Background: Type 2 diabetes is one of the most common diseases in Sweden. Living with type 2 diabetes affects the person’s daily life and life situation. Treatment of type 2 diabetes consists of the patients making lifestyle changes and self-care. Nurses have expressed a need for knowledge regarding how to support and educate patients with type 2 diabetes, in their self-care. Aim: To describe adult’s experiences of living with type 2 diabetes. Method: A qualitative literature study with descriptive approach. Results: The analysis resulted in two themes. The themes were loss of control over daily life, regain stability and hope in life. The persons experienced lack of knowledge about their disease, furthermore, they felt anxiety and anger. The persons experienced that they had difficulties adjusting their diet. After a certain period of illness, the people accepted and managed the disease and got support both from their families and from health care professionals. Conclusion: The care and education that patients with diabetes type 2 are offered need to be more individualized. This can ensure and help the patients with type 2 diabetes perform adequate self-care by their own preconditions, to maintain health and well-being.

Memoria para optar al Título Profesional de Médico Veterinario / La Hem Oxigenasa 1 (HO-1) es una enzima de expresión inducible que degrada el grupo hem liberando hierro libre (Fe), biliverdina y monóxido de carbono (CO). El Fe es potencialmente tóxico, pues cataliza la formación de radicales libres. La diabetes mellitus tipo 2 (DM-2) es una condición inflamatoria que entre otros factores se asocia al daño oxidativo causado por anormalidades en el metabolismo del Fe. El objetivo de este trabajo es determinar la actividad de la HO y el polimorfismo de microsatélite en el promotor del gen de la HO-1 y relacionarlos con el metabolismo del Fe en sujetos diabéticos tipo 2, con insulino resistencia y controles. Se recolectaron muestras sanguíneas de 216 pacientes: 99 diabéticos tipo 2, 50 insulino resistentes y 67 controles, a los cuales se les realizó ensayos de actividad enzimática y de polimorfismo en el promotor del gen de la HO-1, además de establecer parámetros hematológicos, bioquímicos y antropométricos. La distribución de los genotipos entre las distintas condiciones (diabético, insulino resistente y control) presentó diferencias estadísticamente significativas (2υ7=18.05; p<0,05), el genotipo más frecuente en los diabéticos fue el CM. La actividad de la HO en el grupo de diabéticos, fue mayor que la exhibida por los grupos insulino resistente y control (p≤0,05). Los depósitos de Fe (en la forma de Ferritina), en el grupo de diabéticos fue mayor que el grupo control (p≤0,05). Se observó una relación estadísticamente significativa entre la actividad de la HO con el nivel de Fe sérico sólo en el grupo de diabéticos (p<0,0001). Estos resultados sugieren que una mayor actividad de la enzima HO junto a mayores niveles de Fe, favorecerían un mayor deterioro orgánico en el paciente con DM-2. Palabras clave: Hem oxigenasa 1, Hierro, Polimorfismo, Diabetes mellitus tipo 2 / Proyecto FONDECYT 1051006

Tesis Magister En Ciencias Odontológicas Con Mención En Patología Y Medicina Oral / Introducción: El fluido crevicular gingival (FCG) representa una potencial fuente de biomarcadores de enfermedades inflamatorias crónicas que afectan a los tejidos periodontales. Estas patologías constituyen las principales causas de pérdida dentaria en adultos. El objetivo del presente estudio fue evaluar niveles y precisión diagnóstica de un set de marcadores de metabolismo óseo en FCG de sujetos con periodontitis marginal crónica (PC) y de sujetos con periodontitis apical asintomática (PAA). Método: En el presente estudio analítico transversal, los sujetos fueron seleccionados desde la Facultad de Odontología de la Universidad de Chile. Las muestras de FCG se obtuvieron de sitios de dientes de sujetos con diagnóstico de PC (n=30), PAA (n=30) y controles sanos (n=30). La concentración de proteínas totales (CPT) fue determinada con el método del ácido bisciconínico. La