(pollen beetle) gastrointestinal disease experimentally reproduced in sheep.

Intoxication of sheep and cattle by recently occurred in Uruguay and Argentina in association with severe drought. Although the disease was experimentally reproduced in sheep in the 1970s, there is limited information on clinical and pathologic findings of sheep experimentally intoxicated by this beetle. Here, we described the clinical, gross, and microscopic findings in 3 sheep orally dosed with (treatment group, TG) and in 2 control sheep (control group, CG) dosed with distilled water.

Intoxication of dairy cows in Uruguay by ingestion of cocklebur () seeds in sorghum silage.

The ingestion of cotyledons or seeds of cocklebur () causes poisoning as a result of acute liver failure. Here we describe a spontaneous outbreak of toxicity in dairy cows in Uruguay. The outbreak occurred in the winter when the cows were fed sorghum silage contaminated with seeds.

Discovery of CHF-6523, an Inhaled Selective PI3Kδ Inhibitor for the Treatment of Chronic Obstructive Pulmonary Disease.

The design of inhaled selective phosphatidylinositol 3-kinase delta (PI3Kδ) inhibitors for the treatment of inflammatory lung diseases was pursued. Knowledge-based design of a novel isocoumarin scaffold that was able to adopt a topology ensured the desired PI3Kδ selectivity. Achievement of low nanomolar cellular potencies through hinge binder group optimization, reduction of intrinsic permeability through head group optimization to extend lung retention, and screening of crystalline forms suitable for administration as dry powders culminated in the identification of compound .

Discovery and Optimization of Pyridazinones as PI3Kδ Selective Inhibitors for Administration by Inhalation.

A hit-to-lead campaign pursuing the identification of novel inhalant small-molecule phosphatidylinositol 3-kinase (PI3K) inhibitors for the treatment of inflammatory respiratory diseases is disclosed. A synthetically versatile pyridazin-3(2)-one scaffold was designed, and three exit vectors on the core moiety were used to explore chemical diversity and optimize pharmacological and absorption, distribution, metabolism, and excretion (ADME) properties. Desired modulation of PI3Kδ selectivity and cellular potency as well as ADME properties in view of administration by inhalation was achieved.