Genetic polymorphism of CYP2D6 influences susceptibility to papillary thyroid cancer

OBJECTIVE: Xenobiotic-metabolizing enzymes are widely polymorphic and confer interindividual variation in the ability to detoxify carcinogens or to activate pro-carcinogens. A common polymorphism of cytochrome P450 2D6 (CYP2D6) results in lack of enzyme activity and has been associated with an altered susceptibility to several cancers. The aim of this study was to investigate the association between the CYP2D6 poor metaboliser genotype and the risk of papillary thyroid cancer (PTC). DESIGN: Retrospective case-control study. PATIENTS: One hundred and eighty-seven patients with PTC and 256 controls. MEASUREMENTS: Genotyping was performed by PCR and restriction enzyme analysis to detect the presence of the common CYP2D6*4 poor metaboliser allele. RESULTS: The frequency of individuals with the homozygous poor metaboliser genotype was lower in the patient group [1.6 vs. 5.5%, P = 0.037, OR = 0.28 (95% CI 0.09-0.93)]. The CYP2D6*4 allele frequency was also lower in the patient group [13.4 vs. 21.7%, P = 0.002, OR = 0.56 (95% CI 0.39-0.80)]. CONCLUSIONS: The results suggest that the poor metaboliser genotype is associated with a protective effect against PTC. This could be explained by a possible role of CYP2D6 on the metabolic activation of putative environmental chemical thyroid carcinogens or by linkage to another cancer-causing gene. Further research may allow the identification of metabolic risk factors and contribute towards understanding the molecular mechanisms involved in thyroid carcinogenesis

OpenLab ESEV: novas aventuras no desenvolvimento de software

OpenLab ESEV is the Free Software project of the School of Education - Polytechnic Institute of Viseu (ESEV). The project aims to establish a platform to aggregate activities that foster the use of Free/Libre and Open Source Software (F/LOSS), Free Culture and more flexible licenses for creative and educational purposes in the ESEV's domains of activity (education, arts, media). OpenLab exists since 2009. It emerged in an environment characterized by the lack of knowledge of the existing Libre alternatives and by work habits exclusively built around proprietary software. Today, OpenLab activities are implemented within four key areas of action: dissemination, training, support and production. This paper presents two of the most important ongoing projects: Ottographer and StudiozCollabPress. StudiozCollabPress is a customized version of a popular WordPress plugin for project management that was developed to support short movie projects management. We'll present its main features and results from real-case scenarios of use, specifically, finished and ongoing 3D animation students' projects. Ottographer is a webcam time-lapse tool for operating systems based on Debian GNU/Linux. Besides the main features, we'll present some examples and suggestions for educational settings as well as for creative and educational purposes. Both projects are distributed as F/LOSS, meaning that they can be used, studied, and modified without restrictions, as well as copied and redistributed in modified or unmodified form. These projects might help us launch a new trend at our school community that we highly antecipate: the development and sharing of our own tools

Virtual pollination trade uncovers global dependence on biodiversity of developing countries

Nations’ food consumption patterns are increasingly globalized and trade dependent. Natural resources used for agriculture (e.g., water, pollinators) are hence being virtually exchanged across countries. Inspired by the virtual water concept, we, herein, propose the concept of virtual biotic pollination flow as an indicator of countries’ mutual dependence on biodiversity-based ecosystem services and provide an online tool to visualize trade flow. Using information on 55 pollinator-dependent crop markets (2001–2015), we show that countries with higher development level demand high levels of biodiversity-based services to sustain their consumption patterns. Such patterns are supported by importation of virtual biotic pollination (up to 40% of national imports of pollinator-dependent crops) from developing countries, stimulating cropland expansion. Quantifying virtual pollination flow can help develop new global socioeconomic policies to meet the interconnected challenges of biodiversity loss, ecosystem health, and social justice.info:eu-repo/semantics/publishedVersio

Anaplastic thyroid tumor: retrospective analysis of 12 cases

Anaplastic thyroid tumor is a rare tumor and constitutes 5 to 10% of thyroid carcinomas. Is one of the most aggressive solid tumors and the prognosis is always fatal with a mean survival of 3 to 7 months. The current therapeutics are scarce and inefficacious. A retrospective analysis was performed in 12 clinical cases of anaplastic thyroid tumor observed at the Department of Endocrinology, Diabetes and Metabolism of the University Hospital of Coimbra. We analysed data relative to sex, previous thyroid pathology, clinical signs and symptoms, date of diagnosis, treatment and outcome. In this series, the anaplastic thyroid carcinoma showed to be a highly malignant tumor with a mortality rate of 100% with a survival after the diagnosis between 15 days and 9 months

