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Biomedical subjects

A Björk

Publications and source records attributed to A Björk.

At least 19 recordsLinked to original sources
PubMed2000

Inhibition of autoimmune disease by the immunomodulator linomide correlates with the ability to activate macrophages.

Linomide is a potent immunomodulator that has been shown to inhibit autoimmunity in several animal models of autoimmune disease, including experimental autoimmune encephalomyelitis (EAE). Linomide's mechanism of action is unknown, however, it has been suggested to modulate the function of antigen presenting cells (APC) and that this may account for the inhibition of autoimmune disease. In this study we have been able to show that Linomide treatment of SJL/N mice upregulates the cell surface expression of several activation markers on macrophages and B cells. Thus, we found the following markers, expressed as a % of control, to be significantly upregulated following Linomide treatment; MHC class II (260%), Ly-6A/E (520%), CD11a (280%), CD54 (190%) and CD80 (200%) on macrophages and Ly-6A/E (250%) and CD11a (150%) on B cells. The duration and dosage of Linomide required to obtain these effects is similar to those required for EAE inhibition. Several Linomide analogues were made by the introduction of structural modifications into the Linomide molecule, resulting in a number of compounds with varying effects on EAE. We found a linear relationship between the compound's ability to inhibit EAE and its ability to upregulate MHC class II on macrophages (p<0.001), such that compounds which were able to inhibit EAE also upregulated MHC class II expression, whereas those that did not inhibit EAE were unable to do so. These results suggest that drug-mediated activation of distinct APC functions may be protective in autoimmunity.

Adjuvants, Immunologic↗
PubMed2000

Measurements of ECP in serum and the impact of plasma coagulation.

Serum measurement of ECP (eosinophil cationic protein) is used as an indication of eosinophil activation in diseases such as asthma. The levels are dependent on sample handling, since a certain amount of ECP is released during storage. The mechanisms that induce this in vitro release are not known, but are supposed to be related to the coagulation process. The aim of this study was to investigate this further. ECP was measured in EDTA plasma and serum at 22 and 37 degrees C from healthy individuals and patients with asthma and allergy. The serum levels of ECP increased with temperature. Recalcification of citrated plasma in the presence of granulocytes with increasing concentrations of Ca(2+) showed a dissociation between the levels of ECP and the occurrence of coagulation. Further experiments indicated that plasma coagulation is not of any importance for the degranulation of eosinophils, nor did the addition of platelets or mononuclear cells affect the ECP levels. Incubations of granulocytes with fresh or frozen plasma and Ca(2+) suggested the existence of a freezing labile factor in plasma, necessary for the degranulation of healthy eosinophils, but not for allergic/asthmatic eosinophils. Further experiments with pure eosinophils indicated the existence of factors in serum and plasma which facilitate ECP secretion of an active, temperature-dependent nature. We conclude that the raised ECP levels in serum, as compared to EDTA plasma, are unrelated to the coagulation process, but are due to the continuous secretion ex vivo of ECP from active eosinophils. This process is time and temperature dependent and may be facilitated by eosinophil-activating components in the extracellular environment.

Asthma↗
PubMed1997

Interaction of the novel antipsychotic drug amperozide and its metabolite FG5620 with central nervous system receptors and monoamine uptake sites: relation to behavioral and clinical effects.

Behavioral, biochemical, and electrophysiological studies suggest that amperozide affects mesolimbic and mesocortical dopamine neurotransmission. The receptor binding profile of amperozide is discussed and related to behavioral and clinical, i.e., antipsychotic, effects of the drug. As previously reported, amperozide displayed high affinity for serotonin 5-HT2A receptors (Ki = 16 nmol/L), and moderate affinity for striatal dopamine D2 (Ki = 540 nmol/L) and cortical alpha 1-adrenergic receptors (Ki = 172 nmol/L). In the present study amperozide displayed low affinity for several serotonin receptor subtypes as well as for the dopamine D4 receptor transfected in COS7 cells (Ki D4.2 = 769 nmol/L and Ki D4.4 = 384 nmol/L). Amperozide was very weak or did not interact with several other receptor species including adrenergic, histaminergic, muscarinic, benzodiazepine, gamma-aminobutyric acid, amino acid, opiate, and Ca channels; however, amperozide was found to compete for [3H]paroxetine binding for the serotonin transporter in the nanomolar range (Ki = 49 nmol/L). In vitro and in vivo binding potency of amperozide correlates best with behavioral effects, indicating 5-HT2A antagonism, although serotonin uptake inhibition may contribute to the effects of amperozide on dopamine neurotransmission. The metabolite of amperozide, FG5620, displayed 5-10 times lower pharmacologic activity than amperozide. These properties of amperozide may suggest that the antipsychotic effects of amperozide are mediated by 5-HT2A receptors, although 5-HT uptake inhibition and alpha 1-adrenergic receptor-mediated effects may be considered, particularly at higher doses.

