Knowledge, experience, and perception of molar incisor hypomineralisation among dentists in the metropolitan area of Mexico City: a cross-sectional study.

BACKGROUND: Molar-incisor hypomineralisation (MIH) is the most common developmental abnormality observed in teeth. Being a relatively new condition, its treatment can present a challenge for the dentist. There is currently no study available that has evaluated the knowledge of Mexican dental personnel. This study aimed to evaluate the knowledge, experience, and perceptions of dental surgeons regarding the detection, assessment, and treatment of MIH in the metropolitan area of Mexico City. METHODS: A cross-sectional study was designed. Dentists from Mexico City and its metropolitan area were invited through social networks to answer a questionnaire of 30 questions related to MIH. Participants were classified into general practice dentists, paediatric dentists, and other speciality dentists. Pearson's chi-square test was used for data analysis. RESULTS: The questionnaire was answered by 391 dentists. A total of 86% (338 out of 391) of them identified MIH lesions, while 84% of them reported having observed MIH lesions in their practice. The most frequently observed lesions were yellow-brown opacities which accounted for 47% of the lesions, 46% were white opacities, while only 7% were observed as post-eruptive fractures in the enamel as part of the manifestations of MIH. The most frequently reported problem in the management of teeth with MIH was insufficient training for treating children with MIH. A total of 84% of dentists stated that they would like more information on the treatment of MIH lesions. CONCLUSIONS: Most of the surveyed dentists recognised MIH and reported having observed MIH lesions in their practice. Most of the dentists indicated that the main problem for the management of the MIH is the lack of training.

Spatial and Temporal Analysis of Water Quality in High Andean Lakes with Sentinel-2 Satellite Automatic Water Products.

The water of high Andean lakes is strongly affected by anthropic activities. However, due to its complexity this ecosystem is poorly researched. This study analyzes water quality using Sentinel-2 (S2) images in high Andean lakes with apparent different eutrophication states. Spatial and temporal patterns are assessed for biophysical water variables from automatic products as obtained from versions of C2RCC (Case 2 Regional Coast Color) processor (i.e., C2RCC, C2X, and C2X-COMPLEX) to observe water characteristics and eutrophication states in detail. These results were validated using in situ water sampling. C2X-COMPLEX appeared to be an appropriate option to study bodies of water with a complex dynamic of water composition. C2RCC was adequate for lakes with high transparency, typical for lakes of highlands with excellent water quality. The Yambo lake, with chlorophyll-a concentration (CHL) values of 79.6 ± 5 mg/m3, was in the eutrophic to hyper-eutrophic state. The Colta lake, with variable values of CHL, was between the oligotrophic to mesotrophic state, and the Atillo lakes, with values of 0.16 ± 0.1 mg/m3, were oligotrophic and even ultra-oligotrophic, which remained stable in the last few years. Automatic S2 water products give information about water quality, which in turn makes it possible to analyze its causes.

Strengthening public health policies for childhood cancer: Peru's achievements through the WHO Global Initiative for Childhood Cancer.

Objective: To report the progress in Peru, since June 2019, in the implementation of the World Health Organization Global Initiative for Childhood Cancer using the CureAll framework, which can be replicated in low- and middle-income countries. Methods: A mixed method was used of participatory and documentary evaluation. The participatory evaluation included stakeholders from various government institutions, nonprofit organizations, and international partners. The documentary aspect consisted of a review of data on the regulatory environment, national projects, and interventions implemented. The Ministry of Health engaged more than 150 participants to form working committees, which have developed policy and regulatory documents to strengthen care services. Results: Achievements include a decrease in the national treatment abandonment rate from 18.6% to 8.5%, the approval of the Childhood Cancer Law, improvements in the management of patients with febrile neutropenia, and a reduction in rates of events of clinical deterioration and mortality of hospitalized patients. The Cure All implementation framework allows local teams to implement specific strategies and monitor early outcomes in pediatric oncology. Conclusions: The results obtained reflect the teamwork, the leadership of the authorities, the technical support of professionals, and the support of involved organizations. Further actions will be needed to guarantee sustainability, and monitoring tools are needed to assure success in the planned activities.

Strengthening public health policies for childhood cancer: Peru’s achievements through the WHO Global Initiative for Childhood Cancer

[ABSTRACT]. Objective. To report the progress in Peru, since June 2019, in the implementation of the World Health Organization Global Initiative for Childhood Cancer using the CureAll framework, which can be replicated in low- and middle-income countries. Methods. A mixed method was used of participatory and documentary evaluation. The participatory evalu- ation included stakeholders from various government institutions, nonprofit organizations, and international partners. The documentary aspect consisted of a review of data on the regulatory environment, national projects, and interventions implemented. The Ministry of Health engaged more than 150 participants to form working committees, which have developed policy and regulatory documents to strengthen care services. Results. Achievements include a decrease in the national treatment abandonment rate from 18.6% to 8.5%, the approval of the Childhood Cancer Law, improvements in the management of patients with febrile neutropenia, and a reduction in rates of events of clinical deterioration and mortality of hospitalized patients. The Cure All implementation framework allows local teams to implement specific strategies and monitor early outcomes in pediatric oncology. Conclusions. The results obtained reflect the teamwork, the leadership of the authorities, the technical support of professionals, and the support of involved organizations. Further actions will be needed to guarantee sustainability, and monitoring tools are needed to assure success in the planned activities.

[RESUMEN]. Objetivo. Informar sobre los avances de Perú en el periodo transcurrido a partir de junio del 2019, en relación con la puesta en práctica de la Iniciativa Global de la Organización Mundial de la Salud contra el Cáncer Infantil utilizando el marco CureAll, que es posible replicar en los países de ingresos bajos y medianos. Métodos. Se utilizó un método mixto de evaluación participativa y documental. En la evaluación participativa intervinieron las partes interesadas de diversas instituciones gubernamentales, organizaciones sin fines de lucro y asociados internacionales. El aspecto documental consistió en un examen de los datos sobre el entorno regulatorio, los proyectos nacionales y las intervenciones llevadas a cabo. El Ministerio de Salud involucró a más de 150 participantes que formaron los comités de trabajo que han elaborado documentos normativos y regulatorios a fin de reforzar los servicios de asistencia. Resultados. Entre los logros cabe citar la disminución del 18,6% al 8,5% de la tasa nacional de abandono del tratamiento, la aprobación de la Ley de Cáncer Infantil, las mejoras en el tratamiento de los pacientes con neutropenia febril y la reducción de las tasas de episodios de deterioro clínico y de mortalidad en los pacientes hospitalizados. El marco de aplicación de CureAll permite que los equipos locales pongan en práctica estrategias específicas y realicen un seguimiento de los resultados iniciales en el ámbito de la oncología pediátrica. Conclusiones. Los resultados obtenidos reflejan el trabajo en equipo, el liderazgo de las autoridades, el respaldo técnico de los profesionales y el apoyo de las organizaciones implicadas. En el futuro, será necesario adoptar nuevas medidas para asegurar su viabilidad, y será preciso contar con herramientas de seguimiento para garantizar el éxito de las actividades planificadas.

