The effects of adrenaline injections on human platelet monoamine oxidase and related measures.

A double-blind, placebo-controlled, cross-over study in ten normal volunteers assessed the effects of the subcutaneous administration of adrenaline on platelet MAO activity, in an attempt to replicate previous findings of increased MAO activity following adrenaline. Platelet counts, cortisol plasma concentrations, and uptake of metaraminol by the platelets were also determined to elucidate possible mechanisms of action. Blood pressure and heart rate were used as indices of the concentration of adrenaline effectively in circulation. MAO activity towards benzylamine was significantly increased by adrenaline. Non-significant increases were noted in the deamination of tyramine and tryptamine, in platelet counts, cortisol concentrations and metaraminol uptake. Increases in MAO activity were also noted early in the experimental sessions suggesting that other experimental variables such as venepuncture may affect platelet MAO activity. Possible mechanisms for this adrenaline effect are discussed and it is suggested that variables such as "arousal" and "stress" must be taken into account when interpreting clinical data on platelet MAO.

Gamma-glutamyl transpeptidase. Elevated activity in myotonic dystrophy.

gamma-Glutamyl transpeptidase, a membrane-bound enzyme playing an important role in the active amino acid transport across cellular membranes, is shown to be elevated in the serum of patients with myotonic muscular dystrophy. No increase of AP, LAP, GOT and GPT activities in the sera of some of the patients studied is observed. Possible interpretations in relation to the pathogenesis of myotonic dystrophy are discussed.

Effect of moclobemide on clinical and neurochemical variables in depressed patients (preliminary findings).

In this paper the preliminary results from an ongoing investigation on the effect of the MAO-A inhibitor moclobemide on clinicolaboratory variables (antidepressant effect, platelet MAO activity, urinary MHPG and 5-HIAA excretion, plasma prolactin and growth hormone levels and TSH response to TRH) are reported. From the total of 18 patients, 10 (2 males and 8 females) responded favourably (reduction in the HDRS 50% or more) to the treatment. Urine MHPG excretion significantly (p less than 0.001) decreased during treatment, while 5-HIAA secretion showed a less pronounced decrease (p less than 0.05). Plasma PRL and GH remained unchanged, while the TSH-response to TRH increased significantly (p less than 0.025) after 4-week treatment. A significant correlation was found between MHPG pretreatment values and treatment outcome.

The efficacy of amineptine in the treatment of depressive patients with irritable bowel syndrome.

Patients with irritable bowel syndrome (IBS) often suffer from depression. In view of this, the effect of amineptine on the psychopathological condition of depressive patients with IBS was studied. Forty patients who satisfied the criteria for irritable bowel syndrome and had a Hamilton 24-item score above 15 were randomly assigned to receive either amineptine 200 mg/day or placebo in a double-blind clinical trial. Patients on amineptine were more improved at the end of the trial than patients on placebo (total Hamilton score). Amineptine was more effective on depressive mood, retardation, and cognitive dysfunction. Although these findings should be interpreted with caution because the baseline scores were higher in the amineptine than in the placebo group, they provide some evidence that amineptine may be a useful tool for the management of depressive patients with IBS.

Effects of monoamine oxidase A inhibition on plasma biogenic amine metabolites in depressed patients.

The main metabolites of noradrenalin, dopamine, and serotonin-3-methoxy-4-hydroxyphenylglycol (MHPG), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA), respectively--were estimated in plasma of 21 depressed patients before and after 2 and 4 weeks of treatment with the monoamine oxidase-type A (MAO-A) inhibitor moclobemide (mean final daily dose = 8.9 mg/kg body weight). The treatment caused significant mean reductions in plasma MHPG and HVA (46% and 30%, respectively), while plasma 5-HIAA was unchanged. Multiple regression analysis revealed associations between reductions in MHPG and changes on the anxiety-somatization factor of the Hamilton Rating Scale for Depression (HRSD), and between reductions in HVA and changes in the HRSD factors cognitive disturbance and retardation.

Pattern of heat shock factor and heat shock protein expression in lymphocytes of bipolar patients: increased HSP70-glucocorticoid receptor heterocomplex.

Bipolar disorder (BD), a stress-related disease, is characterized by altered glucocorticoid receptor (GR) signalling. Stress response includes activation of heat shock factor (HSF) and subsequent heat shock protein (HSP) synthesis which regulate GR folding and function. The objective of this study was to investigate the possible role of HSFs, HSPs and their interaction with GR in BD. We applied immunoprecipitation, SDS-PAGE/Western blot analysis and electrophoretic mobility shift assay (EMSA) in lymphocytes (whole cell or nuclear extracts) from BD patients and healthy subjects and determined the HSPs (HSP90 and HSP70), the heterocomplexes HSP90-GR and HSP70-GR, the HSFs (HSF1 and HSF4) as well as the HSF-DNA binding. The HSP70-GR heterocomplex was elevated (p < 0.05) in BD patients vs healthy subjects, and nuclear HSP70 was reduced (p ≤ 0.01) in bipolar manic patients. Protein levels of HSF1, HSF4, HSP90, HSP90-GR heterocomplex, and HSF-DNA binding remained unaltered in BD patients vs healthy subjects. The corresponding effect sizes (ES) indicated a large ES for HSP70-GR, HSP70, HSF-DNA binding and HSF4, and a medium ES for HSP90, HSF1 and HSP90-GR between healthy subjects and bipolar patients. Significant correlations among HSFs, HSPs, GR and HSP70-GR heterocomplex were observed in healthy subjects, which were abrogated in bipolar patients. The higher interaction between GR and HSP70 and the disturbances in the relations among heat shock response parameters and GR as observed in our BD patients may provide novel insights into the contribution of these factors in BD aetiopathogenesis.

