumol/L to 728 +/- 26 mumol/L (P less than .001), whereas plasma levels of acetylglutamine exceeded 1,000 mumol/L in all subjects at the end of infusion. The eight-hour urinary excretion of acetylglutamine and glutamine corresponded to 18% of the infused amount of acetylglutamine.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Dose and sex-dependent disposition of ketoconazole in rats.

The disposition of the antifungal drug ketoconazole was studied in mature (60-day-old) male and female rats given single intravenous doses of 10, 20 or 40 mg/kg body weight. The plasma profiles of ketoconazole were characterized by an initial rapid decline, followed by an apparent zero-order decline and a subsequent first-order elimination phase. In male animals the zero-order phase was less pronounced, resulting in a 3-5 times higher overall rate of elimination. A consequence of the dose-dependent disposition was that a 4-fold increase in dose resulted in a 9- and 17-fold increase in the area under the plasma concentration-time curve (AUC) of females and males, respectively. Terminal half-lives were independent of dose in both sexes. The disproportionate increase in AUC with dose, together with the observation that no intact ketoconazole was excreted in urine and only very small amounts in bile (less than 1% of given dose), suggest that the dose-dependent disposition is caused by saturation of metabolizing enzymes. These enzymes are most likely under the influence of androgens, since the capacity of males to eliminate ketoconazole was reduced by castration and in females this capacity was increased by testosterone treatment.

Animals↗
PubMed1987

Protein synthesis in skeletal muscle of rats following starvation and refeeding.

Determination of protein synthesis in individual tissues is important to understand the changes in protein metabolism during catabolic states. Three methods based on different underlying assumptions were compared in assessing muscle protein synthesis during nutritional manipulation. Rats were nonstarved, starved for 1 or 3 days, or refed for 2 days after 3 days of starvation. The extensor digitorum longus (EDL) muscles from the two hindlegs were used for analysis. In one EDL muscle the concentration and size distribution of ribosomes as well as the incorporation of [14C]leucine into protein in a cell-free system were determined. The other EDL muscle was incubated as such and the incorporation of [14C]phenylalanine into protein was measured. The total ribosome concentration per milligram of DNA decreased to 65% on the third day of starvation and remained low after refeeding. The amount of polyribosomes in the percentage of total ribosomes fell to 90% on the first day of starvation, regained the initial level on the third day, and reached 110% upon refeeding. During refeeding amino acid incorporation into protein in a cell-free system decreased to 40% and that in intact muscle to 64% of the prestarvation level. Upon refeeding, the activity increased to or above the original values. The use of several different techniques in parallel to assess protein synthesis in skeletal muscle is recommended since it gives information about the factors involved in regulation of the translational process in intact mammalian tissues.

Animals↗
PubMed1987

The relationship of the pharmacokinetics of chloroquine to dose in the rabbit.

Four albino rabbits were treated with 4 different doses of chloroquine phosphate (30-50 mg kg-1) given intragastrically and 10 others were given the hydrochloride (2.5-12.5 mg kg-1 i.v.). The i.v. doses were given as bolus into the median ear vein over 5-8 min. Samples (3-5 mL) of whole blood were subsequently collected at intervals for up to 6 weeks and analysed by HPLC. From the results, log concentration-time curves were drawn and the i.v. data fitted by computer to 3-compartment (8 rabbits) or 2-compartment curves (2 rabbits). The area under the curve (AUC) and half-lives were calculated for the different doses. A plot of AUC versus dose yielded a straight line but the half-lives showed wide inter-individual variation from the same doses.

Animals↗
PubMed1987

The metabolic response to glycerol during parenteral nutrition.

The use of various nonprotein energy sources in parenteral nutrition regimens has been discussed for many years. Besides glucose, glycerol, xylitol, fructose and sorbitol are currently being used as water-soluble parenteral fuels. Despite the increasing frequency with which these glucose substitutes are being used, little information is available regarding the differences they evoke in host responses. All experimental evidence to date has shown glycerol to be equally effective in sparing body nitrogen as glucose when supplied in hypocaloric amounts. Results from studies in injured animals suggest that exogenously administered glycerol is a more potent inhibitor of fatty acid oxidation than glucose. Although results from human volunteers have been variable, glycerol administration after injury appears to markedly reduce fatty acid oxidation and ketogenesis, as well as increase hepatic glycogen. Glycerol toxicity appears to result only from its excessive administration, or when administered intraperitoneally or subcutaneously. Intravenous administration of hypocaloric quantities of glycerol alone or as a component of total parenteral nutrition is safe and effective.

