Biomedical subjects

K Zahlsen

Publications and source records attributed to K Zahlsen.

36 records · Page 2Linked to original sources

PubMed1994

[Illness caused by water-based paints?].

Illness caused by the indoor environment is a challenging and complicated field to investigate. Emissions from paints may contribute to the problems. Several components of water-based paints evaporate for a long time after painting, and some of them may affect human biology. We describe one patient who has experienced symptoms caused by water-based paint. Different reaction mechanisms may be involved, and these are discussed. Components which may elicit biological effects are listed and discussed. Physicians should be aware of the possibility that a few patients may suffer from illness caused by emissions from modern paints.

Adult↗

PubMed1993

Effect of nicotine on the enterochromaffin like cells of the oxyntic mucosa of the rat.

Smoking has an unfavourable effect on peptic ulcer disease. The pathophysiological mechanisms underlying this effect are not known. The enterochromaffin like (ECL) cell is the cellular source of histamine participating in the regulation of acid secretion. The ECL cell is under functional and trophic control of gastrin and the vagus nerves. Nicotine may affect acid secretion through vagal pathways. Furthermore, nicotine may also stimulate neuroendocrine cells. The present study examined if chronic nicotine administration could stimulate the function and growth of the ECL cell. Rats inhaled nicotine vapour at a concentration of approximately 6.2 mumol/m3, 20 hours/day, 5 days/week for 11 weeks. Steady state plasma nicotine concentration was 461.8 (137.5 (SD)) nmol/l. The ECL cell density, histamine content and histidine decarboxylase activity of the oxynitic mucosa were similar to the controls. We also examined the effect of acute nicotine stimulation on the acid output and histamine release from the totally isolated vascularly perfused rat stomach. Nicotine did not stimulate acid secretion or histamine release. Thus no evidence could be provided to support the hypothesis that nicotine exerts its negative effects on peptic ulcer disease by stimulating the ECL cell.

Administration, Inhalation↗

PubMed1993

Inhalation kinetics of C8 to C10 1-alkenes and iso-alkanes in the rat after repeated exposures.

The toxicokinetic properties of C8 and C10 1-alkenes and iso-alkanes have been investigated in rats during inhalation of 100 p.p.m. of the single hydrocarbons for 3 days, 12 hr/day. The concentration of hydrocarbon was measured in blood, brain, liver, kidneys and perirenal fat at days 1, 2 and 3, immediately after exposure and 12 hr after exposure on day 3. The 1-alkenes showed an efficient absorption to blood combined with extensive accumulation in organs, compared to the iso-alkanes. The concentration of 1-alkenes and iso-alkanes in blood, brain, liver and fat increased with increasing number of carbon atoms. The C9 and C10 1-alkenes and iso-alkanes showed increasing concentration in fat during the exposure period and high concentrations 12 hr after cessation of exposure. The extensive accumulation in both blood and organs of 1-alkenes compared to any of the other groups of hydrocarbons may have a toxicologic relevance. Products which contain 1-alkenes should be handled carefully to minimize the risk of inhalation exposure.

Absorption↗

PubMed1992

Inhalation kinetics of C6 to C10 aliphatic, aromatic and naphthenic hydrocarbons in rat after repeated exposures.

The toxicokinetic properties of C6 to C10 n-alkanes, aromates and naphthenes have been investigated in rats during inhalation of 100 p.p.m. of the single hydrocarbons for 3 days, 12 hr/day. The concentration of hydrocarbon was measured by head space gas chromatography in blood, brain, liver, kidneys and perirenal fat at days 1, 2 and 3, immediately after termination of exposure and 12 hr after exposure on day 3. The main conclusions drawn from the study were: a) Aromatic hydrocarbons show high concentrations in blood and low concentrations in organs. b) Naphthenic hydrocarbons show low concentrations in blood and high concentrations in organs. c) n-Alkanes show very low concentrations in blood, relatively high concentrations in brain and a high potential for accumulation in fat with repeated exposures. d) Biological concentrations of hydrocarbons within one class increase in general with increasing molecular weight, though with specific exceptions. e) Accumulation is obviously influenced by differences in metabolism and enzyme induction potential. f) Lipid solubility is not the only parameter relevant for the evaluation of hydrocarbon accumulation.

Adipose Tissue↗

PubMed1991

Liver, lung and kidney homogenates used as an activation system in mutagenicity studies of airborne particles and of expectorate and urine samples from exposed workers in a coke plant.

