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Biomedical subjects

R Malmgren

Publications and source records attributed to R Malmgren.

At least 37 records · Page 2Linked to original sources
PubMed1987

Serotonin uptake inhibition during treatment of depression with nortriptyline caused by parent drug and not by 10-hydroxymetabolites.

Treatment of endogenous depression with nortriptyline (NT), at a daily dose of 150 mg, resulted in a pronounced improvement of seven of ten patients investigated. The concentration of the norepinephrine metabolite HMPG in cerebrospinal fluid (CSF) decreased by 29% (P less than 0.01) after 3 weeks of treatment. There was no significant effect of treatment on the serotonin and dopamine metabolites 5-HIAA and HVA. In previous larger materials, however, a decrease of 5-HIAA in CSF has been demonstrated. Platelets from the patients showed an increase in Km for serotonin uptake in response to NT treatment. The IC50 value of NT for serotonin uptake inhibition was 940 nM, while the corresponding value of the major metabolite of NT, i.e. E-10-OH-NT, was much higher (6700 nM). Thus, during treatment, the parent drug and not the metabolite was responsible for the serotonin uptake inhibition in platelets. There was a close correlation between Km and the plasma concentration of NT after 1 week of treatment (r = 0.88, P less than 0.01) but not after 3 weeks of treatment (r = 0.48; ns). There was no uniform effect of NT treatment on Vmax. It is concluded that clinical NT treatment results in uptake inhibition not only in norepinephrine but also in serotonin neurons.

Adult↗
PubMed1987

Effect of a carbohydrate-rich diet, low in protein-tryptophan, in classic and common migraine.

Because serotonin, released from platelets, has been suggested to initiate migraine, a decreased platelet serotonin content, attained by a reduced intake of serotonin and the serotonin precursor tryptophan, might be beneficial. In the brain, however, increased serotonin levels, achieved by a high carbohydrate intake, are probably favourable. Seven migraine patients (four with classic, three with common migraine) were placed on a carbohydrate-rich diet, low in protein-tryptophan. Three of the four classic migraineurs, but none of the common migraineurs, noted improvement in their migraine. Platelet serotonin uptake was within the normal range both before and at the end of the diet period. The apparent positive effect in the classic migraineurs could be due to a reduced intake of migraine-precipitating foods and/or increased brain serotonin levels.

Adult↗
PubMed1987

Platelet serotonin uptake and effects of vitamin B6-treatment in premenstrual tension.

The platelet serotonin uptake kinetics was studied in 19 women with premenstrual tension syndrome (PMS) and 19 age-matched symptom-free controls during the pre- and postmenstrual phases. Both groups exhibited stable Vmax and Km values at the two phases of the menstrual cycle. There were no differences between the two groups regarding the level of Vmax and Km, respectively. The effect of season (p less than 0.001), with lowered values of Vmax during spring compared to corresponding values during the later half of the year, was identical in both groups. A tendency to lowered Vmax values in the follicular phase in women with PMS during spring may indicate that women with PMS are more vulnerable to developing depressive episodes during this period than symptom-free women. The blood platelet count in whole blood was decreased in the luteal phase in the control group but remained stable in the PMS group. The effect of vitamin B6 on clinical symptoms and the platelet serotonin uptake during the luteal phase was investigated in a double-blind crossover design. Vitamin B6 treatment did not significantly improve the PMS symptoms. There was no effect of treatment on Km. Vmax increased significantly in response to treatment (F = 9.6; p less than 0.001) in both groups, but there was no significant difference between placebo and vitamin B6.

Adult↗
PubMed1986

Determination of platelet-megakaryocyte regeneration time in painters occupationally exposed to organic solvents.

An improved method for the determination of the regeneration time of human platelets is presented. The platelet-megakaryocyte regeneration times of painters exposed to organic solvents (n = 5; age range 23-48 years) were compared with a reference group (n = 5; age range 23-46 years) not occupationally exposed to solvents. After purification and extraction of the samples, they were analysed by high-performance liquid chromatography. The results showed that the painters have a shorter regeneration time (range 4.4-5.2 days) than the reference group (range 5.2-6.9 days) and indicate that solvent exposure may be associated with an increase in platelet turnover in man.

Adult↗
PubMed1986

ATP-secretion occurs as an initial response in collagen induced platelet activation.

