Immunization with a combination of merozoite surface proteins 4/5 and 1 enhances protection against lethal challenge with Plasmodium yoelii

It is widely believed that subunit vaccines composed of multiple components will offer greater protection against challenge by malaria, and yet there is little experimental evidence to support this view. We set out to test this proposition in the Plasmodium yoelii challenge system in rodents by comparing the degree of protection conferred by immunization with a mixture of merozoite surface proteins to that conferred by single proteins. We therefore examined a defined protein mixture made of the epidermal growth factor-like domains of P. yoelli merozoite surface protein 1 (MSP1) and MSP4/5, the homologue of P. falciparum MSP4 and MSP5. In the present study we demonstrate that this combination of recombinant proteins dramatically enhances protection against lethal malaria challenge compared to either protein administered alone. Many mice immunized with the MSP4/5 plus MSP1(19) combination did not develop detectable parasitemia after challenge. Combined immunization with MSP1(19) and yMSP4/5, a product characterized by lower protective efficacy, also greatly enhanced protection by reducing peak parasitemias and increasing the numbers of survivors. In some combination trials, levels of antibodies to MSP1(19) were elevated compared to the MSP1(19) alone group; however, improved protection occurred regardless of whether boosting of the anti-MSP1(19) response was observed. Boosting of anti-MSP1(19) did not appear to be due to contaminating endotoxin in the EcMSP4/5 material since enhanced protection was observed in C3H/HeJ mice, which are endotoxin insensitive. Collectively, these experiments show that multiantigen combinations offer enhanced levels of protection against asexual stage infection and suggest that combinations of MSP1, MSP4, and MSP5 should be evaluated further for use in humans.     

Tolerance of neonatal rat brain to acute hyperammonemia

The aim of the present work was to study the effects of hyperammonemia on brain energy metabolism in neonatal rats. Rats were rendered hyperammonemic by ammonium acetate administration. This decreased brain ATP concentrations but enhanced brain ammonia and lactate levels in both adult and neonatal rats. In adult rats, the decrease in brain ATP concentrations was accompanied by a plunge in the respiratory control rate (RCR) of brain mitochondria. However, the ammonia-induced effect on RCR was not observed in neonatal rats, suggesting that the fall in ATP levels observed in neonatal rats would not be due to an impairment of mitochondrial respiratory efficiency. However, in neonatal rats the increase in blood and brain ammonia concentrations did not change brain glutamate concentrations but decreased glutamine contents. These results may be of relevance for the understanding of the resistance of neonatal rats observed in this work to acute ammonia toxicity     

Leptomeningeal relapse of multiple myeloma following allogeneic stem cell transplantation

Progressive multiple myeloma may manifest features of 'de-differentiation', including a plasmablastic appearance, failure to secrete paraprotein, extramedullary involvement, and resistance to treatment. A 44-year-old woman with kappa-light chain myeloma underwent allogeneic stem cell transplantation (SCT). Twenty months later she developed paraspinal plasmablastic myeloma in the absence of paraprotein in urine or myeloma in the marrow. The paraspinal masses responded to chemotherapy. At 30 months she developed myelomatous meningitis, which proved resistant to intrathecal chemotherapy, irradiation, and donor lymphocyte infusion (DLI). The leptomeningeal disease led to death at 38 months. This is the first report of leptomeningeal relapse of myeloma after allografting.     

Current advances in the diagnosis and management of intracranial germ cell tumors

Central nervous system (CNS) germ cell tumors (GCT) account for less than 5% of primary brain tumors in children and young adults, but they continue to attract much attention. Over the past decade, two advances have led to re-evaluation of what constitutes conventional therapy for CNS GCT. For pure germinomas, the challenge remains the determination of the optimal field and dose of irradiation and whether or not the use of chemotherapy can lead to a reduced dose or elimination of irradiation altogether without compromising disease control or survival. For non-germinomatous germ cell tumors, an improvement in the current dismal prognosis is imperative.     

Antioxidant defence of the neonatal rat brain against acute hyperammonemia

Oxidative stress associated with the presence of elevated concentrations of ammonia in the brain has been proposed as one possible mechanism involved in ammonia toxicity. In a previous study [Brain Res.973 (2003) 31], we reported that neonatal rats are more resistant to acute ammonia toxicity than adult rats. In the present work, we studied the antioxidant status of the brain in hyperammonemic neonatal rats. Increased activities of the antioxidant enzymes and enhanced glutathione content were found in the brains of the hyperammonemic neonatal rats as compared to the controls. In addition, no changes in brain reactive oxygen species (ROS) levels and lipid peroxidation due to hyperammonemia were found. Therefore, acute ammonia intoxication does not induce oxidative stress in neonatal rats, a fact that may explain the resistance against hyperammonemia shown by neonatal rats.     

Metabolic effects of an enteral nutrition formula for diabetes: comparison with standard formulas in patients with type 1 diabetes

AIM: To evaluate the metabolic response (glucose, cholesterol, triglycerides and beta-hydroxy-butyrate) in patients with type 1 diabetes after a trial breakfast with an enteral nutrition formula designed for patients with diabetes and compare it with standard formulas (with and without fibre). MATERIAL AND METHODS: Each of 11 patients with type 1 diabetes consumed three types of liquid breakfast with a 1 week interval between each. (1). A standard diet (SD) with 49% carbohydrates, 35% lipids, 16% proteins-casein-and without fibre; (2). A fibre-enriched diet (FD): with 49% carbohydrates, 35% lipids, 16% casein and 15 g/1000 ml fibre; (3). A diet designed for patients with diabetes (DD) with 45% carbohydrates, 38% lipids, 16% soy protein and 15 g/1000 ml fibre. Each subject consumed 250 ml of each preparation at 9.00 AM after having administered their usual insulin dose, which was the same for each diet. Blood samples were taken at baseline and each 30 min, up to 150 min. RESULTS: The increase in postprandial glycaemia was lower with DD than with the standard preparations, reaching statistical significance at 60 min. There were no significant variations in the levels of cholesterol, triglycerides or beta-hydroxy-butyrate between the three preparations. CONCLUSIONS: After a trial breakfast, a diet designed for patients with diabetes provoked lower increases in postprandial glycaemia (with no changes in lipid or beta-hydroxy-butyrate levels) compared to the standard diets evaluated (with and without fibre).