actividad gelatinolítica de las metaloptoteinasas de la matriz (MMP) -2 y -9 fue determinada con zimografía y análisis densitométrico. Niveles de MMP-8 fueron determinados mediante ELISA e IFMA, mientras que marcadores óseos directos (DKK-1, osteonectina, periostina, TRAP y OPG), por el método cuantitativo multiplex. Para las comparaciones entre los grupos se realizó la prueba de Kruskal-Wallis utilizando el paquete estadístico Stata V12 y para la evaluación de precisión diagnóstica se realizó la construcción de curvas ROC y el cálculo del área bajo la curva utilizando el programa estadístico SPSS19. Se consideró significación estadística con un valor p<0,05. Resultados: La proenzima, forma activa, tasa de activación de MMP-9 y nivel de MMP- 8 (ELISA e IFMA) fueron significativamente mayores en sitios de individuos con PC, seguidos por PAA, en comparación con individuos sanos, con diferencias estadísticamente significativas entre todos los grupos (p<0,05). La CPT, ProMMP-2, TRAP y OPG fueron significativamente mayores en los sitios de sujetos con PC en comparación con PAA y sanos (p<0,05). Al asociar los niveles moleculares de los marcadores con variables clínico-radiográficas en sujetos con PC, se observó una correlación directa estadísticamente significativa entre los niveles de Pro-MMP-2, MMP-9 activa, porcentaje de activación de MMP-9 y TRAP con profundidad al sondaje (PS) y nivel de inserción clínica (NIC) (p≤ 0,01), de MMP-8 con PS (p≤ 0,01) y de ON con NIC (p< 0,05). Se observó además una correlación indirecta estadísticamente significativa entre TRAP y nivel óseo radiográfico (NOR) (p<0,05). El análisis de precisión diagnóstica de los marcadores reveló que CPT, ProMMP-2, ProMMP-9, MMP-9 activa, MMP-8 (ELISA), y TRAP presentaron un muy alto rendimiento en sitios de sujetos con PC, con áreas bajo la curva mayores a 0,9 y con valores de sensibilidad que fluctuaron entre un 77,42% y 96,77%, y de especificidad entre 80,65% y 100%. A su vez, en sitios de sujetos con PAA, MMP-8 (ELISA) presentó una alta precisión diagnóstica con un área bajo la curva de 0,869, valores de sensibilidad de 92%, y de especificidad de 75,86%. Conclusión: El FCG evidencia cambios en su composición en presencia de procesos inflamatorios crónicos del periodonto, tanto a nivel marginal como apical del diente, a su vez estos cambios se asocian con signos clínicos y radiográficos de destrucción periodontal. La determinación de marcadores moleculares en FCG podría constituir una herramienta útil como potencial método complementario al diagnóstico clínico- radiográfico de periodontitis crónica y periodontitis apical asintomática.

A research report submitted to the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, in partial fulfilment of the requirements for the degree of Master of Medicine in the branch of Anaesthesiology / Background and Objective There has been a recent resurgence of interest in vitamin D and its far-reaching effects in physiology and pathophysiology. Theatre personnel, and all indoor workers, should be cognisant of vitamin D deficiency as a real occupational hazard. Vitamin D deficiency is a global problem that has been studied extensively in colder climates and even been found in warmer climates. No research was identified among medical personnel in South Africa. The primary objective of this study was to describe serum 25-hydroxyvitamin D (25(OH)D) levels of anaesthetists. The secondary objective was to describe and compare factors influencing vitamin D levels in anaesthetists who are vitamin D insufficient to those who are not. These factors included: ethnicity, gender, body mass index (BMI), multivitamin use, calcium or vitamin D supplementation, sun exposure, vitamin D intake from diet alone, vitamin D intake from diet and supplementation and calcium intake (dairy). Methods Data was collected over a period of one month, in winter (mid-July to mid-August 2013). On the morning of sample collection anaesthetists agreeing to participate signed the informed consent (Appendix 2), prior to enrolment in the study. The anaesthetists then completed the questionnaire (Appendix 