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Biomedical subjects

A Carlsson

Publications and source records attributed to A Carlsson.

At least 91 records · Page 5Linked to original sources
PubMed1996

On the importance of hydroxyl groups in the polar head-group of nonionic surfactants and membrane lipids.

In this review properties of natural membrane lipids and surfactants synthesized from natural substances, such as paraffin chain alcohols and carbohydrates, are compared with those of synthetic surfactants of the polyoxyethylene type. Special attention is paid to the characteristic solution properties of nonionic surfactants with hydroxyl groups as the hydrophilic moiety, including alkyl glyceryl ethers and alkyl glucosides and maltosides, which are compared with those with oxyethylene groups. The major properties of the hydrophilic moiety are lipophobicity and hydrophilicity. Lipophobicity is an important property of oil-soluble surfactants, in particular for the polyoxyethylene alkyl ether type of surfactants where a too high lipophobicity may result in solubility in water.

Carbohydrate Sequence↗
PubMed1996

Incorporation of proteins in sphingomyelin-water gel phases.

Sphingomyelin from bovine milk and water form lipid gel phases at room temperature. A sample was used which incorporated of about 55% water, and X-ray diffraction data indicate an aqueous layer thickness of about 28 Angstrom. In order to accommodate proteins in the gel phase, the aqueous layer thickness was increased by solubilizing sodium palmitate into the sphingomyelin bilayer. In this way the gel phase could take up about 80% water. The incorporation of lysozyme, beta-lactoglobulin, and alpha-lactalbumin, was followed and the protein concentration for phase separation to occur was determined. It was found that the degree of incorporation was dependent on the salt concentration, thus the protein used was extensively dialysed. The amount of protein which can be dissolved in the thin aqueous layer of the gel phase was suggested to be limited by the dimensions of the layer. These are likely to be reduced as a consequence of the osmotic stress exerted by the 'outside' solution phase at high enough protein concentration.

Animals↗
PubMed1996

Migration of porous press-fit cups in hip revision arthroplasty. A radiostereometric 2-year follow-up study of 60 hips.

The migration of 60 press-fit cups fixed with screws was evaluated by radiostereometric analysis for 2 years in 57 patients revised because of aseptic loosening. The mean proximal migration of the cup center increased continuously up to 0.36 mm (range, 0.0-1.6 mm), whereas the migration in the other directions reached a level at 0.3 to 0.4 mm after 6 months. Mean rotations of less than 1 degree were recorded. Factors influencing motions were cup size, use of bone-grafts, and position of the cup center in the vertical and horizontal directions. Compared with previous stereoradiographic studies of cemented revisions, the migration of the press-fit cup was smaller, however, still higher than previously reported for uncemented cups of the same design used in primary surgery.

Adult↗
PubMed1996

Social function after cervical hip fracture. A comparison of hook-pins and total hip replacement in 47 patients.

47 patients with a cervical hip fracture Garden 3 or 4 and fully ambulatory before the fracture, were randomized to either fixation with Hansson hook-pins (24 patients, median age 79 years) or to a Charnley hip replacement (23 patients, median age 80 years). The patients were followed for 2 years. Social function was evaluated using a standard questionnaire. There were no postoperative deaths and no significant differences in hospital stay. 9/24 patients treated with hook-pins developed healing complications and 2 dislocations occurred in the THR group. After 1 and 2 years, fewer patients treated with hip replacement used outdoor walking aids; they were also more likely to do their own shopping. Hip replacement is a good choice when treating healthy older people with displaced cervical hip fractures, when primary mortality is expected to be low and the risk of healing complications after nailing is high.

Activities of Daily Living↗
PubMed1995

A comparison of six weeks with six months of oral anticoagulant therapy after a first episode of venous thromboembolism. Duration of Anticoagulation Trial Study Group.

