Tanshinone IIA loaded bioactive nanoemulsion for alleviation of lipopolysaccharide induced acute lung injury via inhibition of endothelial glycocalyx shedding.

Acute lung injury (ALI) and its more serious form; acute respiratory distress syndrome are major causes of COVID-19 related mortality. Finding new therapeutic targets for ALI is thus of great interest. This work aimed to prepare a biocompatible nanoformulation for effective pulmonary delivery of the herbal drug; tanshinone-IIA (TSIIA) for ALI management. A nanoemulsion (NE) formulation based on bioactive natural ingredients; rhamnolipid biosurfactant and tea-tree oil, was developed using a simple ultrasonication technique, optimized by varying oil concentration and surfactant:oil ratio. The selected TSIIA-NE formulation showed 105.7 nm diameter and a PDI âˆ¼ 0.3. EE exceeded 98 % with biphasic sustained drug release and good stability over 3-months. In-vivo efficacy was evaluated in lipopolysaccharide (LPS)-induced ALI model. TSIIA-NE (30 µg/kg) was administered once intratracheally 2 h after LPS instillation. Evaluation was performed 7days post-treatment. Pulmonary function assessment, inflammatory, oxidative stress and glycocalyx shedding markers analysis in addition to histopathological examination of lung tissue were performed. When compared to untreated rats, in-vivo efficacy study demonstrated 1.4 and 1.9-fold increases in tidal volume and minute respiratory volume, respectively, with 32 % drop in wet/dry lung weight ratio and improved levels of arterial blood gases. Lung histopathology and biochemical analysis of different biomarkers in tissue homogenate and bronchoalveolar lavage fluid indicated that treatment may ameliorate LPS-induced ALI symptoms thorough anti-oxidative, anti-inflammatory effects and inhibition of glycocalyx degradation. TSIIA-NE efficacy was superior to free medication and blank-NE. The enhanced efficacy of TSIIA bioactive nanoemulsion significantly suggests the pharmacotherapeutic potential of bioactive TSIIA-NE as a promising nanoplatform for ALI.

Gas in Joints After Diving: Computed Tomography May Be Useful for Diagnosing Decompression Sickness.

A 26-y-old experienced scotoma scintillans after 59 min of scuba diving at a maximum depth of 26 m. After the patient smoked a cigarette, the scotoma scintillans ceased. However, he then developed a headache, general fatigue, and shoulder and elbow pain. He therefore called an ambulance. Based on the rules of the medical cooperative system for decompression sickness in Izu Peninsula, the fire department called a physician-staffed helicopter. After a physician checked the patient, his complaints remained aside from a low-grade fever. A portable ultrasound revealed bubbles in his inferior vena cava. Because of the risk of his being infected with COVID-19, he was transported to our hospital not by air evacuation but via ground ambulance staff while receiving a drip infusion of fluid and oxygen. After arriving at the hospital, his symptoms had almost subsided. Whole-body computed tomography revealed gas around the bladder, left hip, right knee, bilateral shoulder, joints, and right intramedullary humerus. The patient received high-concentration oxygen, infusion therapy, and observational admission. On the second day of admission, his symptoms had completely disappeared, and he was discharged. To our knowledge, this is the first report that computed tomography might be useful for detecting gas in multiple joints, suggesting the onset of decompression sickness after diving. This might be the first report of gas in an intramedullary space after diving as a potential cause of dysbaric osteonecrosis.