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Biomedical subjects

T Koskinen

Publications and source records attributed to T Koskinen.

At least 19 recordsLinked to original sources
PubMed2001

Studies on the involvement of the dopaminergic system in the 5-HT2 agonist (DOI)-induced premature responding in a five-choice serial reaction time task.

The present experiments investigated whether the enhanced premature (impulsive) responding induced by DOI, [(+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride], a 5-HT2A/2C receptor agonist, is mediated by activation of the dopaminergic system and if this effect of DOI occurs in the nucleus accumbens. Therefore, the effects of a dopamine (D1/2) receptor antagonist given alone or combined with DOI were examined on the performance of rats in a five-choice serial reaction time (5-CSRT) task. Secondly, the effects of DOI in nucleus accumbens core and shell were studied, in order to find the target brain area for DOI-induced premature responding. The results indicate that DOI (0.1 mg/kg, subcutaneously) increases the number of premature responses, as found previously. alpha-Flupenthixol (0.03 mg/kg), a D1/2 dopamine receptor antagonist, and raclopride (0.015 mg/kg), a D2 receptor antagonist, attenuated the DOI-induced enhancement in premature responding. SCH 23390 (0.005 mg/kg), a selective D1 receptor antagonist with little affinity to 5-HT2 receptors totally blocked the effect of DOI. Those doses of DA antagonists did not significantly decrease premature responding when given alone. On the other hand, higher doses of all of these dopamine antagonists increased the number of omissions and decreased the number of ITI hole responses. In contrast to subcutaneous administration, direct injections of DOI (1, 3, and 10 microg bilaterally) to the nucleus accumbens shell or core had no effect on premature responding. These results suggest that the activation of the dopamine system mediates, at least in part, the effect of a 5-HT2 agonist on premature responding, but the nucleus accumbens is not the primary site for this action.

Amphetamines↗
PubMed2000

Activation of 5-HT2A receptors impairs response control of rats in a five-choice serial reaction time task.

The present experiments investigated the effects of agents acting at serotonin (5-HT)-2 receptors on the performance of rats in a choice serial reaction time (5-CSRT) task in order to examine the role of 5-HT2 receptors in the modulation of attention and response control. The results indicate that DOI, [(+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride; 0.05, 0.1 and 0.2 mg/kg, subcutaneously], a 5-HT(2A/2C) agonist, slightly impaired the choice accuracy of the well performing rats and markedly increased their premature responding. DOI (0.05 and 0.1 mg/kg) had no effect on the latency to collect earned food pellets or to respond correctly, indicating that these lower doses of DOI did not reduce motivation for the food reward in this task. The selective effect of a low dose of DOI (0.1 mg/kg) on premature responding was completely blocked by ketanserin (0.2 mg/kg), a 5-HT2A antagonist, and ritanserin (0.3 mg/kg), a 5-HT(2A/2C) antagonist, but only partially blocked by a high dose of SER082 (1.0 mg/kg), a 5-HT2C antagonist. In contrast to DOI, mCPP, [1-(3-phenyl)piperazine; 0.05 and 0.15 mg/kg], a 5-HT2C agonist, had no effect on choice accuracy or premature responding, but it reduced behavioral activity and/or arousal as indicated by the decreased number of trials completed and increased the probability of omissions. SER082 (1.0 mg/kg) blocked the effects of mCPP on performance. These data suggest that the overactivation of 5-HT2A receptors impairs response control in a 5-CSRT task, whereas the overactivation of 5-HT2C receptors can affect behavioral activity and/or arousal state of the animals for this food rewarded task.

Adrenergic alpha-Antagonists↗
PubMed2000

The 5-HT(2) receptor activation enhances impulsive responding without increasing motor activity in rats.

The effects of 5-HT(2) receptor ligands on the performance of rats were investigated using a 5-choice serial reaction time (5-CSRT) task. Systemic administration of DOI (0.03 to 0.3 mg/kg subcutaneously [SC]), a 5-HT(2) receptor agonist, did not impair choice accuracy of well-performing rats under either baseline conditions or more demanding conditions of the task, in which the stimulus duration or intensity were reduced or the intertrial interval (ITI) was decreased. DOI (0.1 mg/kg or 0.15 mg/kg) increased premature responding (the probability of intertrial interval hole pokes) in all testing conditions, except under conditions of a short ITI when the rats did not make any hole responses. Ketanserin (0.1 to 0.3 mg/kg SC), a 5-HT(2A) receptor antagonist, had no marked effect on performance. When combined with ketanserin (0.2 mg/kg SC), however, DOI (0.1 mg/kg) did not increase premature responding. The lowest doses of DOI (0.05 and 0.1 mg/kg) that increase premature responding had no effect on open-field performance. Further, the effects of systemically administered DOI were not reproduced by bilateral administration of DOI into the anterior cingulate cortex. These data indicate that excessive activation of 5-HT(2A/2C) receptors interferes with response control rather than visual attention. Furthermore, the DOI-induced enhancement of impulsive responses are not due to locomotor hyperactivity, and the anterior cingulate cortex is not the primary site of action for this enhancement of premature responding.

