La diabetes de tipo 1 (T1D) es una enfermedad compleja caracterizada por la desaparición selectiva de las células beta pancreáticas, responsables de la producción de insulina, debido a un proceso autodestructivo mediado por el propio sistema inmunitario. La cepa murina NOD es el modelo animal más ampliamente utilizado en el estudio de la T1D, ya que estos animales desarrollan, de forma espontánea, una forma de diabetes autoinmunitaria similar a la que se observa en humanos. Aunque se conoce que los linfocitos T son las células responsables de la destrucción directa de la masa celular beta, otros tipos celulares del sistema inmunitario también están implicados en el origen y desarrollo de esta respuesta autoinmunitaria. Entre ellos se encuentran los linfocitos B, los cuales también migran, junto con los linfocitos T, a los islotes pancreáticos durante el desarrollo de la diabetes. Nuestra hipótesis es que la población de linfocitos B que forma parte del infiltrado leucocitario en los islotes pancreáticos puede presentar cualidades funcionales distintivas, que aporten la capacidad de regular in situ la actividad de los linfocitos T autorreactivos. El primer objetivo planteado en este estudio ha sido la caracterización fenotípica y funcional de los linfocitos B infiltrantes en islotes pancreáticos, en diferentes modelos murinos de susceptibilidad/resistencia a la diabetes. Así, se ha observado que la migración de los linfocitos B al entorno intrainsular es más destacada en hembras, especialmente en la etapa pre-diabética. Esta población de linfocitos B infiltrantes muestra un fenotipo correspondiente a células maduras, pero la disminución significativa en superfície de la molécula CD19, que forma parte del complejo correceptor del BCR, sugiere un estado funcional reprimido. Los resultados obtenidos tras la estimulación in vitro de estas células indican que dentro del ambiente del infiltrado existen unas condiciones que mantienen este fenotipo reprimido, pero que estas células son especialmente sensibles a la estimulación vía CD40. Estos datos sugieren que estos linfocitos, aunque no presentan cambio de isotipo en su BCR y por tanto no provienen de una reacción de centro germinal, parecen haber estado en contacto previamente con su antígeno. No obstante, a nivel de producción de citoquinas (IL-4, IL-10, IFN?) y de capacidad estimuladora de la proliferación de linfocitos T, no see han detectado diferencias funcionales de estos linfocitos B infiltrantes de islotes, respecto a linfocitos B de poblaciones periféricas. El segundo objerivo de este estudio ha consistido en la identificación del antígeno reconocido predominantemente por esta población de linfocitos B infiltrantes. En un estudio previo, realizado por nuestro grupo, se habían generado hibridomas productores de anticuerpos, a partir de linfocitos B infiltrantes de islotes, y se había demostrado que la mayoría de estos anticuerpos monoclonales reconocían antígenos expresados en las fibras nerviosas que inervan el páncreas. En este estudio, a partir del aislamiento y posterior identificación molecular del antígeno reconocido por 21 anticuerpos monoclonales con el mismo patrón de reconocimiento pero de diferente origen clonal, se ha demostrado que la periferina es la proteína reconocida por todos ellos. Este antígeno neuroendocrino es una proteína de citoesqueleto que se expresa mayoritariamente en las fibras nerviosas periféricas, aunque también, en niveles menores, en las células del islote pancreático. Estos datos apoyan la hipótesis de que el ataque autoinmunirario que se desarrolla en los afectados por T1D, no es exclusivamente dirigido contra las células beta pancreáticas, y que la desestabilización del sistema nervioso pancreático puede ser un factor implicado en el desarrollo de la enfermedad. / Type 1 diabetes (T1D) is a complex autoimmune disease characterized by selective destruction of pancreatic beta cells by the patient's own immune system.Currently, one of the best animal models of type 1 diabetes is the nonobese diabetic (NOD) mouse. NOD mice spontaneously develop a form of diabetes that closely resembles human type 1 diabetes.Islet-infiltrating T-cells are major effectors of beta-cell damage in T1D, however, other cellular elements of the immune system also play a critical role in the initiation and/or progression of T1D. Among these, B-cells are also recruited to pancreatic islets, during disease development. We hypothesize that islet-infiltrating B-cells may have distinctive functional traits, enabling them to regulate autoreactive T-cell activity in situ. The aim of the present study was the phenotypical and functional characterization of islet-infiltrating B cells, in T1D susceptible/resistant T1D murine models. Thus, it was observed that B-cell recruitment into pancreatic islets is higher in female mice, specially just before diabetes onset. Although they are mature B-cells, they interestingly show an abnormal down-regulation of surface CD19 expression, showing a possible hiporesponsive status of these cells, given the relevance of CD19 in regulating BCR activation. Islet-infiltrating B-cells develop a pronounced costimulator phenotype after in vitro stimulation with anti-CD40, thus revealing to be somehow repressed while in the islets. These results suggest that these B-cells, although not presenting immunoglobin class switch recombination, seem to be antigen-experienced. On the other hand, cytokine expression profile (IL-4, IFN?, IL-10) and T-cell activator quality of islet-infiltrating B-cells have been shown to be similar to that from their splenic counterparts.On the other hand, the second objective of this study was the identification of the autoantigen predominantly targeted by islet-infiltrating B-cells. In a previous study in our laboratory, antibody-producing hybridomas were generated from islet-infiltrating C-cells, and it was shown that most of them targeted peripheral nervous elements. In the present study, the isolation and subsequent molecular characterization of the antigen recognized by 21 of these monoclonal antibodies, proved that peripherin is the protein targeted by them all. This neuroendocrine autoantigen is a cytoskeleton protein mainly expressed by peripheral nervous cells, but it is also expressed, although at lower levels, by islet beta-cells. These data support the hypothesis that T1D autoimmune attack is not exclusively focused on pancreatic beta-cells, and that pancreatic nervous system damage may be involved in disease development.

