Hiperglucemia y su corrección en el trasplante alogénico de islotes de páncreas.

RESUMEN El protocolo de Edmonton ha establecido que la independencia de la insulina puede conseguirse con el trasplante de un adecuado número de islotes. Sin embargo, para lograr este resultado, son necesarios de dos a cuatro páncreas donantes. Objetivos: el objetivo de esta tesis fue determinar si la normoglucemia, obtenida con tratamiento insulínico los días que preceden y siguen al trasplante, reduce el número de islotes necesarios para conseguir la normoglucemia en el trasplante alogénico de islotes de páncreas. Material y métodos: los trasplantes se realizaron sobre un modelo experimental alogénico, utilizando ratones Swiss como donantes y receptores. Para inducir la diabetes se utilizó estreptozotocina intraperitoneal a una dosis de 180 mg/kg. Los ratones diabéticos fueron trasplantados con 300 (n=16), 400 (n=16) ó 500 (n=16) islotes bajo la cápsula renal izquierda. En cada grupo, la mitad de los animales se mantuvieron normoglucémicos mediante tratamiento con insulina desde el día 6 antes del trasplante hasta el día 10 post-trasplante. Como terapia inmunosupresora se utilizó ciclosporina en solución oleosa, administrada vía subcutánea el día del trasplante y los días 1 y 2 post-trasplante, a dosis de 30 mg/kg/día. Se determinó hemoglobina glicosilada (HbA1c) al inicio del estudio, el día 10 post-trasplante y al final del estudio (día 30 post-trasplante). Todos los animales que se habían mantenido normoglucémicos al final del estudio fueron sometidos a un test de tolerancia intraperitoneal a la glucosa (TTIPG). Todos los resultados se compararon con un grupo control de animales sanos, no diabéticos no trasplantados y no tratados con insulina. Para el análisis estadístico se utilizó el software estadístico SPSS versión 10.0, empleando el test T de Student para comparar dos grupos y el análisis de la varianza para comparar varios grupos, con pruebas paramétricas o no según procediera. Resultados: en el grupo de animales trasplantados y no tratados con insulina, sólo uno trasplantado con 500 islotes (13%), se mantuvo con normoglucemia al final del estudio. Por el contrario, en el grupo de los ratones que recibieron tratamiento con insulina en el peritrasplante, el 37.5% de los trasplantados con 400 islotes y el 50% de los trasplantados con 300 y 500 islotes finalizaron el estudio con glucemias normales. La HbA1c determinada al final del estudio fue significativamente más baja en los animales trasplantados y tratados con insulina que finalizaron normoglucémicos, y comparable con el grupo control. El grupo trasplantado con 300 islotes y tratado con insulina consiguió una HbA1c más baja que el grupo trasplantado con 500 islotes y tratado con insulina (2,7 ± 0.2% vs 3.6 ± 0.2%; p< 0,05). Después del TTIPG, el grupo trasplantado con 300 islotes mostró una normal tolerancia a la glucosa, comparable con el grupo control. Sin embargo, los grupos trasplantados con 400 y 500 islotes presentaron una anormal tolerancia a la glucosa. Conclusiones: el tratamiento con insulina los días que preceden y siguen al trasplante mejora los resultados del trasplante alogénico de islotes y permite reducir el número de islotes necesarios para obtener la normoglucemia. Los resultados de la HbA1c y el TTIPG fueron mejores al trasplantar un menor número de islotes, lo que podría explicarse por una menor inmunogenicidad. ____________________________________________________________________________________________________ SUMMARY The Edmonton protocol established that insulin independence could be reached with the transplantation of an appropriate number of islet cells. However, to effect a cure, islets from two or three pancreases are needed. Objetive: The aim of this thesis was to examine wether normoglycemia, with insulin treatment before and after transplantation, reduces the islet number needed to achieve normoglycemia in allogeneic islet transplantation. Material and methods: Swiss mice were used as donors and recipients. Diabetes was induced by intraperitoneal administration of streptozotocin (180 mg/kg). Immunosuppresion therapy with cyclosporine was employed (30 mg/kg/day). Diabetic mice were transplantated with 300 (n=16), 400 (n=16), or 500 (n=16) islets under the left kidney capsule. For every group, half the animals were kept normoglycemic with insulin treatment from day 6 before transplantation to day 10 after transplantation. At the end of the study, all normoglycemic were given an intraperitoneal glucose tolerance test (IPGTT). For statistical analysis, paired or unpaired Student´s t-test or ANOVA was used. Results: Only one mouse not insulin-treated and transplantated with 500 islets achieved normoglycemia by the end of study. However, 37.5% of animals transplantated with 400 islets and 50% of animals transplantated with 300 and 500 islets and insulin-treated achieved normoglycemia. At the end of the study, glycosilated haemoglobin (HbA1c) of normoglycemic mice transplantated not showed differences with HbA1c of healthy control group. HbA1c of animals transplantated with 300 islets was lower than animals transplantated with 500 islets (2,7 ± 0.2% vs 3.6 ± 0.2%; p< 0,05). After the IPGTT, insulin-treated mice transplantated with 400 and 500 islets showed abnormal glucose tolerance; however, insulin-treated mice transplantated with 300 islets showed normal glucose tolerance. Conclusions: Normoglycemia with insulin treatment, before and after transplantation, improved prognosis and reduced the islet number needed to achieve normoglycemia in allogeneic islet transplantation. The HbA1c and IPGTT results were better after transplantation with less islet number. Some studies suggest that this may be due to lower immunogenicit