A comparison was made between lung and kidney homogenates on the one hand and liver S9 from rats on the other hand in order to compare their ability to activate promutagens. The Salmonella reversion assay was used on extracts of airborne particles from the top of coke oven batteries, and of expectorate and urine samples from exposed workers in the same coke plant. The contents of benzo[a]anthracene and benzo[a]pyrene in the different test solutions were measured by high-resolution gas chromatography/mass spectrometry. Both mutagens were detected in the filter extract and in the expectorates from the exposed workers but not in the expectorates from the control groups or in the urine samples. The liver S9 gave significantly higher mutagenicity than lung and kidney activation with both filter samples and expectorate and urine samples.

Adult↗

PubMed1990

Effects of ingested crude oil on thyroid hormones and on the mixed function oxidase system in ducks.

1. Ingestion of Statfjord A crude oil from the North Sea has no apparent effect on the metabolic rate of ducks (Jenssen, 1989). This may be because this particular oil does not affect plasma concentrations of thyroid hormones and enzyme activities in the mixed function oxidase (MFO) system of ducks. 2. To test this hypothesis, plasma concentrations of thyroid hormones (thyroxine and triiodothyronine), and levels of hepatic cytochrome P-450 and enzyme activities (NADPH cytochrome C reductase and GSH-S-transferase) in the MFO system were measured in domestic ducks (Anas platyrhynchos) which had ingested this crude oil. 3. Daily oral of 5 ml crude oil per kg body weight for 6 consecutive days resulted in a 53% increase in plasma triiodothyronine concentration and a 56% increase in the hepatic cytochrome P-450 level. The changes in these parameters were apparently not sufficient to cause any rise in metabolic heat production. 4. This apparent contradiction is probably because activation of the MFO-system is energetically inexpensive. Also, possible metabolic effects caused by increased plasma-triiodothyronine concentration and activation of the MFO-system may have been masked by an inhibitory effect of the crude oil on mitochondrial electrontransport and coupled phosphorylation.

Administration, Oral↗

PubMed1990

Accumulation and distribution of aliphatic (n-nonane), aromatic (1,2,4-trimethylbenzene) and naphthenic (1,2,4-trimethylcyclohexane) hydrocarbons in the rat after repeated inhalation.

The concentrations of the C9 hydrocarbons n-nonane, 1,2,4-trimethylbenzene and 1,2,4-trimethylcyclohexane were measured in rat blood, brain and perirenal fat after exposures to 1000 p.p.m. of the individual compounds. Measurements were made by head space gas chromatography at the end of 12 hr exposures on days 1, 3, 7, 10 and 14 of the exposure periods. The relative concentrations of hydrocarbons in each organ were, brain: n-nonane "trimethylcyclohexane approximately trimethylbenzene, blood: trimethylbenzene "n-C9 greater than trimethylcyclohexane and perirenal fat: trimethylbenzene greater than n-nonane greater than trimethylcyclohexane, showing the widely different distribution properties of the different hydrocarbons. Brain/blood ratios of 11.4, 2.0 and 11.4, and fat/blood ratios of 113, 63 and 135 were found for n-nonane, trimethylbenzene and trimethylcyclohexane, respectively. A marked decrease in biological concentrations of trimethylbenzene and trimethylcyclohexane during the initial phase of exposure indicate that these hydrocarbons are capable of inducing their own metabolic conversion resulting in lower steady state levels. A special attention was made to n-nonane showing the highest concentration in brain concomitantly with a low blood concentration. This observation demonstrate that biological monitoring of occupational exposure by blood measurements not should be performed without knowledge of the distribution properties of the compounds investigated.

Absorption↗

PubMed1988

Toxicity of n-C9 to n-C13 alkanes in the rat on short term inhalation.

