Biomedical subjects

K Svensson

Publications and source records attributed to K Svensson.

At least 91 records · Page 5Linked to original sources

PubMed1991

Alkylation of DNA and hemoglobin in the mouse following exposure to propene and propylene oxide.

Male CBA mice were exposed to propene, unlabelled or 14C-labelled, by inhalation, or to 14C-labelled propylene oxide by intraperitoneal injection. 2-Hydroxypropyl adducts to guanine-N-7 in DNA of various organs and to N-terminal valine and histidine-N pi in hemoglobin were measured. The adduct levels observed show that propylene oxide is the major primary metabolic product of propene. A direct comparison of propylene oxide with the homologous compound ethylene oxide on the basis of adduct levels introduced (in DNA and in hemoglobin) at equimolar injected amounts, shows that propylene oxide is 6-10 times less effective than ethylene oxide.

Alkenes↗

PubMed1991

The effects of 6-OHDA-induced dopamine depletions in the ventral or dorsal striatum on maternal and sexual behavior in the female rat.

The effects of dopamine-depleting 6-OHDA infusions in the ventral or dorsal striatum on maternal and sexual behaviors were examined in female rats. Like sham-operated controls, lactating rats receiving 6-OHDA in the ventral striatum built good nests, nursed the infants and showed maternal aggression toward strange intruders. By contrast, the lesioned females performed poorly in tests for pup retrieval, as reflected in greatly protracted retrieval latencies. There was no effect of ventral striatal DA depletions on proceptive and receptive elements of female sexual behavior, which was studied after lactation following ovariectomy and exogenous administration of ovarian hormones, but these animals did show an attenuated hyperactivity response to a low dose of amphetamine. Females with dopamine lesions in the dorsal striatum did not differ from controls with respect to maternal and sexual behavior, but they did show an enhanced hyperactivity response to amphetamine treatment.

Amphetamine↗

PubMed1991

Mesotelencephalic dopamine system and reproductive behavior in the female rat: effects of ventral tegmental 6-hydroxydopamine lesions on maternal and sexual responsiveness.

The effects of lesions to the mesolimbic dopamine system on maternal and sexual behaviors in the female rat was assessed. Rat dams that were given ventral tegmental area microinfusions of 6-hydroxydopamine (6-OHDA) during lactation showed a persistent deficit in pup retrieval but were not impaired with respect to nursing, nest building, or maternal aggression. In addition, 6-OHDA-lesioned females failed to respond to amphetamine by showing locomotor hyperactivity. Administration of the dopamine blocker raclopride to neurologically intact dams also inhibited pup retrieval but had no effect on nursing. Females given 6-OHDA during pregnancy appeared completely unresponsive to pups, whereas no maternal deficits were seen in females that received 6-OHDA 8 weeks before parturition. Proceptive (hopping and darting) and receptive (lordosis) components of sexual behavior, assessed after ovariectomy and exogenous steroid hormone treatment, were not affected by mesolimbic 6-OHDA lesions.

Animals↗

PubMed1991

Somatostatin levels in plasma in nonsmoking and smoking breast-feeding women.

The objective of the study was to record how somatostatin levels in plasma are altered in response to breast-feeding during the lactation period and to relate somatostatin levels to the success of the lactational performance and to smoking habits. Fifty-two women were investigated 4 days post partum and 3-4 months later. Blood samples were collected and the levels of somatostatin-like immunoreactivity (below referred to as SLI) were measured with radioimmunoassay. The periods of exclusive breast-feeding and of mixed feeding were assessed as well as the milk yield. Smoking habits were noted. SLI levels were found to be significantly lower on day 4 after delivery, compared to 3-4 months later. Also the type of response to breast-feeding was different. Thus, a significant fall of SLI was seen during breast-feeding at the maternity unit, but not 3-4 months later. Smoking women breast-fed fully for a significantly shorter time than nonsmokers and had significantly higher SLI levels at onset of breast-feeding day 4 post partum. Whether the high somatostatin levels recorded in connection with breast-feeding in smokers are related to the shorter period of breast-feeding seen in this group remains to be established. In addition, the highest levels of somatostatin were seen the day after the very last breast-feeding and a possible role for somatostatin in the weaning process should be explored.

