Evaluación de la eficacia anti-arrugas de formulaciones cosméticas con un péptido anti-envejecimiento (Argirelina®)

The purpose of this research was to evaluate, by means of in vivo studies, the efficacy of new cosmetic active ingredients which effect of botox, called Argireline®), so that width and depth of wrinkles could be established. For this, it is prepared two formulations: an emulsion with an external aqueous phase for normal to dry skin, and a gel for oily skin. We likewise study the water content of the skin after the application of both formulas, as this must be one of the priority functions of facial treatments in general, as well as the level of satisfaction from the subjective point of view, fundamental for patients and their continuation of the treatment.After the designed tests, it is possible to verify that there is a remarkable diminution of the wrinkles size tested in each patient during the month of treatment. Besides, it is possible to review how the moisturizing capacity has been increased in all cases.At the end of the visual test, all the volunteers experienced a reduction in the depth of wrinkles, and from the subjective point of view, the appearance and elasticity of the skin were improved. Finally it is possible to conclude that Argireline® (acetyl hexapeptide-8 ) shows a great antiaging capacity in all the cases that have been studied and the tried compounds have increased moisturizing power.El propósito de esta investigación fue evaluar, mediante estudios in vivo, se podrían establecer la eficacia de nuevos ingredientes activos cosméticos que efecto del botox, llamado Argirelina®), de manera que la anchura y la profundidad de las arrugas. Para esto, se preparó dos formulaciones: una emulsión con una fase acuosa externa para piel normal a seca, y un gel para la piel grasa. Del mismo modo se estudia el contenido de agua de la piel después de la aplicación de ambas fórmulas, ya que esta debe ser una de las funciones prioritarias de tratamientos faciales en general, así como el nivel de satisfacción desde el punto de vista subjetivo, tanto para el enfermo y su continuación del tratamiento.Después de las pruebas diseñadas, es posible verificar que hay una notable disminución del tamaño de las arrugas a prueba en cada paciente durante el mes de tratamiento. Además, es posible revisar la forma en la capacidad de hidratación se ha incrementado en todos los casos.Al final de la prueba visual, todos los voluntarios experimentaron una reducción en la profundidad de las arrugas, y desde el punto de vista subjetivo, el aspecto y la elasticidad de la piel se han mejorado. Por último, es posible concluir que Argirelina® (hexapéptido acetil-8) muestra una gran capacidad antienvejecimiento en todos los casos que han sido estudiados y los compuestos probados se han incrementado poder hidratante

Liposomal Triamcinolone acetonide: Infl uence of composition in performance and stability

El acetónido de triamcinolona, antiinfl amatorio esteroideo, presenta por vía tópica los inconvenientes de la corticoterapia.No obstante, su incorporación a un sistema transportador, como los liposomas permitiría prolongar ladosis efectiva en el lugar de acción (dermis y epidermis), reduciendo los efectos secundarios. Así pues, se ha normalizadoel método de elaboración de liposomas multilaminares portadores de acetónido de triamcinolona y evaluadoel grado de captación del fármaco seleccionado, en función de la composición de los liposomas, determinando loscomponentes más idóneos para su obtención y los rendimientos proporcionados al variar las concentraciones de losmismos. La adición de colesterol para mejorar su estabilidad, provoca una reducción media en la captación; noobstante la encapsulación sigue siendo bastante elevada. La evaluación de la estabilidad muestra la infl uencia de latemperatura de conservación, de tal manera que los liposomas mantenidos a temperatura de refrigeración (4-6ºC)poseen una estabilidad mayor que las muestras a temperatura ambiente.In topical presentation, Triamcinolone acetonide, a steroidal anti-infl ammatory preparation, presents all the disadvantagesof corticotherapy. However, on incorporation into a liposomal drug delivery system, the effectiveness of each dosagewithin the area of its activity (dermis and epidermis) is prolonged, serving to reduce secondary side effects. For thisreason, an attempt has been made to standardize a method for the preparation of a multilaminar liposomal deliverysystem of triamcinolone acetonide and to assess how much of the drug could be encapsulated by the varying liposomalformulations tested and consequently, which of these would prove to be the most suitable. The addition of cholesterolto such formulations was found to improve stability. However, although such an addition was found to reduce levelsof encapsulation of the drug, these still remained suffi ciently high. In the assessment of stability, storage temperaturewas found to bear an infl uence. Liposomes kept under cold storage (4-6ºC) presented higher stability than samplesstored at room temperature

Study of Melatonin as Preventive Agent of Gastrointestinal Damage Induced by Sodium Diclofenac