Male Sprague Dawley rats were exposed to inhalation of n-C9 to n-C13 alkanes close to air saturation at 20 degrees (4438, 1369, 442, 142 and 41 p.p.m., respectively) for 8 hours and observed for the following 14 days. In addition, exposure to higher and lower concentrations of n-C9 was performed. The concentration of alkane in the brain after exposure exceeded that of blood for the lower alkanes, while the higher alkanes possessed a brain/blood ratio equal to or less than unity. Gross ataxia, general and focal seizure and spasms were observed in animals exposed to n-C9 in the range from 5280 to 3560 p.p.m. No toxic effects were observed in animals exposed to 2414 p.p.m. of n-C9 or to the other alkanes. An LC50 value for n-C9 of 4467 +/- 189 p.p.m. was estimated. Despite the clinical improvement in animals surviving the n-C9 exposure of 4438 p.p.m. (6/10), severe cerebellar damages were found at autopsy at the end of the observation period, with a loss of Purkinje cells as the most prominent feature. Immediate post mortem examination (4/10) showed marked vascular congestion of the liver as well as slight fatty degeneration but no cerebellar damage. No abnormalities were observed in animals exposed to the other alkanes. The significant distribution in the brain of the n-C9 alkane, the clinical signs of cerebellar dysfunction and the damage of cerebellar neurons would suggest CNS to be a possible target organ for the toxic effects of the n-C9 alkane.

Administration, Inhalation↗

PubMed1985

Oral intake of a toluene-containing thinner. Effects and headspace gas chromatographic analytical diagnosis.

After an accidental oral intake of a paint thinner, the constituents were identified in stomach content using headspace gas chromatography. The composition indicated ingestion of a commonly used thinner containing 60-70% toluene, 20-25% n-butylacetate and 10-15% of ethanol. A toluene concentration of 22.0 mg/kg was measured in serum in contrast to n-butylacetate which was not detected. Ethanol concentration was 1.85 g/kg, most of this was due to ethanol ingestion before the intake of thinner. The half life of toluene in serum was 8.5 h initially, which increased to 14 h after 19 h. An effect on liver function was demonstrated by increased activity of serum transaminases. Compared with the upper normal limits ASAT and ALAT were increased by 6 and 2.5 times, respectively. For both parameters the highest activity was seen 40 hours after admission and normal levels were achieved after 7 days. It is concluded that toluene is readily absorbed by ingestion of toluene-containing thinners, and that the function of the human liver is transiently affected. For screening purposes gas chromatography proved to be a useful method for the analytical diagnosis in cases of organic solvent intoxication. The use of the headspace technique further improved the speed of analysis and eliminated contamination of the gas chromatographic system.

Acetates↗

PubMed1985

Inhalation of butanols: changes in the cytochrome P-450 enzyme system.

After inhalation of different butanol isomers for 3 days (2000 ppm) and 5 days (500 ppm), liver and kidney parameters of the microsomal cytochrome P-450 enzyme system were increased. sec-Butanol caused the highest increase in cytochrome P-450 concentration with a 47% rise in the kidneys (500 ppm for 5 days) and 33% in the liver (2000 ppm for 3 days). A concomitant increase of the in vitro n-hexane metabolism in liver microsomes was observed with a 77% increased formation of the preneurotoxic metabolite 2-hexanol compared with control. iso-Butanol did not alter total cytochrome P-450 concentration but caused a significant 30% decrease in the formation of 2-hexanol. Inhalation of all butanols slightly decreased the enzyme levels in the lung. Changes in microsomal enzymes did not correlate with measured serum concentrations of the different butanols showing different inducing capacities among the butanol isomers themselves or the participation of metabolites in the inducing process. As a conclusion sec-butanol, probably through its metabolite methyl-ethyl-ketone, is the most potent inducer of microsomal cytochrome P-450 in liver and kidney while iso-butanol does not alter total cytochrome P-450.

Animals↗

PubMed1985

Circulating steroids in male rats following inhalation of n-alcohols.

The effect of inhaled methanol, ethanol, n-propanol and n-butanol on male reproductive function as measured by the serum concentration of circulating T (testosterone) and LH (luteinizing hormone) has been investigated. The animals were exposed to concentrations of these alcohols equal to the current threshold limit values in industry (methanol: 200 ppm, ethanol: 1000 ppm, n-propanol, n-butanol: 50 ppm) 6 h a day for up to 1 week. A significant depression in the concentration of circulating T was found after the first 6 h exposure to the respective alcohols with restoration after a recovery period of 18 h, except in rats exposed to n-butanol where a depression of 48% could still measured. The concentration of LH was within the normal range in all experimental groups whereas corticosterone was increased after exposure to n-butanol. Exposure for 1 week was not associated with any significant inability of the rat testis to produce T.

1-Butanol↗

PubMed1985

Inhalation of isopropanol: induction of activating and deactivating enzymes in rat kidney and liver. Increased microsomal metabolism of n-hexane.

