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Biomedical subjects

K Svensson

Publications and source records attributed to K Svensson.

At least 145 records · Page 8Linked to original sources

Effects of long-term exposure to solvents in the paint industry. A cross-sectional epidemiologic study with clinical and laboratory methods.

The effects of organic solvents on 50 male workers exposed 5-46 (mean 18) years were studied with a cross-sectional design. Referents were matched pairwise according to age and education. An analysis of confounders confirmed good comparability between the two groups. As indicators of organic brain dysfunction regional cerebral blood flow was measured and the power spectrum of the subjects' electroencephalograms was analyzed, the former being reduced 4% and the latter showing increased power in the delta and beta bands in the exposed group. Symptoms of brain dysfunction were significantly more frequent among the exposed subjects and showed an exposure-effect relationship. Neuropsychological tests revealed definite indication of brain dysfunction in 14% of the exposed subjects in comparison to none in the reference group. The exposed subjects performed significantly worse than the referents in tests measuring focused attention abilities. A neurophysiological examination of the peripheral nervous system showed no difference between the groups. Clinical chemistry demonstrated no differences that could be explained by solvent exposure.

Adult↗

Anticonflict effect of the putative serotonin receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT).

The putative 5-HT agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OHDPAT) produced in rats an increase in the number of shocks accepted in a modified Vogel's conflict test design. Subchronic pretreatment with p-chlorophenylalanine (PCPA) similarly caused release of the punished behavior. This anticonflict effect of PCPA was antagonized by both 5-hydrotryptophan and 8-OH-DPAT. Thus in naive animals 8-OH-DPAT exerting anticonflict effects acted like a 5-HT antagonist, whereas in subchronically PCPA-pretreated animals with presumably supersensitive 5-HT receptors, 8-OH-DPAT decreasing the number of accepted shocks acted like a 5-HT agonist.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

Relationships between ethylation of hemoglobin, ethylation of DNA and administered amount of ethyl methanesulfonate in the mouse.

Ethylation of guanine-N-7 in the DNA of liver and kidney and of nucleophilic groups in hemoglobin has been studied as a measure of the in vivo dose in the mouse after i.p. administration of radiolabeled ethyl methanesulfonate (EMS). The degree of ethylation in both hemoglobin and DNA of the studied tissues was found to increase proportionally to the injected amount in the range 0.32-100 mumoles EMS/kg b.w. Above this range a somewhat higher than proportional degree of ethylation was found, indicating saturation of a system for detoxification of the compound, resulting in a decreased rate of elimination and consequently an increased dose in the tissues of this directly alkylating agent. The ratio between covalent binding to DNA and to hemoglobin, however, was approximately constant over the wide range of doses studied. For biological effects with a linear dose-response relationship, this demonstrates the validity of hemoglobin alkylation as an indicator of the risk.

Alkylation↗

Kinetics of metabolism of propene and covalent binding to macromolecules in the mouse.

The rate of uptake of propene from air was studied by exposing CBA mice to various concentrations of the gas in a closed, recirculating all-glass chamber. The rate curves showed a saturable dependence on the propene concentration. The inhalational Km and Vmax were calculated to be 800 +/- 60 ppm and 8 +/- 0.5 mg (kg body wt)-1 hr-1, respectively, from a Lineweaver-Burk plot of the rate data. The homologous compound ethene is known to be metabolized in the mouse to ethene oxide. When a trace amount of 14C-labeled ethene was administered in combination with a high concentration of propene, the uptake of [14C]ethene was lower than in the absence of propene, suggesting a competitive interaction in their metabolic pathways. One group of animals were exposed at 20,000 ppm of propene 4 hr/day during 8 consecutive days. Hemoglobin was isolated from the treated group and a control group. After hydrolysis of the protein, two diastereomers of N tau-(2-hydroxypropyl)histidine were identified in the hydrolysate from treated animals, suggesting that propene, analogous to ethene, is metabolized to the corresponding epoxide and showing that the oxidation is not stereospecific. 2-Hydroxypropylated products were found in hemoglobin from mice treated with 14C-labeled propene. The amounts of alkylated products in DNA were below the detection limit.

