Dermic diffusion and stratum corneum: a state of the art review of mathematical models

Transdermal biotechnologies are an ever increasing field of interest, due to the medical and pharmaceutical applications that they underlie. There are several mathematical models at use that permit a more inclusive vision of pure experimental data and even allow practical extrapolation for new dermal diffusion methodologies. However, they grasp a complex variety of theories and assumptions that allocate their use for specific situations. Models based on Fick's First Law found better use in contexts where scaled particle theory Models would be extensive in time-span but the reciprocal is also true, as context of transdermal diffusion of particular active compounds changes. This article reviews extensively the various theoretical methodologies for studying dermic diffusion in the rate limiting dermic barrier, the stratum corneum, and systematizes its characteristics, their proper context of application, advantages and limitations, as well as future perspectives

Ser médico e aprender Medicina na Lusitânia romana

Al elegir un tema pertinente a la Historia de las Ciencias de la Salud, aquellos que se dediquen al estudio de la Lusitania romana ciertamente verán el análisis del estado socio-jurídico de los profesionales de la medicina como una opción más que evidente. Aunque el tópico tradicional de la insuficiencia de datos ha de ser tenido en cuenta también en este caso, poseemos un conjunto sustancial de datos arqueológicos y epigráficos que nos permiten esbozar un panorama de la cuestión. Entre los documentos disponibles existe una inscripción excepcional recientemente descubierta en la capital de la Lusitania (Edmondson, 2009) que llama la atención sobre algunos elementos esenciales para comprender el proceso de formación de los médicos en un contexto provincial romano. Las restantes inscripciones, que a veces también pueden hallarse en la literatura clásica, tienen la gran ventaja de presentar ejemplos concretos de médicos, de los cuales conocemos el nombre y algunos aspectos particulares de su vida, y en los que podemos encontrar explícita o implícitamente también su condición social. Por otra parte, lo que se sabe del amplio repositorio de epígrafes del mundo romano que se refieren a los médicos permite completar el cuadro y servir de punto de comparación sobre esta realidad particular del extremo occidental del Imperio.By choosing a pertinent topic to the History of Medical Sciences, those who dedicate themselves to the study of Roman Lusitania will certainly see the analysis of doctors socio-juridical status as an obvious option. Although the traditional topic of data scarcity can be applied to this subject, we have, nevertheless, a substantial set of archaeological and epigraphic data that allow us to draw a representation of the matter. Among the available documents, an exceptional inscription recently discovered in the capital of Lusitania (Edmondson, 2009), draws attention to some interesting elements to understand the process of medical training in a Roman provincial context. The remaining inscriptions, that sometimes quite suggestively also appear in classical literature, have the great advantage of presenting concrete examples of doctors, of whom we know the name and some particular aspects of their lives, and in which we can find explicitly or implicitly their social status. Moreover, what is known of the wide repository of epigraphs of the Roman world that refer to doctors, allow us to complete the picture and serve of parallel to this particular reality of the extreme west of the empire

Insights on Ultrafiltration-Based Separation for the Purification and Quantification of Methotrexate in Nanocarriers

The evaluation of encapsulation efficiency is a regulatory requirement for the characterization of drug delivery systems. However, the difficulties in efficiently separating nanomedicines from the free drug may compromise the achievement of accurate determinations. Herein, ultrafiltration was exploited as a separative strategy towards the evaluation of methotrexate (MTX) encapsulation efficiency in nanostructured lipid carriers and polymeric nanoparticles. The effect of experimental conditions such as pH and the amount of surfactant present in the ultrafiltration media was addressed aiming at the selection of suitable conditions for the effective purification of nanocarriers. MTX-loaded nanoparticles were then submitted to ultrafiltration and the portions remaining in the upper compartment of the filtering device and in the ultrafiltrate were collected and analyzed by HPLC-UV using a reversed-phase (C18) monolithic column. A short centrifugation time (5 min) was suitable for establishing the amount of encapsulated MTX in nanostructured lipid carriers, based on the assumption that the free MTX concentration was the same in the upper compartment and in the ultrafiltrate. The defined conditions allowed the efficient separation of nanocarriers from the free drug, with recoveries of >85% even when nanoparticles were present in cell culture media and in pig skin surrogate from permeation assays.info:eu-repo/semantics/publishedVersio

