A Novel Calcium-Dependent Protein Kinase 1 Inhibitor Potently Prevents Transmission to Foetuses in Mouse.

Treatments currently used to prevent congenital toxoplasmosis are non-specific of and have grievous side effects. To develop a more specific and less toxic drug, we have designed SP230, an imidazo[1,2-]pyridazine salt targeting the calcium-dependent protein kinase 1 (CDPK1) and active against acute toxoplasmosis in mice. Efficiency of SP230 to inhibit foetal transmission of the parasite was evaluated in a mouse model of congenital toxoplasmosis.

Engineering and Functional Evaluation of Neutralizing Antibody Fragments Against Congenital Toxoplasmosis.

Maternal-fetal transmission of Toxoplasma gondii tachyzoites acquired during pregnancy has potentially dramatic consequences for the fetus. Current reference-standard treatments are not specific to the parasite and can induce severe side effects. In order to provide treatments with a higher specificity against toxoplasmosis, we developed antibody fragments-single-chain fragment variable (scFv) and scFv fused with mouse immunoglobulin G2a crystallizable fragment (scFv-Fc)-directed against the major surface protein SAG1.

[Tricks and misuses of rapid diagnostic testing for malaria diagnosis].

Molecular biology or immunochromatographic tests are conventionally offered as aids in the routine diagnosis of malaria. However, the interpretation of their results requires a precise knowledge of their limits, both by the biologist and the physician. It is in particular conditioned by thorough interview of the patient in order to seek a history of recent or even older malaria disease.

Early life stress in mice is a suitable model for Irritable Bowel Syndrome but does not predispose to colitis nor increase susceptibility to enteric infections.

Neonatal period is characterized by an immature intestinal barrier. Scattered evidence suggests that early life stressful events induce long lasting alterations of intestinal homeostasis mimicking Irritable Bowel Syndrome (IBS). Those observations highlighting defect of intestinal barrier by early life stress questioned its potential role as a risk factor for gastrointestinal disorders such as colitis and infections.

Imidazo[1,2-b]pyridazines targeting Toxoplasma gondii calcium-dependent protein kinase 1 decrease the parasite burden in mice with acute toxoplasmosis.

The current therapeutic arsenal for toxoplasmosis is restricted to drugs non-specific to the parasite which cause important side effects. Development of more efficient and specific anti-Toxoplasma compounds is urgently needed. Imidazo[1,2-b]pyridazines designed to inhibit the calcium-dependent protein kinase 1 of Toxoplasma gondii (TgCDPK1) and effective against tachyzoite growth in vitro at submicromolar ranges were modified into hydrochloride salts to be administered in vivo in a mouse model of acute toxoplasmosis.