Use of glucocorticoids megadoses in SARS-CoV-2 infection in a spanish registry: SEMI-COVID-19.

OBJECTIVE: To describe the impact of different doses of corticosteroids on the evolution of patients with COVID-19 pneumonia, based on the potential benefit of the non-genomic mechanism of these drugs at higher doses. METHODS: Observational study using data collected from the SEMI-COVID-19 Registry. We evaluated the epidemiological, radiological and analytical scenario between patients treated with megadoses therapy of corticosteroids vs low-dose of corticosteroids and the development of complications. The primary endpoint was all-cause in-hospital mortality according to use of corticosteroids megadoses. RESULTS: Of a total of 14,921 patients, corticosteroids were used in 5,262 (35.3%). Of them, 2,216 (46%) specifically received megadoses. Age was a factor that differed between those who received megadoses therapy versus those who did not in a significant manner (69 years [IQR 59-79] vs 73 years [IQR 61-83]; p < .001). Radiological and analytical findings showed a higher use of megadoses therapy among patients with an interstitial infiltrate and elevated inflammatory markers associated with COVID-19. In the univariate study it appears that steroid use is associated with increased mortality (OR 2.07 95% CI 1.91-2.24 p < .001) and megadose use with increased survival (OR 0.84 95% CI 0.75-0.96, p 0.011), but when adjusting for possible confounding factors, it is observed that the use of megadoses is also associated with higher mortality (OR 1.54, 95% CI 1.32-1.80; p < .001). There is no difference between megadoses and low-dose (p .298). Although, there are differences in the use of megadoses versus low-dose in terms of complications, mainly infectious, with fewer pneumonias and sepsis in the megadoses group (OR 0.82 95% CI 0.71-0.95; p < .001 and OR 0.80 95% CI 0.65-0.97; p < .001) respectively. CONCLUSION: There is no difference in mortality with megadoses versus low-dose, but there is a lower incidence of infectious complications with glucocorticoid megadoses.

Long-term consumption of a mediterranean diet or a low-fat diet on kidney function in coronary heart disease patients: The CORDIOPREV randomized controlled trial.

BACKGROUND & AIMS: Lifestyle and dietary habits influence kidney function, playing an important role in the prevention and development of chronic kidney disease (CKD). The effectiveness of the Mediterranean diet in preserving kidney function has been seen in primary prevention. However, no scientific evidence is currently available to determine which dietary pattern is more effective in the management of CKD in secondary cardiovascular disease prevention. Thus, our aim was to evaluate the efficacy of the long-term consumption of two healthy dietary patterns (a Mediterranean diet rich in extra-virgin olive oil (EVOO) compared to a low-fat diet rich in complex carbohydrates) in preserving kidney function in coronary heart disease (CHD) patients. METHODS: CHD patients (n = 1002) from the CORDIOPREV study were randomized to follow a Mediterranean diet (35% fat, 22% MUFA, <50% carbohydrates) or a low-fat diet (28% fat, 12% MUFA, >55% carbohydrates). Kidney function was assessed by the determination of serum creatinine-based estimated glomerular filtration rate (eGFR) at baseline and after 5-years of dietary intervention. Patients were classified according to their type 2 diabetes (T2DM) status, using baseline eGFR (normal eGFR: ≥ 90 mL/min/1.73 m2; mildly-impaired eGFR: 60 to <90 mL/min/1.73 m2, severely-impaired eGFR: <60 mL/min/1.73 m2) to evaluate its influence on the progression of kidney function. Multiple linear regression analysis were performed to determine the contribution of different clinical and anthropometric parameters to changes in eGFR. RESULTS: Although eGFR declined after both dietary interventions compared to baseline (all p < 0.001), the Mediterranean diet produced a lower decline of eGFR compared to the low-fat diet in patients with T2DM (p = 0.040). This effect was also observed when the overall population was considered (p = 0.033). No significant differences were observed in eGFR between the two diets in non-T2DM patients. In addition, this differential effect of the Mediterranean diet was mainly observed in patients with mildly-impaired eGFR in which this diet slowed eGFR progression (p = 0.002). CONCLUSIONS: The long-term consumption of a Mediterranean diet rich in EVOO, when compared to a low-fat diet, may preserve kidney function, as shown by a reduced decline in eGFR in CHD patients with T2DM. Patients with mildly-impaired eGFR may benefit more from the beneficial effect of the consumption of the Mediterranean diet in preserving kidney function. These findings reinforce the clinical benefits of the Mediterranean diet in the context of secondary cardiovascular disease prevention. CLINICAL TRIAL REGISTRATION: URL, http://www.cordioprev.es/index.php/en. Clinicaltrials.gov number, NCT00924937.