Animals↗
PubMed1996

Alcohol intake in high alcohol drinking (HAD) rats is suppressed by FG5865, a novel 5-HT1A agonist/5-HT2 antagonist.

Both the 5-HT2 antagonist, FG5606 (amperozide), and the mixed 5-HT1 agonist/5-HT2 antagonist, FG5893, attenuate significantly the volitional intake of alcohol in the cyanamide treated rat. The purpose of the present study was to investigate the effect on alcohol drinking in the selectively bred, high alcohol drinking (HAD) rat of a new and novel 5-HT1A agonist/5-HT2 antagonist, FG5865 (2-[4-[4,4-bis(4-fluorophenyl)butyl]-1-piperazinyl]-3-pyridinecarboxy lic acid methyl ester), which shares pharmacological properties with FG5893. Initially, a standard three bottle preference test for water vs. 3% to 30% alcohol solutions was given over 11 days to determine the maximally preferred concentration for each animal. Then water and this solution, which ranged between 9% and 20% with an overall mean absolute intake of 6.3 +/- 0.5 g/kg per day, was offered over three consecutive 4-day test sequences: (1) predrug control; (2) SC injections b.i.d. of either 1.0 mg/kg or 2.5 mg/kg FG5865 or saline control vehicle; and (3) postdrug. Whereas saline failed to alter alcohol consumption of the HAD rats, FG5865 caused a significant dose dependent reduction by as much as 75% in the intakes of alcohol during its administration in terms of both g/kg (p < 0.01) and proportion of alcohol to total fluid intake (p < 0.01). During the administration of 2.5 mg/kg FG5865, alcohol drinking declined from 6.5 +/- 0.3 g/kg to as low as 2.3 +/- 0.2 g/kg per day. Neither the body weight of the HAD animals nor their intake of food was affected by either dose of FG5865. These results uphold the concept that the 5-HT1A and 5-HT2 receptor subtypes in the brain play a part in the aberrant drinking of alcohol of the HAD rat. Because FG5865 influences the activity of serotonergic neurons in the mesolimbic system of the rat, it is envisaged that the drug suppresses alcohol drinking by way of its action on these neurons.

Alcohol Drinking↗
PubMed1995

Intramatrix rotation--the frontal bone.

Intramatrix rotation during growth and development was studied by 2-D cephalometric technique with the use of metallic implants in the frontal bone in five patients at the Centre for Craniofacial Anomalies, Malmö General Hospital. The analysis of the frontal bone in the five patients showed rotations of the corpus inside the periosteal matrix from 1 to 9.5 degrees in the mid-sagittal plane. The essential conclusion of these observations is that an intramatrix rotation takes place during the development of the frontal bone. This observation will stimulate further studies of its nature, amount, and direction.

Adolescent↗
PubMed1994

Preclinical pharmacology of FG5893: a potential anxiolytic drug with high affinity for both 5-HT1A and 5-HT2A receptors.

