Pertactin-Deficient Bordetella pertussis with Unusual Mechanism of Pertactin Disruption, Spain, 1986-2018.

Bordetella pertussis not expressing pertactin has increased in countries using acellular pertussis vaccines (ACV). The deficiency is mostly caused by pertactin gene disruption by IS481. To assess the effect of the transition from whole-cell vaccine to ACV on the emergence of B. pertussis not expressing pertactin in Spain, we studied 342 isolates collected during 1986-2018. We identified 93 pertactin-deficient isolates. All were detected after introduction of ACV and represented 38% of isolates collected during the ACV period; 58.1% belonged to a genetic cluster of isolates carrying the unusual prn::del(-292, 1340) mutation. Pertactin inactivation by IS481 insertion was identified in 23.7% of pertactin-deficient isolates, arising independently multiple times and in different phylogenetic branches. Our findings support the emergence and dissemination of a cluster of B. pertussis with an infrequent mechanism of pertactin disruption in Spain, probably resulting from introduction of ACV.

Surfactant administration prior to one lung ventilation: physiological and inflammatory correlates in a piglet model.

OBJECTIVES: To test the hypothesis that surfactant, when given prophylactically during one lung ventilation (OLV), improves physiological stability and reduces inflammation. METHODS: Prospective controlled animal study. After 30 min of mechanical ventilation, surfactant was administered to the left lung of the treatment group. Right lung mechanical ventilation continued for 3 hr, after which the left lung was unblocked. Bilateral mechanical ventilation was continued for 30 min thereafter. Physiological parameters and biomarkers of inflammation in plasma, lung tissue homogenates, and bronchoalveolar lavage (BAL) were measured. MEASUREMENTS AND MAIN RESULTS: Oxygenation improved in the surfactant group, reaching statistical significance at 3 hr of OLV and again after 30 min of bilateral mechanical ventilation following the OLV. Plasma levels of interleukin (IL)-1 ß, IL-6, and tumor necrosis factor (TNF)-α showed a trend for reduction. The lung homogenates from the ventilated lungs had significantly lower levels of IL-1 ß (P < 0.01) and IL-6 (P < 0.01). The BAL specimen showed an overall reduction in the cytokine levels; IL-1 ß was significantly lower in the ventilated lungs (P < 0.01). CONCLUSIONS: Surfactant administration improves oxygenation and decreases inflammation, as evidenced by a decrease in several inflammatory cytokines both in the plasma and lungs of a piglet model of OLV.

Regulation of cadmium-induced apoptosis by PKCdelta in U937 human promonocytic cells.

Pulse treatment with cadmium chloride followed by recovery caused apoptosis in U937 human promonocytic cells. In addition, the treatment-induced PKCdelta translocation from cytosol to membrane fraction, which was already detected at 30 min of treatment; and also caused PKCdelta cleavage to give a 41-kDa fragment, which was detected at 3-6 h of recovery, concomitantly with the execution of apoptosis. All these effects were reduced by the PKCdelta-specific inhibitor rottlerin. By contrast, rottlerin did not prevent the cadmium-provoked stimulation of the stress response (as measured by HSP70 expression), nor inhibited the generation of apoptosis by heat-shock, which failed to cause PKCdelta translocation. Cadmium chloride rapidly induced p38(MAPK) activation, which was not affected by rottlerin. By contrast, the p38(MAPK) inhibitor SB203580 reduced PKCdelta translocation and cleavage, indicating that p38(MAPK) activation precedes and regulates PKCdelta activation. It is concluded that PKCdelta mediates apoptosis induction by cadmium ions via early membrane translocation, and also possibly through late kinase proteolytic cleavage and phosphorylation on tyrosine residues.