Metformin promotes susceptibility to experimental Leishmania braziliensis infection.

BACKGROUND: Metformin (MET) is a hypoglycemic drug used for the treatment of diabetes, despite interference in host immunity against microorganisms. Cutaneous infection caused by pathogens such as Leishmania braziliensis (Lb), the agent responsible for cutaneous leishmaniasis (CL) in Brazil, represents an interesting model in which to evaluate the effects associated with MET. OBJECTIVE: To evaluate the modulatory effect of MET in Lb infection. MATERIAL AND METHODS: Experimental study of Lb infection and MET treatment in BALB/c mice and Raw 264.7 macrophages. FINDINGS: MET treatment interfered with lesion kinetics, increased parasite load and reduced macrophage proliferation. Low concentrations of MET in Lb culture allow for the maintenance of stationary parasite growth phase. Lb-infected cells treated with MET exhibited increased parasite load. While both MET and Lb infection alone promoted the production of intracellular reactive oxygen species (ROS), reduced levels of ROS were seen in MET-treated Lb-infected macrophages. MAIN CONCLUSION: Experimental treatment with MET interfered with the kinetics of cutaneous ulceration, increased Lb parasite load, altered ROS production and modulated cellular proliferation. Our experimental results indicate that MET interfere with the evolution of CL.

Risk Factors for Erectile Dysfunction in Men With HTLV-1.

BACKGROUND: Erectile dysfunction (ED) occurs in more than 50% of patients with human T-cell lymphotropic virus type 1 (HTLV-1) infection. In the general population, atherosclerosis is the main risk factor related to ED. AIM: To compare the contribution of neurologic disorders from HTLV-1 with that of atherosclerosis as risk factors for ED in men with HTLV-1. METHODS: In this cross-sectional study, men 18 to 70 years old with HTLV-1 were classified into one of two groups according to the presence or absence of ED. They were compared for obesity, waist circumference, dyslipidemia, metabolic syndrome, diabetes mellitus, high blood pressure, and neurologic manifestations. Comparisons between proportions were performed using the χ2 or Fisher exact test. Logistic regression analysis was performed to identify predictors of ED. Subjects with HTLV-1 were classified into three groups based on Osame's Disability Motor Scale and the Expanded Disability Status Scale: (i) HTLV-1 carriers; (ii) probable HTLV-1-associated myelopathy or tropical spastic paraparesis; and (iii) definitive HTLV-1-associated myelopathy or tropical spastic paraparesis. The International Index of Erectile Function was used to determine the degree of ED. RESULTS: In univariate logistic regression, age older 60 years (P = .003), diabetes mellitus (P = .042), and neurologic disease (P < .001) were associated with ED. In the multivariate model, the odds of ED was highest in patients with neurologic disease (odds ratio = 22.1, 95% CI = 5.3-92.3), followed by high blood pressure (odds ratio = 6.3, 95% CI = 1.4-30.5) and age older than 60 years (odds ratio = 4.6, 95% CI = 1.3-17.3). CLINICAL IMPLICATIONS: In men infected with HTLV-1, neurologic dysfunction is a stronger predictor of ED than risk factors for atherosclerosis. STRENGTHS AND LIMITATIONS: The small number of patients limited the power of the statistical analysis, but clearly neurologic manifestations had a greater association with ED than risk factors for atherosclerosis, and there was no association between metabolic syndrome and severity of ED. CONCLUSION: Neurologic impairment is the major cause of ED in individuals infected with HTLV-1 and risk factors for atherosclerosis did not have a strong relation with ED in this population. de Oliveira CJV, Neto JAC, Andrade RCP, et al. Risk Factors for Erectile Dysfunction in Men With HTLV-1. J Sex Med 2017;14:1195-1200.

Neurological symptoms and signs in HTLV-1 patients with overactive bladder syndrome.

OBJECTIVE: To compare neurological symptoms and signs in HTLV-1 asymptomatic carriers and HTLV-1 patients with overactive bladder (OB) syndrome. METHODS: We studied 102 HTLV-1 positive individuals without HAM/TSP (HTLV-1 associated myelopathy/tropical spastic paraparesis) divided into two groups according to the presence or absence of OB syndrome. Clinical interview, neurological exam and proviral load was performed in all patients. RESULTS AND CONCLUSIONS: Individuals with OB were more commonly female (84.3 vs. 60.8% of asymptomatics, p=0.01). The prevalence of neurological complaints was higher in OB group, especially hand or foot numbness and arm or leg weakness. There was no difference between the groups in neurological strength and reflexes. Weakness complaint remained strongly associated with OB in multivariate logistic regression analysis adjusting for sex and age [adjusted odds ratio and 95%CI 3.59 (1.45-8.88) in arms and 6.68 (2.63-16.93) in legs]. Proviral load was also different between the two groups with higher level on OB individuals.

