IL-10 gene polymorphism c.-592C>A increases HPV infection susceptibility and influences IL-10 levels in HPV infected women.

Interleukin-10 (IL-10) influences HPV infection and viral persistence, favoring cervical immunosuppression and cervical carcinogenesis. IL-10 levels may be influenced by HPV itself and by IL-10 polymorphisms, including rs1800872 (c.-592C>A). Therefore, we evaluated the influence of IL-10 c.-592C>A polymorphism in HPV infection and in IL-10 plasmatic/cervical levels in HPV infected and non-infected women. The study included 174 infected and 186 non-infected patients. Cervical epithelial scrapings were obtained to determine HPV DNA presence PCR. Peripheral blood samples were obtained to determine IL-10 polymorphism by PCR-RFLP, while IL-10 levels were assessed by ELISA. HPV was more prevalent among allele A carriers (p<0.001), with IL-10 c.-592C>A polymorphism being associated with HPV infection. As demonstrated by binary logistic regression analysis, heterozygotes [ORadj=2.081 95% CI (1.222-3.544), p=0.007] and homozygotes [ORadj=3.745 95% CI (1.695-8.271), p=0.001] showed approximately 2 and 4 time's greater odds, respectively, of presenting HPV when compared to CC patients. Moreover, HPV infected patients carrying polymorphic allele A showed higher IL-10 cervical levels (p=0.039). Binary logistic regression analysis demonstrated that IL-10 cervical levels were not independently associated to CA+AA genotypes (p=0.162), neither to HPV's presence (p=0.061), thus IL-10 cervical levels are possibly increased because of both HPV and allele A presence. Taken together, these findings suggest that IL-10 c.-592C>A polymorphism is independently associated with HPV infection susceptibility exerting influence on IL-10 cervical levels in HPV infected women, thus contributing to cervical carcinogenesis.

Avaliação dos níveis séricos das enzimas hepáticas e proteína C reativa em indivíduos com sobrepeso com e sem Síndrome Metabólica / Evaluation of serum levels of liver enzymes and C-reactive protein (CRP) in overweight individuals with and without metabolic syndrome

A Síndrome Metabólica (SM) é uma doença que envolve diversas alterações metabólicas, dentre elas, dislipidemia, intolerância à glicose, obesidade e hipertensão arterial. A alteração nos níveis das enzimas hepáticas tem se mostrado um marcador útil no diagnostico da SM. Há poucos trabalhos avaliando essas enzimas em indivíduos com sobrepeso com e sem SM. O presente trabalho avaliou os níveis séricos das enzimas hepáticas (ALT, AST,GGT) bem como a proteína C reativa (PCR) como marcador inflamatório em indivíduos com sobrepeso, come sem SM. Foram avaliados 97 indivíduos, sendo 41 controles saudáveis eutróficos (EU), 28 indivíduos com sobrepeso sem SM (OSSM) e 28 indivíduos com sobrepeso com SM (OCSM). As análises de colesterol total,HDL-C. LDL-C, triacilglicerol, glicose, ALT, AST e GGT foram efetuadas em um auto-analisador bioquímico.A determinação de PCR foi realizada por enzima imunoensaio em micropartículas (MEIA). Utilizou-se o teste não paramétrico de Kruskal-Wallis e os resultados foram apresentados sob a forma de mediana (mínimo máximo).Correlação de Spearman foi utilizada neste estudo. Os níveis séricos das enzimas hepáticas (ALT, AST e GGT) não diferiram entre o grupo EU e o grupo OSSM, entretanto, houve diferença estatisticamente significativa quando esses parâmetros foram comparados entre EU e OCSM e OSSM e OCSM (p<0,001). Níveis plasmáticos de glicose foram positivamente correlacionados com ALT, AST e GGT. O grupo OCSM apresentou aumento significativo nos níveis séricos de PCR quando comparado aos demais grupos (p<0,001).Conclui-se que o sobrepeso não foi capaz de alterar os níveis das enzimas hepáticas e da PCR e que a elevação dos níveis séricos de GGT pode ser considerada um fator de risco adicional para SM.

Metabolic syndrome (MetS) is a disease that involves several metabolic changes, including dyslipidemia, glucose intolerance, obesity and hypertension. The changes in liver enzyme levels have been shown to be a useful marker in the diagnosis of MetS. There are few studies evaluating these enzymes in overweight individuals with or without MetS. This study evaluated the serum levels of liver enzymes (ALT, AST, and GGT) as well as C-reactive protein (CRP) as inflammatory markers in overweight individuals with and without MS. We studied 97 subjects, 41 eutrophic healthy controls (EU), 28 overweight individuals without MetS (OSSM) and 28 overweight individuals with MetS (OCSM). Analyses of total cholesterol, HDL-C, LDL-C, triacylglycerol, fasting glucose, ALT, AST and GGT were performed in a biochemical auto analyzer. The determination was performed by CRP enzyme in microparticles (MEIA). The nonparametric Kruskal-Wallis test was performed and the results were presented as median (minimum-maximum). Spearman correlation was also performed in this study. Serum levels of liver enzymes (ALT, AST and GGT) did not differ between group EU and group OSSM, however, statistically significant differences when these parameters were compared between EU and OCSM and OSSM and OCSM (p <0.001). Glucose levels were positively correlated with ALT, AST and GGT.The group showed a significant increase in serum CRP when compared to other groups (p <0.001). We conclude that overweight was not able to alter the levels of liver enzymes and CRP levels and the elevation of serum GGT may be considered an additional risk factor for MetS.