The time course and degree of collagen induced platelet shape change, aggregation and ATP-secretion in citrated human platelet rich plasma was monitored with a lumi-aggregometer. Onset of ATP-secretion was measurable within seconds after collagen challenge and always distinctly before onset of shape change. In absence of platelet aggregation, the degree of collagen stimulation was correlated to onset of secretion, the secretion rate and onset of subsequent shape change. It is concluded that the secretion originated from the collagen-adherent platelets. Oral aspirin [1000 mg] did neither delay onset of secretion nor reduce the final amounts of ATP indicating that formation of TxA2 is not a necessary prerequisite for dense granule secretion during the primary activation process. EDTA and EGTA decreased the initial secretion rate, but may have interfered with the adhesion process. Micromolar concentrations of verapamil and yohimbine also reduced secretion, while the effect of theophylline was 100 times weaker. The results suggest that the primary activation process is vulnerable at the alpha-receptor-level and that the initial ATP-secretion requires Ca2+-entry rather than intra-platelet Ca2+-mobilization.

Adenosine Diphosphate↗
PubMed1986

Circadian rhythm of serotonin transport in human platelets.

The circadian rhythm of serotonin active transport in human platelets was investigated in ten healthy men, aged 27-35 years. Blood was collected at 08.00, 14.00, 20.00, 02.00 and 08.00 hours the next morning. Simultaneous evaluation of the mean platelet volume, platelet distribution width, platelet distribution skewness and platelet number in whole blood was performed. Km and Vmax for serotonin transport varied considerably among individuals over 24 h. However, the mean values and distribution of these kinetic parameters were reduced at 02.00 hours. All platelet size or number parameters were stable and normal over 24 h; therefore, the reduction in mean Km and Vmax values at 02.00 h is not related to morphological platelet differences but either to platelet intrinsic factors or plasmatic variables. Knowledge of the affinity and capacity of serotonin transport throughout the diurnal cycle is important for future comparisons with depressed patients as well as other hormonal rhythms in patients and healthy humans.

Adult↗
PubMed1986

Platelets and biogenic amines. 2. Indications for a discrete low affinity uptake mechanism shared by norepinephrine and 5-hydroxytryptamine in human platelets.

The uptake of norepinephrine (NE) by human platelets at 10(-9)-5 X 10(-4) M of labelled amine concentration was investigated. At physiological concentrations of NE the uptake was unsaturable and could not be inhibited by imipramine or ouabain. At NE concentrations between 25 and 485 microM the uptake also comprised a saturable component that could be completely blocked by imipramine and partly by ouabain. The saturable uptake of NE had an apparent Km of 273 +/- 50 microM and a Vmax of 0.19 +/- 0.05 pmole/10(6) platelets/min. The affinity of NE (IC50) for the 5-HT transporting carrier was 2.3 mM, 8.4 times higher than the apparent Km for saturable NE uptake. The affinity of 5-HT (IC50) for the NE-transporting carrier was 5.8 microM, 5.8 times higher than the apparent Km for saturable 5-HT transport. Imipramine and norzimeldin were equipotent inhibitors of saturable NE uptake, the potency being of the same degree as that for saturable 5-HT uptake. The tertiary amine amitriptyline was 6 times more effective in inhibiting saturable NE uptake than its demethylated product nortriptyline. Nortriptyline and its hydroxylated E- and Z-isomers had a stronger inhibitory effect on saturable NE uptake than on uptake of 5-HT. The results suggest that human platelets possess two separate amine-transporting carriers, both having their highest affinity for 5-HT. The one with the lowest affinity for 5-HT can also accept NE as a substrate. The human platelet does not possess a high-affinity uptake system for NE comparable to that in adrenergic tissue.

Blood Platelets↗
PubMed1986

Lowered glutathione-peroxidase activity in asthmatic patients with food and aspirin intolerance.

In analogy with findings from animal experiments, people with low glutathione-peroxidase (GSH-Px) activity could be expected to have altered sensitivities to effects of drugs, chemicals and possibly food. We have investigated GSH-Px activity in 12 patients with intrinsic asthma and food and aspirin intolerance. Ten of the 12 patients had very low or low GSH-Px activity and the frequency of low GSH-Px activity in this group was statistically significant (P less than 0.001) compared with the control material of age- and sex-matched healthy individuals. Our finding of lowered GSH-Px activity in patients with aspirin intolerance may indicate the involvement of hitherto unknown mechanisms in the pathogenesis of asthmatic disorders.

