Biomedical subjects

T Halonen

Publications and source records attributed to T Halonen.

45 records · Page 3Linked to original sources

PubMed1984

Quantification of a number of biogenic amines and their metabolites in brain homogenates by gas chromatography--mass spectrometry.

A sensitive method is described for the assay of various biogenic amines and their metabolites from brain tissue homogenates. Based on gas chromatography-mass spectrometry and selected ion monitoring, the method allows reliable low-level quantification of the compounds of interest. By careful study of reaction conditions both in the preparation of derivatives for gas chromatography and in the synthesis of deuterated analogues for internal standard use, relatively simple procedures could be applied with good analytical efficiency. Correlation of the results with those obtained by a high-performance liquid chromatographic procedure was also investigated, and a neurologic application of the method is briefly discussed.

Alzheimer Disease↗

PubMed1984

Dopamine-beta-hydroxylase and acetylcholinesterase activities of cerebrospinal fluid in Alzheimer's disease.

Recent neurochemical studies have indicated that in Alzheimer's disease there is disturbance of the cholinergic metabolism of the brain. Defects in other transmitter systems have also been suggested. As a marker of noradrenergic metabolism of the central nervous system, we measured dopamine-beta-hydroxylase (EC. 1.14.17.1) activity in cerebrospinal fluid (CSF) from 60 Alzheimer patients and 20 controls of the same age and sex. Dopamine-beta-hydroxylase activities of the CSF from Alzheimer patients did not differ significantly from those for the controls. The dopamine-beta-hydroxylase activities were not correlated with severity of dementia. As reported previously, the activity of a cholinergic marker, acetylcholinesterase (EC 3.1.1.7), was reduced in the CSF of Alzheimer patients. Interestingly, dopamine-beta-hydroxylase activities were correlated with acetylcholinesterase activities both in Alzheimer patients and control group.

Acetylcholinesterase↗

PubMed1982

Bioluminescent assay of total and brain-specific creatine kinase activity in cerebrospinal fluid.

A bioluminescent assay based on the firefly luciferase reaction has been used for determination of creatine kinase activity in CSF. Activities as low as 0.1 U/L can be measured. The coefficient of variation at an activity level of 0.3-0.4 U/L was between 5 and 6%. The assay conditions optimized for serum specimens can be used for CSF. The adenylate kinase activity is almost completely inhibited, which simplifies the procedure. The creatine kinase/(CK) isoenzyme distribution was obtained using the bioluminescent assay in combination with immunoinhibition or ion exchange chromatography. All specimens contained both MM and BB activity, but no MB was found. The study indicates that the bioluminescent assay is useful in the determination of CK isoenzymes in CSF. The clinical importance of the observed CK levels will be reported in a separate communication.

Adenosine Diphosphate↗

PubMed1981

Acetylcholinesterase activities in cerebrospinal fluid of patients with senile dementia of Alzheimer type.

We have studied, as a possible marker of cholinergic neurons, the acetylcholinesterase (AChE) activity in cerebrospinal fluid (CSF) of 21 SDA patients and 9 controls of similar age with no neurological disease. The AChE activities were significantly lower in the SDA patients compared to the controls. The AChE activities were also lowered in the most severely demented patients compared to those who were less severely demented but the difference was not statistically significant. As a potential glia marker, beta-glucuronidase activity in CSF was studied, but no significant difference was found in the activities of the SDA patients compared to the controls. The reduced AChE activities in the CSF of the SDA patients may be related to the loss of cholinergic neurons or disturbed cholinergic metabolism in the brain.

Acetylcholinesterase↗

PubMedDate not supplied

Inhibitory and excitatory amino acids in CSF of patients suffering from complex partial seizures during chronic treatment with gamma-vinyl GABA (vigabatrin).

The effect of chronic administration of gamma-vinyl GABA (GVG; vigabatrin) on levels of neurotransmission-related amino compounds was studied in lumbar cerebrospinal fluid of 65 patients with complex partial epilepsy. The first sample of cerebrospinal fluid was taken before a 3-month period of treatment with 3 g gamma-vinyl GABA/day, and the second was taken afterwards. From patients who showed a greater than 50% reduction in seizures (responders) or marked improvement in global performance, a third sample was taken at the end of the next 3-month phase, during which 3 g or 1.5 g gamma-vinyl GABA had been administered daily. During treatment with 3 g gamma-vinyl GABA/day, 55% of the patients showed more than 50% reduction in complex partial seizures; and at the same time free GABA, total GABA, homocarnosine, and glycine concentrations in the cerebrospinal fluid increased by 104%, 151%, 194% and 16%, respectively. After reduction of the daily dose to 1.5 g, the levels of free GABA, total GABA and homocarnosine were still increased by 65%, 115% and 102%, respectively. gamma-Vinyl GABA correlated with the levels of free GABA (P less than 0.002) and glycine (P less than 0.001). Concentrations of homocarnosine at baseline and homocarnosine and total GABA during gamma-vinyl GABA treatment were lower (P less than 0.005) in the group of non-responders than in the responder group. Glutamic acid, glutamine, aspartic acid, asparagine, and taurine levels did not change during gamma-vinyl GABA treatment. In conclusion, administration of gamma-vinyl GABA reduces epileptic seizures and produces dosage-dependent increases in levels of free GABA, GABA-containing peptides and of glycine in cerebrospinal fluid, without concomitant change in levels of excitatory amino acids.