Diagnosis and underdiagnosis of comorbidities in psoriasis patients - need for a multidisciplinary approach

Abstract BACKGROUND: Psoriasis is an immune-mediated disease that manifests predominantly in the skin, although systemic involvement may also occur. Although associated comorbidities have long been recognized and despite several studies indicating psoriasis as an independent risk factor for cardiovascular events, little has been done in general medical practice regardind screening. In the United States, less than 50% of clinicians are aware of these recommendations. OBJECTIVE: To identify the prevalence of these comorbidities in 296 patients followed up at a university dermatology clinic. METHODS: Systematically investigated comorbidity frequencies were compared with general practitioners' registry frequencies. Clinical features correlated with comorbidities were also investigated. RESULTS: High prevalences of systematically investigated comorbidities such as hypertension (30%) and dyslipidemia (26.5%) were documented. Conversely, data from general practitioners' records showed that 33% of dyslipidemia cases were undiagnosed and indicated possible underdiagnosis of some comorbidities. Furthermore, an association was found between: the number of comorbidities and psoriasis duration, age and high body mass index an association was found between the number of comorbidities and psoriasis duration, age, high body mass index, waist circumference or waist-to-hip ratio. (p<0.05). CONCLUSION: Disease duration, age and high body mass index, waist circumference or waist-to-hip ratio are possible criteria for choosing which patients should be screened for comorbidities. Underdiagnosis of comorbidities by general practitioners highlights the need for a multidisciplinary approach in psoriasis management.

FOXP3 expression in papillary thyroid carcinoma with and without Hashimoto's thyroiditis / Expressão do FOXP3 no carcinoma papilífero da tireoide com e sem tireoidite de Hashimoto

INTRODUCTION: The forkhead box P3 (FOXP3) plays a role in cell development and control. In the presence of abnormal FOXP3 expression, tumor cells may evade the immunosurveillance of lymphoid cells, the first step for the maintenance of cancer cells in the thyroid tissue. OBJECTIVE: To identify the presence of FOXP3 in papillary thyroid carcinoma (PTC) with and without Hashimoto's Thyroiditis (HT). METHODS: We conducted a series study of cases collected from 2000 to 2008, when 1,438 thyroidectomies were performed. We selected those diagnosed with PTC, comprising 466 cases. 30 patients were randomly selected for purposes of immunohistochemistry with antibodies against FOXP3. RESULT: FOXP3 revealed high positivity for PTC and positive immunostaining was present in 21 (72.4%) from all analyzed cases. There was no difference regarding coexistent HT or not. DISCUSSION AND CONCLUSION: In the present study, it was evidenced that the focal or diffuse FOXP3 expression was commonly observed in neoplastic cells from PTC, hence indicating that the assessment of this molecule expression in suspected cases of thyroid cancer may contribute to its diagnosis.

INTRODUÇÃO: O forkhead box P3 (FOXP3) tem o seu papel no desenvolvimento e no controle celular. Na presença de alterações da sua expressão, células tumorais podem escapar da imunovigilância das células linfoides, sendo o primeiro passo para perpetuação das células cancerígenas no tecido tireoidiano. OBJETIVO: Identificar a presença do FOXP3 no carcinoma papilífero da tireoide (CPT), com e sem tireoidite de Hashimoto (TH). MÉTODOS: Foi realizado um estudo de série de casos coletados no período de 2000 a 2008, quando foram realizadas 1.438 tireoidectomias. Destes, foram selecionados aqueles que apresentaram diagnóstico de CPT, perfazendo um total de 466 casos. Desse total, 30 casos de CPT foram selecionados aleatoriamente para fins de exame imuno-histoquímico com o anticorpo contra o FOXP3. RESULTADO: O FOXP3 apresentou alta positividade no CPT; a marcação positiva na imuno-histoquímica esteve presente em 21 (72,4%) de todos os casos analisados. Não houve diferença com relação à coexistência ou não de TH. DISCUSSÃO E CONCLUSÃO: No presente estudo, foi documentado que a expressão difusa ou focal de FOXP3 foi intensamente observada nas células neoplásicas do CPT, indicando que a avaliação da expressão dessa molécula em casos suspeitos de neoplasia da tireoide pode contribuir para o seu diagnóstico.