Antibody-Antigen Binding Interface Analysis in the Big Data Era

Antibodies have become the Swiss Army tool for molecular biology and nanotechnology. Their outstanding ability to specifically recognise molecular antigens allows their use in many different applications from medicine to the industry. Moreover, the improvement of conventional structural biology techniques (e.g., X-ray, NMR) as well as the emergence of new ones (e.g., Cryo-EM), have permitted in the last years a notable increase of resolved antibody-antigen structures. This offers a unique opportunity to perform an exhaustive structural analysis of antibody-antigen interfaces by employing the large amount of data available nowadays. To leverage this factor, different geometric as well as chemical descriptors were evaluated to perform a comprehensive characterization

Antibody-Antigen Binding Interface Analysis in the Big Data Era

Antibodies have become the Swiss Army tool for molecular biology and nanotechnology. Their outstanding ability to specifically recognise molecular antigens allows their use in many different applications from medicine to the industry. Moreover, the improvement of conventional structural biology techniques (e.g., X-ray, NMR) as well as the emergence of new ones (e.g., Cryo-EM), have permitted in the last years a notable increase of resolved antibody-antigen structures. This offers a unique opportunity to perform an exhaustive structural analysis of antibody-antigen interfaces by employing the large amount of data available nowadays. To leverage this factor, different geometric as well as chemical descriptors were evaluated to perform a comprehensive characterization.Fil: Reis, Pedro B. P. S.. Istituto Italiano Di Technologie; Italia. Universidade Nova de Lisboa; PortugalFil: Barletta Roldan, Patricio German. The Abdus Salam; Italia. The Abdus Salam. International Centre for Theoretical Physics; Italia. Universidad Nacional de Quilmes; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Gagliardi, Lucas. Istituto Italiano Di Technologie; ItaliaFil: Fortuna, Sara. Istituto Italiano Di Technologie; ItaliaFil: Soler, Miguel A.. Istituto Italiano Di Technologie; ItaliaFil: Rocchia, Walter. Istituto Italiano Di Technologie; Itali

Growth factor-free vascularization of marine-origin collagen sponges using cryopreserved stromal vascular fractions from human adipose tissue

The successful integration of transplanted three-dimensional tissue engineering (TE) constructs depends greatly on their rapid vascularization. Therefore, it is essential to address this vascularization issue in the initial design of constructs for perfused tissues. Two of the most important variables in this regard are scaffold composition and cell sourcing. Collagens with marine origins overcome some issues associated with mammal-derived collagen while maintaining their advantages in terms of biocompatibility. Concurrently, the freshly isolated stromal vascular fraction (SVF) of adipose tissue has been proposed as an advantageous cell fraction for vascularization purposes due to its highly angiogenic properties, allowing extrinsic angiogenic growth factor-free vascularization strategies for TE applications. In this study, we aimed at understanding whether marine collagen 3D matrices could support cryopreserved human SVF in maintaining intrinsic angiogenic properties observed for fresh SVF. For this, cryopreserved human SVF was seeded on blue shark collagen sponges and cultured up to 7 days in a basal medium. The secretome profile of several angiogenesis-related factors was studied throughout culture times and correlated with the expression pattern of CD31 and CD146, which showed the formation of a prevascular network. Upon in ovo implantation, increased vessel recruitment was observed in prevascularized sponges when compared with sponges without SVF cells. Immunohistochemistry for CD31 demonstrated the improved integration of prevascularized sponges within chick chorioalantoic membrane (CAM) tissues, while in situ hybridization showed human cells lining blood vessels. These results demonstrate the potential of using cryopreserved SVF combined with marine collagen as a streamlined approach to improve the vascularization of TE constructs.This research has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (Grant agreement No. 805411); Portuguese Foundation for Science and Technology under doctoral fellowship PD/BD/135252/2017 and individual grant IF/00347/2015; European Regional Development Fund, through INTERREG España-Portugal 2014-2020 under BLUEBIOLAB (0474_BLUEBIOLAB_1_E) project, through Atlantic Area Programme under BLUEHUMAN (EAPA_151/2016) project and through NORTE2020/PT2020 Programme under ATLANTIDA (Norte-01-0145-FEDER-000040) project