Esta tesis estudia los efectos y la eficacia de la política monetaria. A grandes rasgos, el banco central cambia los tipos de interés a corto plazo y, a través de la estructura temporal, también se ven afectados los tipos de interés a largo plazo. Los tipos a largo plazo son una variable importante para las decisiones de inversión de las empresas y de ahorro de los hogares. Estas decisiones afectan tanto la producción como los precios y, como consecuencia, los objetivos finales del banco central -por ejemplo, la estabilidad de los precios-. Esta tesis examina detalladamente algunos temas relacionados con la descripción anterior de los mecanismos de transmisión de la política monetaria que hasta ahora no se han estudiado en profundidad.El primer capítulo del documento contiene la introducción. El segundo analiza la transmisión de la política monetaria en economías abiertas teniendo en cuenta que la apertura de una economía es especialmente relevante para los países europeos. En este mismo capítulo se estudian los efectos dinámicos de una acción imprevista del banco central para varios países europeos. Los cambios de estos efectos se estudian mediante una serie de contrastes de estabilidad y la estimación de las fechas de cambio de los parámetros.El tercer capítulo se centra en los determinantes de los tipos de interés a corto plazo. La mayoría de los modelos monetarios asumen que el banco central controla perfectamente estos tipos. No obstante, en la práctica, este control no es nada perfecto. Los mercados determinan los tipos de interés pero el banco central ejerce una fuerte influencia en la oferta de reservas. Por ello, se diseña un modelo de decisión intertemporal para el mercado de reservas y se incluyen todos los aspectos institucionales importantes para el mercado de reservas de la zona euro. Entonces, se estima el modelo con datos de esta zona. La mayoría de los patrones predecibles en la media y en la volatilidad de los tipos de interés a corto plazo están relacionados con la implementación de la política monetaria. También se observa que los bancos reaccionan de manera retardada a las nuevas informaciones. Así, se estudian las implicaciones de la eficiencia del mercado, endogeneidad de la oferta de reservas y el underbidding.La cuarta y última parte de la tesis se centra en los efectos de la implementación de la política monetaria en los mercados de dinero de la zona euro. Más exactamente, se analiza la volatilidad de los tipos de interés con varios vencimientos y la transmisión de la volatilidad de los tipos de corto a largo plazo. Estos análisis concluyen que la manera en la que se aplica la política monetaria acaba afectando a la volatilidad de la mayoría de los tipos de los mercados de dinero salvo los tipos de un año. Se puede observar claramente que estos efectos son mucho más fuertes para los tipos a corto plazo. No obstante, las decisiones de inversión de las empresas como las de ahorro de los hogares dependen mayoritariamente de los tipos a largo plazo. De ello se desprende que los procedimientos que se utilizan en la actualidad aplican de una manera muy eficaz las decisiones de política monetaria sin tener ninguna repercusión en la economía real. Asimismo, se han encontrado algunos efectos en los días del calendario, una curva de volatilidad en forma de U y un apoyo consistente a para la hipótesis de expectativas. / This thesis studies the effects and effectiveness of monetary policy. In a stylized way, the central bank changes the short-term interest rate and, via the term structure, long-term interest rates are affected. Long-term rates are the relevant variables for firms' investment and households' saving decisions, which influence output and prices and, as a consequence, the final objectives of a central bank, e.g. price stability. This thesis looks carefully at some particular, and widely overlooked, issues along the above described transmission mechanism of monetary policy.The first chapter contains the introduction. The second chapter analyses the transmission of monetary policy in open economies. Taking into account the openness of an economy is especially important for European countries. The dynamic effects of an unexpected monetary policy action for several European countries are studied. Changes over time are investigated by using a range of stability tests and estimating break dates. The third chapter looks at the determinants of the short-term interest rate. Most monetary models assume that the central bank perfectly controls this interest rate. However, this control is far from perfect in practice. Interest rates are determined on markets, with the central bank having a strong influence on the supply of reserves. The intertemporal decision problems in the reserve market for both central and commercial banks are modeled. All important institutional features of the euro area reserve market are included. The model is then estimated with euro area data. Most of the predictable patterns for the mean and volatility of the short-term interest rate are related to monetary policy implementation. Banks react sluggish to new information. Implications for market efficiency, endogeneity of reserve supply and underbidding are studied. Chapter four studies the effects of monetary policy implementation on the euro area money market. In particular, volatility of interest rates with various maturities and volatility transmission along the yield curve is analyzed. It is found that the way how monetary policy is implemented affects volatility of most money market rates, except the twelve-month rate. These effects are strongest at the short end of the yield curve. Notwithstanding, firms' investment and households' consumption decisions depend mostly on longer term rates, which indicates that the operating procedures in place implement monetary policy decisions very efficiently, without inducing real costs on the economy. Furthermore, some calendar day effects, a U-shaped volatility curve and strong evidence in favour of the expectation hypothesis are documented.