Chronodisruption and diet associated with increased cardiometabolic risk in coronary heart disease patients: the CORDIOPREV study.

Individuals with evening chronotypes are prone to suffer chronodisruption and display worse lifestyle habits than morning-types, exhibiting higher cardiovascular diseases (CVD). However, it is unknown whether CVD patients, who are evening chronotypes, have higher cardiometabolic risk than morning-types. This study explored whether individual chronotypes were associated with cardiometabolic risk in patients from the CORDIOPREV study (n = 857). We also investigated whether potential associations were moderated by long-term consumption of two healthy diets (Mediterranean and Low-fat diets). This population was classified into chronotypes using the Morningness-Eveningness Questionnaire. Seven-day daily rhythms in wrist temperature (T), rest-activity (A) and position (P) were recorded in a subset of patients (n = 168), and an integrative variable TAP was determined. Metabolic Syndrome (MetS) was determined at baseline, and metabolic and inflammation markers were measured at baseline and yearly during the 4 years of follow-up. Differences in several lifestyle factors were analyzed according to chronotype. At all times, evening-types had higher triglycerides, C-reactive protein and homocysteine and lower high density lipoprotein cholesterol than morning-types (P < 0.05). Evening-types had a higher prevalence of MetS (OR 1.58 IC 95% [1.10 - 2.28], P = 0.01). Moreover, they were more sedentary, displayed less and delayed physical activity and ate and slept later. In addition, evening-types had lower amplitude, greater fragmentation, lower robustness and less stable circadian pattern at TAP (P < 0.01), all related to a less healthy circadian pattern. In conclusion, evening-types with CVD had higher cardiometabolic risk and less robust circadian-related rhythms than morning-types, regardless of the nutritional intervention.

Mediterranean Diet Reduces Atherosclerosis Progression in Coronary Heart Disease: An Analysis of the CORDIOPREV Randomized Controlled Trial.

Background and Purpose: Lifestyle and diet affect cardiovascular risk, although there is currently no consensus about the best dietary model for the secondary prevention of cardiovascular disease. The CORDIOPREV study (Coronary Diet Intervention With Olive Oil and Cardiovascular Prevention) is an ongoing prospective, randomized, single-blind, controlled trial in 1002 coronary heart disease patients, whose primary objective is to compare the effect of 2 healthy dietary patterns (low-fat rich in complex carbohydrates versus Mediterranean diet rich in extra virgin olive oil) on the incidence of cardiovascular events. Here, we report the results of one secondary outcome of the CORDIOPREV study. Thus, to evaluate the efficacy of these diets in reducing cardiovascular disease risk. Intima-media thickness of both common carotid arteries (IMT-CC) was ultrasonically assessed bilaterally. IMT-CC is a validated surrogate for the status and future cardiovascular disease risk. Methods: From the total participants, 939 completed IMT-CC evaluation at baseline and were randomized to follow a Mediterranean diet (35% fat, 22% monounsaturated fatty acids, <50% carbohydrates) or a low-fat diet (28% fat, 12% monounsaturated fatty acids, >55% carbohydrates) with IMT-CC measurements at 5 and 7 years. We also analyzed the carotid plaque number and height. Results: The Mediterranean diet decreased IMT-CC at 5 years (−0.027±0.008 mm; P<0.001), maintained at 7 years (−0.031±0.008 mm; P<0.001), compared to baseline. The low-fat diet did not modify IMT-CC. IMT-CC and carotid plaquemax height were higher decreased after the Mediterranean diet, compared to the low-fat diet, throughout follow-up. Baseline IMT-CC had the strongest association with the changes in IMT-CC after the dietary intervention. Conclusions: Long-term consumption of a Mediterranean diet rich in extravirgin olive oil, if compared to a low-fat diet, was associated with decreased atherosclerosis progression, as shown by reduced IMT-CC and carotid plaque height. These findings reinforce the clinical benefits of the Mediterranean diet in the context of secondary cardiovascular prevention. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00924937.

