Davide Carvalho

Thickening of the pituitary stalk: a finding suggestive of intrasellar tuberculoma? Case report.

We describe the case of a patient with an exclusively intrasellar mass, disclosed because of a left sixth nerve palsy and headaches. No other manifestation of disease, namely, endocrinological, was present. The lesion was approached transsphenoidally, and the pathological examination revealed a tuberculoma. Complete removal was achieved, and the patient started postoperative antituberculous therapy. In some circumstances, thickening of the infundibulum and the pituitary stalk could preoperatively suggest the diagnosis of hypophysial tuberculoma.

Fat Mass Ratio: An Objective Tool to Define Lipodystrophy in HIV-Infected Patients Under Antiretroviral Therapy

Human immunodeficiency virus (HIV) infection and its treatment with antiretroviral therapy (ART) have been associated with lipodystrophy. Different clinical methodologies have been used to define the syndrome. The aim of this study was to propose gender-specific reference values using objective measurements for defining lipodystrophy in HIV-infected patients. Using dual-energy X-ray absorptiometry (DXA), total body composition was analyzed in 221 HIV-infected patients under ART (146 men). We used fat mass ratio (FMR) as the ratio between the percent of the trunk fat mass and the percent of the lower-limb fat mass. One hundred forty patients (63.6%) presented clinically defined lipodystrophy. In men, the optimal cutoff value for the FMR was 1.961 (area under the receiver operating characteristic curve [AUC]: 0.74 [95% confidence interval (CI): 0.66-0.82], p<0.001), with a sensitivity 58.3%, a specificity 83.7%, a positive predictive value (PPV) of 89.6% and a negative predictive value (NPV) of 45.5%. In women, the optimal cutoff value for the FMR was 1.329 (AUC: 0.74 [95% CI: 0.63-0.86], p<0.001), with a sensitivity 51.4%, a specificity 94.6%, a PPV of 90.5%, and an NPV of 66.0%. The FMR evaluated by DXA with the gender-specific cutoffs defined here is an objective way to define HIV-related lipodystrophy.

Human infertility: are endocrine disruptors to blame?

Over recent decades, epidemiological studies have been reporting worrisome trends in the incidence of human infertility rates. Extensive detection of industrial chemicals in human serum, seminal plasma and follicular fluid has led the scientific community to hypothesise that these compounds may disrupt hormonal homoeostasis, leading to a vast array of physiological impairments. Numerous synthetic and natural substances have endocrine-disruptive effects, acting through several mechanisms. The main route of exposure to these chemicals is the ingestion of contaminated food and water. They may disturb intrauterine development, resulting in irreversible effects and may also induce transgenerational effects. This review aims to summarise the major scientific developments on the topic of human infertility associated with exposure to endocrine disruptors (EDs), integrating epidemiological and experimental evidence. Current data suggest that environmental levels of EDs may affect the development and functioning of the reproductive system in both sexes, particularly in foetuses, causing developmental and reproductive disorders, including infertility. EDs may be blamed for the rising incidence of human reproductive disorders. This constitutes a serious public health issue that should not be overlooked. The exposure of pregnant women and infants to EDs is of great concern. Therefore, precautionary avoidance of exposure to EDs is a prudent attitude in order to protect humans and wildlife from permanent harmful effects on fertility.

