Physicians' Perception of Oral Nutritional Supplement Acceptance and Tolerability in Malnourished Outpatients: PerceptiONS Study.

Malnutrition is a common condition associated with various pathologies such as infections, neoplasms and digestive system disorders. Patients can be managed using different strategies, which include dietary modifications or oral nutritional supplements (ONS). It is important to promote good ONS adherence in order to attain clinical efficacy and cost-effectiveness. Several factors (amount, type, duration and tolerability) may have an impact on ONS adherence. PerceptiONS is a descriptive, cross-sectional observational study based on an ad hoc electronic survey designed to explore physicians' perception of malnourished outpatients prescribed ONS. The survey considered adherence, acceptance/satisfaction, tolerability and benefits within the context of Spain's healthcare system. The perceptions of 548 physicians regarding the experience of 2516 patients were analyzed. From the physicians' perspective, 57.11% of patients adhered to over 75% of the prescribed ONS. The organoleptic properties of ONS represented the aspect with the most positive impact on adherence, with smell (43.72%) ranking as the top characteristic. In general, patients were satisfied (90.10%) with the ONS, with their related benefits (88.51%) and their organoleptic properties (90.42%), and accepted ONS in their daily diet (88.63%). ONS improved patients' general condition (87.04%), quality of life (QoL) (81.96%) and vitality/energy (81.28%). Physicians would prescribe the same ONS again in 96.4% of the cases.

Auditoría de la dispensación de antibióticos en la farmacia comunitaria (proyecto ‘Happy Patient’) / Audit of antibiotic dispensing in the community pharmacy ('Happy Patient' project)

Resumen: La dispensación y la prescripción de antibióticos no se adecúa a los estándares científicos en muchos de los países en la Unión Europea, entre los que se encuentra España, resultando una amenaza para la salud de la población. Para hacer frente al crecimiento de las resistencias antimicrobianas surgió el proyecto “Happy Patient” bajo el auspicio de la Comisión Europea. Objetivos: conocer las características de la dispensación de antibióticos en farmacias comunitarias españolas. Comparar la variabilidad entre las diferentes farmacias comunitarias españolas. Material y métodos: se utilizó el método “Audit Project Odense®” para conocer cómo eran las dispensaciones de antibióticos en las farmacias comunitarias, pidiendo a los farmacéuticos participantes registrar durante 5 días consecutivos entre los meses de febrero y abril de 2022, las actuaciones llevadas a cabo durante la dispensación de antibióticos por vía oral para uso humano y para el tratamiento de infecciones agudas. Resultados: se entrevistaron a 573 usuarios (59,9 % mujeres) de todas las edades. Los usuarios conocían en un 83,6 % para qué había sido prescrito el antibiótico siendo el más demandado la amoxicilina seguido de la amoxicilina con ácido clavulánico. En un 15 % de las dispensaciones (n=86) se realizaron los tres controles de seguridad: interacciones, contraindicaciones y alergias. El dispensador contactó muy raramente con el prescriptor (4 veces), pero cuando lo hizo, éste cambió la prescripción. En el 62,3 % de los casos se ofreció información sobre la duración del tratamiento y la amoxicilina con y sin ácido clavulánico fue el antibiótico dispensado en el que en más ocasiones se advirtió de los efectos secundarios. En un 24,6 % de las dispensaciones no se ofreció ninguna información personalizada del medicamento. En el 81,7 % el farmacéutico estuvo de acuerdo con el tratamiento prescrito (AU)

ShcA promotes chondrocyte hypertrophic commitment and osteoarthritis in mice through RunX2 nuclear translocation and YAP1 inactivation.

