Jan Sääf

Melatonin in rat pineal gland and serum; rapid parallel decline after light exposure at night.

Melatonin content in the rat pineal decreases at night after exposure of animals to light, from 20 to 2 pmol/gland in 15 min. Melatonin concentration in serum fell precipitously in a manner almost identical to the drop in pineal melatonin only with a 5 min time lag. It is concluded that the rapid decrease in the pineal melatonin content is mainly due to an inhibited synthesis of melatonin.

White matter hyperintensities in dementia : does it matter ?

The aim of the study was to investigate whether the regional distribution of white matter hyperintensities (WMH) observed by magnetic resonance imaging differed between vascular dementia and patients with late onset Alzheimers disease. Another aim was to investigate the relations between the occurrence and degree of WMH and clinical and laboratory data as well as measures of cognitive decline. White matter hyperintensities were assessed with a low field magnetic resonance imager on 23 subjects with probable Alzheimers disease, 25 with possible Alzheimers disease and 31 subjects with vascular dementia. The degree and regional distribution of the WMH (expressed as relative volumes) were calculated and compared in the three groups. The relation between cognitive impairment and the degree of the WMH was also studied. The regional distribution of the WMH differed between the groups with significantly more changes in the posterior part of the brain (p < .0001) as well as in the right hemisphere (p < .0005) in the vascular demented as compared to the patients with Alzheimers disease. No significant correlations between cognitive impairment and the degree of the WMH were found in any of the groups. The total volume of the WMH as well as the regional distribution of these changes differed significantly between vascular dementia and Alzheimers disease. White matter hyperintensities seem not to be related to the degree of global cognitive decline in dementia and whether it plays a causative role in the development of dementia symptoms needs to be more thoroughly investigated.

Calcium and magnesium concentrations in affective disorder: difference between plasma and serum in relation to symptoms

ABSTRACT— Morning (0800) plasma and. serum and mean diurnal (24‐h) serum calcium (Ca) and magnesium (Mg) concentrations were investigated in 56 depressed patients, 32 with acute major depression, 26 of these restudied in remission, 24 patients with longstanding depression, mainly treated with lithium, and in 27 healthy controls. All subjects were rated with the Comprehensive Psychopathological Rating Scale (CPRS). Significant differences between the groups were found for 0800 and 24‐h serum Ca and Mg, 0800 plasma Mg, but not for 0800 plasma Ca. Elevations of serum Ca and Mg, plasma Mg but not plasma Ca were noted in the lithium‐treated patients. Sex differences for plasma but not serum levels were seen in remission and in the controls. Depressive symptoms were negatively correlated to 0800 plasma Ca in the acute state and positively to 0800 and 24‐h serum Ca and Mg in remission and longstanding depression. This difference between plasma and serum in relation to symptoms could reflect a change in a calcium binding factor present in plasma but not in serum, connected with biological factors of affective disease.

Concentration and Uptake of 5-Hydroxytryptamine in Platelets from Cluster Headache and Migraine Patients

Concentrations of 5-hydroxytryptamine (5-HT) in platelets were determined in 33 cluster headache patients (17 males) and in 34 migraine patients (16 males) outside attacks. The 5-HT uptake into platelets was measured and the kinetic constants Vmax and Km determined in 26 cluster patients (14 males) and in 30 migraine patients (13 males). Significantly lower 5-HT concentrations in whole blood were found in cluster headache and migraine patients than in 50 healthy controls (19 males). The Vmax and Km values of the 5-HT uptake were significantly lower in cluster headache and migraine patients compared with 22 healthy controls (9 males). The 5-HT concentrations and the kinetics of the 5-HT uptake did not differ between cluster headache and migraine. In healthy controls a significant positive correlation was found between the 5-HT uptake rate at 0.25 μM and Km but not in cluster headache and migraine patients. The 5-HT concentrations in whole blood correlated positively with Vmax and Km, respectively, in cluster headache and with Km in healthy controls but not with Vmax nor with Km in migraine. There was no obvious relation between the kinetics of platelet monoamine oxidase (MAO) and the 5-HT uptake except for an increased incidence of low Vmax of MAO and low Km of the 5-HT uptake in cluster headache. The kinetics of the 5-HT uptake was apparently not related to the state of migraine. The results indicate a possible constitutional trait in cluster headache and migraine expressed as low 5-HT concentrations in whole blood and low Vmax and Km of the 5-HT uptake into platelets.

Cognitive functions and brain structures: A quantitative study of CSF volumes on Alzheimer patients and healthy control subjects

In the present study we have investigated the connection between cerebrospinal fluid spaces and cognitive function in patients with senile dementia of Alzheimer type (SDAT) and in successfully aged control subjects. The cerebrospinal fluid (CSF) volumes were measured using a low field MRI technique, and the cognitive functions were assessed with a number of psychometric tests. We found that the SDAT patients showed significantly larger relative volumes in all examined CSF spaces. The largest differences between the groups were found in the volumes of the temporal horns. We also found a significant correlation between the relative CSF volumes in the basal parts of the brain, and episodic memory tests. Significant correlations were also detected between the relative volumes of the lateral ventricles, and degree of dementia as well as between the relative volumes of the lateral ventricles and episodic memory tests.

