Serotonergic interhemispheric asymmetry: Neurochemical and pharmaco-EEG evidence

1. Postmortem neurochemical investigations revealed interhemispheric asymmetry in the mediofrontal region of human brain. Significantly higher right hemisphere serotonin metabolite (5HIAA) content as well as increased maximal imipramine binding (IB) were found in the right hemisphere than in the left side.

2. IB did not show a gender difference in the mediofrontal area. However, women had higher IB in the right orbital frontal cortex than did men.

3. In vivo pharmaco-EEG results tend to support the postmortem neurochemical data. Intravenous chlorimipramine resulted in an asymmetric topographic distribution of the P300 auditory evoked potential, peak amplitudes were shifted to the right hemisphere.     

Gene probe for P0 messenger RNA used to index acrylamide toxic neuropathy in rats.

Cumulative exposure to the neurotoxicant acrylamide produces axonal damage in the distal ends of both central (CNS) and peripheral (PNS) nerve fibers and subsequent hind-limb paralysis. The messenger RNA which codes for the PNS myelin glycoprotein P0 (P0-mRNA) was used to monitor this toxic neuropathy in Sprague Dawley rats prior to, concurrent with, and subsequent to, ultrastructurally and immunocytochemically defined nerve damage. Rats were dosed every other day with acrylamide (50 mg/kg, IP) and sampled intermittently throughout a 4 week exposure period. Slot blot and Northern gel analyses of the proximal and distal sciatic nerve were used to determine a quantitated measure of P0-mRNA. Twenty-four hours after the first treatment, in the absence of ultrastructural damage, P0-mRNA increased 55% over control levels in the distal sciatic nerve. After 12 treatments, and concomitant with the appearance of spinal cord and PNS neuropathic damage and hindlimb dysfunction, P0-mRNA decreased 45% below control levels. Levels of P0-mRNA from rats exposed to 12 treatments of acrylamide but allowed to recover for 40 days, returned to 79% of control values to reflect the regeneration and remyelination occurring in the distal sciatic nerve. In spite of these fluctuations in levels of P0-mRNA, immunocytochemical staining of P0 protein in plastic sections of the distal sciatic nerve was present throughout all sample times. These results suggest that changes in neural specific mRNAs are sensitive to neurotoxic damage and can be used to monitor the pathogenesis of nerve degeneration.     

Effect of a protein binding change on unbound and total plasma concentrations for drugs of intermediate hepatic extraction

For substances eliminated from blood by the liver, the effect of a change in unbound fraction of drug (fu _b )on steady state total (C _b )and unbound (Cu _b )blood concentrations has hitherto only been considered for the two limiting cases, i.e., at the upper and lower extremes of hepatic intrinsic clearance (CL _int ).For a substance of very low CL _int ,if fu _b changes, C _t will change and Cu _b will remain constant, whereas if CL _int isvery high, Cu _b will change and C _b will remain constant.The present study defines the effects of a change in fu _b on C _b and Cu _b over the whole CL _int range. Computer simulations were undertaken which predicted that, for a given change in fu _b ,absolute and relative changes in C _b would decreasenonlinearly with increasing CL _{int, twhile the relative change in} Cu _{b would} increasewith CL _int .The absolute change in Cu_b would be independent of CL _int .Significant changes in C_b and Cu _{b would be observed at intermediate values of} CL _{int not just at the high and low extremes. These theoretical predictions were investigated experimentally in the isolated perfused rat liver by examining the effects of a change in} fu _{b of sodium taurocholate a substance with intermediate} CL _int (such that at fu _b =0.27,hepatic extraction ratio=0.71) induced by concurrent administration of sodium oleate. Sodium 24- ¹⁴ C-taurocholate (specific activity 52 Ci/mmol) was infused into the reservoir in a recycling system at 30 mol/hr for 105 min (n=6). At 45 min a bolus dose of sodium oleate (50 mmol) was administered to the reservoir, followed by a constant infusion of 143 mmol/hr for 1 hr. Following the administration of oleate, taurocholate fu _{b fell promptly by 55% (0.27–0.12). There was a relative increase of taurocholate} C _{b of 22.7% and a relative decrease in} Cu _{b of 45.4%, in accordance with the simulations (p<0.05). We conclude that important changes in unbound steady-state concentration, the pharmacologically active moiety, can occur upon changes in unbound fraction with compounds of intermediate hepatic intrinsic clearance}.This study was supported by the National Health and Medical Research Council of Australia.     

Tardive dyskinesia on Hungarian psychiatric wards

The authors found tardive dyskinesia (TD) in 23.5% of 200 hospitalized schizophrenic patients, most of whom had received neuroleptic treatment for at least two years. The frequency and severity of TD increased with age, and the more advanced the age at which the patient started taking neuroleptics, the more likely it was that TD would develop. Severe TD was more common in men than in women. Prolonged treatment with neuroleptics or the use of antiparkinsonism drugs increased the risk of TD.     

Effect of vinpocetine on retrograde axoplasmic transport

Vinpocetine, a derivate of vincamine, is widely used in the clinical pharmacotherapy of cerebral circulatory diseases. Herewith we report on a novel effect of vinpocetine: inhibition of retrograde axoplasmic transport of nerve growth factor (NGF) in the peripheral nerve. Blockade of retrograde transport of NGF results in transganglionic degenerative atrophy (TDA) in the segmentally related ipsilateral superficial spinal dorsal horn, which is characterized by depletion of the marker enzymes fluoride-resistant acid phosphatase (FRAP) and thiamine monophosphatase (TMP). At the same time, pain-related neuropeptides such as substance P (SP) and calcitonin gene-related peptide (CGRP), are depleted from lamina I-III from the segmentally related, ipsitateral Rolando substance of the spinal cord. On the basis of these experiments it is suggested that vinpocetine may result in a locally restricted decrease of nociception, that might be useful in clinical treatment of intractable pain. Pilot self-experiments support this assumption.     