Late onset congenital adrenal hyperplasia due to 21-hydroxylase deficiency: revision of literature and preconception genetic study of five couples

The deficiency of the enzyme 21-hydroxylase (21-HO) is responsible for about 90% to 95% of all cases of congenital adrenal hyperplasia (HCSR). This disorder is one of the most frequent hereditary illnesses of autosomal recessive trait. The illness can be presented in two clinical forms: 1 - classic, subdivided in saltwasting form and simple virilizing form; 2 - nonclassic or late-onset. The severity of the illness is correlated with the degree of enzymatic activity of 21-HO, which depends on the type of mutation that occurs in gene CYP21A2. The late onset congenital adrenal hyperplasia is that one where the enzymatic blockade is less intense. The clinical is variable: precocious pubarche, polycystic ovaries, hirsutism, oligoamenorrhea, acne and infertility. Gold standard for the diagnosis of late onset congenital adrenal hyperplasia consists on the test of the tetracosactide, considering itself diagnostic positive when 17-hidroxiprogesterona (17-OHP) is higher of 10-15 ng per mL. Many patients don't need treatment; however, if necessary, such a treatment essentially consists on the Administration of glucocorticoids and antiandrogens. Considering that affected individuals and the carriers may have a severe mutation in CYP21A2, they can have descendents with the classic form (if their partner is also a carrier of a severe mutation), it is mandatory the genetic study of the couple. The authors illustrate the importance of this genetic study through five clinical cases, whose common link is the desire to have children, as well as the presence on the feminine element of late onset congenital adrenal hyperplasia. The genetic study of the couple allows adequate pre-conception counseling and also prevents the use of corticoids throughout the pregnancy (if there's no risk of descendents being affected with the classic form). This aspect must be had in account in programming the pregnancy, in order to prevent therapeutics and unnecessary distrusts

Techno-economic and life-cycle assessments of small-scale biorefineries for isobutene and xylo-oligosaccharides production: a comparative study in Portugal and Chile

ABSTRACT: This work presents a comparative simulation study involving the techno-economic and environmental assessment of lignocellulosic-based small-scale biorefineries, integrated with a piggery waste-based anaerobic digestion platform (ADB), located in Portugal and Chile. Two main products are obtained: isobutene and xylo-oligosaccharides (XOS). The bioproduction of isobutene using a genetically engineered organism (Escherichia coli), coupled with the removal and purification of high added-value XOS, obtained after a feedstock hydrothermal pre-treatment, was evaluated. Two lignocellulosic agricultural wastes were used: corn stover in the Portuguese case study and wheat straw in Chilean case study. Both processes were simulated using the Aspen Plus modeling software tool, while the Aspen Process Economic Analyzer was used to carry out the economic evaluation. The simulation results were validated with experimental data from the laboratory and the literature. An economic assessment was performed considering the different locations of both biorefineries. A life-cycle analysis (LCA) was also applied to evaluate the differences in environmental impacts on both locations. The results showed that the isobutene / XOS biorefinery concept was economically viable in both Portugal and Chile, mainly due to the high market value of XOS. The biorefinery has lower production costs for isobutene and XOS (1 US$/kg of isobutene and 1.18 US$/kg of XOS) when located in Portugal, as compared with Chile (1.14 US$/kg of isobutene and 1.56 US$/kg of XOS). Conversely, it leads to less environmental impact when located in Chile: 48.8 kg(CO2eq.)/GJ(isobutene), in comparison to 60.7 kg(CO2eq.)/GJ(isobutene) in Portugal.info:eu-repo/semantics/publishedVersio

Recurrent hypercortisolism after removal of an ACTH secretor pituitary adenoma associated with an adrenal macronodule

