Dispersion and release of embelin from electrospun biodegradable, polymeric, membranes

In this work, microfiber meshes containing embelin, a poorly water-soluble bioactive agent, were prepared by solubilizing embelin in a biodegradable and biocompatible polymer matrix of poly(ε-caprolactone) (PCL). Plain or drug-loaded, highly porous, fibrous membranes with a high area-to-volume ratio were obtained by electrospinning. Non-woven microfibrous meshes were formed by uniform bead-free fibers with a mean diameter of 1.2 μm. Non-porous films were obtained by solution casting, and were used for comparison. The drug-loading content of the prepared systems was appropriate for topical applications. The thermal properties revealed that the crystallinity of embelin significantly decreased, the drug having almost completely dissolved in the PCL fibers. The in situ bioavailability of embelin, an antimycotic agent, is an important aspect to consider in topical drug applications. The drug-loaded systems presented different contact areas with the biological environment. When comparing the ability to expose embelin with the biological environment of the prepared systems, drug-loaded fibrous scaffolds showed a higher bioavailability of the bioactive agent because of an increase by 86% in the area-to-volume ratio, providing an effective area per unit mass that was 5.8-fold higher than that of the film. For the meshes, 90% embelin release was observed after 12h of exposure to phosphate-buffered saline, whereas for the films a comparable level of release occurred only after 72h.Fil: Cortez Tornello, Pablo Roberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mar del Plata. Instituto de Investigación En Ciencia y Tecnología de Materiales (i); Argentina. Universidad Nacional de San Juan. Facultad de Ingeniería. Instituto de Biotecnología; ArgentinaFil: Feresin, Gabriela Egly. Universidad Nacional de San Juan. Facultad de Ingeniería. Instituto de Biotecnología; ArgentinaFil: Tapia, Alejandro. Universidad Nacional de San Juan. Facultad de Ingeniería. Instituto de Biotecnología; ArgentinaFil: Veiga, Itiara G.. Universidade Estadual de Campinas; BrasilFil: Moraes, Ângela M.. Universidade Estadual de Campinas; BrasilFil: Abraham, Gustavo Abel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mar del Plata. Instituto de Investigación En Ciencia y Tecnología de Materiales (i); Argentina. Universidad Nacional de Mar del Plata. Facultad de Ingeniería; ArgentinaFil: Cuadrado, Teresita Raquel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mar del Plata. Instituto de Investigación En Ciencia y Tecnología de Materiales (i); Argentina. Universidad Nacional de Mar del Plata. Facultad de Ingeniería; Argentin

Differential and shared genetic effects on kidney function between diabetic and non-diabetic individuals

A large-scale GWAS provides insight on diabetes-dependent genetic effects on the glomerular filtration rate, a common metric to monitor kidney health in disease.Reduced glomerular filtration rate (GFR) can progress to kidney failure. Risk factors include genetics and diabetes mellitus (DM), but little is known about their interaction. We conducted genome-wide association meta-analyses for estimated GFR based on serum creatinine (eGFR), separately for individuals with or without DM (nDM = 178,691, nnoDM = 1,296,113). Our genome-wide searches identified (i) seven eGFR loci with significant DM/noDM-difference, (ii) four additional novel loci with suggestive difference and (iii) 28 further novel loci (including CUBN) by allowing for potential difference. GWAS on eGFR among DM individuals identified 2 known and 27 potentially responsible loci for diabetic kidney disease. Gene prioritization highlighted 18 genes that may inform reno-protective drug development. We highlight the existence of DM-only and noDM-only effects, which can inform about the target group, if respective genes are advanced as drug targets. Largely shared effects suggest that most drug interventions to alter eGFR should be effective in DM and noDM.</p

Dispersion and release of embelin from electrospun, biodegradable, polymeric membranes

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)In this work, microfiber meshes containing embelin, a poorly water-soluble bioactive agent, were prepared by solubilizing embelin in a biodegradable and biocompatible polymer matrix of poly(e-caprolactone) (PCL). Plain or drug-loaded, highly porous, fibrous membranes with a high area-to-volume ratio were obtained by electrospinning. Non-woven microfibrous meshes were formed by uniform bead-free fibers with a mean diameter of 1.2 mu m. Non-porous films were obtained by solution casting, and were used for comparison. The drug-loading content of the prepared systems was appropriate for topical applications. The thermal properties revealed that the crystallinity of embelin significantly decreased, the drug having almost completely dissolved in the PCL fibers. The in situ bioavailability of embelin, an antimycotic agent, is an important aspect to consider in topical drug applications. The drug-loaded systems presented different contact areas with the biological environment. When comparing the ability to expose embelin with the biological environment of the prepared systems, drug-loaded fibrous scaffolds showed a higher bioavailability of the bioactive agent because of an increase by 86% in the area-to-volume ratio, providing an effective area per unit mass that was 5.8-fold higher than that of the film. For the meshes, 90% embelin release was observed after 12 h of exposure to phosphate-buffered saline, whereas for the films a comparable level of release occurred only after 72 h. Polymer Journal (2012) 44, 1105-1111; doi:10.1038/pj.2012.80; published online 16 May 2012441111051111CONICETConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Argentinean National Agency of Scientific and Technological Promotion [PICT 448]National Research Council [PIP 522]CYTEDConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Argentinean National Agency of Scientific and Technological Promotion [PICT 448]National Research Council [PIP 522

Clinopodium gilliesii (Benth.) Kuntze

Clinopodium gilliesii (Benth.) Kuntze is an aromatic species from the Andean region, from southern Peru to northern-central Argentina. It is mainly known as muña-muña and its leaves and tender stems are used as a flavoring and medicinal: stimulant, against mountain sickness, aphrodisiac, digestive, antispasmodic, among others traditional uses. Its bioactive constituents are essential oils, to which the plant owes its aroma and many of its therapeutic properties. The presence of flavonoids and phenolic compounds has also been detected. The essential oil composition of aerial organs is variable according to geographical location and ecological conditions, soil-type, weather-conditions and altitude of the population. Regarding its popular uses, the majority of uses has not been validate by pre-clinical tests, therefore they require experimental founding. Some of its biological activities, e.g.: aphrodisiac (in particular, erectile dysfunction), against some gastrointestinal disorders, antibacterial, antifungal, antiplasmodial, trypanocidal, insect repellent, antioxidant, and cytotoxic activities have already been analyzed. Some data about the similar species: C. bolivianum (Benth.) Kuntze and C. odorun (Griseb.) Harley is additionally commented.Fil: Hurrell, Julio Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Laboratorio de Etnobotánica y Botánica Aplicada; Argentin

Differential and shared genetic effects on kidney function between diabetic and non-diabetic individuals

Reduced glomerular filtration rate (GFR) can progress to kidney failure. Risk factors include genetics and diabetes mellitus (DM), but little is known about their interaction. We conducted genome-wide association meta-analyses for estimated GFR based on serum creatinine (eGFR), separately for individuals with or without DM (nDM = 178,691, nnoDM = 1,296,113). Our genome-wide searches identified (i) seven eGFR loci with significant DM/noDM-difference, (ii) four additional novel loci with suggestive difference and (iii) 28 further novel loci (including CUBN) by allowing for potential difference. GWAS on eGFR among DM individuals identified 2 known and 27 potentially responsible loci for diabetic kidney disease. Gene prioritization highlighted 18 genes that may inform reno-protective drug development. We highlight the existence of DM-only and noDM-only effects, which can inform about the target group, if respective genes are advanced as drug targets. Largely shared effects suggest that most drug interventions to alter eGFR should be effective in DM and noDM