Alkenes↗

8-Hydroxy-2-(alkylamino)tetralins and related compounds as central 5-hydroxytryptamine receptor agonists.

A series of 2-(alkylamino)tetralins related to 8-hydroxy-2-(di-n-propylamino)tetralin (21) were prepared and tested as dopamine (DA) and 5-hydroxytryptamine (5-HT) receptor agonists. Several of the compounds were potent 5-HT agonists devoid of DA-mimetic effects. N-Ethyl or N-propyl substitution of 8-hydroxy-2-aminotetralin gave the most potent agonists. It was shown that the most potent compound, (+)-21, has the 2R configuration. 5,8-Di-methoxy-2-(di-n-propylamino)tetralin (31) was found to be a weak DA agonist devoid of 5-HT activity. The corresponding indan derivative, 4,7-dimethoxy-2-(di-n-propylamino)indan (39), has been reported to be active on both DA and 5-HT receptors. The 5-HT-stimulating properties of compounds 21 and 39 as compared to the incapability of compound 31 to activate the 5-HT receptor is tentatively explained by the assumed mode of binding of the compounds to the 5-HT receptor.

Animals↗

Resolved 3-(3-hydroxyphenyl)-N-n-propylpiperidine and its analogues: central dopamine receptor activity.

Seven enantiomeric pairs of N-alkyl analogues of 3-(3-hydroxyphenyl)-N-n-propylpiperidine (3-PPP, 12) have been synthesized and evaluated pharmacologically (biochemistry and behavior) in order to examine their ability to interact with central dopamine (DA) receptors, particularly DA autoreceptors. In the R series it seems as if all compounds behave as classical DA receptor agonists with affinity and intrinsic activity for both pre- and postsynaptic receptors. The same bifunctional profile seems to be valid for the S enantiomers with N-substituents larger or bulkier than n-propyl. Likewise, the S enantiomers with ethyl or n-propyl N-substituents seem to have affinity for both pre- and postsynaptic receptors. In the total series, (S)-(-)-3-PPP [(S)-12] seems to be the most interesting compound both from the theoretical and the therapeutical point of view, possibly attenuating DA function in two different ways by stimulating the presynaptic receptors and blocking the postsynaptic receptors. This compound has been selected for extended pharmacological studies as a potential antipsychotic drug.

Animals↗

Elevated granulocyte strontium in inflammatory arthritides is related to the inflammatory activity.

Total cellular strontium and calcium were measured by the nuclear microprobe technique. Increased mass fraction of both elements was found in granulocytes isolated from patients with active rheumatoid arthritis and other kinds of inflammatory arthritides. Increased granulocyte calcium but only marginally elevated granulocyte strontium was demonstrated in patients with scleroderma. The granulocyte accumulation of strontium and calcium seems to be linked to the degree of inflammatory activity, because the granulocyte content of both elements was positively correlated to the plasma concentration of acute-phase proteins. Corticosteroid therapy induced a marked reduction of granulocyte strontium but a more modest decrease of granulocyte calcium. The serum levels of strontium and calcium were within the normal ranges in all patients and were not significantly altered by corticosteroids.

Adolescent↗

Dosimetry of ethylene oxide in the rat by quantitation of alkylated histidine in hemoglobin.

Blood samples were obtained from male Fischer 344 rats exposed to controlled air concentrations of ethylene oxide; 0, 10, 33, and 100 ppm, 6 h/day, 5 days/week, for 2 years. N tau-(2-hydroxyethyl)histidine was isolated from hemoglobin hydrolysates and analyzed quantitatively by means of gas chromatography--mass fragmentography and by amino acid analysis. The degrees of alkylation found were 1.3 and 2.8 nmol hydroxyethylhistidine per gram hemoglobin in two groups of unexposed rats, and 14, 34, and 82 nmol per gram hemoglobin, respectively, at the three air levels of ethylene oxide. Rats of the same breed were given two concentrations of radiolabeled ethylene oxide by IP injection. The degrees of alkylation of amino acids in hemoglobin and of guanine-N-7 in DNA from livers and testes were determined. The degrees of alkylation of liver and testicular DNA were about 150% and 50%, respectively, of the values expected from the degree of alkylation of hemoglobin, basing the expectancy on a direct proportionality between the reactivity of the specific nucleophilic sites and the degree of alkylation obtained at these sites, assuming that the dose of ethylene oxide was the same in the different tissues studied. The in vivo dose of ethylene oxide determined from data on hemoglobin alkylation thus gives a reasonable approximation of the DNA dose. The data were in agreement with a fast elimination of ethylene oxide from the tissues, the biological half-life being estimated as about 10 min.