A 29 years old patient was sent to our Outpatient Clinic of Endocrinology presenting clinic of hypercortisolism. Laboratorial study: High urinary free cortisol (UFC); serum cortisol - 25 microg/dl (8 am) (5-25) and 20 microg/dL (11pm); ACTH - 20 pg/mL (9-52) (8 am) and 14 pg/mL (11 pm); serum cortisol after dexamethasone suppression test: 14,9 mg/dL; CRH test: elevation of ACTH; Pituitary MRI: microadenoma; abdominal CT: nodule on the left adrenal. During inferior petrosal sinus sampling with CRH stimulation, ACTH reached 368 pg/mL on the right and 136 pg/mL on the left side. The patient was submitted to transsphenoidal surgery. After surgery, hypertension and physical stigmata improved. In 2006, a relapse of Cushing syndrome was suspected due to worsening of hypertension and increase of weight. A slight increase of UFC, undetectable ACTH and serum cortisol after dexamethasone suppression test equal to 16 microg/dL were found. On abdominal CT, the adrenal nodule kept the same characteristics. In December 2006, the patient was submitted to left adrenalectomy. After surgery, blood pressure normalized, UFC and serum cortisol were reduced, needing substitutive therapy. Progressive tapering of hydrocortisone doses lead to discontinuation in March 2007. He is clinically well, without any treatment. This is an unusual case, in which after surgical cure of Cushing disease, secretory autonomy of a coexisting adrenal nodule occurred. This clinical case is relevant, pointing out the complexity of hypercortisolism cases and the need of long follow-up

Novel Antiretroviral Therapeutic Strategies for HIV.

When the first cases of HIV infection appeared in the 1980s, AIDS was a deadly disease without any therapeutic alternatives. Currently, there is still no cure for most cases mainly due to the multiple tissues that act as a reservoir for this virus besides the high viral mutagenesis that leads to an antiretroviral drug resistance. Throughout the years, multiple drugs with specific mechanisms of action on distinct targets have been approved. In this review, the most recent phase III clinical studies and other research therapies as advanced antiretroviral nanodelivery systems will be here discussed. Although the combined antiretroviral therapy is effective in reducing viral loading to undetectable levels, it also presents some disadvantages, such as usual side effects, high frequency of administration, and the possibility of drug resistance. Therefore, several new drugs, delivery systems, and vaccines have been tested in pre-clinical and clinical trials. Regarding drug delivery, an attempt to change the route of administration of some conventional antiretrovirals has proven to be successful and surpassed some issues related to patient compliance. Nanotechnology has brought a new approach to overcoming certain obstacles of formulation design including drug solubility and biodistribution. Overall, the encapsulation of antiretroviral drugs into nanosystems has shown improved drug release and pharmacokinetic profile.This work was supported with Gilead GÉNESE Ref. PGG/006/2016.info:eu-repo/semantics/publishedVersio

ACTH-dependent Cushing's syndrome: a revision of 43 cases

AIM: To evaluate the characteristics and outcomes of the patients diagnosed as ACTH-dependent Cushing syndrome, registered in the department. MATERIAL AND METHODS: We reviewed the files of forty-three patients followed from 1974 to 2002. RESULTS: A progressive rise in the number of patients diagnosed was found, being 80% females. Clinical suspicion was based mostly on the typical fat distribution; hirsutism and amenorrhoea were important in women. The more reliable diagnostic tests were: 11 pm cortisol, day curve of ACTH and cortisol, and dexamethasone suppression tests. The ACTH response to CRH during inferior petrosal sinus sampling permitted the diagnosis of ectopic source. In thirty-seven patients a pituitary adenoma was diagnosed. The three patients diagnosed before 1985 went for bilateral adrenalectomy (Nelson's syndrome in two); the others were submitted to transsphenoidal pituitary adenomectomy, obtaining remission in twenty six at the first operation and in two others at the second. Three patients had a recidive. Of the six patients with persistent disease (all treated with metyrapone or ketoconazole), three were submitted to radiotherapy, two to bilateral adrenalectomy, and one was waiting for surgery. Four patients had a bronchial carcinoid, successfully removed in three. One patient was lost to follow-up and another was still being evaluated. CONCLUSIONS: We found a positive evolution in the capacity to diagnose and treat these patients. Neurosurgical ability to achieve remission was 80% in the operated cases. More effective technical methods and drugs, as well as a multidisciplinary and dedicated medical team, lead to long lasting remissions in most of the patients

The CTLA4 +49 A/G polymorphism is not associated with susceptibility to type 1 diabetes mellitus in the Portuguese population

CTLA4 genetic polymorphisms have been associated with type 1 diabetes. We genotyped 207 patients and 249 controls for the most frequently investigated polymorphism of the CTLA4 gene (+49A/G (rs231775)). No significant differences were observed, suggesting that this polymorphism is not strongly associated with type 1 diabetes in the Portuguese population