Influencia del polimorfismo del receptor de andrógenos en la masa grasa corporal y la respuesta lipolítica al ejercicio

Programa de doctorado: Actividad Física, Salud y Rendimiento Deportivo Premio Extraordinario de Doctorado en la rama de Ciencias Sociales y Jurídicas, 2011-2012

Prevalencia del déficit de vitamina B12 en mayores de 60 años hospitalizados. Estudio del polimorfismo C677T de la enzima 5-10 MTHFR en pacientes con déficit de vitamina B12

Programa de doctorado: Avances en Medicina Interna.

Valutazione dell'impatto della farmacogenetica in ambito di Sanità Pubblica. Analisi del polimorfismo genetico dell'enzima CYP2D6 metabolizzante xenobiotici.

Pharmacogenetic testing provides an outstanding opportunity to improve prescribing safety and efficacy. In Public health policy pharmacogenetics is relevant for personalized therapy and to maximize therapeutic benefit minimizing adverse events. CYP2D6 is known to be a key enzyme responsible for the biotransformation of about 25-30% of extensively used drugs and genetic variations in genes coding for drug-metabolizing enzymes might lead to adverse drug reactions, toxicity or therapeutic failure of pharmacotherapy. Significant interethnic differences in CYP2D6 allele distribution are well established, but immigration is reshaping the genetic background due to interethnic admixture which introduces variations in individual ancestry resulting in distinct level of population structure. The present thesis deals with the genetic determination of the CYP2D6 alleles actually present in the Emilia-Romagna resident population providing insights into the admixture process. A random sample of 122 natives and 175 immigrants from Africa, Asia and South America where characterized considering the present scenario of migration and back migration events. The results are consistent with the known interethnic genetic variation, but introduction of ethnic specific variants by immigrants predicts a heterogeneous admixed population scenario requiring, for drugs prescription and pharmacogenetics studies, an interdisciplinary approach applied in a properly biogeographical and anthropological frame. To translate pharmacogenetics knowledge into clinical practice requires appropriated public health policies, possibly guiding clinicians to evaluate prospectively which patients have the greatest probability of expressing a variant genotype.

Relação do polimorfismo BDNF val66met e níveis periféricos de BDNF com a doença de Parkinson e sua sintomatologia

Neurodegenerative diseases are frequently studied due to the increasing number of cases associated with the populational ageing and to the impact on the conditions on the quality of life. Parkinson’s disease (DP) is the second most frequent neurodegenerative disease. Despite the fact that its etiology is not completely understood, it is known that DP is caused by environmental and genetic factors. Thus, the investigation of etiologic factors and mechanisms responsible for the changes that lead to DP may help early diagnostic and prevention. A possible association between DP and the common polymorphism of Brain Derived Neurotrophic Factor (BDNF) G196A (Val66Met) has been suggested by different studies with contrasting results. For this reason, the aim of this study is to investigate if the BDNF Val66Met polymorphism is related to susceptibility to DP in a cohort of Brazilian patients. Additionaly, we verify if the presence of the polymorphism implies in alterations in the BDNF whole blood concentrations, as well as variations in symptomatology. The sample comprised Brazilian patients accompanied by the neurology service of the Onofre Lopes University Hospital (HUOL) and healthy controls (CTRL). The motor aspects of DP were evaluated by Hoehn e Yahr Scale (HY), Unified Parkinson’s Disease Rating Scale (UPDRS) and Schwab & England Scale (SE). For the evaluation of non-motor symptoms were used the following instruments: Frontal Assessment Battery (BAF), Mini-Mental State Examination (MEEM), Beck Depression Inventory (IDB) and the Beck Anxiety Inventory (IAB). Blood samples were collected for BDNF Val66Met polymorphism genotyping and BDNF whole blood measurement. As expected, DP patients performed worse in motor, cognitive and emotional battery of questionnaires. Alleles distribution between DP and CTRL was not significantly different, but the A/G genotype was significantly associated with a protector factor for DP. In contrast, the G/G genotype was significantly associated with depression and anxiety development in DP patients. However, BDNF concentrations were not different between genotypes or groups. This is the first study of genetic association of this polymorphism with DP in Brazilian subjects and the first one that associate A/G genotype with protection against DP.

Il polimorfismo del paracetamolo: indagine mediante spettroscopia Raman e metodi computazionali

Lo studio del polimorfismo gioca un ruolo fondamentale in diversi ambiti di ricerca, con applicazioni importanti nel campo dei semi conduttori organici e dei farmaci, dovuto al fatto che i diversi polimorfi di una sostanza presentano proprietà chimico-fisiche distinte. Questo lavoro di tesi si è focalizzato sullo studio del polimorfismo del paracetamolo, principio attivo (API) di diversi farmaci molto utilizzati, attraverso l’utilizzo della microscopia Raman. La microscopia Raman è una tecnica efficace per l’indagine del polimorfismo di materiali organici ed inorganici, in quanto permette di monitorare la presenza di diverse fasi solide e le loro trasformazioni su scala micrometrica. Le differenze di struttura cristallina che caratterizzano i polimorfi vengono analizzate attraverso gli spettri Raman nella regione dei modi reticolari (10-150 cm^{-1}), le cui frequenze sondano le interazioni inter-molecolari, molto sensibili anche a lievi differenze di impaccamento molecolare. Con questa tecnica abbiamo caratterizzato le forme I, II, III (quella elusiva) e diverse miscele di fase di paracetamolo su campioni ottenuti con numerose tecniche di crescita dei cristalli. Per questa tesi è stato svolto anche uno studio computazionale, attraverso metodi Density Functional Theory (DFT) per la molecola isolata e metodi di minimizzazione dell’energia e di dinamica reticolare per i sistemi cristallini. Abbiamo inoltre verificato se il modello di potenziale di letteratura scelto (Dreiding [Mayo1990]) fosse adatto per descrivere la molecola di paracetamolo, le strutture dei suoi polimorfi e i relativi spettri vibrazionali.

