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Biomedical subjects

A Carlsson

Publications and source records attributed to A Carlsson.

At least 181 records · Page 10Linked to original sources
PubMed1989

Dramatic synergism between MK-801 and clonidine with respect to locomotor stimulatory effect in monoamine-depleted mice.

The present study corroborates previous findings showing that the selective, non-competitive N-methyl-D-aspartate (NMDA) antagonist MK-801 [(+)-5-methyl-10,11-dihydroxy-5H-dibenzo(a,d)-cyclohepten-5,10-imi ne] produces a dose-dependent increase in locomotion in mice pretreated with a combination of the monoamine-depleter reserpine and the catecholamine synthesis inhibitor alpha-methyl-para-tyrosine. Moreover, the present investigation demonstrates a synergistic interaction between MK-801 and the alpha-adrenergic agonist clonidine in monoamine-depleted mice: MK-801 in a dose of 1 mg/kg and clonidine in a dose of 2 mg/kg hardly affected locomotion when given separately, but when the two drugs were combined a dramatic enhancement of motor activity was observed. This effect was effectively antagonized by the alpha 2-adrenergic blockers idazoxan and yohimbine, as well as by the "atypical" neuroleptic clozapine. Likewise, a clear-cut synergism was observed when a low dose of the dopamine receptor agonist apomorphine (0.1 mg/kg), which did not per se affect motor activity, was combined with MK-801 (1.5 mg/kg); however, the synergism between apomorphine and MK-801 was less dramatic than that observed between MK-801 and clonidine. The results may have important neuropsychiatric implications related to, e.g. the treatment of Parkinson's disease and the pathogenesis of schizophrenia.

Animals↗
PubMed1989

The NMDA antagonist MK-801 causes marked locomotor stimulation in monoamine-depleted mice.

It was shown in the present study that the selective non-competitive N-methyl-D-aspartate (NMDA) antagonist MK-801 [(+)-5-methyl-10,11-dihydroxy-5H-dibenzo(a,d)cyclohepten-5,10-imin e] caused a pronounced and dose-dependent increase in locomotion in mice pretreated with a combination of reserpine and alpha-methyl-para-tyrosine. Haloperidol pretreatment did not antagonize the MK-801-induced stimulation of locomotion. The findings are discussed in relation to the concept of a corticostriatothalamocortical negative feedback loop serving to protect the cortex from an overload of information and hyperarousal. Such a feedback loop would encompass i.a. corticostriatal glutamatergic neurons and it would be modulated by mesencephalostriatal dopaminergic neurons.

Animals↗
PubMed1989

A marked rise in 5-S-cysteinyl-dopamine levels in guinea-pig striatum following reserpine treatment.

Reserpine administration (5 mg/kg, i.p.) to guinea pigs resulted in marked and long lasting dopamine (DA) depletion and a rapid, short lasting, increase of 3,4-dihydroxyphenylacetic acid (DOPAC) in the striatum. A marked and sustained increase of the level of 5-S-cysteinyl-dopamine, which is an adduct presumably formed following autoxidation of DA, started 3-4 h following the DA and DOPAC changes. Only small changes in the levels of the 5-S-cysteinyl adducts of DOPAC and 3,4-dihydroxyphenylalanine (DOPA) were found.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1989

The apparent autoxidation rate of catechols in dopamine-rich regions of human brains increases with the degree of depigmentation of substantia nigra.

The concentrations of the 5-S-cysteinyl adducts of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC) and 3,4-dihydroxyphenylalanine (DOPA) and the levels of noradrenaline (NA), DA, DOPAC and DOPA were determined in the putamen (PUT), caudate nucleus (CN) and substantia nigra (SN) of human post mortem brains with or without depigmentation and degeneration of the SN. The levels of DA, DOPAC and DOPA decreased with the degree of depigmentation and degeneration in the three brain regions while NA levels only decreased in SN and PUT. In general, the concentrations of the 5-S-cysteinyl adducts did not differ, but the ratios of 5-S-cysteinyl-DA/DA, 5-S-cysteinyl-DOPAC/DOPAC and 5-S-cysteinyl-DOPA/DOPA were higher in patients with a more depigmentated and degenerated SN, except for the 5-S-cysteinyl-DA/DA ratio in the PUT. Higher ratios were also found in the cell body areas compared to the neuron terminal areas. Thus depigmentation and degeneration of dopaminergic SN neurons, seem to be correlated to enhanced rates of autoxidation, possibly due to an impaired antioxidant capacity.

