Inmunosupresión en donantes renales

La lesión por isquemia y reperfusión (IRI) es uno de los principales problemas en el trasplante. Nuestro objetivo fue evaluar el efecto del pre - acondicionamiento al donante con rapamicina y tacrolimus para prevenir la lesión por IRI. Las ratas Wistar donantes, 12 horas antes de la nefrectomía, recibieron fármacos inmunosupresores. La muestra se dividió en cuatro grupos experimentales: un grupo con intervención simulada (sham), un grupo control sin tratamiento, otro tratado con rapamicina (2 mg/kg) y el restante tratado con tacrolimus (0.3 mg/kg). Se retiró el riñón izquierdo y después de tres horas de isquemia fría, se lo trasplantó. Veinticuatro horas después, el órgano trasplantado se recuperó para el análisis histológico y la evaluación de la expresión de citoquinas. El tratamiento de pre-acondicionamiento con rapamicina o con tacrolimus redujo significativamente el nitrógeno ureico en sangre y los niveles de creatinina en comparación con el control (BUN: p < 0.001; creatinina: p < 0.001). La necrosis tubular aguda fue significativamente menor en las ratas donantes tratadas con inmunosupresores en comparación con el grupo control (p < 0.001). Finalmente, las citoquinas inflamatorias, como TNF-α, IL-6 y rIL-21, mostraron niveles más bajos en el injerto de los animales que recibieron tratamiento. Este estudio experimental exploratorio muestra que el pre-acondicionamiento en donantes con rapamicina y tacrolimus en dos grupos distintos mejora los resultados clínicos y anatomopatológicos en receptores, con una reducción in situ de citoquinas pro-inflamatorias relacionadas con la diferenciación Th17, y de este modo crea un ambiente favorable para la diferenciación de células T regulatorias (Tregs).The ischemia-reperfusion injury (IRI) remains a major problem in transplantation. The objective of this study was to evaluate the effects of preconditioning a donor group with rapamycin and another donor group with tacrolimus to prevent IRI. Twelve hours before nephrectomy, donor Wistar rats received immunosuppressive drugs. The sample was divided into four experimental groups: a sham group, an untreated control group, a group treated with rapamycin (2 mg/kg) and a group treated with tacrolimus (0.3 mg/kg). Left kidneys were removed and, after three hours of cold ischemia, grafts were transplanted. Twenty-four hours later, the transplanted organs were recovered for histological analysis and evaluation of cytokine expression. The pre-conditioning treatment with rapamycin or tacrolimus significantly reduced donor blood urea nitrogen and creatinine levels compared with control group (BUN: p < 0.001 vs. control and creatinine: p < 0.001 vs. control). Acute tubular necrosis was significantly lower in donors treated with immunosuppressant drugs compared with the control group (p < 0.001). Finally, inflammatory cytokines such as TNF-α, IL-6 and rIL-21 showed lower levels in the graft of pre-treated animals. This exploratory experimental study shows that preconditioning donors with rapamycin and tacrolimus in different groups improves clinical outcome and pathology in recipients and reduces in situ pro-inflammatory cytokines associated with Th17 differentiation, creating a favorable environment for the differentiation of regulatory T cells (Tregs)

Immunosuppression in kidney donors with rapamycin and tacrolimus: Proinflammatory cytokine expression

