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Biomedical subjects

J Hietala

Publications and source records attributed to J Hietala.

At least 109 records · Page 6Linked to original sources
PubMed1988

Chronic treatment with SCH 23390, a selective dopamine D-1 receptor antagonist, decreases dopamine metabolism in rat caudate nucleus.

Chronic treatment (18 days; 0.1 and 0.5 mg/kg per day) with the selective dopamine (DA) D-1 receptor antagonist, SCH 23390, significantly reduced the concentration of homovanillic acid (HVA) and the ratios of HVA/DA and DOPAC/DA in the nucleus caudatus of the rat but did not change the metabolism of DA in the prefrontal cortex, substantia nigra or the A10 area. Furthermore, the concentrations of noradrenaline were dose dependently decreased in the A10 area during SCH 23390 treatment. It is concluded that chronic DA D-1 receptor blockade causes changes in the metabolism of DA similar to those caused by classical neuroleptics.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1988

Effects of DA-1- and DA-2-dopamine antagonists on apomorphine-induced inhibition of peripheral sympathetic neurotransmission.

1. Apomorphine, a dopamine receptor agonist, caused a dose-dependent inhibition of the electrically induced increase in diastolic blood pressure in the pithed rat. The anti-apomorphine effects of a range of dopamine antagonists with different DA-1/DA-2 selectivities were evaluated to characterize the dopamine receptor subtype(s) involved in this response. 2. Selective DA-2 antagonists domperidone and (-)-sulpiride and combined DA-2/DA-1 antagonists haloperidol, fluphenazine and (+)-sulpiride were active in this model, whereas the DA-1 antagonist SCH 23390 and the alpha-2 adrenoceptor antagonist idazoxan (RX-781094) were inactive. The rank order of potency of the dopamine antagonists was domperidone greater than fluphenazine greater than or equal to (-)-sulpiride greater than or equal to haloperidol greater than (+)-sulpiride much greater than SCH 23390. (-)-Sulpiride was about 25 times more potent than the (+)-isomer. 3. The observed antagonist profile suggests that the apomorphine-induced inhibition of neurogenic vasoconstriction in the pithed rat is mediated via dopamine receptors of the DA-2 subtype. The sympatho-inhibitory dopamine receptors in the cat heart have similar pharmacological characteristics. 4. The dopamine antagonists were devoid of influences on the vasoconstrictor response to electrical stimulation in the absence of apomorphine, whereas idazoxan potentiated it. This provides evidence against the participation of dopamine receptors in the modulation of the vasoconstrictor response to sympathetic stimulation in the pithed rat model.

Animals↗
PubMed1988

Decrease in the number of rat brain dopamine and muscarinic receptors after chronic alcohol intake.

The effect of 32 weeks' alcohol treatment on the number and affinity of dopamine and muscarinic receptor sites in rat striatum were measured using 3H-spiperone and 3H-quinuclidinylbenzilate (3H-QNB) as radioligands. The number of dopamine receptor sites was 38 per cent and the number of muscarinic receptor sites 36 per cent lower in the alcohol group than in control rats. The differences in receptor affinities were less marked. In conclusion, a long-term alcohol intake with rather moderate doses seems to induce a pronounced down-regulation in dopamine and muscarinic receptor systems in rat striatum.

Alcoholism↗
PubMed1988

Effect of prophylactic acetaminophen administration on reaction to DTP vaccination.

The effectiveness of acetaminophen in preventing post-vaccination fever was studied in a double-blind randomized manner. Healthy five-month-old infants vaccinated with diphtheria-tetanus-pertussis (DTP) or DTP-inactivated polio vaccine were randomly allocated to receive either placebo (n = 130) or 75 mg of acetaminophen (n = 133) four hours after the vaccination. Rectal temperatures of the infants were measured in the post-vaccination evening and next morning by the parents. The mean values of rectal temperatures were equal in both groups, i.e. 37.6 degrees C, both in the evening and in the morning. No significant difference was found in the occurrence of other minor adverse reactions. Antibody titres to diphtheria and tetanus toxoids and pertussis bacteria of the placebo (n = 25) and acetaminophen (n = 34) groups did not differ significantly from each other. It is concluded that acetaminophen in a single dose schedule is ineffective in decreasing post-vaccination fever and other symptoms.

Acetaminophen↗
PubMed1988

Antigen detection in the diagnosis of viral infections.

The value of viral antigen detection from nasopharyngeal secretion (NPS) by enzyme immunoassay (EIA) in everyday clinical practice was evaluated in 570 children hospitalized because of infections. NPS-EIA gave a positive result in 32% of all cases. Virus isolation was positive in the NPS in 25%, virus isolation in stool samples in 14%, and virus serology in 28% of the cases. NPS-EIA was superior for detecting adenovirus, respiratory syncytial (RS) and parainfluenza viruses. In a series of 124 patients in whom 3 methods were compared, NPS-EIA was the only positive method in 48% of all findings positive for adenoviruses, in 73% for RSV, and in 58% for parainfluenza viruses. Antigen detection by NPS-EIA markedly increased the diagnostic potential in everyday clinical practice, especially for viral respiratory diseases.