Aged↗
PubMed1989

Marked locomotor stimulation in monoamine-depleted mice following treatment with atropine in combination with clonidine.

The present study demonstrates that the muscarinic antagonist atropine and the alpha-adrenergic agonist clonidine, though ineffective when administered separately, produced a pronounced locomotor stimulation in monoamine-depleted mice when combined. The atropine + clonidine-induced locomotor stimulation was counteracted by both the alpha 2-adrenoceptor antagonist idazoxan and the acetylcholinesterase inhibitor physostigmine. Thus, it is clear that simultaneous manipulations with cholinergic and adrenergic systems are as effective in restoring locomotion in monoamine-depleted mice as increasing central dopaminergic tone. This finding may have implications for the treatment of a movement disorder like Parkinson's disease.

Animals↗
PubMed1989

Simultaneous determination of lactate, pyruvate, and ascorbate in microdialysis samples from rat brain, blood, fat, and muscle using high-performance liquid chromatography.

An isocratic high-performance liquid chromatographic (HPLC) method was developed for the simultaneous determination of lactate, pyruvate, and ascorbate in tissue and blood, sampled in vivo using the microdialysis technique. The compounds were separated on a silica-based, reversed-phase column or on a resin-based, cation exchange column. The acids were monitored by ultraviolet detection.

Adipose Tissue↗
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

Synthesis and release of dopamine in rat brain: comparison between substantia nigra pars compacts, pars reticulata, and striatum.

Dopamine (DA) is synthesized and released not only from the terminals of the nigrostriatal dopaminergic neuronal pathway, but also from the dendrites in the substantia nigra. We have investigated the regulation of the DA turnover, the DA synthesis rate, and the DA release in the substantia nigra pars compacts (SNpc) and pars reticulata (SNpr) in vivo. As a measure of DA turnover, we have assessed the concentrations of 3,4-dihydroxyphenylacetic acid and homovanillic acid. As a measure of the DA synthesis rate, we have determined the 3,4-dihydroxyphenylalanine accumulation after inhibition of aromatic L-amino acid decarboxylase by 3-hydroxybenzylhydrazine. As a measure of DA release, we have investigated the disappearance rate of DA after inhibition of its synthesis by alpha-methyl-p-tyrosine and the 3-methoxytyramine accumulation following monoamine oxidase inhibition by pargyline. Both the DA turnover and the DA synthesis rate increased following treatment with the DA receptor antagonist haloperidol and decreased following treatment with the DA receptor agonist apomorphine in the SNpc and in the SNpr, but the effects of the drugs were less pronounced than in the striatum. gamma-Butyrolactone treatment, which suppresses the firing of the dopaminergic neurons, increased the DA synthesis rate in the striatum (165%), but had no such effect in the SNpc or SNpr. Haloperidol, apomorphine, and gamma-butyrolactone increased, decreased, and abolished, respectively, the DA release in the striatum, but the drugs had no or only slight effects on the alpha-methyl-p-tyrosine-induced DA disappearance and on the pargyline-induced 3-methoxytyramine accumulation in the SNpc or SNpr. Taken together, these results indicate that the DA synthesis rate, but not the DA release, are influenced by DA receptor activity and neuronal firing in the SNpc and SNpr. This is in contrast to the situation in the striatum, where both the DA synthesis rate and the DA release are under such control.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1989

Neurotransmitter deficits in a non-multi-infarct category of vascular dementia.

Brain tissue from 9 severely demented patients cared for in psychiatric long-term wards and with records of stroke episodes, macroscopic signs of brain infarcts and with no clinical evidence of senile dementia of the Alzheimer type was investigated and compared with control material. The mean volume of the brain infarcts in this vascular dementia group was only 6.8 ml. Pronounced disturbances of the serotoninergic and cholingergic systems were found in subcortical and cortical grey matter. These widespread neurotransmitter changes can hardly be explained by the localized brain infarcts per se, but suggest the existence of another category of vascular dementia. Since the neurotransmitter disturbances were found to be similar to those of Alzheimer's disease and senile dementia of the Alzheimer type, it seems more likely that they indicate a common pathway for dementia disorders than that they serve as markers of different dementia categories.

Aged↗
PubMed1989

Lactoferrin and lysozyme in milk during acute mastitis and their inhibitory effect in Delvotest P.