[RESUMO]. Objetivo. Relatar o progresso, desde junho de 2019, da implementação da Iniciativa Global da Organização Mundial da Saúde para o Câncer Infantil no Peru, no âmbito do marco CureAll, que pode ser replicado em países de baixa e média renda. Método. Foi utilizado um método misto de avaliação participativa e documental. A avaliação participativa incluiu interessados diretos de diferentes instituições governamentais, organizações sem fins lucrativos e parceiros internacionais. O aspecto documental consistiu em uma revisão de dados sobre o ambiente regulatório, projetos nacionais e intervenções implementadas. O Ministério da Saúde do Peru contou com mais de 150 participantes para a formação de comitês de trabalho, que elaboraram políticas e documentos normati- vos para fortalecer os serviços de atenção primária à saúde. Resultados. Entre os resultados alcançados estão a redução da taxa nacional de abandono do tratamento, de 18,6% para 8,5%, a aprovação da Lei do Câncer Infantil, melhorias no manejo de pacientes com neu- tropenia febril e redução nas taxas de deterioração clínica e mortalidade de pacientes hospitalizados. A implementação do CureAll permite que as equipes locais adotem estratégias específicas e monitorem os resultados iniciais em oncologia pediátrica. Conclusões. Os resultados obtidos refletem o trabalho em equipe, a liderança das autoridades, o suporte técnico dos profissionais e o apoio das organizações envolvidas. Serão necessárias mais ações para garantir a sustentabilidade, além de ferramentas de monitoramento para assegurar o sucesso das atividades planejadas.

Strengthening public health policies for childhood cancer: Peru's achievements through the WHO Global Initiative for Childhood Cancer / Fortalecimiento de las políticas de salud pública contra el cáncer infantil: logros de Perú en el marco de la Iniciativa Mundial de la OMS contra el Cáncer Infantil / Fortalecimento das políticas públicas de saúde para o câncer infantil: As conquistas do Peru por meio da Iniciativa Global da OMS para o Câncer Infantil

ABSTRACT Objective. To report the progress in Peru, since June 2019, in the implementation of the World Health Organization Global Initiative for Childhood Cancer using the CureAll framework, which can be replicated in low- and middle-income countries. Methods. A mixed method was used of participatory and documentary evaluation. The participatory evaluation included stakeholders from various government institutions, nonprofit organizations, and international partners. The documentary aspect consisted of a review of data on the regulatory environment, national projects, and interventions implemented. The Ministry of Health engaged more than 150 participants to form working committees, which have developed policy and regulatory documents to strengthen care services. Results. Achievements include a decrease in the national treatment abandonment rate from 18.6% to 8.5%, the approval of the Childhood Cancer Law, improvements in the management of patients with febrile neutropenia, and a reduction in rates of events of clinical deterioration and mortality of hospitalized patients. The Cure All implementation framework allows local teams to implement specific strategies and monitor early outcomes in pediatric oncology. Conclusions. The results obtained reflect the teamwork, the leadership of the authorities, the technical support of professionals, and the support of involved organizations. Further actions will be needed to guarantee sustainability, and monitoring tools are needed to assure success in the planned activities.

RESUMEN Objetivo. Informar sobre los avances de Perú en el periodo transcurrido a partir de junio del 2019, en relación con la puesta en práctica de la Iniciativa Global de la Organización Mundial de la Salud contra el Cáncer Infantil utilizando el marco CureAll, que es posible replicar en los países de ingresos bajos y medianos. Métodos. Se utilizó un método mixto de evaluación participativa y documental. En la evaluación participativa intervinieron las partes interesadas de diversas instituciones gubernamentales, organizaciones sin fines de lucro y asociados internacionales. El aspecto documental consistió en un examen de los datos sobre el entorno regulatorio, los proyectos nacionales y las intervenciones llevadas a cabo. El Ministerio de Salud involucró a más de 150 participantes que formaron los comités de trabajo que han elaborado documentos normativos y regulatorios a fin de reforzar los servicios de asistencia. Resultados. Entre los logros cabe citar la disminución del 18,6% al 8,5% de la tasa nacional de abandono del tratamiento, la aprobación de la Ley de Cáncer Infantil, las mejoras en el tratamiento de los pacientes con neutropenia febril y la reducción de las tasas de episodios de deterioro clínico y de mortalidad en los pacientes hospitalizados. El marco de aplicación de CureAll permite que los equipos locales pongan en práctica estrategias específicas y realicen un seguimiento de los resultados iniciales en el ámbito de la oncología pediátrica. Conclusiones. Los resultados obtenidos reflejan el trabajo en equipo, el liderazgo de las autoridades, el respaldo técnico de los profesionales y el apoyo de las organizaciones implicadas. En el futuro, será necesario adoptar nuevas medidas para asegurar su viabilidad, y será preciso contar con herramientas de seguimiento para garantizar el éxito de las actividades planificadas.

RESUMO Objetivo. Relatar o progresso, desde junho de 2019, da implementação da Iniciativa Global da Organização Mundial da Saúde para o Câncer Infantil no Peru, no âmbito do marco CureAll, que pode ser replicado em países de baixa e média renda. Método. Foi utilizado um método misto de avaliação participativa e documental. A avaliação participativa incluiu interessados diretos de diferentes instituições governamentais, organizações sem fins lucrativos e parceiros internacionais. O aspecto documental consistiu em uma revisão de dados sobre o ambiente regulatório, projetos nacionais e intervenções implementadas. O Ministério da Saúde do Peru contou com mais de 150 participantes para a formação de comitês de trabalho, que elaboraram políticas e documentos normativos para fortalecer os serviços de atenção primária à saúde. Resultados. Entre os resultados alcançados estão a redução da taxa nacional de abandono do tratamento, de 18,6% para 8,5%, a aprovação da Lei do Câncer Infantil, melhorias no manejo de pacientes com neutropenia febril e redução nas taxas de deterioração clínica e mortalidade de pacientes hospitalizados. A implementação do CureAll permite que as equipes locais adotem estratégias específicas e monitorem os resultados iniciais em oncologia pediátrica. Conclusões. Os resultados obtidos refletem o trabalho em equipe, a liderança das autoridades, o suporte técnico dos profissionais e o apoio das organizações envolvidas. Serão necessárias mais ações para garantir a sustentabilidade, além de ferramentas de monitoramento para assegurar o sucesso das atividades planejadas.

Improving the remote estimation of soil organic carbon in complex ecosystems with Sentinel-2 and GIS using Gaussian processes regression.

