Search PubMed⌕ Search

Biomedical subjects

R Blomstrand

Publications and source records attributed to R Blomstrand.

At least 19 recordsLinked to original sources
PubMed1989

Non-linear kinetics of 4-methylpyrazole in healthy human subjects.

In order to evaluate the pharmacokinetic profile of the alcohol dehydrogenase inhibitor 4-methylpyrazole 4-MP, a placebo-controlled, double-blind, single-dose, randomized, sequential, ascending-dose "Phase-I study" was performed in healthy male volunteers at dose levels of 10 (n = 4), 20 (n = 4), 50 (n = 4) and 100 mg.kg-1 (n = 3). In the 10 and 20 mg.kg-1 group, the elimination of 4-MP from the plasma followed non-linear kinetics with mean rates of concentration decline of 3.66 and 5.05 mumol.l-1.h-1, respectively. In the two highest dose groups, the elimination also appeared to be non-linear although the patterns were not followed long enough to confirm this. The mean rates of concentration decline at the higher doses were significantly increased, up to 14.9 mumol.l-1.h-1 at 100 mg.kg-1. The average renal clearance of 4-MP was low, 0.016 ml.min-1.kg-1, and only 3% of the administered dose was excreted unchanged in the urine, indicating metabolism as the major route of elimination. Because of the apparently unusual kinetics following single dose treatment, thorough multiple dose studies need to be carried out to determine a safe dosage regimen for 4-MP.

Adult↗
PubMed1988

4-Methylpyrazole: a controlled study of safety in healthy human subjects after single, ascending doses.

4-Methylpyrazole (4-MP), an inhibitor of alcohol dehydrogenase, is a possible future drug for the treatment of methanol and ethylene glycol intoxications and the severe ethanol-disulfiram reaction. Therefore a placebo-controlled, double-blind, single-dose, randomized, sequential, ascending-dose "Phase I study" was performed in healthy volunteers in order to determine the tolerance of 4-MP at dose levels of 10 (n = 4), 20 (n = 4), 50 (n = 4), and 100 mg/kg (n = 3). Along with each dose group, there were two placebos except with the 100 mg/kg group where there was only one placebo. In the 10 and 20 mg/kg group there were no side-effects in any subject. At the 50 mg/kg level, three out of four subjects experienced slight to moderate nausea and dizziness from 0 to 2.5 h after dosing. In the 100 mg/kg group all three subjects reported side-effects like nausea, dizziness, and vertigo, that were short-lived in two subjects, but lasted up to 30 h in one subject. The study was stopped after evaluation of the latter subject, so fewer subjects were completed in this last group. Despite these subjective side-effects, there were no significant changes in objective clinical parameters like pulse, blood pressure, body temperature, or blood and urine chemistries. We conclude that at a single dose of 4-MP (10-20 mg/kg) producing plasma levels within a probable therapeutic range, no side-effects were attributed to 4-MP.

Adult↗
PubMed1986

Occurrence of short chain aliphatic diols in human blood: identification by gas chromatography-mass spectrometry.

Patients attending a general hospital for various reasons were screened for raised serum gamma glutamyltransferase (gamma-GT) and positive blood alcohol concentration (BAC). The results served as objective biochemical tests of heavy drinking. Among 419 individuals, 50 (11.9%) met these requirements and blood samples were used to determine the presence of low molecular mass aliphatic diols. 1,2-Propanediol, 2,3-butanediol and 2,2-dimethyl-1,3-propanediol were determined by gas liquid chromatography-mass spectrometry (GC-MS). In patients with blood ethanol concentration less than 2 mmol/l, 1,2-propanediol and 2,2-dimethyl-1, 3-propanediol mainly occurred together at median concentrations of about 200 mumol/l. When blood ethanol was 2-42 mmol/1,2,3-butanediol was also present covering a wide concentration range: three patients had concentrations between 6 and 10 mmol/l. There was no apparent correlation between the concentration of 2,3-butanediol and the concentration of blood ethanol. The diols were below the limits of detection in blood from nonintoxicated control individuals and hospital in-patients.

