Cerebral malaria (CM) is a leading cause of death in Plasmodium falciparum infections. In the berghei ANKA (PbA) murine model, CM pathogenesis associated with low nitric oxide (NO) bioavailability and brain microcirculatory complications, marked decrease cerebral blood flow, vasoconstriction, vascular plugging by adherent cells, hemorrhages. Using intravital microscopy through closed cranial window, here we show that NO supplementation form donor (dipropylenetriamine NONOate [DPTA-NO])...

The murine model of cerebral malaria (ECM) caused by Plasmodium berghei ANKA (PbA) infection in susceptible mice has been extensively used for studies pathogenesis and identification potential targets human CM therapeutics. However, the seldom explored to evaluate adjunctive therapies this complication. A first step toward goal is define a treatment protocol with an effective antimalarial drug able rescue presenting late-stage ECM. We evaluated efficacy artemisinin, artemether, artesunate,...

Cerebrovascular dysfunction plays a key role in the pathogenesis of cerebral malaria. In experimental malaria (ECM) induced by Plasmodium berghei ANKA, cerebrovascular characterized vascular constriction, occlusion and damage results impaired perfusion reduced blood flow oxygenation, has been linked to low nitric oxide (NO) bioavailability. Here, we directly assessed function ECM using novel cranial window method for intravital microscopy pial microcirculation probed NOS isoforms...

Abstract Background Cerebral malaria (CM) is a lethal complication of Plasmodium falciparum infections. In the berghei ANKA (PbA) murine model, CM associated with marked brain inflammation, increased expression endothelial cell adhesion molecules and leukocyte platelet accumulation in vessels, causing vascular occlusion decreased blood flow, damaging endothelium leading to blood-brain barrier breakdown, leakage hemorrhages. Exogenous nitric oxide (NO) administration largely prevents...

Immune responses to malaria blood stage infection are in general defective, with the need for long-term exposure parasite achieve immunity, and development of immunopathology states such as cerebral many cases. One potential reasons difficulty developing protective immunity is poor memory responses. In this paper, association cellular reactivity lymphoid organs (spleen, lymph nodes Peyer's patches) pathology was evaluated during Plasmodium berghei ANKA CBA mice.CBA mice were infected 1 x...

Ten 1-phenyl-1H-pyrazolo[3,4-b]pyridine derivatives connected by a linker group to benzenesulfonamide moieties with different substituents in the 4-position were synthesized and assayed against Plasmodium falciparum. These ten compounds exhibited activity vitro chloroquine-resistant clone W2 IC50 values ranging from 3.46 9.30 μM. The most active substituent R2 = Cl or CH3 at moiety lowest IC50. Compounds an R1 CO2Et 5-position of 1H-pyrazolo[3,4-b]pyridine ring presented lower than those CN...

Background Low nitric oxide (NO) bioavailability plays a role in the pathogenesis of human as well experimental cerebral malaria (ECM) caused by Plasmodium berghei ANKA (PbA). ECM is partially prevented administration NO-donor dipropylenetriamine NONOate (DPTA-NO) at high concentration (1 mg/mouse), which also induces major side effects such sharp drop blood pressure. We asked whether alternative strategies to improve NO with minor would be effective preventing ECM. Methodology/Principal...

Abstract Background Babesiosis represents a veterinary and medical threat, with need for novel drugs. Artemisinin-based combination therapies (ACT) have been successfully implemented malaria, human disease caused by related parasites, Plasmodium spp. The aim of this study was to investigate whether ACT is active against Babesia in vitro vivo . Methods Mefloquine, tafenoquine, primaquine, methylene blue lumefantrine, alone or artesunate, were tested bovis Parasite growth verified using SYBR...

Background: Experimental models using Plasmodium berghei ANKA (PbA)-infected mice have been essential for uncovering cerebral malaria (CM) pathogenesis. However, variability in experimental CM (ECM) incidence, onset, and mortality introduce challenges when analyses rely solely on infection day, which may reflect different disease stages among animals. Methods: We applied machine learning to predict ECM risk onset a cohort of 153 C57BL/6, 164 CBA, 53 Swiss Webster mice. First, we fitted...

Abstract The immunogenicity and protective efficacy of various antigen‐adjuvant formulations derived either from the merozoite‐surface protein‐3 (MSP‐3) or glutamate‐rich protein (GLURP) Plasmodium falciparum were evaluated in Saimiri sciureus monkeys. These proteins selected for studies based primarily on their capacity inducing an antibody‐dependent cellular inhibition effect parasite growth. Some S. monkeys immunized with MSP‐3 212−380 ‐AS02 GLURP 27−500 ‐alum able to fully partially...

Plasmodium berghei ANKA infection in C57Bl/6 mice induces cerebral malaria (CM), which reproduces, to a large extent, the pathological features of human CM. However, experimental CM incidence is variable (50-100%) and period may present range as wide 6-12 days post-infection. The poor predictability when infected will develop can make it difficult determine causal relationship early changes outcome. With purpose contributing solving these problems, algorithms for prediction were built....

This experimental model was designed to assess the mouse pial microcirculation during acute and chronic, physiological pathophysiological hemodynamic, inflammatory metabolic conditions, using in vivo fluorescence microscopy. A closed cranial window is placed over left parieto-occipital cortex of mice. Local recorded real time through epi illumination, measurements vessels diameters red blood cell (RBC) velocities are performed. RBC velocity measured real-time cross-correlation and/or...

ABSTRACT The immunogenicity and efficacy of a hybrid recombinant protein derived from the N-terminal end glutamate-rich (GLURP) C-terminal portion merozoite surface 3 (MSP3) Plasmodium falciparum was evaluated in Saimiri sciureus monkeys. GLURP/MSP3 protein, expressed Lactococcus lactis , administered association with alum, Montanide ISA720, or complete incomplete Freund adjuvant (CFA/IFA) groups five animals each. three formulations were shown to be immunogenic, but one alum weak compared...

The understanding of the mechanisms immunity in malaria is crucial for rational development interventions such as vaccines. During blood stage infection, spleen considered to play critical roles both and immunopathology Plasmodium falciparum infections.Saimiri sciureus monkeys were inoculated with stages P. (FUP strain) spleens removed during acute disease (days 7 13 infection) convalescence (15 days after start chloroquine treatment). Cytokine (IFNγ, TNFα, IL2, IL6, IL10, IL12) responses...

Human cerebral malaria (HCM) is a life-threatening complication caused by Plasmodium falciparum infection that continues to be major global health problem despite optimal anti-malarial treatment. In the experimental model of (ECM) berghei ANKA, bolus administration nimodipine at high doses together with artemether, increases survival mice ECM. However, dose and route used associated cardiovascular side effects such as hypotension bradycardia in humans mice, which could preclude its potential...

Hybrid products in which the dihydroartemisinin scaffold is combined with NO-donor furoxan and NONOate moieties have been synthesized studied as potential tools for treatment of cerebral malaria (CM). The designed were able to dilate rat aorta strips precontracted phenylephrine a NO-dependent mechanism. All hybrid compounds showed preserved antiplasmodial activity vitro vivo against Plasmodium berghei ANKA, comparable artesunate artemether. 10, selected additional studies, was capable...

Abstract Vascular dysfunction associated with low nitric oxide (NO) biavailability and plasma L-arginine levels is observed in both human experimental cerebral malaria (ECM). In ECM, cerebrovascular constriction results decreased pial blood flow hypoxia, administration of NO donors reverses increases survival. Supplementation L-arginine, the substrate for synthesis by synthases, has been considered as a strategy to improve vascular health act adjunctive therapy severe malaria. We...