A flow-through microfluidic system for the detection of circulating melanoma cells.

We report the fabrication of polyaniline nanofiber (PANI)-modified screen-printed electrode (PANI/SPE) incorporated in a poly-dimethylsiloxane (PDMS) microfluidic channel for the detection of circulating tumor cells. We employed this device to detect melanoma skin cancer cells through specific immunogenic binding of cell surface biomarker melanocortin 1 receptor (MC1R) to anti-MC1R antibody. The antibody-functionalized PANI/SPE was used in batch-continuous flow-through fashion. An aqueous cell suspension of ferri/ferrocyanide at a flow rate of 1.5 mL/min was passed over the immunosensor, which allowed for continuous electrochemical measurements. The sensor performed exceptionally well affording an ultralow limit of quantification of 1 melanoma cell/mL, both in buffer and when mixed with peripheral blood mononuclear cells, and the response was log-linear over the range of 10-9000 melanoma cells/10 mL.

Patient-specific organotypic blood vessels as an in vitro model for anti-angiogenic drug response testing in renal cell carcinoma.

BACKGROUND: Anti-angiogenic treatment failure is often attributed to drug resistance, unsuccessful drug delivery, and tumor heterogeneity. Recent studies have speculated that anti-angiogenic treatments may fail due to characteristics inherent to tumor-associated blood vessels. Tumor-associated blood vessels are phenotypically different from their normal counterparts, having defective or permeable endothelial monolayers, abnormal sprouts, and abnormal vessel hierarchy. Therefore, to predict the efficacy of anti-angiogenic therapies in an individual patient, in vitro models that mirror individual patient's tumor vascular biology and response to anti-angiogenic treatment are needed. METHODS: We used a microfluidic in vitro organotypic model to create patient-specific biomimetic blood vessels from primary patient-specific tumor endothelial cells (TEnCs) and normal endothelial cells (NEnC). We assessed number of sprouts and vessel organization via microscopy imaging and image analysis. We characterized NEnC and TEnC vessel secretions via multiplex bead-based ELISA. FINDINGS: Using this model, we found that TEnC vessels exhibited more angiogenic sprouts than NEnC vessels. We also found a more disorganized and gap-filled endothelial monolayer. NEnCs and TEnC vessels exhibited heterogeneous functional drug responses across the five patients screened, as described in the clinic. INTERPRETATION: Our model recapitulated hallmarks of TEnCs and NEnCs found in vivo and captured the functional and structural differences between TEnC and NEnC vessels. This model enables a platform for therapeutic drug screening and assessing patient-specific responses with great potential to inform personalized medicine approaches. FUNDING: NIH grants R01 EB010039, R33 CA225281, R01CA186134 University of Wisconsin Carbone Cancer Center (CA014520), and University of Wisconsin Hematology training grant T32 HL07899.

Microbial volatile communication in human organotypic lung models.

We inhale respiratory pathogens continuously, and the subsequent signaling events between host and microbe are complex, ultimately resulting in clearance of the microbe, stable colonization of the host, or active disease. Traditional in vitro methods are ill-equipped to study these critical events in the context of the lung microenvironment. Here we introduce a microscale organotypic model of the human bronchiole for studying pulmonary infection. By leveraging microscale techniques, the model is designed to approximate the structure of the human bronchiole, containing airway, vascular, and extracellular matrix compartments. To complement direct infection of the organotypic bronchiole, we present a clickable extension that facilitates volatile compound communication between microbial populations and the host model. Using Aspergillus fumigatus, a respiratory pathogen, we characterize the inflammatory response of the organotypic bronchiole to infection. Finally, we demonstrate multikingdom, volatile-mediated communication between the organotypic bronchiole and cultures of Aspergillus fumigatus and Pseudomonas aeruginosa.

