Prediction of the flexible pipe annulus pH at high CO2 content and high temperature

International audiencePrevious works have shown that the typical ratio between the volume of electrolyte and the exposed steel surface observed in the annulus of flexible pipelines leads to a specific corrosive environment whose pH deviate from the classical thermodynamic models. In this case, due to the supersaturation in iron ions in the annulus, the commercial models even with their most recent updates cannot precisely predict the measured pH. Due to these specificities, tests are necessary to overcome these limitations and to improve with a better accuracy the pH considered in the design of the flexible pipes. Nowadays, with the development of the Brazilian oil and gas pre-salt basins, a high CO2 partial pressure associated with high temperature are observed in the flexible pipe annulus. Due to the lack of experimental data concerning the pH evolution under these conditions, tests were carried out with a continuous pH monitoring at CO2 partial pressure and temperature up to, respectively, 70 bara and 84 °C. The test results presented in this article show an amplitude between the experimental data and the predicted pH values of at least +0.4 pH units which confirms the conservatism of the thermodynamic models at saturation. In all the tests, the pH reached a maximum value after the first days of immersion followed by a decrease and fast stabilization after this event. An impact of the temperature was verified on the pH behavior in these tests. Keywords Flexible pipes; annulus pH; high pressure; high temperature

Mutagenicity of New Lead Compounds to Treat Sickle Cell Disease Symptoms in a Salmonella/Microsome Assay

A series of phthalimide derivatives planned as drugs candidates to treat the symptoms of sickle cell anemia were evaluated in a mutagenicity test using strains of Salmonella typhimurium TA100 and TA102, without and with addition of S9 mixture, with the aim to identify the best structural requirements for a drug candidate without genotoxic activity. The compounds (1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl nitrate (1); (1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl nitrate (2); 3-(1,3-dioxo-1,3-dihydro-2H-iso-indol-2-yl)benzyl nitrate (3); 4-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-N-hydroxy-benzenesulfonamide (4); 4-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)benzyl nitrate (5) and 2-[4-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)phenyl]ethyl nitrate (6) presented mutagenic potency ranging between 0–4,803 revertants/μmol. These results allowed us to propose that a methyl spacer linked to a nitrate ester subunit associated to meta aromatic substitution decreases mutagenicity

BacPROTACs targeting Clp protease: a promising strategy for anti-mycobacterial drug discovery

Tuberculosis (TB) has claimed more lives over the course of two millennia than any other infectious disease worldwide. In 2021, the World Health Organization (WHO) estimated that 10.6 million people were diagnosed with TB, resulting in the deaths of 1.4 million HIV-negative individuals. The emergence of multidrug-resistant TB (MDR-TB), defined as resistance to at least rifampicin (RIF) and isoniazid (INH), and extensively drug-resistant TB (XDR-TB), poses the primary challenge to overcome in the coming years. We have recently conducted an extensive analysis of investments and research endeavours in the field, with the overarching objective of achieving the established milestone of TB eradication by the year 2030. Over the past several years, there has been notable progress in advancing a multitude of promising compounds, each possessing distinct mechanisms of action, into clinical phases of development. However, it is worth noting that strains of mycobacteria resistant to current antitubercular drugs have already emerged for some of these compounds The exploration of the innovative Proteolytic Target Chimeras (PROTACs) protein degradation approach has emerged as a viable avenue for the discovery of novel antimicrobials. While the ubiquitin system is exclusive to eukaryotic cells, certain bacteria use a similar degradation system that relies on the recognition of phosphorylated arginine residues (pArg) by the ClpC:ClpP (ClpCP) protease, thereby leading to protein degradation. In this opinion article, we have described and analized the advances in the use of PROTACs that leverage bacterial proteolytic machinery (BacPROTACs) to design new antitubercular agents. Scope Statement. The development of novel pharmaceuticals for tuberculosis treatment is deemed urgently necessary due to the emergence of resistant strains. In this context, the introduction of new technologies capable of alleviating the disease and attaining the objectives outlined by the World Health Organization is imperative. Among the innovative strategies, the degradation of proteins that are crucial for the survival of the bacillus holds promise for generating new medications, particularly those that are effective at treating latent (non-replicating) Mycobacterium tuberculosis. Within this perspective, we present the advancements and obstacles encountered in the exploration of new BacPROTAC compounds, with the intention of encouraging research and illuminating challenges associated with the implementation of BacPROTACs to address to the global tuberculosis crisis