Microbiological methods for detection of antibiotic residues in milk give no explanations regarding the identity of the inhibitory substance(s). Natural antibacterial substances, present at higher concentrations in mastitic milk and in colostrum, occasionally cause false positive results in antibiotic assays. In an earlier investigation, lysozyme and lactoferrin were shown to inhibit the growth of Bacillus stearothermophilus var. calidolactis spores, used as test organism in Delvotest P. To study the effect of high lysozyme and lactoferrin concentrations in milk on the Delvotest P, cows were subjected to acute experimental mastitis by infusion of Salmonella typhimurium SH 4809 endotoxin. Milk samples were collected up to 11 h postinfusion. Concentrations of lactoferrin and lysozyme, somatic cell count, and effect on Delvotest P were determined. A positive reaction in the Delvotest correlated well with an increase in lactoferrin and lysozyme concentrations. The nature of the inhibitory effect is briefly discussed.

Acute Disease↗
PubMed1989

Implantation of orthopaedic devices in patients with metal allergy.

Patients with a contact allergy to chromium, cobalt and/or nickel, patch test verified before implantation of a metallic orthopaedic device, were followed up years later by clinical and radiographic examination as well as with epicutaneous and intracutaneous tests. Eighteen patients had been exposed to an orthopaedic implant for several years (mean 6.3 years) containing a metal to which they were allergic. None had suffered any dermatologic or orthopaedic complications attributable to the contact allergy.

Chromium↗
PubMed1988

Striatal and cortical acetylcholine release in vivo in rats with unilateral decortication: effects of treatment with monosialoganglioside GM1.

Striatal and cortical extracellular acetylcholine (ACh) and choline (Ch) levels were determined in samples collected under in vivo conditions using microdialysis in normal (naive) and decorticated rats treated with saline or the monoganglioside GM1. ACh and Ch were assayed using a sensitive high performance liquid chromatography technique coupled to a postcolumn reactor with immobilized enzymes. Picomole amounts of ACh could be measured in the presence of an acetylcholinesterase inhibitor (neostigmine) in the microdialysis perfusion medium (striatal ACh = 0.2-0.4 microM; cortical ACh = 0.03-0.04 microM). Ch was detected both in the presence and in the absence of neostigmine (striatal Ch = 0.5-0.6 microM; cortical Ch = 0.6-2 microM). ACh, but not Ch, was strongly stimulated by 100 mM of KCl included in the perfusion medium. Decortication produced by devascularization did not significantly modify the cortical or striatal basal levels of ACh. However, in the cortex, KCl produced a higher ACh stimulation in the GM1-treated than in the saline-treated decorticated or naive rats. The present results indicate that GM1-treatment increases the ability of cortical cholinergic terminals to release ACh and support the idea that trophic factors such as monoganglioside GM1 can promote recovery following injuries of the central nervous system.

Acetylcholine↗
PubMed1988

Dopamine (DA) autoreceptor efficacy of 3-PPP enantiomers after short-term synaptic DA deprivation.

We have compared the central dopamine (DA) autoreceptor-stimulatory properties of the 'atypical' DA agonist, (-)-3-PPP, its (+)-antipode and the reference DA agonist, apomorphine, following a 5 or an 18 h interruption of synaptic dopaminergic transmission by means of reserpine. The results are consistent with the notion that even a relatively short period (18 h) of synaptic DA deprivation results in a functional 'supersensitivity' of central DA synthesis-modulating autoreceptors. Interestingly, the data demonstrate a clearcut and significant enhancement of the intrinsic agonist efficacy of (-)-3-PPP in limbic and striatal parts after an 18 h as compared to a 5 h reserpine-induced impairment of synaptic DA transmission. In addition, there was a tendency towards a reduction in the doses of apomorphine and the 3-PPP enantiomers needed to inhibit DA synthesis in 18 vs. 5 h reserpinized rats in both brain regions. The findings indicate that the adaptive state of the DA autoreceptors had been altered, tentatively as a result of the reduced (endogenous) agonist occupancy. This is consistent with the suggestion that DA autoreceptors are influenced by a certain, albeit presumably low, endogenous dopaminergic tone under in vivo physiological conditions. The data obtained provide further support for the contention that receptor responsiveness is a critical determinant of the intrinsic efficacy displayed by DA receptor agonists such as (-)-3-PPP.

Animals↗
PubMed1988

How far does prophylaxis against infection in total joint replacement offset its cost?