OBJECTIVE: Chondrocyte hypertrophic differentiation, a key process in endochondral ossification, is also a feature of osteoarthritis leading to cartilage destruction. Here we investigated the role of the adaptor protein Src homology and Collagen A (ShcA) in chondrocyte differentiation and osteoarthritis. METHODS: Mice ablated for ShcA in osteochondroprogenitor cells were generated by crossing mice carrying the Twist2-Cre transgene with ShcAflox/flox mice. Their phenotype (n = 5 to 14 mice per group) was characterized using histology, immuno-histology and western-blot. To identify the signaling mechanisms involved, in vitro experiments were conducted on wild type and ShcA deficient chondrocytes (isolated from n = 4 to 7 littermates) and the chondroprogenitor cell line ATDC5 (n = 4 independent experiments) using western-blot, cell fractionation and confocal microscopy. RESULTS: Deletion of ShcA decreases the hypertrophic zone of the growth plate (median between group difference -11.37% [95% confidence interval -17.34 to -8.654]), alters the endochondral ossification process, and leads to dwarfism (3 months old male mice nose-to-anus length -1.48 cm [-1.860 to -1.190]). ShcA promotes ERK1/2 activation, nuclear translocation of RunX2, the master transcription factor for chondrocyte hypertrophy, while maintaining the Runx2 inhibitor, YAP1, in its cytosolic inactive form. This leads to hypertrophic commitment and expression of markers of hypertrophy, such as Collagen X. In addition, loss of ShcA protects from age-related osteoarthritis development in mice (2 years old mice OARSI score -6.67 [-14.25 to -4.000]). CONCLUSION: This study reveals ShcA as a new player in the control of chondrocyte hypertrophic differentiation and its deletion slows down osteoarthritis development.

Poor cervical proprioception as a risk factor for concussion in professional male rugby union players.

BACKGROUND: Concussion is one of the most common injuries in male professional Rugby Union ('rugby') and accounts for significant time loss from training and competition. Despite the most recent Concussion in Sport Group consensus statement recommending a focus on the identification of modifiable risk factors, limited evidence for their existence is available. OBJECTIVE: To investigate the association between cervical proprioception and concussion incidence in a group of professional male rugby players over the course of a full season. METHODS: 165 players were assessed at pre-, mid- and end of season time points using the Cervical Joint Position Error Test (CJPET). Associations with diagnosed concussion injuries are presented as incidence rate ratios with 95% confidence intervals. We present the Incidence Rate Ratios (IRR) for a 10% increase in each variable and compared results against concussion using match minutes to account for risk exposure. RESULTS: During the study period, 45 concussions were incurred by 44 players [or 19.7 concussions per 1000 player-match hours]. There was a significant association between right rotation repositioning error and concussion, with a 5% increase in concussion rate for each 10% increase in gross right rotation error (P = 0.021). CONCLUSION: Poor gross right rotation repositioning error is a modifiable intrinsic risk factor for concussion in professional male rugby players. Interventions to improve proprioceptive function may act as an effective method for reducing concussion incidence in this population.

Immediate effects of rhythmic joint mobilization of the temporomandibular joint on pain, mouth opening and electromyographic activity in patients with temporomandibular disorders.

BACKGROUND: Rhythmic joint mobilizations (RJM) of the temporomandibular joint (TMJ) are employed to relieve pain and improve function in patients with temporomandibular disorders (TMD). However, the evidence on the immediate effects of RJM in patients with TMD is scarce. The aim of this study was to assess the immediate clinical and functional effects of RJM in patients with TMD. MATERIALS AND METHODS: This was a one-group quasi-experimental before and after study. Thirty-eight patients with TMD were assessed by means of pain intensity (visual analogue score, VAS), pressure pain threshold (PPT, measured through pressure algometry on the masseter and temporal muscles), mouth opening (MO, measured with a ruler), and surface electromyographic activity of the masseter and temporal muscles (asymmetry index, AI). Measurements were performed before and after a single, 1-min session of RJM of each TMJ. All statistical analyses were performed using the SPSS version 20.0 statistical package. RESULTS: A statistical significant difference was found in pain intensity, PPT and MO after the intervention (p < 0.05). No difference was found in the AI. A large effect size was observed for pain intensity, PPT of the left and right masseter muscles and MO (d = 0.85-1.13), whereas for the left and right temporal muscles the effect size was moderate (d = 0.62) and small, respectively (d = 0.49). CONCLUSION: In this sample of patients with TMD, a single session of RJM of the TMJ seemed to be effective in reducing pain intensity, increasing PPT and improving MO immediately after the intervention, without differences in the AI.