Adaptation of a Simple Microfluidic Platform for High-Dimensional Quantitative Morphological Analysis of Human Mesenchymal Stromal Cells on Polystyrene-Based Substrates.

Multipotent stromal cells (MSCs, often called mesenchymal stem cells) have garnered significant attention within the field of regenerative medicine because of their purported ability to differentiate down musculoskeletal lineages. Given the inherent heterogeneity of MSC populations, recent studies have suggested that cell morphology may be indicative of MSC differentiation potential. Toward improving current methods and developing simple yet effective approaches for the morphological evaluation of MSCs, we combined passive pumping microfluidic technology with high-dimensional morphological characterization to produce robust tools for standardized high-throughput analysis. Using ultraviolet (UV) light as a modality for reproducible polystyrene substrate modification, we show that MSCs seeded on microfluidic straight channel devices incorporating UV-exposed substrates exhibited morphological changes that responded accordingly to the degree of substrate modification. Substrate modification also effected greater morphological changes in MSCs seeded at a lower rather than higher density within microfluidic channels. Despite largely comparable trends in morphology, MSCs seeded in microscale as opposed to traditional macroscale platforms displayed much higher sensitivity to changes in substrate properties. In summary, we adapted and qualified microfluidic cell culture platforms comprising simple straight channel arrays as a viable and robust tool for high-throughput quantitative morphological analysis to study cell-material interactions.

A Microfluidic Method to Mimic Luminal Structures in the Tumor Microenvironment.

Microscale 3D in vitro systems have attracted significant interest as tools for cancer research because the microscale systems offer better organization of the cellular microenvironment and enhance throughput of the systems by lowering costs and reducing the amount of reagents and cells. Lumens (i.e., tubular structures) are ubiquitous in vivo being present in blood vessels, mammary ducts, prostate ducts, and the lymphatic system. Lumen structures of varying size and geometry are involved in key normal and disease processes including morphogenesis, angiogenesis, cancer development, and drug delivery. Therefore, there is a need for practical methods that create various lumen structures having different size and geometries to investigate how cells in the lumen structure respond to certain microenvironmental conditions during cancer development and progression. Here, we present a method to create multiple three-dimensional (3D) luminal structures, where parameters, such as size, geometry, and distance, can easily be controlled using simple poly-dimethylsiloxane (PDMS) micro-molds.

Diseño de un aplicativo para el registro de implantes, gestión de alertas e incidentes relacionados con productos sanitarios como herramienta para el responsable de vigilancia de productos sanitarios / Design of a computer program for the registration of implantable medical device, field safety corrective action and advers events, as a tool for medical device surveillance

Objetivo: Describir las funcionalidades de un programa informático de soporte a la actividad del responsable de vigilancia de productos sanitarios (PS). Analizar su utilidad tras un año de implantación. Método: Las etapas del proceso fueron: descripción de actividades básicas del responsable de vigilancia, definir las funcionalidades y datos a procesar, crear los formularios de registro y opciones de la herramienta SIVIPS, implantación en un hospital privado que gestiona PS, validación del programa y análisis de su utilidad al año. Resultados: Se desarrolló la herramienta SIVIPS en Acces® por farmacéuticos. Se describieron las variables básicas para todas las actividades del responsable de vigilancia de PS (registro implantes, registro de alertas, registro de incidentes con PS, incluidos los de diagnóstico in vitro) y las funcionalidades del programa. Al año de su implantación se encontraron registros de 564 implantes con la posibilidad de desglose por tipo de implante, 31 alertas con PS y 6 incidentes con PS, permitiendo el seguimiento de las actuaciones realizadas en estos casos. Conclusiones: SIVIPS® es la primera herramienta de soporte a la actividad del responsable de vigilancia de PS. Es una herramienta sencilla que permite de forma ágil el registro de alertas e incidentes con PS, así como el registro de los implantes realizados en el centro, consiguiendo mejorar la trazabilidad del PS (AU)

