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Biomedical subjects

K Andersson

Publications and source records attributed to K Andersson.

At least 307 records · Page 17Linked to original sources

Involvement of cholinergic nicotine-like receptors as modulators of amine turnover in various types of hypothalamic dopamine and noradrenaline nerve terminal systems and of prolactin, LH, FSH and TSH secretion in the castrated male rat.

The effects of high repeated subcutaneous doses (4 X 2 mg/kg) of nicotine have been evaluated on dopamine (DA) and noradrenaline (NA) levels and turnover in the long-term castrated male rat using catecholamine (CA) fluorescence histochemistry in combination with quantitative microfluorometry. The CA turnover was evaluated by studying the decline of the CA stores following tyrosine hydroxylase inhibition using alpha-methyltyrosine methyl ester (H 44/68). In the same experiments trunk blood was collected for the determination of serum prolactin, LH, FSH and TSH levels using standard radioimmunoassay procedures. The nicotine treatment produced a significant depletion of CA stores and an increase of CA turnover in DA and NA nerve terminals of the median eminence and in peri- and paraventricular NA systems. These effects were significantly counteracted by pretreatment with mecamylamine. Nicotine significantly reduced serum prolactin and TSH levels, and after H 44/68 it also reduced LH and FSH serum levels. These actions were counteracted by mecamylamine pretreatment, except the effects on serum TSH levels after H 44/68, which were even enhanced by pretreatment with mecamylamine. Overall intraindividual correlations showed a significant correlation between reduced CA turnover in several hypothalamic areas and increased serum LH and FSH levels, increased NA turnover in the paraventricular hypothalamic nucleus and increased serum TSH levels, and reduced DA turnover in the median eminence and increased serum LH levels. It is suggested that in the castrated male rat nicotine can activate cholinergic nicotine-like receptors facilitating DA and NA turnover and release in various hypothalamic CA nerve terminal systems including those inhibiting the secretion of prolactin and LH (DA terminals in medial and lateral palisade zone, respectively) and facilitating secretion of TSH (NA terminals in the parvocellular part of the paraventricular hypothalamic nucleus).

Animals↗

Visualization of active 75 S RNA genes in the Balbiani rings of Chironomus tentans.

The active 75 S RNA genes in the Balbiani rings of Chironomus tentans were investigated by two complementing electron microscopy procedures: spreading of isolated chromosomes according to Miller and serial sectioning of Balbiani rings. The Miller spreads show that the transcription products, the ribonucleoprotein (RNP) fibers, increase gradually in length along the 75 S RNA genes. The morphology of the active genes in situ suggests the following sequence of events: during transcription a 20 nm RNP fiber is formed which is oriented roughly perpendicular to the chromosomal axis. When an RNP fiber corresponding to one quarter of the gene has been generated, packaging of the fiber into a dense globular structure begins at the free end of the RNP fiber. The processes of transcription and packaging go on in parallel in such a way that the length of the 20 nm fiber is kept constant, while the globular part is steadily increasing in size. When transcription is completed, a globular product is released, 50 nm in diameter. A thin (5 nm) chromosomal axis as well as a low DNA compaction (3.6) imply that the DNA in the chromosome fiber of an active 75 S RNA gene is more extended than the DNA in a nucleofilament. On the basis of our electron microscopy data and other information available on the Balbiani ring genes, we discuss the activation of the 75 S RNA genes in terms of a two-step process.

Animals↗

Effects of subchronic antidepressant drug treatment on central serotonergic mechanisms in the male rat.

These studies have examined the effects of a 2 week oral treatment with zimelidine, desipramine and imipramine in clinically relevant doses on 5-HT-1 and 5-HT-2 receptors, on 5-HT synthesis, on 5-HT dependent behaviours and on prolactin secretion in the male rat. 1. Zimelidine, desipramine and imipramine produced the same type of changes in 5-HT-1 and 5-HT-2 binding sites of the cerebral cortex. 2. A marked and selective reduction of 5-HT synthesis could be observed following long-term zimelidine treatment. 3. Long-term zimelidine and desipramine treatment reduced head twitch behaviour in mice induced by 5-HTP and 5-MeODMT. 4. Long-term treatment with zimelidine produced a reduction of basal prolactin secretion. These results suggest that long-term treatment with zimelidine desipramine and imipramine may reduce 5-HT neurotransmission at least in some 5-HT synapses in the brain which may represent part of the basis for their therapeutic activity. The indication of large numbers of low affinity binding sites (10-40 nM) for 3H-5-HT sites may lead to less steep dose effect curves and to a staprolactin secretion while long-term treatment with zimelidine results in significant reductions of prolactin secretion (11). These results support the view of the existence of a reduction of 5-HT neurotransmission at least within the hypothalamus following long-term treatment with zimelidine. Also other behavioural findings suggest that adaptive changes occur in 5-HT synapses involved in regulating the "serotonin syndrome" after long-term antidepressant treatment. Thus, the 5-HT syndrome is no longer enhanced by 5-HT uptake blocking agents. The ability of fluoxetine to enhance haloperidol-induced increases of dopamine metabolites in the striatum also disappears following chronic fluoxetine treatment (6,34).

