Amyotrophic lateral sclerosis: oxidative energy metabolism and calcium homeostasis in peripheral blood lymphocytes.

There is evidence of oxidative injury in postmortem brain, spinal cord, and CSF of patients with sporadic amyotrophic lateral sclerosis (SALS patients). We investigated the oxidative metabolism and calcium homeostasis in peripheral blood lymphocytes from such patients and did not find statistical differences in the basal oxygen consumption rate (QO2), cytochrome c oxidase activity, catalase activity, and lactate production. However the increase in QO2, induced by an uncoupler of oxidative phosphorylation, was depressed and the basal (resting) level of free cytosolic calcium ([Ca2+]in) was higher in lymphocytes from SALS patients (p < 0.01). Further increase in free [Ca2+]in challenged by a K+ channel blocker or by an uncoupler of oxidative phosphorylation was similar in SALS and control lymphocytes. The results show that systemic changes consistent with the presence of mitochondrial and of calcium metabolism dysfunction are present in SALS.

Blood noradrenaline and 5-HT levels in depressed women during amitriptyline or lithium treatment.

Noradrenaline levels and platelet and free serotonin concentrations were studied in depressed women in-patients (n=78) before and during amitriptyline (n=41) or lithium treatment (n=37). Pronounced monthly differences in platelet serotonin level have been shown in these subjects before treatment. In all clinical subgroups (neurotic, involutional, manic-depressive patients) a significant fall in platelet serotonin level was observed with amitriptyline medication while an increase was noted with lithium. No significant correlations between serotonin concentrations and clinical outcome were found. Amitriptyline treatment also produced a decrease in peripheral noradrenaline concentration in all subgroups, while an increase was observed with lithium. Some correlations between noradrenaline level and degree of depression were noted in patients treated with amitriptyline or lithium. A more extended analysis of blood amine levels could supply meaningful information on the peripheral action of antidepressive drugs on noradrenaline and serotonin concentrations in depression.

Aspects of amitriptyline and nortriptyline plasma levels monitoring in depression.

Fifty-nine depressed female inpatients were treated with 100 mg amitriptyline (AMT) IM for 4 weeks. Depression ratings and determinations of the parent drug and nortriptyline (NT) were performed weekly. No direct relationship between plasma AMT + NT concentrations and therapeutic response was apparent, but beneficial therapeutic responses and significantly lower side-effect scores were more frequently noted in subjects with concentrations in the 100-200 ng/ml range. AMT + NT concentrations were significantly correlated with age. No significant difference was found in the number of responders between younger and older subjects with two clinical improvement criteria; however, a significant difference emerged when a third more restrictive clinical outcome criterion was adopted. The implications of the present findings for patient treatment and for the interpretation of previous studies are discussed. The data collected point to a possible usefulness of monitoring AMT and NT plasma levels, even if further investigations are needed.

Mirror speaking after neurosurgery. A case history.

The case is reported of a 23 year old patient, who at the age of nine underwent neurosurgery for an angiomatous meningioma of the right temporal lobe, and immediately afterwards realized he was able to speak backwards nearly as well as normally. Presently, the patient still retains this ability which is associated with analogous mirror reading and writing. Neurological examination and EEG, CT data as well as the scores of some neuropsychological tests are added.

PHA-stimulated cellular immune function and T-lymphocyte subsets in major depressive disorders.

We measured some immunological parameters in 20 hospitalized patients with major depression and 20 age- and sex-matched healthy controls. Both enumeration of immune cells, including T-lymphocyte subpopulations, and assay of T-cell function were studied. White blood cells were evaluated with an automated cell counter, T-cell subsets with an immunobead technique, and T-cell function with a phytohemagglutinin-induced proliferation in vitro assay. We found that T-lymphocyte responses to the mitogen were significantly lower in depressed patients than in controls. All the other parameters were normal. These findings suggest that functional but not numerical changes in T-lymphocytes characterize major depressive disorders.

Effects of lithium salts on pain experience in depressed patients.