Selection of a cost effective method of prophylaxis against infection for patients undergoing total joint replacement was shown to depend on the number of arthroplasties performed each year at individual hospitals. When 100 arthroplasties were performed each year the prophylactic use of systemic antibiotics minimised the total costs of the department--that is, the combined costs of prophylaxis and reoperation for deep sepsis. Some departments also used local antibiotic prophylaxis in the form of polymethylmethacrylate cement impregnated with gentamicin or a combination of systemic and local prophylaxis at almost as low a total cost and with comparable effect. Selection of a method of prophylaxis should not be determined solely on the basis of reducing costs. When a value was assigned to the effects of loss of health an economic optimum was established that allowed selection of a more costly method of prophylaxis together with further reductions in the incidence of infection and the need for reoperation.

Anti-Bacterial Agents↗
PubMed1988

In vivo evidence for a greater brain tryptophan hydroxylase capacity in female than in male rats.

Previous studies have revealed that brain levels of tryptophan, 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) are moderately higher in female than in male rats. Since tryptophan hydroxylase is only about half saturated with substrate, the greater availability of precursor in female rats might contribute to their higher 5-hydroxyindole levels. The present investigation was aimed at clarifying whether there is a sex difference in central tryptophan hydroxylase capacity. Hence, both sexes received a high dose of L-tryptophan (400 mg/kg), which resulted in a tenfold increase in brain tryptophan concentrations and presumably a virtual saturation of tryptophan hydroxylase. Following such treatment, 5-hydroxytryptophan (5-HTP) levels, measured after L-amino acid decarboxylase inhibition, were compared in males and females. Both in saline- and L-tryptophan-treated rats, 5-HTP levels were generally higher in females. In another group of animals, receiving 400 mg/kg of L-tryptophan as sole treatment, 5-HT and 5-HIAA concentrations were measured. As in the case of 5-HTP, the higher 5-HT and 5-HIAA levels observed in females persisted after L-tryptophan treatment. The present data suggest that brain tryptophan hydroxylase activity is greater in females; this sex difference probably contributes to the higher 5-HT and 5-HIAA levels in females.

5-Hydroxytryptophan↗
PubMed1988

NSD 1034: an amino acid decarboxylase inhibitor with a stimulatory action on dopamine synthesis not mediated by classical dopamine receptors.

The accumulation rates of 3,4'-dihydroxyphenylalanine (DOPA) and 5-hydroxytryptophan (5-HTP) after inhibition of aromatic amino acid decarboxylase (AADC) by 3-hydroxybenzylhydrazine (NSD 1015) or 1-(DL-seryl)-2- (2,3,4-trihydroxybenzyl)hydrazine (Ro 4-4602) have widely been used as measurements of the in vivo synthesis rates of monoamines. However, the values of dopamine (DA) turnover in rat striatum obtained using these drugs are much lower than values obtained by other methods. This discrepancy prompted us to further investigate the AADC inhibitor 1-(3-hydroxybenzyl)-1-methylhydrazine (NSD 1034) which earlier has been shown to give a DOPA accumulation rate in the striatum of the same magnitude as other measures of DA turnover. NSD 1034 was found to give a more than twofold higher DOPA accumulation rate than NSD 1015, NSD 1024, NSD 1039, NSD 1055 and Ro 4-4602 in the striatum. Also, in the limbic region and the hemispheres, but not in the substantia nigra, the DOPA accumulation was higher after NSD 1034 than after NSD 1015, but the difference was less pronounced. There was, however, no difference in 5-HTP accumulation between the drugs in any of the brain parts investigated. Although the DOPA accumulation rates are higher after NSD 1034 than after NSD 1015, the NSD 1015-induced DOPA accumulation seems to be more sensitive to changes in dopamine receptor occupancy. The different DOPA accumulation rates obtained with NSD 1015 and NSD 1034 are not due to differences in MAO inhibition, to interference with classical DA receptors, or to different degrees of AADC inhibition, but to an ability of NSD 1034 to stimulate DA synthesis. In addition, under certain conditions NSD 1034 also has a DA releasing action, like amphetamine. It is proposed that NSD 1034 and amphetamine stimulate DA synthesis and release by a common mechanism. The low value of DA synthesis rate, obtained when measured as DOPA accumulation after NSD 1015, is due to a substantial efflux of DOPA from the brain. The efflux of DOPA is equally large after NSD 1034 but the loss is compensated for by an increase in DOPA synthesis.

5-Hydroxytryptophan↗