: Safety profile of nonsteroidal anti‐inflammatory drugs (NSAIDs) has been widely studied and both therapeutic and side effects at the gastric and cardiovascular level have been generally associated with the inhibitory effect of isoform 1 (COX‐1) and 2 (COX‐2) cyclooxygenase enzymes. Now there are evidences of the involvement of multiple cellular pathways in the NSAIDs‐mediated‐gastrointestinal (GI) damage related to enterocyte redox state. In a previous review we summarized the key role of melatonin (MLT), as an antioxidant, in the inhibition of inflammation pathways mediated by oxidative stress in several diseases, which makes us wonder if MLT could minimize GI NSAIDs side effects. So, the aim of this work is to study the effect of MLT as preventive agent of GI injury caused by NSAIDs. With this objective sodium diclofenac (SD) was administered alone and together with MLT in two experimental models, ex vivo studies in pig intestine, using Franz cells, and in vivo studies in mice where stomach and intestine were studied. The histological evaluation of pig intestine samples showed that SD induced the villi alteration, which was prevented by MLT. In vivo experiments showed that SD altered the mice stomach mucosa and induced tissue damage that was prevented by MLT. The evaluation by quantitative reverse transcription PCR (RT‐qPCR) of two biochemical markers, COX‐2 and iNOS, showed an increase of both molecules in less injured tissues, suggesting that MLT promotes tissue healing by improving redox state and by increasing iNOS/NO that under non‐oxidative condition is responsible for the maintenance of GI‐epithelium integrity, increasing blood flow and promoting angiogenesis and that in presence of MLT, COX‐2 may be responsible for wound healing in enterocyte. Therefore, we found that MLT may be a preventive agent of GI damages induced by NSAIDs. Keywords: melatonin; NSAIDs; gastric injuries; antioxidan

Validation of an Ex Vivo Permeation Method for the Intestinal Permeability of Different BCS Drugs and Its Correlation with Caco-2 In Vitro Experiments

The absorption study of drugs through different biological membranes constitutes an essential step in the development of new pharmaceutical dosage forms. Concerning orally administered forms, methods based on monolayer cell culture of Caco-2 (Caucasian colon adenocarcinoma) have been developed to emulate intestinal mucosa in permeability studies. Although it is widely accepted, it has disadvantages, such as high costs or high technical complexity, and limitations related to the simplified structure of the monolayer or the class of molecules that can be permeated according to the transport mechanisms. The aim of this work was to develop a new ex vivo methodology which allows the evaluation of the intestinal apparent permeability coefficient (Papp) while using fewer resources and to assess the correlation with Caco-2. To this end, pig (Sus scrofa) duodenum segments were mounted in Franz diffusion cells and used to permeate four different drugs: ketorolac tromethamine (Kt), melatonin (Mel), hydrochlorothiazide (Htz), and furosemide (Fur). No statistically significant differences (p > 0.05) were observed corelating Papp values from Franz diffusion cells and Caco-2 cell experiments for Kt, Htz, and Fur. However, there were statistically significant differences (p < 0.05) correlating Papp values and Mel. The difference is explained by the role of Mel in the duodenal epithelial paracellular permeability reduction. Ex vivo permeation may be an equivalent method to Caco-2 for drugs that do not produce intestinal membrane phenomena that could affect absorption

¿ES NECESARIO PROFESIONALIZAR LA FIGURA DEL TUTOR DE ESPECIALISTAS EN FORMACIÓN SANITARIA?

The training system of health care professionals in our country is mature enough, but it has to face new challenges, as it is the case of the professionalization of the academic advisor of specialists in formation. The current regulation governing the specialized training, attaches importance to this figure but scarcely portrays it. The large structural transformation raises the need to conceive new professionals to which to attribute competencies that have not been required to date. To assist the adaptation to all these changes, we need new teaching-learning systems based on competencies to facilitate learning throughout life, to contribute to birth of the kind of professional required and demanded in the XXI century. We are aware that neither the health care organizations, nor the profile of health care professionals have remained on the sidelines of the new requirements of the environment. Therefore, we wonder if the academic advisor of specialists in training is prepared to assume these responsibilities, being necessary and priority, its professionalization.El sistema de formación de especialistas sanitarios en nuestro país es suficientemente maduro, pero se ha de enfrentar a nuevos retos, como es el caso de la profesionalización del tutor de especialistas en formación. La actual normativa que regula la formación especializada atribuye importancia a esta figura pero apenas la perfila. La gran transformación estructural, replantea la necesidad de concebir nuevos profesionales a los que se les pueda atribuir competencias no requeridas hasta el momento. Para ayudar a la adaptación de todos estos cambios, es preciso nuevos sistemas de  enseñanza-aprendizaje basados en competencias que faciliten un aprendizaje a lo largo de la vida, para contribuir al nacimiento del profesional requerido y demandado en el siglo XXI. Somos conscientes que ni las organizaciones sanitarias ni el perfil del profesional de la salud han quedado al margen de las nuevas exigencias del entorno, por lo que nos preguntamos si el tutor de especialistas en formación está preparado para asumir estas responsabilidades, siendo necesario y prioritario su profesionalización

Development and characterization of a poloxamer hydrogel composed of human mesenchymal stromal cells (hMSCs) for reepithelization of skin injuries