Dexamethasone suppression and multiple hormonal responses (TSH,prolactin and growth hormone) to TRH in some psychiatric disorders

Summary Baseline and TRH-induced changes of thyroid stimulating hormone (TSH), prolactin (PRL), and growth hormone (GH) were measured in 15 healthy control subjects and 63 psychiatric inpatients with DSM-III diagnoses of major depression (n = 19), schizophrenic disorder (n = 20), alcohol dependence (n = 10), and adjustment disorder (n = 14); baseline and postdexamethasone cortisol (CS) were also determined 3–6 days after the TRH-challenge. All patients and controls were women of similar mean age, weight, height, and they were free from interfering illness or drugs.Baseline TSH and PRL were lower in depression, TRH-induced TSH and PRL responses were lower in the whole patient group, but most markedly in depression and alcohol dependence. Postdexamethasone CS was significantly higher in depression, schizophrenia and alcohol dependence. Basal GH did not differentiate the subgroups; TRH-induced pathological GH responses were sometimes found in the patient groups. The differences were most marked quantitatively in major depression: a multivariate analysis of variance showed that TSH, postdexamethasone CS and PRL were the most important variables in separating patients from controls. A discriminant function derived from these variables classified all controls and 18 of 19 depressed patients correctly; however, 25 of the 44 other patients were also classified with depression.It was confirmed that psychiatric patients show significantly more endocrine disturbances than controls, and this was seen not only in major depression but also in at least three other conditions. Further work is needed to identify other neuroendocrine patterns more specific to depressive disorder.     

Two cases of malignant and benign systemic mastocytosis

The authors give a short account about the clinical histories of two patients: one with malignant systemic mastocytosis resulting in acute myeloid leukaemia, the other with indolent systemic mastocytosis. A brief review is reported about the physiological and pathophysiological role of mastocyte system. Benign and malignant types, classification of mastocyte proliferation are detailed, several distinct characteristics of clinical appearance, main aspects of diagnosis, therapy and prognosis in patients with different forms of systemic mastocytosis are briefly discussed.     

A ventral approach to stereotaxy of the guinea pig brain

For skeletal muscles, a well-known match exists between the properties of motoneurones and those of their muscle fibres. Hence, the intramuscular distribution of different kinds of motoneuronal nerve endings (e.g. ‘slow’ versus ‘fast’) can be mapped by determining the distribution of the corresponding types of muscle fibre. As a background for further studies of motoneuronal plasticity, we needed precise measures of such distributions. Simple quantitative methods were developed for defining the position and extent of sub-populations of cells within a structure (e.g. the regional distribution of slow versus fast muscle fibres within a muscle cross-section): (a) The ‘mass vector method’ defined the relative position of the target cell cloud. A line was drawn between the calculated centre of mass for the target cells and that for the whole structure. The direction (a1) and length (a2) of this line gave a measure of the direction and degree of target cell eccentricity within the structure. (b) The ‘sector method’ delineated the region containing the target fibres. A circle around the centre of mass for the target fibres was subdivided into a number of equal sectors (standard setting: 20). The most remote point was found within each sector and a line joining these points defined the region of the target fibres. When applied to the ‘slow’ type I fibres of cross-sections from rat hindlimb muscles, the regional area estimates obtained by the sector method were highly correlated with, but 10% lower than those achieved by the well-established ‘convex hull’ method. Highly significant inter-muscular differences were observed for each one of the three new parameters described in this paper (a1, a2, b).     

Atrial pacing with two-dimensional echocardiography for evaluation of chest pain: comparison with thallium 201 scintigraphy

Atrial pacing was performed with two-dimensional (2-D) echocardiography and thallium 201 scintigraphy in 40 men with stable chest pain. Coronary angiography showed significant (one or more lesions greater than or equal to 50%) coronary artery disease (CAD) in 36 patients and no or insignificant CAD in 4. Two dimensional echocardiography showed a left ventricular wall motion abnormality (WMA) either at rest or with pacing in 28 (78%) patients with CAD, with 17 (47%) showing a new or worsened WMA with pacing. A thallium scan showing abnormality (reversible or fixed perfusion defect) was seen in 26 (72%) patients with CAD; 18 (50%) had a reversible defect. In all, 34 of the 36 patients with CAD (94%) had a WMA, a perfusion defect, or both (specificity 50%). Occurrence of both a WMA and a perfusion defect in individual segments ranged from 10 of 25 patients with septal abnormalities to 0 of 12 with abnormalities of the lateral segment. Sensitivity of 2-D echocardiography for identifying CAD in specific vessels was 81% for the left anterior descending (LAD) artery, 30% for the right coronary artery, and 20% for the circumflex artery (both p less than .001 compared with the LAD artery). Corresponding sensitivities for thallium 201 imaging were 54% (p less than .05 compared with 2-D echocardiography), 27%, and 8% (both p less than .05 compared with the LAD artery). When combined with atrial pacing, 2-D echocardiography and thallium 201 perfusion imaging are of similar value for diagnosing the presence of CAD in patients with stable chest pain. Two-dimensional echocardiography is superior to thallium 201 imaging for identifying the presence of significant CAD in the LAD artery, but both tests are limited in their ability to detect lesions of the right coronary or circumflex arteries.