La tesis adapta modelos macroeconómicos recientes de economías abiertas para analizar los problemas que caracterizan los países emergentes de Europa del Este. En particular, se estudia los efectos que el crecimeinto asimétrico de la productividad tiene sobre el tipo de cambio real, el tipo de cambio real interno, esto es, el precio relativo de los bienes comerciables respecto a los no comerciables y el tipo de cambio real externo, esto es, el precio relativo entre los bienes comerciables nacionales y extranjeros. Se demuestra que la discriminación de precios es una condición necesaria para explicar la correlación entre los tipos de cambio nominales y reales, y la apreciación del tipo de cambio real observadas en estas economías emergentes. También se demuestra como los supuestos de inversiones específicas y de costes de ajuste en la inversión ayudan a reproducir el ajuste lento de los precios relativos en respuesta a diferenciales de productividad así como la apreciación del tipo de cambio real externo.En tercer lugar, la tesis estudia como determinar óptimamente el tipo de cambio de estas monedas con respecto al Euro cuando estos países entren en la Union Monetaria Europea. En vez de utilizar criterios exógenos para determinar este tipo de cambio, este trabajo emplea una función de bienestar social derivada del modelo teórico. Asimismo, se propone un algoritmo para determinar el tipo de cambio óptimo en función de las variables exógenas y de estado en el momento de la unión. Se demuestra que aunque las desviaciones del tipo de cambio real sobre su nivel de equilibrio tienen un papel principal en la determinación del tipo de cambio óptimo, no es la única variable a considerar. Otras variables como la inflación pasada o los salarios reales también influencian la elección de la paridad óptima. Además, la fase del ciclo exterior, la demanda de exportaciones y las perturbaciones de productividad son importantes variables exógenas a tener en cuenta para una adecuada decisión política. Se muestra la importancia de este tipo de evaluaciones basadas en modelos y como decisiones basadas en criterios exógenos pueden llevar a resultados subóptimos.Por último, la tesis considera las implicaciones sobre el bienestar de introducir explícitamente el desempleo en los modelos macroeconómicos de economías abiertas. En particular, se comparan los efectos de una devaluación inesperada en economías con y sin desempleo. En modelos con mercados laborales Walrasianos las devaluaciones disminuyen el bienestar si el deteriore de los términos de intercambio compensa el aumento del consumo doméstico. Sin embargo, cuando existe desempleo, una devaluación puede aumentar el bienestar social ya que se mejora la distribución del consumo en la población. / The thesis adapts the models of new open economy macroeconomics to the special problems of a certain group of emerging market economies, namely the economies of European post-communist countries.It studies the effects of asymmetric productivity growth for the CPI-based real exchange rate, the internal real exchange rate, i.e. the relative price of non-tradables to tradables, and the external real exchange rate, i.e. the relative price of domestic and foreign tradables. It is demonstrated that pricing to market is necessary to reproduce the empirically observable correlation of the nominal and real exchange rates, and the appreciation of the real exchange rate. It is also shown that the assumption of firm specific investments and investments adjustment costs helps explaining the slow adjustment of domestic relative prices to productivity differentials and the appreciation of the external real exchange rate.The thesis studies how to set optimally the Euro conversion rate of the new Member States of the European Union. Instead of ad-hoc objective functions it uses a model based social welfare function for the analysis. The thesis provides an algorithm to determine how to peg the nominal exchange rate optimally if the accession date values of state and exogenous variables are known. It is shown that the deviation from the equilibrium real exchange rate has a principal but not exclusive role in determining the optimal conversion rate. It is demonstrated that the past inflation rate and the level of real wages also influence the optimal choice. Furthermore, the foreign-business-cycle, exports demand and productivity shocks are the most important exogenous factors necessary for a proper policy decision. The thesis demonstrates the importance of a utility-based and that evaluations based on ad-hoc welfare criteria may result in misleading results.The thesis also considers the welfare implications of introducing unemployment in models of new open economy macroeconomics. The effects of an unexpected devaluation of the nominal exchange rate in a model with and without unemployment is compared. In models with Walrasian labor markets a devaluation decreases social welfare if the deterioration of the terms of trade offsets the rise in domestic consumption. However, in the presence of unemployment even such a situation can enhance social welfare, since the distribution of consumption becomes more even.