Dose-Response Relationship, Drug↗
PubMed1987

New developments in lipid emulsions for parenteral nutrition.

More than one thousand publications have demonstrated the safety and efficacy of today's lipid emulsions including long chain fatty acids under experimental and clinical conditions. This has resulted in a general acceptance of a dual energy system comprising both carbohydrates and lipids as non-protein calories in total parenteral nutrition. Non-carnitine-dependent fatty acid has been suggested as a superior energy source in clinical situations where carnitine may be in the subnormal range. A medium chain triglyceride (MCT) emulsion would provide an energy source with a more readily oxidizable substrate. The tolerance of MCT is less than that of long chain triglyceride (LCT), whereby only physical mixtures of these emulsions will be used in humans. A structured lipid (SL) is a triglyceride which includes both medium and long chained fatty acids within the same triglyceride. Emulsions including SL have demonstrated a decreased protein energy expenditure and increased serum albumin in burned animal. The SL has also been superior to LCT emulsions in stimulating muscle protein synthesis and maintaining body weight in hepatectomized animals. These positive effects on protein kinetics have been concomitant with a lower RES involvement during septicemia in burned guinea pigs. Emulsions including fatty acids with odd-number carbons give a possibility to provide a fat emulsion which also could contribute positively to the glucose homeostasis. The omega-3 family of fatty acids has demonstrated a potential pharmacologic effect with regard to their ability to decrease blood viscosity and improve survival rate in endotoxin shock in an experimental model. These observations have been ascribed to changes in thromboxin A2 levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Fat Emulsions, Intravenous↗
PubMed1987

Toxicity study of the new glucocorticosteroid budesonide in rats.

16 alpha,17 alpha-Butylidenedioxy-11 beta,21-dihydroxypregna-1,4-diene-3,20- dione (budesonide) was administered subcutaneously to male and female Wistar rats at the doses 0.01, 0.1 and 5 micrograms/kg/d (10 animals/group), and 5, 20 and 80 micrograms/kg/d (15 animals/group) for 26 weeks in two separate studies. A dose-dependent decrease in body weight gain in the groups given 5, 20 and 80 micrograms/kg/d compared with the control group was noted as well as a dose-related reduction in food intake in males receiving 20 or 80 micrograms/kg/d. Increased values for packed cell volume, hemoglobin concentration and erythrocyte counts were found for both sexes at the dose levels 20 and 80 micrograms/kg/d. Also a marked decrease in the number of lymphocytes was seen for both sexes at 80 micrograms/kg/d, and for females also at 20 micrograms/kg/d. Pathological changes associated with treatment with budesonide were found in the liver--panacinar hepatocytic fine vacuolation in females receiving 80 micrograms/kg/d; cervical lymph nodes--low numbers of small lymphocytes in both males and females receiving 20 or 80 micrograms/kg/d; mesenteric lymph nodes--low numbers of small lymphocytes in females receiving 20 or 80 micrograms/kg/d; thymus--low numbers of small lymphocytes in females receiving 80 micrograms/kg/d; mammary glands--acinar hyperplasia and secretion in both sexes receiving 20 and 80 micrograms/kg/d; uterus--dilation of the lumen in females receiving 20 or 80 micrograms/kg/d. Treatment with budesonide at doses of 5 micrograms/kg/d and below was without effect upon the morphology.

Animals↗
PubMed1986

Effects of tumor-load and malnutrition on myocardial function in the isolated working rat heart.

