Praziquantel-Solid Lipid Nanoparticles Produced by Supercritical Carbon Dioxide Extraction: Physicochemical Characterization, Release Profile, and Cytotoxicity.

Solid lipid nanoparticles (SLNs) can be produced by various methods, but most of them are difficult to scale up. Supercritical fluid (SCF) is an important tool to produce micro/nanoparticles with a narrow size distribution and high encapsulation efficiency. The aim of this work was to produce cetyl palmitate SLNs using SCF to be loaded with praziquantel (PZQ) as an insoluble model drug. The mean particle size (nm), polydispersity index (PdI), zeta potential, and encapsulation efficiency (EE) were determined on the freshly prepared samples, which were also subject of Differential Scanning Calorimetry (DSC), Fourier-Transform Infrared Spectroscopy (FTIR), drug release profile, and in vitro cytotoxicity analyses. PZQ-SLN exhibited a mean size of ~25 nm, PdI ~ 0.5, zeta potential ~-28 mV, and EE 88.37%. The DSC analysis demonstrated that SCF reduced the crystallinity of cetyl palmitate and favored the loading of PZQ into the lipid matrices. No chemical interaction between the PZQ and cetyl palmitate was revealed by FTIR analysis, while the release or PZQ from SLN followed the Weibull model. PZQ-SLN showed low cytotoxicity against fibroblasts cell lines. This study demonstrates that SCF may be a suitable scale-up procedure for the production of SLN, which have shown to be an appropriate carrier for PZQ.

Pneumomediastinum and subcutaneous emphysema complicating a patient with a lung abscess.

Pneumomediastinum and subcutaneous emphysema are conditions that carry significant morbidity. They are uncommonly seen as complications of lung abscess formation and prompt recognition and treatment is necessary. We present a 59-year-old male patient who complained of shortness of breath and chest pain for 2 weeks. Computed tomography (CT) of the thorax showed a left lower lobe lung abscess. This was associated with leucocytosis and raised C-reactive protein. Ultrasound-guided drainage revealed viscous pus requiring manual aspiration for adequate drainage. The patient later developed extensive pneumomediastinum and subcutaneous emphysema involving the pretracheal space, without evidence of pneumothorax. Left lower lobectomy was performed to control sepsis. The patient achieved a complete recovery following his surgery and antibiotic treatment, with interval resolution of pneumomediastinum and subcutaneous emphysema. We present the radiological and clinical features leading to the diagnosis of pneumomediastinum and subcutaneous emphysema.

Collection of lower respiratory specimen by bronchoscopy for the diagnosis of COVID-19.

Bronchoscopy, as an aerosol-generating procedure, is not routinely performed in patients with high-risk of coronavirus disease-2019 (COVID-19) owing to potential transmission to healthcare workers. However, to obtain lower respiratory specimens from bronchoscopy with bronchoalveolar lavage (BAL) is necessary to confirm COVID-19 or other diagnosis that will change clinical management. We report a case of diagnostic difficulty with five negative SARS-CoV-2 RT-PCR testing in four upper respiratory tract and one stool samples following presentation with fever during the quarantine period and a strong epidemiological linkage to an index patient with COVID-19. The final diagnosis was confirmed by BAL. Special precautions to be taken when performing bronchoscopy in high-risk non-intubated patients were discussed.

Native and modified LDL activate extracellular signal-regulated kinases in mesangial cells.

Glycation and/or oxidation of LDL may promote diabetic nephropathy. The mitogen-activated protein kinase (MAPK) cascade, which includes extracellular signal-regulated protein kinases (ERKs), modulates cell function. Therefore, we examined the effects of LDL on ERK phosphorylation in cultured rat mesangial cells. In cells exposed to 100 microg/ml native LDL or LDL modified by glycation, and/or mild or marked (copper-mediated) oxidation, ERK activation peaked at 5 min. Five minutes of exposure to 10-100 microg/ml native or modified LDL produced a concentration-dependent (up to sevenfold) increase in ERK activity. Also, 10 microg/ml native LDL and mildly modified LDL (glycated and/or mildly oxidized) produced significantly greater ERK activation than that induced by copper-oxidized LDL +/- glycation (P < 0.05). Pretreatment of cells with Src kinase and MAPK kinase inhibitors blocked ERK activation by 50-80% (P < 0.05). Native and mildly modified LDL, which are recognized by the native LDL receptor, induced a transient spike of intracellular calcium. Copper-oxidized (+/- glycation) LDL, recognized by the scavenger receptor, induced a sustained rise in intracellular calcium. The intracellular calcium chelator (EGTA/AM) further increased ERK activation by native and mildly modified LDL (P < 0.05). These findings demonstrate that native and modified LDL activate ERKs 1 and 2, an early mitogenic signal, in mesangial cells and provide evidence for a potential link between modified LDL and the development of glomerular injury in diabetes.