La relevancia de la cognición social en la esquizofrenia

La investigación realizada en los últimos años ha mostrado la existencia de una correlación entre los déficits cognitivos y el funcionamiento social en esquizofrenia. Mientras que los déficits en la atención, la memoria y el funcionamiento ejecutivo han sido ampliamente estudiados, se ha puesto menos atención a la investigación en cognición social. Sin embargo, la cognición social se está convirtiendo en el foco de interés porque la evidencia empírica está mostrando su relevancia funcional como variable mediadora entre neurocognición y el nivel de funcionamiento social del paciente con esquizofrenia. En consecuencia, se han desarrollado nuevas intervenciones centradas en los componentes clave de la cognición social que están deteriorados en la esquizofrenia (procesamiento emocional, percepción social, teoría de la mente, esquemas sociales/conocimiento social y estilo atribucional), con el objetivo de mejorar el funcionamiento cognitivo social. Los objetivos de este trabajo son: sintetizar cuál es la concepto actual de cognición social, indicar cuáles son los componentes que incluye, presentar algunos de los instrumentos disponibles para evaluar la cognición social y revisar los programas de intervención más destacados que están dirigidos a mejorar la cognición social en las personas con esquizofrenia.Research conducted in recent years has shown correlations between neurocognitive deficits and functional outcome in schizophrenia. Whereas deficits such as attention, memory and executive functioning have been widely studied, less attention has been paid to social cognition. However social cognition is moving into the focus of interest because empirical evidence is showing the functional significance of social cognition as a mediating variable between neurocognition and the social level of functioning in schizophrenic patients. Consequently, new interventions have been developed focusing on the key domains of social cognition that are impaired in schizophrenia (emotion perception, social perception, theory of main, social schemata, and attributional style), with the goal of improving social cognitive functioning. The purpose of this present work is: to summarize the current conceptualisation of social cognition and the domains included under this concept; to present some of the instruments available to evaluate social cognition; and to review the main intervention programs devoted to improving social cognition in schizophrenia.Universidad de Valencia UV-AE- 20060248Ministerio de Educación y Ciencia SEJ2006-0705