Adolescent↗
PubMed1986

Dietary modulation of retina phospholipids and photoreceptor function with particular reference to phosphatidylinositol.

The effect of dietary partially hydrogenated herring oil (HHO) on the fatty acid composition of the phospholipids of rat retina and on the amplitude of the a-wave of the electroretinogram (ERG) was studied in rats raised for several generations on an essential fatty acid poor diet. The most significant effect of the dietary treatment was a decreased content of arachidonic acid (C20:4 omega 6) and an increased concentration of docosahexaenoic acid (C22:6 omega 2) and 18:1 isomers associated with the phosphatidylinositol (PI). The a-wave of the ERG showed a decreasing amplitude during the experiment and was reduced with about 30% (P less than 0.004) of the initial value in all rats at the end of the experiment. The pronounced change in the arachidonic content in PI and the decreased amplitude of the a-wave of the ERG suggest that arachidonic acid of the PI has an important function in the visual phototransduction process.

Animals↗
PubMed1986

Peripheral hormone levels in healthy subjects during controlled fasting.

The effect of one week of controlled fasting (31 of fluid containing 50 g of carbohydrate/day) upon the serum levels of hormones, sex hormone binding globulin, and albumin was studied in healthy subjects. Fasting caused decreased levels of prolactin and T3, no changes in the levels of TSH, FSH, LH, dehydroepiandrosterone, 4-androstene-3, 17-dione, total oestrone, and total testosterone, and increased levels of cortisol, dehydroepiandrosterone sulphate and albumin. A significant positive correlation was found between albumin and dehydroepiandrosterone sulphate. Fasting rapidly increased the levels of sex hormone binding globulin and decreased the percentage of free testosterone and the calculated free testosterone level in both sexes. A decreased metabolic clearance of certain steroids (cortisol, dehydroepiandrosterone sulphate) owing to an increased protein binding may be one of the endocrine consequences of fasting. An increased protein binding of testosterone may be outweighed by a decreased gonadal production, thus resulting in an unchanged total testosterone level. The increased sex hormone binding globulin level could not be explained by changes in gonadal and thyroid hormones.

Adult↗
PubMed1986

Simple diagnosis of the Zellweger syndrome by gas-liquid chromatography of dimethylacetals.

The absence of peroxisomes in patients with the cerebrohepatorenal syndrome of Zellweger leads to several biochemical abnormalities, including deficient synthesis of plasmalogens as well as accumulation of very long-chain fatty acids and intermediates in bile acid biosynthesis. Accumulation of very long-chain fatty acids in serum and fibroblasts has hitherto been used most extensively for diagnosis. Due to the relatively small amounts of the very long-chain fatty acids also in the Zellweger patients, and the risk for interfering impurities, such analyses are difficult. Direct assay of plasmalogens is also relatively difficult and time-consuming. In this report, we describe a relatively simple method for diagnosis, based on gas-liquid chromatography of a lipid extract of erythrocytes after methyl transesterification. The alpha, beta-unsaturated ether in the plasmalogen is converted to the dimethylacetal of the corresponding aldehyde, and the relative amount of plasmalogen is thus reflected by the ratio between 18:0 dimethylacetal and methyl stearate as well as by the ratio between 16:0 dimethylacetal and methyl palmitate. The ratio 18:0 dimethylacetal/methyl stearate was found to be 0.28 +/- 0.03 (mean +/- SD) after analyses of erythrocytes from healthy or non-Zellweger infants, but less than 0.02 in erythrocytes from three infants with the Zellweger syndrome. Preliminary work with amniotic fluid suggests that this analysis may be suitable also for prenatal diagnosis of the Zellweger syndrome.

Acetals↗
PubMed1985

Influence of dietary partially hydrogenated vegetable and marine oils on membrane composition and function of liver microsomes and platelets in the rat.

