Similarities and Differences in the Peripheral Actions of Thyroid Hormones and Their Metabolites

Thyroxine (T4) and 3,5,3'-triiodothyronine (T3) are secreted by the thyroid gland, while T3 is also generated from the peripheral metabolism of T4 by iodothyronine deiodinases types I and II. Several conditions like stress, diseases, and physical exercise can promote changes in local TH metabolism, leading to different target tissue effects that depend on the presence of tissue-specific enzymatic activities. The newly discovered physiological and pharmacological actions of T4 and T3 metabolites, such as 3,5-diiodothyronine (3,5-T2), and 3-iodothyronamine (T1AM) are of great interest. A classical thyroid hormone effect is the ability of T3 to increase oxygen consumption in almost all cell types studied. Approximately 30 years ago, a seminal report has shown that 3,5-T2 increased oxygen consumption more rapidly than T3 in hepatocytes. Other studies demonstrated that exogenous 3,5-T2 administration was able to increase whole body energy expenditure in rodents and humans. In fact, 3,5-T2 treatment prevents diabetic nephropathy, hepatic steatosis induced by high fat diet, insulin resistance, and weight gain during aging in Wistar male rats. The regulation of mitochondria is likely one of the most important actions of T3 and its metabolite 3,5-T2, which was able to restore the thermogenic program of brown adipose tissue (BAT) in hypothyroid rats, just as T3 does, while T1AM administration induced rapid hypothermia. T3 increases heart rate and cardiac contractility, which are hallmark effects of hyperthyroidism involved in cardiac arrhythmia. These deleterious cardiac effects were not observed with the use of 3,5-T2 pharmacological doses, and in contrast T1AM was shown to promote a negative inotropic and chronotropic action at micromolar concentrations in isolated hearts. Furthermore, T1AM has a cardioprotective effect in a model of ischemic/reperfusion injury in isolated hearts, such as occurs with T3 administration. Despite the encouraging possible therapeutic use of TH metabolites, further studies are needed to better understand their peripheral effects, when compared to T3 itself, in order to establish their risk and benefit. On this basis, the main peripheral effects of thyroid hormones and their metabolites in tissues, such as heart, liver, skeletal muscle, and BAT are discussed herein

Banana peel and grape stalk: potential of valorization through the evaluation of chemical composition and physical-chemical properties

CHISA 2008 - 18th International Congress of Chemical and Process Engineering (CD-ROM of Full Texts)Bioconversion of food processing residues (agr o-based industrial residues) in valuable products has been receiving an increasing attention in the last years. In fact, the main problem experienced by agro-based industries in several c ountries is the management of their residues. As a consequence, many research centers and government departments are preparing scientific strategies in order to develop biotechnological processes capable of transforming these residues in new bio-products or as sources of other chemicals. Most of these agro-industrial residues are lignocellulosic materials constituted basically of cellulose, hemicelluloses, and lignin. In particular, banana production is one of the main economic resources of several regions in many countries, an important crop in the tropical and sub- tropical regions and one of the most consumed fruits in the world. Grapes are other of the world’s largest fruit crops, mainly grown for direct consumption, grape juice and wine- making processes. These agricultural/industrial activities generate large amounts of residues such as banana fruit peel and grape stalk. Taking in consideration these facts, it is fundamental to know their chemical composition and physical-chemical properties, in order to evaluate perspectives of applications and improvement of procedures towards an efficient utilization of these residues. For this reason, following hydrolysis, the residues obtained were analyzed by HPLC, FTIR, TGA and DSC. Preliminary results indicate the attractiveness of these materials for further applications due to their chemical composition and physical-chemical properties: glucan and xylan contents of banana peel are 23.2 ± 0.2% and 18.9 ± 0.5%, respectively, while grape stalk contains 26.5 ± 1.5% and 16.8 ± 0.4%, respectively. These results are in agreement with those obtained with some other agro-industrial residues. These approaches offer several advantages, since the several fractions obtained from the hydrolysis of these annually produced materials can be applied as raw-materials to reduce the existence of environmentally hazardous situations and/or to increase the supply of energy or chemicals produced from renewable resourcesFCT(Portugal), FAPESP(Brazil) and CAPES/GRICES(Brazil/Portugal)info:eu-repo/semantics/publishedVersio