Rats were exposed to isopropanol by inhalation of 200,2000 and 8000 ppm for 2 weeks with a daily exposure of 6 h. A pilot group exposed to 8000 ppm was given a recovery period of 4 weeks. Kidney and liver microsomal metabolism of n-hexane was investigated in vitro concomitant with activities of cytochrome P-450 and GSH enzymes and blood concentration of isopropanol and its metabolite acetone. A dose dependent increase was observed in the formation of all metabolites of n-hexane in both organs. Of special interest was the 9%, 80% and 198% increase of the preneurotoxic metabolite 2-hexanol in kidney microsomes. Cytochrome P-450 was increased 14%, 40% and 43% in kidney after 200, 2000 and 8000 ppm, respectively, and 10% and 19% in liver at 2000 and 8000 ppm. The activity of glutathione S-transferase was unaffected in kidney but elevated in liver, while GSH levels were elevated in both organs. The elevated level of kidney cytochrome P-450 did not return to normal during the 4-week-recovery period in contrast to liver cytochrome P-450. It is thus indicated that cytochrome P-450 and associated microsomal enzymes are more easily inducible and the changes more persistent in kidney than in liver. Our observations suggest that cytochrome P-450-mediated metabolic activation of n-hexane in the kidneys may have toxicological relevance in addition to liver metabolism, and that coexposure to isopropanol and n-hexane may represent an enhancement of the health hazard from n-hexane, possibly due to the isopropanol metabolite acetone.

1-Propanol↗

PubMed1984

Increased microsomal metabolism of n-hexane in rat kidney and liver after inhalation of isopropanol.

Inhalation of 200, 2,000, and 8,000 ppm isopropanol for 2 weeks enhanced the in vitro metabolism of n-hexane in microsomal preparations. The formation of the preneurotoxic metabolite 2-hexanol increased 9, 80, and 198%, respectively, in the kidney and 9, 22, and 132% in the liver. The concentration of cytochrome P-450 was also increased in a dose-dependent way with increases of 14, 40, and 43%, respectively, in the kidney and 6, 12, and 18% in the liver. The present investigation demonstrates similar effects of isopropanol after inhalation on kidney and liver microsomal enzymes. In both organs isopropanol was shown to potentiate the formation of neurotoxic metabolites from n-hexane. However, cytochrome P-450 appears to be more easily induced in kidney than in liver.

1-Propanol↗

PubMedDate not supplied

Macrolide pharmacokinetics and dose scheduling of roxithromycin.

The 150- and 300-mg single-dose pharmacokinetics of roxithromycin were investigated in 12 healthy subjects in a crossover study. Serum concentrations were determined by high-performance liquid chromatography (HPLC) and microbiologic assay (MA). Peak serum levels as measured by HPLC were 6.7 +/- 2.6 (150 mg) and 11.0 +/- 2.2 micrograms/ml (300 mg) and did not differ significantly from the values obtained by MA. Mean serum roxithromycin levels 12 hr after the 150-mg dose and 24 hr after the 300-mg dose were 2.50 and 2.55 micrograms/ml, respectively. HPLC analysis of a comparable macrolide, clarithromycin, showed peak serum levels of 1.2 +/- 0.6 and 2.3 +/- 0.6 micrograms/ml after oral dosing with 250 and 500 mg in the same subjects. The 14-OH metabolite reached a level that was 50% and 40%, respectively, of that of the parent compound. Roxithromycin showed a prolonged elimination half-life compared with clarithromycin and its 14-OH metabolite. Mean values of 14.6, 3.5, and 5.5 hr, respectively, indicate the need for less frequent dosing of roxithromycin.

Administration, Oral↗

PubMedDate not supplied

A rapid gas chromatographic method for determination of ethylene glycol in serum and urine.

Intoxications with the antifreeze constituent ethylene glycol (EG) occur infrequently, but may be fatal if not recognized and treated promptly. The aim of the present work was to develop an analytical method for rapid diagnosis of EG poisoning and for monitoring EG removal by hemodialysis. EG was measured by gas chromatography upon direct injection of serum or urine samples (50 microL diluted in 200 microL of distilled water containing 2,3-butanediol as internal standard). A 2-m x 2-mm glass column with Chromosorb 101 (80/100 mesh) separates these glycols within four minutes at 200 degrees C, using nitrogen as the carrier gas. The glycols 1,2- and 1,3-propanediol were separated from EG and the internal standard. Acetone, methanol, and isopropanol did not interfere with the analysis. The limit of quantitation of EG was close to 0.5 mM. Because no derivatization, extraction, or concentration procedures were necessary, EG may be determined quantitatively within 30 min, allowing for monitoring of hemodialysis, which should be performed for 15 h in severe cases. The diagnosis of ethylene glycol intoxication in a late stage may be secured by analysis of urine collected on admission.