Adolescent↗

PubMed1991

Distribution of the intermediate elements operating in ER to Golgi transport.

We have used a 58 kDa membrane protein (p58) as a marker to study the transport pathway between the rough endoplasmic reticulum (ER) and the Golgi apparatus. Immunolocalization of p58 in fibroblasts showed its presence in a single cisterna and in small tubular and vesicular elements at the cis side of the Golgi apparatus. In addition, the protein was detected in large (200-500 nm in diameter) tubulovesicular structures, clustered in the Golgi region but also found in peripheral locations. These represent intermediates in ER to Golgi transport since they contained newly synthesized viral glycoproteins, arrested in cells at 15 degrees C. The peripheral structures accumulated at low temperature but reclustered rapidly to the Golgi region upon shift of cells back to 37 degrees C. This movement involved long intracellular distances and was efficiently inhibited by nocodazole, indicating that it requires the integrity of microtubules. In contrast, reclustering was unaffected by brefeldin A (BFA), suggesting that this compound affects ER to Golgi transport prior to the temperature-sensitive step. In BFA-treated cells p58 was localized to scattered, tubular, smooth ER clusters, found in close association with rough ER cisternae. The cellular distribution of the intermediate elements indicates that the sites of protein exit are widely distributed within the rough ER network. We suggest that the smooth ER locations where p58 accumulates in BFA-treated cells could represent such peripheral exit sites.

Animals↗

PubMed1991

Bambuterol: a new long acting bronchodilating prodrug.

Bambuterol, a carbamate prodrug of terbutaline as a 5, 10, or 20-mg tablet, was given once every evening to patients with asthma in a randomized double-blind crossover study. Twenty milligrams improved pulmonary functions over 24 hours; 5 and 10 mg did not. Few side effects were observed.

Administration, Oral↗

PubMed1990

Increased dopamine release by the autoreceptor antagonist (+)-AJ 76 is Ca2(+)-dependent.

The effects of the preferential autoreceptor antagonist (+)-AJ 76 on dopamine release and metabolism were studied in the brain microdialysis model. The Ca2+ dependence of the effects of (+)-AJ 76 and d-amphetamine were compared. We found that (+)-AJ 76 increased the release and metabolism of dopamine and that the release was saturable. The release of dopamine by (+)-AJ 76 was dependent on extracellular Ca2+. However, the effects of (+)-AJ 76 on dopamine metabolism were independent of extracellular Ca2+. The effects of d-amphetamine on dopamine release and metabolism were independent of Ca2+. We conclude that the dopamine released by (+)-AJ 76 is dependent on neuronal impulse flow and that the dopamine released is of vesicular origin. The effects on dopamine metabolism and release may be exerted via different mechanisms. In contrast, the release and metabolism of dopamine by d-amphetamine were independent of impulse flow and extracellular Ca2+. We suggest that (+)-AJ 76 and d-amphetamine release dopamine from different pools.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1990

Acute changes in dopamine levels in rat adrenal glands after administration of dopamine receptor agonists and antagonists.

The study was aimed at in vivo pharmacological identification of the possible dopamine (DA) receptor(s) involved in changes of the DA level in rat adrenal glands. Previous work in this laboratory has shown that the DA level is largely controlled by the rate of catecholamine synthesis. The rats were killed by decapitation after various periods of drug administration and the catecholamine content of adrenal glands and forebrain was measured by high-performance liquid chromatography with electrochemical detection. Administration of the DA D-1 + D-2 receptor agonist, apomorphine, induced a statistically significant increase in DA levels in the adrenal glands. The same effect was noted after administration of the DA D-2 receptor agonist, quinpirole. The DA D-2 receptor antagonist, raclopride, blocked the apomorphine-induced increase in adrenal DA levels but had no effect per se on these levels. The DA D-1 receptor agonist, SKF 38393, and the DA D-1 receptor antagonist, SCH 23390, did not have any effect on apomorphine-induced changes in DA content in the adrenals. The DA elevating effect of the DA D-2 receptor agonist, quinpirole, in the adrenals was completely blocked by the DA D-2 receptor antagonist, domperidone. This compound does not cross the blood-brain barrier readily and is thus supposed to act mainly on peripheral tissues. In support of this, the dose of domperidone used did not affect brain DOPAC levels. Our data, together with observations reported in the literature, indicate that the adrenal medulla contains DA receptors of the D-2 subtype, which are capable of controlling the DA level in rat adrenal glands.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