5). The following data was obtained from the questionnaire: age, gender, ethnic group, dietary supplementation, sun exposure, sunscreen use, BMI and diet. Each participant had 5 ml of blood collected in a standardised manner into a purple top ethylenediaminetetraacetic acid blood specimen tube. The processing of samples was done by qualified laboratory personnel using standard chemical pathology equipment and procedures. High Performance Liquid Chromatography was performed to determine 25(OH)D levels using a Shimadzu® Nexera X2 Ultra performance liquid chromatography system with a photodiode array detector (Shimadzu®, Japan). Results The median 25(OH)D was 43.8 nmol/l (IQR 26-76), with 51 of 89 (57.30 %) anaesthetists being vitamin D insufficient. There was a statistically significant association between ethnicity and vitamin D status (p<0.001). Twenty-one (80.77 %) Indian anaesthetists and 14 (70.00 %) black anaesthetists were vitamin D insufficient, as compared to only 10 (28.57%) white anaesthetists. There was no significant association between the other secondary objectives-gender (p=0.60), sun exposure (p = 0.93), vitamin D intake from diet alone (p= 0.07), vitamin D intake from diet and supplementation (p=0.05) and calcium intake (p=0.55) and vitamin D status. There was no significant difference between BMI and vitamin D status. When a comparison was made between the two groups of BMI <25 and BMI ≥25, using a Mann-Whitney test the two-tailed P value was 0.6791. There was a significant association between multivitamin use (p=0.01) and vitamin D status. Conclusion Vitamin D should no longer be a forgotten vitamin. The insufficient vitamin D levels of anaesthetist in this study, puts them at risk for pathology far beyond bone health. Adequate vitamin D levels should be seen as essential, rather than optional, even in “sunny” climates. / MT2016

Background: Sputum culture conversion at two months is an important indicator for the effectiveness of treatment and the infectivity of a patient with pulmonary TB. This study aimed at investigating factors that are associated with tuberculosis culture conversion at two months as well as investigating whether sputum culture conversion at two months is a reliable predictor of relapse. Methods: The study makes use of data obtained from 347 newly diagnosed tuberculosis patients who participated in a randomized placebo controlled immunotherapy trial at King George V hospital in Durban. Above objectives were met by carrying out statistical analysis of the secondary data. Chi-square tests for categorical explanatory variables such as HIV status and smoking status and (b) t-tests for continuous variables such as age were used for investigating factors associated with 2-month culture conversion. Multivariate models were used to find the most important variables for predicting 2-month culture conversion. Kaplan Meier curves were used for investigating whether culture conversion at two months is a reliable predictor of relapse. Findings: Of the 347 tuberculosis patients, 34 % were HIV sero-positive. Age, body mass index (BMI), smoking status and gender were found to be important variables that affect sputum culture conversion at two months. At 5 % significance level there was no evidence that those who culture convert at two months were less likely to relapse than those who had not culture converted at two months (p=0.1165). However the trend shown is striking to report as it may be of clinical significance. Among those who had not culture converted at two months, more people (40) than expected (34) relapsed an among those who had culture converted at to months, less people (19) than expected (24) relapsed. Interpretation and recommendations: Some behavioral and biological factors affect two month tuberculosis culture conversion therefore successful tuberculosis management need to take into account the effect of these factors. This study did not show that the sterilizing potential of an anti-tuberculosis regimen can be obtained by evaluation of the culture conversion rates at two months and this may be due to small sample size.