Objetivos: estimar la frecuencia de ansiedad y depresión, así como su asociación con el control glicémico en pacientes con diabetes tipo 2 atendidos en el Hospital Nacional Almanzor Aguinaga Asenjo de Chiclayo durante el año 2011. Materiales y métodos: estudio descriptivo transversal. La muestra fue de 270 pacientes diabéticos tipo 2 entre 19 a 60 años que acudieron al consultorio externo de endocrinología. Se utilizó como instrumentos los inventarios de depresión y ansiedad de Beck y una ficha epidemiológica. Se calcularon frecuencias absolutas y relativas y un análisis inferencial exploratorio mediante el cálculo de razones de prevalencia, intervalos de confianza al 95% y valores p. Resultados: hubieron 172 mujeres (64%) y 98 hombres (36%). El promedio de edad fue de 52 años ± 6,5. Se hallaron 156 pacientes con depresión (57,78%) y 176 con ansiedad (65,19%). No se halló asociación entre el control glicémico con depresión (RP= 0,77, IC95% 0,42 –1,38, p >0,05) y ansiedad (RP= 0,86, IC95% 0,47–1,59, p >0,05). Conclusiones: la frecuencia de depresión y ansiedad en los pacientes diabéticos tipo 2 de este hospital de Chiclayo fue elevada. En una exploración inicial no se encontró asociación entre depresión y ansiedad con el control glicémico.

El 90% de casos mundiales representa a la diabetes tipo II, una enfermedad de salud pública que se debe en gran medida a un sobrepeso e inactividad física de las personas. Esta investigación tuvo como objetivo medir la efectividad de una intervención educativa de enfermería en los estilos de vida en adultos con diabetes tipo II, San José - Chiclayo - 2012. Con la finalidad de concientizar a la población en el control de sus estilos de vida en dieta y ejercicio, aportando a la ciencia de enfermería en el trabajo comunitario mediante programas extramurales; fue de tipo cuantitativo cuasi experimental, la población fue de 32 adultos, la muestra estuvo integrada por 18 adultos con diabetes tipo II, con edades mayor a 40 años; el muestreo fue no probabilístico de tipo intencional. Los datos se recolectaron pre y post-intervención educativa, utilizando la escala Likert con 26 preguntas sobre dieta y ejercicio, y la lista de cotejo con 4 indicadores (IMC, presión arterial, perímetro abdominal y glicemia capilar). La intervención educativa duró 4 meses, donde se aplicaron 3 sesiones educativas a cada participante con una hora de duración cada una. Para el procesamiento y análisis, se creó una base de datos en el programa SPSS versión 20 para el análisis estadístico descriptivo y la t-student para el análisis estadístico inferencial. Los resultados mostraron que la intervención educativa de enfermería en dieta y ejercicio solamente fue efectiva en el índice de masa corporal (p=0.00049) y presión arterial (p=0.00016).