Animals↗

A cohort study on mortality among long-time employed Swedish chimney sweeps.

A cohort study on mortality among all members of the Swedish Chimney Sweeps Union who were active in 1950 or later and have been members for at least 10 a has been performed; 2,071 chimney sweeps fulfilled the criteria and the loss in the follow-up was less than 1 %. The observed numbers of death before the age of 80 were compared with sex-, calendar year-, and age class specific expectancy values from the national statistics of 1951-1979. Two hundred and thirty deaths were observed versus 197.6 expected. This result was due to a significant excess of deaths from tumors, particularly lung and esophageal cancer, and from nonmalignant chronic respiratory diseases. The multifold increased risk from these diseases could hardly be explained by extreme smoking or alcohol habits but rather by exposure to polycyclic aromatic hydrocarbons, nitrogen compounds, arsenic, and asbestos in combination with exposure to sulfur dioxide. The excess mortality had occurred in spite of favorable selection factors as demonstrated in different subcohorts. Preventive actions to diminish inhalation of soot and combustion gases should be taken.

Adult↗

Rat prolactin and hypothalamic catecholamine nerve terminal systems. Evidence for rapid and discrete increases in dopamine and noradrenaline turnover in the hypophysectomized male rat.

Rat prolactin produces in a dose of 100 micrograms/kg a rapid and marked increase of dopamine turnover in the medial palisade zone of the median eminence and of noradrenaline turnover in the posterior periventricular hypothalamic region as well as a possible minor increase of noradrenaline turnover in the magnocellular part of the paraventricular hypothalamic nucleus of the hypophysectomized male rat. The rat prolactin serum levels measured 2 h following injection were within the upper physiological range of lactating rats. The findings suggest that dopamine in the medial palisade zone may be released as a prolactin inhibitory factor and respond rapidly to increases in serum prolactin levels. Furthermore, rat prolactin can acutely modify noradrenergic mechanisms in discrete areas of the hypothalamus indicating that prolactin can participate in the regulation of types of hypothalamic functions other than regulation of its own secretion.

Animals↗

Acute sino-aortic denervation in rats produces a selective increase of adrenaline turnover in the dorsal midline area of the caudal medulla oblongata and a reduction of adrenaline levels in the anterior and posterior hypothalamus.

Acute sino-aortic denervation produces an acute reduction of adrenaline stores in the anterior and posterior hypothalamus and a reduction of noradrenaline stores in the dorsal midline area of the caudal medulla oblongata. Furthermore, removal of baroreflex afferents results in an increase of adrenaline turnover in the DCMO but not in the hypothalamus. The present findings give evidence for participation of adrenergic mechanisms in central baroreflex regulation. The findings can be interpreted according to the adrenaline vasodepressor hypothesis of hypertension.

Animals↗

Long-term treatment with zimelidine leads to a reduction in 5-hydroxytryptamine neurotransmission within the central nervous system of the mouse and rat.

Male rats and mice received a 14 day peroral treatment with zimelidine, a novel antidepressant drug. Zimelidine produced a 70 and 60% reduction in the number of high affinity [3H]5-hydroxytryptamine (5-HT) and [3H]D-lysergic acid diethylamide (LSD) binding sites, respectively, and induced low affinity binding sites for [3H]5-HT and for [3H]D-LSD. The head twitch behaviour induced by 5-hydroxytryptophan and 5-methoxydimethyltryptamine was attenuated and reductions of prolactin and growth hormone were observed. These findings give further evidence that long-term treatment with zimelidine can produce a reduction of 5-HT neurotransmission in several brain regions.

Animals↗

Characterization of normal and supersensitive dopamine receptors: effects of ergot drugs and neuropeptides.

