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Biomedical subjects

T Halonen

Publications and source records attributed to T Halonen.

At least 37 records · Page 2Linked to original sources
PubMed1993

Gamma-vinyl GABA decreases voluntary alcohol consumption in alcohol-preferring AA rats.

The effect of a GABA transaminase inhibitor, gamma-vinyl GABA, on the voluntary alcohol consumption of alcohol-preferring AA rats produced by selective breeding for high alcohol preference, was studied. The rats were first trained to voluntarily drink 10% (v/v) ethanol solution until their ethanol consumption stabilized. Gamma-vinyl GABA (100, 200 or 500 mg/kg) was then injected intraperitoneally in three groups of rats, with saline-injected animals serving as a control group. The rats continued to have a free choice between 10% ethanol and plain tap water for five days after the injection, and their ethanol, water and food consumptions were measured daily. Gamma-vinyl GABA decreased ethanol consumption by the rats in a dose-dependent way. The consumption remained significantly decreased for three days in the two groups receiving the highest doses, with only a small concomitant tendency to decreased food intake. The results suggest that an increase in brain GABA concentration decreases alcohol drinking, possibly through potentiation of the pharmacological action of ethanol.

4-Aminobutyrate Transaminase↗
PubMed1992

Amino acid levels in cerebrospinal fluid of rats after administration of pentylenetetrazol.

1. We studied the effect of pentylenetetrazol (PTZ)-induced myoclonic jerks and generalized clonic-tonic convulsions (GC) on the levels of neurotransmitter amino acids in the cisternal CSF of rats. 2. The levels of aspartate, glutamate, glycine, and taurine were elevated in the CSF during myoclonic jerks and more distinctly immediately after GC. 3. During the recovery period of postictal depression seen in EEG (5 min after GC), the CSF levels of transmitter amino acids were lower than in the control group. 4. PTZ-induced irritative activity in the EEG disappeared in 24 hr but the levels of amino acids remained abnormal. 5. Amino acid changes in the CSF following PTZ-induced convulsions might indicate that the release of amino acids into the extracellular space is increased before and during the propagation of PTZ-induced seizure and decreased during postictal depression.

Amino Acids↗
PubMed1992

Cognitive effects of oxcarbazepine and phenytoin monotherapy in newly diagnosed epilepsy: one year follow-up.

We evaluated the effect of initial oxcarbazepine (OXC) monotherapy on memory, attention and simple psychomotor speed in 14 patients; 15 patients with initial phenytoin (PHT) monotherapy served as reference patients. Neuropsychological assessments were performed before starting the treatment and after 6 and 12 months follow-up with steady-state drug treatment. Differential cognitive effects of OXC and PHT were not apparent in our study. As the efficacy of present antiepileptic drugs in adult epilepsy is analogous, the choice of drug is determined by the comparative side effects of the drugs. In the present study the number of successfully treated patients was similar in both OXC and PHT groups. As far as cognitive side effects are concerned our results revealed no evidence favoring either antiepileptic over the other.

Adult↗
PubMed1991

The effect of subchronic administration of vigabatrin on learning and memory in nonepileptic rats.

The present experiments investigated whether subchronic administration of vigabatrin, a GABA-mimetic drug, affects the performance of normal rats in the behavioural tasks assessing learning and memory. The effects of vigabatrin [50-200 mg/kg (IP)/day] administration on the acquisition and retention of water maze and passive avoidance task were studied. According to the results of three experiments, vigabatrin treatment did not markedly impair the acquisition or retention of water maze task. Furthermore, vigabatrin-treated rats were not inferior to saline-treated rats in reversal learning of water maze task. On the other hand, vigabatrin treatment slightly increased the speed of swimming in rats. The administration of vigabatrin did not affect the performance (training latency, number of training trials, testing latency) of rats in the passive avoidance task. According to these results, the effects of vigabatrin, a new antiepileptic drug, on the performance of nonepileptic rats were modest in behavioural tasks used to assess learning and memory.

Amino Acids↗
PubMed1990

Administration of vigabatrin (gamma-vinyl-gamma-aminobutyric acid) affects the levels of both inhibitory and excitatory amino acids in rat cerebrospinal fluid.

