Thioridazine chronic administration: a behavioural and autoradiographic study

In rats the effects of chronic treatment with thioridazine (5 mg/kg orally administered for 22 days) were studied by means of behavioural supersensitivity to apomorphine and by means of dopamine (DA) receptors quantitative autoradiography. Locomotion and stereotypies induced by apomorphine increased after thioridazine chronic administration, whereas grooming behaviour decreased. Autoradiographic data showed an increase in DA receptors density both in the striatum and in the olfactory tubercle, to which the increase in stereotypies and locomotion could be respectively attributed. DA receptors increased also in the medial and dorsal frontal cortex. Moreover a decrease in DA receptors density appeared in the nucleus accumbens septi and in the lateral frontal cortex. Receptors decrease found in these regions might be associated with thioridazine-induced chronic inactivation of A10 DA neurons, to which the antipsychotic effect of the drug is attributed.     

Changes of plasma volume and plasma composition in water-deprived rats

Summary Plasma volume, hematocrit, protein and electrolyte concentrations in plasma were measured in control and water-deprived rats every three days after starting the experiment until the 15th day. Plasma volume variations, as related to body weight, suggest that water loss from plasma was proportional to total body water at three days and after 9 days of water deprivation. Greater plasma water than body water loss was found during the period between 3 and 9 days. Plasma protein and electrolyte variations suggest that during water deprivation there is a loss of protein, sodium and potassium from plasma, which is proportionally less than that of plasma water. Potassium, calcium and inorganic phosphorus were lost proportionally to plasma water. The variations in plasma volume changes were partially explained as due to variations in plasma protein and electrolyte concentrations.     

Amino acid release from the cerebral cortex of the rabbit, its relationship with the electrocorticogram

The rate of release of five amino acids (alanine, glutamine, glutamic acid, glycine, GABA) from the surface of the sensorimotor cortex has been determined in rabbits under local anesthesia immobilized with gallamine. Concomitant recording of the electroencephalogram and of blood pressure has been carried out. The scope of the research was to determine if a difference in the release of these aminoacids could be correlated with variations in cerebral electrical activity. Two open-ended silver cylinders were adapted to the cortex and filled with saline. Every 10 min, the liquid was removed and assayed using a dansylating procedure followed by thin layer chromatographic separation and fluorimetric determination of the amino acids. The EEG of non treated animals, followed for a period of 100 min, remained synchronized for the majority of the recording; the biochemical determinations indicated a slight but constant fall in the rate of release of all the amino acids. A significant increase in the release accompanied the EEG desynchronisation induced either with eserine (0.2 mg/kg), amphetamine (2 mg/kg), or with electrical stimulation of the reticular formation.     

Failure of averaging in the construction of a conductance-based neuron model

Parameters for models of biological systems are often obtained by averaging over experimental results from a number of different preparations. To explore the validity of this procedure, we studied the behavior of a conductance-based model neuron with five voltage-dependent conductances. We randomly varied the maximal conductance of each of the active currents in the model and identified sets of maximal conductances that generate bursting neurons that fire a single action potential at the peak of a slow membrane potential depolarization. A model constructed using the means of the maximal conductances of this population is not itself a one-spike burster, but rather fires three action potentials per burst. Averaging fails because the maximal conductances of the population of one-spike bursters lie in a highly concave region of parameter space that does not contain its mean. This demonstrates that averages over multiple samples can fail to characterize a system whose behavior depends on interactions involving a number of highly variable components.     

The effect of amiloride on sodium and potassium fluxes in red cells

1. The effect of amiloride on the influx and efflux of (24)Na and (42)K in red cells was studied. The drug was added to the bathing Ringer or else incorporated in resealed ghosts.2. Amiloride does not inhibit the active or the passive (ouabain insensitive) extrusion of (24)Na.3. Amiloride inhibits the influx of (24)Na into red cells by 70%.4. Whether added to the inside or to the outside of the cells amiloride has no effect on the efflux of (42)K.5. Amiloride does not modify the uptake of (42)K from control Ringer. This uptake is strongly inhibited by the removal of Na. Amiloride has no effect on the extent of this inhibition.6. It is concluded that amiloride specifically inhibits the passive penetration of Na, and has no effect on the Na-K-pumping mechanism. However, at the concentration which inhibits 70% of the influx, amiloride fails to produce an observable effect on the ouabain-insensitive Na-efflux.7. On the basis that the information obtained could be extrapolated to other membranes, the effect of amiloride on epithelial membranes is discussed.     