Amphetamines↗
PubMed1999

Serum estrogen level, attention, memory and other cognitive functions in middle-aged women.

OBJECTIVE: To evaluate the relationship between serum estradiol level and cognitive processing efficiency and memory. METHODS: Sixty-three healthy women aged 45-65 years were recruited through a newspaper announcement. The subjects were divided into two subgroups (low-estrogen group, n = 37 and high-estrogen group, n = 26) according to their serum follicle stimulating hormone (FSH) and estradiol levels. In the high-estrogen group, estrogen was either endogenous or supplied by estrogen replacement therapy. Automatic and controlled cognitive processing and attentional resources were measured using CogniSpeed software, together with conventional tests of cognitive performance: similarities, digit span, digit symbol, block design, object naming and recall, paired word associates (PWA) recall, Benton visual retention and paced auditory serial addition test (PASAT). The Beck depression inventory was also assessed. RESULTS: Cognitive reaction speeds were similar in both groups. Women with low estrogen levels made more errors in the vigilance test (sustained attention, p = 0.040). There were no differences in short-term or long-term memory, or verbal, visual or working memory between the study groups. Older women were slower in the ten-choice reaction time (10-CRT) test (r = 0.25, p = 0.047) and made more errors in the test of suppressing attention (Stroop incongruence test; r = 0.34, p = 0.007) and in the sustaining attention test (vigilance test; r = 0.47, p < 0.001). Depression scores did not correlate with cognitive variables. CONCLUSIONS: Cognitive performance was well preserved in healthy middle-aged women. Cognitive speed, accuracy, attentional resources and memory did not show impairment with decline of serum estrogen level in this age group.

Attention↗
PubMed1997

Climacteric symptoms do not impair cognitive performances in postmenopause.

OBJECTIVE: To investigate whether information processing and attention performances are affected by climacteric vasomotor symptoms. METHODS: The study group comprised 66 healthy hysterectomized postmenopausal women. The subjects were divided into two subgroups (high symptomatic and low symptomatic) according to the quantity of climacteric vasomotor symptoms. Information processing was examined using CogniSpeed, a reaction time software that separates, for example, pure controlled processing and working memory from perceptual and motor components. Attention was examined by using visual and auditory tasks. The role of climacteric depression as a determinant of cognitive performance was evaluated by the Beck Depression Inventory and dividing subjects according to self-reported climacteric mood symptoms. The effects of serum oestrogen level and ageing on cognitive performances were also studied. RESULTS: Cognitive performances were similar in high symptomatic and low symptomatic women. On the Verification test younger women had shorter reaction times (P = 0.002) and on the Subtraction test they had fewer errors (P = 0.015) than older women. These tests required working memory and decision making. Accuracy in the tests of sustained and auditory attention worsened slightly with age. Cognitive performances neither correlated with scores on the Beck Depression scale nor with serum oestrogen level. Climacteric mood symptoms did not impair cognitive performance. CONCLUSIONS: Despite subjective complaints of memory impairment in association with climacteric vasomotor symptoms, our results did not support a direct cause-and-effect relationship. Thus, the minor deficits found in cognitive processing efficiency seem to be related rather to age than climacteric symptoms.

Aging↗
PubMed1995

Primary hypogonadism in females with infantile onset spinocerebellar ataxia.