The effect of vigabatrin (gamma-vinyl-gamma-aminobutyric acid), a new anticonvulsant drug, on the transmitter amino acids in rat cisternal CSF was studied. CSF was collected through a permanently implanted polyethylene cannula from freely moving rats at 5, 24, 48, and 96 h after administration of 1,000 mg/kg of vigabatrin. The free gamma-aminobutyric acid (GABA) level was elevated maximally (13.5-fold; p less than 0.01) at 24 h after injection. The homocarnosine (GABA-histidine) level also was increased (123%; p less than 0.01) at 24 h after injection, and its concentration remained at the same level for the next 3 days. Glycine and taurine concentrations had increased [31% (p less than 0.05) and 63% (p less than 0.01), respectively] at 5 h after injection. It is interesting that the levels of glutamate and aspartate increased [330% (p less than 0.05) and 421% (p less than 0.01), respectively] at 96 h after injection, the time when the free GABA level had returned to the baseline concentration and the vigabatrin level was 3% of the maximal concentration. The present study indicates that a single dose of vigabatrin in rats elevates levels of both the inhibitory and excitatory amino acids in CSF. However, the temporal profile of observed changes in relation to vigabatrin injection shows that neither the long-lasting elevation of GABA content nor the increase in glutamate and aspartate levels correlates with the level of vigabatrin in CSF. These findings suggest that the excitatory mechanisms are also augmented following acute administration of vigabatrin, especially when the content of GABA had decreased to the baseline level and the level of vigabatrin was low.

Amino Acids↗
PubMed1989

Inhibitory and excitatory amino acids in cerebrospinal fluid of chronic epileptic patients.

We studied the levels of excitatory and inhibitory amino acids in the cerebrospinal fluid (CSF) of 28 epileptic patients (24 with partial type seizures, 4 with primary generalized seizures) and 12 controls. The levels of aspartate were 63% (p less than 0.01), glutamine 129% (p less than 0.001), and homocarnosine 127% (p less than 0.005) that of controls. The concentrations of glutamate, asparagine, total GABA, free GABA, taurine, and glycine did not differ between epileptic patients and controls. Patients with partial epilepsy had a pattern of amino acids in CSF similar to that in patients with primary generalized seizures. In the present study we did not observe increased excitation or decreased inhibition in the seizure-active brains of epileptics, as far as the CSF levels of amino acids reflect their levels in the brain.

Adolescent↗
PubMed1989

Cerebrospinal fluid GABA and seizure control with vigabatrin.

1. To evaluate the relationship between the clinical response and enhancement of GABAergic neurotransmission, for 6 months we administered vigabatrin (gamma-vinyl-GABA, GVG) to 75 patients with complex partial epilepsy. Total GABA (TGABA), free GABA (FGABA), homocarnosine (HC), and GVG concentrations were measured in CSF of these patients before and during GVG treatment. 2. Over 50% reduction in seizures was found in 55% of the patients. Dose-reduction resulted in a relapse, i.e. the return of seizures. 3. At baseline TGABA, FGABA, and HC did not differ in responders and nonresponders. After GVG treatment, the TGABA and HC levels were lower in nonresponders (P less than 0.001), but the GVG and FGABA levels did not differ. The GVG dose reduction resulted in a concomitant decrease in TGABA, FGABA, HC and GVG (P less than 0.001). 4. According to our results GVG is an effective anticonvulsant drug in complex partial seizures. In nonresponders the poor anticonvulsant response may be related to the lower elevation of the CSF markers of GABAergic neuronal activity in this group compared with the responders.

Adolescent↗
PubMed1989

Specificity of vigabatrin for the GABAergic system in human epilepsy.

The therapeutic action of vigabatrin (gamma vinyl GABA, GVG) has been reported to be mediated by GABAergic neurotransmission. In the present study, we evaluated different neurotransmitter systems in the cerebrospinal fluid (CSF) of patients with complex partial epilepsy, before and during GVG treatment. The markers of the GABAergic system (free GABA, total GABA, homocarnosine) showed a two- to threefold elevation. There was also an increase in glycine during the 6 months of GVG treatment. In contrast, we did not find any constant CSF changes in either excitatory amino acids or in markers of the cholinergic (acetylcholinesterase), dopaminergic (homovanillic acid), serotonergic (5-hydroxyindoleacetic acid), or peptidergic (somatostatin, prolactin, beta-endorphin) systems. This finding (except an elevation in glycine) was in agreement with previous studies which suggest a specific action of GVG on the GABAergic system. The role of glycine in antiepileptic efficacy of GVG needs further evaluation.

Adult↗
PubMed1988

Free amino acids in the brain of patients with Parkinson's disease.