ABSTRACT Background: A prerequisite for diabetes complications to be prevented or at least delayed is that the person with type 2-diabetes has a well-controlled blood sugar. Self-monitoring blood glucose is part of self-management, therefore it is important to find out how this is experienced by people with type 2-diabetes so that the diabetes-nurse can provide the support the person needs. Purpose: The aim of this study was to describe experiences of self-monitoring blood glucose for persons with type 2-diabetes. Method: The study was performed with descriptive qualitative method. To gain access to the material, semi-structured interviews were conducted in two focus groups. A group of women (67-87 years) and a group of men (40-80 years). Qualitative content analysis was used to analyze the transcribed material. Results: After processing and analysis, the categories emotions and knowledge and support emerged. The parent theme was identified as "knowing but not doing". To the category of emotions was found the subcategories of shame and bad conscience, fear of high and low values, discomfort and disgust, confirmation and control, and affinity with others. To the category of knowledge and support, three subcategories were identified, self-monitoring blood glucose and technology, as well as support, help and education. Conclusion: In summary, it can be said that people with type 2 diabetes experiences and experiences of measuring their blood sugar show that it is associated with both positive and negative emotions and a need for continuous support from the diabetes nurse. The results of the study are supported by previous research in the field. Keywords: self-monitoring blood glucose, self-measuring blood glucose, type 2-diabetes, self-management / SAMMANFATTNING Bakgrund: En förutsättning för att diabeteskomplikationer ska kunna förhindras eller i alla fall fördröjas, är att personen med typ 2-diabetes har ett välkontrollerat blodsocker. Blodsockermätning är en del av egenvården, därför är det betydelsefullt att ta reda på hur detta moment upplevs av personer med typ 2-diabetes så att diabetessjuksköterskan kan ge det stöd personen behöver. Syfte: Syftet med studien var att beskriva upplevelser och erfarenheter av att mäta blodsocker för personer med typ 2-diabetes. Metod: Studien utfördes med beskrivande kvalitativ metod. För att få tillgång till materialet genomfördes halvstrukturerade intervjuer i två fokusgrupper. En grupp med kvinnor (67-87 år) och en grupp med män (40-80 år). Kvalitativ innehållsanalys användes vid analys av det transkriberade materialet. Resultat: Efter bearbetning och analys framträdde kategorierna känslor samt kunskap och stöd. Det överordnade temat identifierades som ”att veta men inte göra”. Till kategorin känslor hittades subkategorierna skam och dåligt samvete, rädsla för höga och låga värden, obehag, olust och äckel, bekräftelse och kontroll samt samhörighet med andra. Till kategorin kunskap och stöd identifierades de tre subkategorierna samsyn, blodsockermätning och teknik samt stöd, hjälp och utbildning. Slutsats: I studien framkom att både upplevelser och erfarenheter av att mäta blodsockret påverkar om personer med typ 2-diabetes genomför mätningar i den utsträckning som rekommenderas. Därför är det betydelsefullt att diabetessjuksköterskan arbetar personcentrerat för att kunna ge det stöd till egenvård som personen vill ha.   Nyckelord: Blodsockermätning, typ 2-diabetes, egenvård

O sistema da procineticina desempenha um papel importante na migração dos neurônios secretores de GnRH e na neurogênese do bulbo olfatório. Camundongos com ablação dos genes que codificam a procineticina 2 (PROK2) e seu receptor (PROKR2) apresentaram fenótipos semelhantes ao da síndrome de Kallmann descrita em humanos. Mutações inativadoras nos genes PROK2 e PROKR2 foram identificadas em pacientes com hipogonadismo hipogonadotrófico isolado. Com base nestes achados, investigamos a presença de alterações estruturais nos genes PROK2 e PROKR2 em 107 pacientes brasileiros (63 com síndrome de Kallmann e 47 com hipogonadismo hipogonadotrófico isolado normósmico). Cem indivíduos brasileiros que relataram desenvolvimento puberal normal foram utilizados como grupo controle. As regiões codificadoras dos genes PROK2 e PROKR2 foram amplificadas utilizando-se oligonucleotídeos intrônicos específicos, seguida de purificação enzimática e sequenciamento automático. Duas mutações no gene PROK2 foram identificadas: a mutação p.G100fsX121 em homozigose presente em dois irmãos com síndrome de Kallmann; e a mutação p.I55fsX56 em heterozigose identiificada em um paciente com HHIn. Quatro mutações foram identificadas no gene PROKR2 (p.R80C, p.Y140X, p.L173R e p.R268C) em cinco pacientes com síndrome de Kallmann e um paciente com HHIn. Essas mutações não foram encontradas no grupo controle. As mutações do tipo missense, p.R80C, p.L173R e p.R268C foram identificadas em heterozigose. Mutações nos genes FGFR1, GnRHR, KiSS-1 e GPR54 foram excluídas nesses pacientes. O paciente portador da mutação p.R268C do PROKR2 apresentou deleção dos exons 1 e 2 do gene KAL1. Adicionalmente, as mutações p.R80C e p.R268C foram identificadas em heterozigose em parentes de primeiro grau assintomáticos dos casos índices. A nova mutação p.Y140X do PROKR2, única alteração em homozigose, foi identificada em um paciente com micropênis, criptorquidia bilateral, anosmia e palato ogival. Os pais deste paciente eram portadores da mutação p.Y140X em heterozigose e relataram desenvolvimento puberal normal e ausência de anormalidades olfatórias. Estudos in vitro da nova mutação p.R80C localizada na primeira alça intracelular demonstraram que o acúmulo de fofatidil-inositol (IP), assim como a ativação da via da MAPK foram significativamente afetadas em células transfectadas com o receptor mutado em relação ao receptor selvagem, indicando que a mutação p.R80C determina uma menor atividade do receptor. Avaliação da expressão por Western blot mostrou uma diminuição na expressão do receptor mutado R80C e uma maior expressão de receptores imaturos. Esses achados sugeriram o papel crítico da arginina localizada na posição 80 na atividade normal do receptor. Em conclusão, expandimos o repertório de mutações deletérias nos genes PROK2 e PROKR2 em pacientes com hipogonadismo hipogonadotrófico isolado. A haploinsuficiência do PROKR2 não foi suficiente para causar síndrome de Kallmann ou HHIn, entretanto mutações inativadoras em homozigose nos genes PROK2 e PROKR2 foram responsáveis pelo fenótipo reprodutivo e olfatório anormal, em concordância com os estudos prévios de ablação gênica em modelos animais. Arginina localizada na posição 80 do PROKR2 desempenha um papel crucial na adequada maturação do receptor / Physiological activation of the prokineticin pathway has a critical role in olfactory bulb morphogenesis and GnRH secretion. Knock-out mice for genes that encode prokineticin 2 (PROK2) and the prokineticin receptor 2 (PROKR2) exhibited a phenotype similar to the Kallmann syndrome (KS). Inactivating mutations in PROK2 and PROKR2 have been identified in patients with isolated hypogonadotropic hypogonadism. Based on these findings, we investigated the presence of inactivating mutations of the genes PROK2 and PROKR2 in Brazilian patients with isolated hypogonadotropic hypogonadism associated or not with olfactory abnormalities and performed in vitro studies of the new identified mutations. We studied 107 patients with HH (63 with Kallmann syndrome and 44 with normosmic HH) and 100 control individuals. The coding regions of PROK2 and PROKR2 were amplified by polymerase chain reaction followed by enzymatic purification and direct automatic sequencing. In PROK2, two known frameshift mutations were identified. Two brothers with Kallmann syndrome harbored the homozygous p.G100fsX121 mutation, whereas one male with normosmic HH harbored the heterozygous p.I55fsX56 mutation. In PROKR2, four distinct mutations (p.R80C, p.Y140X, p.L173R and p.R268C) were identified in five patients with Kallmann syndrome and in one patient with normosmic HH. These mutations were not found in the control group. The p.R80C and p.R268C missense mutations were identified in heterozygous state in the HH patients and in their asymptomatic first-degree relatives. The p.L173R was also identified in heterozygous state. In addition, no mutations of FGFR1, GnRHR, KiSS-1 or GPR54 were identified in these patients. The patient with the PROKR2 mutation p.R268C also has a deletion of the exon 1 and 2 in the gene KAL1. Notably, the new nonsense mutation (p.Y140X) was identified in homozygous state in an anosmic boy with micropenis, bilateral cryptorchidism and high-arched palate. His asymptomatic parents were heterozygous for this severe defect. In vitro studies of the new mutation, p.R80C, were performed in order to access the mechanism by which this mutation could affect the activity of the PROKR2. In