Quantitative estimations of cerebrospinal fluid spaces and brain regions in healthy controls using computer-assisted tissue classification of magnetic resonance images: Relation to age and sex

Computer-assisted tissue classification based on MR intensity values in spin echo and inversion recovery images were used for area measurements of different brain structures in 76 apparently healthy volunteers of various ages. The classification was made from transaxial sections through the basal ganglia and discriminated between brain tissue and cerebrospinal fluid. The measurements based on this discrimination demonstrated larger intracranial areas in men than women. In the total group, sex differences were not observed when the measured structures were corrected for interindividual differences in cranial size. In subjects older than 60 years relative lateral ventricular area was larger and relative brain area smaller in men than women. The lateral ventricles, the Sylvian fissures and the brain area showed the most marked relation to age. The age-relation was more marked for left hemispheric structures.

Plasma prostaglandin E2 metabolite—measured as 11 -deoxy-15 -keto-13,14-dihydro-11 β, 16ξ-cyclo-PGE2—in twins with schizophrenic disorder

Blood samples were obtained from 18 twin pairs, and the major prostaglandin E2 (PGE2) plasma metabolite 15-keto-13,14-dihydro-PGE2 was measured by RIA after its conversion to 11-deoxy-15-keto-13,14-dihydro-11 beta,16 xi-cyclo-PGE2. Significant positive correlations were found in all the twin pairs, in 11 pairs diagnosed as DSM-III schizophrenic disorder and schizoid/schizotypal personality disorder, and in the 5 nonschizophrenic pairs. These results indicate that synthesis of prostaglandins (PGs) is in part genetically determined. With regard to absolute PGE2 metabolite levels, the data did not support the hypothesis of increased PGE2 in schizophrenia. Thus, seven of eight schizophrenic probands had lower metabolite concentrations than their healthy twin siblings, and in one pair they were similar. Furthermore, schizophrenic probands and their healthy sibling controls, taken as a group, had lower PGE2 metabolite levels than the group comprised of affective disorder probands and their respective controls. These findings raise the possibility that a change in PGE2 may be associated with schizophrenic and also possibly with affective disorders.

Classification of patients with affective disorders using platelet monoamine oxidase activity, serum melatonin and post-dexamethasone cortisol

Platelet monoamine oxidase activity (MAO), melatonin and Cortisol post‐dexamethasone suppression test (DST) were examined in 28 patients with major affective disorder and in 20 controls. MAO activity was lower and Cortisol post‐dexamethasone was higher in depressed patients. Platelet MAO activity and Cortisol in depressed and controls yielded high sensitivity (90%) and specificity (89%). The patients were re‐examined after 10 years and categorized into affective psychosis or neurotic depression (ICD‐9). Multidimensional analysis identified one subgroup coinciding in 92% with affective psychosis and another subgroup coinciding in 87% with neurotic depression. Combination of MAO, melatonin and post‐DST Cortisol may be useful in the diagnosis of subgroups of depressed patients and in choice of therapy.

Monoamine oxidase in human platelets: Kinetics and methodological aspects

Abstract The kinetic properties of human platelet monoamine oxidase (MAO) were examined in 20 apparently healthy controls. The mean value (±S.D.) of the maximum velocity ( V ) was found to be 5.36 ± 1.97 pmoles of product formed/10° platelets/min and the Michaelis-Menten constants were for phenethylamine ( K PEA m ) 14.6 ± 8.20 μ M and for oxygen ( K m O 2 )254 ± 125 μ M, when assayed in 0.1 M phosphate buffer, pH 7.4. The relation between the value of the corresponding apparent constants was studied. Inhibition of the enzyme activity was seen at 20 μM of PEA and 180 μM of oxygen. The enzyme kinetics were also studied at different pH. Two p K values were found, p K 1 = 6.65 and p K 2 = 6.95. The influence of homogenization on the MAO activity was compared with the activity in the undisrupted platelet. At PEA concentrations below 10 μM higher MAO activities were found in the intact cell. A 15 per cent loss of activity was detected in platelet samples after storing at −20° for three and a half years.

Kinetics and Thermolability of Platelet Monoamine Oxidase in Cluster Headache and Migraine

Platelet monoamine oxidase activity (MAO) from 33 cluster headache patients (17 males, 16 females) and 34 migraine patients (16 males, 18 females) was assayed. The kinetic constants (apparent V max and apparent K m ) and the thermolability, measured as the ratio of the platelet MAO activity after and before heat treatment (+52°C, 30 min), were determined. The MAO activity and V max values were significantly lower in cluster headache than in migraine and in both headache disorders compared to a control group (62 males, 66 females). When comparing all groups, K m was not significantly different except for migraine females, who had lower K m values compared to control females. Thermolability was significantly higher in cluster headache than in migraine and in both headache disorders compared to the control group. Smokers of five cigarettes or more per day had significantly lower Vmax values but similar K m and thermolability values compared to those smoking less or nothing. The findings of low maximal velocities and high thermolability of platelet MAO in cluster headache and migraine are suggested to represent constitutionally different enzyme properties.