Seeing or not seeing where your hands are

Previous findings have demonstrated the existence of a visual peripersonal space centered on the hand in humans and its modulatory effects on tactile perception. A strong modulatory effect of vision on touch perception was found when a visual stimulus was presented near the hand. In contrast, when the visual stimulus was presented far from the hand, only a weak modulatory effect was found. The aim of the present study was to verify whether such cross-modal links between touch and vision in the peripersonal space centered on the hand could be mediated by proprioceptive signals specifying the current hand positions or if they directly reflect an interaction between two sensory modalities, i.e., vision and touch. To this aim, cross-modal effects were studied in two different experiments: one in which patients could see their hands and one in which vision of their hands was prevented. The results showed strong modulatory effects of vision on touch perception when the visual stimulus was presented near the seen hand and only mild effects when the vision of the hand was prevented. These findings are explained by referring to the activity of bimodal neurons in premotor and parietal cortex of macaque, which have tactile receptive fields on the hand, and corresponding visual receptive fields in the space immediately adjacent to the tactile fields. One important feature of these bimodal neurons is that their responsiveness to visual stimuli delivered near the body part is reduced or even extinguished when the view of the body part is prevented. This implies that, at least for the hand, the vision of the hand is crucial for determining the spatial mapping between vision and touch that takes place in the peripersonal space. In contrast, the proprioceptive signals specifying the current hand position in space do not seem to be relevant in determining the cross-modal interaction between vision and touch.     

The aniridia-Wilms tumor association: The critical role of chromosome band 11p13

The role of del (11)(p13) as a cause of aniridia, with and without Wilms tumor, is strengthened by demonstration of this chromosome aberration in 3 patients: monozygous twin girls, both of whom have aniridia and mental retardation and one of whom has a Wilms tumor; and an unrelated boy with aniridia and ambiguous genitalia. The break points defining the interstitial deletion for the twins are 11p13 and 11p15.1, while for the boy they are 11p1302 and 11p14.1. These patients and their karyotypes substantiate the critical importance of chromosome band 11p13 (or its hemizygous representation) in the development of aniridia and an associated Wilms tumor diathesis, as had been suggested previously (Riccardi VM, Sujansky E, Smith AC, Francke U, (1978): Pediatrics 61, 604-610).     

Nonmyeloablative stem cell transplantation is an effective therapy for refractory or relapsed hodgkin lymphoma: results of a spanish prospective cooperative protocol.

We report the results of reduced-intensity conditioning allogeneic stem cell transplantation (allo-RIC) in patients with advanced Hodgkin lymphoma (HL). Forty patients with relapsed or refractory HL were homogeneously treated with an RIC protocol (fludarabine 150 mg/m(2) intravenously plus melphalan 140 mg/m(2) intravenously) and cyclosporin A and methotrexate as graft-versus-host disease (GVHD) prophylaxis. Twenty-one patients (53%) had received >2 lines of chemotherapy, 23 patients (58%) had received radiotherapy, and 29 patients (73%) had experienced treatment failure with a previous autologous stem cell transplantation. Twenty patients (50%) were allografted in resistant relapse, and 38 patients received hematopoietic cells from an HLA-identical sibling. Five patients (12%) died from early transplant-related mortality (before day +100 after allo-RIC). One-year transplant-related mortality was 25%. Acute GVHD developed in 18 patients (45%). Chronic GVHD developed in 17 (45%) of the 31 evaluable patients. The response rate 3 months after the allo-RIC was 67% (21 [52%] complete remissions and 6 [15%] partial remissions). Eleven patients received donor lymphocyte infusions (DLIs) for disease relapse. The response rate after DLI was 54% (3 complete remissions and 3 partial remissions). Overall survival (OS) and progression-free survival (PFS) were 48% +/- 10% and 32% +/- 10% at 2 years, respectively. Refractoriness to chemotherapy was the only adverse prognostic factor for both OS (63% +/- 12% versus 35% +/- 13%; P = .05) and PFS (55% +/- 16% versus 10% +/- 9%; P = .006). For patients with failure of a prior autologous hematopoietic stem cell transplantation, results were especially good for those who experienced late relapses (>/=12 months: 2-year OS and PFS were 75% +/- 16% and 70% +/- 18%, respectively). These data suggest that allo-RIC is feasible in heavily pretreated HL patients and has an acceptable early transplant-related mortality. Results are better in patients allografted in sensitive disease. Both responses observed after the development of GVHD and DLI may suggest a graft-versus-HL effect. Allo-RIC has to be considered an effective therapeutic approach for patients who have had treatment failure with a previous autologous hematopoietic stem cell transplantation.