We recently described an infantile onset spinocerebellar ataxia (IOSCA) in 19 Finnish patients. The classification of hereditary ataxias of unknown etiology is difficult because of the heterogeneity of these diseases. The clinical course of IOSCA is homogeneous. Ataxia, muscle hypotonia, athetosis, and loss of deep tendon reflexes in the legs appeared around the age of 1 year. Ophthalmoplegia and deafness were found by school-age, and sensory axonal neuropathy and optic atrophy by adolescence. An acute crisis with epilepsy was a late manifestation. The female patients had hypogonadism. In order to define the type of hypogonadism and to exclude other endocrine defects we measured serum concentrations of SHBG, DHEAS, prolactine, testosterone/estradiol, FSH and LH in postpubertal patients. ACTH, hCG and GnRH tests were performed to both pre- and postpubertal patients. Growth was analysed, and the brain and pituitary region were examined with magnetic resonance imaging (MRI). The estradiol values were low and FSH and LH values were high in the female patients, which indicates that the hypogonadism was of the hypergonadotropic type. The growth of the female patients was steady without a significant pubertal growth acceleration. The growth and pubertal development of the male patients were normal. The adrenal cortical and thyroidea functions were normal in all patients.

Adolescent↗
PubMed1995

Infantile-onset spinocerebellar ataxia: MR and CT findings.

PURPOSE: To report the MR and CT findings in a hereditary disease, infantile-onset spinocerebellar ataxia (IOSCA). METHODS: We studied the brains of 17 patients with infantile-onset spinocerebellar ataxia with CT and/or MR to determine the presence of cerebellar and brain stem atrophy and parenchymal lesions. RESULTS: Cerebellar cortical atrophy was seen in 13 patients. The degree of atrophy correlated with increasing age and clinical deterioration. Brain stem atrophy was seen in 8 patients. It was never severe, and the basis pontis was not flattened even in the most severe cases. Hyperintense lesions were noted within the white matter of cerebellum, in the dentate nuclei, and in the middle cerebellar peduncles in 3 patients. The upper cervical cord was seen in 9 patients and showed mild to moderate atrophy in 4. The basal ganglia and cerebral hemispheres were normal, except in 2 patients transient cortical and subcortical lesions developed during episodes of status epilepticus; mild cortical brain atrophy subsequently developed. CONCLUSION: The brain MR and CT findings of patients with infantile-onset spinocerebellar ataxia correspond to the neuropathologic entities of cerebellar cortical atrophy, olivopontocerebellar atrophy, and spinocerebellar atrophy. The appearance of the findings followed a uniform time sequence from cerebellar cortical atrophy in the early stage of the disease to olivopontocerebellar atrophy and spinocerebellar atrophy in the later stage. The severity of atrophy correlated with clinical deterioration.

Adolescent↗
PubMed1995

Random search for shared chromosomal regions in four affected individuals: the assignment of a new hereditary ataxia locus.

Infantile-onset spinocerebellar ataxia (IOSCA) is an autosomal recessively inherited progressive neurological disorder of unknown etiology. This ataxia, identified so far only in the genetically isolated Finnish population, does not share gene locus with any of the previously identified hereditary ataxias, and a random mapping approach was adopted to assign the IOSCA locus. Based on the assumption of one founder mutation, a primary screening of the genome was performed using samples from just four affected individuals in two consanguineous pedigrees. The identification of a shared chromosomal region in these four patients provided the first evidence that the IOSCA gene locus is on chromosome 10q23.3-q24.1, which was confirmed by conventional linkage analysis in the complete family material. Strong linkage disequilibrium observed between IOSCA and the linked markers was utilized to define accurately the critical chromosomal region. The results showed the power of linkage disequilibrium in the locus assignment of diseases with very limited family materials.

Age of Onset↗
PubMed1994

Sensory neuropathy in infantile onset spinocerebellar ataxia (IOSCA).

Infantile onset spinocerebellar ataxia with sensory neuropathy is a new, inherited multisystem disorder discovered in 19 Finnish patients. In order to define the neuropathy of the disease, we measured sensory nerve action potentials and nerve conduction velocities in 18 patients, and recorded somatosensory evoked potentials (SEP) in 10 patients and performed a sural nerve biopsy in 13 patients. The fixed and teased nerve fascicles were examined by light and electron microscopy, and the whole transverse section of a nerve fascicle was photographed and enlarged for morphometric measurements. Our investigation revealed an early onset, rapidly progressive axonal neuropathy: the sensory action potentials were decreased after the age of 2 and a severe loss of mainly large myelinated fibers was found.

Adolescent↗
PubMed1994

Infantile onset spinocerebellar ataxia with sensory neuropathy: a new inherited disease.

