Glucagon-like peptide 1: A potential anti-inflammatory pathway in obesity-related asthma.

Alterations in arginine metabolism and accelerated formation of advanced glycation end-products (AGEs), crucial mechanisms in obesity-related asthma, can be modulated by glucagon-like peptide 1 (GLP-1). l-arginine dysregulation in obesity promotes inflammation and bronchoconstriction. Prolonged hyperglycemia, dyslipidemia, and oxidative stress leads to production of AGEs, that bind to their receptor (RAGE) further potentiating inflammation. By binding to its widely distributed receptor, GLP-1 blunts the effects of RAGE activation and arginine dysregulation. The GLP-1 pathway, while comprehensively studied in the endocrine and cardiovascular literature, is under-recognized in pulmonary research. Insights into GLP-1 and the lung may lead to novel treatments for obesity-related asthma.

Bronchial Artery Pseudoaneurysm With Major Hemorrhage After Bronchial Thermoplasty.

Bronchial thermoplasty has been found to be a safe and effective therapy for severe asthma. We report the case of a mediastinal hematoma and hemothorax developing in a 66-year-old woman several days after an uneventful bronchial thermoplasty of the right lower lobe. Evaluation revealed a bleeding right bronchial artery pseudoaneurysm. Pseudoaneuryms have been reported in association with other procedures involving the therapeutic application of thermal energy, and a single case of hemoptysis requiring bronchial artery embolization occurred in a clinical trial of bronchial thermoplasty. However, bronchial artery pseudoaneurysm with hemomediastinum and hemothorax has not previously been reported after bronchial thermoplasty.

Ratiometric Imaging Using a Single Dye Enables Simultaneous Visualization of Rac1 and Cdc42 Activation.

Biosensors that report endogenous protein activity in vivo can be based on environment-sensing fluorescent dyes. The dyes can be attached to reagents that bind selectively to a specific conformation of the targeted protein, such that binding leads to a fluorescence change. Dyes that are sufficiently bright for use at low, nonperturbing intracellular concentrations typically undergo changes in intensity rather than the shifts in excitation or emission maxima that would enable precise quantitation through ratiometric imaging. We report here mero199, an environment-sensing dye that undergoes a 33 nm solvent-dependent shift in excitation. The dye was used to generate a ratiometric biosensor of Cdc42 (CRIB199) without the need for additional fluorophores. CRIB199 was used in the same cell with a FRET sensor of Rac1 activation to simultaneously observe Cdc42 and Rac1 activity in cellular protrusions, indicating that Rac1 but not Cdc42 activity was reduced during tail retraction, and specific protrusions had reduced Cdc42 activity. A novel program (EdgeProps) used to correlate localized activation with cell edge dynamics indicated that Rac1 was specifically reduced during retraction.

Diffuse alveolar damage in a patient receiving dronedarone.

Dronedarone is an amiodarone-like antiarrhythmic with a modified structure. The addition of a methyl sulfonyl group theoretically reduces the toxicity of amiodarone, specifically, adverse thyroid and pulmonary effects. Although animal studies have implicated dronedarone as a cause of lung injury, to date controlled trials in humans have not demonstrated an association. A 68-year-old woman developed a dry cough and worsening respiratory distress after receiving dronedarone for 6 months. Discontinuation of dronedarone therapy and subsequent steroid therapy led to a dramatic improvement of symptoms. Dronedarone may be associated with interstitial lung disease. We believe that patients receiving dronedarone should have their diffusing capacity of lung for carbon monoxide and lung volumes monitored prior to initiation of therapy and frequently thereafter.

Merocyanine dyes with improved photostability.

Merocyanine dyes have proven valuable for live cell fluorescence imaging applications, but many structures have been limited by rapid photobleaching. We show that photostability is substantially enhanced for merocyanines having a cyano group at a specific position in the central polymethine chain. Evidence is presented that this is due to reduction in reactivity of the dyes with singlet oxygen. These results point toward cyano-substitution as a general strategy for improving dye performance in imaging applications.

Simple one-pot preparation of water-soluble, cysteine-reactive cyanine and merocyanine dyes for biological imaging.

A simple one-pot-procedure for preparation of protein-reactive, water-soluble merocyanine and cyanine dyes has been developed. The 1-(3-ammoniopropyl)-2,3,3-trimethyl-3H-indolium-5-sulfonate bromide (1) was used as a common starting intermediate. The method allows easy preparation of dyes with chloro- and iodoacetamide side chains for covalent attachment to cysteine. By placing a sulfonato group directly on the dye fluorophore system, dyes with high fluorescence quantum yields in water were generated. Both iodo- and chloroacetamido derivatives were shown to be useful in protein labeling. Less reactive chloroacetamides will be preferential for selective labeling of the most reactive cysteines.