Role of mononuclear phagocytes in elimination of Plasmodium chabaudi AS infection

Summary The role of mononuclear phagocytes in acquired immunity resulting in the intraerythrocytic destruction and elimination of malarial parasites was investigated in the murine model of infection with Plasmodium chabaudi AS. Mice were treated 1 day before or 6 days after infection with agents which either result in augmentation or activation of the non–specific, microbicidal effector function of mononuclear phagocytes or in depletion of cells of this lineage. To examine the effect of agents which activate mononuclear phagocytes, A/J mice, which are susceptible to P. chabaudi AS and exhibit fulminant parasitaemia and death within 10 days of intraperitoneal infection with 10⁶ P–RBC, were treated intravenously with muramyl dipeptide (MDP) or liposome–encapsulated MDP–glycerol dipalmitate (MDP–GDP). Treatment administered 1 day before infection was ineffective. Treatment on day 6 post–infection with liposome–encapsulated MDP–GDP (1 ftg) resulted in a significant decrease in parasitaemia on day 8 and survival, while treatment with free MDP (100 ^g) resulted only in a significant decrease in parasitaemia. To examine the effect of depletion of mononuclear phagocytes, C57BL/6 mice, which are resistant to P. chabaudi AS infection and eliminate the parasite by 4 weeks, were treated intravenously with 3 mg silica. Silica administered 1 day before or 6 days post–infection abrogated resistance resulting in a delay in elimination of the parasite and host mortality. Treatment on day 6 was more effective, with death by day 13 post–infection of 70% of the normally resistant C57BL/6 mice which exhibited fulminant parasitaemia levels. These results thus provide in–vivo evidence that mononuclear phagocytes play a critical role in the elimination of infection with the murine malaria species P. chabaudi AS. Furthermore, these results suggest that the time of administration of agents which alter mononuclear phagocyte function may be important in determining their effect on host antimalarial defences.     

Structural and functional changes of the gastric mucosa in rats with portal hypertension

Structural and functional changes of the gastric mucosa were studied in rats made portal hypertensive by partially ligating the portal vein. Studies were carried out at either 3 or 12 days after ligation or sham operation. At 3 days, structural changes were greater than at 12 days, the major effects being vascular congestion in the lamina propria, muscularis mucosa, submucosa, and submucosal oedema. Transmission electron microscopy showed only a mild hyperplasia in the muscularis mucosa. Gastric blood flow appeared to decrease at 3 days post-ligation compared to sham-operated control rats, but was significantly increased by 12 days after ligation (P less than 0.01). Cardiac output also appeared to increase in the portal hypertensive rats by 12 days post-ligation but this was not statistically significant. Portal venous inflow was significantly increased by 12 days (P less than 0.05) but after correction for collateral circulation liver blood flow had returned to normal values by 12 days post-ligation.     

A Permanently Implanted Endocardial Electrode Complicating Ventricular Tachycardia with A Second VT

A VVI pacemalter was permanently implanted for the purpose of suppressing recurrent ventricular tachycardia (VT). Not only did the device fail to suppress the VT, but also the permanent endocardial electrode caused a second VT which was more rapid and clinically more severe. When a new VT occurs in the presence of a permanently implanted ventricular pacing system, the implanted electrode should he considered as one of the possible etiologic causes for the VT.     

Closed Loop Control of Rate Adaptive Pacing: Clinical Assessment of a System Analyzing the Ventricular Depolarization Gradient

Closed loop control of rate adaptive pacing has theoretical advantages over current rate responsive pacemakers. The first available system (which senses the ventricular depolarization gradient) has been evaluated in ten patients. The pacing response to a variety of exercise and nonexercise stimuli was assessed. Response to isotonic exercise was prompt and proportional to the exertion involved while isometric exercise and mental stress produced obvious but more gradual increases in pacing rate. In seven patients, comparison between the intrinsic P wave and pacing rate showed a high correlation during exercise (r = 0.91) and mental activity (r = 0.87). Postural changes induced a paradoxical response. Closed loop rate responsive pacing based upon analysis of the ventricular depolarization gradient produces a fast and appropriate rate response to most physiological stimuli.     

Radionuclide Evaluation of Dual Chamber Pacing: Comparison Between Variable AV Intervals and Ventricular Pacing

We prospectively evaluated changes in left ventricular ejection fraction, end diastolic volume, and stroke volume via radionuclide multigated acquisition study, Comparison was made between ventricular pacing and dual chamber pacing with varying AV intervals. The volumes and changes in ejection fraction were determined at rest, at set increased pacing rates, and during physiological stress. AV sequential pacing shows overall improvement in cardiac function in the majority of patients regardless of left ventricular function. The shorter AV interval would be appropriate for the majority of patients who have an atrial tracking mechanism (adequate intrinsic sensed atrial activity followed by ventricular pacing) and who undergo significant physiological stress.     

Impedance of Pacemaker Leads: Correlation of Different Methods

This study compares three different pacing system analyzers, which measure impedance at different points during an impulse, with measurements telemetered from implanted pacemakers from four different manufacturers. Measurements were obtained at the time of implantation in a group of 103 patients. The measurements obtained by these different methods differ significantly from each other; the later during the impulse the impedance is measured, the higher in general its value. Interpretation of impedance values should take into account the technique of measurement.     

The effects of albumin bound fatty acids on the platelet inhibitory function of human endothelial cells

Abstract. This study was carried out to evaluate the effects of albumin-bound fatty acids on the anti-platelet effects of endothelial cells. Primary cultures of human endothelial cells (ECM), grown in confluent monolayers, were incubated with plasma or growth medium enriched with albumin-bound fatty acids (FA) for 2–20 h. The effects of ECM on ADP-induced platelet aggregation (PA) and collagen-induced PA and prostaglandin synthesis in platelet-rich plasma were tested.
ECM released an inhibitor of platelet reactions which resembled the activity of PGI₂ (prostacyclin). The inhibitory activity was increased by preincubation of ECM with arachidonic acid (AA). A moderate decrease of the activity was obtained by incubation with longchain saturated, monoenoic and dienoic unsaturated fatty acids. A pronounced decrease of the inhibitor was obtained by incubation with di-homo-γ-linolenic acid (DHLA).
Paired combinations of AA with the other fatty acids in the incubation medium partially restored the inhibitor activity obtained by the separate FA.
The stimulation of the inhibitor by AA was dose dependent and high concentrations of AA reduced this activity.
The present study indicates that the quantity and quality of the plasma free fatty acids can affect the endothelial cells' ability to act as a non-thrombogenic surface.