Histidine Self-assembly and Stability on Mineral Surfaces as a Model of Prebiotic Chemical Evolution: An Experimental and Computational Approach.

The abiotic synthesis of histidine under experimental prebiotic conditions has proven to be chemically promising and plausible. Within this context, the present results suggest that histidine amino acid may function as a simple prebiotic catalyst able to enhance amino acid polymerization. This work describes an experimental and computational approach to the self-assembly and stabilization of DL-histidine on mineral surfaces using antigorite ((Mg, Fe)3Si2O5(OH)4), pyrite (FeS2), and aragonite (CaCO3) as representative minerals of prebiotic scenarios, such as meteorites, and subaerial and submarine hydrothermal systems. Experimental results were obtained through polarized-light microscopy, IR spectroscopy (ATR-FTIR), and differential scanning calorimetry (DSC). Molecular dynamics was performed through computational simulations with the MM + method in HyperChem software. IR spectra suggest the presence of peptide bonds in the antigorite-histidine and aragonite-histidine assemblages with the presence of amide I and amide II vibration bands. The FTIR second derivative inspection supports this observation. Moreover, DSC data shows histidine stabilization in the presence of antigorite and aragonite by changes in histidine thermodynamic properties, particularly an increase in histidine decomposition temperature (272ºC in antigorite and 275ºC in aragonite). Results from molecular dynamics are consistent with DSC data, suggesting an antigorite-histidine closer interaction with decreased molecular distances (cca. 5.5 Å) between the amino acid and the crystal surface. On the whole, the experimental and computational outcomes support the role of mineral surfaces in prebiotic chemical evolution as enhancers of organic stability.

Deep learning enables the automation of grading histological tissue engineered cartilage images for quality control standardization.

OBJECTIVE: To automate the grading of histological images of engineered cartilage tissues using deep learning. METHODS: Cartilaginous tissues were engineered from various cell sources. Safranin O and fast green stained histological images of the tissues were graded for chondrogenic quality according to the Modified Bern Score, which ranks images on a scale from zero to six according to the intensity of staining and cell morphology. The whole images were tiled, and the tiles were graded by two experts and grouped into four categories with the following grades: 0, 1-2, 3-4, and 5-6. Deep learning was used to train models to classify images into these histological score groups. Finally, the tile grades per donor were averaged. The root mean square errors (RMSEs) were calculated between each user and the model. RESULTS: Transfer learning using a pretrained DenseNet model was selected. The RMSEs of the model predictions and 95% confidence intervals were 0.49 (0.37, 0.61) and 0.78 (0.57, 0.99) for each user, which was in the same range as the inter-user RMSE of 0.71 (0.51, 0.93). CONCLUSION: Using supervised deep learning, we could automate the scoring of histological images of engineered cartilage and achieve results with errors comparable to inter-user error. Thus, the model could enable the automation and standardization of assessments currently used for experimental studies as well as release criteria that ensure the quality of manufactured clinical grafts and compliance with regulatory requirements.

Angiogenesis in cardiopulmonary dirofilariosis: does the Wolbachia surface protein have a pro- or anti-angiogenic effect?

Cardiopulmonary dirofilariosis caused by Dirofilaria immitis produces inflammation, blood vessel obstruction and hypoxia, which are required conditions for the beginning of the process of neovascularization. Since D. immitis harbours intracellular symbiotic Wolbachia bacterium, the global understanding of the angiogenic process requires the analysis of the effect of the parasite molecules, but also that of Wolbachia. Canine primary lung microvascular endothelial cells were treated with the recombinant Wolbachia surface protein (rWSP) and the expression of angiogenic factors like Vascular Endothelial Growth Factor-A (VEGF-A), sFlt, membrane Endoglin (mEndoglin) and soluble Endoglin (sEndoglin), as well as the in vitro formation of pseudocapillaries, were measured. The analyses showed a significant increase in the expression of pro-angiogenic VEGF-A and anti-angiogenic sEndoglin, together with a significant decrease in both pro-angiogenic mEndoglin and pseudocapillary formation, compared to untreated controls. Due to the complexity of the angiogenic process and its relationship with other physiological processes like inflammation and fibrinolysis, these results might suggest that rWSP participate in various mechanisms related to each other and its effects might depend either on the balance between them or on the moment of their occurrence.