The short analysis of vibromotors (VM) and rolamite type mechanisms is submitted, their advantages are revealed. Dynamic processes, occurring in vibromotor, are investigated experimentally in which the slanting impact of the converter of longitudinal fluctuations (CLF) to a rotor is used, and rotates it. It is established optimum angle of elastic pressing of the converter of longitudinal fluctuations to a rotor makes 125º- are getting the greatest revolutions of a rotor. The size elastic pressing of the converter of longitudinal fluctuations to a rotor unsignificantly influences the form of the mechanical characteristics. It is recommending for precision systems working in a wide temperature range and at linear and vibrating overloads to use the circuits with included in a contour of the generator by converters or to construct auto ascillatory generators working on resonant frequency of the converter. The value of non synchronicity of rotation of rotors most grows in elementary vibromotor with two rotors, least - in rolamite vibromotor, in which the converter of longitudinal fluctuations rotates both rotors. The variant of rolamite vibromotor, in which the converter of longitudinal fluctuations rotates both rotors, is optimum. Four problems inherent vibromotors are established and ways of their decision are offered. Expediently CLF fix in its middle. Thus it is provided the least damping of vibrations. Expediently to use waveguides in the construction of VM. Thus it is... [to full text]

Various real processes, occurring in the nature, technology, etc., are usually described by differential equations. Due to the development of computer software, computers have become the main tool for solving problems of different fields. They enable not only to solve complex differential equations or their systems, but also to analyze the dependence of differential equations solutions on various parameters and initial values. Up to the present many methods for the solution of differential equations have been developed, therefore, the user can solve differential equation, using several different methods. Different methods of solution enable to avoid various mistakes and to reduce errors. Differential equations can be solved not only using numerical methods, but also by applying methods of algebraic operator equations. When the latter method is being used, solutions are expressed in power series, the convergence of which has to be analyzed separately. This paper includes the analysis of Mathieu-type differential equations solutions dependence on initial conditions and parameters, as well as the establishment of solutions attractor zones and curves, which separate different attractor zones. It is very important to indicate the most exact crossing limits among different attractor zones. In order to avoid huge errors, we carried out the research by using two methods: operator and Runge-Kutta.

SANTRAUKA Vilniaus universiteto Medicinos fakultetas Reabilitacijos, sporto medicinos ir slaugos institutas Slaugos magistrantūros programa SERGANČIŲJŲ 2 TIPO CUKRINIU DIABETU GYVENIMO KOKYBĖS ĮVERTINIMAS Slaugos magistro baigiamasis darbas Darbo autorė: Aliona Zaborovskytė Darbo vadovė: prof. habil..dr. Danutė Kalibatienė Vilnius, 2008 m. Pagrindinės sąvokos: 2 tipo cukrinis diabetas, gyvenimo kokybė, SF-36 klausimynas. Tyrimo tikslas. Įvertinti 2 tipo sergančiųjų cukriniu diabetu gyvenimo kokybę. Tyrimo uždaviniai. Ištirti ir palyginti grupės sergančiųjų 2 tipo cukriniu diabetu gyvenimo kokybės skirtumus, atsižvelgiant į tiriamųjų lytį, amžių ir kūno masės indeksą. Įvertinti grupės sergančiųjų 2 tipo cukriniu diabetu gyvenimo kokybę, atsižvelgiant į socialinius veiksnius. Įvertinti grupės sergančiųjų 2 tipo cukriniu diabetu gyvenimo kokybę, atsižvelgiant į cukrinio diabeto komplikacijas. Tyrimo populiacija. Tyrime dalyvavo 196 asmenys, sergantys 2 tipo cukriniu diabetu. 67 vyrai (34,2 proc.) ir 129 moterys (65,8 proc.), kurių amžius buvo nuo 41 iki 77 metų (vidurkis – 60,5 ± 8,1 m.). Pacientai gydėsi Vilniaus miesto ligoninėse ir poliklinikose. Tyrimo metodai. Atliktas epidemiologinis tyrimas pritaikant anoniminės apklausos metodą. Analizuoti sergančiųjų 2 tipo cukriniu diabetu pacientų gyvenimo kokybės skirtumai, atsižvelgiant į tokius veiksnius, kaip lytis, amžius, KMI, socialinius veiksnius, diabeto trukmę, ligos kontrolę, diabeto gydymą, šeimos sergamumą cukriniu... [toliau žr. visą tekstą] / SUMMARY Vilnius University Faculty of Medicine Institute of Rehabilitation, Sport Medicine and Nursing Master’s degree Nursing Programme EVALUATION OF LIFE QUALITY OF PATIENS WITH TYPE 2 DIABETES Master’s degree final scientific research work Author of the master’s degree scientific research work: Aliona Zaborovskytė Head of the master’s degree scientific research work: prof. Danutė Kalibatienė Vilnius, 