The aim of the present study was to investigate the influence of partially hydrogenated vegetable and marine oils on membrane composition and function of liver microsomes and platelets with particular reference to the metabolism of linoleic acid and the production of arachidonic acid metabolites. Four groups of male weanling rats were fed linoleic acid supplemented diets containing 20% (w/w) of partially hydrogenated low erucic acid rapeseed oil (HLRSO), partially hydrogenated herring oil (HHO), olive oil (OO) and trierucin + triolein (TE) for 10 weeks. An additional two groups were fed partially hydrogenated low erucic acid rapeseed oil and partially hydrogenated herring oil without linoleic acid supplementation (HLRSO- and HHO-, respectively). Substantial amounts of trans fatty acids were incorporated into liver microsomes (12.6% in group HLRSO) and platelets (7.0% in group HLRSO-). This incorporation was not dependent on the dietary linoleic acid level. Hepatic microsomal delta5 -desaturase activity was significantly increased after HLRSO feeding compared to 00 feeding. Delta6 -Desaturase activity did not vary in the linoleic acid supplemented groups. Both delta5 -and delta6 -desaturase activities were significantly increased in groups without linoleic acid supplementation. Docosenoic acid was incorporated into platelet phospholipids in contrast to liver microsomes. In the platelet, docosenoic acid seemed to have a special preference for phosphatidylserine. Very small amounts were incorporated into platelet phosphatidylinositol. Feeding diets HLRSO, HHO and 00 did not influence rat platelet cyclooxygenase or 12-lipoxygenase activity. Platelets from rats fed TE, however, produced significantly less 12-hydroxy-5,8,10,14-eicosatetraenoic acid (12-HETE) than platelets from rats fed OO. Feeding of HLRSO- and HHO- resulted in a significantly diminished production of the arachidonic acid metabolites 12-HETE, 12-hydroxy-5,8,10-heptadecatrienoic acid (HHT) and 6-keto-prostaglandin F1alpha in stimulated platelets and aorta. Thus, high dietary levels of trans isomers of monoenoic acids do not interfere with platelet cyclooxygenase or lipoxygenase activity provided sufficient amounts of linoleic acid are available.

Animals↗
PubMed1985

Hydrogen concentration in expired air analyzed with a new hydrogen sensor, plasma glucose rise, and symptoms of lactose intolerance after oral administration of 100 gram lactose.

A rapid breath hydrogen analyzer to detect lactose malabsorption is described. After ingestion of a lactose solution the patient expires into a mouthpiece attached to a hydrogen sensor at 30-min intervals for 3 1/2 h. The hydrogen of the expired air causes a voltage change that can be transformed into ppm from a calibration curve. A tolerance test with a load of 100 g lactose was performed in 43 consecutive patients with various gastrointestinal disturbances, referred to the laboratory for the commonly used lactose tolerance test based on plasma glucose measurements. Eleven patients developed symptoms of lactose intolerance during the test. Biopsy specimens from the distal duodenum or proximal jejunum showed partial villous atrophy in one, in whom celiac disease with lactose intolerance was diagnosed; the other 10 had normal specimens. In nine of them lactose intolerance was diagnosed and confirmed by observation for months on a lactose-poor diet. The 10th patient (H.P.L.) did not improve on such a diet. He also showed pronounced symptoms of intolerance during a test with monosaccharides (glucose + galactose). His intestinal disease remained undiagnosed. The 11 patients with symptoms of intolerance and 3 patients without symptoms during the lactose load showed a flat plasma glucose curve after drinking the lactose solution--that is, a maximum rise of the glucose concentration of 1.5 mmol/l. One of the symptom-free patients dropped out and could not be observed, another did not improve on a lactose-poor diet, and the third noticed a favorable effect of the diet on stool consistency but not on other abdominal symptoms.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1984

Studies on the effect of 4-methylpyrazole on methanol poisoning using the monkey as an animal model: with particular reference to the ocular toxicity.