15 depressed female patients were studied for sensitivity to pain stimuli before and after 1 month of treatment with lithium salts. By electric stimulation techniques, an aspecific sensitivity threshold, a pain sensitivity threshold and a pain tolerance threshold were measured and their relationship were evaluated. In this investigation, we evaluated the influence of the improvement of the clinical picture and of the blood levels of the drug on pain perception. Our data seem to suggest an analgesic action of lithium, which, however, appears to be partially masked by the effects on pain perception induced by the evolution of the depressive picture.

Memory performances in depressed patients during prophylactic treatment with lithium salts.

The study involved 42 subjects suffering from unipolar depression (35 females and 7 males) who had received 600-1,200 mg of lithium carbonate daily for periods ranging from 6 months to 7 years. Concurrently with the memory tests, the patients were also submitted to the Hamilton test for the evaluation of depression and blood samples were taken in order to measure lithium blood levels. In the groups of subjects examined by us (grouped according to lithemia, time on the drug and degree of depression, as, evaluated by Hamilton's test), significant differences were found only in the short-term figure test and, partially, in the long term memory verbal test.

Plasma and erythrocyte concentrations of lithium.

The authors have studied the clinical response, EMG and EEG changes in 12 depressed patients after 28 days of lithium carbonate treatment of 1,200 mg daily. The findings confirm: (1) a high correlation between the degree of improvement and the RBC lithium: plasma lithium ratio on the 28th day; (2) a slight decrease in motor conduction velocity (m.c.v.) and increase of M-response duration during lithium treatment; (3) no correlation between EEG and lithium levels and percentage of improvement.

[Long-term treatment with lithium salts and cerebral electric activity. Experimental research]. / Trattamento cronico con sali di litio ed attivita' elettrica cerebrale. Ricerche sperimentali.

An eeg study was carried out in rabbits to investigate the neurophysiological effects of chronic lithium clorure treatment. The Monnier and Gangloff's stereotaxic method was used for recording cortical and deep structure activity. Lithium clorure was administered i.p. at doses of 20 mg/Kg/die for 15-22 days (mean plasmatic levels: 0.04 mEq/l). The eeg changes consisted in synchronization of the cortical activity, slowing of the deep structure activity and increase of CAD spiking. The most interesting finding was the appearance of peculiar periodic spikes in the CAD and subcortical structures. A similar pattern has been previously described by us in rabbits treated with repeated ECT.

Acute effects of levodopa plus carbidopa on evoked potentials in Parkinson's disease.

Visual evoked potentials by flash (VEP-f) and pattern reversal (VEP-p) stimulation and BAEPs were performed in parkinsonian patients before and after 1 and 4 hours levodopa + Carbidopa administration in two separate experiments. In the first experiment (9 patients and 9 controls) an increase of latencies of peaks III and IV of VEP-f was observed in parkinsonian patients but not in controls. In the second experiment (6 patients) an increase of latencies of peaks N70 and P100 of VEP-p and an increase of latency of peak III and of III-V interval of BAEPs was observed. The results confirm the influence of dopaminergic systems on visual pathways and suggest that the effects of acute 1-DOPA administration may differ from those of chronic treatment. Moreover some evidence exists that dopaminergic systems are involved also in acoustic pathways.

Chemiluminescent determination of choline in cerebrospinal fluid and red blood cells.

The concentration of choline in the cerebrospinal fluid (CSF) of patients affected by primary dementia and in red blood cells (RBC) of depressed patients before and after treatment with lithium salts was determined using a chemiluminescent assay. The mean CSF concentration of choline was found to be 60 pmoles/ml (SD = 20 pmoles/ml) and this was lower than values obtained previously by spectrophotometric-colorimetric methods. Mean RBC choline concentrations before and after therapy with lithium salts were 20 nmoles/ml (SD = 16 nmoles/ml and 328 nmoles/ml (SD = 206 nmoles/l) respectively and these are similar to those reported previously (obtained by chemiluminescent and non-chemiluminescent methods).

Computed tomography and pattern reversal visual evoked potentials in chronic schizophrenic patients.