2008 Keywords: type 2 diabetes, quality of life, SF-36 questionnaire. The aim of research was to evaluate quality of life patients who has type 2 diabetes. The main tasks were to analyse and compare differences of quality of life patients with type 2 diabetes, considering their gender, age and the body mass index. To evaluate quality of life patients with type 2 diabetes considering social factors. To evaluate quality of life of patients with type 2 diabetes considering complications of diabetes. Population of research. This study focused on 196 subjects with Type 2 Diabetes between the age of 41 and 77 years-old (average 60,5 ± 8,1 year). They were recruited from Vilniaus hospitals and an Out patient Clinic. The distribution consisted of 67 males and 129 females. Methods. There was used epidemiologic research of prevalence method. A questionnaire was administered to determine and access specific demographic characteristics including the type and duration of onset of diabetes, prescribed treatments, complications, social factors and other relevant data. Short-Form Health... [to full text]

Orientador: Leticia Helena Theodoro / Coorientador: Valdir Gouveia Garcia / Banca: Renato Corrêa Viana Casarin / Banca: Raquel Mantuaneli Scarel Caminaga / Resumo: Introdução: Diabetes melito e periodontite crônica são doenças crônicas comuns que apresentam uma relação bidirecional entre si. A terapia fotodinâmica antimicrobiana (aPDT) apresenta-se como uma terapia que promove redução bacteriana e pode aumentar os benefícios da terapia periodontal. O objetivo deste estudo foi comparar, por meio de análise clínica, o uso de múltiplas aplicações da aPDT como terapia coadjuvante ao tratamento periodontal não cirúrgico no tratamento da periodontite em pacientes diabéticos tipo 2. Métodos: Trinta e quatro pacientes diabéticos tipo 2 descompensados portadores de periodontite crônica foram selecionados e randomicamente divididos em dois grupos: Grupo RAR (n=17): pacientes que receberam raspagem e alisamento radicular (RAR) em sessão única. Grupo RAR+aPDT (n=17): pacientes que receberam RAR em sessão única seguido de 3 aplicações de aPDT (0h, 48h e 96h) após o término da RAR nas bolsas moderadas e profundas. Os exames clínicos foram realizados no início (baseline), 90 e 180 dias após o tratamento. Foram avaliados os parâmetros clínicos de profundidade de sondagem (PS), nível de inserção clínica (NIC), recessão gengival (RG), sangramento à sondagem (SS) e índice de placa vísivel (IPV) de boca toda. Os dados foram submetidos à análise estatística. Resultados: Aos 90 e 180 dias foi verificada melhora significativa em PS e SS em ambos os grupos (p<0,05). No grupo RAR+aPDT, houve redução estatisticamente significante do número de bolsas com PS≥5mm e... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Background: Diabetes mellitus and chronic periodontitis are common chronic diseases that have a two-way relationship with each other. The antimicrobial photodynamic therapy (aPDT) presents itself as a therapy, which promotes bacterial reduction and can increase the benefits of periodontal therapy. The aim of this study was to compare, through clinical analysis, the use of multiple applications of the aPDT as adjunct therapy to non-surgical periodontal treatment in the treatment of periodontitis in diabetic type 2 patients. Methods: Thirty-four patients with decompensated diabetic type 2 and chronic periodontitis were selected and randomly divided into two groups: SRP Group (n=17): patients who received scaling and root planing (SRP); SRP+aPDT Group (n=17): patients who received SRP and aPDT (0h, 48h and 96h) in moderated and deep pockets. Clinical parameters analyzed were probing depth (PD), clinical attachment level (CAL), gingival resection (GR), bleeding on probing (BOP) and plaque index (PI) at baseline, 90 and 180 days after treatment. The data were statistically analyzed. Results: There was a significant reduction in PD and BOP of the full mouth at 90 and 180 days after treatment in both groups (p<0.05). SRP+aPDT group presented a significant reduction of number of residual pockets at 90 and 180 days (p<0.05). Both groups reduced number of moderated pockets, mean of PD of moderated pockets at two periods and mean of PS in deep pockets at 90 days (p<0.05). Only SRP+aPDT ... (Complete abstract click electronic access below) / Mestre