vitro studies showed that the amount of fofatidil-inositol (PI) and the activation of MAPK were significantly lower in cells transfected with the R80C mutant receptor than in cells transfected with the wild receptor, indicating that this variant is a loss-of-function mutation. Binding studies and Western blot showed a reduction in the expression levels of the receptor in the plasma membrane and in whole cell, respectively. Additionally, Western blot analysis of R80C PROKR2 revealed an additional smaller molecular weight band that represents the presence of immature unglycosylated receptors. The arginine 80 in ICL1 is important for post-translational processing of PROKR2. In conclusion, we expanded the repertoire of PROK2 and PROKR2 mutations in patients with HH and showed that PROKR2 haploinsufficiency is not sufficient to cause Kallmann syndrome or normosmic HH, whereas homozygous loss-of-function mutations either in PROK2 or PROKR2 are sufficient to cause disease phenotype, in accordance with the Prokr2 and Prok2 knockout mouse models. In vitro studies suggested that the arginine located at position 80 of the receptor seems to play an important role in the receptor function

O diabetes mellitus (DM) é uma doença metabólica associada a danos, disfunção e insuficiência de diversos órgãos, sendo a fragilidade óssea apontada por estudos recentes como também associada ao DM. Os mecanismos que justificam o maior risco de fraturas em diabéticos tipo 2 não são bem compreendidos. A influência do trato gastrointestinal e seus hormônios no remodelamento ósseo tem sido comprovada em animais e em indivíduos sadios, sendo o Glucagon-like peptide-2 (GLP-2) e a serotonina hormônios com produção intestinal estimulada pela ingestão de nutrientes, existindo algumas evidências de que os mesmos têm efeitos no metabolismo ósseo. O presente estudo comparou a dinâmica dos marcadores ósseos, da serotonina e do GLP-2 em resposta à refeição mista em mulheres pósmenopausadas diabéticas em relação a controles não diabéticas. Foram incluídas 43 mulheres pós-menopausadas com densidade mineral óssea (DMO) reduzida, 23 com diabetes (grupo DM) e 20 controles (grupo CO). Depois do jejum de 12 horas, essas mulheres foram submetidas ao teste de refeição padrão, e as amostras de sangue foram coletadas nos tempos 0, 30, 60, 120 e 180 minutos para a dosagem de telopeptídeo C-terminal do colágeno tipo I sérico (CTX), osteocalcina (OC), GLP-2 e serotonina. O grupo DM apresentou maior índice de massa corporal, bem como maior densidade mineral óssea (DMO) de colo de fêmur e quadril. Nos tempos basais as mulheres diabéticas apresentaram concentrações plasmáticas de LH e FSH, bem como dos marcadores ósseos osteocalcina e CTX menores que no grupo CO. Em resposta a refeição padrão houve, em ambos os grupos, diminuição na concentração do CTX e da osteocalcina, e aumento na de GLP-2, sem alteração significativa da serotonina. A resposta do CTX à refeição foi menor no grupo DM, e a da serotonina maior no grupo CO em um único tempo do teste. Em relação a OC e ao GLP-2, não houve diferença entre os grupos avaliados ao longo do teste de refeição. As mulheres diabéticas tipo 2 tiveram maior DMO de fêmur. Além disso, os resultados sugerem que o remodelamento ósseo das mulheres diabéticas está alterado, com os marcadores ósseos reduzidos. A influência da ingestão de nutrientes na reabsorção óssea também foi alterada pela DM, não se reconhecendo nesse estudo qualquer papel do GLP-2 ou da serotonina na alteração do metabolismo ósseo em mulheres diabéticas tipo 2 / Type 2 diabetes mellitus is metabolic disease associated with long-term damage, dysfunction, and failure of various organs; recent studies indicate that diabetes itself is associated with bone fragility. The mechanisms underlying the increased fracture risk in type 2 diabetes are not well understood. The influence of the gastrointestinal tract and its hormones in bone remodeling has been demonstrated in animals and in healthy subjects. Glucagon-like peptide-2 (GLP-2) and serotonin are enteric hormones stimulated by nutrient intake, and there is some evidence that these hormones could have some effects on bone metabolism. We studied the dynamics of bone markers, serotonin and GLP- 2 in response to a mixed meal in diabetic postmenopausal women, in comparison with nondiabetic controls. 