Alkylation↗

Central dopamine receptor agonist and antagonist actions of the enantiomers of 3-PPP.

The two enantiomers of the putative centrally acting dopamine (DA) autoreceptor agonist 3-(3-hydroxyphenyl)-N-n-propylpiperidine, 3-PPP (Hjorth et al. 1981), were pharmacologically evaluated. An extensive series of biochemical and behavioural experiments unexpectedly revealed that both (+)- and (-)-3-PPP showed clear, but differential, effects on the DA receptors. Thus, (+)-3-PPP is a DA agonist with autoreceptor as well as postsynaptic receptor stimulatory properties. In contrast, although (-)-3-PPP similarly activates DA autoreceptors it acts concomitantly as an antagonist at postsynaptic DA receptors. Moreover, both behavioural and biochemical data on motor activity and DA synthesis and turnover suggest a preferential limbic action for the (-)-enantiomer. These results are discussed in terms of the dual antidopaminergic action of (-)-3-PPP coupled with anatomical differences in the feedback organisation in central (viz, limbic vs striatal) DA systems. It is suggested that compounds like (-)-3-PPP may be of potential clinical utility in the treatment of psychotic disorders, whilst lacking the seriously incapacitating motor dysfunctions produced by current neuroleptic therapy.

Animals↗

Prediction of growth pattern after ankle fractures in children.

The importance of different factors in predicting post-traumatic growth was evaluated using multivariate statistical techniques. Forty-nine children with physeal fractures of the distal tibia or fibula or both were studied. The post-traumatic growth pattern was determined by roentgen stereophotogrammetry. The cases showed various types of growth patterns. The predictors used included sex, skeletal maturity, traumatological and anatomical classification, displacement, treatment, and associated tibial shaft fracture. Prediction of a specific growth pattern could be made only with low accuracy, whereas separation of the growth patterns into two groups--one group with symmetrical growth, initial and temporary growth retardation, and growth stimulation and the other with progressive growth retardation and growth arrest--resulted in a higher predictive accuracy. Comparing the predicted outcome with the actual resulted in two of three fractures being correctly classified. Considered individually, treatment, displacement and skeletal maturity were important, whereas the Salter-Harris classification system could not significantly predict the growth pattern. In summary, displaced physeal injuries treated by reduction showed the highest risk of developing deformity. These injuries were mainly combined fractures of the distal tibia and fibula with the physeal injury localized to one or both of the bones. The limited accuracy in predicting the post-traumatic growth pattern after ankle fractures in children indicates that in many cases there are grounds for radiographic follow-up to detect growth disturbance.

Adolescent↗

The search for selective dopaminergic autoreceptor agonists.

In the course of a search for new selective dopamine (DA) autoreceptor agonists the DA analogue 3-(3-hydroxyphenyl)-N-n-propylpiperidine, 3-PPP, was resolved into its dextro-(+) and levo-(-) rotatory enantiomers. The compounds were pharmacologically evaluated by means of behavioural and biochemical methods. Surprisingly, both (+)-and (-)-3-PPP show clearcut, but differential, effects on the DA receptors. Thus, (+)-3-PPP is a DA receptor agonist with activity on autoreceptors as well as postsynaptic receptors, whereas (-)-3-PPP similarly activates DA autoreceptors but, in contrast, concomitantly acts as an antagonist on postsynaptic DA receptors. Moreover, the behavioural/biochemical profile seems to indicate a preferential limbic action for the (-)-enantiomer. Such an action could be explained on the basis of different feedback arrangements in the nigrostriatal and mesolimbic DA systems and it is suggested that compounds such as (-)-3-PPP may find future clinical application as "second-generation" antipsychotic agents, lacking in the debilitating motor side effects produced by drugs in current therapeutic use.

