Effects of budesonide on P38 MAPK activation, apoptosis and IL-8 secretion, induced by TNF-alpha and Haemophilus influenzae in human bronchial epithelial cells.

Non-typeable Haemophilus influenzae (NTHi) is one of the most frequently involved pathogens in bacterial exacerbations of chronic obstructive pulmonary disease (COPD). In the airways, the main tissue target of NTHi is bronchial epithelium, where this pathogen can further amplify the inflammatory and structural changes induced by proinflammatory cytokines such as tumour necrosis factor-alpha (TNF-alpha). Therefore, the aim of this study is to investigate, in primary cultures of human bronchial epithelial cells, the effects of NTHi on signal transduction pathways, apoptotic events and chemokine production activated by TNF-alpha. Moreover, we also evaluated the effects exerted on such cellular and molecular phenomena by a corticosteroid drug. p38 mitogen-activated protein kinase (MAPK) phosphorylation was analyzed by Western blotting, using an anti-phospho-p38 MAPK monoclonal antibody. Apoptosis was assayed by active caspase-3 expression. Interleukin-8 (IL-8/CXCL8) was detected in cell-free culture supernatants by ELISA. TNF-alpha induced a significant increase in p38 MAPK phosphorylation. NTHi was able to potentiate the stimulatory actions of TNF-alpha on caspase-3 expression and, to a lesser extent, on IL-8 secretion. These effects were significantly (P less than 0.01) inhibited by a pharmacological pre-treatment with budesonide. These results suggest that TNF-alpha is able to stimulate, via activation of p38 MAPK signalling pathway, IL-8 release and airway epithelial cell apoptosis; the latter effect can be markedly potentiated by NTHi. Furthermore, budesonide can be very effective in preventing, through inhibition of p38 MAPK phosphorylation, both structural and proinflammatory changes elicited in bronchial epithelium by TNF-alpha and NTHi.

Solitons in DNA.

DNA is modeled as a homogeneous, cylindrical rod with nonlinear elasticity using the Ostrovskii-Sutin equation (OSE) with periodic boundary conditions. This equation predicts that longitudinal sound waves will be concentrated into packets called solitons. From a study of the damped OSE, we conclude that decay time is almost independent of the solitonic character of the solution. For the damped, driven OSE, on the other hand, we find that spectral features (such as absorption line widths and fine structure) are strongly influenced by the presence of anharmonicity. This effect is enhanced as the length of the DNA is increased.

[Bone marrow scanning (author's transl)]. / La scintigrafi midollare ossea

Personal experience of Technetium-99m-sulfur colloid in the scintiscanning of bone marrow is reported. The method offers technical advantages over other methods and superior protection, while its only limitation is that it does not permit a dynamic study of hematopoiesis. Four pathologic scans typical of four groups of diseases may be distinguished. Further, metastatic bone marrow localisations can be diagnosed much earlier and more precisely than by radiography.