We report the clinical findings in 19 Finnish patients, including six pairs of siblings, with a new, early onset spinocerebellar ataxia. The slowly progressive clinical symptoms manifested between one and two years of age in previously healthy infants. The first manifestation of children at that age was clumsiness and loss of ability to walk. Ataxia, athetosis and muscle hypotonia with loss of deep tendon reflexes were discovered on clinical examination. By school age ophthalmoplegia and hearing loss were diagnosed, while sensory neuropathy developed by adolescence. In addition, an acute crisis with status epilepticus was a late manifestation. We found a marked decrease in sensory nerve condition velocities, a progressive loss of myelinated fibers in sural nerve specimen, and abnormal background activity in EEG with advancing age. The main finding in neuroradiological investigations was cerebellar atrophy. The occurrence of the disease in siblings and lack of manifestations in parents indicate recessive inheritance.

Adolescent↗
PubMed1994

Antidepressant efficacy and quality of life in depression: a double-blind study with moclobemide and fluoxetine.

The efficacy of moclobemide (300-450 mg/day) was compared with fluoxetine (20-40 mg/day) in a double-blind, multicentre study in 209 patients with new episodes of depression selected from 612 consecutive depressed patients representative of those consulting psychiatric services in Finland. Antidepressant efficacy was assessed with the Hamilton Depression Rating Scale (HDRS), Montgomery-Asberg Depression Rating Scale and Clinical Global Impression (CGI). The Medical Outcome Study Short-form General Health Survey (SF-20) and 15D Measure of Quality of Life were used to measure effectiveness in terms of health-related quality of life. Efficacy was evident with both drug treatments, with 67% in the moclobemide group and 57% in the fluoxetine group having a reduction in HDRS of more than 50%. Similarly, 77% of the patients in the moclobemide group and 67% in the fluoxetine group were assessed on the CGI as much better or very much better after 6 weeks of treatment. The most commonly reported adverse events were nausea, other gastrointestinal symptoms, nervousness, dizziness and sleep disorders. Nausea was significantly more common in the fluoxetine group and was found especially in women. Premature terminations of treatment were 18% in the moclobemide and 21% in the fluoxetine group. A significant change for the better in quality of life was found in both treatment groups, even at week 2 but especially after 6 weeks of treatment. Improvement was not only seen in dimensions measuring depression or mental health but also in other dimensions.

Adult↗
PubMed1994

Infantile onset spinocerebellar ataxia represents an allelic disease distinct from other hereditary ataxias.

Hereditary ataxias are a heterogeneous group of progressive neurodegenerative disorders characterized by symptoms and signs originating mainly in the CNS. A new representative of this disease group is infantile onset spinocerebellar ataxia, an autosomal recessively inherited syndrome so far reported only in the genetically isolated Finnish population. The etiology of hereditary ataxias still remains unknown, but the gene loci behind many of them have been mapped to different chromosomal regions. We have carried out linkage analyses with markers on the regions of the previously identified ataxia loci to determine whether the infantile onset spinocerebellar ataxia syndrome represents the same allelic disease as any of the previously identified hereditary ataxias. Here we report that the infantile onset spinocerebellar ataxias syndrome does not segregate with any of the markers closely linked to the other hereditary ataxias. Consequently, it represents a genetically distinct disease, the gene locus of which still has to be identified.

Age of Onset↗
PubMed1993

Moclobemide versus imipramine in depressed out-patients: a double-blind multi-centre study.

One hundred and twenty seven patients with major depressive episode were included in a double-blind, four-week, prospective, randomized, multi-centre parallel-group trial comparing moclobemide and imipramine. The dose of moclobemide was 150-525 mg/day and that of imipramine 50-175 mg/day; the mean daily doses during the last week of treatment were 307 mg and 100 mg of moclobemide and imipramine, respectively. The decrease of the total scores of the Hamilton Depression Scale (HDRS) as well as the Overall Assessment of Efficacy by the Investigators showed significant amelioration of depression in both treatment groups (p < 0.001). No significant differences were found between the moclobemide and imipramine groups with regard to treatment outcome. The onset of the antidepressant activity was faster in the moclobemide group as measured by the Assessment of the Investigators. This difference was not observed when the therapeutic index figures calculated on the basis of the changes in the HDRS scores were scrutinized. Treatment-emergent side effects were somewhat more frequent during imipramine than during moclobemide treatment. Nevertheless, a total of only four patients discontinued the trial prematurely because of poor tolerability. Imipramine-treated patients reported more anticholinergic side effects, whereas tiredness and headache were observed more frequently in the moclobemide-treated patients. Restlessness, nervousness and sleep disturbances were noted with equal incidence in both patient groups.

Adult↗
PubMed1991

Alprazolam and oxazepam in the treatment of anxious out-patients with depressive symptoms: a double-blind multicenter study.