BACKGROUND: The optimal duration of oral anticoagulant therapy after a first episode of venous thromboembolism is still a matter of debate. METHODS: We performed a multicenter trial comparing six weeks of oral anticoagulant treatment with six months of such therapy in patients who had a first episode of venous thromboembolism. Anticoagulant therapy consisted of warfarin or dicumarol. Of the 902 patients enrolled, 5 were later excluded because they had congenital protein C deficiency; 443 were randomly assigned to receive six weeks of oral anticoagulant therapy with a targeted international normalized ratio (INR) of 2.0 to 2.85, and 454 were randomly assigned to receive six months of such therapy. The initial diagnoses were confirmed by means of venography in cases of deep-vein thromboses (n = 790) and with perfusion-ventilation scanning or angiography in cases of pulmonary embolism (n = 107); recurrences were confirmed in the same way. RESULTS: After two years of follow-up, there had been 123 recurrences of venous thromboembolism that met the diagnostic criteria, 80 in the six-week group (18.1 percent; 95 percent confidence interval, 14.5 to 21.6) and 43 in the six-month group (9.5 percent; 95 percent confidence interval, 6.8 to 12.2). The odds ratio for recurrence in the six-week group was 2.1 (95 percent confidence interval, 1.4 to 3.1). There was no difference in mortality or the rate of major hemorrhage between the six-week and six-month groups. CONCLUSIONS: Six months of prophylactic oral anticoagulation after a first episode of venous thromboembolism led to a lower recurrence rate than did treatment lasting for six weeks. The difference between the two groups occurred between 6 weeks and 6 months after the start of treatment, and the rates of recurrence remained nearly parallel for 1 1/2 years thereafter.

Anticoagulants↗
PubMed1995

Structure-activity relationships in the 8-amino-6,7,8,9-tetrahydro-3H-benz[e]indole ring system. 1. Effects of substituents in the aromatic system on serotonin and dopamine receptor subtypes.

A series of 1-, 3-, and 4-substituted analogs to the potent 5-HT1A against 8-(dipropylamino)-6,7,8,9-tetrahydro-3H-benz[e]indole-1-carbaldehyde (5) were prepared and tested in vitro at 5-HT1A, 5-HT1D alpha, 5-HT1D beta, D2, and D3 receptors and in vivo for agonist activity in the 5-HTP and DOPA accumulation assays in reserpine-pretreated rats. Some of the compounds were resolved. The substituents used in the 1-position were chosen from a principal component analysis (PCA) plot constructed from both tabulated variables and variables calculated by semiempirical methods (PM3) and molecular mechanics software (MMX). Among the analogs prepared, some, e.g., compound 21, were equipotent to compound 5 with respect to 5-HT1A effects. All compounds were more or less selective for the 5-HT1A receptor, but many of the compounds displayed higher affinities for 5-HT1D alpha than for 5-HT1D beta receptors.

Animals↗
PubMed1995

In vivo activity of tyrosine hydroxylase in rat adrenal glands following administration of quinpirole and dopamine.

Using adrenal dopamine as indicator we have previously obtained evidence that quinpirole and several other agonists on dopamine D2-like receptors acutely stimulate the synthesis of adrenal catecholamines. In the present study we measured the effect of quinpirole and dopamine on the hydroxylation of tyrosine in the adrenals, using the method of DOPA (3,4-dihydroxyphenylalanine) accumulation following the administration of the inhibitor of aromatic L-amino acid decarboxylase NSD 1015 (3-hydroxybenzylhydrazyne). In view of the large amounts of catecholamines in the adrenal tissue samples, this necessitated a modification of the method for analysing DOPA. Both quinpirole and dopamine significantly enhanced the rate of DOPA accumulation in the adrenals, indicating stimulation of adrenal tyrosine hydroxylase. The effect of dopamine was blocked by domperidone, a dopamine D2 receptor antagonist that penetrates poorly into the central nervous system. Thus the effect of dopamine, which itself penetrates poorly into the central nervous system, was presumably mediated peripherally. Similarly epinine, i.e. the N-methyl derivative of dopamine, appeared to enhance adrenal catecholamine synthesis, as indicated by an elevated adrenal dopamine level. The data support the view that stimulation of peripherally located dopamine D2-like receptors can enhance the rate of adrenal catecholamine synthesis by stimulating the activity of tyrosine hydroxylase.