Marked differences in cardiac associated morbidity and mortality have been reported between patients with and without malnutrition. Tumor-associated cachexia may impair heart function, which further aggravate host wasting and thereby create a vicious circle. The aim of this study was to evaluate to what extent a malignant tumor may influence heart function under well-defined experimental conditions. The perfused working rat heart was used as a model. Study groups of freely-fed sarcoma-bearing rats, starved and protein-calorie malnourished (PCM) non-tumor rats were compared to freely-fed control animals. All groups of malnourished animals (tumor-bearing, starved and PCM) lost significant amounts of body and heart mass compared to freely-fed controls. Loss of heart contractile mass in tumor-bearing rats and malnourished animals did not lead to impaired heart function in any respect. The rate of oxygen uptake was significantly higher under all experimental conditions in perfused hearts from tumor-bearing rats compared with hearts from starved, PCM and freely-fed control rats. Oxygen uptake per left ventricular work was significantly higher in tumor-bearing rats but significantly lower in starved and PCM rats compared with control animals. Norepinephrine at various concentrations (10(-9)-10(-5) mol/l) in the perfusate stimulated the contractility and the left ventricular peak pressure significantly more in hearts from malnourished animals compared with that of freely-fed controls. The results show that adaptive functional changes can be recorded in the isolated perfused rat heart from sarcoma-bearing rats and after a period of comparatively acute undernutrition in non-tumor rats. A malignant tumor or the associated malnutrition does not induce impaired pumping performance despite a reduction in contractile heart mass. Increased oxygen consumption in hearts from tumor-bearing animals may contribute to elevated energy expenditure in a cancer-bearing host.

Animals↗
PubMed1986

Comparison of the pharmacokinetics of chloroquine after single intravenous and intramuscular administration in healthy Africans.

The pharmacokinetics of chloroquine were studied after intramuscular and intravenous administration of the drug to healthy African adults. Chloroquine was analysed in plasma using an h.p.l.c. method and pharmacokinetic parameters were derived from the concentration-time data using a non-linear computer programme. A two-compartment open model was assumed. Chloroquine was rapidly absorbed from an intramuscular site, producing a plasma concentration-time profile similar to that obtained after a 15 min i.v. infusion of a comparable dose. The pharmacokinetics of chloroquine after i.m. and i.v. administration were characterised by a long half-life and a very large volume of distribution. There was no significant difference between the values of each parameter obtained from the different routes. It is suggested that the high Cmax obtained after i.m. and i.v. administration of chloroquine might contribute to its toxicity when these routes are used in treatment.

Adult↗
PubMed1985

Metabolic effects of nutritional support to cancer patients.

An adequate understanding of the utilization of administered nitrogen and energy sources as well as the regulation of whole body energy expenditure are important factors for maintaining body weight and body composition. The efficacy and metabolic consequences of adjunct nutritional support to cachectic cancer patients has recently been investigated in a number of studies. This review examines some recent investigations in this area. Depleted cancer patients seem to have a slightly higher resting energy expenditure but a normal metabolic and energetic response to administration of energy substrates. Studies of protein metabolism suggest that depleted cancer patients have a disturbed metabolic response of protein anabolism compared with depleted controls. This could be due to differences in peripheral versus visceral tissues. Adjunct nutritional support plays an important role in restoring the depleted cancer patients although clear correlation to functional parameters is still lacking.

Body Weight↗
PubMed1985

Metabolic response of simultaneous versus sequential intravenous administration of amino acids and energy substrates to rats.

Three groups of rats were maintained on total intravenous nutrition for ten days. Group SA and SB were infused sequentially (2 X 12 h periods per day), SA received amino acids (AA) during the night and carbohydrates (CHO) + FAT during the day. The SB group received nutrients in the opposite order. A control group received a mixed solution simultaneously for 24 h/day. The sequentially fed groups showed a lower weight gain (2.4 +/- 0.4, 2.6 +/- 0.2 vs 4.9 +/- 0.3 g/day), nitrogen balance (95 +/- 7, 95 +/- 6 vs 139 +/- 7 mg/day) and nitrogen utilization (69 +/- 3, 67 +/- 3 vs 87 +/- 3%) compared with the control group. Administration of energy substrate in the SA and SB was a stronger denominator for O2 consumption and changes in RQ than the periods of physical activity. Control animals did not show any diurnal variations in O2 and RQ. Glucose, FFA and insulin were higher with CHO + FAT administration compared to AA infusion or simultaneous AA/CHO/FAT administration. In conclusion, the results suggest that simultaneous administration of a mixture of AA/CHO/FAT is preferable for whole body nitrogen economy during TPN.

Amino Acids↗
PubMed1985

Determination of chloroquine and its desethyl metabolite in whole blood: an application for samples collected in capillary tubes and dried on filter paper.