The impact of prenatal environment on postnatal life and performance: Future perspectives for prevention and treatment.

The present review aims to offer a non-comprehensive outline of the current state-of-the-art and future perspectives on management and therapeutic tools for intrauterine growth restriction (IUGR) and associated prenatal programming in both human and animal species. Animals are used as models for the study of phenomena related to IUGR, but also for research on prenatal therapies with the main objective of designing and developing preventive and therapeutic strategies. The research is currently paying attention on maternal-focused pharmacological treatments and nutritional strategies but also on fetal-focused treatments. Fetal-focused treatments, administered either directly at the fetus or by using infusion of umbilical cord, amniotic sac or placenta, which avoids the administration of substances at high doses to the mother for allowing their availability at the fetoplacental level. The results obtained in this area of research using large animals (rabbits, pigs and ruminants) have a dual interest, for translational biomedicine and for veterinary medicine and animal production.

Estudio de prototipos de formulaciones farmacéuticas de soluciones hidratantes para situaciones de estrés hídrico / Study of prototypes of pharmaceutical formulations of hydration solutions for situations of dry stress

Introducción: La actividad desarrollada por miembros de las Fuerzas Armadas, fuerzas de seguridad y personal dedicado a labores de rescate y salvamento, pueden dar lugar a procesos de deshidratación que conduzcan a situaciones de estrés hídrico caracterizadas por el impedimento del normal desarrollo de la actividad realizada. La disponibilidad de un preparado que prevenga la deshidratación y se adapte a las condiciones de uso de estos colectivos resulta de interés. Objetivos: Desarrollar una formulación capaz de generar una adecuada rehidratación y que permita su aplicación en las condiciones de actividad de estos colectivos especiales bajo la forma de mezcla pulverulenta, envasada en sobres estancos, para su reconstitución con agua, que contenga electrolitos, carbohidratos y otros posibles nutrientes (proteínas). Material y métodos: Se ha utilizado cloruro sódico y potásico, sacarosa y dextrosa. Se ha evaluado e grado de fluidez de las mezclas mediante medición de ángulo de reposo, índice de Carr y velocidad de flujo. Resultados: Los parámetros evaluados (I.Carr y velocidad flujo) de las mezclas con dextrosa arrojan mejores valores que las que contiene sacarosa. La fórmula propuesta inicialmente presenta un aporte energético (400Kcal) que puede enlentecer el vaciamiento gástrico, se procede a ajustar su composición hasta 348 Kcal. Discusión: Todas las formulaciones realizadas resultan aptas para su ensobrado, aunque las preparadas con dextrosa granulada presentan una capacidad de deslizamiento superior (p<0,05). Ante la posibilidad de incorporar proteínas a la mezcla, se establece una nueva fórmula ajustada calóricamente, siguiendo las indicaciones mayoritarias de la comunidad científica, con una proporción de proteínas de suero de leche en su composición (1:4 PRO: HC). Conclusiones: Se diseña una bebida para evitar la aparición de estrés hídrico en la actividad militar. El diseño permite incorporar proteínas de suero de leche aunque no existe unanimidad científica respecto a las ventajas en la rehidratación aportadas por este producto

