Genetic variants used as predictors of response in the pharmacological treatment of depression in the brazilian population

Depression is one of the most frequent mental illnesses in the world and the lack of response to antidepressants are linked to genetic variants. The genetic diversity of Brazilian population may contribute to a variability in the response to these drugs, and this study aimed to assess how genetic variants are clinically and scientifically in the context of therapeutic response to depression in the Brazilian population. This work was carried out through a survey in literature and information obtained from genetic laboratories about the variants used in Brazil as biomarkers of response to antidepressants. Data from scientific studies published since 2000 that evaluated genetic variants that are related to the response to antidepressants in Brazilian populations, in the PubMed, Scielo, Scopus and Web of Science databases were also collected and compared with the international scenario. All laboratories evaluated included variants of CYP2D6 and CYP2C19 genes approved by Food and Drug Administration (FDA) as biomarkers. However, the Brazilian genetic panels include variants that lack proven efficacy in PharmGKB and are not FDA-approved, highlighting the need for more regulation of commercialized tests and further studies on genetic variant analysis for depression treatment in our population. A limited number of Brazilian studies in this field were verified, highlighting the need for more regulation of commercialized tests and further studies on genetic variant for depression treatment in our population

Clinical Manifestations of Giant Cell Arteritis

Giant cell arteritis (GCA), also known as temporal arteritis or Horton disease, is categorized as a large- and medium-sized vessels vasculitis. Systemic symptoms are common in GCA and although vascular involvement may be widespread, the cranial branches of the aortic arch are responsible for the hallmark symptoms of GCA: headache, jaw claudication and ocular symptoms, particularly visual loss. The large vessel (LV)-GCA phenotype may differ or overlap from cranial arteritis. Clinical consequences of LV-GCA comprise aneurysms and dissections of the aorta, as well as stenosis, occlusion and ectasia of large arteries. Symptoms of polymyalgia rheumatica occurring in a patient with GCA include characteristic proximal polyarthralgias and myalgias, sometimes accompanied by remitting seronegative symmetrical synovitis with pitting edema (RS3PE), Less common manifestations reported include central nervous system involvement, audiovestibular and upper respiratory symptoms, pericarditis, mesenteric ischemia and female genital tract involvement

An In Silico Study of the Antioxidant Ability for Two Caffeine Analogs Using Molecular Docking and Quantum Chemical Methods

The antioxidant activity of molecules constitutes an important factor for the regulation of redox homeostasis and reduction of the oxidative stress. Cells affected by oxidative stress can undergo genetic alteration, causing structural changes and promoting the onset of chronic diseases, such as cancer. We have performed an in silico study to evaluate the antioxidant potential of two molecules of the zinc database: ZINC08706191 (Z91) and ZINC08992920 (Z20). Molecular docking, quantum chemical calculations (HF/6-31G**) and Pearson’s correlation have been performed. Molecular docking results of Z91 and Z20 showed both the lower binding affinity (BA) and inhibition constant (Ki) values for the receptor-ligand interactions in the three tested enzymes (cytochrome P450—CP450, myeloperoxidase—MP and NADPH oxidase—NO) than the control molecules (5-fluorouracil—FLU, melatonin—MEL and dextromethorphan—DEX, for each receptor respectively). Molecular descriptors were correlated with Ki and strong correlations were observed for the CP450, MP and NO receptors. These and other results attest the significant antioxidant ability of Z91 and Z20, that may be indicated for further analyses in relation to the control of oxidative stress and as possible antioxidant agents to be used in the pharmaceutical industry

Perturbations in the carbon budget of the tropics

The carbon budget of the tropics has been perturbed as a result of human influences. Here, we attempt to construct a ‘bottom-up’ analysis of the biological components of the budget as they are affected by human activities. There are major uncertainties in the extent and carbon content of different vegetation types, the rates of land-use change and forest degradation, but recent developments in satellite remote sensing have gone far towards reducing these uncertainties. Stocks of carbon as biomass in tropical forests and woodlands add up to 271 ± 16 Pg with an even greater quantity of carbon as soil organic matter. Carbon loss from deforestation, degradation, harvesting and peat fires is estimated as 2.01 ± 1.1 Pg annum(−1); while carbon gain from forest and woodland growth is 1.85 ± 0.09 Pg annum(−1). We conclude that tropical lands are on average a small carbon source to the atmosphere, a result that is consistent with the ‘top-down’ result from measurements in the atmosphere. If they were to be conserved, they would be a substantial carbon sink. Release of carbon as carbon dioxide from fossil fuel burning in the tropics is 0.74 Pg annum(−1) or 0.57 MgC person(−1) annum(−1), much lower than the corresponding figures from developed regions of the world