Background and aims: The quantitative retrieval of soil organic carbon (SOC) storage, particularly for soils with a large potential for carbon sequestration, is of global interest due to its link with the carbon cycle and the mitigation of climate change. However, complex ecosystems with good soil qualities for SOC storage are poorly studied. Methods: The interrelation between SOC and various vegetation remote sensing drivers is understood to demonstrate the link between the carbon stored in the vegetation layer and SOC of the top soil layers. Based on the mapping of SOC in two horizons (0-30 cm and 30-60 cm) we predict SOC with high accuracy in the complex and mountainous heterogeneous páramo system in Ecuador. A large SOC database (in weight % and in Mg/ha) of 493 and 494 SOC sampling data points from 0-30 cm and 30-60 cm soil profiles, respectively, were used to calibrate GPR models using Sentinel-2 and GIS predictors (i.e., Temperature, Elevation, Soil Taxonomy, Geological Unit, Slope Length and Steepness (LS Factor), Orientation and Precipitation). Results: In the 0-30 cm soil profile, the models achieved a R2 of 0.85 (SOC%) and a R2 of 0.79 (SOC Mg/ha). In the 30-60 cm soil profile, models achieved a R2 of 0.86 (SOC%), and a R2 of 0.79 (SOC Mg/ha). Conclusions: The used Sentinel-2 variables (FVC, CWC, LCC/Cab, band 5 (705 nm) and SeLI index) were able to improve the estimation accuracy between 3-21% compared to previous results of the same study area. CWC emerged as the most relevant biophysical variable for SOC prediction. Supplementary Information: The online version contains supplementary material available at 10.1007/s11104-022-05506-1.

Multi-predictor mapping of soil organic carbon in the alpine tundra: a case study for the central Ecuadorian páramo.

BACKGROUND: Soil organic carbon (SOC) affects essential biological, biochemical, and physical soil functions such as nutrient cycling, water retention, water distribution, and soil structure stability. The Andean páramo known as such a high carbon and water storage capacity ecosystem is a complex, heterogeneous and remote ecosystem complicating field studies to collect SOC data. Here, we propose a multi-predictor remote quantification of SOC using Random Forest Regression to map SOC stock in the herbaceous páramo of the Chimborazo province, Ecuador. RESULTS: Spectral indices derived from the Landsat-8 (L8) sensors, OLI and TIRS, topographic, geological, soil taxonomy and climate variables were used in combination with 500 in situ SOC sampling data for training and calibrating a suitable predictive SOC model. The final predictive model selected uses nine predictors with a RMSE of 1.72% and a R2 of 0.82 for SOC expressed in weight %, a RMSE of 25.8 Mg/ha and a R2 of 0.77 for the model in units of Mg/ha. Satellite-derived indices such as VARIG, SLP, NDVI, NDWI, SAVI, EVI2, WDRVI, NDSI, NDMI, NBR and NBR2 were not found to be strong SOC predictors. Relevant predictors instead were in order of importance: geological unit, soil taxonomy, precipitation, elevation, orientation, slope length and steepness (LS Factor), Bare Soil Index (BI), average annual temperature and TOA Brightness Temperature. CONCLUSIONS: Variables such as the BI index derived from satellite images and the LS factor from the DEM increase the SOC mapping accuracy. The mapping results show that over 57% of the study area contains high concentrations of SOC, between 150 and 205 Mg/ha, positioning the herbaceous páramo as an ecosystem of global importance. The results obtained with this study can be used to extent the SOC mapping in the whole herbaceous ecosystem of Ecuador offering an efficient and accurate methodology without the need for intensive in situ sampling.

Strategies for COVID-19 transmission control and mitigation in a psychiatric hospital in Mexico.

In the context of the emerging COVID-19 pandemic, one of the great challenges is to generate effective strategies for the control of nosocomial infections, specifically in psychiatric hospitals with populations considered at risk (older adults or individuals with comorbidities). This article describes the strategies for prevention, containment and treatment of infection transmission implemented during a COVID-19 outbreak that occurred in July 2020 in a psychiatric hospital of the State of Mexico. The population was comprised by women with prolonged hospital stay (mean = 24 years), mostly geriatric (mean = 64 years), with various psychiatric disorders and comorbidities. In total, 19 COVID-19-positive cases were diagnosed, out of which thirteen had mild symptoms and six were asymptomatic. There were no alterations in mental state, psychiatric symptoms or underlying diseases. Algorithms were developed for the management and treatment of suspected/confirmed COVID-19 cases. Finally, the generation of comprehensive strategies, quick and timely actions, as well as adequate management of human resources favoring interdisciplinary work, were deemed to have contributed to contain and mitigate the COVID-19 outbreak, which constitutes a precedent in the psychiatric field with institutionalized patients.

En el contexto de la emergente pandemia de COVID-19, uno de los grandes desafíos es generar estrategias eficaces de control de infecciones nosocomiales, específicamente en hospitales psiquiátricos con población considerada de riesgo (adultos mayores o con comorbilidades). En el presente artículo se describen las estrategias de prevención, contención y tratamiento de contagio, a partir de un brote de COVID-19 ocurrido en julio de 2020 en un hospital psiquiátrico del Estado de México. La población estuvo constituida por mujeres con estancia hospitalaria prolongada (media = 24 años), en su mayoría geriátricas (media = 64 años), con trastornos psiquiátricos diversos y comorbilidades. En total se diagnosticaron 19 casos positivos de COVID-19, de los cuales 13 cursaron con sintomatología leve y seis resultaron asintomáticos. No se presentaron alteraciones en el estado mental, en la sintomatología psiquiátrica ni en las enfermedades de base. Se realizaron algoritmos para el manejo y tratamiento de los casos sospechosos o confirmados de COVID-19. Finalmente, se consideró que la generación de estrategias integrales, acciones rápidas y oportunas, así como una adecuada gestión de recursos humanos favorecedora del trabajo interdisciplinario contribuyeron a contener y mitigar el brote de COVID-19, constituyéndose en un precedente en el ámbito psiquiátrico con pacientes institucionalizadas.

Hiperglucemia de estrés en infarto agudo de miocardio: ¿Se asocia con aumento de mortalidad?. También una valoración de la conducta terapéutica / Stress hyperglycemia in acute miocardial infarction: is it associated with increased mortality? A concer of therapeutic behavior too