PubMed1990

Pre- and postsynaptic dopaminergic activities of indolizidine and quinolizidine derivatives of 3-(3-hydroxyphenyl)-N-(n-propyl)piperidine (3-PPP). Further developments of a dopamine receptor model.

Pre- and postsynaptic dopaminergic activities of a series of indolizidine and quinolizidine analogues of 3-(3-hydroxyphenyl)-N-(n-propyl)piperidine (3-PPP) have been studied. The pharmacological data have been interpreted in terms of a previously reported model for interactions with dopamine pre- and postsynaptic D2-receptors and molecular mechanics (MM2(85] calculated geometries and conformational energies. The model has been further developed with respect to the receptor topography in the vicinity of the nitrogen binding site. In particular, a novel spatial orientation of the important "propyl cleft" has been proposed. This cleft is suggested to be located mainly above a plane through the receptor-bound substrate. The biologically active agonist and antagonist conformations of the enantiomers of 3-PPP have been reinvestigated.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1990

Synthesis and pharmacology of the enantiomers of cis-7-hydroxy-3-methyl-2-(dipropylamino)tetralin.

The enantiomers of cis-7-hydroxy-3-methyl-2-(dipropylamino)tetralin (3) have been synthesized and evaluated for activity at central dopamine (DA), 5-hydroxytryptamine, and norepinephrine (NE) receptors, by use of biochemical and behavioral tests in rats. In addition, the affinities of the compounds for striatal [3H]spiroperidol and [3H]N-propylnorapomorphine binding sites were determined. The absolute configuration of the enantiomers was determined by X-ray diffraction of (+)-3. The pharmacological effects of both enantiomers are complicated, but (2R,3S)-7-hydroxy-3-methyl-2-(dipropylamino)tetralin [(-)-3] produced biochemical effects in vivo similar to those elicited by classical DA D2-receptor antagonists.

5-Hydroxytryptophan↗

PubMed1989

The putatively antipsychotic agent amperozide produces behavioural stimulation in the rat. A behavioural and biochemical characterization.

Amperozide (FG 5606; N-ethyl-4-[4',4'-bis(p-fluorophenyl)butyl]-1-piperazinecarboximide ) is a new putatively antipsychotic compound with a postulated 5-HT2 antagonistic profile. Somewhat surprisingly amperozide dose dependently induced a behavioural stimulation in reserpinized and in nonpretreated rats. The behaviour consisted of both forward and backward locomotion as well as forepaw circling and a grooming like behaviour. Since the behavioural pattern clearly differ from that produced by classical dopaminergic or serotonergic agonists (e.g. apomorphine or 8-hydroxy-2-(di-n-propylamino)tetralin, 8-OH-DPAT), and has not been previously reported, we decided to investigate the origin of this effect. In the behavioural paradigms it was not possible to antagonize the amperozide stimulation in reserpinized rats with the dopamine receptor blockers haloperidol, raclopride or R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1 H-3-benzazepine, SCH 23390. Neither the 5-HT2 receptor blocking agent ritanserin nor the tryptophan and tyrosine hydroxylase inhibitor DL-3,4-dihydroxy-phenyl-alpha-propylacetamide, H22/54, could block the motoric stimulation or the forepaw circling behaviour produced by amperozide. However, the noradrenaline synthesis inhibitor bis-(4-methyl-1-homopiperazinylthiocarbonyl)-disulfide, FLA 63, as well as the alpha-adrenoceptor antagonist phenoxybenzamine, could partly inhibit the locomotor stimulation. Hence, noradrenaline seems to be, at least in part, involved in the behavioural stimulatory effect of amperozide. Biochemically amperozide had no effect on the dopamine synthesis rate (DOPA formation) in normal or reserpinized animals in the striatal or the limbic brain regions. In reserpinized animals amperozide also failed to antagonize the decrease in DOPA formation after apomorphine and 3-hydroxy-benzylhydrazine HCl, NSD 1015, in these regions.(ABSTRACT TRUNCATED AT 250 WORDS)

5-Hydroxytryptophan↗

PubMed1989

Resolved 6,7,8,9-tetrahydro-N,N-dimethyl-3H-benz[e]indol-8-amine: central dopamine and serotonin receptor stimulating properties.