Objective: To describe the features of computer program to support the activity of the responsible for surveillance of medical devices. To evaluate their use after one year of implementation in a hospital. Method: The stages of the process were: description of the activities of medical devices surveillance and implant registration, definition of functionality and data processing, creation of databases, implementation in a private hospital which manages PS, validation of the program and analysis of their usefulness. Results: SIVIPS was developed using Acces®. Main variables were described for all the activities of the responsible for medical device surveillance (implants, alert, medical device incidents, including for in vitro diagnostics) and all the functionalities of the computer program. SIVIPS was introduced in a pharmacy service with one pharmacist for the management of medical devices. One year after its implementation we had registered 564 implants with a description by type of implant, 31 alerts and 6 incidents. SIVIPS allow monitoring of the actions taken in these cases. Conclusions: SIVIPS® is the first tool to support the activity of medical device surveillance. It is an easy tool that allows the registration of alerts and medical device related incidents, and registration of implants performed in the center, which will improve the traceability of the PS (AU)

[Design of a computer program for the registration of implantable medical device, field safety corrective action and advers events, as a tool for medical device surveillance]. / Diseño de un aplicativo para el registro de implantes, gestión de alertas e incidentes relacionados con productos sanitarios como herramienta para el responsable de vigilancia de productos sanitarios.

OBJECTIVE: To describe the features of computer program to support the activity of the responsible for surveillance of medical devices. To evaluate their use after one year of implementation in a hospital. METHOD: The stages of the process were: description of the activities of medical devices surveillance and implant registration, definition of functionality and data processing, creation of databases, implementation in a private hospital which manages PS, validation of the program and analysis of their usefulness. RESULTS: SIVIPS was developed using Acces. Main variables were described for all the activities of the responsible for medical device surveillance (implants, alert, medical device incidents, including for in vitro diagnostics) and all the functionalities of the computer program. SIVIPS was introduced in a pharmacy service with one pharmacist for the management of medical devices. One year after its implementation we had registered 564 implants with a description by type of implant, 31 alerts and 6 incidents. SIVIPS allow monitoring of the actions taken in these cases. CONCLUSIONS: SIVIPS is the first tool to support the activity of medical device surveillance. It is an easy tool that allows the registration of alerts and medical device related incidents, and registration of implants performed in the center, which will improve the traceability of the PS.

Objetivo: Describir las funcionalidades de un programa informático de soporte a la actividad del responsable de vigilancia de productos sanitarios (PS). Analizar su utilidad tras un año de implantación. Método: Las etapas del proceso fueron: descripción de actividades básicas del responsable de vigilancia, definir las funcionalidades y datos a procesar, crear los formularios de registro y opciones de la herramienta SIVIPS, implantación en un hospital privado que gestiona PS, validación del programa y análisis de su utilidad al año. Resultados: Se desarrolló la herramienta SIVIPS en Acces® por farmacéuticos. Se describieron las variables básicas para todas las actividades del responsable de vigilancia de PS (registro implantes, registro de alertas, registro de incidentes con PS, incluidos los de diagnóstico in vitro) y las funcionalidades del programa. Al año de su implantación se encontraron registros de 564 implantes con la posibilidad de desglose por tipo de implante, 31 alertas con PS y 6 incidentes con PS, permitiendo el seguimiento de las actuaciones realizadas en estos casos. Conclusiones: SIVIPS® es la primera herramienta de soporte a la actividad del responsable de vigilancia de PS. Es una herramienta sencilla que permite de forma ágil el registro de alertas e incidentes con PS, así como el registro de los implantes realizados en el centro, consiguiendo mejorar la trazabilidad del PS.

LumeNEXT: A Practical Method to Pattern Luminal Structures in ECM Gels.