The effects of FG5893 were evaluated by several different methods; rats were used as experimental animals. Receptor binding studies revealed that FG5893 (2-(4-(4,4-bis(4-fluorophenyl)butyl)-1-piperazinyl)-3-pyridinecarboxy lic acid methyl ester) binds with high affinity to both 5-HT1A (Ki = 0.7 nM) and 5-HT2A receptors (Ki = 4.0 nM) but has only low affinity for the 5-HT2C receptor (Ki = 170 nM). FG5893 dose dependently reduced body temperature, and this effect was inhibited by pretreatment with (+/-)-pindolol. FG5893 (0.1 mg/kg) significantly inhibited head twitch behaviour induced by DOI (1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane) and FG5893 was also a potent inhibitor of ultrasound vocalization in rat pups (0.3 mg/kg) and of a passive avoidance response (0.1 mg/kg) in mature animals. FG5893 inhibited the cage-leaving response and induced part of the 5-HT behavioural syndrome, but only at very high doses (5 and 10 mg/kg, respectively). At increased doses (1 mg/kg), FG5893 also elicited corticosterone release and reduced the immobility time in the forced-swim test (1 mg/kg). Together, these data indicate that the mixed 5-HT1A receptor agonist/5-HT2A receptor antagonist FG5983 is a potent stimulator of presynaptic 5-HT1A receptors but is less active at the postsynaptic site. FG5893 had potent anxiolytic-like effects both on separation-induced ultrasound vocalization in rat pups and on a passive avoidance response. At increased doses, FG5893 possessed an antidepressant-like property.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1994

Endovascular treatment of a spinal arteriovenous malformation in a 21-month-old boy.

Reports of spinal arteriovenous malformations in children are rare. This case report describes a 21-month-old boy whose first symptom was attacks of abdominal pain, followed gradually by neurological symptoms. The diagnosis was made using magnetic resonance imaging and spinal angiography, and the patient was successfully treated with embolization.

Aortography↗
PubMed1994

In the search for a novel class of antipsychotic drugs: preclinical pharmacology of FG5803, a 1-piperazinecarboxamide derivative.

Comparative studies of the 1-piperazinecarboxamide derivative 4-[3-(4-fluorobenzoyl)propyl]-N-cyclohexyl-1-piperazinecarboxamide hydrochloride (FG5803) were made with clozapine and haloperidol. Receptor studies revealed that FG5803 potently and selectively bound to the serotonin type 2A receptors (Ki = 13 nM). FG5803 inhibited 5-hydroxytrophan- and 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane-induced head twitches, which indicated potent in vivo serotonin type 2A receptor antagonism. FG5803 caused an acute activation of the tuberoinfundibular dopamine neurons and produced only a transient rise in plasma prolactin. In behavioral studies in rats, FG5803 showed strong antagonistic action on presynaptic dopaminergic autoreceptors but only weak postsynaptic dopamine D2 blockade. FG5803 was not cataleptogenic and did not antagonize amphetamine-induced stereotypies. FG5803 was active in the reduction of aggressive behavior and spontaneous exploratory behavior in mice and rats. Therefore, FG5803 is expected to constitute a promising approach in the search for a novel class of antipsychotic drugs that have a broader spectrum of activity and fewer adverse effects than the conventional, antidopaminergic antipsychotics.

Animals↗
PubMed1993

Amperozide, a 5-HT2 antagonist, attenuates craving for cocaine by rats.

Amperozide, a novel 5-HT2 receptor antagonist with little affinity for the dopamine receptor, suppresses the intake of alcohol in rats without affecting food intake or inducing other side effects. Because of these actions, amperozide was examined for its efficacy on the oral preference by the rat for a solution of cocaine. In this study, rats were selected for their voluntary consumption of at least 10 mg/kg of cocaine per day in a two-choice paradigm. A solution of 0.02% to 0.06% cocaine plus 0.03% saccharin in water was offered to each animal simultaneously with a solution of only 0.03% saccharin in water. The consumption of food and both fluids, as well as body weight, was recorded daily for three successive periods: 4 days of pretreatment baseline; 3 days during injections of either amperozide or the saline vehicle solution; and 4 days postinjections. Amperozide was administered SC twice daily in a dose of 0.5, 1.0, or 2.5 mg/kg. The volitional intake of cocaine was significantly reduced not only during the 3-day period of injections of amperozide but also during the 4-day posttreatment period. Amperozide exerted little or no effect on the intake of food or on body weight. Radioligand binding experiments confirmed that amperozide has at least a twentyfold greater affinity for 5-HT2 receptors in the frontal cortex of the rat, as compared to striatal DA1 and DA2 receptors, with the proportion value similar to that of the 5-HT2 receptor antagonist, ritanserin.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

5-HT2 receptor blockade by amperozide suppresses ethanol drinking in genetically preferring rats.