Finding new posttranslational modifications in salivary proline‐rich proteins

Proline‐rich proteins (PRPs) are the most complex family of salivary peptides with distinct isoforms and PTMs. Up to date, only the serine phosphorylation at positions 8, 17, and 22 have been experimentally observed on acidic PRP (aPRPs), and at position 8 on basic PRP1 and 2. The presence of a glucoronyl group at Ser17 was also noticed on aPRP. The main goal of this study was to identify new PTMs and distinct isoforms of salivary PRPs using LC‐MALDI‐TOF/TOF. Through the salivary peptidome characterization of 20 different subjects from Control, Diabetic, and Head and Neck Cancer groups, it was possible to identify the following species: (i) N‐glycosylation sites: two in basic proline‐rich protein 2 (bPRP2), one in bPRP3 and one in bPRP4; (ii) O‐glycosylation sites: two in bPRP2 and one in aPRP; (iii) other terminal monosaccharide sites: six in bPRP1, two in bPRP2 and two in bPRP3; (iv) other modifications such as N‐terminal pyro‐Glu (two in bPRP1, six in bPRP2, eight in bPRP3 and nine in bPRP4); (v) phosphorylation in serine, three in bPRP1, one in bPRP2, one in bPRP3 and one in aPRP1; (vi) bPRP1 (allele S, allele M and variant CP5) and bPRP4 (allele M). In summary, salivary peptidome data analysis allowed the identification of 45 new PRP‐modified residues, mainly due to glycosylation, phosphorylation and conversion of Gln to pyro‐Glu. Moreover, comparing all subject groups, it was noticed a predominance of N‐acetyl hexosamine modification on bPRPs in the Head and Neck Cancer patients.

A polymorphism in the promoter region of the selenoprotein S gene (SEPS1) contributes to Hashimoto's thyroiditis susceptibility.

CONTEXT The association between selenium and inflammation and the relevance of selenoproteins in follicular thyroid cell physiology have pointed to a putative role of selenoproteins in the pathogenesis of autoimmune thyroid diseases. OBJECTIVE The aim of this study was to evaluate the role of a promoter variation in SEPS1, the selenoprotein S gene, in the risk for developing Hashimotos thyroiditis (HT). DESIGN A case-control study was performed to assess the association of genetic variation in the SEPS1 gene (SEPS1 -105G/A single-nucleotide polymorphism, rs28665122) and HT. SETTING The study was conducted in north Portugal, Porto, in the period of 2007-2013. PATIENTS OR OTHER PARTICIPANTS A total of 997 individuals comprising 481 HT patients and 516 unrelated controls were enrolled in the study. MAIN OUTCOME MEASURES Genetic variants were discriminated by real-time PCR using TaqMan single-nucleotide polymorphism genotyping assays. RESULTS There is a significant association between the SEPS1 -105 GA and AA genotypes and HT [odds ratio (OR) 2.24, confidence interval (CI) 1.67-3.02, P < 5.0 × 10(-7), and OR 2.08, CI 1.09-3.97, P = .0268, respectively]. The A allele carriers are in higher proportion in the patient group than in the control population (46.2% vs 28.1%, P < 5.0 × 10(-7)) with an OR (CI) of 2.22 (1.67-2.97). The proportion of patients carrying the A allele is significantly higher in male patients with HT, representing a 3.94 times increased risk (P = 7.9 × 10(-3)). CONCLUSION Our findings support the existence of a link between SEPS1 promoter genetic variation and HT risk.

Thickening of the Pituitary Stalk

: We describe the case of a patient with an exclusively intrasellar mass, disclosed because of a left sixth nerve palsy and headaches. No other manifestation of disease, namely, endocrinological, was present. The lesion was approached transsphenoidally, and the pathological examination revealed a tuberculoma. Complete removal was achieved, and the patient started postoperative antituberculous therapy. In some circumstances, thickening of the infundibulum and the pituitary stalk could preoperatively suggest the diagnosis of hypophysial tuberculoma.

PROP1 gene analysis in Portuguese patients with combined pituitary hormone deficiency

Objective  Mutations of the PROP1 gene lead to combined pituitary hormone deficiency (CPHD), which is characterized by a deficiency of GH, TSH, LH/FSH, PRL and, less frequently, ACTH. This study was undertaken to investigate the molecular defect in a cohort of patients with CPHD.

Impact of Lipodystrophy on the prevalence and components of metabolic syndrome in HIV-infected patients.