Arachidonic Acid↗
PubMed1985

Effects of different anticoagulants on human platelet size distribution and serotonin (5-HT) induced shape change and uptake kinetics.

The effect of collecting blood with disodium ethylene diamine tetraacetate (EDTA), citrate (NAC) or acid sodium citrate-dextrose (ACD) as anticoagulants on platelet count and size distribution was investigated. No difference between the three preparations regarding platelet count was found in whole blood. Preparation of platelet-rich plasma (PRP) significantly reduced the platelet count in NAC-PRP (p less than 0.01) to a value of 288 X 10(9)/l compared to those of 365 X 10(9)/l and 368 X 10(9)/l in EDTA and ACD blood respectively. A significant shift in the platelet size in EDTA-PRP towards larger cell volumes was observed. There were no differences in the size distribution pattern between NAC-PRP and ACD-PRP in spite of the differences in platelet count. Platelet 5-HT uptake kinetics in EDTA-PRP showed a 50 per cent reduction in both Km and Vmax compared to that in ACD-PRP. The study shows that the receptor mediating 5-HT induced shape change has a direct opposite pH dependence than that of the 5-HT carrier. Interference of receptor-mediated responses in 5-HT uptake studies in human platelets is clearly minimized at a lowered pH. The finding is probably of importance in disorders associated with platelet hyperaggregability.

Adenosine Diphosphate↗
PubMed1985

The effects of citalopram (Lu 10-171) on the serotonin (5-HT) uptake kinetics in platelets from endogenously depressed patients.

The uptake kinetics of serotonin (5-HT) in platelets from eight patients with endogenous depression was determined in platelet rich plasma (PRP). From the uptake data the Scatchard correlation coefficient (r[S] ), Sips' index of heterogeneity (alpha), Km and Vmax (Lineweaver-Burk) were calculated. The measurements were performed before and after two weeks treatment with Citalopram, 1-(3-dimethylaminopropyl)-1-(p-fluorophenyl)-5-phtalan carbonitrile (Lu 10-171), a selective 5-HT uptake inhibitor. After two weeks treatment with Citalopram (5, 25 or 50 mg/day) a lowered platelet count in whole blood and PRP was observed and none of the patients had a measurable 5-HT uptake for which kinetic parameters (Km and Vmax, Lineweaver-Burk) could be calculated. However, all the patients but one improved significantly in Global score.

Adult↗
PubMed1985

Alaproclate a novel antidepressant? A biochemical and clinical comparison with zimeldine.

Clinical and biochemical effects of two selective 5-HT uptake inhibitors, zimeldine and alaproclate, were studied in 24 hospitalized patients with endogenous depression. According to a randomized parallel group design 14 patients were treated with zimeldine and 10 with alaproclate. The dosage of both zimeldine and alaproclate was 200 mg daily. For the evaluation of the clinical effect, Montgomery & Asberg Depression Rating Scale (MADRS) was used. Seven of 14 patients treated with zimeldine and seven of 10 treated with alaproclate improved. 5-HT uptake inhibition in patients' platelets and concentration of amine metabolites (5-HIAA, HVA, HMPG) in CSF were studied before and during treatment. After 3 weeks of treatment with zimeldine 5-HIAA and HMPG in CSF decreased significantly while HVA in CSF increased significantly. Zimeldine produced a significant 5-HT uptake inhibition in platelets. During treatment with alaproclate no significant change in amine metabolites concentration in CSF was found and there were no mean changes on 5-HT uptake inhibition in platelets.

Adult↗
PubMed1984

Platelets and biogenic amines. 1. Platelets are poor investigative models for dopamine re-uptake.