Introducción: la hiperglucemia de estrés puede aumentar el riesgo de muerte en infarto agudo de miocardio (IAM). Objetivos: en una muestra se observó retrospectivamente la relación entre la hiperglucemia y la mortalidad en IAM, y también se consideró qué conducta terapéutica se adoptaba en los pacientes hiperglucémicos. Materiales y métodos: se evaluó la mortalidad al alta en 349 pacientes que ingresaron por IAM en 11 hospitales entre mayo de 2000 y abril de 2001. Resultados: n=349 pacientes. Edad: 64,3±12,9 años. Glucemia al ingreso: 158,8±96 mg/dl. Score de Killip =ó> 2 en 25%. La mortalidad global fue del 19,1%. En el análisis univariado se asoció con edad (p<0,001), score de Killip (p<0,001) arritmias en la internación (p<0,001) y glucemia (p<0,001). Se halló relación inversa con la tensión arterial (TA) (p<0,001) En el análisis multivariado la mortalidad al egreso se asoció a: edad (OR: 1,03 por año IC95% 1,00-1,06, p=0,03), score de Killip (OR: 3,93 por punto, IC95% 2,63-5,87, p<0,001), presencia de arritmias (OR=3,49 IC95%: 1,64-7,43, p=0,001), glucemia al ingreso >177 mg/dl (Qs) (OR=2,87, IC95% 1,34-6,17p=0,007). De la muestra 79,6% era no diabético. La diferencia de mortalidad en no diabéticos hiperglucémicos y no hiperglucémicos fue significativa (40,5% vs 14,1% p<0,001). El efecto de la hiperglucemia fue significativa en pacientes con score de Killip 2 (10,8% en los no hiperglucémicos vs 55% en los hiperglucémicos [p< 0,05]). Considerando el tratamiento de la glucemia en internación, la media de glucemia del grupo tratado fue de 265,6±120,4 mg/dl mientras que la del grupo sin tratamiento fue 131,6±61,6 mg/dl (p<0,001). En los tratados la glucemia media fue un 50% más alta que la media considerada para hiperglucemia. Sólo el 64,4% de los pacientes en el cuartilo superior (177 mg/dl) recibió tratamiento de su glucemia, el 89,6% de ellos insulina (el 20,3% por vía endovenosa y un 3,6% de los pacientes hiperglucémicos (Qs) tratamiento con drogas orales. Los pacientes que recibieron insulina subcutánea tenían una glucemia media de 155,6±110,9 mg/dl, mientras que quienes la recibieron por venoclisis su glucemia media fue de 278,5±120,3 mg/dl (p<0,0001). Se trataron 41 de 50 (82%) pacientes que se conocían diabéticos y tenían hiperglucemia, mientras que fueron tratados sólo 10 de 27 pacientes (41,8%) sin diabetes conocida a pesar que también estaban hiperglucémicos. Conclusiones: la mortalidad se asoció positivamente con el sexo, la edad, score de Killip, arritmia en internación e hiperglucemia al ingreso >Qs, y en forma inversa con TA. Dentro de los pacientes con hiperglucemia la mortalidad fue, comparativamente con los no hiperglucémicos, muy superior en los no diabéticos comparado con los diabéticos. El efecto de la hiperglucemia fue especialmente evidente en los pacientes admitidos con score de Killip 2. Aproximadamente una tercera parte de los pacientes hiperglucémicos no recibió tratamiento para ello. El 90% de los pacientes tratados recibió insulina y sólo un 20% por vía intravenosa. Los valores de glucemia tomados en cuenta para iniciar tratamiento fueron un 50% más elevados que el valor considerado en nuestro estudio como hiperglucemia. La conducta terapéutica se enfocó en intervenir la glucemia de los diabéticos conocidos más que en el valor de la misma (82% vs 41,8%) aunque los pacientes estuvieran hiperglucémicos.

Introduction: stress hyperglycemia could increase mortality after acute myocardial infarction (AMI). Objectives: we explored the association between hyperglycemia and mortality after AMI in a retrospective cohort study. We consider the treatment behavior of hyperglycemia too. Materials and methods: the mortality rate at hospital discharge post AMI was obtained from a sample of 349 patients assisted in 11 hospitals, between May 2000 and April 2001. Results: N=349. Age: 64.3±12.9. Glycemia at admission: 158.8±96.0 mg/dl. Killip score >2 in 25% of the subjects. Global mortality rate was 19.4%. In the univariate analysis, mortality was associated to age (p<0.001), Killip score (p<0.001), arrhythmia (p<0.001) and glycaemia at admission (p<0.001). Mortality was inversely correlated to BP (p<0.001). In the multivariate analysis, mortality was associated to age (OR=1.03 per year; 95%CI= 1.00-1.06, p=0.03), Killip score (OR=3.93 per point; 95%CI= 2.63-5.87, p<0.001), arrhythmia (OR=3.49; 95%CI=1.64-7.43, p=0.001) and glycaemia at admission equal or higher than the upper quartile [177 mg/dl] (OR=2.87; 95%CI=1.34-6.17, p=0.007). From the total sample 79.6% were no diabetics. In these patients mortality was statistically significant in hyperglycemic versus non-hyperglycemic (40.5% vs 14.1%, p<0.001). The effect of hyperglycemia was significant in patients admitted in Killip 2 (moderate heart failure) (10.8% in non-hyperglycemic vs 55% in hyperglycemic patients. [p<0.005]). If we consider the treatment of glycaemia, the mean value of glycaemia in the treated group was 265.6±120.4 mg/dl and in untreated group it was 131.6±61.6 mg/dl (p<0.001). That mean value of glycaemia in treated patients was 50% higher than the value of glycaemia that we consider as hyperglycemic. Only 64.4% of the patients with glycaemia at upper quartile (177 mg/dl) received treatment to control glycaemia, 89.6% of them were treated with insulin (20.3% intravenously) and 3.6% of patients with hyperglycemia receied oral pharmacological agents to treat itThe mean value of glycaemia in patients who received insulin by subcutaneous route was 155.6±110.9 mg/dl and the mean value of glycemia in those that received intravenous insulin treatment was 278.5±120.3 mg/dl (p<0.0001). There was treated 41 of 50 patients (82%) that with known diabetes that were hyperglycemic (>177 mg/dl), while was treated only 10 of 27 pacientes (41.8%) with unknown diabetes although they were hyperglycemic too. Conclusions: post-acute myocardial infarction mortality was significantly associated to age, Killip score, arrhythmia and glycaemia at admission above the upper quartile (177 mg/dl). It was inversely associated to blood pressure values. Mortality was higher in hyperglycemic patients with and without diabetes. The effect of hyperglycemia was especially noticed in patients admitted with moderate heart failure (Killip score 2). Approximately one third of patients remained untreated in spite of being clearly hyperglycemic. 90% of hyperglycemic patients received insulin and only 20% received insulin intravenously. Glycemic values taken into account to prescribe insulin treatment were 50% higher than hyperglycemic value considered. The therapeutic behavior was to treat mainly diabetics patients in despite of non-diabetic patients (82% vs. 41.8% respectively) although they were both hyperglycemic

Actualización del tratamiento de la polineuropatía diabética periférica dolorosa 2015. Comité de Neuropatía Diabética. Sociedad Argentina de Diabetes / Treatment update of painful peripheral diabetic neuropathy. Diabetic Neuropathy Committee 2015. Argentine Society of Diabetes

La diabetes es una enfermedad crónica y progresiva que se asocia a complicaciones potencialmente discapacitantes, entre ellas, la neuropatía diabética es probablemente la afectación sintomática más frecuente con importante impacto social y económico. El tratamiento de la neuropatía somática dolorosa y del sistema nervioso autónomo ha sido un desafío durante años. Nuevas terapéuticas se encuentran disponibles, las cuales mejoran el dolor y brindan esperanza de lograr alivio a personas que padecen esta complicación

Neuropatía en el contexto del Síndrome Metabólico y de la disglucemia no diabética / Neurpathy in metabolic síndrome and non-diabetic disglycemia

La neuropatía diabética (ND) es la complicación microvascular más frecuente y más precoz asociada a la diabetes mellitus (DM), no obstante esta situación, es la más olvidada y la menos diagnosticada. Al mismo tiempo es de amplio conocimiento que el síndrome metabólico (SM) tiene una elevada prevalencia, y que la relación entre este estado y el compromiso macrovascular está documentada. Es de interés para el Comité de Neuropatía Diabética analizar la afectación neuropatía en el marco del SM y en el de uno de sus componentes constitutivos como es la disglucemia no diabética. El subdiagnóstico de esta entidad y el aumento del riesgo de la morbimortalidad de los pacientes que la padecen hacen importante alertar a la comunidad médica de la existencia de esta complicación microvascular que excede el marco de la DM y se presenta también en el SM y en la disglucemia tanto de ayunas como posprandial.