Adrenal Glands↗
PubMed1995

Synthesis and evaluation of pharmacological and pharmacokinetic properties of monopropyl analogs of 5-, 7-, and 8-[[(trifluoromethyl)sulfonyl]oxy]-2-aminotetralins: central dopamine and serotonin receptor activity.

In order to explore further the structure-activity relationships of serotonergic and dopaminergic ligands, a series of enantiopure 5-, 7-, or 8-triflate (-OTf)-substituted 2-(monopropylamino)-tetralins have been synthesized and evaluated in in vitro binding and in vivo biochemical and behavioral assays in rats. Consequently, the 8-OTf-substituted compound R-(+)-6 was found to be a potent and selective 5-HT1A (5-hydroxytryptamine) receptor agonist inducing a full-blown 5-HT syndrome in normal rats, while the corresponding 5-OTf-substituted compound S-(-)-12 was found to be a preferential dopamine (DA) autoreceptor agonist. A partial 5-HT syndrome was also observed for S-(-)-12, while the corresponding R-(+)-12 was found to be inactive at the DA and 5-HT receptors both in vitro and in vivo. Compounds 6 and 12 were found to be major urinary metabolites following oral administration of their dipropyl analogs (2 and 13, respectively). Thus 6 was proposed to be the metabolite responsible for the full-blown 5-HT syndrome seen after oral (but not subcutaneous) administration of 2. Similarly, 12 was proposed to be the metabolite responsible for the partial 5-HT syndrome seen after oral (but not subcutaneous) administration of 13. The bioavailability of R-(+)-6 (7.6 +/- 1.1%) appeared to be slightly lower than that of 2 (11.2 +/- 5.2%), although the in vitro metabolism of R-(+)-6 appeared to be slower than that of 2. Therefore first-pass metabolism was not thought to be the reason for the lower bioavailability of R-(+)-6, as compared to 2.

Animals↗
PubMed1995

Acute dopaminergic influence on plasma adrenaline levels in the rat.

This study was aimed at in vivo characterisation of the possible role of dopamine receptors in the modulation of adrenaline release from the adrenal medulla in rats. Quinpirole (0.3, 1 and 3 mg/kg s.c., 30 min), an agonist at dopamine D2-like receptors induced a statistically significant increase not only in adrenal dopamine but also in plasma and heart adrenaline levels. The effects of the lowest dose of quinpirole were blocked by domperidone (5 mg/kg s.c., 150 min). Implantation of catheters followed by blood sampling appeared to be a stressful procedure, inducing itself an elevation of adrenal dopamine and of heart adrenaline by 100 and 250%, respectively. To explore the possibility of determining the plasma levels of adrenaline without blood sampling, regression modelling was performed by means of partial least squares regression (PLS) using treatment and levels of heart adrenaline and adrenal dopamine as predictor variables. The selected variables were found to be good predictors of plasma adrenaline levels. Accordingly, the increase in adrenal dopamine and heart adrenaline levels following administration of the dopamine autoreceptor agonist, talipexole, and the classical non-selective dopamine receptor agonist, apomorphine, were interpreted as indicators of the increased adrenomedullary adrenaline release. Neither of the dopamine D2 receptor antagonists used, i.e. domperidone, supposed to have only peripheral effects, nor raclopride, had significant effects on adrenal dopamine and heart adrenaline. Our results support the presence of peripherally located dopamine D2-like receptors, capable of acutely stimulating not only the synthesis of catecholamines, but also the release of adrenaline from adrenals in the conscious rat.

Adrenal Medulla↗
PubMed1995

Crucial role of the accumbens nucleus in the neurotransmitter interactions regulating motor control in mice.