In vitro biomimetic modeling of physio-logical structures bridges the gap between 2D in vitro culture and animal models. Lumens (tubular structures) are ubiquitous in vivo, being present in blood vessels, mammary ducts, and the lymphatic system. A method 'LumeNEXT' is presented here that allows the fabrication of 3D embedded lumens where size, structure, distance, and configuration can be controlled using standard poly-dimethylsiloxane micromolding methods.

Técnicas de obtención del plasma rico en plaquetas y su empleo en terapéutica osteoinductora / Methods to obtain platelet-rich plasma and osteoinductive therapeutic use

Introducción: El Plasma Rico en Plaquetas (PRP) es un plasma autólogo con una cifra de plaquetas superior a la del plasma basal, por haber sido sometido a algún proceso de extracción y concentración. El empleo del PRP como osteoinductor es conflictivo dado que, no existen estudios clínicos rigurosos que permita extraer conclusiones firmes respecto a su utilidad. Objetivo: Proporcionar información sobre las técnicas de obtención del PRP, las consideraciones legales sobre su obtención y empleo, el mecanismo de acción molecular, así como la evidencia disponible sobre su seguridad y tolerancia. Resultado: El PRP se obtiene de forma manual, mediante 'técnica abierta', o mediante kits desechables con 'técnica cerrada', siendo estos últimos productos sanitarios clasificados como IIa. La Agencia Española de Medicamentos y Productos Sanitarios (AEMPS) considera el PRP como medicamento, estableciendo unos requisitos mínimos para garantizar su seguridad, trazabilidad, farmacovigiliancia e información. El PRP, por su elevado contenido en factores de crecimiento, reúne cualidades para ser un potente papel osteoinductor, capaz de acelerar la consolidación de fracturas o de osteointegrar rápida y eficientemente distintos tipos de implantes óseos. La tolerancia a la infiltración es generalmente buena, aunque hay que tener en cuenta su elevado potencial angiogénico. Conclusiones: El PRP, dadas las características de producción y aplicación, es considerado por la AEMPS como un medicamento de dispensación bajo prescripción médica restringida, por lo que los servicios de farmacia hospitalaria deberían, cuando menos, supervisar su gestión y manipulación (AU)

Introduction: Platelet-Rich Plasma (PRP) is autologous plasma with higher concentration of platelet than basal level, because of an extracting and concentration process. PRP therapeutical use, as osteinductor role, is a controversial issue, due to there are no clinical studies with rigorous design and no firm conclusions can be drawn regarding its uses. Propose: To provide information about methods to obtain PRP, legal considerations about its extraction and use, molecular mechanism of action, as well as available evidence about security and tolerance. Results: PRP can be obtained by manual procedures (opened technique) or disposable kits (closed technique), the latter being medical devices classified as type IIa. AEMPS considers PRP as a drug, establishing some minimum requirements to guarantee safety, traceability, pharmacovigilance and information. PRP provides ideal qualities to play a powerful osteoinductor role to speed up fracture healing or to produce an efficiently and quickly osseointegration of different bone implants, due to the high growth factors content. Infiltration tolerance is generally good, however, it has to be taken into account its great angiogenical potential. Conclusions: In view of its production and application characteristics, PRP is considered as a drug on restricted medical prescription by the AEMPS, so pharmacy department must, at least, supervise its management and handling (AU)

[Methods to obtain platelet-rich plasma and osteoinductive therapeutic use]. / Técnicas de obtención del plasma rico en plaquetas y su empleo en terapéutica osteoinductora.

INTRODUCTION: Platelet-Rich Plasma (PRP) is autologous plasma with higher concentration of platelet than basal level, because of an extracting and concentration process. PRP therapeutical use, as osteinductor role, is a controversial issue, due to there are no clinical studies with rigorous design and no firm conclusions can be drawn regarding its uses. Propose: To provide information about methods to obtain PRP, legal considerations about its extraction and use, molecular mechanism of action, as well as available evidence about security and tolerance. RESULTS: PRP can be obtained by manual procedures (opened technique) or disposable kits (closed technique), the latter being medical devices classified as type IIa. AEMPS considers PRP as a drug, establishing some minimum requirements to guarantee safety, traceability, pharmacovigilance and information. PRP provides ideal qualities to play a powerful osteoinductor role to speed up fracture healing or to produce an efficiently and quickly osseointegration of different bone implants, due to the high growth factors content. Infiltration tolerance is generally good, however, it has to be taken into account its great angiogenical potential. CONCLUSIONS: In view of its production and application characteristics, PRP is considered as a drug on restricted medical prescription by the AEMPS, so pharmacy department must, at least, supervise its management and handling.