Influência da vitamina D nas doenças endocrinometabólicas / Influence of vitamin D in endocrine metabolic diseases

A deficiência de vitamina D tem sido relacionada com o desenvolvimento de diversas doenças endocrino metabólicas, como por exemplo, síndrome metabólica, obesidade, hipertensão e diabetes mellitus tipo 2. Este trabalho apresenta uma visão geral sobre as evidências científicas disponíveis para algumas das ações não-calcêmica da vitamina D nos seres humanos, através de pesquisa bibliográfica em bases de dados científicos. A deficiência de vitamina D pode predispor à intolerância à glicose, a alterações na secreção de insulina e, assim, ao desenvolvimento de diabetes mellitus tipo 2. Esse possível mecanismo ocorre em razão da presença do receptor de vitamina D em diversas células e tecidos, incluindo células β do pâncreas,no adipócito e no tecido muscular. Em indivíduos obesos, as alterações do sistema endócrino da vitamina D, caracterizada por elevados níveis de paratormônio e da 1,25 dihidroxicolecalciferol são responsáveis pelo feedback negativo da síntese hepática de 25-hidroxicolecalciferol e também pelo maior influxo de cálcio para o meio intracelular, que pode prejudicar a secreção e a sensibilidade à insulina. Na hipertensão, a vitamina D pode atuar via sistema renina-angiotensina e também na função vascular. Há evidências de que a 1,25-dihidroxicolecalciferol inibe a expressão da renina e bloqueia a proliferação da célula vascular muscular lisa. São necessários mais estudos prospectivos e ensaios clínicos randomizados, incluindo estudos de suplementação, que estabeleçam melhor os efeitos clínicos e metabólicos das variações na concentração de 25-hidroxicolecalciferol na evolução clínica dessas doenças.

The vitamin D deficiency has been linked to the development of several endocrine metabolic diseases such as metabolic syndrome, obesity, hypertension and Type 2 diabetes mellitus. This paper presents an overview of the available scientific evidence for some of the non-calcemic actions of vitamin D in humans, through literature search in scientific databases. The deficiency of vitamin D may predispose to glucose intolerance, changes in insulin secretion and thus the development of type 2 diabetes mellitus. This mechanism is possible due to the presence of the vitamin D receptor in several tissues and cells, including pancreatic β cells, adipocyte and muscle tissue. In obese individuals, the changes of the vitamin D endocrine system, characterized by high levels of parathyroid hormone and 1,25-dihydroxycholecalciferol are responsible for the negative feedback of hepatic synthesis of 25-hydroxycholecalciferol and also by increased influx of calcium into the intracellular environment, which can damage the secretion and insulin sensitivity. In hypertension, vitamin D could act on the renin-angiotensin system and also in vascular function. There is some evidence that 1,25-dihydroxycholecalciferol inhibits the renin gene expression and blocks the proliferation of vascular smooth muscle cell. Further prospective studies and randomized clinical trials, including studies of supplementation, are required to establish better clinical and metabolic effects of variations in the concentration of 25-hydroxycholecalciferol in the clinical course of these diseases.

Artin M enhances TNF-α production and phagocytosis of Candida albicans mediated by dectin-1 and mannose receptors.

The activities of dectin-1 and mannose receptors on phagocytosis of Candida albicans and the production of TNF-α by macrophages from mice pretreated for 3 days with extract of Artocarpus intergrifolia seeds (jack extract), Artin M or jacalin were studied. Macrophages from these mice were coincubated with C. albicans CR15 (yeast), in the presence of mannose (50mM) plus mannan (100 µg) or laminarin (1mg). Phagocytosis was significantly enhanced to 52% in macrophages from mice pretreated intraperitoneally for 3 days with jack extract (500 µg/250 µl PBS). Reduction in phagocytosis from 52% to 34% (P<0.05) occurred in the presence of mannose receptor inhibitors and from 52% to 16% (P<0.01) in the presence of dectin-1 inhibitor laminarin, whereas only 20% of control macrophages phagocytosed blastoconidia. Similar results were verified for pretreatment of mice with Artin M (2.5 µg/250 µl PBS), but not for jacalin (25 µg/250 µl PBS). Macrophages from mice pretreated 3 days previously with jack extract or Artin M and then coincubated for 2h with C. albicans presented a significant increase in TNF-α production, correlating with significantly less transition of yeast to filamentous forms compared to pretreatment with jacalin. These results suggest that Artin M, but not jacalin present in jack extract significantly increased TNF-α production and the activity of mannose and dectin-1 receptors.