Young cynomolgus monkeys (Macaca fascicularis) were chosen as a model to investigate the ocular toxicity in animals poisoned with methanol and treated with 4-methylpyrazole (4-MP). The metabolism of methanol in the monkey was investigated after administration of 4-MP. Plasma levels of methanol, formic acid, 4-MP and 4-hydroxy-MP (4-OH-MP) were determined. After intramuscular injection, 4-MP was rapidly absorbed and depressed the elimination rate of methanol as well as the accumulation of formate in the blood. The results show the same great individual variations in monkeys as in humans regarding the susceptibility to methanol poisoning. Administration of a single dose of 5 g/kg induces a serious intoxication in most monkeys, causing death to some of them. Two monkeys receiving a single dose of 6 g/kg of methanol developed a serious initial inebriation and were treated with 4-MP. These monkeys survived and showed no signs of toxicity on ocular examinations which included ophtalmoscopy and electroretinogram (ERG) recordings.

Alcohol Oxidoreductases↗
PubMed1984

Normal electroretinogram and no toxicity signs after chronic and acute administration of the alcohol dehydrogenase inhibitor 4-methylpyrazole to the cynomolgus monkey (Macaca fascicularis)--a possible new treatment of methanol poisoning.

High doses of 4-methylpyrazole (4-MP) could be administered to monkeys in long- and short-term experiments without yielding any general toxicity or any toxic influence on the retinal photoreceptors, the conduction of impulses through the retina or on the activity in the inner nuclear layer detectable by recording the electroretinogram (ERG). Both series included a low dose (20 mg/kg) and a high dose level (100 mg/kg), the former being a tentative therapeutic dose. In the first series the substance was administered for 6 weeks and the toxicity regarding clinical signs, hematology and blood chemistry, and gross and microscopic pathology evaluated. Furthermore ophthalmoscopy with assessment of the fundus structures and recordings of the ERG were performed. The second series was mainly concerned with revealing of any direct effect of 4-MP on the ERG. Because of the low toxicity of 4-MP and its powerful inhibitory capacity on alcohol dehydrogenase, the substance should prove a potential tool in clinical alcohol research and an effective antidote in clinical situations where inhibition of alcohol dehydrogenase (ADH) is the key to a successful outcome of, for example, methanol and ethylene glycol poisoning.

Alcohol Oxidoreductases↗
PubMed1984

Effect of ursodeoxycholic acid treatment on intestinal absorption of triglycerides in man.

The aim of the present study was to evaluate whether treatment with ursodeoxycholic acid (UDCA) may affect the absorption of dietary fat in man. Fifteen healthy subjects volunteered for the study. They were treated with UDCA in a daily dose of 15 mg/kg body weight for 4 weeks. Before and during treatment fat absorption was measured with a 14C-triolein breath test. In addition, fasting serum bile acids were measured in 11 of the subjects. The maximum specific activity of 14CO2 was not significantly changed during the treatment period. However, the cumulative output of 14CO2 during a 6-h period was decreased by about 25% (p less than 0.03). Several subjects with decreased outputs also lost 1-2 kg of body weight during the study period. UDCA treatment raised the serum level of this bile acid from 0.18 +/- 0.11 mumol/l to 5.98 +/- 1.08 mumol/l. The concentrations of the other bile acids were not significantly changed. It is suggested that UDCA treatment may in some patients be associated with an impaired fat absorption. Whether this effect is of any clinical importance remains to be elucidated.

Adult↗
PubMed1983

The effects of partially hydrogenated marine oils on the mitochondrial function and membrane phospholipid fatty acids in rat heart.