Development and characterization of edible films based on mucilage of Opuntia ficus-indica (L.).

Mucilage of Opuntia ficus-indica (OFI) was extracted and characterized by its composition and molecular weight distribution. Mucilage film-forming dispersions were prepared under different pHs (3, 4, 5.6, 7, and 8) and calcium concentration (0% and 30% of CaCl(2), with respect to mucilage's weight), and their particle size determined. Mucilage films with and without calcium (MFCa and MF, respectively) were prepared. The effect of calcium and pH on mucilage films was evaluated determining thickness, color, water vapor permeability (WVP), tensile strength (TS), and percentage of elongation (%E). The average molecular weight of the different fractions of mucilage was: 3.4 x 10(6) (0.73%), 1 x 10(5) (1.46%), 1.1 x 10(3) (45.79%), and 2.4 x 10(2) Da (52.03%). Aqueous mucilage dispersions with no calcium presented particles with an average size d(0.5) of 15.4 microm, greater than the dispersions with calcium, 13.2 microm. MFCa films showed more thickness (0.13 mm) than the MF films (0.10 mm). The addition of calcium increased the WVP of the films from 109.94 to 130.45 gmm/m(2)dkPa. Calcium and pH affected the mechanical properties of the films; the largest TS was observed on MF films, whereas the highest %E was observed on MFCa films. The highest differences among MF and MFCa films were observed at pHs 5.6 and 7 for TS and at pHs 4 and 8 for %E. No effect of pH and calcium was observed on luminosity and hue angle. Chroma values were higher for MF when compared with MFCa, and increased as pH of the films increased. Practical Application: In this study mucilage from nopal was extracted and characterized by its ability to form edible films under different pHs, and with or without the addition of calcium. Opuntia ficus-indica mucilage had the ability to form edible films. In general, it can be considered that mucilage films without modification of pH and without the addition of calcium have the best water vapor barrier properties and tensile strength. Mucilage from nopal could represent a good option for the development of edible films in countries where nopal is highly produced at low cost, constituting a processing alternative for nopal.

Endomorphin peptides: pharmacological and functional implications of these opioid peptides in the brain of mammals. Part two / Las endorfinas: implicaciones farmacológicas y funcionales de estos péptidos opioides en el cerebro de los mamíferos. Segunda parte

Endomorphin-1 (EM1) and Endomorphin-2 (EM2) represent the two endogenous C-terminal amide tetrapeptides shown to display a high binding affinity and selectivity for the µ-opioid receptor as reported previously (see previous paper, Part I). Endomorphins injected into the VTA were shown to enhance the development of behavioral sensitization responses to amphetamine (AMPH), besides of inducing an increase of locomotion (horizontal) activity in animals. These studies showed that EM2 was significantly more potent than EM1 in modulating the increased opioid-mediated ambulatory responses by altering the dopamine (DA) projecting system in the globus pallidus in tested animals. Several transmission systems (e.g., GABA) have been shown to participate in the endormorphin-induced locomotor responses. EM1 injected into the VTA produced potent rewarding effects in rodents, similar to the rewarding responses produced by distinct opiate compounds. The opioid rewarding responses induced by EM1-2 were shown to be mediated via the activation of both GABAergic and the dopamine (VTA-NAc-PFCx) transmission systems in the brain. Moreover, EM1-2 peptides injected into the VTA, but not in the NAc, produced similar related-rewarding responses induced by low doses of morphine. However, ICV administration of EM1 was shown to enhance a significant conditioned-place preference (CPP); whereas EM2 displayed a place aversion in tested animals. With regard to stress-related behaviors and physiological responses in mammals, endomorphin peptides have been proposed to modulate the HPA axis function via activation of the NTS-projecting neural system impinging on hypothalamic neurons, and/or via activation of the PAG (ventrolateral area) mediating analgesic responses-induced by stress. EM1-2 peptides have been shown to induce mood-related behaviors. For instance, administration of EM1 induced an increased anxiolytic response in mice when tested in elevated plus maze paradigms, results that showed that the µ-opioid receptor modulates mood-related responses in animals and humans, as well. Interesting enough is the recent observation that EM1-2 peptides may induce antidepressant-like behaviors in animals models of stress and depression, whereby EM1-2 peptides have been shown to up-regulate in a dose-dependent manner the neuronal expression of the BDNF mRNA in rat limbic areas involved in stress and depressive-like behaviors. Thus, these studies led to the proposition that endomorphin peptides may play crucial roles in psychiatric disorders (e.g., depression, schizophrenia). Furthermore, over the past years, it has been shown that µ-opioid receptor agonists (e.g., morphine, DAMGO; morphine-6β-glucuronide) displayed potent orexigenic activities in the CNS of mammals, similar to that displayed by EM1-2 peptides, whose dose-dependent orexigenic activity appears to be mediated by the endogenous opioid peptide, Dynorphin A, acting on its cognate κ-opioid receptor at the hypothalamus. Extensive studies revealed the activity of the EOS (e.g., β-endorphin) on the regulation of gonadal hormones and sexually-induced behaviors (e.g., lordosis) in female rats. β-endorphin or morphiceptin have been shown to facilitate lordosis behaviors in estrogen- and/or estrogen/progesterone primed rats, whereas EM1-2 peptides injected into third ventricle or into the diagonal band (DB) produced dose- and time-dependent, naloxone-reversible lordosis responses in female rats. These results posit that EM1-2 peptides produce their sexual behaviors and mating responses via modulating the cell release of LHRH and modulating GABA transmission system in the brain. Endomorphins have been shown to impair short- and long-term memory processing in mice when exposed to different learning paradigms. These opioid mediated effects appear to be regulated through the interaction of both cholinergic and dopaminergic transmissions in the brain. In addition, endomorphins have been shown to modulate cardiovascular and respiratory bioactivities, acting on several rostrocaudal areas of the CNS of mammals. Administration of EM1-2 peptides induced a significant reduction of heart rate and blood pressure in normotensive and hypertensive rats, via regulation of GABA and glutamate transmission systems. Although the exact endogenous mechanisms by which EM1-2 peptides produce their vasoactive responses are still unclear, several studies suggested that the peptide activity depends on the synthesis and release of nitric oxide (NO) from endothelial cells enhanced by activation of µ-opioid receptors. Studies on respiratory function showed that EM1-2 peptides attenuate and produce significant respiratory depression in tested animals. Finally, EM1-2 peptides have been shown to induce important inhibitory gastrointestinal effects via the activation of µ-opioid receptors localized in myenteric-plexus neurons that innervate smooth-muscle cells producing a dose-dependent- and CTOP-reversible inhibition of electrically-induced twitch ileum contractions, probably mediated through a reduced release response of several peptide and non-peptide transmitters.