To study free brain amino acids and their relation to dementia, the levels of glutamate, glutamate, asparagine, aspartate, glycine, taurine, homocarnosine and gamma-aminobutyric acid were determined in the temporal cortex and caudate nucleus in demented and non-demented patients with Parkinson's disease. In the temporal cortex, the levels of aspartate and asparagine were significantly increased in non-demented parkinsonian patients as compared both to demented patients and to controls. In the caudate nucleus no significant changes in amino acid levels were seen. Thus, the cortical and striatal glutamate/aspartate systems seem to be preserved in dementia in Parkinson's disease.

Aged↗
PubMed1988

Effect of gamma-vinyl GABA treatment on cholinergic and aminergic neurotransmission and on cyclic nucleotides in human complex partial epilepsy--a CSF study.

1. Gamma-vinyl GABA (GVG) is a new anticonvulsant drug that enhances levels of GABA in the brain by irreversibly inhibiting GABA transaminase. 2. To further evaluate the effects and mechanism of action of GVG in the human brain, we measured acetylcholinesterase (AChE) activity and levels of homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA), cyclic nucleotides (cAMP, cGMP), total GABA (TGABA), and GVG in CSF of 78 patients with complex partial epilepsy. The CSF samples were taken at baseline and after 3 months of GVG administration (3 g GVG per day). Thereafter, the responders (= 50% decrease in number of seizures) were divided (double-blind) into two groups that received either 1.5 g or 3 g of GVG per day for the next 3 months. The third CSF sample was taken after this double-blind period. 3. TGABA levels were increased during the GVG treatment (p less than 0.001). In the whole group of patients AChE, HVA, 5-HIAA, and cAMP did not differ from baseline values, cGMP levels were slightly elevated after 3 months of GVG administration (p = 0.019), but were no longer elevated after 6 months. Responders had slightly lower AChE activity than nonresponders (p = 0.041). After 6 months of drug treatment the cGMP levels of patients receiving 1.5 g of GVG did not differ from those receiving 3 g. 4. In conclusion, GVG administration elevates levels of TGABA in the CSF without any clear of constant change to cholinergic and aminergic transmission or effect on cyclic nucleotides. Our study further emphasizes the specific mechanism of action of GVG via GABAergic transmission.

Acetylcholinesterase↗
PubMed1987

Decreased muscarinic receptor binding in cerebral cortex and hippocampus in Alzheimer's disease.

Muscarinic (cholinergic) receptor binding sites (MRB) were studied by determining the 3H-QNB binding in four cortical areas and hippocampus of 20 histologically confirmed Alzheimer patients and comparing these with corresponding controls. Alzheimer patients dying at younger age (less than or equal to 80) with profound decrease in choline-acetyltransferase activity (by 61-85%) and without any, possibly MRB modifying, drug treatment showed 30% decrease in MRB in the frontal cortex (p less than 0.05), 28% in the temporal cortex (p less than 0.05) and 37% in the hippocampus (p less than 0.01). These findings further suggest that muscarinic receptors are affected in Alzheimer's disease, at least in advanced state of the disease.

Aged↗
PubMed1987

Amino acid levels in human CSF after generalized seizure.

We studied the possible role of excitatory and inhibitory amino acids and their balance during generalized convulsions. The levels of amino acids in postictal cerebrospinal fluid (CSF) were compared with amino acid concentrations in interictal CSF of ten patients with generalized tonic-clonic convulsions. Glu, Gln, Asp, Asn, Tau, Gly, total GABA (t-GABA), free GABA (f-GABA), and homocarnosine levels and Glu/Gln, Asp/Asn, t-GABA/Glu, f-GABA/Glu, f-GABA/Asp, and Glu/Asp ratios were similar in both samples (Student's paired t-test). Our results suggest that in humans possible changes in amino acids in brain tissue during the ictal stage are not reflected in the lumbar CSF.

Adult↗
PubMed1987

Lysosomal hydrolases in cerebrospinal fluid of multiple sclerosis patients. A follow-up study.

The change in activity of lysosomal hydrolases in the brain tissue of patients with demyelinating disease has been suggested to reflect the demyelination process. In this study we measured neutral proteinase (NP), acid proteinase (AP), and beta-glucuronidase (BG) activities in CSF of 32 patients with multiple sclerosis (MS) (remitting, remitting and relapsing, or chronic progressive course of the disease), 62 controls, and 4 patients with chronic inflammatory disease of central nervous system (ID). Samples from MS patients were taken at different clinical conditions of the disease during the 22-month follow-up. Elevated NP activity was found in patients with relapsing course of MS and also in patients with ID (P less than 0.05). NP activity correlated with the number of leucocytes in CSF of both MS (P less than 0.005, r = 0.50) and control (P less than 0.05, r = 0.21) patients. AP activity decreased in the MS group, especially in patients with remitting or remitting and relapsing courses of the disease (P less than 0.05), but even more in patients with ID (P less than 0.01). During the follow-up the increase in NP activity seemed to be associated with the clinical relapses of MS patients. Other enzymes did not fluctuate with the disease. This study suggests that the change in activity of lysosomal hydrolases is not specific for MS. The increase in NP activity in CSF is associated with clinical relapse of individual MS patients during the follow-up and may indicate immunological activation of the demyelination process in the brain. The large intra- and interindividual variation in enzyme activities in the CSF, however, makes the use of these enzymes difficult for diagnosis of MS and follow-up of MS activity.