Previously, it was shown that the unique diphenylbutylpiperazinecarboxamide derivative, amperozide (FG 5606), inhibits the volitional drinking of ethanol induced in the rat by the inhibitor of aldehyde dehydrogenase, cyanamide. In this study, the efficacy of this long-acting psychotropic agent and potent 5-hydroxytryptamine2 (5-HT2) receptor antagonist was examined in the genetic line of ethanol-preferring (P) and -nonpreferring (NP) rats. In both lines, the pattern of drinking of ethyl alcohol was determined by a standard preference test for 3-30% ethanol vs. water. Then, the maximally preferred concentration of ethanol was determined for each individual, which ranged from 9-15% for P rats and 9-13% for NP animals. After a 4-day predrug test, either the saline control vehicle or amperozide was administered SC b.i.d. at 1600 and 2200 h. The drug was given over a 3-day period in one of three doses: 0.5, 1.0, or 2.5 mg/kg. The intake of ethanol of P rats was reduced significantly in a dose-dependent manner in terms of both absolute g/kg and proportion of ethanol to water during injections of amperozide. The same doses of amperozide had no effect on the low intake of ethanol in NP rats. The saline control vehicle also did not alter the consumption of ethanol of P or NP rats. Further, neither the consumption of food nor level of body weight was affected by amperozide either during or after its administration. These results demonstrate that in the individual predisposed genetically to drink ethanol amperozide exerts a palliative effect on the aberrant preference for ethanol consumed in a pharmacologically significant amount. Presently, dopaminergic and serotonergic synapses in the brain are implicated in the genetic differences in the patterns of ethanol consumption that distinguish the P from the NP line of rats. Because amperozide influences the functional activity of both dopaminergic and serotonergic neurons in the mesolimbic system, it is envisaged that the drug attenuates ethanol drinking by way of its direct action on these neurons.

Alcohol Drinking↗
PubMed1992

Selective reduction by the 5-HT antagonist amperozide of alcohol preference induced in rats by systemic cyanamide.

This investigation was undertaken to determine the effect of a unique psychotropic agent on the volitional drinking of alcohol induced pharmacologically in the rat by an inhibitor of aldehyde dehydrogenase. Following administration of cyanamide in a dose of 10 mg/kg twice daily for 3 days, the pattern of drinking of ethyl alcohol was determined in each of 12 Sprague-Dawley rats by means of a standard preference test for 3-30% alcohol vs. water. Then, each rat was offered water and its maximally preferred concentration of alcohol, which ranged from 7-15%. After a 4-day predrug test, either the saline control vehicle or the diphenylbutylpiperazinecarboxamide derivative, amperozide, was administered subcutaneously. The injections of amperozide were given b.i.d. at 1600 and 2200 h over 3 days in a dose of 0.5, 1.0, or 2.5 mg/kg. The intake of alcohol during the sequence of amperozide injections was significantly reduced in a dose-dependent manner in terms of both absolute g/kg and proportion of alcohol to water intake, whereas the saline control vehicle was without any effect on alcohol consumption. Although the highest dose of amperozide reduced the total intake of fluid due to the sharp decline in alcohol drinking, neither the consumption of food nor level of body weight was affected by any dose of the drug either during or after its administration. Because amperozide acts centrally on the synaptic activity of dopaminergic and serotonergic neurons in limbic system structures, it is envisaged that the drug ameliorates the aberrant drinking of alcohol by virtue of a direct effect on either one or both of these classes of neurons.(ABSTRACT TRUNCATED AT 250 WORDS)

Alcohol Drinking↗
PubMed1992

Long-term effect of rapid maxillary expansion studied in one patient with the aid of metallic implants and roentgen stereometry.