Low dosage lithium augmentation in venlafaxine resistant depression: an open-label study.

Lithium augmentation is one of the best studied strategies for resistant depression. The lithium dosage usually given is around 900 mg/day and plasma level is maintained in the range of 0.5-0.8 mEq/L. However, the administration of lithium in this dosage necessitates monitoring of plasma concentration and increases the risk of toxicity and side effects. Since it has been shown that low lithium levels increase serotonin turnover and enhance serotonin neurotransmission, we thought it of interest to assess the efficacy of low dosage lithium augmentation for patients with resistant depression. Fifty one patients suffering from severe unipolar or bipolar depression who had failed to respond to treatment with venlafaxine 300-375 mg/day were included in the study and treated as outpatients. Patients had previously been exposed to unsuccessful treatment with various antidepressants, mostly SSRIs. After a washout period for previously administered antidepressants of one week, the dosage of venlafaxine was rapidly titrated to 300 or 375 mg/day, corresponding to about 5 mg/kg. The dose remained stable during the next six weeks. Additional antipsychotic medication was allowed to treat psychotic symptoms. Forty seven severely depressed patients who failed to respond to 300-375 mg/day venlafaxine were, in addition, given lithium carbonate in low dosage (300-450 mg/day). The Clinical Global Impression Improvement scale was used as the treatment outcome. A score of 1 or 2 was considered as non-response. All patients gave informed consent to participate in the study. Ratings were performed at baseline and after 1,2 and 5 weeks. Lithium plasma concentration measurements were performed after 1 and 4 weeks. After 5 weeks of augmentation, 51% of the patients were rated as "much" or "very much" improved. Bipolar patients showed a better response than unipolar (64.3% vs 45.5%, p<0.038). Most patients (76%) showed a rapid response (up tp 7 days), and only 2 patients (4.6%) responded after more than 2 weeks The mean lithium plasma level was 0.33±0.09 mEq/L. No significant differences were found in treatment response with regard to sex, family history, psychotic symptomatology and suicidal ideation. No troublesome side effects were reported. Our results show that treatment augmentation with low lithium dosage may be as effective as augmentation with higher dosage, is well tolerated and does not necessitate monitoring of plasma level. Hence, an initial trial of ugmentation at low dosage lithium may be the preferred first choice in non-emergent situations. The low dosage also minimizes the risk of side effects and drug-drug interactions. Prospective controlled studies to confirm our findings are needed as are larger scale comparisons with therapeutic dose lithium augmentation.

2,3 diphosphoglycerate in Parkinson's disease.

The red cell 2,3 DPG, the most important factor for oxygen delivery in the tissues, was found to be increased in Parkinsonism patients compared with controls. The aging process seems not to be a factor in the increased 2,3 DPG concentration. Other factors relevant to raised 2,3 DPG level such as physical activity, increased oxygen requirements, and metabolic changes are discussed.

Enzyme activity of G-6-PD, gamma-GT and lysozyme in white cells of schizophrenics.

In a controlled study the activity of glucose-6-phosphate dehydrogenase (G-6-PD) in red and white blood cells, gamma-glutamyl transpeptidase (gamma-GT) and lysozyme in serum and white blood cells was studied in 22 drug-free schizophrenic patients and 17 healthy volunteers. The activities of the above enzymes were found to be reduced in the white cells of schizophrenics compared with controls. The differences in activity of G-6-PD in red cells and of gamma-GT and lysozyme in serum between the two groups were not revealed as significant. The observed low enzyme activities might provide a further basis for interpreting the reported functional deficiency in neutrophils of schizophrenics. Possible mechanisms in relation to biological abnormalities in schizophrenia are discussed.

Cataract and gamma-glutamyl cycle in myotonic dystrophy.

Gamma-Glutamyl transpeptidase (gamma-GT) may be responsible for the rapid catabolism and low levels of lenticular glutathione often associated with cataract formation. Elevated levels of serum gamma-GT in patients with myotonic dystrophy suggest that since the defect could be present in all tissues it might be responsible for the cataracts frequently observed in this genetic disease.

Clinical, endocrine and neurochemical effects of moclobemide in depressed patients.