Identification of Potential Inhibitors from Pyriproxyfen with Insecticidal Activity by Virtual Screening

Aedes aegypti is the main vector of dengue fever transmission, yellow fever, Zika, and chikungunya in tropical and subtropical regions and it is considered to cause health risks to millions of people in the world. In this study, we search to obtain new molecules with insecticidal potential against Ae. aegypti via virtual screening. Pyriproxyfen was chosen as a template compound to search molecules in the database Zinc_Natural_Stock (ZNSt) with structural similarity using ROCS (rapid overlay of chemical structures) and EON (electrostatic similarity) software, and in the final search, the top 100 were selected. Subsequently, in silico pharmacokinetic and toxicological properties were determined resulting in a total of 14 molecules, and these were submitted to the PASS online server for the prediction of biological insecticide and acetylcholinesterase activities, and only two selected molecules followed for the molecular docking study to evaluate the binding free energy and interaction mode. After these procedures were performed, toxicity risk assessment such as LD50 values in mg/kg and toxicity class using the PROTOX online server, were undertaken. Molecule ZINC00001624 presented potential for inhibition for the acetylcholinesterase enzyme (insect and human) with a binding affinity value of -10.5 and -10.3 kcal/mol, respectively. The interaction with the juvenile hormone was -11.4 kcal/mol for the molecule ZINC00001021. Molecules ZINC00001021 and ZINC00001624 had excellent predictions in all the steps of the study and may be indicated as the most promising molecules resulting from the virtual screening of new insecticidal agents.Federal University of Amapá, Program in Biotechnology and Biodiversity-Network BIONORTE, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) for funding in the publication of this article

Macrophage fumarate hydratase restrains mtRNA-mediated interferon production

Metabolic rewiring underlies the effector functions of macrophages1-3, but the mechanisms involved remain incompletely defined. Here, using unbiased metabolomics and stable isotope-assisted tracing, we show that an inflammatory aspartate-argininosuccinate shunt is induced following lipopolysaccharide stimulation. The shunt, supported by increased argininosuccinate synthase (ASS1) expression, also leads to increased cytosolic fumarate levels and fumarate-mediated protein succination. Pharmacological inhibition and genetic ablation of the tricarboxylic acid cycle enzyme fumarate hydratase (FH) further increases intracellular fumarate levels. Mitochondrial respiration is also suppressed and mitochondrial membrane potential increased. RNA sequencing and proteomics analyses demonstrate that there are strong inflammatory effects resulting from FH inhibition. Notably, acute FH inhibition suppresses interleukin-10 expression, which leads to increased tumour necrosis factor secretion, an effect recapitulated by fumarate esters. Moreover, FH inhibition, but not fumarate esters, increases interferon-β production through mechanisms that are driven by mitochondrial RNA (mtRNA) release and activation of the RNA sensors TLR7, RIG-I and MDA5. This effect is recapitulated endogenously when FH is suppressed following prolonged lipopolysaccharide stimulation. Furthermore, cells from patients with systemic lupus erythematosus also exhibit FH suppression, which indicates a potential pathogenic role for this process in human disease. We therefore identify a protective role for FH in maintaining appropriate macrophage cytokine and interferon responses

I am the chosen one: Narcissism in the backdrop of self-determination theory

© 2018 Wiley Periodicals, Inc. Objective: This theoretical article discusses the relevance of self-determination theory (SDT) for narcissism, a classic topic in self-theory. Method and Results: The trait of narcissism reflects a self-aggrandizing, dominant, and manipulative interpersonal orientation that feeds on exaggerated perceptions of agency, but not communion. The article embeds narcissism in the five mini-theories of SDT (organismic integration, causality orientations, basic needs, cognitive evaluation, and goal contents) and considers research directions that can explore synergies between key constructs from SDT and narcissism. Conclusions: SDT can serve as a foundation for a deeper understanding of narcissism. From the other end, narcissism can enrich SDT by explaining variations in motivational processes