Previous work, based on systemic drug administration, has shown that neurotransmitter interactions between dopaminergic, adrenergic, glutamatergic and cholinergic systems are involved in locomotor control in mice. In an attempt to identify the target sites in the brain of these interactions, we have started a series of experiments, where the drugs are administered intracerebrally in mice. The locomotor threshold doses of the competitive NMDA antagonist AP-5 and the noncompetitive NMDA antagonist MK-801 were investigated by means of local application in the accumbens nucleus of monoamine-depleted and monoaminergically intact mice, respectively. The threshold dose of AP-5 was lower in depleted than in intact animals, whereas the threshold dose of MK-801 was lower in monoaminergically intact than monoamine-depleted mice. The locomotor effects of AP-5 and the AMPA-kainate receptor antagonist CNQX were registered in monamine-depleted mice after local application in the accumbens or entopeduncular nucleus (= medial pallidum). Both AP-5 and CNQX stimulated locomotor activity in the accumbens, but had no effects in the entopeduncular nucleus. We have previously shown synergistic interactions with regard to locomotor stimulation in monoamine-depleted mice, between an NMDA antagonist and an alpha 2-adrenoceptor agonist or a dopamine D1 agonist (all drugs given systemically). In the present study the alpha 2-adrenoceptor agonist alpha-methylnoradrenaline was applied intracerebrally in combination with a subthreshold dose of MK-801 given intraperitoneally: Locomotor stimulation was produced after alpha-methyl-noradrenaline injection into the accumbens nucleus, but not after injection into the dorsal striatum, prefrontal cortex or thalamus. Likewise, local application of the D1 agonist SKF 38393, in combination with a subthreshold dose of MK-801 given intraperitoneally, point to an important role of the accumbens nucleus in motor control. Previous experiments based on systemic drug administration have also shown a synergistic interaction between a muscarine antagonist and an alpha 2-adrenoceptor agonist in monoamine-depleted mice. Local application of the muscarine antagonist methscopolamine, in combination with the alpha 2-adrenoceptor agonist clonidine given intraperitoneally, showed that the striatum, in this case both the ventral and dorsal parts of the striatum, is an important target for the muscarine antagonist. Unilateral injection of AP-5 into the accumbens nucleus of mice induces rotational behaviour: Previous findings have shown that the rotation is ipsilateral in monoaminergically intact animals, whereas monoamine-depleted animals rotate contralaterally. In addition, these findings have shown that dopamine D2 receptor stimulation seems to determine whether AP-5 will induce ipsilateral or contralateral rotation. In the present study we report further evidence for a crucial role of the D2 receptor in this respect. Finally, the rotational effects of AP-5 injected into the dorsal striatum or hippocampus were investigated: As after AP-5 application into the accumbens nucleus, monoaminergically intact mice rotated ipsilaterally, whereas monoamine-depleted animals rotated contralaterally, following AP-5 application in the dorsal striatum or the hippocampus. The present data show that the accumbens nucleus has an important role in motor control. Both glutamatergic, muscarine cholinergic, dopaminergic and alpha-adrenergic systems are involved in the control of motor functions in the accumbens nucleus.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1995

Migration of uncemented, long-stem femoral components in revision hip arthroplasty. A 2-8 year clinical follow-up of 45 cases and radiostereometric analysis of 13 cases.

We reviewed after 48 (24-90) months the clinical results in 45 cases of revision hip arthroplasties where an uncemented, long-stem femoral prosthesis (BIAS, Zimmer) had been used. A subgroup of 13 cases was followed with radiostereometric analysis (RSA) for 2 years. 3/45 cases had been revised, another 12 had unsatisfactory pain scores. The median Harris score was 69 (26-99). 12/13 stems migrated; 11 subsided 4.1 (0.4-7.9) mm, and 8 migrated posteriorly 2.9 (1.9-9.6) mm. The poor clinical results and large migrations speak against the use of this prosthesis in revision hip arthroplasty.

Adult↗
PubMed1995

Does tranexamic acid reduce blood loss in knee arthroplasty?

