Isothiocyanate-Corticosteroid Conjugates against asthma: Unity makes strength.

Asthma is a major noncommunicable disease, affecting both children and adults, and represents one of the major causes leading to high health care costs due to the need for chronic pharmacological treatments. The standard gold therapy of inflammation in asthmatic patients involves the use of glucocorticoids even if their chronic use is often related to serious adverse effects. Growing evidence suggests the biological relevance of hydrogen sulfide (H2S) in the pathogenesis of airway diseases. Hence, aiming to associate the beneficial effects of steroidal anti-inflammatory drugs (SAIDs) to H2S biological activity, we designed and synthesized novel multi-target molecules by chemically combining a group of glucocorticoids, usually employed in asthma treatment, with an isothiocyanate moiety, well-known for its H2S releasing properties. Firstly, the synthesized compounds have been screened for their H2S-releasing profile using an amperometric approach and for their in vitro effects on the degranulation process, using RBL-2H3 cell line. The physicochemical profile, in terms of solubility, chemical and enzymatic stability of the newly hybrid molecules, has been assessed at different physiological pH values and in esterase-rich medium (bovine serum albumin, BSA). The selected compound 5c, through both its corticosteroid and H2S releasing component, has been evaluated in vivo in experimental model of asthma. The compound 5c inhibited in vivo all asthma features with a significative effect on the restoration of pulmonary structure and reduction of lung inflammation.

Prednisone-hydrogen sulfide releasing hybrid shows improved therapeutic profile in asthma.

Introduction: Hydrogen sulfide (H2S) is emerging as an important potential therapeutic option for respiratory inflammatory diseases. In this study, we investigated the effectiveness of a novel corticosteroid derivative, that is chemically linked to an H2S donor, in managing asthma features. Methods: The effects of prednisone (PS), H2S donor (4-hydroxybenzamide; TBZ), and their combination (PS-TBZ) have been evaluated in vitro and in vivo. The in vitro experiments were conducted using lipopolysaccharidestimulated J774 macrophages, while the in vivo experiments utilizing an experimental asthma model. Results: In the in vitro study we found that PS-TBZ exhibited an increased effect compared to the individual parent compounds in modulating the production of inflammatory mediators. TBZ also significantly reduced bronchial contractility and enhanced bronchial relaxation. In the in vivo experiments, where we administered PS, TBZ, or PS-TBZ to ovalbumin-sensitized BALB/c mice, we confirmed that PS-TBZ had a significantly better action in controlling airway hyperreactivity as compared to TBZ or PS alone. Moreover, PS-TBZ was more effective in restoring salbutamol-induced relaxation. The immunohistochemistry analysis demonstrated a significant reduction in the production of α-SMA and procollagen III, indicating the efficacy of PS-TBZ in controlling airway remodeling. Moreover, PS-TBZ also promoted epithelial repair, recovery of the bronchial and parenchyma structure and inhibited mucin production. Discussion: In conclusion, PS-TBZ offers an important opportunity to optimize the beneficial impact of corticosteroids on asthma features.

Recovery of laryngeal nerve function with sugammadex after rocuronium-induced profound neuromuscular block.

STUDY OBJECTIVE: The aim of this study was to evaluate the efficacy of sugammadex in reversing profound rocuronium-induced neuromuscular block at the laryngeal adductor muscles using motor-evoked potentials (mMEPs). DESIGN: A prospective observational study. SETTING: University surgical center. PATIENTS: Twenty patients with American Society of Anesthesiologists physical class I-II status who underwent propofol-remifentanil anesthesia for the surgery of the thyroid gland. INTERVENTIONS: Patients were enrolled for reversal of profound neuromuscular block (sugammadex 16 mg/kg, 3 minutes after rocuronium 1.2 mg/kg). To prevent laryngeal nerve injury during the surgical procedures, all patients underwent neurophysiologic monitoring using mMEPs from vocal muscles. At the same time, the registration of TOF-Watch acceleromyograph at the adductor pollicis muscle response to ulnar nerve stimulation was performed; recovery was defined as a train-of-four (TOF) ratio ≥0.9. MEASUREMENT AND MAIN RESULTS: After injection of 16 mg/kg of sugammadex, the mean time to recovery of the basal mMEPs response at the laryngeal adductor muscles was 70 ± 18.2 seconds. The mean time to recovery of the TOF ratio to 0.9 was 118 ± 80 seconds. In the postoperative period, 12 patients received follow-up evaluation of the vocal cords and no lesions caused by the surface laryngeal electrode during electrophysiological monitoring were noted. CONCLUSIONS: Recovery from profound rocuronium-induced block on the larynx is fast and complete with sugammadex. In urgent scenarios, "early" extubation can be performed, even with a TOF ratio ≤0.9. However, all procedures to prevent postoperative residual curarization should still be immediately undertaken.

Tracheal Intubation with Aura-i and aScope-2: How to Minimize Apnea Time in an Unpredicted Difficult Airway.

The supraglottic airway's usefulness as a dedicated airway is the subject of continuing development. We report the case of an obese patient with unpredicted difficult airway management in which a new "continuous ventilation technique" was used with the Aura-i laryngeal mask and the aScope-2 devices. The aScope-2/Aura-i system implemented airway devices for the management of predictable/unpredictable difficult airway. The original technique required the disconnection of the mount catheter from Aura-i, the introduction of the aScope-2 into the laryngeal mask used as a conduit for video assisted intubation and then towards the trachea, followed by a railroading of the tracheal tube over the aScope-2. This variation in the technique guarantees mechanical ventilation during the entire procedure and could prevent the risk of hypoventilation and/or hypoxia.