The clinical efficacy of the monoamine oxidase A inhibitor moclobemide and its effect on the dexamethasone suppression test (DST) and plasma and urine methoxyhydroxyphenylglycol (MHPG) were investigated in 26 depressed patients during a 4-week clinical trial. Fourteen patients (54%) responded favourably to the treatment (50% or more reduction of the Hamilton Rating Scale for Depression score). All (8) patients with an abnormal DST responded to treatment; 11 of 16 patients with a normal DST did not respond. Patients with low pretreatment MHPG excretion, according to the median value, were more frequently treatment responders. Plasma and urine MHPG were significantly decreased by treatment. The results indicate that low excretion of MHPG and cortisol nonsuppression may be considered as predictors of favourable clinical response to moclobemide treatment.

Resistant bipolar disorder precipitated by Behcet's syndrome.

OBJECTIVE: To report a case of a patient with Behcet's syndrome who developed treatment resistant bipolar disorder (BD) several years after the onset of Behcet's syndrome. METHODS: A 62-year-old woman suffering from Behcet's syndrome since the age of 38, who developed a typical BD 6 years after the first manifestations of the syndrome was described. RESULTS: Once BD occurred, Behcet's syndrome became milder, while BD deteriorated and evolved into a rapid cycling illness. Lithium and carbamazepine were ineffective in controlling the affective symptoms, while sodium valproate combined with low doses of carbamazepine and olanzapine resulted in sufficient stabilization of her mood state. CONCLUSIONS: Behcet's syndrome may have been the organic substrate for BD in this case. The appearance of BD in the setting of an organic-immune disorder, like Behcet's syndrome, suggests that such disorders may be the neurobiologic substrate or contributor for BD, at least in certain cases.

Peptic ulcer in adults. Psychopathological, environmental, characterological and hereditary factors.

34 male peptic ulcer patients were compared to (a) a group of 37 healthy controls and (b) a group of 36 hospitalized controls suffering from illnesses unrelated to the gastrointestinal tract. Patients and controls were submitted to the Eysenck personality inventory, Foulds' hostility questionnaire, Langner's 22-item questionnaire, the Hopkins symptom checklist, Zung's self-rating anxiety scale, Spielberger's state-trait anxiety inventory, Zung's and Beck's rating scales for depression, and the 43-item life event inventory by Holmes and Rahe. All patients suffered from duodenal ulcer. The parameters that differentiated to a statistically significant degree the peptic ulcer patients from either one or both groups of controls were: (a) neuroticism, (b) trait and state anxiety, (c) guilt, (d) general psychopathology, and (e) stressful life events. Additionally, more than 50% of patients had at least one first-degree relative with peptic ulcer. These observations indicate that psychopathological, psychosocial, characterological and hereditary factors are important pathogenetic contributors in peptic ulcer.

Antidepressant effect of Ro 11-1163, a new MAO inhibitor.

In an open clinical trial, Ro 11-1163, a newly developed MAO inhibitor, was given to 11 depressed patients, in a flexible dose, for 6 weeks. The clinical effect was measured on the 3rd day and at weekly intervals using the Hamilton and the Beck rating scales for depression and an overall self-assessment. A marked antidepressant effect was observed in almost all cases, which became evident as early as the 2nd day and resulted in complete remission in most patients at the end of the treatment period, with doses ranging between 100 and 400 mg/day. No serious side effects were noted, except for a transient agitation and insomnia. A battery of clinical and laboratory tests also failed to reveal any marked change during treatment. The results suggest that Ro 11-1163 is an effective antidepressant that has to be further evaluated by double-blind clinical trials.

Anxiety and adipose essential fatty acid precursors for prostaglandin E1 and E2.

OBJECTIVE: The purpose of the present study was to investigate the relation state and trait anxiety and adipose tissue essential fatty acid precursors for prostaglandins E1 and E2. METHODS: The sample consisted of 144 male and female Cretan adults, 23 to 69 years of age. Anthropometric and arterial blood pressure measurements were taken, and adipose tissue samples as well as data concerning general health habits were collected. Dietary data were collected using the weekly food frequency questionnaire and the 24-hour dietary recall method, while state and trait anxiety was assessed through the use of the Spielberger State-Trait Anxiety Inventory (STAI) and the Zung anxiety scale. RESULTS: State anxiety (STAI) related positively with sex (p < 0.0003) and negatively with adipose fat myristic acid (C14:0) (p < 0.004). Similarly, Zung trait anxiety related positively with sex (p < 0.0001) and negatively with adipose tissue myristic acid (C14:0) (p < 0.04). Spielberger trait anxiety related positively with adipose (LA + ALA)/(AA + EPA) ratio (p < 0.0002) and negatively with (C14:0) (p < 0.02) and dietary monounsaturated fat (p < 0.03). CONCLUSION: It appears that the positive relation between trait anxiety and adipose (LA + ALA)/(AA + EPA) ratio may stem from the inhibiting role of catecholamines on delta 6 and delta 5 desaturases.