The articulatory displacement of maxillary bones during and after rapid maxillary expansion (RME) was studied with metallic implants and roentgen stereometry (RSA) for 3653 days in a girl aged 12 at start of treatment. She had a narrow upper dental arch with anterior crowding and a normal incisor relationship, and a normal sagittal molar relationship with bilateral cross-bite. Three implants were inserted in each maxillary bone and they remained stable in the bones during the 10-year observation period. In the 3-D analysis of the articulatory displacement, the left maxillary bone was studied in relation to the right bone in three periods: RME (23 days), retention (108 days) and follow-up (3522 days). Extensive relapse of rotations as well as translations was found and the long-term effect of RME was limited. In our opinion the relapse was caused mainly by the resistance to deformation from circum-maxillary sutures and surrounding soft tissue matrix, and inadequate bone formation in the involved sutures. As is generally known in clinical oral orthopaedics, changes obtained by short-term simple mechanical interference with a complex biological system tend to reverse spontaneously. Thus, the rationale for RME treatment may be seriously questioned.

Biomechanical Phenomena↗
PubMed1991

Effects of amperozide in schizophrenia. An open study of a potent 5-HT2 receptor antagonist.

Ten male inpatients (aged 29 +/- 6 years) with a DSM-III diagnosis of schizophrenia participated in a 4-week open dose escalation study of amperozide, a novel 5-HT2 receptor antagonist. The maximum daily dose of amperozide was 20 mg. A close dose-plasma concentration relationship showed considerable interindividual variation in the steady-state plasma levels at a given dose. Approximately equal concentrations of amperozide and its metabolite, N-deethylated amperozide, were seen in plasma. The prolactin levels were not increased during amperozide treatment. No changes occurred in hematological or other laboratory parameters. ECG showed changes in T-wave morphology and a prolongation of the QTc time. One patient was withdrawn from the trial due to aggravation of psychotic symptoms, and two patients had a brief, temporary discontinuation of the drug due to somatic illness. Six patients were improved during amperozide treatment, as assessed by the Clinical Global Improvement Scale. Among the responders the total CPRS was reduced by a mean of 64% and total BPRS score by a mean of 46%. Mild tremor was a frequent side effect, but other extrapyramidal symptoms were rare. Nausea was seen in six patients and of a more pronounced character in one patient. In general, the severity of the side effects increased with increasing doses of amperozide.

Adult↗
PubMed1991

[Achondroplasia: craniofacial growth in a boy followed for a 10-year period analyzed by an implant method].

The present report deals with the description of craniofacial morphology and growth in an achondroplastic boy followed for a 10-year period. The methods included roentgencephalometry, and metallic implants were inserted in both jaws. Thereby it became possible to differentiate between displacement of the jaws and their bone remodelling. The study showed that in the patient analyzed the primary cause of the worsening of the sagittal jaw relationship was to be found in the growth disturbances of the cranial base rather than in the growth of the jaws per se.

Achondroplasia↗
PubMed1991

Facial growth rotation--reflections on definition and cause.

The phenomenon of growth rotation of the jaws during facial development is examined by means of profile roentgencephalometric analysis of a male subject followed from age 4 years to adulthood, with reference to metallic implants and stable natural bony structures. The rotation of the corpora of the jaws, termed total rotation, and its components, matrix and intramatrix rotation, are defined. A description is given of the compensatory remodelling process. The concept of facial growth rotation as essentially a primary phenomenon is supported by a report of an identical facial rotation pattern in growing Macaca mulatta, suggesting that facial growth rotation is common in primates.

Adolescent↗
PubMed1990

A comparative study of two different methods of measuring stature and the velocity of growth in children and adults.

The stretched technique of measuring the stature described by Tanner (1962) is claimed to minimize the variation which occurs during the course of the day. This study examines differences in the calculated growth rate for the stretched and the conventional methods. The data for the analysis was drawn from a larger longitudinal growth study (Björk, 1968), where the stature of the individuals was measured both by the conventional unstretched technique according to Hrdlicka (1939) and by the stretched method described by Tanner (1962). A total of 84 individuals (48 boys and 36 girls) representing a total of 805 measurements of stature for each of the methods were included in the study. The individuals were measured annually until adult age, after which the measurements were made at intervals of 2-5 years. This represents a total range of 6-32 years of age, with individual series of observation varying over a period of 4-16 years. In accordance with the definition the stature measured by the stretched technique was significantly higher than measured by the unstretched method. The growth rate, however, at any age level did not differ significantly for the two methods and the variability in growth rate was the same. It was concluded that the unstretched technique gives similar values for estimating growth-velocity curves as does the stretched technique.

Adolescent↗