Curcumin-loaded lipid and polymeric nanocapsules stabilized by nonionic surfactants: An In Vitro and In Vivo antitumor activity on B16-F10 melanoma and macrophage uptake comparative study

Curcumin is a polyphenol obtained from the plant Curcuma longa (called turmeric) that displays several pharmacological activities, including anti-inflammatory, antioxidant, antimicrobial and antitumoral activity, but clinical use has been limited by its poor solubility in water and, consequently, minimal systemic bioavailability. We have therefore formulated the drug into nanocarrier systems in an attempt to improve its therapeutic properties. This study evaluates the effect of intraperitoneally administered nanocapsules containing curcumin on subcutaneous melanoma in mice inoculated with B16-F10 cells, and on the cytotoxicity activity against B16-F10 cells in vitro. Phagocytic uptake of formulations was also evaluated upon incubation with macrophage J774 cells by fluorescence microscopy. Lipid and polymeric nanocapsules were prepared by the phase inversion and nanoprecipitation methods, respectively. The uptake of the lipid nanocapsules prepared using Solutol HS15 was significantly reduced in J774 cells. Curcumin, as free drug or as drug-loaded nanocapsules, was administrated at a dose of 6 mg/kg twice a week for 21 days. Free drug and curcuminloaded nanocapsules significantly reduced tumor volume (P < 0.05 vs. control), but no difference was found in the antitumor activity displayed by lipid and polymeric nanocapsules. This assumption was supported by the in vitro study, in which free curcumin as well as loaded into nanocapsules caused significant reduction of cell viability in a concentration- and time-dependent manner.Fil: Mazzarino, Letícia. Universidade Federal de Santa Catarina; BrasilFil: Silva, Luís F. C.. Universidade Federal de Santa Catarina; BrasilFil: Curta, Juliana C.. Universidade Federal de Santa Catarina; BrasilFil: Licínio, Marley A.. Universidade Federal de Santa Catarina; BrasilFil: Costa, Aline. Universidade Federal de Santa Catarina; BrasilFil: Pacheco, Letícia K.. Universidade Federal de Santa Catarina; BrasilFil: Siqueira, Jarbas M.. Universidade Federal de Santa Catarina; BrasilFil: Martinetti Montanari, Jorge Anibal. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Romero, Eder. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; ArgentinaFil: Assreuy, Jamil. Universidade Federal de Santa Catarina; BrasilFil: Santos Silva, Maria C.. Universidade Federal de Santa Catarina; BrasilFil: Lemos Senna, Elenara. Universidade Federal de Santa Catarina; Brasi

Coronary computed tomography angiography based assessment of endothelial shear stress and its association with atherosclerotic plaque distribution in-vivo

© 2015 Hetterich et al. The relationship between low endothelial shear stress (ESS) and coronary atherosclerosis is well established. ESS assessment so far depended on invasive procedures. The aim of this study was to demonstrate the relationship between ESS and coronary atherosclerosis by using non-invasive coronary computed tomography angiography (CTA) for computational fluid dynamics (CFD) simulations. Methods A total number of 7 consecutive patients with suspected coronary artery disease who received CTA and invasive angiography with IVUS analysis were included in this study. CTA examinations were performed using a dual-source scanner. These datasets were used to build a 3D mesh model. CFD calculations were performed using a validated CFD solver. The presence of plaque was assumed if the thickness of the intima-media complex exceeded 0.3 mm in IVUS. Plaque composition was derived by IVUS radiofrequency data analysis. Results Plaque was present in 32.1%of all analyzed cross-sections. Plaque prevalence was highest in areas of low ESS (49.6%) and high ESS (34.8%). In parts exposed to intermediatelow and intermediate-high ESS few plaques were found (20.0% and 24.0%) (p<0.001). Wall thickness was closely associated with local ESS. Intima-media thickness was 0.43±0.34mm in low and 0.38±0.32mm in high ESS segments. It was significantly lower when the arterial wall was exposed to intermediate ESS (0.25±0.18mmand 0.28±0.20mm) (p<0.001). Fibrofatty tissue was predominately found in areas exposed to low ESS (p<.023). Conclusions In this study a close association of atherosclerotic plaque distribution and ESS pattern could be demonstrated in-vivo. Adding CFD analysis to coronary CTA offers the possibility to gather morphologic and physiologic data within one non-invasive examination

Benefit of Contact Force Sensing Catheter Technology for Successful Left Atrial Anterior Line Formation: A Prospective Randomized Trial

Introduction. The value of contact force information for ablation of LA anterior line is unknown. In a prospective randomized clinical trial, we investigated if information on contact force during left atrial (LA) anterior line ablation reduces total radiofrequency time and results in higher rates of bidirectional line block in patients undergoing pulmonary vein isolation (PVI) plus substrate modification. Methods. We included patients with indication for pulmonary vein isolation (PVI) and additional substrate modification. For LA anterior line ablation, patients were randomized to contact force information visible (n=35) or blinded (n=37). Patients received contrast enhanced cardiac magnetic resonance imaging (cMRI) before and 3-6 months after ablation to visualize the LA anterior line. Primary endpoint was radiofrequency time to achieve bidirectional line block. Secondary endpoints were completeness of the LA anterior line on cMRI, distribution of contact force, procedural data, adverse events, and 12 months success rate. Results. In 72 patients (64±9 years, 68% male), bidirectional LA anterior line block was achieved in 70 (97%) patients. Radiofrequency time to bidirectional block did not differ significantly across groups (contact force information visible 23±18min versus contact force information blinded 21±15min, p=0.50). The LA anterior line was discernable on cMRI in 40 patients (82%) without significant differences across randomization groups (p=0.46). No difference in applied contact force was found depending on cMRI line visibility. Twelve-month success and adverse event rates were comparable across groups. Conclusion. Information on contact force does not significantly improve the ablation of LA anterior lines. Clinical Trial Registration. The trial was registered at http://www.clinicaltrials.gov by identifier: NCT02217657

Fecal microbiota transplantation for recurrent C. difficile infection in patients with inflammatory bowel disease: experience of a large-volume European FMT center

Inflammatory bowel disease (IBD) is a risk factor for C. difficile infection (CDI), which, in turn, complicates the clinical course of IBD. Fecal microbiota transplantation (FMT) is safe and effective in patients with IBD and recurrent CDI (rCDI). In our study, patients with IBD and rCDI received FMT by colonoscopy and were followed-up for 8&nbsp;weeks. The primary outcome was negative C. difficile toxin 8&nbsp;weeks after FMT. Eighteen patients with IBD were enrolled. Eight patients received sequential FMT either for pseudomembranous colitis or failure of single fecal infusion. At 8-week follow-up the C. difficile toxin was negative in 17 patients, and most (83%) experienced also improvement of IBD disease activity. Overall, we did not observe any serious adverse event. FMT appears to be highly effective and safe in patients with IBD and rCDI and is likely not only to eradicate CDI but also to improve disease activity of IBD