Adenovirus Infections, Human↗
PubMed1988

Comparison of neuroleptic binding characteristics in rat striatum and renal cortex.

The binding characteristics of the dopaminergic ligand, 3H-spiperone, were compared in renal cortical and striatal membrane homogenates of the rat. This ligand labelled a single class of high affinity binding sites in striatum with an apparent dissociation constant (Kd) of 0.13 nM and a maximal number of binding sites (Bmax) of 890 fmol/mg protein representing D-2 receptors. In the renal cortex, 3H-spiperone identified a population of binding sites with a Bmax and a Kd of 310 fmol/mg protein and 5.1 nM, respectively. The antagonist displacing profile suggests the dopaminergic nature of the renal binding site. The affinities of dopamine antagonists for the peripheral 3H-spiperone binding site were in general in the micromolar range while the affinities of D-2 or D-2/D-1 dopamine antagonists in striatum were in the nanomolar range. Moreover, these sites showed differential stereoselectivity for (+)- and (-)-isomers of sulpiride. In conclusion, the presence of a D-2/DA-2 dopamine receptor population in renal cortex could not be confirmed. The pharmacological properties of the peripheral 3H-spiperone binding site are also different from the DA-1 receptor but seem to resemble those previously reported for dopamine receptors in sympathetic ganglia and adrenal medulla.

Animals↗
PubMed1987

Noradrenergic and dopaminergic effects of nomifensine in healthy volunteers.

Intravenous doses (100 mg in 20 minutes) of the antidepressant drug nomifensine, administered to male volunteers, increased heart rate and blood pressure, elevated the plasma levels of norepinephrine and its metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG), and powerfully stimulated growth hormone release and inhibited the secretion of prolactin. Oral nomifensine, either as a single 100 mg dose or as a similar dose after 2 weeks' treatment with the drug (150 mg/day), caused none of the above effects. This was in line with the limited (less than 30%) oral bioavailability of the active, unconjugated form of the drug, estimated in the same subjects. MHPG in plasma was slightly but consistently reduced by the 2 weeks' treatment, suggesting reduced turnover of norepinephrine. The observed clinical effects of nomifensine are compatible with uptake inhibition and augmented release of norepinephrine and dopamine and possibly direct agonistic effects on dopamine receptors. Although nomifensine was withdrawn from the market because of immunologic complications, it serves as a model compound of a new pharmacologic class of antidepressants, devoid of many of the disturbing side effects of the tricyclic drugs.

Adult↗
PubMed1987

Alterations in peripheral and central dopamine receptor sensitivity after subchronic treatment with fluphenazine and sulpiride.

The effects of subchronic treatment with the antipsychotic drugs fluphenazine and sulpiride on the sensitivity of peripheral neuronal dopamine receptors and central dopamine autoreceptors were evaluated. The ability of apomorphine, a dopamine agonist, to inhibit electrically induced sympathetic vasoconstriction in pithed rats, and apomorphine-induced inhibition of spontaneous locomotor activity in awake rats were used as indices of peripheral and central dopamine receptor sensitivity, respectively. A single injection of fluphenazine decanoate, a long-acting preparation of fluphenazine, enhanced the central locomotor inhibitory effect of low doses of apomorphine 4 and 6 weeks after drug administration, whereas the antidopaminergic effect on peripheral dopamine receptors was prolonged and persisted at least up to 6 weeks. In another set of experiments rats were treated with fluphenazine hydrochloride and sulpiride for 10 days and subsequently challenged with apomorphine after various withdrawal times. Both antipsychotic drugs augmented the inhibitory effect of apomorphine in the periphery, although the time courses of the potentiation were different. Both treatments also enhanced the locomotor inhibitory effect of apomorphine. These results are in line with our previous finding that long-term treatment with dopamine antagonists can induce neuronal dopamine receptor up-regulation also outside the central nervous system. Peripheral neuronal dopamine receptors thus show similar adaptive responses to long-term blockade as central dopamine autoreceptors, and may serve as a useful experimental model in studies concerned with mechanisms of dopaminergic autoregulation in the central nervous system.

Animals↗
PubMed1986

Presynaptic dopamine receptors in the pithed rat: characterization with apomorphine and comparison with central dopamine autoreceptors.