La endomorfina-1 (EM1) y la endomorfina-2 (EM2) son dos péptidos bioactivos que poseen la más alta afinidad de unión selectiva por el receptor opioide µ en comparación con la unión de distintos ligandos agonistas a este subtipo de receptor opioide (véase resumen y texto del capítulo anterior, parte I). Estudios farmacológicos y conductuales han demostrado que la inyección de las EM1-2 en el área ventrotegmental (AVT) genera respuestas conductuales de sensibilización locomotora a la anfetamina (AMPH), además de incrementar la actividad locomotora de tipo horizontal en los roedores tratados. Estos estudios mostraron que la EM2 fue significativamente más potente que la EM1 en inducir las respuestas locomotoras detectadas, mediadas a través de la alteración de la actividad sináptica de dopamina (DA) y en el globus pallidus de los animales tratados. Asimismo, estudios fármaco-conductuales similares demostraron que otros sistemas de transmisión participan conjuntamente con el sistema dopaminérgico en la generación de los efectos locomotores inducidos por las EM1-2, como es el caso del sistema gabaérgico (GABA). Más aún, la inyección de EM1 en la región AVT del cerebro de roedores mostró generar respuestas potentes de recompensa placentera, similares a las reportadas por distintos alcaloides opiáceos de alto potencial adictivo, posterior a su administración sistémica. Más aún, la inyección de endomorfinas en la región AVT del cerebro del roedor, mas no en el núcleo accumbens (NAc), mostró generar respuestas de recompensa paralela a la generada posteriormente a la administración de dosis bajas de morfina. En línea con los efectos farmacológicos inducidos por las EM1-2, estudios fármaco-conductuales demostraron que la administración ICV de la EM1 fue capaz de generar respuestas de preferencia de lugar en roedores tratados CPP, por sus siglas en inglés, conditioned place preference, en tanto que la administración de EM2 generó respuestas opuestas, esto es, respuestas de aversión al lugar. Estudios conductuales relacionados con el fenómeno de estrés mostraron que las EM1-2 son capaces de modular la actividad funcional del eje HHA (eje hipotálamo/hipófisis/glándula adrenal) a través de la activación del sistema de proyección neuronal del tracto solitario (NTS, por sus siglas en inglés), al hipotálamo y/o a través de la activación del área ventrolateral de la sustancia gris periacueductal (PAG, por sus siglas en inglés); componente importante del sistema opioide endógeno, que median respuestas analgésicas (antinociceptivas) inducidas por estímulos estresantes. Asimismo, la administración de endomorfinas (v.g., EM1) mostró generar incrementos de conductas de naturaleza ansiolítica en ratones expuestos a paradigmas experimentales de generación de conductas estresantes (v.g., laberinto elevado). Estos estudios sugieren que la generación de conductas de estrés-emocional inducidas por las endomorfinas es mediada a través de la activación del receptor opioide µ en neuronas del hipotálamo responsables de regular la secreción de factores liberadores de distintas hormonas hipofisiarias (v.g., CRH, LHRH). Más aún, resulta interesante que las endomorfinas sean capaces de inducir conductas antidepresivas o de tipo antidepresivos como se ha reportado recientemente en modelos animales de estrés y depresión. Estos estudios mostraron que las respuestas conductuales de reacción al estrés y las conductas antidepresivas mediadas por las EM1-2 están ligadas con la expresión neuronal del mensajero de RNA que codifica para el factor trófico (BDNF, por sus siglas en inglés, brain derived neurotrophic factor), en áreas del sistema limbico, y que es inducida en forma dosis-dependiente por las endomorfinas, posterior a su administración ICV. Por lo tanto, estos estudios han permitido proponer que las endomorfinas cumplen un papel relevante durante el curso o desarrollo de las enfermedades mentales (v.g., esquizofrenia y depresión). En extensión a estos estudios conductuales, estudios recientes han demostrado la actividad orexigénica de las endomorfinas en forma similar a lo previamente detectado con distintos ligandos agonistas del receptor opioide µ (v.g., morfina, DAMGO; morfina-6β-glucurónido). Si bien estos estudios mostraron que tanto las EM1-2 como diversos agonistas del receptor opioide µ exhiben potentes actividades orexigénicas en el SNC de roedores, la actividad de las EM1-2 parece depender de la actividad de la dinorfina A y su unión sobre su receptor opioide K en neuronas hipotalámicas. Más aún, diversos estudios han mostrado que el sistema opioide endógeno (a través de la β-endorfina) regula conductas de naturaleza sexual y apareamiento (v.g., lordosis), además de modular la secreción y/o actividad de hormonas de origen gonadal (estrógenos, progesterona). Estudios similares en roedores hembras mostraron que la microinyección de EM1-2 en áreas específicas del sistema límbico y/ o la administración IT de ambos péptidos era capaz de generar respuestas sexuales de apareamiento, similares a las detectadas por la p-endorfina y morficeptina en la misma especie de animal, siendo bloqueados los efectos por la administración de naloxona. Estas respuestas conductuales inducidas por las EM1-2 mostraron estar ligadas a la liberación neuronal de LHRH, como de la activación y modulación del sistema de transmisión gabaérgico. En cuanto a las funciones de memoria y aprendizaje, diferentes estudios han demostrado que la administración ICV de EM1-2 en ratones expuestos a diferentes paradigmas de aprendizaje experimental, los péptidos opioides alteran significativamente los mecanismos de procesamiento y consolidación de memoria a corto y largo plazo en los animales tratados. Estos efectos parecen depender de la modulación del sistema opioide (v.g., el receptor opioide µ) sobre los sistemas de transmisión colinérgica y dopaminérgica en el cerebro de los mamíferos. Asímismo, diversos estudios han demostrado que tanto las EM1-2 como los alcaloides opiáceos y opioides endógenos modulan funciones cardiovasculares y respiratorias. En este contexto, diversos estudios mostraron que la administración de EM1-2 en ratas normotensas e hipertensas produce cambios fisiológicos significativos en la presión sanguínea y la frecuencia cardiaca. Si bien no están del todo esclarecidos los mecanismos por los cuales las endomorfinas producen sus respuestas cardiovasculares, diversos estudios sugieren que la actividad de estos péptidos está en función de la actividad e interacción de los sistemas de transmisión gabaérgico y glutamatérgico, respectivamente. Más aún, otros estudios sugieren que las respuestas fisiológicas de estos péptidos dependen de la actividad del óxido nitroso (NO, por sus siglas en inglés) liberado de los vasos sanguíneos, en respuesta de la activación del receptor opioide µ. Finalmente, diversos estudios han mostrado que las EM1-2 y la activación del receptor opioide µ producen efectos inhibitorios sobre la contracción del músculo liso del tracto gastrointestinal, generados a través de una reducción sostenida en la liberación de neurotransmisores de terminales sinápticas del plexo mientérico, mismas que inervan el tejido muscular liso del tracto gastrointestinal.

