Obstructive fibrinous pseudomembrane tracheitis after double-lumen tube intubation -a case report.

BACKGROUND: Obstructive fibrinous pseudomembrane tracheitis (OFPT) is a rare complication of endotracheal intubation. CASE: We describe the case of a 73-year-old woman who underwent short-term intubation for video-assisted thoracoscopic surgery and developed an acute life-threatening stridor two days after extubation. The patient required an emergency tracheostomy to maintain airway patency and a microscopic direct laryngoscopy procedure was performed thereafter with removal of the obstructive pseudomembrane. Subsequently, the patient also suffered a non-ST-elevation myocardial infarction. The patient successfully recovered, and the tracheostomy was subsequently decannulated two months later. Histological examination revealed mucosal ulcerations and inflammatory changes. CONCLUSIONS: OFPT is an uncommon cause of life-threatening airway obstruction after extubation that is not often recognized immediately but can usually be treated with early bronchoscopic intervention or microscopic direct laryngoscopy.

Site-directed mutagenesis on human cystathionine-gamma-lyase reveals insights into the modulation of H2S production.

In recent years, increased interest has been directed towards hydrogen sulfide (H2S) as the third gasotransmitter and its role in various diseases. Cystathionine-gamma-lyase (CSE) is one of the enzymes responsible for the endogenous production of H2S in mammals. With the aid of the crystal structures of human CSE and site-directed mutagenesis studies, we have identified several amino acid residues in CSE that are actively involved in the catalysis of H2S production. Contrary to reports suggesting that Tyr114 is required for substrate binding, our results reveal a significant increase in the production of H2S upon mutation of Tyr114 to phenylalanine. This is attributed to an increased rate of pyridoxal 5'-phosphate (PLP) regeneration due to weakened pi-stacking interactions between Phe114 and PLP. Thr189 is also identified as a crucial residue where hydrogen bonding to Asp187 keeps the latter in an optimal position for hydrogen bonding to the pyridoxal nitrogen of PLP. Furthermore, mutation of Glu339 to lysine, alanine or tyrosine reveals the importance of the hydrophobicity of the 339th amino acid in determining the specificity of the enzyme for the catalysis of alpha,gamma-elimination or alpha,beta-elimination reaction. Our study also shows that the rate of H2S production is increased with increasing exogenous PLP concentration, hence supporting our hypothesis that apo-CSE is formed during the catalysis of H2S production. Taken together, these findings suggest novel routes towards the design of activators or inhibitors that modulate the production of H2S; these modulators may also serve as lead compounds in the development of drugs or mechanistic probes in the study of various H2S-related diseases.

MicroRNAs: biogenesis, function and applications.

MicroRNAs (miRNAs) belong to the group of non-coding, small RNAs (19 to 21 nucleotide-long oligonucleotides) that are endogenously produced from their own genes. miRNAs interfere with or affect the transcription or translation of other genes, resulting in gene silencing or activation by a process known as RNAi or RNA activation, respectively. The discovery of miRNAs and related small RNAs within the last 10 years has opened up a new field in biology, called RNomics, which investigates differences in RNA populations and offers great potential in correcting the regulation of abnormally expressed and disease-causing genes, as well as in the development of novel therapeutic agents. This review focuses on the developments in miRNAs and their potential therapeutic applications.