Implant treatment in patients with osteoporosis

Osteoporosis is very common, particularly in post-menopausal women and is characterized by a decrease in bone mass and strength. Osteoporosis also affects the jawbone and it is considered a potential contraindication to placement of dental implants. The present paper reviews the literature regarding the effect of osteoporosis on osseointegration of implants. Experimental models have shown that osteoporosis affects the process of osseointegration, which can be reversed by treatment. However, studies in subjects with osteoporosis have shown no differences in survival of the implants compared to healthy individuals. Therefore, osteoporosis cannot be considered a contraindication for implant placement. Oral bisphosphonates are the most commonly used pharmacological agents in the treatment of osteoporosis. Although there have been cases of osteonecrosis of the jaw in patients treated with bisphosphonates, they are very rare and it is more usually associated with intravenous bisphosphonates in patients with neoplasms or other serious diseases. Nevertheless, patients treated with bisphosphonates must be informed in writing about the possibility of this complication and must give informed consent. Ceasing to use bisphosphonates before implant placement does not seem to be necessary

Effects of diabetes on the osseointegration of dental implants

The increased prevalence of diabetes mellitus has become a public health problem. Hyperglycaemia entails a rise in the morbidity and mortality of these patients. Although a direct relationship with periodontal disease has already been shown, little is known about the results of dental implants in diabetics. The present paper reviews the bibliography linking the effect of diabetes on the osseointegration of implants and the healing of soft tissue. In experimental models of diabetes, a reduced level of bone-implant contact has been shown, and this can be reversed by means of treatment with insulin. Compared with the general population, a higher failure rate is seen in diabetic patients. Most of these occur during the first year of functional loading, seemingly pointing to the microvascular complications of this condition as a possible causal factor. These complications also compromise the healing of soft tissues. It is necessary to take certain special considerations into account for the placement of implants in diabetic patient. A good control of plasma glycaemia, together with other measures, has been shown to improve the percentages of implant survival in these patients

Epigenetic profiling linked to multisystem inflammatory syndrome in children (MIS-C): A multicenter, retrospective study

BACKGROUND: Most children and adolescents infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remain asymptomatic or develop a mild coronavirus disease 2019 (COVID-19) that usually does not require medical intervention. However, a small proportion of pediatric patients develop a severe clinical condition, multisystem inflammatory syndrome in children (MIS-C). The involvement of epigenetics in the control of the immune response and viral activity prompted us to carry out an epigenomic study to uncover target loci regulated by DNA methylation that could be altered upon the appearance of MIS-C. METHODS: Peripheral blood samples were recruited from 43 confirmed MIS-C patients. 69 non-COVID-19 pediatric samples and 15 COVID-19 pediatric samples without MIS-C were used as controls. The cases in the two groups were mixed and divided into discovery (MIS-C = 29 and non-MIS-C = 56) and validation (MIS-C = 14 and non-MIS-C = 28) cohorts, and balanced for age, gender and ethnic background. We interrogated 850,000 CpG sites of the human genome for DNA methylation variants. FINDINGS: The DNA methylation content of 33 CpG loci was linked with the presence of MIS-C. Of these sites, 18 (54.5%) were located in described genes. The top candidate gene was the immune T-cell mediator ZEB2; and others highly ranked candidates included the regulator of natural killer cell functional competence SH2D1B; VWA8, which contains a domain of the Von Willebrand factor A involved in the pediatric hemostasis disease; and human leukocyte antigen complex member HLA-DRB1; in addition to pro-inflammatory genes such as CUL2 and AIM2. The identified loci were used to construct a DNA methylation profile (EPIMISC) that was associated with MIS-C in both cohorts. The EPIMISC signature was also overrepresented in Kawasaki disease patients, a childhood pathology with a possible viral trigger, that shares many of the clinical features of MIS-C. INTERPRETATION: We have characterized DNA methylation loci that are associated with MIS-C diagnosis. The identified genes are likely contributors to the characteristic exaggerated host inflammatory response observed in these patients. The described epigenetic signature could also provide new targets for more specific therapies for the disorder.We thank the Health Department and the Centres de Recerca de Catalunya (CERCA) Programme of the Generalitat de Catalunya, the Josep Carreras Leukaemia Foundation, Fundació La Marató de TV3 and the Cellex Foundation for institutional support. We also wish to thank all the patients, family members and staff from all the units that participated in the studyPeer Reviewed"Article signat per 22 autors/es: Veronica Davalos, Carlos A. García-Prieto, Gerardo Ferrer, Sergio Aguilera-Albesa, Juan Valencia-Ramos, Agustí Rodríguez-Palmero, Montserrat Ruiz, Laura Planas-Serra, Iolanda Jordan, Iosune Alegría, Patricia Flores-Pérez, Verónica Cantarín, Victoria Fumadó, Maria Teresa Viadero, Carlos Rodrigo, Maria Méndez-Hernández, Eduardo López-Granados, Roger Colobran, Jacques G. Rivière, Pere Soler-Palacín, Aurora Pujol, Manel Esteller"Postprint (published version