Endomorphin peptides: pharmacological and functional implications of these opioid peptides in the brain of mammals. Part one / Las endomorfinas: Implicaciones farmacológicas y funcionales de estos péptidos opioides en el cerebro de los mamíferos

The present paper describes several aspects of the biological activities, physiological and behavioral responses displayed by the most recent discovered opioid peptides: endomorphins. Endormorphins comprise two endogenous C-terminal amide tetrapeptides, named as endomorphin-1 (EM1; Tyr-Pro-Trp-Phe-NH2) and endomorphin-2 (EM2; Tyr-Pro-Phe-Phe-NH2), which were discovered a decade ago (1997) by Zadina's group. Initially, they reported the identification of two endogenous opioid peptides that displayed high binding affinities and selectivities for the µ-opioid receptor among other identified and cloned opioid receptors. These led authors to support the hypothesis that endomorphin peptides represent the endogenous ligand agonists for the µ-opioid receptor. Both peptides were identified and isolated from bovine and human brains. They consist of four amino acids that share a 75% structural homology among amino acids, and which display the structural α-amidated form of C-terminal -Phe- residue, as demonstrated for many other bioactive neuropeptides. These peptides are structurally distinct from other endogenous opioid substances identified in the brain of mammals, although they share some similarities with other amide terapeptides such as Tyr-W-MIF-1, found also in the mammalian brain. Here, we review the structure-relationship activity of both endomorphin molecules comparing their binding properties to different opioid receptors. Both EM1/EM2 peptides appear to be vulnerable to enzymatic degradation when exposed to the activities of different proteolytic enzymes, as occurs with many other neuroactive peptides found in the SNC of mammals. Immunohistochemical studies showed the wide and asymmetric distribution of both EM1-2 peptides in the brain, leading to the extensive pharmacological, cellular, and physiological studies that demonstrated the wide and varied bioactivities displayed by these peptides at both central and peripheral tissues. These studies led several authors to suggest the potential endogenous role of these peptides in major physiological processes (e.g. analgesia or antinociception). Based on the generation of specific (rabbit) polyclonal antibodies and the use of combined radioimmunoassay (RIA) techniques and immunohistochemical procedures, it was shown the wide distribution of EM1-2-LI (endomorphin1-2-like immunoreactivities) throughout the brain of different species (e.g. rat, primate, human), particularly co-localized in specific areas where µ-opioid receptor has been shown to be expressed. IHC mapping of endomorphin material in the CNS showed a parallelism with the neuroanatomical distribution of other endogenous opioid peptides (e.g. Met/Leu-enk, Dynorphin A, β-endorphin) previously reported. These studies showed for instance that, whereas EM1-LI was shown to be widely and densely distributed throughout the brain, particularly in forebrain structures (e.g. nucleus accumbens [NAc]; cortex [Cx]; amygdale [AMG]; thalamus [Th], the hypothalamus [Hyp], the striatum [CPu]), including the upper brainstem (BS); and dorsal root ganglia (DRG); EM2-LI is highly expressed in spinal cord and lower brainstem. Interesting enough is the demonstration of the expression of EM1-2-LI outside the CNS (e.g. spleen, thymus and blood), and detected in immune cells (e.g. macrophages/monocytes, lymphocytes, and polymophonuclear leucocytes) surrounding inflammatory foci. Pharmacological studies showed that these peptides displace with high potency several µ-opioid receptor ligands agonists in a concentration-dependent manner. Moreover, EM1-2 peptides have been shown to modulate the release of several conventional transmitters from neurons (e.g. DA, NA, 5-HT, ACh) besides on active neurohormones. Additionally, in vitro and in vivo studies showed that both EM-1/EM-2 peptides produce their pharmacological and biological effects by stimulating either µ1 or µ2-opioid receptors, which mediate the distinct pharmacological activities detected for each peptide. Cellular studies showed that both EM-1/EM-2 peptides induce a potent granule/vesicle endocytosis and trafficking of µ-opioid receptor in cells transfected with the µ-opioid receptor cDNA; following some endocytosis responses and µ-opioid receptor trafficking mechanisms shown in enteric neurons; cells previously reported to express naturally µ-opioid binding sites on cells. Endomorphins have been shown to induce potent antinociceptive responses after ICV or IT administration into mice; to modulate nociceptive transmission and pain sensation into the brain after stimulating peripheral nociceptors on primary neuronal afferents; and to generate cross-tolerance between endomorphin peptides and between EM1 and opiate compounds, such as morphine.