Está bem estabelecido que fatores genéticos têm um papel importante no desenvolvimento do diabetes mellitus tipo 2 (DM2) bem como de suas complicações crônicas e que indivíduos geneticamente suscetíveis podem desenvolver essa doença após exposição a fatores de risco ambientais. Sendo assim, grandes esforços têm sido feitos para se identificar os genes associados com DM2 e suas complicações crônicas. As proteínas desacopladoras 1 a 3 (UCP1-3) são membros de uma superfamília de proteínas localizadas na membrana mitocondrial interna. A UCP1 é expressa principalmente no tecido adiposo marrom, a UCP2 é amplamente distribuída em diversos tecidos, enquanto a UCP3 é basicamente restrita ao músculo esquelético. Essas proteínas desacoplam a oxidação dos substratos da síntese de ATP pela ATP-sintase, dissipando o potencial de membrana e, consequentemente, diminuindo a produção de ATP pela cadeia respiratória mitocondrial. A dissipação de energia pelas UCPs está associada a diversas funções: produção de calor (UCP1), regulação do metabolismo e transporte de ácidos graxos livres (UCP2 e UCP3), diminuição da formação de espécies reativas de oxigênio (EROs) (UCP1-3) e regulação negativa da secreção de insulina (UCP2), mecanismos envolvidos na patogênese do DM2 e/ou de suas complicações crônicas. Dessa forma, polimorfismos nos genes UCP1-3 podem estar envolvidos no desenvolvimento destas doenças. A relação entre polimorfismos nos genes UCP1-3 e suscetibilidade ao DM2 tem sido investigada em diversas populações. No entanto, o impacto desses polimorfismos no DM2 ainda está em debate, com resultados contraditórios sendo relatados. Sendo assim, realizou-se um estudo de caso-controle na nossa população, seguido de uma revisão sistemática e metanálise dos estudos disponíveis na literatura para se avaliar se os seguintes polimorfismos estavam associados com suscetibilidade ao DM2: -3826A/G (UCP1); -866G/A, Ala55Val e Ins/Del (UCP2) e -55C/T (UCP3). Cabe ressaltar que os resultados do nosso estudo caso-controle foram incluídos na metanálise. No estudo de caso-controle, em indivíduos brancos, não encontramos nenhuma associação dos polimorfismos analisados com suscetibilidade ao DM2. Nossos resultados da meta-análise demonstraram que os polimorfismos -3826A/G (UCP1; rs1800592), -866G/A (UCP2; rs659366) e Ins/Del (UCP2), não estão associados com DM2. Por outro lado, o alelo Ala do polimorfismo Ala55Val (rs660339) no gene UCP2 e o alelo C do polimorfismo -55C/T (rs1800849) no gene UCP3 foram associados com risco para o DM2 em asiáticos, mas não em europeus. Está bem definido que as UCP1-3 diminuem a formação de EROs pela mitocôndria e que a superprodução de EROs é um dos principais fatores envolvidos na patogênese das complicações crônicas diabéticas. Entre as UCPs, a UCP2 é a mais expressa na retina e rins; portanto, polimorfismos neste gene podem estar envolvidos na patogênese dessas complicações. Recentemente, nós relatamos que o haplótipo mutado - 866A/55Val/Ins no gene UCP2 foi associado com risco aumentado para retinopatia diabética proliferativa em pacientes diabéticos tipo 1 e 2. Posteriormente, também demonstramos que portadores deste haplótipo mutado tinham uma expressão diminuída de UCP2 na retina humana de doadores de córnea em comparação aos homozigotos para o haplótipo de referência (-886G/55Ala/Del). No presente estudo, nós investigamos se os polimorfismos -866G/A, Ala55Val e Ins/Del (UCP2) estavam associados com doença renal do diabético (DRD) em pacientes com DM2 (delineamento caso-controle) e também se existia algum efeito destes polimorfismos sobre a expressão de UCP2 em biópsias de tecido renal humano (delineamento transversal). No estudo de caso-controle foram analisados 287 pacientes com DM2 e DRD (casos) e 281 pacientes com DM2 sem esta complicação e com mais de 10 anos de duração do DM2 (controle). No estudo transversal foram incluídas 42 amostras de biópsia de rim obtidas a partir de indivíduos que sofreram nefrectomia terapêutica. No grupo de pacientes com DM2, a homozigose para o haplótipo - 866A/55Val/Ins foi um fator de risco independente para DRD (RC = 2,136, IC 95% 1,036-4,404). Interessantemente, pacientes com DM2 portadores do haplótipo mutado apresentaram diminuição da taxa de filtração glomerular estimada (TFGe) quando comparados com indivíduos com o haplótipo de referência. Em amostras de biópsias renais, a expressão do gene UCP2 foi significativamente menor em portadores do haplótipo mutado quando comparados com o haplótipo de referência (0,32 ± 1,20 vs. 1,85 ± 1,16 n fold change; p ajustado < 0,000001). Em conclusão, os polimorfismos -3826A/G (UCP1), -866G/A, A55Val e Ins/Del (UCP2) e -55C/T (UCP3) não estão associados com DM2 em indivíduos brancos da nossa população. Entretanto, nossa meta-análise mostrou uma associação significativa entre os polimorfismos A55Val e -55C/T e risco para DM2 em populações asiáticas. Já a presença do haplótipo UCP2 -866A/55Val/Ins foi associada com aumento do risco para DRD e com diminuição da TFGe em pacientes com DM2. Além disso, este haplótipo foi associado com a diminuição da expressão do gene UCP2 em rins humanos. / It is well established that genetic factors play an important role in the development of type 2 diabetes mellitus (T2DM) and its chronic complications, and