Rodas de diálogos: construindo a agroecologia do DF e Entorno

Em outubro de 2014 ocorreu o IV Seminário de Agroecologia do Distrito Federal e Entorno, no Centro de Convenções Ulysses Guimarães, em Brasília – DF. O seminario reuniu cerca de 1.200 participantes entre agricultores/as, extensionistas, pesquisadores/as, professores/as, gestores/as públicos, estudantes, representantes de movimentos sociais e sindicais, para discutir os temas de agricultura familiar e políticas públicas no contexto da Agroecologia. O presente trabalho se propõe a relatar o desenvolvimento e resultados da dinâmica “Rodas de Diálogos: Construindo a Agroecologia do DF e Entorno”, realizada no âmbito do seminário. A partir dessa dinâmica, foi possível sistematizar as opiniões dos participantes sobre a Agroecologia no DF relacionada ao futuro ideal, situação presente e, em como como chegar ao futuro ideal. As Rodas de Diálogos contaram com grande integração dos, aproximadamente, 400 participantes, para compreender de forma colaborativa o cenário da Agroecologia na região e projetar estrategicamente um cenário futuro ideal, a partir de tudo que foi visto no seminario, que se encaixam em categorias específicas: Articulação; Educação; Meio Ambiente; Mercado; Políticas Públicas.Eje: B5 Sistemas de conocimiento (Relatos de experiencias)Facultad de Ciencias Agrarias y Forestale

Outcomes of TB Treatment by HIV Status in National Recording Systems in Brazil, 2003–2008

BACKGROUND: Although the Brazilian national reporting system for tuberculosis cases (SINAN) has enormous potential to generate data for policy makers, formal assessments of treatment outcomes and other aspects of TB morbidity and mortality are not produced with enough depth and rigor. In particular, the effect of HIV status on these outcomes has not been fully explored, partly due to incomplete recording in the national database. METHODOLOGY/PRINCIPAL FINDINGS: In a retrospective cohort study, we assessed TB treatment outcomes, including rates of cure, default, mortality, transfer and multidrug resistant TB (MDR-TB) among a purposively chosen sample of 161,481 new cases reported in SINAN between 2003 and 2008. The study population included all new cases reported in the six States with the highest level of completeness of the HIV status field in the system. These cases were mostly male (67%), white (62%), had pulmonary TB (79%) and a suspect chest X ray (83%). Treatment outcomes were best for those HIV negative cases and worst for those known HIV positive patients (cure rate of 85.7% and 55.7% respectively). In multivariate modeling, the risk of having an unfavorable outcome (all outcomes except cure) was 3.09 times higher for those HIV positive compared with those HIV negative (95% CI 3.02-3.16). The risk of death and default also increased with HIV positivity. The group without a known HIV status showed intermediate outcomes between the groups above, suggesting that this group includes some with HIV infection. CONCLUSIONS: HIV status played an important role in TB treatment outcomes in the study period. The outcomes observed in those with known HIV were poor and need to be improved. Those in the group with unknown HIV status indicate the need for wider HIV testing among new TB cases

Indole-Containing Pyrazino[2,1-b]quinazoline-3,6-diones Active against Plasmodium and Trypanosomatids

The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acsmedchemlett.1c00589.Malaria, leishmaniasis, and sleeping sickness are potentially fatal diseases that represent a real health risk for more than 3,5 billion people. New antiparasitic compounds are urgent leading to a constant search for novel scaffolds. Herein, pyrazino[2,1-b]quinazoline-3,6-diones containing indole alkaloids were explored for their antiparasitic potential against Plasmodium falciparum, Trypanosoma brucei, and Leishmania infantum. The synthetic libraries furnished promising hit compounds that are species specific (7, 12) or with broad antiparasitic activity (8). Structure-activity relationships were more evident for Plasmodium with anti-isomers (1S,4R) possessing excellent antimalarial activity, while the presence of a substituent on the anthranilic acid moiety had a negative effect on the activity. Hit compounds against malaria did not inhibit β-hematin, and in silico studies predicted these molecules as possible inhibitors for prolyl-tRNA synthetase both from Plasmodium and Leishmania. These results disclosed a potential new chemotype for further optimization toward novel and affordable antiparasitic drugs.publishersversionpublishe