La lesión por isquemia y reperfusión (IRI) es uno de los principales problemas en el trasplante. Nuestro objetivo fue evaluar el efecto del pre - acondicionamiento al donante con rapamicina y tacrolimus para prevenir la lesión por IRI. Las ratas Wistar donantes, 12 horas antes de la nefrectomía, recibieron fármacos inmunosupresores. La muestra se dividió en cuatro grupos experimentales: un grupo con intervención simulada (sham), un grupo control sin tratamiento, otro tratado con rapamicina (2 mg/kg) y el restante tratado con tacrolimus (0.3 mg/kg). Se retiró el riñón izquierdo y después de tres horas de isquemia fría, se lo trasplantó. Veinticuatro horas después, el órgano trasplantado se recuperó para el análisis histológico y la evaluación de la expresión de citoquinas. El tratamiento de pre-acondicionamiento con rapamicina o con tacrolimus redujo significativamente el nitrógeno ureico en sangre y los niveles de creatinina en comparación con el control (BUN: p < 0.001; creatinina: p < 0.001). La necrosis tubular aguda fue significativamente menor en las ratas donantes tratadas con inmunosupresores en comparación con el grupo control (p < 0.001). Finalmente, las citoquinas inflamatorias, como TNF-α, IL-6 y rIL-21, mostraron niveles más bajos en el injerto de los animales que recibieron tratamiento. Este estudio experimental exploratorio muestra que el pre-acondicionamiento en donantes con rapamicina y tacrolimus en dos grupos distintos mejora los resultados clínicos y anatomopatológicos en receptores, con una reducción in situ de citoquinas pro-inflamatorias relacionadas con la diferenciación Th17, y de este modo crea un ambiente favorable para la diferenciación de células T regulatorias (Tregs).The ischemia-reperfusion injury (IRI) remains a major problem in transplantation. The objective of this study was to evaluate the effects of preconditioning a donor group with rapamycin and another donor group with tacrolimus to prevent IRI. Twelve hours before nephrectomy, donor Wistar rats received immunosuppressive drugs. The sample was divided into four experimental groups: a sham group, an untreated control group, a group treated with rapamycin (2 mg/kg) and a group treated with tacrolimus (0.3 mg/kg). Left kidneys were removed and, after three hours of cold ischemia, grafts were transplanted. Twenty-four hours later, the transplanted organs were recovered for histological analysis and evaluation of cytokine expression. The pre-conditioning treatment with rapamycin or tacrolimus significantly reduced donor blood urea nitrogen and creatinine levels compared with control group (BUN: p < 0.001 vs. control and creatinine: p < 0.001 vs. control). Acute tubular necrosis was significantly lower in donors treated with immunosuppressant drugs compared with the control group (p < 0.001). Finally, inflammatory cytokines such as TNF-α, IL-6 and rIL-21 showed lower levels in the graft of pre-treated animals. This exploratory experimental study shows that preconditioning donors with rapamycin and tacrolimus in different groups improves clinical outcome and pathology in recipients and reduces in situ pro-inflammatory cytokines associated with Th17 differentiation, creating a favorable environment for the differentiation of regulatory T cells (Tregs).Fil: Cicora, Federico. Universidad Nacional de La Plata. Facultad de Ciencias Médicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Roberti, Javier. Universidad de Belgrano; ArgentinaFil: Lausada, Natalia Raquel. Universidad Nacional de La Plata. Facultad de Ciencias Médicas; ArgentinaFil: Gonzalez, Pedro. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas; ArgentinaFil: Guerrieri, Diego. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Stringa, Pablo Luis. Universidad Nacional de La Plata. Facultad de Ciencias Médicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Raimondi, Clemente. Universidad Nacional de La Plata. Facultad de Ciencias Médicas; Argentin

Immunosuppression in kidney donors with rapamycin and tacrolimus: Proinflammatory cytokine expression

La lesión por isquemia y reperfusión (IRI) es uno de los principales problemas en el trasplante. Nuestro objetivo fue evaluar el efecto del pre - acondicionamiento al donante con rapamicina y tacrolimus para prevenir la lesión por IRI. Las ratas Wistar donantes, 12 horas antes de la nefrectomía, recibieron fármacos inmunosupresores. La muestra se dividió en cuatro grupos experimentales: un grupo con intervención simulada (sham), un grupo control sin tratamiento, otro tratado con rapamicina (2 mg/kg) y el restante tratado con tacrolimus (0.3 mg/kg). Se retiró el riñón izquierdo y después de tres horas de isquemia fría, se lo trasplantó. Veinticuatro horas después, el órgano trasplantado se recuperó para el análisis histológico y la evaluación de la expresión de citoquinas. El tratamiento de pre-acondicionamiento con rapamicina o con tacrolimus redujo significativamente el nitrógeno ureico en sangre y los niveles de creatinina en comparación con el control (BUN: p < 0.001; creatinina: p < 0.001). La necrosis tubular aguda fue significativamente menor en las ratas donantes tratadas con inmunosupresores en comparación con el grupo control (p < 0.001). Finalmente, las citoquinas inflamatorias, como TNF-α, IL-6 y rIL-21, mostraron niveles más bajos en el injerto de los animales que recibieron tratamiento. Este estudio experimental exploratorio muestra que el pre-acondicionamiento en donantes con rapamicina y tacrolimus en dos grupos distintos mejora los resultados clínicos y anatomopatológicos en receptores, con una reducción in situ de citoquinas pro-inflamatorias relacionadas con la diferenciación Th17, y de este modo crea un ambiente favorable para la diferenciación de células T regulatorias (Tregs).The ischemia-reperfusion injury (IRI) remains a major problem in transplantation. The objective of this study was to evaluate the effects of preconditioning a donor group with rapamycin and another donor group with tacrolimus to prevent IRI. Twelve hours before nephrectomy, donor Wistar rats received immunosuppressive drugs. The sample was divided into four experimental groups: a sham group, an untreated control group, a group treated with rapamycin (2 mg/kg) and a group treated with tacrolimus (0.3 mg/kg). Left kidneys were removed and, after three hours of cold ischemia, grafts were transplanted. Twenty-four hours later, the transplanted organs were recovered for histological analysis and evaluation of cytokine expression. The pre-conditioning treatment with rapamycin or tacrolimus significantly reduced donor blood urea nitrogen and creatinine levels compared with control group (BUN: p < 0.001 vs. control and creatinine: p < 0.001 vs. control). Acute tubular necrosis was significantly lower in donors treated with immunosuppressant drugs compared with the control group (p < 0.001). Finally, inflammatory cytokines such as TNF-α, IL-6 and rIL-21 showed lower levels in the graft of pre-treated animals. This exploratory experimental study shows that preconditioning donors with rapamycin and tacrolimus in different groups improves clinical outcome and pathology in recipients and reduces in situ pro-inflammatory cytokines associated with Th17 differentiation, creating a favorable environment for the differentiation of regulatory T cells (Tregs).Fil: Cicora, Federico. Universidad Nacional de La Plata. Facultad de Ciencias Médicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Roberti, Javier. Universidad de Belgrano; ArgentinaFil: Lausada, Natalia Raquel. Universidad Nacional de La Plata. Facultad de Ciencias Médicas; ArgentinaFil: Gonzalez, Pedro. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas; ArgentinaFil: Guerrieri, Diego. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Stringa, Pablo Luis. Universidad Nacional de La Plata. Facultad de Ciencias Médicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Raimondi, Clemente. Universidad Nacional de La Plata. Facultad de Ciencias Médicas; Argentin