Influencia del polimorfismo del receptor de andrógenos en la masa ósea, masa muscular y condición física en niños y niñas

Programa de doctorado: Actividad Física, Salud y Rendimiento Deportivo

Importância do polimorfismo OGG1 Ser326Cys no estudo dos efeitos para a saúde que resultam da exposição ocupacional a genotóxicos: o caso da exposição a antioneoplásicos

O ensaio cometa é um dos ensaios de avaliação de genotoxicidade mais promissores de avaliação do risco humano, sendo recomendado para a monitorização de populações com exposição crónica a agentes genotóxicos. Os laboratórios são ambientes profissionais em que os trabalhadores podem encontrar-se expostos a agentes químicos. As drogas antineoplásicas são agentes químicos que são considerados carcinogénicos e, desta forma, medidas de protecção especiais devem ser adoptadas. O objectivo desta comunicação é contribuir para o desenvolvimento de um programa de biomonitorização que inclui a avaliação de genotoxicidade relacionada com biomarcadores de susceptibilidade genética.

Asociación del polimorfismo de IL1b +3954 en partos pretérmino y productos de bajo peso al nacer en mujeres con enfermedad periodontal

Objetivo: En este trabajo se analizó la posible asociación en pacientes que tienen parto pretéremino y productos de bajo peso al nacer con la predisposición del polimorfismo genético 3954 de IL 1B en pacientes con enfermedad periodontal. Metodología: Las pacientes incluidas en el estudio se valoraron clínicamente para incluirlas en el grupo control (sin enfermedad periodontal) o en el grupo experimental (con enfermedad periodontal). La detección del polimorfismo se realice mediante PCR en tiempo final. Se determine como parto pretérmino a aquellos partos antes de las 37 semanas y productos de bajo peso aquellos < 2500kg. Resultados: Se incluyeron 10 pacientes en el grupo control y 11 en el grupo observacional. El 100% de los pacientes que integraron el grupo control presentaron un parto a término normal (40 semanas). Mientras tanto dentro del grupo experimental se encontró el 30% de pacientes con parto pretérmino (

Polimorfismo do alelo HLA-B27 no desenvolvimento das espondilartropatias

A associação da molécula HLA-B27 com a espondilite anquilosante (AS) e outras espondilartropatias (SpA), permanece como uma das mais fortes verificada entre moléculas HLA e doenças humanas. Desde que foi descrita, em 1973, tem sido alvo de intensa investigação na tentativa de compreender o mecanismo patogénico que lhe está subjacente. Este artigo tem como objectivo fazer uma revisão dos conhecimentos actuais relativos à estrutura e polimorfismo da molécula HLA-B27, bem como descrever os modelos propostos para explicar o seu papel no desenvolvimento das espondilartropatias.

Quality evaluation of DNA obtained from stored human saliva and its applicability to identification in Forensic Dentistry

PURPOSE: This study evaluated the quality of DNA obtained from stored human saliva and its applicability to human identification. METHODS: The saliva samples of 20 subjects, collected in the form of saliva in natura and from mouth swabs and stored at -20ºC, were analyzed. After 7 days, the DNA was extracted from the 40 saliva samples and subjected to PCR and electrophoresis. After 180 days, the technique was repeated with the 20 swab samples. RESULTS: The first-stage results indicated that DNA was successfully extracted in 97.5% of reactions, 95% of saliva in natura and 100% of swab saliva samples, with no statistically significant difference between the forms of saliva. In the second phase, the result was positive for all 20 analyzed samples (100%). Subsequently, in order to analyze the quality of the DNA obtained from human saliva, the SIX3-2 gene was tested on the 20 mouth swab samples, and the PCR products were digested using the MbO1 restriction enzyme to evaluate polymorphisms in the ADRA-2 gene, with positive results for most samples. CONCLUSION: It was concluded that the quantity and quality of DNA from saliva and the techniques employed are adequate for forensic analysis of DNA.

Population genetic structuring in pacu (Piaractus mesopotamicus) across the Paraná-Paraguay basin: evidence from microsatellites

The Paraná-Paraguay basin encompasses central western Brazil, northeastern Paraguay, eastern Bolivia and northern Argentina. The Pantanal is a flooded plain with marked dry and rainy seasons that, due to its soil characteristics and low declivity, has a great water holding capacity supporting abundant fish fauna. Piaractus mesopotamicus, or pacu, endemic of the Paraná-Paraguay basin, is a migratory species economically important in fisheries and ecologically as a potential seed disperser. In this paper we employ eight microsatellite loci to assess the population structure of 120 pacu sampled inside and outside the Pantanal of Mato Grosso. Our main objective was to test the null hypothesis of panmixia and to verify if there was a different structuring pattern between the Pantanal were there were no physical barriers to fish movement and the heavily impounded Paraná and Paranapanema rivers. All loci had moderate to high levels of polymorphism, the number of alleles varied from three to 18. The average observed heterozygosity varied from 0.068 to 0.911. After the Bonferroni correction three loci remained significant for deviations from Hardy-Weinberg, and for those the frequency of null alleles was estimated. F ST and R ST pairwise comparisons detected low divergence among sampling sites, and differentiation was significant only between Paranapanema and Cuiabá and Paranapanema and Taquari. No correlation between genetic distance and the natural logarithm of the geographic distance was detected. Results indicate that for conservation purposes and for restoration programs small genetic differences detected in the Cuiabá and Paranapanema rivers should be taken in consideration.