Therapeutic Options Targeting Oxidative Stress, Mitochondrial Dysfunction and Inflammation to Hinder the Progression of Vascular Complications of Diabetes

Type 2 diabetes mellitus is a leading cause of morbidity and mortality worldwide, given its serious associated complications. Despite constant efforts and intensive research, an effective, ubiquitous treatment still eludes the scientific community. As such, the identification of novel avenues of research is key to the potential discovery of this evasive “silver bullet.” We focus on this review on the matter of diabetic injury to endothelial tissue and some of the pivotal underlying mechanisms, including hyperglycemia and hyperlipidemia evoked oxidative stress and inflammation. In this sense, we revisited the most promising therapeutic interventions (both non-pharmacological and antidiabetic drugs) targeting oxidative stress and inflammation to hinder progression of vascular complications of diabetes. This review article gives particular attention to the relevance of mitochondrial function, an often ignored and understudied organelle in the vascular endothelium. We highlight the importance of mitochondrial function and number homeostasis in diabetic conditions and discuss the work conducted to address the aforementioned issue by the use of various therapeutic strategies. We explore here the functional, biochemical and bioenergetic alterations provoked by hyperglycemia in the endothelium, from elevated oxidative stress to inflammation and cell death, as well as loss of tissue function. Furthermore, we synthetize the literature regarding the current and promising approaches into dealing with these alterations. We discuss how known agents and therapeutic behaviors (as, for example, metformin, dietary restriction or antioxidants) can restore normality to mitochondrial and endothelial function, preserving the tissue’s function and averting the aforementioned complications

Modulation of subventricular zone oligodendrogenesis: a role for hemopressin?

Neural stem cells (NSCs) from the subventricular zone (SVZ) have been indicated as a source of new oligodendrocytes to use in regenerative medicine for myelin pathologies. Indeed, NSCs are multipotent cells that can self-renew and differentiate into all neural cell types of the central nervous system. In normal conditions, SVZ cells are poorly oligodendrogenic, nevertheless their oligodendrogenic potential is boosted following demyelination. Importantly, progressive restriction into the oligodendrocyte fate is specified by extrinsic and intrinsic factors, endocannabinoids being one of these factors. Although a role for endocannabinoids in oligodendrogenesis has already been foreseen, selective agonists and antagonists of cannabinoids receptors produce severe adverse side effects. Herein, we show that hemopressin (Hp),a modulator of CB1 receptors, increased oligodendroglial differentiation in SVZ neural stem/progenitor cell cultures derived from neonatal mice. The original results presented in this work suggest that Hp and derivates may be of potential interest for the development of future strategies to treat demyelinating diseases

Blueberry consumption challenges hepatic mitochondrial bioenergetics and elicits transcriptomics reprogramming in healthy wistar rats

An emergent trend of blueberries’ (BB) “prophylactic” consumption, due to their phytochemicals’ richness and well-known health-promoting claims, is widely scaled-up. However, the benefits arising from BB indiscriminate intake remains puzzling based on incongruent preclinical and human data. To provide a more in-depth elucidation and support towards a healthier and safer consumption, we conducted a translation-minded experimental study in healthy Wistar rats that consumed BB in a juice form (25 g/kg body weight (BW)/day; 14 weeks’ protocol). Particular attention was paid to the physiological adaptations succeeding in the gut and liver tissues regarding the acknowledged BB-induced metabolic benefits. Systemically, BB boosted serum antioxidant activity and repressed the circulating levels of 3-hydroxybutyrate (3-HB) ketone bodies and 3-HB/acetoacetate ratio. Moreover, BB elicited increased fecal succinic acid levels without major changes on gut microbiota (GM) composition and gut ultra-structural organization. Remarkably, an accentuated hepatic mitochondrial bioenergetic challenge, ensuing metabolic transcriptomic reprogramming along with a concerted anti-inflammatory pre-conditioning, was clearly detected upon long-term consumption of BB phytochemicals. Altogether, the results disclosed herein portray a quiescent mitochondrial-related metabolomics and hint for a unified adaptive response to this nutritional challenge. The beneficial or noxious consequences arising from this dietary trend should be carefully interpreted and necessarily claims future research.info:eu-repo/semantics/publishedVersio