43 post-menopausal women with reduced bone mineral density (BMD) were enrolled, 23 with diabetes (DM group) and 20 normal control (CO group). After an overnight fast (12h), subjects were submitted to a standard meal test. Blood samples were drawn for C-terminal crosslinked telopeptide (CTX), osteocalcin (OC), GLP-2 and serotonin at 0, 30, 60, 120 and 180 minutes. The DM group had higher body mass index, and higher BMD of the femoral neck and hip. The basal values of of LH and FSH as well as the bone markers osteocalcin and CTX were lower in the DM group than in the CO group. After the standard meal test, there was a decrease in the concentration of CTX and osteocalcin, and an increase in GLP-2 in both groups. No changes in concentrations of serotonin were observed over the test meal. The response of the CTX meal was lower in the DM group, and the serotonin concentration was greater in the CO group in a single test time. In relation to e OC and GLP-2, there were no differences among the groups throughout the test meal. Type 2 diabetic women had higher bone mineral density (BMD) in the femur. Furthermore, the results suggest that the bone remodeling of diabetic women is altered, with their biochemical bone markers reduced. The influence of nutrient intake on bone resorption was also altered by DM, but in this study we could not recognize the role of GLP- 2 and serotonin in influencing the bone metabolism in type 2 diabetic

Neste trabalho estudamos loops de Bol 2-nilpotentes e de expoente 2. Além disso, mostramos que o ideal de aumento de uma álgebra de loop, de um loop finito p-nilpotente em característica p > 0, é nilpotente. Com este resultado conseguimos caracterizar os elementos inversíveis da álgebra de loop de um loop 2-nilpotente sobre um corpo de dois elementos. Provamos também que loops de Bol finitos 2-nilpotentes e de expoente 2 podem ser mergulhados em um loop de Bol à direita de elementos inversíveis de uma álgebra alternativa à direita, sobre um corpo de característica dois. / In this work we study 2-nilpotent Bol loops of exponent 2. Besides, we prove that the augmentation ideal of a loop algebra, of a finite p-nilpotent loop in characteristic p > 0, is nilpotent. With this result we characterized the invertible elements of the loop algebra of a 2-nilpotent loop over a field with two elements. We also proof that 2-nilpotent Bol loops of exponent 2 may be embedded into a right Bol loop of invertible elements of a right alternative algebra, over a field of characteristic 2.

Neste trabalho investigamos o efeito de doadores de H2S no prurido agudo mediado por PAR-2 em camundongos. A injeção i.d. do agonista PAR-2 SLIGRL-NH2, induziu prurido que não foi afetado pelo pré-tratamento com o antagonista H1 pirilamina. A coinjeção dos doadores de H2S GYY4137 (lento) ou NaHS (espontâneo) com SLIGRL-NH2 reduziu significativamente o prurido (P<0,05). A glibenclamida (bloqueador de canais KATP) e o SNP (doador de NO), mas não o ODQ (inibidor da sGC), evitaram estes efeitos. O antagonista TRPA1 HC-030031 reduziu significativamente o prurido induzido pelo SLIGRL-NH2 (P<0,05), mas o prurido induzido pelo agonista TPRA1 AITC não foi afetado por NaHS. Ensaios de Western blot mostraram que ambos PAR-2 e TRPA1 são expressos constitutivamente na pele de camundongos. Nossos dados mostram que o prurido secundário à ativação do PAR-2 pode ser reduzido por H2S, atuando via a abertura dos canais KATP e ativação da via NO-GMPc. Ademais, o receptor TRPA1 pode mediar o prurido induzido por SLIGRL-NH2, mas o H2S não interfere nesta via. / In this study we investigated the effect of H2S donors in PAR-2-mediated acute pruritus in mice. The i.d. injection of the PAR-2 agonist SLIGRL-NH2 induced itching that was unaffected by pre-treatment with the H1 antagonist pyrilamine. Co-injection of the H2S donors GYY4137 (slow) or NaHS (spontaneous) with SLIGRL-NH2 significantly reduced pruritis (P <0.05). Glibenclamide (a KATP channel blocker) and SNP (a NO donor), but not ODQ (a sGC inhibitor) prevented these effects. The TRPA1 antagonist HC-030031 significantly reduced SLIGRL-NH2-induced pruritus (P<0.05), but the pruritus induced by the TPRA1 agonist AITC was unaffected by NaHS. Western blot assays showed that both TRPA1 and PAR-2 are constitutively expressed in the mouse skin. Our data show that itching secondary to PAR-2 activation can be reduced by H2S which acts via the opening of KATP channels and activation of the NO-cGMP pathway. Furthermore, TRPA1 receptors may mediate SLIGRL-NH2-induced pruritus, however, H2S does not interfere with this pathway.