The influence of dietary partially hydrogenated marine oils containing docosenoic acid on rat heart mitochondrial membrane phospholipid fatty acid composition was studied with particular reference to cardiolipin and oxidative phosphorylation. Five groups of male weanling rats were fed diets containing 20% (w/w) peanut oil (PO), partially hydrogenated peanut oil (HPO), partially hydrogenated Norwegian capelin oil (HCO), partially hydrogenated herring oil (HHO), and rapeseed oil (RSO) for 10 weeks. All the cardiac phospholipids investigated were influenced by the experimental diets. An increased amount of arachidonic acid observed in phosphatidylethanolamine (PE) after feeding partially hydrogenated oils suggests a changed regulation of the arachidonic acid metabolism in comparison with PO treatment. 22:1 originating from the dietary oils was incorporated only to a small extent into phosphatidylcholine (PC) and PE. A selective incorporation of 18:1 isomers into the 1- and 2-positions of PC and PE with respect to geometry and position of the double bond was observed. Large amounts of 18:1 trans were incorporated into the 1-position of PC and PE, irrespective of the amount of 18:2 supplemented to the diets, replacing a considerable proportion of stearic acid in this position. After feeding HHO and RSO, the content of 22:1 in mitochondrial cardiolipin of rat heart was found to be 3% (mainly cetoleic acid) and 10% (mainly erucic acid), respectively, indicating a high affinity for cis isomers of 22:1, but also a considerable resistance against incorporation of trans isomers was observed. The ability of rat cardiac mitochondria to oxidize palmitoylcarnitine and to synthesize ATP was depressed after feeding HHO and RSO. Dietary cis isomers of 22:1 seem to have a specific ability to interfere with cardiac ATP synthesis and also to alter the fatty acid composition of cardiolipin of rat heart.

Adenosine Triphosphate↗
PubMed1983

14C-triolein breath test as a rapid and convenient screening test for fat malabsorption.

The 14C-triolein breath test was evaluated as a screening test for fat malabsorption in 50 consecutive patients. After the ingestion of a 30-g fat meal containing 5 microCi 14C-triolein, the breath excretion of 14CO2 was measured at hourly intervals for 6 h and compared with a 3-day faecal excretion of fat. Nineteen patients had steatorrhoea and 31 patients normal fat excretion. The maximum specific activity of CO2 in the breath provided the best means of distinguishing between the two groups, with no false-negative values and nine false-positive values (29%). Our findings confirm that the 14C-triolein breath test is sensitive and has sufficient specificity for screening fat malabsorption, especially among outpatients. If a normal 14C-triolein breath test is obtained, it seems unnecessary to perform measurements of excretion of faecal fat.

Adult↗
PubMed1982

Comparison of two isotope dilution/mass spectrometric methods for determination of total serum cholesterol.

Isotope dilution/mass spectrometric methods for total serum cholesterol, developed separately at the Karolinska Institutet (KI) and the National Bureau of Standards (NBS), were compared by applying them to a common set of serum pools. A search for the cause of a systematic difference of a few percent in results from the two methods revealed that the KI cholesterol standard contained lathosterol, which interfered with the calibration of the method. With NBS Standard Reference Material cholesterol used for new analyses at the KI, the average difference in mean values dropped to 0.2%. The NBS results are more precise. This is attributed to the protocols NBS used for sample preparation and mass spectrometry. However, these protocols make the NBS method more complex and time-consuming. A recent critical article on the use of this technique for total cholesterol is also examined.

Cholesterol↗
PubMed1981

Accuracy of some routine method used in clinical chemistry as judged by isotope dilution-mass spectrometry.

Serum from patients was pooled, filtered, dispensed, and frozen. This pooled specimen was used for accuracy control in 64 participating laboratories in Sweden. Mean values ("state-of-the-art" values) were obtained for creatinine, cholesterol, glucose, urea, uric acid, and cortisol. These values were compared with values obtained with highly accurate reference methods based on isotope dilution-mass spectrometry. Differences were marked in the case of determination of creatinine and cortisol. Concerning the other components, the differences between the state-of-the-art value and the values obtained with the reference methods were negligible. Moreover, the glucose oxidase and the oxime methods for determination of glucose and urea were found to give significantly lower values than the hexokinase and urease methods, respectively. We conclude that methods with a higher degree of accuracy are required for routine determination of creatinine and cortisol.

Blood Chemical Analysis↗