In a retrospective study of 179 total knee arthroplasties, 70 patients received tranexamic acid (Cyklokapron, Kabi Pharmacia, Uppsala, Sweden) before the tourniquet was released to reduce postoperative blood loss. A group of 109 patients who underwent surgery before this treatment was introduced served as controls. Multiple regression analysis showed that the average postoperative blood loss was 340 mL less in treated patients compared with controls. Blood transfusions were reduced from 2 to 0 units (median values). Complications did not differ between the two groups apart from the number of postoperative hematomas.

Aged↗
PubMed1995

Neurocircuitries and neurotransmitter interactions in schizophrenia.

This review describes an attempt to widen the perspective on schizophrenia and to go beyond the dopamine hypothesis. In recent animal experiments corticofugal glutamatergic pathways have emerged as powerful regulators of a variety of subcortical mechanisms, where the dorsal and ventral striatum appear to play a major role in feedback loops controlling a thalamic filter function. These loops appear to be important regulators of wakefulness and psychomotor activity. A deficient filter function will lead to an overload of sensory input to the cerebral cortex and hyperarousal and may ultimately cause breakdown of the integrative capacity of the cerebral cortex and psychosis. Both negative and positive feedback loops appear to be driven by corticofugal glutamatergic pathways, and deficient functions of these loops may cause or contribute to the positive and negative symptomatology of schizophrenia, respectively. In addition to dopamine and glutamate, several other neurotransmitters, including gamma-aminobutyric acid, noradrenaline, serotonin and acetylcholine, appear to play an important role in psychomotor activity and psychotogenesis. Behavioural and biochemical animal models illustrate the interplay between the various neurotransmitters in these respects.

Animals↗
PubMed1994

Behavioral and neurochemical data suggest functional differences between dopamine D2 and D3 receptors.

In an in vitro model for mitogenic activity in cloned Chinese hamster ovary (CHO) cells expressing rat dopamine D2 or D3 receptors, the EC50D2/EC50D3 ratios for the agonists, apomorphine, (+)-3-hydroxy-N-n-propyl-phenylpiperidine ((+)-3-PPP), quinpirole, R-(+)-7-hydroxy-2-(di-n-propylamino)tetralin (R-(+)-7-OH-DPAT) and pramipexole (SND919) were found to be 0.36, 0.41, 1.3, 3.7 and 7.0, respectively. In locomotor activity experiments with actively exploring rats, the more dopamine D3 preferring agonists, R-(+)-7-OH-DPAT and pramipexole, were most efficacious to reduce locomotion. The hypoactivity was also observed at doses that did not affect brain dopamine synthesis rate (DOPA accumulation) or release (measured in in vivo dialysis experiments). In contrast, for apomorphine, (+)-3-PPP and quinpirole there was a closer correlation between doses that reduced exploratory activity and doses that reduced brain dopamine release and synthesis. The present data support the hypothesis that the functional dopamine D3 receptor is a postsynaptic receptor inhibitory on rat locomotion.

Analysis of Variance↗
PubMed1994

6,7,8,9-Tetrahydro-N,N-di-n-propyl-3H-benzindol-8-amines. Derivatives as potent and orally active serotonin 5-HT1A receptor agonists.

Derivatives and isosteric derivatives of the potent 5-HT1A agonist 8-(di-n-propylamino)-6,7,8,9- tetrahydro-3H-benz[e]indole-1-carbaldehyde (5) were prepared and evaluated in vivo and in vitro for serotonergic and dopaminergic activity. The 1-cyano analog 8 was found to be almost equipotent to 5 and the previously described 2-cyano derivative 6, while a 1-chloro and 1-(1,1,1-trifluoroethyl) substituent (9 and 10, respectively) formed less potent derivatives. The isosteric 6,7,8,9-tetrahydro-1H-benz[g]indoles 4 and 12-15 showed surprisingly low affinity or activity at both serotonergic and dopaminergic systems. The interpretations of these results by means of drug-receptor interactions at the 5-HT1A subtype are discussed. Compounds 6 and 8 were found to have high oral bioavailability in the rat (63% and 54%, respectively).

Animals↗