The enantiomers of 6,7,8,9-tetrahydro-N,N-dimethyl-3H-benz[e]indol-8- amine (1a) were prepared and tested for their actions on central dopamine and serotonin (5-HT) receptors. The dopaminergic effects were shown to reside in the (1)-R enantiomer. It was shown that compound 1a and its (+)-R enantiomer possess potent central 5-HT1A receptor stimulating properties.

Animals↗

PubMed1989

Adducts of malonaldehyde and a few other aldehydes to hemoglobin.

A method for the determination of hemoglobin (Hb) adducts of malonaldehyde (MA), one of the main products of lipid peroxidation, was developed. The method was based on a sodium borohydride reduction of MA-adducts to stable 3-hydroxypropyl adducts and quantification of the adduct to the N-terminal valine of Hb by a modified Edman procedure. Background levels of approximately 0.2 and 3.8 nmol/g Hb were recorded in one human volunteer and in control mice, respectively. Increased adduct levels were observed in mice after induction of lipid peroxidation with carbon tetrachloride. The kinetics of the reaction of MA with Hb and the stability of adducts formed were studied in in vitro experiments. Based on the adduct levels in Hb and the rate constant for adduct formation, the concentration of free MA in erythrocytes in mice was estimated. The background levels of adducts of some other aldehydes in Hb were also measured and the possibility that these adducts are formed as artefacts was studied.

Acrolein↗

PubMed1989

Increased mortality in men with ST segment depression during 24 h ambulatory long-term ECG recording. Results from prospective population study 'Men born in 1914', from Malmö, Sweden.

'Men born in 1914', from Malmö, Sweden, is a cohort study of the morbidity and mortality of cardiovascular diseases among 68-year-old men in an urban population. Ambulatory long-term ECG recording was part of the health examination that these men were invited to undergo in 1982. Five hundred attended (80.5%) of the 621 invited. Ninety-eight of the 394 men in whom the ECG recording was technically satisfactory had at least one episode with horizontal or downsloping ST segment depression greater than or equal to 0.1 mV. The median total duration of ST segment depression was 135 min. 90% of these episodes were not preceeded by any increase in heart rate. In only eight of the 47 men who reported an occurrence of chest symptoms during the recording period did ST segment depression and chest symptoms occur simultaneously. 43 months after the health examination, 33 (8.4%) men had died. The mortality in men without ST segment depression and without any history of coronary heart disease was 6.5%. The incidence of fatal and non-fatal myocardial infarction in men without ST depression greater than or equal to 0.1 mV and without a history of IHD was 2.3%. Men with ST depression greater than or equal to 0.1 mV in comparison with this group had a 4.4 times greater relative risk. The risk in men with both ST segment depression greater than or equal to 0.1 mV and history of coronary heart disease was 16.0 times greater. This study shows that asymptomatic ST segment depression is a frequent finding in elderly men. The occurrence of asymptomatic ST segment depression is associated with an increased cardiovascular mortality. This increased mortality is independent of a history compatible with angina pectoris or previous myocardial infarction.

Aged↗

PubMed1989

Peak flow in children aged 4-16 years. Normal values for Vitalograph peak flow monitor, Wright and Mini Wright peakflow meters.

Peak expiratory flow rate was measured in 318 Swedish children aged 4-16 years on Wright peak flow meter, Mini Wright peak flow meter and Vitalograph peak flow monitor. We found that height, age and sex had a significant effect on the regression equation. Weight and body surface area did not add any significant information. The curves for the Wright and Mini Wright peakflow meters are presented and may be used as normal references in the clinic. Mini Wright peakflow meter and Vitalograph peak flow monitor are cheap and handy but results on different instruments should not be directly compared.