Modelling potential dependent surface-enhanced raman scattering: electric field and charged cluster dual model

The computation of electrochemical systems is very challenging because of the many variables involved. Among them, the effect of the electrode potential is particularly complex to be introduced in atomistic models. In this work, we propose a model where the surface excess of charge has been modelled with the tetrahedral-like clusters [Ag19]+, [Ag20]0 and [Ag19]-. We then modulate the effect of other surface charges implicitly as an external electric field and correlated a calculated magnitude like the electric charge on the adsorbate with the electrode potential, a purely experimental one. This model is tested with the potential-dependent Surface-Enhanced Raman Scattering (SERS) of pyridine. Namely, we investigated the changes in the Raman shifts and relative intensities due to the potential, and evaluated the different contributions (electromagnetic, charge-transfer) to the SERS spectra. Our preliminary results nicely reproduce the experimental trends and reveal that enhancement factors up to 10 to the 7th are achieved when the charge-transfer state interact with the bright local excitations of the metal cluster

Decontamination of dental implant surface in peri-implantitis treatment: a literature review

Etiological treatment of peri-implantitis aims to reduce the bacterial load within the peri-implant pocket and decontaminate the implant surface in order to promote osseointegration. The aim of this literature review was to evaluate the efficacy of different methods of implant surface decontamination. A search was conducted using the PubMed (Medline) database, which identified 36 articles including in vivo and in vitro studies, and reviews of different decontamination systems (chemical, mechanical, laser and photodynamic therapies). There is sufficient consensus that, for the treatment of peri-implant infections, the mechanical removal of biofilm from the implant surface should be supplemented by chemical decontamination with surgical access. However, more long-term research is needed to confirm this and to establish treatment protocols responding to different implant characterics

Electric field and charged cluster dual model for Potential Depdendent Surface-Enhanced Raman Spectroscopy

The computation of electrochemical systems is very challenging because of the many variables involved.1 Among them, the effect of the electrode potential is particularly complex to be introduced in atomistic models. In this work, we propose a model where the surface excess of charge has been modelled with the tetrahedral-like clusters [Ag19]+, [Ag20]0 and [Ag19]-. We then modulate the effect of other surface charges implicitly as an external electric field and correlated a calculated magnitude like the electric charge on the adsorbate with the electrode potential, a purely experimental one. This model is tested with the potential-dependent Surface-Enhanced Raman Scattering (SERS) of pyridine. Namely, we investigated the changes in the Raman shifts and relative intensities due to the potential, and evaluated the different contributions (electromagnetic, charge-transfer) to the SERS spectra. Our preliminary results nicely reproduce the experimental trends and reveal that enhancement factors up to 107 are achieved when the charge-transfer state interact with the bright local excitations of the metal cluster.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tec

About the Unexpected Structure and Properties of Molecules Bonded to Metal Nanoclusters.