Aspartic Acid Endopeptidases↗
PubMed1987

Somatostatin, beta-endorphin, and prolactin levels in human cerebrospinal fluid during the gamma-vinyl-GABA treatment of patients with complex partial epilepsy.

The anticonvulsant action of the new anticonvulsant drug gamma-vinyl-GABA (GVG) is obviously mediated by elevation of the concentration of GABA in the brain. The effect of GVG administration on other transmitter systems is not fully known in humans. We studied the possible interactions of GVG administration with peptidergic systems. Included in this study were 67 patients with complex partial epilepsy (CPS). The first CSF sample was taken before GVG administration. The second CSF sample was taken after 3 months of GVG treatment (3 g/day). Thereafter half of the responders (50% decrease in seizure frequency or clear improvement in global performance) received 3 g/day and the other half received 1.5 g/day for the next three months, after which the third CSF sample was taken. Somatostatin (SLI), beta-endorphin (beta-EP), and prolactin (PROL) levels in CSF were measured by radioimmunoassay. Total GABA (tGABA) and GVG levels in CSF were measured by high performance liquid chromatography. After 3 months of GVG treatment there was a slight increase in the beta-EP (p = 0.027, Student's paired t-test), which was not found after 6 months of GVG administration. Both SLI and PROL were stable during the study. Peptide levels were not connected to the clinical response to GVG, GVG dosage, or to tGABA levels in the CSF. In conclusion, the elevation of GABA levels in the brain during GVG treatment apparently does not induce long-term interactions with the peptidergic systems studied.

Adult↗
PubMed1987

Comparison of oxcarbazepine and carbamazepine: a double-blind study.

The antiepileptic efficacy and side-effects of oxcarbazepine (OXC), a new carbamazepine derivate, were evaluated in a double-blind study. Forty ambulatory epileptics with unsatisfactory seizure control or unwanted effects due to phenytoin monotherapy were changed to OXC or carbamazepine (CBZ) and were then followed for 48-50 weeks. Thirty-four of the patients completed the study. The seizure frequencies on the trial drugs were not significantly different and the antiepileptic efficacy of OXC was comparable to CBZ. The incidence of side-effects during the initiation phase was lower with OXC suggesting better tolerability of OXC compared to CBZ.

Adolescent↗
PubMed1986

The effect of sorbinil treatment on red cell sorbitol levels and clinical and electrophysiological parameters of diabetic neuropathy.

A randomized placebo-controlled double-blind cross-over study was conducted in order to examine the effect of an aldose reductase inhibitor, sorbinil (100 mg daily for 4 weeks), on red cell sorbitol concentration and clinical and electrophysiological parameters of diabetic neuropathy. A total of 31 diabetic patients with either clinically or electrophysiologically verified diabetic neuropathy were studied. Red cell sorbitol levels decreased significantly to the levels reported in non-diabetic subjects, but there were no significant changes in symptoms, signs, vibration perception thresholds or nerve conduction variables. One patient had transient skin rash, fever, myalgia and leucopenia, but no other significant adverse effects were found.

Adult↗
PubMed1986

Somatostatin-like immunoreactivity in the cerebrospinal fluid of patients with Parkinson's disease and its relation to dementia.

Acetylcholinesterase, somatostatin-like immunoreactivity, and homovanillic acid levels were measured in the cerebrospinal fluid of 36 patients with early stages of Parkinson's disease and in 19 control patients. In patients with Parkinson's disease the levels of somatostatin-like immunoreactivity were lower than in the controls (p less than 0.01); these values were lowest in the demented Parkinsonian patients. Concentrations of homovanillic acid were also significantly lower in Parkinsonian patients (p less than 0.05). In contrast, no changes were observed in the acetylcholinesterase activity of patients with Parkinson's disease. The reduced somatostatin-like immunoreactivity in CSF agrees with previous post-mortem studies and indicates that Parkinson's disease and Alzheimer's disease may have some neurochemical features in common.

Acetylcholinesterase↗