In a four-week double-blind study comparing alprazolam with oxazepam, 62 outpatients suffering from anxiety with depressive symptoms were evaluated. The average daily doses of alprazolam and oxazepam were 1.48 mg and 44.4 mg, respectively. According to all rating scales applied, both alprazolam and oxazepam were effective in relieving anxiety associated with mild depression (p less than 0.01). Alprazolam proved somewhat more effective than oxazepam especially with regard to overall performance (p less than 0.05). Treatment-emergent adverse effects were few and mild for both compounds tested.

Adult↗
PubMed1991

Zuclopenthixol decanoate and haloperidol decanoate in chronic schizophrenia: a double-blind multicentre study.

Zuclopenthixol decanoate (ZPT-D) and haloperidol decanoate (HAL-D) were compared in the maintenance treatment of chronic schizophrenic patients. All patients were treated with either ZPT-D or HAL-D for at least 3 months and were then randomly allocated to treatment with either ZPT-D (100-600 mg every 4 weeks) or HAL-D (38-200 mg every 4 weeks) for 9 months. Sixty-four patients entered the study. Three patients were only assessed at baseline. Four patients in the HAL-D group were withdrawn because of deterioration. One patient in the ZPT-D group committed suicide. Fifty-six patients completed the trial. The assessment programme comprised Clinical Global Impressions by psychiatrists and nurses, the Brief Psychiatric Rating Scale (BPRS), Montgomery-Asberg Depression Rating Scale (MADRS), UKU Side Effect Scale and Simpson-Angus Scale, Ratings were made at baseline and after 12, 24 and 36 weeks of treatment. The severity of illness scores remained almost constant. The only between-group difference was recorded at month 6 in favour of ZPT-D. The BPRS total scores were reduced significantly in both groups with no between-group differences. The depression scores on the MADRS were very low. Both treatments caused few and mild side effects according to the UKU Side Effect Scale and the Simpson-Angus scale, and there were no significant differences between the groups. Both ZPT-D and HAL-D seem to be effective in the maintenance treatment of chronic schizophrenic patients and cause few side effects. The injections of ZPT-D and HAL-D can be given at 4-week intervals.

Adult↗
PubMed1990

Comparison of the effect of gluconate, lactose, and xylitol on bone recalcification in calcium-deficient rats.

The therapeutic value of three calcium absorption promoting carbohydrates, lactose, gluconate and xylitol, in bone calcification was evaluated in 7-week-old male rats which were fed on a semisynthetic Ca-deficient diet for 3 weeks. Lactose + CaCO3, xylitol + CaCO3, Ca-gluconate, or CaCO3 alone were administered to the Ca-deficient rats for 2 weeks; the carbohydrate and Ca contents of the diets were 5% and 0.5%, respectively. The Ca-deficient rats showed a decrease in serum total Ca and ionized Ca2+ and in tibial Ca, Mg, P and density, with a concomitant increase in bone hydroxyproline concentration. Bone and serum tartrate-resistant acid phosphatase activities were increased 2-fold and the serum 1,25(OH)2D3 level 5-fold. Smaller increases were found in serum calcitonin, PTH, alkaline phosphatase and osteocalcin levels. These changes (except calcitonin) were reversed by the administration of Ca and the carbohydrates. It was observed that all three agents improved the recalcification of bones compared with the effect of CaCO3 alone. The effect of lactose and xylitol was superior to that of gluconate. These results suggest advantages in the use of xylitol in Ca-supplements.

Acid Phosphatase↗
PubMed1989

Sulpiride and perphenazine in schizophrenia. A double-blind clinical trial.

Seventeen patients with acute schizophrenia and 30 with chronic schizophrenia were included in a randomized, double-blind parallel-group trial comparing sulpiride and perphenazine. Patients were evaluated using the 16-item Brief Psychiatric Rating Scale (BPRS) prior to the onset of treatment and 1 and 2 weeks, and 1, 2, 3, and 4 months thereafter. In patients with acute schizophrenia, total BPRS scores declined significantly at the end of the trial compared with pretreatment values in sulpiride-treated patients but not in schizophrenics treated with perphenazine. Differences in response between the groups did not reach statistical significance, however. For patients suffering from chronic schizophrenia, a statistically significant decline was observed in total BPRS scores at 4 months compared with pretreatment scores in both sulpiride and perphenazine groups. There was no significant difference in the treatment response between the groups. Sulpiride appeared to be somewhat more effective than perphenazine for treatment of acute schizophrenia. Efficacy of both compounds was less marked in chronic forms of schizophrenia.

Acute Disease↗