Integrando ensino, pesquisa e extensão universitária em assistência farmacêutica

University extension events in form of seminars, courses, workshops and round table discussions are realce associated with thedevelopment of strategies that allow advances in certain areas of knowledge. In this paper, we report the experience of seven years of the accomplishing the International Meeting on Pharmaceutical Care, highlighting the obtained advances by proposed performance indicators and the articulation created with the public health system enabling the promotion and development of a recent area within the Pharmaceutical Sciences. The indivisibility of teaching, research and extension is evident and shows how the extension events can strengthen research and stimulate change even in the curricular structure at a graduate and post-graduate level. Among the results that stand out are: increase in the number of extension projects (05), book publishing (03), scientific articles (06), acquiring resources in development agencies (03) and awards (04). It is concluded that the integration with the public health system, research on pharmacotherapeutic following, management and optimization of pharmacotherapy, changes in the undergraduate curriculum disciplines and other actions catalysed by the event have been possibilitating the promotion and strengthening of the Pharmaceutical care area in the Faculty of Pharmaceutical Sciences (UNESP-Araraquara).  Este trabajo presenta las experiencias de un proyecto de extensión hecho de forma independiente en un lugar en Rio do Sul, entre los años de 2007 y 2016. A través del proyecto se pusieron en práctica los conceptos de educación ambiental. Fue seleccionada un área que se extraían rocas y sufría con problemas ambientales. Con los propietarios, trabajadores y moradores de la propiedad, fue hecho un trabajo sobre los conceptos y prácticas de educación ambiental. Metodológicamente, las visitas se llevaron a cabo y fueron exteriorizados conceptos de educación ambiental. Se rodeó de la zona, y las actividades de restauración ambiental iniciaron. Con el entrenamiento y la exposición de experiencias se pasó a la gente la importancia de las cuestiones ambientales en la sociedad. El proyecto resultó en un aumento en la preservación del medio ambiente del local estudiado.Eventos de extensão universitária permanente em formato de seminários, cursos, oficinas e mesas redondas estão diretamente associados ao delineamento de estratégias que permitem avanços em determinadas áreas do conhecimento. Neste trabalho, relata-se a experiência de sete anos de realização do International Meeting on Pharmaceutical Care destacando-se os avanços obtidos por meio de indicadores de resultados propostos e a articulação criada com o sistema público de saúde e possibilitando-se o fomento e o desenvolvimento de uma área recente no âmbito das Ciências Farmacêuticas. Assim, não só a indissociabilidade entre ensino, pesquisa e extensão fica evidenciada mas também fica evidente como os eventos de extensão podem fortalecer a pesquisa e promover alterações inclusive na estrutura curricular da graduação e pós-graduação. Entre os resultados diretamente relacionados ao evento, destacam-se: ampliação no número de projetos de extensão (05), publicação de livros (03), artigos científicos (06), captação de recursos em agencias de fomentos (03) e prêmios (04). Conclui-se que a integração com o sistema público de saúde, pesquisas sobre seguimento farmacoterapêutico, gerenciamento e otimização da farmacoterapia, modificação no conteúdo programático de disciplinas da graduação entre outras ações catalisadas/proporcionadas pelo evento tem possibilitado o fomento e o fortalecimento da área de Assistência Farmacêutica na Faculdade de Ciências Farmacêuticas (UNESP-Araraquara).

Integrando ensino, pesquisa e extensão universitária em assistência farmacêutica

University extension events in form of seminars, courses, workshops and round table discussions are realce associated with thedevelopment of strategies that allow advances in certain areas of knowledge. In this paper, we report the experience of seven years of the accomplishing the International Meeting on Pharmaceutical Care, highlighting the obtained advances by proposed performance indicators and the articulation created with the public health system enabling the promotion and development of a recent area within the Pharmaceutical Sciences. The indivisibility of teaching, research and extension is evident and shows how the extension events can strengthen research and stimulate change even in the curricular structure at a graduate and post-graduate level. Among the results that stand out are: increase in the number of extension projects (05), book publishing (03), scientific articles (06), acquiring resources in development agencies (03) and awards (04). It is concluded that the integration with the public health system, research on pharmacotherapeutic following, management and optimization of pharmacotherapy, changes in the undergraduate curriculum disciplines and other actions catalysed by the event have been possibilitating the promotion and strengthening of the Pharmaceutical care area in the Faculty of Pharmaceutical Sciences (UNESP-Araraquara).  Este trabajo presenta las experiencias de un proyecto de extensión hecho de forma independiente en un lugar en Rio do Sul, entre los años de 2007 y 2016. A través del proyecto se pusieron en práctica los conceptos de educación ambiental. Fue seleccionada un área que se extraían rocas y sufría con problemas ambientales. Con los propietarios, trabajadores y moradores de la propiedad, fue hecho un trabajo sobre los conceptos y prácticas de educación ambiental. Metodológicamente, las visitas se llevaron a cabo y fueron exteriorizados conceptos de educación ambiental. Se rodeó de la zona, y las actividades de restauración ambiental iniciaron. Con el entrenamiento y la exposición de experiencias se pasó a la gente la importancia de las cuestiones ambientales en la sociedad. El proyecto resultó en un aumento en la preservación del medio ambiente del local estudiado.Eventos de extensão universitária permanente em formato de seminários, cursos, oficinas e mesas redondas estão diretamente associados ao delineamento de estratégias que permitem avanços em determinadas áreas do conhecimento. Neste trabalho, relata-se a experiência de sete anos de realização do International Meeting on Pharmaceutical Care destacando-se os avanços obtidos por meio de indicadores de resultados propostos e a articulação criada com o sistema público de saúde e possibilitando-se o fomento e o desenvolvimento de uma área recente no âmbito das Ciências Farmacêuticas. Assim, não só a indissociabilidade entre ensino, pesquisa e extensão fica evidenciada mas também fica evidente como os eventos de extensão podem fortalecer a pesquisa e promover alterações inclusive na estrutura curricular da graduação e pós-graduação. Entre os resultados diretamente relacionados ao evento, destacam-se: ampliação no número de projetos de extensão (05), publicação de livros (03), artigos científicos (06), captação de recursos em agencias de fomentos (03) e prêmios (04). Conclui-se que a integração com o sistema público de saúde, pesquisas sobre seguimento farmacoterapêutico, gerenciamento e otimização da farmacoterapia, modificação no conteúdo programático de disciplinas da graduação entre outras ações catalisadas/proporcionadas pelo evento tem possibilitado o fomento e o fortalecimento da área de Assistência Farmacêutica na Faculdade de Ciências Farmacêuticas (UNESP-Araraquara).