Wound healing is a natural physiological reaction to tissue injury. Hydrogels show attractive advantages in wound healing not only due to their biodegradability, biocompatibility and permeability but also because provide an excellent environment for cell migration and proliferation. The main objective of the present study was the design and characterization of a hydrogel loaded with human mesenchymal stromal cells (hMSCs) for use in would healing of superficial skin injures. Poloxamer 407® was used as biocompatible biomaterial to embed hMSCs. The developed hydrogel containing 20 % (w/w) of polymer resulted in the best formulation with respect to physical, mechanical, morphological and biological properties. Its high swelling capacity confirmed the hydrogel’s capacity to absorb wounds’ exudate. LIVE/DEAD® assay confirm that hMSCs remained viable for at least 48 h when loaded into the hydrogels. Adding increasing concentrations of hMSCs-loaded hydrogel to the epithelium did not affect keratinocytes’ viability and healing capacity and all wound area was closed in less than one day. Our study opens opportunities to exploit poloxamer hydrogels as cell carriers for the treatment of skin superficial wound

Developing Transdermal Applications of Ketorolac Tromethamine Entrapped in Stimuli Sensitive Block Copolymer Hydrogels

Purpose: In order to obtain dermal vehicles of ketorolac tromethamine (KT) for the local treatment of inflammation and restrict undesirable side effects of systemic levels hydrogels (HGs) of poloxamer and carbomer were developed. / Methods: KT poloxamer based HG (KT-P407-HG) and KT carbomer based HG (KT-C940-HG) were elaborated and characterized in terms of swelling, degradation, porosity, rheology, stability, in vitro release, ex vivo permeation and distribution skin layers. Finally, in vivo anti-inflammatory efficacy and skin tolerance were also assessed. / Results: HGs were transparent and kept stable after 3 months exhibiting biocompatible near neutral pH values. Rheological patterns fitted to Herschel-Bulkley for KT-C940-HG and Newton for KT-P407-HG due to its low viscosity at 25°C. Rapid release profiles were observed through first order kinetics. Following the surface the highest concentration of KT from C940-HG was found in the epidermis and the stratum corneum for P407-HG. Relevant anti-inflammatory efficacy of KT-P407-HG revealed enough ability to provide sufficient bioavailability KT to reach easily the site of action. The application of developed formulations in volunteers did not induce any visual skin irritation. / Conclusions: KT-P407-HG was proposed as suitable formulation for anti-inflammatory local treatment without theoretical systemic side effect

Advanced glycoxidation and lipoxidation end products (AGEs and ALEs): an overview of their mechanisms of formation

Advanced lipoxidation end products (ALEs) and advanced glycation end products (AGEs) have a pathogenetic role in the development and progression of different oxidative-based diseases including diabetes, atherosclerosis, and neurological disorders. AGEs and ALEs represent a quite complex class of compounds that are formed by different mechanisms, by heterogeneous precursors and that can be formed either exogenously or endogenously. There is a wide interest in AGEs and ALEs involving different aspects of research which are essentially focused on set-up and application of analytical strategies (1) to identify, characterize, and quantify AGEs and ALEs in different pathophysiological conditions ; (2) to elucidate the molecular basis of their biological effects ; and (3) to discover compounds able to inhibit AGEs/ALEs damaging effects not only as biological tools aimed at validating AGEs/ALEs as drug target, but also as promising drugs. All the above-mentioned research stages require a clear picture of the chemical formation of AGEs/ALEs but this is not simple, due to the complex and heterogeneous pathways, involving different precursors and mechanisms. In view of this intricate scenario, the aim of the present review is to group the main AGEs and ALEs and to describe, for each of them, the precursors and mechanisms of formation

Modeling-Dependent Protein Characterization of the Rice Aldehyde Dehydrogenase (ALDH) Superfamily Reveals Distinct Functional and Structural Features

The completion of the rice genome sequence has made it possible to identify and characterize new genes and to perform comparative genomics studies across taxa. The aldehyde dehydrogenase (ALDH) gene superfamily encoding for NAD(P)+-dependent enzymes is found in all major plant and animal taxa. However, the characterization of plant ALDHs has lagged behind their animal- and prokaryotic-ALDH homologs. In plants, ALDHs are involved in abiotic stress tolerance, male sterility restoration, embryo development and seed viability and maturation. However, there is still no structural property-dependent functional characterization of ALDH protein superfamily in plants. In this paper, we identify members of the rice ALDH gene superfamily and use the evolutionary nesting events of retrotransposons and protein-modeling–based structural reconstitution to report the genetic and molecular and structural features of each member of the rice ALDH superfamily in abiotic/biotic stress responses and developmental processes. Our results indicate that rice-ALDHs are the most expanded plant ALDHs ever characterized. This work represents the first report of specific structural features mediating functionality of the whole families of ALDHs in an organism ever characterized