Andrological, pathologic, morphometric, and ultrasonographic findings in rams experimentally infected with Brucella ovis

AbstractBrucella ovis is considered the most important infectious cause of reproductive disorders in sheep. The disease is characterized by epididymitis, subfertility and infertility in rams. B. ovis occasionally results in abortion in ewes, as well. The aim of this study was to evaluate kinetic changes in the reproductive organs of rams experimentally infected with B. ovis. Nine rams were experimentally inoculated intrapreputially with 2mL of a suspension containing 1.2×109CFU (colony-forming units)/mL of B. ovis (strain ATCC25840). In addition, 50μL of a suspension containing 1.2×1010CFU/mL of the same B. ovis strain was inoculated into each conjunctival sac, resulting in 3.6×109CFU total per ram. Six of nine infected rams had developed clinical changes in the tail of the epididymis at 30 days post-infection (dpi), but these changes regressed in 50% of these rams. Ultrasound demonstrated an increase in the area of the tail of the epididymis (P<0.001), reduction in the area of the testes (P<0.001), and an increased length and width of the seminal vesicles (P<0.001) during the course of infection. A sperm granuloma was diagnosed on the basis of ultrasonography findings. Microscopically, there was epididymitis, testicular degeneration, and seminal vesiculitis. Inflammatory cells were detected in the semen even before the development of epididymitis. Moreover, inflammatory cells were also found in the semen of asymptomatic rams, indicating that the presence of leukocytes in the ejaculate is a valuable method for screening potential carriers of infections in the genital tract

Inhalation of the prodrug PI3K inhibitor CL27c improves lung function in asthma and fibrosis

PI3K activation plays a central role in the development of pulmonary inflammation and tissue remodeling. PI3K inhibitors may thus offer an improved therapeutic opportunity to treat non-resolving lung inflammation but their action is limited by unwanted on-target systemic toxicity. Here we present CL27c, a prodrug pan-PI3K inhibitor designed for local therapy, and investigate whether inhaled CL27c is effective in asthma and pulmonary fibrosis. Mice inhaling CL27c show reduced insulin-evoked Akt phosphorylation in lungs, but no change in other tissues and no increase in blood glycaemia, in line with a local action. In murine models of acute or glucocorticoid-resistant neutrophilic asthma, inhaled CL27c reduces inflammation and improves lung function. Finally, inhaled CL27c administered in a therapeutic setting protects from bleomycin-induced lung fibrosis, ultimately leading to significantly improved survival. Therefore, local delivery of a pan-PI3K inhibitor prodrug reduces systemic on-target side effects but effectively treats asthma and irreversible pulmonary fibrosis