BackgroundIn HIV-infected patients, combination antiretroviral therapy (cART) is associated with clinical lipodystrophy (CL) and metabolic abnormalities (MA). This study aimed to evaluate the prevalence of the metabolic syndrome (MS) and its components, and to determine whether patients with or without CL had a different prevalence of MA.MethodsWe evaluated 345 HIV-infected patients on cART using two different MS definitions (NCEP-ATPIII-2005 and IDF-2005) and the Framingham risk score.ResultsCL was present in 58.7% of the patients. The prevalence of the MS was 52.2% (ATPIII) and 43.2% (IDF), and it was not significantly different between patients with (W) or without (WT) CL, regardless of the definition used (ATPIII WCL 52.9% vs WT CL 51.1%; p = 0.738; IDF WCL 41.3% vs WTCL 46.0%; p = 0.379). Moderate concordance was observed between the 2 definitions (kappa = 0.484; p < 0.001) and after gender stratification there was good concordance in women (kappa = 0.759; p < 0.001). Patients with CL had lower waist circumference and HDL-C and higher triglycerides levels. In women, CL was significantly associated with MS, hypertriglyceridemia and low HDL cholesterol independently of age, cART and BMI. Patients with CL had a significantly higher risk of coronary heart disease at 10 years, measured by the Framingham risk score, than patients without CL. Those with CL and with MS had higher frequencies of moderate and high risk categories than those without MS.ConclusionsThe prevalence of the MS was high in these HIV-infected patients with an age average of 40 years and this finding could explain why HIV patients have an increased risk for cardiovascular disease (CVD).

Genetics of glucocorticoid regulation and posttraumatic stress disorder--What do we know?

CASTRO-VALE, I., E.F.C. van Rossum, J.C. Machado, R. Mota-Cardoso and D. Carvalho. Genetics of glucocorticoid regulation and posttraumatic stress disorder-What do we know? NEUROSCI. BIOBEHAV. REV. 43 (1) XXX-XXX, 2014 - Posttraumatic stress disorder (PTSD) develops in a small proportion of those who have been exposed to a traumatic event. Genetic factors are estimated to be responsible for 30% of the variance in PTSD risk. Dysfunction of the hypothalamic-pituitary-adrenal (HPA)-axis in PTSD has been found, particularly hypersensitivity of the glucocorticoid receptor (GR). In this review we aim to understand the genetic factors that influence glucocorticoid function in PTSD. Glucocorticoid action is regulated by a corticotrophin-releasing hormone, arginine vasopressin (AVP)/oxytocin pathway, GR, and regulators such as co-chaperone FKBP5. Single nucleotide polymorphisms (SNPs) in the GR gene, CRHR1 gene and FKBP5 gene affect HPA-axis sensitivity. The GR gene SNP BclI has been associated with hypersensitivity to glucocorticoids and PTSD symptoms. FKBP5 gene SNPs interacted with childhood adversity to moderate PTSD risk and in particular, the rs9470080 SNP was independently associated with lifetime PTSD. SNPs in the CRHR1 gene were also associated with PTSD risk. Gene-environment interaction studies have highlighted the importance of multifactorial vulnerability in PTSD, with epigenetic mechanisms contributing to the equation.

Gut Microbiota: Association with NAFLD and Metabolic Disturbances.

Nonalcoholic fatty liver disease is the hepatic expression of metabolic syndrome, being frequently associated with obesity, insulin resistance, and dyslipidemia. Recent lines of evidence have demonstrated a role of gut microbiota in insulin resistance, obesity, and associated metabolic disturbances, raising the interest in its relationship with NAFLD pathogenesis. Therefore, intestinal microbiota has emerged as a potential factor involved in NAFLD, through different pathways, including its influence in energy storage, lipid and choline metabolism, ethanol production, immune balance, and inflammation. The main objective of this review is to address the pathogenic association of gut microbiota to NAFLD. This comprehension may allow the development of integrated strategies to modulate intestinal microbiota in order to treat NAFLD.