Correlation of prolactin and macroprolactin levels with activity of Systemic Lupus Erythematosus before and after treatment

Introdução: A prolactina (PRL) exerce efeitos imunoestimulatórios in vitro e in vivo, porém a literatura é controversa quanto ao papel deste hormônio na atividade do Lúpus Eritematoso Sistêmico (LES). A macroprolactina possui menor atividade biológica in vivo e poderia explicar os resultados díspares. Objetivos: avaliar a prevalência de hiperprolactinemia e macroprolactinemia em pacientes lúpicas; analisar a correlação entre a atividade do LES e PRL, e interferência da macroprolactina nesta associação. Casuística e Métodos: Em 73 mulheres com LES ativo foi dosada a PRL pelo Immulite 2000®, e a macroprolactina pelo método do Polietilenoglicol (momento 1); em 62 destas pacientes foi colhida uma segunda amostra com a menor atividade do LES ao longo do tratamento (momento 2). Os controles foram 29 mulheres hígidas no menacme (grupo C) e 34 gestantes no terceiro trimestre (grupo G). Resultados: Houve 15 casos (20,55%) de hiperprolactinemia nas lúpicas, e nenhum entre as mulheres hígidas (p = 0,005). Todas as gestantes apresentaram hiperprolactinemia. A concentração de PRL foi maior (Med = 11,70 ng/ml) (p = 0,01) no LES do que no grupo C (Med = 8,81ng/ml), e correlacionou-se com a atividade da doença pelo SLEDAI (r = 0,41; p = 0,0003) no momento 1. No LES muito ativo os níveis de PRL foram maiores do que na doença inativa (Med = 17,10 ng/ml vs. Med = 8,36 ng/ml) (p< 0,01), e moderadamente ativa (Med = 7,75 ng/ml) (p < 0,05). Dentre as lúpicas hiperprolactinêmicas, 04 casos (26,7%) foram devidos à macroprolactina, e nas gestantes, 02 casos (5,9%). O LES foi tão ativo na macroprolactinemia quanto nos casos pela forma monomérica, porém a correlação entre PRL e SLEDAI foi maior para a PRL livre (r = 0,44; p = 0,0001). O tratamento das pacientes lúpicas hiperprolactinêmicas resultou em diminuição da concentração de PRL (Me momento 1 = 56,71 ± 43,87 ng/ml vs. Me momento 2 = 18,68 ± 24,20 ng/ml) (p = 0,015). Conclusões: pacientes lúpicas apresentam hiperprolactinemia mais frequentemente do que mulheres hígidas, e a PRL correlaciona-se com a atividade do LES. A macroprolactinemia não é marcador de doença inativa/pouco ativa.Introduction: Prolactin (PRL) is a hormone with widespread influences in the cells of the immune system, which have been demonstrated by several in vitro and in vivo studies. However, the role of this hormone in the pathogenesis of Systemic Lupus Erythematosus (SLE) is controversial within the medical literature. The potentially lower biological activity of macroprolactin could explain the disparity of the results. Methods: PRL levels were determined by chemo luminescence method (Immulite 2000®) in 73 women with active SLE (group L), while the screening for macroprolactinemia was determined by the polyethylene glycol precipitation method (first moment). Sixty two of these patients had their PRL levels determined in a second occasion, when the disease was inactive or with the lowest activity observed after treatment (second moment). The control groups were 29 healthy women (group C) and 34 third-trimester healthy pregnant (group P). The levels of PRL were correlated with the SLE Disease Activity Index (SLEDAI). Results: In the study group there were 15 (20.55%) cases of hyperprolactinemia, while in the group C there were none (p = 0,005). All pregnant women presented hyperprolactinemia. Prolactin levels were higher in group L (Med = 11,70 ng/ml) then in group C (Med = 8,81ng/ml) (p = 0,01) and correlated with the SLEDAI in the first moment (r = 0,41; p = 0,0003). We also detected that PRL levels were higher at highly active SLE (SLEDAI ¡Ý 11) than when the disease was inactive (SLEDAI = 0) (Med = 17,10 ng/ml vs. Med = 8,36 ng/ml) (p< 0,01) or moderately active SLE (6 ¡Ü SLEDAI ¡Ü 10) (Med = 7,75 ng/ml) (p<0,05). In the 15 patients of group L with hyperprolactinemia, there were 04 cases of macroprolactinemia (26.7%), while 02 subjects in group P presented it (5.9%). SLE was as active in the patients with hyperprolactinemia caused by the monomeric form of the hormone, as in the ones with macroprolactinemia. The correlation of the PRL levels and the SLEDAI was, nevertheless, stronger for free PRL (r = 0,44; p = 0,0001). The SLE treatment in the hyperprolactinemic patients reduced PRL levels from 56,71 ng/ml (sd = 43,87) to 18,68 ng/ml (± 24,20) (p = 0,015). Discussion: the frequency of hyperprolactinemia is higher in SLE than in the general population, and the levels of PRL correlate with the activity of the disease. Macroprolactin is also associated to active SLE