Introduction: The activity carried out by members of the Armed Forces, security forces and personnel dedicated to rescue and rescue work, may lead to dehydration processes that lead to situations of dry stress characterized by the impediment of the normal development of the activity carried out. The availability of a preparation that prevents dehydration and adapts to the conditions of use of these groups is of interest. Objetive: Develop a formulation capable of generating an adequate rehydration and allowing its application under the conditions of activity of these special groups in the form of powder mix, packed in sealed envelopes, for reconstitution with water, containing electrolytes, carbohydrates and other possible nutrients (proteins). Material and methods: Sodium and potassium chloride, sucrose and dextrose have been used. The degree of fluidity of the mixtures has been evaluated by measuring the angle of repose, Carr index and flow velocity. Results: The parameters evaluated (I.Carr and flow velocity) of the mixtures with dextrose give better values than those that contain sucrose. The formula proposed initially presents an energy contribution (400Kcal) that can slow down the gastric emptying, proceeding to adjust its composition to 348 Kcal. Discussion: All the formulations made are suitable for enveloping, although those prepared with granulated dextrose have a superior sliding capacity (p <0.05). Given the possibility of incorporating proteins into the mixture, a new calorically adjusted formula is established, following the majority indications of the scientific community, with a proportion of whey proteins in its composition (1: 4 PRO: HC). Conclusions: A drink is designed to avoid the appearance of dry stress in military activity. The design allows the incorporation of whey proteins, although there is no scientific unanimity regarding the advantages in rehydration provided by this product

Nose to back: compatibility of nasal chondrocytes with environmental conditions mimicking a degenerated intervertebral disc.

Nasal chondrocytes (NCs) have gained increased recognition for cartilage tissue regeneration. To assess NCs as a source for cell therapy treatment of intervertebral disc (IVD) degeneration, tissue-forming properties of NCs under physiological conditions mimicking the degenerated IVD were compared to those of mesenchymal stromal cells (MSCs) and articular chondrocytes (ACs), two cell sources presently used in clinical trials. Cells were cultured in a combination of low glucose, hypoxia, acidity and inflammation for 28 d. Depending on the conditions, cells were either cultured in the absence of instructive growth factors or underwent chondrogenic instructional priming by addition of transforming growth factor ß1 (TGFß1) for the first 7 d. Histology, immunohistochemistry, biochemistry, enzyme-linked immunosorbent assay (ELISA) and quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR) analyses demonstrated limited cell maintenance and accumulation of cartilaginous extracellular matrix for MSCs in IVD conditions. ACs maintained a steady accumulation of glycosaminoglycans (GAGs) throughout all non-acidic conditions, with and without priming, but could not synthesise type II collagen (Col2). NCs accumulated both GAGs and Col2 in all non-acidic conditions, independent of priming, whereas MSCs strongly diminished their GAG and Col2 accumulation in an inflamed environment. Supplementation with inflammatory cytokines or an acidic environment affected NCs to a lower extent than ACs or MSCs. The data, overall indicating that in an inflamed IVD environment NCs were superior to ACs and MSCs, encourage further assessment of NCs for treatment of degenerative disc disease.

Changes in renal hemodynamics of undernourished fetuses appear earlier than IUGR evidences.

The present study used a sheep model of intrauterine growth restriction, combining maternal undernutrition and twinning, to determine possible markers of early damage to the fetal kidney. The occurrence of early deviations in fetal hemodynamics which may be indicative of changes in blood perfusion was assessed by Doppler ultrasonography. A total of 24 sheep divided in two groups were fed with the same standard grain-based diet but fulfilling either their daily maintenance requirements for pregnancy (control group; n=12, six singleton and six twin pregnancies) or only the 50% of such quantity (food-restricted group; n=12; four singleton and eight twin pregnancies). All the fetuses were assessed by both B-mode and Doppler ultrasonography at Day 115 of pregnancy. Fetal blood supply was affected by maternal undernutrition, although there were still no evidences of brain-sparing excepting in fetuses at greatest challenge (twins in underfed pregnancies). However, there were early changes in the blood supply to the kidneys of underfed fetuses and underfed twins evidenced decreases in kidney size.

Adipose stromal cells mediated switching of the pro-inflammatory profile of M1-like macrophages is facilitated by PGE2: in vitro evaluation.