SERS (Surface-Enhanced Raman Scattering) is a very powerful technique to gain insight into the nature of metal-molecule hybrids on a molecular level. We show the results of combining SERS and theoretical calculations (1) to analyze the subtle electronic structure of metal-molecule (M-A) interfaces, especially to study the dependence of their structure and properties on applied electric potentials or fields. An example of this is the huge efficiency of the potential (EV) in tuning the energies (E) of metal-molecule charge transfer (CT) states. An equivalence between both quantities is expected on the basis of classical electrochemistry (G=E/EV=1 eV/V) but observed energy gains up to G=4 or 5 eV/V can be explained by combining the dependence of the CT energies (E) on the excess of charge of the metal (qeff) (see Graphical Abstract) and the capacitive enhancement located at metallic nanostructures (2). Moreover, theoretical calculations predict a dual electronic structure of the M-A surface complex in the case of charged molecules bonded to charged metals. These two types of surface states of the same hybrid system are of a very different nature and are selected by the sign of the metal charge (qeff). It is predicted that a single M-A complex can be very strongly bonded (chemisorbed) or form weak and very polarizable complexes (physisorbed) depending on the charges of both the ionic species and the surface excess of the metal which is modulated by the applied potential. These two types of complexes determine the properties of the overall system in the ground electronic state, like the behavior of the wavenumbers of the CN stretching band adsorbed on metals (3-4), as well as in excited states, like the forward and reverse metal-molecule CT states of the isonicotinate anion bonded to positive (chemisorbed, G~0 eV/V) or negative (physisorbed, high G) silver clusters (5), respectively (see Graphical Abstract).Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Consenso sobre la detección y el manejo de la prediabetes. Grupo de trabajo de consensos y guías clínicas de la Sociedad Española de Diabetes

En España, según datos del estudio [email protected], un 13,8% de la población adulta padece diabetes y un 14,8% algún tipo de prediabetes (intolerancia a la glucosa, glucemia basal alterada o ambas). Puesto que la detección precoz de la prediabetes puede facilitar la puesta en marcha de medidas terapéuticas que eviten su progresión a diabetes, consideramos que las estrategias de prevención en las consultas de atención primaria y especializada deberían consensuarse. La detección de diabetes y prediabetes mediante un cuestionario específico (test de FINDRISC) y/o la determinación de la glucemia basal en pacientes de riesgo permiten detectar los pacientes con riesgo de desarrollar la enfermedad y es necesario considerar cómo debe ser su manejo clínico. La intervención sobre los estilos de vida puede reducir la progresión a diabetes o hacer retroceder un estado prediabético a la normalidad y es una intervención coste-efectiva. Algunos fármacos, como la metformina, también se han mostrado eficaces en reducir la progresión a diabetes aunque no son superiores a las in tervenciones no farmacológicas. Finalmente, aunque no hay pruebas sólidas que apoyen la eficacia del cribado en términos de morbimortalidad, sí que ha observado una mejora de los factores de riesgo cardiovascular.El Grupo de Trabajo de Consensos y Guías Clínicas de la Sociedad Española de Diabetes (SED) ha elaborado unas recomendaciones que han sido consensuadas con la Sociedad Española de Endocrinología y Nutrición (SEEN), la Sociedad Española de Endocrinología Pediátrica (SEEP), la Sociedad Española de Farmacia Familiar y Comunitaria (SEFAC), la Sociedad Española de Medicina Familiar y Comunitaria (SEMFYC), la Sociedad Española de Médicos Generales (SEMG), la Sociedad Española de Médicos de Atención Primaria (SEMERGEN), la Sociedad Española de Medicina Interna (SEMI), la Asociación de Enfermería Comunitaria (AEC) y la Red de Grupos de Estudio de la Diabetes en Atención Primaria (RedGDPS)