Apomorphine, a dopamine agonist with high affinity for presynaptic dopamine receptors, caused dose-dependent inhibition (10-300 micrograms/kg intravenously) of the stimulation-induced increase in diastolic blood pressure in the pithed rat. This effect of apomorphine could be antagonized with (-)-sulpiride or haloperidol but not with yohimbine or atropine, indicating the involvement of inhibitory dopamine receptors. The alpha-1-adrenoceptor mediated pressor response to phenylephrine (5 micrograms/kg intravenously) was not significantly attenuated by apomorphine. The sensitivity of peripheral presynaptic dopamine receptors was then studied in the cardiovascular system of rats treated subchronically with haloperidol (2 mg/kg, twice daily intraperitoneally for 10 days). The inhibition of sympathetic vasoconstrictor responses exerted by apomorphine was found to be enhanced after subchronic haloperidol treatment suggesting the development of presynaptic dopamine receptor supersensitivity in the periphery. In addition, the previously reported supersensitivity of central dopamine autoreceptors to low doses of apomorphine could be confirmed in behavioural experiments.

Animals↗
PubMed1986

Effects of intravenous and subcutaneous administration of apomorphine on the clinical symptoms of chronic schizophrenics.

The effects of apomorphine, a stimulant of dopamine autoreceptors, were studied in 12 chronic schizophrenics on neuroleptic treatment; both subcutaneous and intravenous administration were used. Apomorphine has been reported to have therapeutic effects in previous studies but, we were not able to confirm any significant and specific differences in psychotic symptoms or tardive dyskinesia scores with apomorphine administration, compared with placebo. These results do not support the importance of dopamine autoreceptors in the regulation of schizophrenic and dyskinetic symptoms in chronic neuroleptic-treated patients.

Adult↗
PubMed1985

Effects of apomorphine on blood levels of homovanillic acid, growth hormone and prolactin in medicated schizophrenics and healthy control subjects.

Two doses of apomorphine (0.005 mg/kg as a subcutaneous injection and 0.015 mg/kg as a 90 min i.v. infusion), and corresponding placebo treatments, were administered to 11 chronic medicated schizophrenic patients and to 8 healthy control subjects. The purpose of the study was to asses the usefulness of drug-induced alterations in the concentration of homovanillic acid (HVA) in plasma as indicators of dopamine autoreceptor sensitivity in the central nervous system. Growth hormone and prolactin in serum were also measured and used as indicators of postsynaptic dopaminergic drug effects. In the control subjects, i.v. apomorphine increased growth hormone in serum from 1.8 +/- 0.2 to 28.3 +/- 4.6 ng/ml and reduced prolactin by 57 +/- 7%. In the patients, apomorphine caused only weak neuroendocrine effects. HVA in plasma was not affected by apomorphine in either group of subjects. The results for growth hormone and prolactin indicate that postsynaptic dopamine receptors in the tubero-infundibular system are antagonized to a considerable degree also during chronic treatment with neuroleptics. The lack of effect of apomorphine on HVA levels suggests that HVA in plasma is not a sensitive indicator of the inhibition of dopamine release caused by small doses of apomorphine and mediated through dopamine auto-receptors. Supersensitivity of this class of receptors could not be demonstrated in our patients, which contrasts with some earlier results.

Adult↗
PubMed1985

Neuroendocrine aspects in monitoring of dopaminergic drugs in man.

The role of plasma homovanillic acid together with serum growth hormone and prolactin in monitoring of central dopaminergic activity was studied in healthy volunteers and psychiatric patients. Both dopaminergic agonists (apomorphine, bromocriptine and L-dopa) and antagonists (metoclopramide) were used. Apomorphine, bromocriptine and metoclopramide, which exerted the expected neuroendocrine effects caused no significant changes in plasma homovanillic acid. L-dopa increased the concentration of homovanillic acid in plasma. This effect was not potentiated by L-deprenyl, although L-dopa-induced growth hormone secretion was increased after L-deprenyl premedication. There was negative correlation between growth hormone secretion and the increase of plasma homovanillic acid after L-dopa. This indicates that the L-dopa-induced rise in plasma homovanillic acid probably reflects more peripheral L-dopa metabolism than central dopaminergic activity. Thus, it seems that plasma homovanillic acid cannot be regarded as a sensitive indicator of drug-induced changes in central dopaminergic activity in man, which is in contrast with some earlier findings in animals.

Apomorphine↗
PubMed1983

Serum iron, copper, zinc, ferritin, and ceruloplasmin after intense heat exposure.