OBJECTIVE: To define if adipose mesenchymal stromal cell (ASC) treatment mediated switching of the pro-inflammatory profile of M1-like macrophages as a means to develop a tailored in vitro efficacy/potency test. DESIGN: We firstly performed immunohistochemical analysis of CD68, CD80 (M1-like) and CD206 (M2-like) macrophages in osteoarthritic (OA) synovial tissue. ASC were co-cultured in contact and in transwell with activated (GM-CSF + IFNγ)-M1 macrophages. We analyzed IL1ß, TNFα, IL6, MIP1α/CCL3, S100A8, S100A9, IL10, CD163 and CD206 by qRT-PCR or immunoassays. Prostaglandin E2 (PGE2) blocking experiments were performed using PGE2 receptor antagonist. RESULTS: In moderate grade OA synovium we did not always find a higher percentage of CD80 with respect to CD206. M1-like-activated macrophage factors IL1ß, TNFα, IL6, MIP1α/CCL3, S100A8 and S100A9 were down-modulated both in contact and in transwell by ASC. However, in both systems ASC induced the typical M2-like macrophage markers IL10, CD163 and CD206. Activated-M1-like macrophages pre-treated with PGE2 receptor antagonist failed to decrease secretion of TNFα, IL6 and to increase that of IL10, CD163 and CD206 when co-cultured with ASC confirming a PGE2 specific role. CONCLUSIONS: We demonstrated that ASC are responsible for the switching of activated-M1-like inflammatory macrophages to a M2-like phenotype, mainly through PGE2. This evidenced that activated-M1-like macrophages may represent a relevant cell model to test the efficacy/potency of ASC and suggests a specific role of ASC as important determinants in therapeutic dampening of synovial inflammation in OA.

Allogeneic Umbilical Cord-Derived Mesenchymal Stem Cells as a Potential Source for Cartilage and Bone Regeneration: An In Vitro Study.

Umbilical cord (UC) may represent an attractive cell source for allogeneic mesenchymal stem cell (MSC) therapy. The aim of this in vitro study is to investigate the chondrogenic and osteogenic potential of UC-MSCs grown onto tridimensional scaffolds, to identify a possible clinical relevance for an allogeneic use in cartilage and bone reconstructive surgery. Chondrogenic differentiation on scaffolds was confirmed at 4 weeks by the expression of sox-9 and type II collagen; low oxygen tension improved the expression of these chondrogenic markers. A similar trend was observed in pellet culture in terms of matrix (proteoglycan) production. Osteogenic differentiation on bone-graft-substitute was also confirmed after 30 days of culture by the expression of osteocalcin and RunX-2. Cells grown in the hypertrophic medium showed at 5 weeks safranin o-positive stain and an increased CbFa1 expression, confirming the ability of these cells to undergo hypertrophy. These results suggest that the UC-MSCs isolated from minced umbilical cords may represent a valuable allogeneic cell population, which might have a potential for orthopaedic tissue engineering such as the on-demand cell delivery using chondrogenic, osteogenic, and endochondral scaffold. This study may have a clinical relevance as a future hypothetical option for allogeneic single-stage cartilage repair and bone regeneration.

Developmental Origins of Health and Disease in swine: implications for animal production and biomedical research.

The concept of Developmental Origins of Health and Disease (DOHaD) addresses, from a large set of epidemiological evidences in human beings and translational studies in animal models, both the importance of genetic predisposition and the determinant role of maternal nutrition during pregnancy on adult morphomics and homeostasis. Compelling evidences suggest that both overnutrition and undernutrition may modify the intrauterine environment of the conceptus and may alter the expression of its genome and therefore its phenotype during prenatal and postnatal life. In fact, the DOHaD concept is an extreme shift in the vision of the factors conditioning adult phenotype and supposes a drastic change from a gene-centric perspective, only modified by lifestyle and nutritional strategies during juvenile development and adulthood, to a more holistic approach in which environmental, parental, and prenatal conditions are strongly determining postnatal development and homeostasis. The implications of DOHaD are profound in all the mammalian species and the present review summarizes current knowledge on causes and consequences of DOHaD in pigs, both for meat production and as a well-recognized model for biomedicine research.

5-HT2 receptor blockade exhibits 5-HT vasodilator effects via nitric oxide, prostacyclin and ATP-sensitive potassium channels in rat renal vasculature.