that genetically susceptible subjects might develop the disease after being exposed to environmental risk factors. Therefore, great efforts have been made to identify genes associated with T2DM and its chronic complications. Uncoupling proteins 1, 2 and 3 (UCP1-3) are members of an anion-carrier protein family located in the mitochondrial inner membrane. UCP1 is mainly expressed in brown adipose tissue, UCP2 is widely distributed in several tissues, whereas UCP3 is mainly restricted to the skeletal muscle. These proteins act by uncoupling the oxidation of substrates from ATP synthesis by ATP-synthase, thereby dissipating the membrane potential and, consequently, decreasing the ATP production by the mitochondrial respiratory chain. This uncoupling effect then leads to different functions, such as thermogenesis (UCP1), regulation of free fatty acids metabolism and transport (UCP2 and UCP3), reduction in reactive oxygen species (ROS) formation (UCP1-3), and negative regulation of insulin secretion (UCP2), mechanisms involved in the pathogenesis of T2DM and/or its chronic complications. Therefore, polymorphisms in UCP1-3 genes might be associated with the development of these diseases. The relationship between UCP1-3 polymorphisms and susceptibility to T2DM has been investigated in several populations. Nevertheless, the impact of these polymorphisms on T2DM is still under debate, with contradictory results being reported. Thus, we performed a case-control study in our population followed by a systematic review and meta-analysis of published studies in order to evaluate whether the following polymorphisms were associated with T2DM susceptibility: -3826A/G (UCP1), -866G/A, Ala55Val and Ins/Del (UCP2) and -55C/T (UCP3). It is worth noting that results obtained in our case-control study were also included in the metaanalysis. In the case-control study, analyzing white subjects, we did not found any association between the analyzed polymorphisms and susceptibility for T2DM. Metaanalysis results showed that the -3826A/G (UCP1; rs1800592), -866G/A (UCP2; rs659366) and Ins/Del (UCP2) polymorphisms were not associated with T2DM. In contrast, the A allele of the Ala55Val polymorphism (UCP2; rs660339) and the C allele of the -55C/T polymorphism (UCP3; rs1800849) were significantly associated with risk to T2DM in Asians but not in Europeans. It is well stablished that UCP1-3 decrease ROS formation by mitochondria, and that ROS overproduction is one of the major contributors to the pathogenesis of chronic diabetic complications. Among UCPs, UCP2 has the higher expression in human retina and kidneys; therefore, polymorphisms in this gene could be involved in the pathogenesis of these complications. Recently, we reported that the -866A/55Val/Ins haplotype in the UCP2 gene was associated with increased risk for proliferative diabetic retinopathy in both type 1 and type 2 diabetic patients. Afterwards, we also demonstrated that mutated haplotype carriers had a decreased UCP2 gene expression in retina from cornea donors when compared to retina from subjects homozygous for the reference haplotype (-886G/55Ala/Del). In the present study, we investigated whether the -866G/A, Ala55Val and Ins/Del polymorphisms (UCP2) were associated with diabetic kidney disease (DKD) in T2DM patients (case-control design), and also if they had any effect on UCP2 gene expression in human kidney tissue biopsies (cross-sectional design). In the case-control study, we analyzed 287 T2DM patients with DKD (cases) and 281 T2DM patients without this complication and with more than 10 years of T2DM duration (controls). In the cross-sectional study, we included 42 kidney biopsy samples obtained from patients who undergone therapeutic nephrectomy. In the T2DM group, homozygosis for the mutated haplotype (-866A/55Val/Ins) was an independent risk factor for DKD (OR = 2.136, 95% CI 1.036-4.404). Interestingly, T2DM patients carrying the mutated haplotype showed decreased estimated glomerular filtration rate (eGFR) when compared to subjects with the reference haplotype. In kidney biopsy samples, UCP2 gene expression was significantly decreased in UCP2 mutated haplotype carriers when compared to reference haplotype (0.32 ± 1.20 vs. 1.85 ± 1.16 n fold; adjusted P < 0.000001). In conclusion, -3826A/G (UCP1), -866G/A, A55Val and Ins/Del (UCP2) and - 55C/T (UCP3) polymorphisms are not associated with T2DM in white subjects from our population. However, our meta-analysis showed a significant association between Ala55Val and -55C/T polymorphisms and risk for T2DM in Asians but not in Europeans. The presence of the UCP2 -866A/55Val/Ins haplotype seems to be associated with risk for DKD and with a decreased eGFR in T2DM patients. Moreover, this mutated haplotype was associated with decreased UCP2 gene expression in human kidneys.