Craniofacial development and physiological state after early oral breathing in rats.

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.

Effects of short term forced oral breathing: physiological changes and structural adaptation of diaphragm and orofacial muscles in rats.

OBJECTIVE: We studied adaptation of diaphragm and orofacial muscles as well as hormonal responses to forced oral breathing (lasting for only 4 days) following reversible bilateral nasal obstruction performed on day 8 post-natal male rats. DESIGN: Muscle myosin heavy chain (MHC) composition and hormone levels were analysed during two periods: 1 and 3 days after obstruction (days 9 and 11 post-natal), and following 3 months recovery with nasal breathing (90 days, adult). RESULTS: Diaphragm muscle showed significant increases in adult isoforms (MHC 1, 2a) in oral breathing group versus control. We observed increases in MHC neonatal and adult type 1 isoforms in muscles involved with oral breathing, masseter superficialis and anterior digastric. No changes were observed in the levator nasolabialis muscle involved with nasal breathing. Reversible nasal obstruction was associated with reduced growth of the olfactory bulbs lasting into adulthood, and an initial decrease in lung growth followed by recovery at 90 days. Adrenal hypertrophy was observed after 1 day of nasal obstruction and lasted into adulthood. The "stress" hormone response was variable, increased (over 1000%) during the obstruction but normal by adulthood. An increase in plasma testosterone was observed during the obstruction, and a decrease in thyroid hormone levels throughout. CONCLUSIONS: Very short term nasal obstruction, i.e. forced oral breathing, leads to long term hormonal changes and respiratory muscle fibre adaptation.

Potent inhibition of store-operated Ca2+ influx and superoxide production in HL60 cells and polymorphonuclear neutrophils by the pyrazole derivative BTP2.

Store-operated calcium entry (SOCE) is a key regulator in the activation of leukocytes. 3,5-Bistrifluoromethyl pyrazole (BTP) derivatives have been identified recently as inhibitors of T lymphocyte activation. The inhibitory effect of one of these compounds, N-(4-[3,5-bis(trifluoromethyl)-1H-pyrazol-1-yl]phenyl)-4-methyl-1,2,3-thiadiazole-5-carboxamide (BTP2), appears to be a result of inhibition of SOC 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 SOCE. 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 microM BTP2 and after 24 h with lower concentrations. With 24 h incubation, the effect appeared irreversible, as the removal of BTP2 3 h before the experiment did not reduce this inhibition in granulocyte-differentiated HL60 cells. In human neutrophils, BTP2 reduced superoxide anion production by 82% after 24 h of incubation. On the contrary, phagocytosis, intraphagosomal radical production, and bacterial killing by neutrophils were not reduced significantly, even after 24 h treatment with 10 microM 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.