The aim of this study was to determine whether orally sarpogrelate (selective 5-HT2 antagonist) treatment (30 mg/kg/day; 14 days) could modify 5-HT renal vasoconstrictor responses, characterizing 5-HT receptors and mediator mechanisms involved in serotonergic responses in the in situ autoperfused rat kidney. Intra-arterial (i.a.) injections of 5-HT (0.00000125 to 0.1 µg/kg) decreased renal perfusion pressure (RPP) but did not affect the mean blood pressure (MBP). i.a. agonists 5-CT (5-HT1/7), CGS-12066B (5-HT1B), L-694,247 (5-HT1D) or AS-19 (5-HT7) mimicked renal 5-HT vasodilator effect. However, neither 8-OH-DPAT (5-HT1A) nor 1-phenylbiguanide (5-HT3) modified RPP. Moreover: (i) GR-55562 (5-HT1B antagonist) and L-NAME (nitric oxide synthase [NOS] inhibitor) blocked CGS-12066B-induced vasodilator response, (ii) LY310762 (5-HT1D antagonist) and indomethacin (non-selective cyclooxygenase inhibitor) blocked L-694,247-induced vasodilator response; (iii) SB-258719 (5-HT7 antagonist) and glibenclamide (ATP-sensitive K+ channel blocker) blocked AS-19-induced vasodilator response; and (iv) 5-HT- or 5-CT-elicited renal vasodilation was significantly blocked by the mixture of GR-55562 + LY310762 + SB-258719. Furthermore, eNOS and iNOS proteins and prostacyclin levels are overexpressed in sarpogrelate-treated rats. Our data suggest that 5-HT exerts renal vasodilator effect in the in situ autoperfused sarpogrelate-treated rat kidney, mediated by 5-HT1D, 5-HT1B and 5-HT7 receptors, involving cyclooxygenase-derived prostacyclin, nitric oxide synthesis/release and ATP-sensitive K+ channels, respectively.

Niveles de células progenitoras endoteliales circulantes en pacientes hipertensos tratados / Circulating endothelial progenitor cell levels in treated hypertensive patients

Introducción: Muchos pacientes hipertensos óptimamente tratados de sus factores de riesgo cardiovascular (FRCV) siguen presentando complicaciones cardiovasculares. Las células progenitoras endoteliales (CPE) han demostrado ser fundamentales para la reparación del daño endotelial en tejidos isquémicos. Por ello, hemos estudiado los niveles de CPE y del factor de crecimiento del endotelio vascular (VEGF) en pacientes hipertensos en tratamiento con buen control de la presión arterial (PA). Material y métodos: Se recogió una muestra de sangre de pacientes hipertensos tratados que presentaban unas cifras de PA adecuadas para los objetivos individuales. Los niveles plásticos de CPE CD34+/KDR+ y CD34+/VE-cadherina+ se midieron mediante citometría de flujo. La concentración de VEGF se cuantificó mediante ELISA. Como controles se incluyó un grupo de sujetos sin FRCV tradicionales. Resultados: Hemos incluido 108 pacientes (61 ± 12 años, 47,2% hombres), de los cuales un 82,4% presentaba PA < 140/90 mmHg, un 91,7% control de la diabetes (HbA1c < 7%), el 81,5% cLDL < 130 o 100 mg/dl y el 85,2% no fumaba, aunque el 45,4% presentaba obesidad (IMC ≥ 30 kg/m2). A pesar de que, en conjunto, sus parámetros bioquímicos no diferían de los del grupo control, los pacientes hipertensos presentaban una disminución significativa de los niveles plasmáticos de células CD34+/KDR+ y CD34+/VE-cadherina+, aunque la concentración plasmática de VEGF era significativamente mayor en los pacientes hipertensos que en los sujetos control. Conclusiones: Los pacientes hipertensos tratados muestran una disminución significativa de los niveles plasmáticos de CPE que podría ser responsable, al menos en parte, del riesgo residual que presentan estos pacientes, sugiriéndose que las CPE podrían ser una importante diana terapéutica