The uptake of 14C-dopamine (DA) by human platelets at 10(-7) -2.5 X 10(-4) M of labelled amine concentration was studied in human platelet-rich plasma. The total uptake could be resolved into two components, one of which was saturable and completely inhibited by 10(-5) imipramine and another which was unsaturable but temperature-dependent. The saturable uptake of DA had an apparent Km of 75 X 10(-6) M and Vmax of 1.34 pmol/10(6) platelets/min. The uptake of unsaturable DA was 1.33 pmol/10(6) platelets/min at 10(-4) M DA. Dopamine exerted a mixed non-competitive inhibition of the saturable 5-HT transport and vice versa. Thus the increase in Km was paralleled by a decrease in Vmax. The low-affinity transport of DA by the human platelets does not share any of the dopamine uptake characteristics found in neuronal tissue. The platelet therefore seems to be a poor model for the presynaptic function of the dopamine neurons.

Biogenic Amines↗
PubMed1984

Effect on the uptake kinetics of serotonin (5-hydroxytryptamine) in platelets from workers with long-term exposure to organic solvents. A pilot study.

Six workers from a paint industry were examined concerning the concentration of solvents in the breathing zone, the platelet count and kinetic uptake of serotonin [5-hydroxytryptamine (5-HT)], the serum concentration of calcium, potassium and sodium, and pH. The degree of exposure was found to be moderate. The results showed a decrease in platelet count in whole blood and platelet-rich plasma. The maximum uptake rate for serotonin in platelets (Vmax) was significantly increased compared to that of nonexposed subjects. No changes in the ionic concentration and pH of serum were observed. One worker was reexamined after a six-week period of nonexposure. Though the measured platelet variables were still aberrant, the values approached normal.

Adult↗
PubMed1983

Effects of dietary protein-tryptophan restriction upon 5-HT uptake by platelets and clinical symptoms in migraine-like headache.

Ten women with recurrent migraine-like headache, flush, urticaria and itching excoriations were put on a protein/tryptophan reduced diet. The 5-HT uptake kinetics in platelets, the frequency of headache attacks and skin symptoms were recorded. On customary food the 5-HT uptake kinetics were severely disturbed. On diet, the platelet 5-HT uptake was normalized and, in parallel, the migraine-like symptoms and skin manifestations were reduced. The parallel between the improvement in active 5-HT uptake by platelets and clinical symptoms during dietary protein/tryptophan restriction supports the idea that impairment of the 5-HT uptake in platelets is a contributory factor in the pathogenesis of migraine-like headache and other 5-HT related symptoms.

Adult↗
PubMed1983

Increased uptake of serotonin in platelets from car painters occupationally exposed to mixtures of solvents and organic isocyanates.

Twelve car painters occupationally exposed to mixtures of solvents and organic isocyanates were investigated concerning serotonin uptake in platelets. The data from the exposed workers were compared to data from a reference group consisting of 50 nonexposed volunteers. The mean platelet count in whole blood of the exposed workers was markedly lower than the corresponding value of the reference group. Three workers had values below the lower limit of the 95% tolerance interval of the referents. In both groups the serotonin transport strictly obeyed Michaelis-Menten's simple saturation kinetics. Nine of the twelve exposed workers had uptake rates which were significantly higher (p = 0.05) than those of the referents. The obtained data suggest that the present method may be used to reveal early organ damage, prior to the appearance of clinical symptoms, due to intermittent exposure to organic solvents and isocyanates.

Adult↗
PubMed1982

Defective serotonin (5-HT) transport mechanism in platelets from patients with endogenous and allergic asthma.

The kinetics of the 5-HT-uptake by platelets in platelet-rich plasma (PRP) and PRP diluted with autologous platelet-poor plasma (PRP/PPP) were determined in normal subjects, patients with asymptomatic exogenous asthma and those with symptomatic endogenous asthma. In normal subjects the 5-HT-uptake by platelets strictly obeyed Michaelis-Menten's kinetics. In patients with asymptomatic exogenous asthma, the active 5-HT-transport was moderately distorted in PRP and severely altered in PRP/PPP. Patients with symptomatic endogenous asthma exhibited already in PRP a dramatic transport disturbance. The alteration of the active 5-HT-transport was characterized by increasing uptake inhibition by rising 5-HT concentrations in plasma. This phenomenon could be due to changes in the platelet environment, defects in the platelet membrane or intrinsic platelet disorders. It is concluded that asthmatics have genetically or later acquired platelet disorder, which is more clearly observed in patients with symptomatic endogenous asthma than in those with asymptomatic exogenous asthma.

Adolescent↗