Adult↗

PubMedDate not supplied

Uptake of nicotine in hair during controlled environmental air exposure to nicotine vapour: evidence for a major contribution of environmental nicotine to the overall nicotine found in hair from smokers and non-smokers.

Hair from smokers and non-smokers has been exposed in a dynamic exposure chamber to air nicotine concentrations ranging from 1.5 to 45 and from 20 to 2000 micrograms/m3 for 8 weeks and 72 hr, respectively. Accumulated hair nicotine was quantified by GC/MS. Hair was also collected for direct measurements of nicotine in 0-2, 2-4 and 4-6 cm segments from the scalp. Human hair showed a high affinity for air nicotine and the chamber experiments revealed a linear relationship between the initial hair uptake rates of nicotine and the duration of exposure at all air nicotine concentrations applied. Hair nicotine uptake rate decreased with time after 4 to 6 weeks exposure to 15 and 45 micrograms/m3 air concentrations of nicotine, but not to the 1.5 micrograms/m2 nicotine concentration. Ratio between the hair uptake rate of nicotine and the applied air concentration of nicotine decreased with increasing air concentrations of nicotine. Segment analysis of hair revealed an outward increasing gradient of nicotine in hair. Hair uptake pattern of air nicotine suggests the uptake to be governed by an equilibrium between nicotine in air and nicotine on the hair surface, possibly combined with a slower diffusion process of nicotine from the hair surface into the hair core. The hair segment analysis of nicotine indicates that environmental nicotine is the dominating contributor to the overall nicotine found in hair both from smokers and non-smokers.

Adult↗

PubMedDate not supplied

Nicotine in hair of smokers and non-smokers: sampling procedure and gas chromatographic/mass spectrometric analysis.

A gas chromatographic/mass spectrometric method for analysis of nicotine in scalp hair and measurements of nicotine in hair from 20 smokers and non-smokers with a one year interval are presented. The gas chromatographic/mass spectrometric method, based on selected ion monitoring of the ion m/z 162, with ions m/z 133 and 84 as qualifier ions, allows a highly selective and sensitive detection of nicotine in hair samples avoiding interference from other chemicals present in hair. Nicotine is extracted after alkaline dissolution i 5M NaOH. The sampling procedure takes into account that significant amounts of nicotine in hair is probably adsorbed and deposited from atmospheric air. In consequence, the hair samples must be taken from a site with sufficient contact with surrounding air and the measured concentration of nicotine must be related to the length of the hair segment and its distance from the scalp. Our study demonstrated very clear and statistically significant differences in the concentrations of nicotine in hair from smokers and non-smokers, a high reproducibility of hair nicotine measurements over time, and that the presented method is sensitive enough to detect individual changes not only in smoking habits, but also in environmental nicotine exposure.

Adult↗

PubMedDate not supplied

Hair nicotine concentrations in mothers and children in relation to parental smoking.

The health effects of environmental tobacco smoke (ETS) exposure constitute a main public health problem. Lack of presice methods for assessing personal tobacco smoke exposure, makes it difficult to estimate the health effects of such exposure. Measuring hair nicotine concentrations could be an improvement in the assessment of personal tobacco smoke exposure. The objective of the present study was to estimate quantitatively the relation between hair nicotine concentrations in mothers and children and tobacco smoke exposure assessed by questionnaires. Mothers' and children's hair nicotine concentrations in the proximal 2 cm of hair were measured in 94 families with children 12-36 months of age: 25 nonsmoking families, 40 families with one smoking parent, and 29 families with both parents smoking. Questionnaire information on tobacco smoke exposure was collected from the same families. In multivariate linear regression analysis, children's nicotine levels were linearly related to daily number of cigarettes smoked at home by both mothers (0.8 mg/g increase per cigarette, 95% confidence interval [CI] 0.43-1.18), and fathers (1.3, 0.81-1.73). Mothers' nicotine levels were linearly related to both personal smoking (2.7, 1.75-3.55) and fathers' smoking at home (2.1,0.74-3.49). Hair nicotine seems to be a good quantitative measure of exposure to tobacco smoke during the previous months both among active and passive smokers. The non-invasive and simple collection procedure makes the method especially suitable for estimating tobacco smoke exposure in children.

Child, Preschool↗