Tumor necrosis factor alpha -308 promoter polymorphism and insulin resistance inoverweight and obese adolescent

Study Model/Methodology: This is a cross-sectional study with a sample of 104 overweight/obese adolescents, with a mean weight of 52.98 kg ± 22.00, mean age 16.01 ± 2.91 years. We used the homeostasis model assessment-estimated IR (HOMA-IR) index to quantify the insulin resistance (IR). The -308 polymorphism of the promoter of TNF-α was performed using polymerase chain reactionrestriction fragment length polymorphism technique. Statistical analysis of the quantitative measures was conducted with a student’s t-test. For correlation between the genotype and alleles, we used chisquare statistical test. To test the heterogeneity between HOMA-IR and the anthropometric parameters the Mann-Whitney test was used, associated with the Hardy-Weinberg equilibrium. The association between -308G/A polymorphism of the promoter of TNF-α and HOMA-IR was tested by univariate linear regression analysis. Objective: Investigate the association between -308G/A polymorphism in the promoter of tumor necrosis factor-alpha (TNF-α) and susceptibility to IR in overweight/obese adolescents. Results: The prevalence of IR was 18.30% according to the HOMA-IR. The frequency of GG, AG and AA genotype was found 75 (72.12%), 28 (26.92%) and 1.0 (0.96%) respectively. Allele frequencies for guanine (G) and adenine (A) were 178 (85.58%) and 30 (14.42%), respectively. The allele A as well as GA and AA genotype contributed to increase RI (14.42% and 27.88% respectively). Conclusion: The - 308 G/A polymorphism of the promoter of TNF-α can contribute to the IR increase in obese adolescents with GA and AA genotypes.Modelo de Estudo / Metodologia: Trata-se de um estudo transversal, com uma amostra de 104 adolescentes com sobrepeso/ obesidade, com peso médio de 52,98 kg ± 22,00, média de idade de 16,01 ± 2,91 anos. Utilizamos o índice estimado (HOMA-IR) do modelo de homeostase para quantificar a resistência insulínica (RI). O polimorfismo do promotor -308 do TNF-α foi realizado utilizando a técnica de polimorfismo de comprimento de fragmento de restrição. A análise estatística das medidas quantitativas foi realizada com o teste t student. Para a correlação entre o genótipo e os alelos, utilizamos o teste estatístico qui-quadrado. Para testar a heterogeneidade entre HOMA-IR e os parâmetros antropométricos foi utilizado o teste de Mann-Whitney associado ao equilíbrio de Hardy-Weinberg. A associação entre o polimorfismo -308G/A do promotor do TNF-α e HOMA-IR foi testada por análise de regressão linear univariada. Objetivo: investigar a associação entre o polimorfismo -308G/A no promotor do fator de necrose tumoral alfa (TNF-α) e a susceptibilidade à RI em adolescentes com sobrepeso/ obesidade. Resultados: A prevalência de RI foi de 18,30% de acordo com o HOMA-IR. A frequência dos genótipos GG, AG e AA encontrados foram 75 (72,12%), 28 (26,92%) e 1,0 (0,96%), respectivamente. As frequências de alelos para guanina (G) e adenina (A) foram 178 (85,58%) e 30 (14,42%), respectivamente. O alelo A, bem como o genótipo GA e AA, contribuíram para aumentar o RI (respectivamente 14,42% e 27,88%). Conclusão: O polimorfismo -308 G / A do promotor do TNF-α pode contribuir para o incremento de RI em adolescentes sobrepesos/obesos com genótipos GA e AA

SEQUENCE SIMILARITY BETWEEN THYROID SELF-PROTEIN AND HEPATITIS C VIRUS POLYPROTEIN: possible triggering mechanism of autoimmune thyroiditis

ABSTRACT Background - Exposure to viral antigens that share amino acid sequence similar with self- antigens might trigger autoimmune diseases in genetically predisposed individuals, and the molecular mimicry theory suggests that epitope mimicry between the virus and human proteins can activate autoimmune disease. Objective - The purpose of this study is to explore the possible sequence similarity between the amino acid sequences of thyroid self-protein and hepatitis C virus proteins, using databanks of proteins and immunogenic peptides, to explain autoimmune thyroid disease. Methods - Were performed the comparisons between the amino acid sequence of the hepatitis C virus polyprotein and thyroid self-protein human, available in the database of National Center for Biotechnology Information on Basic Local Alignment Search Tool. Results - The sequence similarity was related each hepatitis C virus genotype to each thyroid antigen. The similarities between the thyroid and the viral peptides ranged from 21.0 % (31 identical residues out of 147 amino acid in the sequence) to 71.0% (5 identical residues out of 7 amino acid in the sequence). Conclusion - Bioinformatics data, suggest a possible pathogenic link between hepatitis C virus and autoimmune thyroid disease. Through of molecular mimicry is observed that sequences similarities between viral polyproteins and self-proteins thyroid could be a mechanism of induction of crossover immune response to self-antigens, with a breakdown of self-tolerance, resulting in autoimmune thyroid disease

Off-label prescriptions in diabetic foot

Prescription of a drug outside of the indications for which it was originally approved by regulators is internationally known as "off-label" prescription. We describe off-label treatments for the diabetic foot reported in international scientific literature. This is a qualitative and descriptive bibliographical review based on the results of a search of the Medline international database. The criteria for review were publication between January 1985 and November 2013, and the MeSH (Medical Subject Heading) keywords "off-label use" OR "off-label" OR "off-label prescribing" plus "diabetic foot" were input on the search form. Nine studies were selected that contained information about off-label treatments for the diabetic foot. We conclude that the practice of off-label prescribing has potential benefits. In some situations an off-label prescription is the only treatment available for patients, either because a more targeted drug does not exist, or because other methods of treatment are ineffective or unavailable due to patient intolerance