Adolescent↗

PubMed1988

Comparative pharmacokinetics of unlabeled and deuterium-labeled terbutaline: demonstration of a small isotope effect.

An equimolar mixture of terbutaline and [2H6]terbutaline was given as an oral solution to six healthy volunteers (three men and three women). Frequent blood samples were collected during a 24-h period and the plasma concentrations of unlabeled and deuterium-labeled terbutaline were measured by GC-MS. The overall geometric mean plasma concentration ratio of terbutaline to [2H6]terbutaline (isotope ratio) was 1.04 and differed significantly from unity. The difference can be explained by a difference in lipophilicity between the analogues, affecting their absorption. No trend in isotope ratio over the experimental time was observed. For unknown reasons, the isotope ratio was higher for women (1.07) than for men (1.00). Deuterium-labeled terbutaline can be used, intravenously or orally, as an absolute reference in bioavailability studies on terbutaline. If deuterium-labeled terbutaline is given orally in a single-day relative bioavailability study, a correlation should be made for the observed isotope effect.

Adult↗

PubMed1988

In vivo dopamine (DA) receptor binding and behavioural effects of the putative DA autoreceptor antagonists (+)-AJ 76 and (+)-UH 232 in rats with a unilateral nigral 6-OH-DA lesion.

The in vivo dopamine (DA) receptor binding and behavioural properties of the recently characterised putative preferential DA autoreceptor antagonists (+)-AJ 76 and (+)-UH 232 were studied in rats with a unilateral 6-OH-DA lesion of the substantia nigra. The main findings were a) that (+)-UH 232 and (+)-AJ 76 per se failed to produce significant turning behaviour, b) that both agents antagonised contralateral rotation caused by the DA agonist apomorphine, including a change of the characteristic two-peak apomorphine rotation pattern into a single peak, indicating that the DA antagonist properties of (+)-UH 232 and (+)-AJ 76 are retained also at denervation-sensitised postsynaptic DA receptors and--in support of this notion--c) that (+)-UH 232 and (+)-AJ 76 were able to displace the specific in vivo binding of the DA receptor agonist DP-5,6-ADTN in the denervated as well as in the intact striata of the 6-OH-DA-lesioned animals. Interestingly, in this regard (+)-UH 232 was significantly less efficient on the lesioned as compared to the intact side. The DP-5,6-ADTN-displacing effect of (+)-AJ 76 did not, however, differ between the intact and the denervated striatum. The implications of the present findings are discussed with particular reference to DA receptor sensitivity and adaptational phenomena.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1988

Breast feeding-induced effects on plasma gastrin and somatostatin levels and their correlation with milk yield in lactating females.

Maternal gastrin and somatostatin levels have been shown to be influenced during suckling in dogs and pigs. The present study was performed to investigate whether the levels of gastrin and somatostatin are influenced by breast feeding in lactating women. Repeated blood samples were drawn in connection with nursing in 15 females and plasma levels of gastrin and somatostatin were measured by radioimmunoassay. Gastrin levels rose significantly (P = 0.01) within two minutes after onset of suckling. Somatostatin levels either decreased or increased as an effect of breast feeding. The direction of the change was correlated to the pre-suckling somatostatin levels (P less than 0.01). The somatostatin level recorded 60 min after start of breast feeding was significantly lower than basal levels (P less than 0.01) indicating a long-term inhibitory effect on somatostatin secretion. The suckling-induced effect on somatostatin levels was correlated with the amount of milk ejected (Rs - 0.52, P less than 0.05). The mechanism by which suckling influences circulating gastrin and somatostatin levels is unknown, but we suggest that suckling leads to a reflex activation of the vagal nerves, which influence the release of these hormones from the stomach. The size of the gastrointestinal tract is increased during pregnancy and lactation, illustrating that the maternal digestive capacity is adapted to the high demand for energy intake occurring during lactation. We speculate that the suckling stimulus enhances gastric functions by influencing the release of gastrin and somatostatin, which stimulate and inhibit gastric functions and growth, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