Dopamine receptors have been characterized by the use of radiolabelled dopamine agonists and antagonists. Using ibotenic acid induced lesions of the striatum, evidence was obtained that 3H-N-propylnorapomorphine (3H-NPA) binding sites and 3H-bromocriptine binding sites are located both on intrastriatal nerve cells and on extrinsic nerve terminals probably mainly originating in the cerebral cortex. Development of dopamine receptor supersensitivity as evaluated in 6-hydroxydopamine lesioned rats was associated with an 50% increase in the number of 3H-NPA binding sites in the striatum. Furthermore, one year following the 6-hydroxydopamine induced lesion of the dopamine pathways two binding sites for 3H-NPA could be demonstrated in the striatum. However, at this time interval the total number of 3H-NPA binding sites was not increased. The functional significance of these two binding sites for 3H-NPA in the striatum is unknown, but they are probably coupled to the biological effector in view of the marked behavioural supersensitivity demonstrated in these old animals. The dopamine receptor agonists and especially the dopaminergic ergot derivatives have been characterized by studying their affinities for 3H-bromocriptine, 3H-spiperone, 3H-ADTN and 3H-NPA binding sites in vitro. It is suggested that the Ki ratios for agonist and antagonist radioligands may be one useful way to characterize the agonist-antagonist character of the drug. Another important method is to study the effects of dopamine receptor agonists on the specific in vivo binding of 3H-spiperone and 3H-NPA. The correlation analysis of DA agonist affinities for the four radioligands of DA receptors used in the present study give evidence for the existence of at least 3 types of DA receptors. Actions of dopaminergic ergot drugs have been evaluated at supersensitive dopamine receptors. The findings suggest that the shift to the left of the threshold dose to activate supersensitive dopamine receptors could be due to a lowering of the stereoselectivity of agonist interaction at the dopamine agonist sites of supersensitive dopamine receptors. Such a change may explain the highly preferential action of CF 25-397 at supersensitive dopamine receptors, since its affinity for 3H-NPA binding sites was not increased in the present experiments. In agreement with previous work, evidence have also been presented that prolonged treatment with a potent dopaminergic drug, pergolide, can produce a down regulation of normal dopamine receptors by reducing the density of such receptors. Evidence has also been presented that CCK-8 and the desulphated CCK-8 (10(-6) M) can in vitro reduce the number of 3H-NPA binding sites in the striatum. These results indicate that cholecystokinin peptides via activation of cholecystokinin receptors can regulate the movements of the 3H-NPA binding sites across the plane of the membrane in such a way as to make them less available to the external surface of the membrane...

Animals↗

Nicotine-induced increases of noradrenaline turnover in discrete noradrenaline nerve terminal systems of the hypothalamus and the median eminence of the rat and their relationship to changes in the secretion of adenohypophyseal hormones.

The effects of acute single doses (0.3 and 1 mg/kg) of nicotine on various hypothalamic catecholamine nerve terminal systems and on the secretion of adenohypophyseal hormones in the rat were studied. Nicotine, in a dose of 1.0 mg/kg, increased noradrenaline turnover in the median eminence and in the peri- and paraventricular hypothalamic regions. The dopamine and noradrenaline nerve terminal systems in the median eminence and the dorsomedial hypothalamic nucleus respectively were unaffected. Serum GH levels were decreased and serum prolactin levels increased after a dose of 1 mg/kg. In the presence of tyrosine hydroxylase inhibition, nicotine in a dose of 1 mg/kg, instead increased GH and also LH secretion. It is suggested that the preferential increases of noradrenaline turnover in various hypothalamic noradrenaline nerve terminal systems by nicotine may be partly responsible for the nicotine induced increases of serum prolactin. GH and LH levels observed.

Animals↗

Chemosorption sampling and analysis of formaldehyde in air. Influence on recovery during the simultaneous sampling of formaldehyde, phenol, furfural and furfuryl alcohol.

A method based on trapping formaldehyde on a 2,4-dinitrodinitrophenylhydrazine-coated porous polymer (Amberlite XAD-2) was evaluated for air sampling in occupational environments. The aldehyde is converted to its 2,4-dinitrophenylhydrazone on the adsorbent. The influence of some organic compounds which often occur together with formaldehyde-furfural, phenol and furfuryl alcohol--was studied. The results show that the method allows the sampling of formaldehyde in the range 0.01--1.0 mg/m3 of air, based on a 3-1 (15 min) sample and a coating of 1%. Furfural, phenol, and furfuryl alcohol do not interfere and may be conveniently sampled at the same time. Formaldehyde and furfural hydrazones were analyzed by high-performance liquid chromatography, phenol and furfuryl alcohol by gas chromatography.

Air Pollution↗