Store operated calcium entry is a key regulator in the activation of leukocytes. 3,5-bistrifluoromethyl pyrazole (BTP) derivatives have recently been identified as inhibitors of T lymphocyte activation. The inhibitory effect of one of these compounds, BTP2, appears to be due to inhibition of store operated calcium influx. Polymorphonuclear neutrophils provide effective protection against bacterial infection but they are also involved in tissue damage during chronic inflammation. As for T lymphocytes, their activation relies on store operated calcium entry. We therefore investigated the effect of BTP2 on calcium homeostasis and functional responses of human neutrophils. BTP2 significantly inhibited the calcium influx after stimulation with thapsigargin or fMLF. This inhibition was seen after 5 min of incubation with 10 µM BTP2 and after 24h with lower concentrations. With 24h incubation, the effect appeared irreversible since the removal of BTP2 3 hours before the experiment did not reduce this inhibition in granulocyte differentiated HL60 cells. In human neutrophils BTP2 reduced superoxide anion production by 82% after 24h of incubation. On the contrary, phagocytosis, intraphagosomal radical production and bacterial killing by neutrophils were not significantly reduced even after 24h treatment with 10 µM BTP2. This work suggests that BTP2 could become an important tool to characterize calcium signaling in neutrophils.Furthermore, BTP2 or related compounds could constitute a new approach to the down regulation of neutrophils in chronic inflammatory disease without compromising antibacterial host defense.

In this study we determined whether craniofacial development in rats could be influenced by an early temporary (3 d) nasal obstruction associated with forced oral breathing. The rats were killed at specific time points after surgery. Plasma samples were taken for biochemical analyses, and cephalometric measurements were performed. Shortly after nasal obstruction, the vertical nasomaxillary complex and the longitudinal skull base proved to be smaller in both sexes of test rats compared with controls. This was maintained in male rats but not in female rats. In female rats, only the longitudinal skull base remained somewhat shorter as the animals grew older. Reversible nasal obstruction was further associated with reduced dimensions of the olfactory bulbs lasting into adulthood and an initial decrease in lung weight. One day after implementing nasal obstruction, basal corticosterone levels had increased (by over 1,000%) and stayed at a high level in female rats. In male rats, however, the corticosterone level seemed to return to normal by day 90. Oral breathing was also associated with a lower level of thyroid hormone, especially at the shorter term intervals in both sexes. We conclude that a 3-d nasal obstruction period in young rats leads to long-term hormonal changes and to craniofacial structural adaptation.

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The FERTILE experiment was twice performed onboard the Mir space station during the Cassiopée and Pégase French space missions. The goal was to analyze the effects of microgravity on fertilization and embryonic development, and then on further development on the ground in the amphibian Pleurodeles waltl. The present paper reports development that occurred in the laboratory after landing. Recovered on the ground at the hatching stage, young larvae reared at room temperature underwent metamorphosis and became adults without obvious abnormalities. Of particular interest was the rearing temperature that induced a delayed metamorphosis for animals from the Cassiopée space mission, but not for animals from the Pégase mission. The rate of development and the morphology were analogous in these animals and in ground controls reared in a similar annual period. Analysis of offspring was performed using these animals. Males born in space were first mated with control ground-born females and then with females born in space. The mating gave progeny that developed normally. Depending on the methods used and on the limits of the analyses, the results clearly demonstrated that animals born in space were able to live and reproduce after return to the ground.