Preconditioning donor with a combination of tacrolimus and rapamacyn to decrease ischaemia-reperfusion injury in a rat syngenic kidney transplantation model

Reperfusion injury remains one of the major problems in transplantation. Repair from ischaemic acute renal failure (ARF) involves stimulation of tubular epithelial cell proliferation. The aim of this exploratory study was to evaluate the effects of preconditioning donor animals with rapamycin and tacrolimus to prevent ischaemia–reperfusion (I/R) injury. Twelve hours before nephrectomy, the donor animals received immunosuppressive drugs. The animals were divided into four groups, as follows: group 1 control: no treatment; group 2: rapamycin (2 mg/kg); group 3 FK506 (0, 3 mg/kg); and group 4: FK506 (0, 3 mg/kg) plus rapamycin (2 mg/kg). The left kidney was removed and after 3 h of cold ischaemia, the graft was transplanted. Twenty-four hours after transplant, the kidney was recovered for histological analysis and cytokine expression. Preconditioning treatment with rapamycin or tacrolimus significantly reduced blood urea nitrogen and creatinine compared with control [blood urea nitrogen (BUN): P < 0·001 versus control and creatinine: P < 0·001 versus control]. A further decrease was observed when rapamycin was combined with tacrolimus. Acute tubular necrosis was decreased significantly in donors treated with immunosuppressants compared with the control group (P < 0·001 versus control). Moreover, the number of apoptotic nuclei in the control group was higher compared with the treated groups (P < 0·001 versus control). Surprisingly, only rapamycin preconditioning treatment increased anti-apoptotic Bcl2 levels (P < 0·001). Finally, inflammatory cytokines, such as tumour necrosis factor (TNF)-α and interleukin (IL)-6, showed lower levels in the graft of those animals that had been pretreated with rapamycin or tacrolimus. This exploratory study demonstrates that preconditioning donor animals with rapamycin or tacrolimus improves clinical outcomes and reduce necrosis and apoptosis in kidney I/R injury.Facultad de Ciencias MédicasComisión de Investigaciones Científicas de la provincia de Buenos Aire

Overview of the Large-Scale Biosphere–Atmosphere Experiment in Amazonia Data Model Intercomparison Project (LBA-DMIP)

A fundamental question connecting terrestrial ecology and global climate change is the sensitivity of key terrestrial biomes to climatic variability and change. The Amazon region is such a key biome: it contains unparalleled biological diversity, a globally significant store of organic carbon, and it is a potent engine driving global cycles of water and energy. The importance of understanding how land surface dynamics of the Amazon region respond to climatic variability and change is widely appreciated, but despite significant recent advances, large gaps in our understanding remain. Understanding of energy and carbon exchange between terrestrial ecosystems and the atmosphere can be improved through direct observations and experiments, as well as through modeling activities. Land surface/ecosystem models have become important tools for extrapolating local observations and understanding to much larger terrestrial regions. They are also valuable tools to test hypothesis on ecosystem functioning. Funded by NASA under the auspices of the LBA (the Large-Scale Biosphere–Atmosphere Experiment in Amazonia), the LBA Data Model Intercomparison Project (LBA-DMIP) uses a comprehensive data set from an observational network of flux towers across the Amazon, and an ecosystem modeling community engaged in ongoing studies using a suite of different land surface and terrestrial ecosystem models to understand Amazon forest function. Here an overview of this project is presented accompanied by a description of the measurement sites, data, models and protocol

