Malarial PI4K inhibitor induced diaphragmatic hernias in rat: Potential link with mammalian kinase inhibition.

Background: MMV390048 is an aminopyridine plasmodial PI4K inhibitor, selected as a Plasmodium blood-stage schizonticide for a next generation of malaria treatments to overcome resistance to current therapies. MMV390048 showed an acceptable preclinical safety profile and progressed up to Phase 2a clinical trials. However, embryofetal studies revealed adverse developmental toxicity signals, including diaphragmatic hernias and cardiovascular malformations in rats but not rabbits.

Quantification of Drug-Induced Inhibition of Canalicular Cholyl-l-Lysyl-Fluorescein Excretion From Hepatocytes by High Content Cell Imaging.

We describe the use of a commercially available high content cell imaging algorithm (Cellomics Arrayscan Spot Detector) to quantify biliary excretion of the fluorescent probe substrate cholyl-l-lysyl-fluorescein (CLF) from rat hepatocytes cultured in collagen/matrigel sandwich configuration and to explore inhibition of this process by a variety of test compounds. The method provided robust, reproducible data. Twenty-nine pharmaceuticals inhibited biliary CLF efflux from hepatocytes and a broad range of potencies of inhibition were observed (IC50 values ranged between <1 and 794 µM).

Canopy effects droplet size distribution and meteorological change.

Wind speed fluctuations measured via a 3-dimensional sonic anemometer recording at 10 Hz returned detailed information both above and within the canopy. The information returned facilitated detailed descriptions of atmospheric energy. In short, large energetic motions equal spray transfer into the target zone, the plant canopy.

Field tests of malathion and permethrin applied via a truck-mounted cold fogger to both open and vegetated habitats.

Field tests of formulated permethrin (Permanone 30:30) and malathion applied by ground ultra-low volume equipment were conducted using caged, laboratory-reared, adult Ochlerotatus taeniorhynchus. Cages were placed in an open field and also in semi-dense scrub pine. Two doses, a high and a medium dose of each compound, were applied as suggested by the label.

A comparison of two ultra-low-volume spray nozzle systems by using a multiple swath scenario for the aerial application of fenthion against adult mosquitoes.

Two hydraulic spray nozzle systems, a flat fan and a high-pressure hollow cone, were used for ultra-low-volume application of the mosquito adulticide fenthion under a multiple swath scheme. Eight swaths at 322-m intervals were applied from a height of 91 m to simulate operational conditions. Deposition, effects on nontarget organisms (fiddler crabs), aerial flux, and mosquito (Ochlerotatus taeniorhynchus) mortality were monitored for 8,230 m downwind, including the area under all 8 swaths.

A comparison of two spray nozzle systems used to aerially apply the ultra-low-volume adulticide fenthion.

Field experiments with the mosquito adulticide fenthion (Baytex) compared the conventional flat-fan nozzle system (Tee Jet 8002SS) and a new high-pressure hollow-cone nozzle system (1/8 MISS). Ground deposition and aerial flux of the mosquito adulticide fenthion were measured up to 4.83 km downwind by using filter paper and yarn collectors, respectively.