Twelve voluntary adult subjects twice took a 30-min sauna bath, at a temperature of 80 degrees C with a 30-min rest between each, every 12 h for 1 week. Measurements of serum iron, copper, zinc, ferritin and ceruloplasmin were performed before the experiment, after the first and second 30 min in the sauna and at the end of the week. The first two sauna baths did not significantly change the concentrations of the trace elements measured. After the week the mean serum copper concentration had decreased from 15.0 (SD 1.7) mumol x 1-1 to 13.5 (SD 2.0) mumol x 1-1 (p less than 0.02). The mean zinc concentration decreased from 13.8 (SD 2.4) mumol x 1-1 to 9.8 (SD 1.8) mumol x 1-1 (p less than 0.001) during the week of the experiment. At the beginning of the study period two subjects had zinc concentrations below the reference values and after the week nine subjects had zinc concentrations below the reference values. The concentration of serum ferritin decreased from 142.2 (SD 103) micrograms x 1-1 to 111.3 (SD 89) micrograms x 1-1 (p less than 0.02) whereas the values of ceruloplasmin remained unchanged. Our findings confirm the earlier suggestion that heavy exposure to heat can cause a loss of some trace elements, especially zinc.

Adolescent↗
PubMed1983

An association between epileptic seizures and increased serum bacterial antibody levels.

Increased serum levels of a variety of bacterial antibodies were more common in unselected patients with recent epileptic seizures than in healthy control subjects (17/29 versus 2/31; p less than 0.001). In most of these cases no infections were recognized clinically or bacteriologically. Although infections have been considered as one of the possible provocations for the manifestation of epileptic seizures, the demonstrated strong association may give a new approach to the pathogenetic mechanisms of epileptic seizures or may mean a nonspecific immune response. The explanation for the higher antibody titers in epileptic patients and their etiologic significance are uncertain, but these results also suggest that epileptic seizures may very often be triggered by bacterial infections even when no clinically apparent bacterial infection has been recognized.

Adult↗
PubMed1982

Acute phase proteins, humoral and cell mediated immunity in environmentally-induced hyperthermia in man.

The effects of repeated hyperthermia, caused by a Finnish sauna bath over 1 week, on the serum levels of some acute phase reactant proteins and on both humoral and cell-mediated immunity on twelve healthy young volunteers are presented. The mean rise in rectal temperature during each 30-min period in the bath was about 1.3 degrees C. Heat exposure caused significant increases in the serum concentrations of two of the acute phase reactant proteins, alpha1-antitrypsin (from a mean value of 1.8 (0.1) to 1.9 (0.2) g X l-1, p less than 0.01) and transferrin (from a mean value of 36.9 (3.4) to 38.3 (4.4) mumol X l-1, p less than 0.05), but no changes occurred in immunoglobulins or cell-mediated immunity. These findings suggest that environmentally induced hyperthermia can initiate the acute phase reaction associated with fever.

Adolescent↗
PubMedDate not supplied

Adaptations and resistance of zooplankton to stress: effects of genetic, environmental, and physiological factors.

The ability of a species to adapt to stress factors such as exposure to toxicants depends to a large extent on the presence of individuals that are able to respond to the exposure in a successful way. Several strategies can be employed to cope with different stress factors. Investments on growth and reproduction, for instance, can be varied to meet the requirements of the environment. Large individuals generally have a high resistance against stress, but a large body size is often achieved at the cost of other characteristics. In the present study, the resistance of several clones of Daphnia to different stress factors, such as toxic cyanobacteria, a predator released chemical, and starvation, was investigated. The focus was on interactions among different factors and whether observed responses can be regarded as evolved adaptations for the different conditions.

Adaptation, Physiological↗
PubMedDate not supplied

Age-related dopamine D2/D3 receptor loss in extrastriatal regions of the human brain.

Loss of dopamine D2-like receptors in the striatum has been associated with both normal human aging and impairment of cognitive and motor functions in the elderly. To investigate whether there are age-associated changes in dopamine D2 and D3 receptor subtypes (D2/3Rs) outside the striatum, a D2/3R selective high-affinity radioligand [11C]FLB 457 was used in positron emission tomography (PET) examinations for 24 normal healthy male subjects (age range 19-74 years). Significant age-related declines of D2/3Rs were detected in all the brain regions studied: the anterior cingulate cortex (decline of 13% per increase of a decade in age, P < 0.001). the frontal cortex (11%, P < 0.001), the lateral temporal cortex (10%, P < 0.001), the hippocampus (10%, P < 0.01), the medial temporal cortex (9%, P < 0.001), the amygdala (7%, P < 0.01), the medial thalamus (6%, P < 0.001) and the lateral thalamus (5%, P < 0.01). The rate of D2/3R decline was significantly faster in the frontal cortex as compared to the medial temporal cortex (P < 0.05, Bonferroni corrected) and as compared to the medial thalamus (P < 0.05, Bonferroni corrected). These results indicate that the previously demonstrated age-related decline in striatal dopamine D2 receptors extends to several extrastriatal regions in normal human males. Further, the rate of D2/3R decline may be faster in the frontal cortex as compared to the temporal and thalamic regions.

Adult↗