Detection of Apoptosis in Peripheral Blood Cells of 31 Subjects Affected by Down Syndrome Before and After Zinc Therapy

Thirty-one patients affected by Down syndrome (DS) were investigated to study the presence of apoptosis in peripheral blood cells in relation to the plasma levels of zinc. Twelve patients had undergone therapy with ZnSO₄, while the remaining 19 were untreated. The presence of programmed cell death was evaluated by means of electron microscopy, in situ nick translation (NT), and agarose gel electrophoresis of DNA. These approaches evidenced the presence of apoptosis in peripheral blood cells of patients before therapy with ZnSO₄, while after zinc supplementation there was a reduction in the number of apoptotic cells. These results suggest that the process of programmed cell death in peripheral blood cells of patients with Down syndrome is related to the plasma levels of zinc ion.     

Localization of tissue plasminogen activator mRNA in adult rat brain

The distribution of tissue plasminogen activator (tPA) messenger RNA in rat brain was studied using in situ hybridization with ³⁵S UTP-labeled RNA probes derived from a fulllength tPA cDNA. Sense strand controls produced low, even backgrounds, with small elevations in the hippocampus. Full-length antisense probes produced strong signals over cerebral ventricular ependyma (including ependyma of the subcommissural organ), meninges, blood vessels, and Purkinje cell layer of the cerebellum, as well as strong signals over scattered cells throughout the brain. Some of these scattered labeled cells were large with lightly stained nuclei, while others were small with darkly stained nuclei. The large labeled cells, which were probably neurons, constituted 8% and 8% of cells in the brain stem and neocortex, respectively, and 100% of Purkinje cells. The small cells, which were present in all areas of the brain, constituted 3–11 % of cells in individual brain areas.     

Evaluation of late cardiotoxicity with pulsed Doppler echocardiography in patients treated for Hodgkin's disease

Summary. The impact of valvular, myocardial and pericardial abnormalities on cardiac haemodynamics in patients treated for Hodgkin's disease with COPP/ABVD with and without mediastinal irradiation was determined in 49 patients 2–10 years after induction therapy. Diagnostic procedures to evaluate cardiac function consisted of history, physical examination, exercise bicycle stress test, M-mode two-dimensional and pulsed Doppler echocardiography. No patient reported symptoms related to cardiomyopathy, and only one of the 49 had evidence of coronary heart disease. Pericardial thickening was seen on echocardiograms in 19/49 patients (38.8%), valvular thickening in 21/49 (42·9%), and reduced fractional shortening in 9/49 (18·4%). The Doppler-derived mean E and A (±SD) of transmitral flow were 0·75 ± 0·14 m/s and 0·56 ± 0·09 m/s, respectively, in patients receiving chemotherapy and 0·81 ± 0.19 m/s and 0·63 ± 0·20 m/s in those with additional mediastinal irradiation. There was no statistically significant difference between mean E and A in transmitral flow in patients treated for Hodgkin's disease and control subjects. Furthermore, the transtricuspid and hepatic vein flow velocities did not differ significantly. Although the present study demonstrates high frequencies of pericardial and valvular thickening in patients treated for Hodgkin's disease with the COPP/ABVD regimen with or without mediastinal irradiation, it showed no impact on cardiac flow velocities. The abnormalities might thus be of minor clinical relevance in these patients.     

Effect of intravenous ketanserin on the human action potential duration at fixed heart rate

Summary In this study any changes in action potential duration or Q-T interval due to acute doses of ketanserin were monitored. The effect of a bolus dose (10 or 20 mg) followed by an infusion (10 or 20 mg over 20 minutes) of ketanserin on the Q-T interval and action potential duration was studied in six patients undergoing routine cardiac catheterization. Action potential duration was measured with a silver-silver chloride electrode catheter while heart rate was kept constant by atrial pacing and reflex effects avoided by -adrenergic blockade. There were some prolongations of the action potential duration but they were not in excess of 40 msec and did not reach statistical significance (control 263±46.0 msec; bolus 269±52.1 msec; infusion 262±53.6 msec; nor were there any significant changes in Q-T interval. Thus acute intravenous doses of ketanserin, in the absence of hypokalaemia or other Q-T interval-prolonging drugs, have no consistent effect on Q-T interval or action potential duration; prolongation of the action potential, when it occurs, is small.     

Actions of nitric oxide on the acute gastrointestinal damage induced by PAF in the rat

The actions of nitric oxide (NO) on the acute gastrointestinal damage induced by platelet-activating factor (PAF) have been investigated in the rat.S-nitroso-N-acetyl penicillamine, which spontaneously generates NO, dose-dependently inhibited PAF-induced gastrointestinal plasma leakage, a measure of the initiation of vascular damage. The inhibitor of NO synthase,N^G-monomethyl-l-arginine substantially potentiated gastrointestinal damage and plasma leakage induced byE. coli endotoxin, but had no effect on that induced by intravenous infusion of PAF.Endogenous NO may thus have a protective role in the gastrointestinal vascular that can be mimicked by generators of NO. The protection afforded by endogenous NO may, however, be dependent on the nature of the inflammatory stimulus used to induce gastrointestinal damage.     

Effect of moderate exercise on salivary immunoglobulin A and infection risk in humans

The incidence of upper respiratory tract infections (URTI) and salivary immunoglobulin A concentrations [IgA_s] of nine individuals were examined during 12 weeks of moderate exercise training, and compared to ten sedentary controls. Changes in maximal oxygen uptake were assessed at initial, mid-point and final evaluations (T1–3), while changes in [IgA_s] and salivary immunoglobulin concentration-salivary albumin concentration ratio ([IgA_s]:[Alb_s]) were monitored at T1 and T3. During the 12 week period, symptoms of URTI were self-recorded daily. During the period of training the level of fitness significantly increased (P<0.05) in the exercise group. The number of days recording symptoms of influenza, but not of cold, and total light URTI symptoms was significantly reduced in the exercise group during the last weeks of training. A significant increase in [IgA_s] and in [IgA_s]:[Alb_s] was found in the exercise group after training. Both [IgA_s] and [IgA_s]:[Alb_s] were significantly related to the number of days showing symptoms of influenza (P<0.01) and the total number of days of sickness (P<0.05). These data provide quantitative support for the belief that regular, moderate exercise results in an increased [IgA_s] at rest and [IgA_s]:[Alb_s], which may contribute to a decreased risk of infection. Electronic Publication