Methylation profile of POMC and FTO genes in Polycystic Ovaries Syndrome (PCOS): a case control study

A Síndrome dos Ovários Policísticos (SOP) associa-se ao risco aumentado de resistência insulínica (RI) e intolerância à glicose (IG), condições exacerbadas em vigência de obesidade. O fenótipo obeso é altamente prevalente na SOP, e possui etiologia multifatorial. Estudos tem sugerido a participação de mecanismos epigenéticos, como a metilação gênica, na aquisição do traço fenotípico obeso. Por outro lado, não está claro qual método é mais adequado para avaliar a adiposidade das mulheres com SOP. No presente estudo o objetivo primário foi avaliar o perfil de metilação de fragmento da região promotora dos genes produtor de proopiomelanocortina (POMC) e do fat and obesity gene (FTO), envolvidos no controle de apetite e peso corporal, em portadoras de SOP. Foi objetivo secundário analisar em portadoras de SOP e em controles as correlações entre resistência insulínica (RI) e intolerância à glicose (IG) com a adiposidade corporal. Estudo caso-controle, com 39 mulheres com SOP e 35 controles, pareadas por idade e índice de massa corporal (IMC). Para a análise da metilação gênica, o DNA extraído de leucócitos de sangue periférico foi modificado por bissulfito de sódio, amplificado por PCR em tempo real, e a porcentagem de metilação foi determinada utilizando a técnica de High Resolution Melting. Foram realizados teste oral de tolerância à glicose (TOTG, 75g glicose), índice HOMA-IR, bioimpedância elétrica (BIA), densitometria de corpo inteiro (DXA), medidas antropométricas (relação cintura/quadril (RCQ), relação cintura/estatura (RCE), IMC) e índice de adiposidade visceral (IAV). Os resultados da metilação foram agrupados nos seguintes padrões: hipometilado (0 - 20%); parcialmente metilado (50%) ou hipermetilado (>= 80%). O perfil de metilação dos genes POMC e FTO não foi diferente entre os grupos. Para o gene POMC, observou-se perfil hipermetilado na maioria das pacientes (~90%), parcialmente metilado em uma mulher com SOP e duas controles, e não houve perfil hipometilado. De maneira antagonista, para o gene FTO, o perfil foi hipometilado na maioria das pacientes (~90%), parcialmente metilado em duas mulheres SOP e uma controle, e não houve perfil hipermetilado. Na sequência, os grupos foram subdivididos em eutróficos (IMC = 25,0 Kg/m2); não houve diferença no perfil de metilação de ambos os genes entre os subgrupos constituídos por IMC. Foi concluído que embora o perfil de metilação das regiões estudadas dos genes POMC e FTO tenha sido semelhante entre os grupos, não estão descartadas diferenças em outras regiões dos mesmos genes, ou das mesmas regiões gênicas em outros tecidos. Quanto às variáveis metabólicas e adiposidade, os níveis médios da TOTG foram mais elevados no grupo SOP, enquanto o índice de gordura apendicular (obtido pela DXA) foi mais elevado nos controles. Entre as mulheres com SOP as correlações observadas entre IMC, RCE e o IAV com variáveis do metabolismo glicídico foram semelhantes às obtidas para a DXA, enquanto no grupo SOP eutrófico houve correlação somente entre TOTG e a gordura androide pela DXA. Foi concluído que IMC, RCE e IAV são adequados para avaliar a adiposidade na SOP. Mulheres SOP eutróficas podem se beneficiar da DXA, devido ao aumento do risco metabólico associado à maior quantidade de gordura androide.Polycystic Ovaries Syndrome (PCOS) is associated with increased risk of insulin resistance (RI) and glucose intolerance (GI), conditions which are exacerbated in obesity. The etiology for the high prevalence of the obese phenotype in PCOS is multifactorial, and studies have suggested the participation of epigenetic mechanisms, such as gene methylation, in the acquisition of this phenotypic trait. On the other hand, it is not clear which method is best suited to assess the adiposity of PCOS women. In the present study, the primary objective was to evaluate in PCOS women the methylation profile of a fragment pro-opiomelanocortin gene (POMC) and fat and obesity gene (FTO), involved in appetite control and body weight. It was secondary objective to correlate the values obtained in the assessment of adiposity by four different methods, with the values of insulin resistance (IR) and glucose intolerance (GI). A case-control study was performed, with 39 women with PCOS and 35 controls, matched for age and body mass index (BMI). For the gene methylation analysis, DNA extracted from peripheral blood leucocytes was modified by sodium bisulfite, amplified by real-time PCR, and subjected to the High Resolution Melting technique. The adiposity assessment was done using the electrical bioimpedance (BIA); whole body densitometry (DXA); anthropometric measurements (waist / hip ratio (WHR), waist-to-height ratio (WHeR), BMI) and visceral adiposity index (VAI) that were correlated to HOMA-IR and glycemia after oral overload with 75g of glucose (GTT). The methylation results were grouped into the following patterns: hypomethylated (0-20%); partially methylated (50%) or hypermethylated (>= 80%). The methylation profile of the POMC and FTO genes was not different between groups. For the POMC gene, hypermethylated profile was observed in most patients (~ 90%), partially methylated in one PCOS woman and two controls, and there was no hypomethylated profile. Antagonistically, for the FTO gene, the profile was hypomethylated in most patients (~ 90%), partially methylated in two PCOS women and one control, and there was no hypermethylated profile. Subsequently, the groups were subdivided by categories of BMI in eutrophic (BMI up to 24.9 kg / m2) and overweight (BMI >= 25.0 kg / m2). There was no difference in the methylation pattern of POMC and FTO genes among the subgroups constituted by BMI. It was concluded that although the methylation profile of the studied regions of the POMC and FTO genes was similar between the groups, differences in other regions of the same genes or in the same gene regions in other tissues are not ruled out. Regarding metabolic and body composition variables, the average TOTG levels were higher in the PCOS group, while the appendicular fat index (obtained by DXA) was higher in the controls. The correlations observed between BMI, WHtR and VAI with glycemic metabolism variables were similar to those obtained for DXA. Among eutrophic PCOS women there was moderate correlation between android fat and GTT. Considering the cost-effectiveness, it was concluded that BMI, WHtR and VAI are adequate to evaluate PCOS adiposity. Eutrophic PCOS women, by contrast, can benefit from DXA