Introduction: Most optimally treated hypertensive patients still have an around 50% increased risk of any cardiovascular event, suggesting the possible existence of unidentified risk factors. In the last years there has been evidence of the essential role of circulating endothelial progenitor cells (EPCs) in the maintenance of endothelial integrity and function, increasing the interest in their involvement in cardiovascular disease. In this study, the circulating levels of EPCs and vascular endothelial growth factor (VEGF) are investigated in treated hypertensive patients with adequate control of blood pressure (BP). Material and methods: Blood samples were collected from treated hypertensive patients with controlled BP. Plasma levels of EPCs CD34+/KDR+ and CD34+/VE-cadherin+ were quantified by flow cytometry. Plasma concentration of VEGF was determined by ELISA. A group of healthy subjects without cardiovascular risk factors was included as controls. Results: A total of 108 hypertensive patients were included (61±12 years, 47.2% men) of which 82.4% showed BP < 140/90 mmHg, 91.7% and 81.5% controlled diabetes (HbA1c <7%) and cLDL (<130 or 100 mg/dL), respectively, and 85.2% were non-smokers. Around 45% of them were obese. Although patients had cardiovascular parameters within normal ranges, they showed significantly lower levels of CD34+/KDR+ and CD34+/VE-cadherin+ compared with healthy control group, although plasma VEGF concentration was higher in patients than in controls. Conclusions: Despite an optimal treatment, hypertensive patients show a decreased number of circulating EPCs that could be, at least in part, responsible for their residual cardiovascular risk, suggesting that these cells could be a therapeutic target

Permeability of Soft Particles at Electrical Fields.

The influence of the charge on the permeability of microgel particles is studied in the presence of electric fields. Electrophoresis experiments performed on pH-ionizable pNIPAM-AA microgels show that particles behave as permeable spheres when the network is ionized. However, they keep non-permeable in the absence of charge. The ionic nature of the network thus controls the permeability of the soft particles. A salt-dependent local viscosity explains these permeability changes. This is confirmed by NMR as alternative independent technique. Strongly hydrated counterions located around fixed charges on the network are considered responsible for the local viscosity variations.

[Circulating endothelial progenitor cell levels in treated hypertensive patients]. / Niveles de células progenitoras endoteliales circulantes en pacientes hipertensos tratados.

INTRODUCTION: Most optimally treated hypertensive patients still have an around 50% increased risk of any cardiovascular event, suggesting the possible existence of unidentified risk factors. In the last years there has been evidence of the essential role of circulating endothelial progenitor cells (EPCs) in the maintenance of endothelial integrity and function, increasing the interest in their involvement in cardiovascular disease. In this study, the circulating levels of EPCs and vascular endothelial growth factor (VEGF) are investigated in treated hypertensive patients with adequate control of blood pressure (BP). MATERIAL AND METHODS: Blood samples were collected from treated hypertensive patients with controlled BP. Plasma levels of EPCs CD34+/KDR+ and CD34+/VE-cadherin+ were quantified by flow cytometry. Plasma concentration of VEGF was determined by ELISA. A group of healthy subjects without cardiovascular risk factors was included as controls. RESULTS: A total of 108 hypertensive patients were included (61±12 years, 47.2% men) of which 82.4% showed BP<140/90 mmHg, 91.7% and 81.5% controlled diabetes (HbA1c <7%) and cLDL (<130 or 100 mg/dL), respectively, and 85.2% were non-smokers. Around 45% of them were obese. Although patients had cardiovascular parameters within normal ranges, they showed significantly lower levels of CD34+/KDR+ and CD34+/VE-cadherin+ compared with healthy control group, although plasma VEGF concentration was higher in patients than in controls. CONCLUSIONS: Despite an optimal treatment, hypertensive patients show a decreased number of circulating EPCs that could be, at least in part, responsible for their residual cardiovascular risk, suggesting that these cells could be a therapeutic target.

Multifunctional hybrid nanogels for theranostic applications.

This paper reviews a wide set of theranostic applications based on the special properties associated with composite nanogels. The nanogels presented here are mostly hybridized with quantum dots, magnetic nanoparticles, and plasmonic metal noble nanoparticles. These inorganic components confer nanogels multifunctional properties that extend their applications from drug delivery systems to diagnosis and therapy. Nanogels can also be surface functionalized with specific ligands to achieve targeted therapy and reduce toxicity. This versatility makes hybrid nanogels very promising agents for imaging, diagnosis and treatment of cancer and other diseases.