Eighteen chronic schizophrenic subjects treated with a uniform dosage (4-6 mg/day p.o.) of haloperidol were submitted to computed tomography (CT) and to pattern reversal visual evoked potentials (VEPs). Compared to age-matched controls, schizophrenic patients showed lateral and third ventricular enlargement, greatly delayed VEP latencies and reduced amplitudes. These abnormalities were not related to diagnostic subgroups. Schizophrenic patients with a positive family history for major psychiatric disorders showed normal CT scan measures and greatly abnormal VEP measures, whereas patients with a negative family history showed CT scan signs of atrophy and less pronounced VEP abnormalities.

P300 and CT scan in patients with chronic schizophrenia.

Twenty chronic male schizophrenic subjects aged 30-50 years were examined by an auditory event-related potential procedure for the evaluation of the P300 component, a CT scan and a neuropsychological test battery. The P300 latency was increased and its amplitude was reduced. CT scan measures showed lateral and third ventricle enlargement, and there was a global neuropsychological impairment. Poor neuropsychological performances were consistently associated with delayed P300 latencies, but not with CT scan measures. Ventricular enlargement was more pronounced among subjects with a negative family history for major psychiatric disorders.

[Depression and home environment]. / Depressione e ambiente domestico.

The Authors consider the higher frequency of depressive disorders in women and examine the correlations between psychopathological expressions of depression and women's social and cultural roles. The condition of life at home, that is peculiar to housewife, sometimes can be a psychopathological risk factor or psychosocial stressor, as well as other work conditions (whether the woman is employed or not), that have to be examined in relation to each person, according to the individual's biological, psychosocial and cultural features.

[Study of memory in cerebral damaged patients related to the side of lesion (author's transl]. / Studio della memoria in pazienti cerebrolesi in rapporto al lato della lesione.

Twenty-four subjects with cerebral lesions, 21 of vascular and 3 of neoplastic origin, have been tested by the Authors with a battery of tests for memory evaluation. They comprehended short term, middle term and long term memory tests. For the last ones, the subjects was requested to recall remote events presented under visual, verbal and auditory modality. For each test, results comparison between left and right hemispheric cerebral damaged patients was performed. The diagnosis of the hemispherical localisation, on the basis of clinical data established, have been confirmed by instrumental exams (EEG, CAT, Angiography). A clear difference in the results between the two groups of patients does not appear except in specific tests related to memory selective types, in which the sensitive modality of tests administration seems to be more closely in relation with the damaged hemispherical functions. Ribot's law on the longer life of old memories has not been confirmed by the long term memory tests in cerebral damaged patients.

P 300 latency, age and cognitive styles.

20 normal subjects were submitted to seven auditory ERP paradigms in which they were required to count regularly presented cliks (A1, A2, A3), cliks presented in pseudorandom order (B) and in which they had to discriminate relevant from non relevant stimuli characterized by side of provenience (C1, C2) or intensity difference (D). In paradigms C and D a P 300 component was evoked. Age was significantly correlated with P 300 latency only in paradigm D. There was a significant relationship between differences in subjective feelings of difficulty or engagement in performing the counting tasks in C and D and P 300 latency.

Neuroendocrinological aspects of depression and symptomatological picture.

Cortisol and prolactin circadian rhythms were determined in a group of depressed hospitalized women who were submitted the next day to the dexamethasone suppression test. The depressed were classified as endogenous and non-endogenous according to symptomatological criteria. Some significant differences were found between the two groups when compared to control subjects in cortisol as well as prolactin biorhythms, and the cortisol suppression percentages were significantly lower in the endogenous than in the non-endogenous. This difference is abolished by benzodiazepine treatment.

Effects of lithium administration on central and peripheral nervous system in rats. Biochemical and morphological findings.

The effect of 4 weeks' treatment with lithium chloride on the central and peripheral nervous system of Wistar albino rats was studied. Normal activity values of some brain enzymes related to energy transduction (LDH, MDH, COX, NADH-ccRT) and neuro-transmission (ACHe), evaluated both in the homogenate in toto and in the crude mitochondrial fraction, were obtained. Fine changes in mitochondrial organelles and nerve processes of neurocytes were ultrastructurally observed. The peripheral nerve studies revealed in some treated rats a slight motor nerve conduction velocity impairment by electro-physiological methods, but no significant alterations in the sciatic nerve specimens examined by electron microscopy.