Frequency of Strongyloides stercoralis Infection in Alcoholics

Several studies have shown that chronic alcoholics have increased susceptibility to infections due to higher exposure to infectious agents as well as breakdown in their immune defenses. As Strongyloides stercoralis   infection is usually more relevant in immunocompromised patients, the aim of this study was to evaluate the frequency of S. stercoralis infection in alcoholics. Thus, coproparasitological examination was carried out in 145 subjects, from which 45 were chronic alcoholics (mean age of 45.7 ± 11.0 years), 10 were nonalcoholic cirrhotic patients (mean age of 50.2 ± 13.1 years), and 90 were asymptomatic nonalcoholic subjects (mean age of 46.7 ± 10.1 years), which served as controls. From the alcoholics, 9 had hepatic cirrhosis, 9 had chronic pancreatitis and 27 had neither cirrhosis nor pancreatitis. For the diagnosis of strongyloidiasis, the Baermann-Moraes and Lutz methods were used in three fecal samples from each subject. Samples were collected at alternated days, and three slides of each sample were analyzed for each method, thus totalizing 2,610 slides examined. The frequency of strongyloidiasis in the total alcoholic group (33.3%) and in the subgroups of alcoholics, i.e., patients with hepatic cirrhosis (44.4%), with chronic pancreatitis (33.3%), and those with no cirrhosis or pancreatitis (29.6%) was statistically higher than that found in the control group (5.5%). None of the individuals with nonalcoholic hepatic cirrhosis had S. stercoralis infection. Our results showed that the chronic alcoholism itself is an important factor that predisposes to strongyloidiasis

Hysteroscopy as a standard procedure for assessing endometrial lesions among postmenopausal women

CONTEXT AND OBJECTIVES: Endometrial cancer is the most prevalent type of malignant neoplasia of the genital tract. The objective of this study was to calculate the sensitivity, specificity, accuracy and positive and negative predictive values for diagnostic hysteroscopy, in comparison with histopathological tests, for all lesions of the endometrial cavity. DESIGN AND SETTING: Retrospective descriptive study at the public tertiary-level university hospital of Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo. METHODS: Diagnostic hysteroscopy was indicated in the following instances: endometrial thickness > 4 mm in asymptomatic patients; postmenopausal bleeding; and irregular endometrium or endometrium difficult to assess from ultrasound, with or without vaginal bleeding. Ultrasound evaluations were carried out no more than three months prior to hysteroscopy. RESULTS: There were 510 patients, with a mean age of 61.1 ± 2.0 years and mean time elapsed since the menopause of 12.7 ± 2.5 years. Endometrial biopsies were performed on 293 patients (57.5%). Histopathological analysis showed that 18 patients presented endometrial carcinoma or typical or atypical hyperplasia, and none of them presented endometrial thickness of less than 8 mm. No significant differences were found between the median thicknesses of the various benign lesions (p > 0.05). In our data, the sensitivity, specificity, accuracy and positive and negative predictive values for cancer or hyperplasia were 94.4%, 97.0%, 96.8%, 68% and 99.6%, respectively. CONCLUSIONS: Our results suggest that hysteroscopy is valuable as a diagnostic tool for malignant/hyperplastic and benign lesions, except for submucous myomas, for which the sensitivity was only 52.6%