Introduccion: El Plasma Rico en Plaquetas (PRP) es un plasma autólogo con una cifra de plaquetas superior a la del plasma basal, por haber sido sometido a algún proceso de extracción y concentración. El empleo del PRP como osteoinductor es conflictivo dado que, no existen estudios clínicos rigurosos que permita extraer conclusiones firmes respecto a su utilidad. Objetivo: Proporcionar información sobre las técnicas de obtención del PRP, las consideraciones legales sobre su obtención y empleo, el mecanismo de acción molecular, así como la evidencia disponible sobre su seguridad y tolerancia. Resultado: El PRP se obtiene de forma manual, mediante "técnica abierta", o mediante kits desechables con "técnica cerrada", siendo estos últimos productos sanitarios clasificados como IIa. La Agencia Española de Medicamentos y Productos Sanitarios (AEMPS) considera el PRP como medicamento, estableciendo unos requisitos mínimos para garantizar su seguridad, trazabilidad, farmacovigiliancia e información. El PRP, por su elevado contenido en factores de crecimiento, reúne cualidades para ser un potente papel osteoinductor, capaz de acelerar la consolidación de fracturas o de osteointegrar rápida y eficientemente distintos tipos de implantes óseos. La tolerancia a la infiltración es generalmente buena, aunque hay que tener en cuenta su elevado potencial angiogénico. Conclusiones: El PRP, dadas las características de producción y aplicación, es considerado por la AEMPS como un medicamento de dispensación bajo prescripción médica restringida, por lo que los servicios de farmacia hospitalaria deberían, cuando menos, supervisar su gestión y manipulación.

Use of Cross-Linked Poly(ethylene glycol)-Based Hydrogels for Protein Crystallization.

Poly(ethylene glycol) (PEG) hydrogels are highly biocompatible materials extensively used for biomedical and pharmaceutical applications, controlled drug release, and tissue engineering. In this work, PEG cross-linked hydrogels, synthesized under various conditions, were used to grow lysozyme crystals by the counterdiffusion technique. Crystallization experiments were conducted using a three-layer arrangement. Results demonstrated that PEG fibers were incorporated within lysozyme crystals controlling the final crystal shape. PEG hydrogels also induced the nucleation of lysozyme crystals to a higher extent than agarose. PEG hydrogels can also be used at higher concentrations (20-50% w/w) as a separation chamber (plug) in counterdiffusion experiments. In this case, PEG hydrogels control the diffusion of the crystallization agent and therefore may be used to tailor the supersaturation to fine-tune crystal size. As an example, insulin crystals were grown in 10% (w/w) PEG hydrogel. The resulting crystals were of an approximate size of 500 µm.

The importance of being a lumen.

Advances in tissue engineering and microtechnology have enabled researchers to more easily generate in vitro tissue models that mimic the tissue geometry and spatial organization found in vivo (e.g., vessel or mammary duct models with tubular structures). However, the widespread adoption of these models for biological studies has been slow, in part due to the lack of direct comparisons between existing 2-dimensional and 3-dimensional cell culture models and new organotypic models that better replicate tissue structure. Using previously developed vessel and mammary duct models with 3-dimensional lumen structures, we have begun to explore this question. In a direct comparison between these next generation organotypic models and more traditional methods, we observed differences in the levels of several secreted growth factors and cytokines. In addition, endothelial vessel geometry profoundly affects the phenotypic behavior of carcinoma cells, suggesting that more traditional in vitro assays may not capture in vivo events. Here, we seek to review and add to the increasing evidence supporting the hypothesis that using cell culture models with more relevant tissue structure influences cell fate and behavior, potentially increasing the relevance of biological findings.