Health, economic and social burden of tobacco in Latin America and the expected gains of fully implementing taxes, plain packaging, advertising bans and smoke-free environments control measures : a modelling study

OBJECTIVE: To investigate the tobacco-attributable burden on disease, medical costs, productivity losses and informal caregiving; and to estimate the health and economic gains that can be achieved if the main tobacco control measures (raising taxes on tobacco, plain packaging, advertising bans and smoke-free environments) are fully implemented in eight countries that encompass 80% of the Latin American population. DESIGN: Markov probabilistic microsimulation economic model of the natural history, costs and quality of life associated with the main tobacco-related diseases. Model inputs and data on labour productivity, informal caregivers' burden and interventions' effectiveness were obtained through literature review, surveys, civil registrations, vital statistics and hospital databases. Epidemiological and economic data from January to October 2020 were used to populate the model. FINDINGS: In these eight countries, smoking is responsible each year for 351 000 deaths, 2.25 million disease events, 12.2 million healthy years of life lost, US$22.8 billion in direct medical costs, US$16.2 billion in lost productivity and US$10.8 billion in caregiver costs. These economic losses represent 1.4$63.8, US$12.3, US$11.4 and US$5.7 billions in economic gains, respectively, on top of the benefits being achieved today by the current level of implementation of these measures. CONCLUSIONS: Smoking represents a substantial burden in Latin America. The full implementation of tobacco control measures could successfully avert deaths and disability, reduce healthcare spending and caregiver and productivity losses, likely resulting in large net economic benefits

From Hospital to Home Care: Creating a Domotic Environment for Elderly and Disabled People

Advances in medicine have led to a significant increase in human life expectancy and, therefore, to a growing number of disabled elderly people who need chronic care and assistance [1]. The World Health Organization reports that the world's population over 60 years old will double between 2000 and 2050 and quadruple for seniors older than 80 years, reaching 400 million [2]. In addition, strokes, traffic-related and other accidents, and seemingly endless wars and acts of terrorism contribute to an increasing number of disabled younger people.Fil: López Celani, Natalia Martina. Universidad Nacional de San Juan. Facultad de Ingeniería. Departamento de Electrónica y Automática. Gabinete de Tecnología Médica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Juan; ArgentinaFil: Ponce, Sergio Damián. Universidad Tecnológica Nacional. Facultad Regional San Nicolás; ArgentinaFil: Piccinini, David. Universidad Tecnológica Nacional. Facultad Regional San Nicolás; ArgentinaFil: Pérez Berenguer, María Elisa. Universidad Nacional de San Juan. Facultad de Ingeniería. Departamento de Electrónica y Automática. Gabinete de Tecnología Médica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Juan; ArgentinaFil: Roberti, Martín Adrián. Universidad Tecnológica Nacional. Facultad Regional San Nicolás; Argentin

Il profilo dello stato nutrizionale in pazienti “grandi anziani” (≥ 80 anni ospedalizzati

Per introdurre sistematicamente scale di valutazione dei problemi dei pazienti geriatrici (valutazione dello stato nutrizionale, delle funzioni cognitive e del profilo generale di rischio, nelle UO di medicina generale e lungodegenza, è stato attivato uno studio osservazionale che ha consentito l’identificazione dei pazienti a rischio. Metodi. I dati sono stati raccolti su 198 degenti, per 5 mesi. Risultati. L’età media dei pazienti era di 86.6 anni (range 80-99). Non è stato possibile raccogliere alcuni dati (ad esempio un calo ponderale nei tre mesi precedenti il ricovero) per 54 pazienti: avevano tutti >90 anni. Il 49% dei pazienti avevano un livello elevato di dipendenza ed il 30% erano gravemente malnutriti (la malnutrizione era prevalente tra i pazienti oncologici). Dei 19 pazienti morti durante lo studio, 6 erano malnutriti, 6 a rischio e per 6 non è stato possibile effettuare una valutazione completa. Discussione. È ampiamente riconosciuto il valore prognostico di un calo ponderale nei precedenti 6 mesi, però questa informazione non è sempre facilmente ricavabile nei pazienti geriatrici. La raccolta di dati sullo stato nutrizionale consente di identificare i pazienti che hanno bisogno di una stretta sorveglianza e dell’applicazione di interventi preventivi