Animals↗

Selective blockade of brain alpha 2-autoreceptors by yohimbine: effects on motor activity and on turnover of noradrenaline and dopamine.

The motor activity of groups of three mice was increased by yohimbine at doses up to 3 mg/kg intraperitoneally. The turnover of dopamine and noradrenaline in the mouse brain, as assessed by the disappearance of catecholamines following treatment with the tyrosine hydroxylase inhibitor alpha-methyltyrosine, was accelerated by yohimbine with a peak effect after 10 mg/kg intraperitoneally. Prazosin (3 mg/kg i.p.) completely antagonized the stimulatory effect of yohimbine on motor activity and on dopamine turnover but it somewhat potentiated the stimulatory effect on the turnover of noradrenaline. Amphetamine reversed the prazosin-induced hypomotility, indicating that prazosin can selectively block postsynaptic alpha 1-receptors. Yohimbine did not stimulate motor activity following 10 mg/kg and it retarded the turnover of dopamine following 30 mg/kg. These actions might be due to blockade of postsynaptic alpha-receptors by yohimbine. The data indicate that yohimbine at low doses stimulates motor activity and dopamine turnover by selectively blocking alpha 2-autoreceptors leading to increased release of noradrenaline and subsequent activation of post-synaptic alpha 1-receptors.

Animals↗

Incidence of fractures on the distal radius and proximal femur: comparison of patients in a mental hospital and the general population.

A statistically significant increase in the incidence of fractures of the distal radius was found in the general population of southern Sweden during recent decades. As regards fractures of the proximal femur, an increase in the incidence of trochanteric fractures was observed only in women. In male patients at a mental hospital the fracture rate of the distal radius was the same as in the general population but the fracture rate of the proximal femur was about twelve times higher. In female patients at the same mental hospital the fracture rate of the distal radius was three times greater and that of proximal femur about seven times greater than that of the general population. This difference may not only be due to an increased skeletal fragility in patients in mental institutions but may also suggest poorer protective mechanisms against falls. Undiagnosed cardiovascular or neurological diseases, for example intermittent cardiac arrhythmia or transient cerebral ischaemic attacks, may cause falls. Early diagnosis and treatment of such diseases may reduce the number of fractures of the proximal femur.

Adult↗

Statistical prediction of rehabilitation in elderly patients with hip fractures.

A statistical investigation using multivariate techniques was made of the rehabilitation outcome of 103 consecutive elderly hip fracture patients, all admitted from their own homes. Cluster analysis revealed two main groups of variables, i.e., background variables (age, general medical condition, type of fracture, sex, living with someone) and functional variables (prefracture ability to visit someone and to shop, ability to walk and to manage activities of daily living two weeks postsurgery). A stepwise linear discriminant analysis was used, to estimate the probability of a given patient returning home. At discharge from hospital, certain factors, i.e., ability to walk two weeks postsurgery, living with someone, general medical condition, and type of fracture, were found to be most important for direct return home. At one year after hip fracture, the prefracture ability to visit someone and the age of the patient were of most prognostic significance for having returned and remained at home. The accuracy of the prediction tested by a "jackknife" procedure showed an over all increasingly correct classification during the follow-up year, more than 80% correct for all patients at discharge and 86% correct at one year. This approach to the analysis of soft data concerning hip fracture rehabilitation may prove of prognostic value also in sociomedical systems elsewhere.

Aged↗

Non-equilibrium enzyme immunoassay of gentamicin.

We describe a fast, accurate non-equilibrium enzyme immunoassay for serum gentamicin. With use of isokinetic conditions an assay takes a total of 12 min, including regeneration of the immunosorbent. The coefficient of correlation between the present method and conventional microbiological assays was 0.98.

Catalase↗