A high performance liquid chromatography method for analysis of chloroquine and desethylchloroquine was adapted for 75 microliters aliquots of whole blood obtained by finger-prick and dried on filter paper. The precision of the method was satisfactory at whole blood concentrations of 40 nmol/L (coefficient of variation, 5%). The dried samples were stable for at least 7 weeks at 20 degrees C. The concentrations in venous whole blood and in dried samples correlated well. The correlation coefficient was 0.99 for chloroquine and 0.97 for desethylchloroquine. Chloroquine concentrations were marginally but significantly higher in venous whole blood. When fitted to a linear equation (y = bx + a) the relationship was y = 0.96x + 0.03. Desethylchloroquine concentrations did not differ significantly in venous whole blood and in finger-prick blood dried on filter paper. The method is specific and sensitive enough for pharmacokinetic studies and can be used in areas with limited technical facilities.

Blood Specimen Collection↗
PubMed1985

A simplified technique for measurements of energy expenditure and substrate oxidation in man.

A technique is described for simultaneous measurements of energy expenditure and oxidation of exogenous substrates in man. The equipment comprised a semi-opened respiratory hood operated by a negative-flow pressure of the gas flow through the system. The system was constructed by assembling commercially available components with high analytical precision into an integrated constellation. We present results of instrument accuracy, assessed by calibration, and the coefficient of variation (CV) for calibration procedures of the total system, as well as findings with regard to the degree of reproducibility of applied investigations on both healthy volunteers and hospitalized patients. The overall coefficient of variation was 3-4% of the mean values for RQ and energy expenditure. This includes both biological and methodological variation. The cost of this system is less than that for a commercially available system with a similar performance.

Adult↗
PubMed1985

Toxicological studies on omeprazole.

As part of the safety evaluation of the gastric antisecretory drug, omeprazole, toxicological studies have been performed in several species of animals. The acute toxicity after oral administration to rodents was low. The oral LD50 value was above 4 g/kg. The general toxicity after repeated administration has been studied in rats and dogs. No clinical signs of adverse reactions were seen. Some minor changes in hematology parameters were observed. In rats and mice decreases in the erythrocyte count, hematocrit and hemoglobin have occasionally been found at doses of 125 mumol/kg/day and more. Hyperplasia of oxyntic mucosal cells, concomitant with increases in stomach weight, oxyntic mucosal thickness and folding, has been observed in the species investigated, the dog, rat and mouse. In addition, slight chief cell atrophy and eosinophilia of the chief cell granules were observed in rats. The oxyntic mucosal effects were reversible upon treatment being discontinued. In the oncogenicity studies, gastric carcinoids occurred in the rat but not in the mouse. Investigations of the carcinoids showed that the vast majority of the endocrine cells could be characterised as ECL-cells. The hyperplasia of oxyntic mucosal cells, including hyperplasia of endocrine ECL-cells and development of gastric carcinoids in rats, is attributable to the pronounced hypergastrinemia produced as a secondary effect of almost complete inhibition of acid secretion by the large doses of omeprazole used in the toxicity studies. In agreement with this hypothesis, the hyperplasia of the oxyntic cells was prevented by antrectomy. The reproduction studies performed in rats and rabbits showed no sign of fetal toxicity or teratogenic effect. The results of the short-term mutagenicity tests, Ames test, the micronucleus test in mice and the mouse lymphoma test were all negative.

Administration, Oral↗
PubMed1984

Metabolic consequences of nutritional support of the cancer patient.

The year 1983-1984 has been a period of evaluation and examination of efficacy of nutritional support of the cancer patient. The early observation that individual patients, unable to ingest, digest, or absorb food could be nutritionally maintained by intravenous nutrition has been repeated in every cancer center. The premature application of parenteral nutrition as an adjunct to cancer care and the results of clinical trials with small numbers of patients have initiated a reevaluation of this therapy, as a routine. The most exciting advances have come from the opportunity to utilize nutritional support as a means of investigating the basic mechanisms by which the cancer patient disposes of exogenously delivered substrate. This opportunity had been initially under-appreciated and is only now receiving the full and intensive clinical and laboratory research necessary to delineate abnormalities of metabolism that occur in the cancer-bearing host. Studies have not been performed not only in intact man, but in specific organ systems in man during nutritional support. These studies, using stable and radioactive isotopes, have given us new insight into the way that the cancer patient handles glucose and amino acids. Whether these abnormalities of metabolism are due to the cancer or are due to treatment, complications of treatment, or inherent starvation accompanying progressive cancer cachexia is being examined. Such studies should indicate whether or not therapeutic interventions in limiting substrate availability for the tumor while preserving the host are possible.

Body Composition↗