Adolescent↗

PubMedDate not supplied

Dopaminergic system and monoamine oxidase-B activity in Alzheimer's disease.

The possible involvement of dopaminergic neurons in dementia of Alzheimer type (AD/SDAT) was studied in autopsied brains from 20 patients with AD/SDAT. Dopamine (DA) concentrations were decreased significantly in the temporal cortex, hippocampal cortex and hippocampus in AD/SDAT patients. Levels of homovanillic acid (HVA) were not altered compared to controls. The HVA/DA ratio was significantly higher in the hippocampus of AD/SDAT patients, suggesting overactivity of the remaining DA neurons. Histological findings of substantia nigra suggesting coexistent pathology of Parkinson's disease (PD) found in 25% of cases were associated with lowered levels of DA in striatum and with reduced HVA in CSF. The activity of monoamine oxidase-B was significantly increased in the cortical areas and in the hippocampus, obviously reflecting the underlying cell loss and substantial gliosis in these areas of the brain. In general, DA neurons seemed to be only mildly involved in AD/SDAT. Coexistent PD pathology can explain the loss of DA in the striatum and the presence of clinical PD symptoms in some patients with AD/SDAT. Otherwise the clinical relevance of these dopaminergic alterations is unclear.

Aged↗

PubMedDate not supplied

Effects of vigabatrin (gamma-vinyl GABA) on neurotransmission-related amino acids and on GABA and benzodiazepine receptor binding in rats.

The effect of 12-day intraperitoneal i.p. administration of vigabatrin (GVG, gamma-vinyl GABA) to rats on the neurotransmission-related amino acids in various brain regions (cortex, hippocampus, cerebellum, and spinal cord), cisternal fluid (CSF) and blood was studied. Results showed that GVG administration increased the levels of GABA in cortical and subcortical regions of the brain and CSF without affecting GABA and benzodiazepine receptors in the cortex. In addition, a dose-dependent decrease was noted in the concentration of glutamate in the hippocampus and in the concentrations of aspartate and glutamine in the cortex, hippocampus, and cerebellum. The changes in the levels of amino acids in the brain, except for that of GABA, were not reflected in the CSF, however, and the levels of amino acids in discrete brain regions did not show any correlation with those in the serum or in the CSF. The results suggest that GVG administration might suppress development and spread of seizures not only by elevating the level of the inhibitory amino acid GABA, but also by decreasing the levels of excitatory amino acids in the brain.

Amino Acids↗

PubMedDate not supplied

Gamma-vinyl GABA (vigabatrin) in epilepsy: clinical, neurochemical, and neurophysiologic monitoring in epileptic patients.

We report long-term clinical, neurochemical, and electrophysiologic data of gamma-vinyl GABA (GVG, vigabatrin) in three groups of patients. GVG was started as add-on therapy for 75 patients with refractory complex partial seizures (group A) and for 36 mentally handicapped patients with severe epilepsy (group B). The third group (C) consisted of 20 patients with carbamazepine (CBZ) monotherapy, in half of whom GVG monotherapy was substituted. After 3 months, 55% of patients in group A and 42% in group B were responders (reduction in seizure frequency greater than 50%). After 6 (group A) and 3 years (group B) of follow-up, 27 and 33% of the patients, respectively, still had good response to GVG. Neurochemical measurements showed a twofold increase in CSF GABA concentrations and minimal or no changes in other neurotransmitter-related parameters. In group C, substitution of GVG as medication tended to normalize the lengthened latencies in somatosensory evoked potentials (SEPs) observed during CBZ treatment.

Adult↗

PubMedDate not supplied

Effect of vigabatrin on the electroencephalogram in rats.

Vigabatrin (gamma-vinyl GABA; GVG) is a new antiepileptic drug (AED) that increases the level of the inhibitory transmitter, gamma-aminobutyric acid (GABA) in the brain. We evaluated the effect of GVG on the EEG of normal rats. GVG was administered intraperitoneally (i.p.) at a dose of 100 mg/kg once a day for 12 days. EEG was recorded at baseline, on the fourth day, at the end of the 12-day GVG period and 10 days after discontinuation of GVG. GVG increased the amplitude of delta (1-4 Hz) and theta (4-8 Hz) frequency bands and resulted in slowing of the peak frequency (Fp) and mean frequency (Fm) in both the frontal and occipital cortex, especially during waking-immobility. EEG changes normalized within 10 days after the last GVG injections. The results suggest that a relationship may exist between the EEG changes and increase in GABA levels with GVG.

Aminocaproates↗