Este artículo resume varios aspectos de las múltiples actividades biológicas, celulares, efectos farmacológicos, respuestas fisiológicas y conductuales de dos nuevas sustancias peptídicas de naturaleza opioide, descubiertas recientemente y denominadas endomorfinas. Las endomorfinas son dos péptidos opioides, clasificados como endomorfina-1 (EM1, Tyr-Pro-Trp-Phe-NH2) y endomorfina-2 (EM2, Tyr-Pro-Phe-Phe-NH2), cuyas secuencias peptídicas fueron identificadas y aisladas del cerebro de bovino y humano por el grupo de Zadina en 1997. Estudios de unión radioligando-receptor demostraron que estos péptidos se unen con alta afinidad de unión al receptor opioide µ en relación con su capacidad de unión a otros subtipos de receptores opioides (kappa [κ], delta [δ] ), previamente identificados en el SNC de mamíferos. Ambos péptidos están compuestos por cuatro aminoácidos y son estructuralmente distintos de las demás sustancias opioides endógenas conocidas. Esta revisión detalla con precisión diversos aspectos de la farmacología y actividades celulares de estos opioides y sus implicaciones en la modulación de distintas circuitos o vías neurales y funcionamiento del SNC de los mamíferos, respectivamente. Los estudios relacionados con la función estructura-actividad de estos péptidos han mostrado que, al igual que la mayoría de los péptidos bioactivos endógenos de naturaleza opioide y no opioide, son vulnerables a la escisión peptídica por cortes enzimáticos mediante la exposición a distintas enzimas proteolíticas que pudiesen participar en la degradación endógena de las endomorfinas, y la obtención de diversos productos de degradación. Asimismo, este artículo menciona la amplia distribución neuroanatómica que poseen las endomorfinas en distintas regiones del cerebro, particularmente en aquellas que regulan el procesamiento y la transmisión de la información nociceptiva y que, por tanto, reflejan el papel potencial de estos péptidos en procesos fisiológicos de analgesia, entre muchos otros (memoria y otro aprendizaje). En este contexto, diferentes estudios basados en el empleo de ensayos inmunológicos (radioinmunoensayos [RIA] y técnicas de inmunohistoquímica [IHC]) que requieren el uso de anticuerpos específicos generados contra las secuencias consenso de las endomorfinas mostraron una amplia distribución de material inmunoreactivo a endomorfina (vg., EM1-LI, EM2-LI) en tejidos neurales de humano, bovino y roedores. Por ejemplo, la EM1-LI mostró una distribución relativamente abundante en una gran mayoría de las regiones del SNC de mamíferos estudiados, particularmente en la región rostral y superior del tallo cerebral, así como en el núcleo accumbens (NAc), la corteza prefrontal y frontal (PFCx), la amígdala (AMG), el tálamo (TH), el hipotálamo (HPT), el estriado (CPu) y fibras nerviosas de la raíz del ganglio dorsal (DRG). En contraste, la expresión de EMZ mostró ser muy abundante en la región de la médula espinal y en la región caudal del tallo cerebral. La distribución de material inmunoreactivo a EM1-2 en el SNC de mamíferos mostró similitudes en cuanto a la distribución neuroanatómica reportada para otros péptidos opioides endógenos, previamente identificados (vg., encefalinas, dinorfinas, endorfinas). Así mismo, estudios paralelos lograron identificar la presencia de EM1-2-LI en órganos periféricos (vg., bazo, timo, células inflamatorias del tipo de macrófagos-monocitos, linfocitos y leucocitos PMN) y en plasma. Más aún, diversos estudios farmacológicos han mostrado que las actividades biológicas y respuestas fisiológicas de las EM1-2 están mediadas a través de la estimulación de los subtipos de receptores opioides µ1 y µ2. Estudios de inmunohistoquímica (IHC) demostraron la colocalización del receptor opioide µ y las EM1-2 en diversas regiones del SNC de mamiferos. Esto ha permitido proponer que las EM1-2 representan una nueva familia de péptidos opioides con funciones neuromoduladoras relevantes en el SNC, las cuales intervienen en la regulación de los procesos biológicos de percepción del dolor; respuestas de estrés; funciones límbicas de placer y recompensa inducidas por incentivos naturales y/o sustancias psicotrópicas; funciones de estado de alerta y vigilia, funciones cognitivas (de aprendizaje y memoria) y actividades de regulación neuroendócrina. Además, diversos estudios celulares han mostrado que ambos péptidos opioides son capaces de inducir la internalización aguda o endocitosis del receptor opioide µ en células somáticas transfectadas con el ADN (ADNc) que codifica este mismo receptor opioide. Al igual que otros péptidos opioides (v.g., encefalinas), diversos estudios mostraron el catabolismo enzimático de estos péptidos amidados mediante la actividad de enzimas proteolíticas (v.g., carboxipeptidasa Y, aminopeptidasa M), lo que ha permitido sugerir que estos péptidos opioides son degradados por rutas de degradación enzimática similares que rigen para múltiples péptidos bioactivos moduladores en el SNC de los mamíferos. Al igual que otros péptidos endógenos, ambas endomorfinas mostraron la capacidad de modular la liberación neuronal de neurotransmisores (DA, NA, 5-HT, ACh) y hormonas peptídicas en áreas específicas del cerebro de los mamíferos. Asimismo, ambos péptidos mostraron una capacidad de generar efectos antinociceptivos potentes en forma dosis-dependiente posterior a su administración ICV o IT en animales experimentales, además de generar respuestas de tolerancia cruzada entre ambas endomorfinas y/o entre la EM1 y alcaloides opiáceos del tipo de la morfina.

Preclinical evaluation of the therapeutic effect of adenoviral vectors in human papillomavirus-dependent neoplasias.

Gene therapy with adenoviral vectors can eliminate neoplasic cells through selective replication and/or through pro-apoptotic, immunogenic or suicide gene expression. However, an adenoviral vector may provide anti-cancerous effects even in the absence of replication or therapeutic gene expression. The present study evaluates the therapeutic effects caused by the administration of an adenoviral vector, alone, in HPV-dependent neoplasias (HPV-N). In vivo trials were carried out in two HPV-N mouse models. One model was immunocompetent and the other was immunodeficient. In both models, the effect of intratumoral administration of saline solution (PBS) was compared with administration of an adenoviral vector that had no replicative capacity or therapeutic gene (Ad-BGal). In the immunocompetent mice, Ad-BGal adenoviral vector administration significantly reduced tumor growth, compared with PBS. No differences were observed in the immunodeficient mice. In conclusion, the present study lends support to the use of adenoviral vectors in HPV-N treatment since they are capable of generating an antitumoral effect in immunocompetent individuals, even in the absence of a therapeutic gene or viral vector replication.

Improved diagnosis of pleural tuberculosis using the microscopic- observation drug-susceptibility technique.

Tests for pleural tuberculosis are insensitive and expensive. We compared nonproprietary microscopic-observation drug-susceptibility (MODS) culture with Löwenstein-Jensen culture for evaluation of pleural specimens. MODS culture was associated with greatly increased diagnostic sensitivity and shorter time to diagnosis, compared with Löwenstein-Jensen culture (sensitivity of culture of biopsy specimens, 81% vs.51%; time to diagnosis, 11 days vs. 24 days; P < .001). The MODS technique is inexpensive, allows drug-susceptibility testing, and is a considerably improved diagnostic method for pleural tuberculosis.

A potent replicative delta-24 adenoviral vector driven by the promoter of human papillomavirus 16 that is highly selective for associated neoplasms.

BACKGROUND: Several human epithelial neoplasms are associated with high-risk strains of human papillomavirus (HPV) such as cervical, anorectal, and other carcinomas. For some tumor types the current therapeutic tools are only palliative. Conditionally replicative adenoviruses (CRAds) are promising antineoplastic agents, which also can trigger confined antitumor effects. METHODS: We constructed a series of CRAds driven by the upstream regulatory promoter region (URR) of an Asian-American variant of HPV-16, which contained different mutations at the E1A region (dl1015 and/or Delta24) and wild-type. All vectors were tested in vitro for viral replication and cytotoxicity. Viral DNA replication and E1A expression were also assessed by quantitative PCR. Finally, we confirmed the antitumoral efficacy of this vector in injected and non-injected xenotransplanted cervical tumors in a murine model for tumor regression and survival studies. RESULTS: A vector denominated Ad-URR/E1ADelta24 displayed a potent cytopathic effect associated with high selectivity for HPV+ cell lines. We found that the oncolytic effect of this CRAd was comparable to Ad-wt or Ad-Delta24, but this efficacy was significantly attenuated in HPV- cell lines, an effect that was contributed by the URR promoter. Ad-URR/E1ADelta24 was very effective to control tumor growth, in both, injected and non-injected tumors generated with two different HPV+ cell lines. CONCLUSIONS: CRAd Ad-URR/E1ADelta24 is a highly selective vector for HPV+ cell lines and tumors that preserves the oncolytic efficacy of Ad-wt and Ad-Delta24. Our preclinical data suggest that this vector may be useful and safe for the treatment of tumors induced by HPV, like cervical cancers.

Serrania sagrada de los Urus

Los Urus; El paisaje; El hombre y los mitos; Quwak y wari; Las arrias de los dioses; Uru-Uru, "axis mundi"