IMPACT OF DIFFERENT USE SYSTEMS ON TOTAL AND MINERALIZABLE ORGANIC CARBON IN A SANDY SOIL

O objetivo deste trabalho foi avaliar o impacto de diferentes sistemas de uso nos teores e estoques de carbono orgânico total (COT) e a evolução diária e total do carbono mineralizável (C-CO2) em um Argissolo Vermelho Amarelo de textura arenosa. O estudo foi realizado no município de Eldorado, MS, em uma área de referência de Mata Nativa (MN), e em três áreas manejadas: pastagem permanente (PP), semeadura direta (SD) e área de Reserva Particular de Patrimônio Natural em processo de regeneração natural (RPPN). Amostras de solo das camadas 0,0-0,05, 0,05-0,10 e 0,10-0,20 m foram coletadas para avaliação de densidade do solo (Ds), teores de COT, com posteriores cálculos do índice de estratificação (IE), estoque de carbono (EstC) e variação do estoque de carbono orgânico total (∆EstC), além da determinação da emissão diária e cálculo do acúmulo total de C-CO2. A área de MN apresentou os maiores teores e estoques de COT, chegando a 16,42 g kg-1 e 20,90 Mg ha-1, respectivamente. Já as áreas de PP e RPPN os menores teores e EstC. As áreas de PP, SD, RPPN e MN apresentaram valores de IE de 1,08, 1,13, 1,32 e 1,61, respectivamente. A área de MN apresentou maiores picos e maior acúmulo total de C-CO2. Pela análise multivariada, nenhuma das áreas manejadas se aproximou em qualidade a MN. Os piores resultados nos atributos avaliados são observados nas áreas de PP e RPPN devido ao estágio de degradação destas áreas em função do histórico de exploração e uso do solo.This study aimed to evaluate the impact of different land use systems on total organic carbon (TOC) contents and stocks and the daily and total evolution of mineralizable carbon (C-CO2) in a sandy-textured Argissolo Vermelho Amarelo. The study was carried out in Eldorado, MS, in a reference area of Native Forest (NF) and three managed areas: Permanent Pasture (PP), Direct Sowing b(DS), and an area of Private Natural Heritage Reserve (PNHR) in the process of natural regeneration. Soil samples from the 0.0-0.05, 0.05-0.10, and 0.10-0.20 m layers were collected to assess soil density (Sd), TOC contents, with subsequent calculations of the stratification index (SI), carbon stock (StockC), and variation of the total organic carbon stock (∆StockC), in addition to the determination of daily emission and calculation of total C-CO2 accumulation. The NF area had the highest levels and stocks of TOC, reaching 16.42 g kg-1 and 20.90 Mg ha-1, respectively. On the other hand, the PP and PNHR areas had the lowest content and StockC. The areas of PP, DS, PNHR, and NF presented SI values of 1.08, 1.13, 1.32, and 1.61, respectively. The NF area showed higher peaks and a higher total accumulation of C-CO2, inferring the highest biological activity in this area. By multivariate analysis, none of the managed areas was close to the NF in quality. The worst results considering the evaluated attributes were observed in the areas of PP and PNHR due to the stage of degradation of these areas as a result of exploration and land use history

Sickle Cell Disease – Current Treatment and New Therapeutical Approaches

Sickle cell disease (SCD) is one of the most common genetic disorders worldwide. It is caused by a point mutation that changes glutamic acid (Glu6) to valine (Val6) in the β chain of hemoglobin. Vaso-occlusion is the most well-known problem associated with SCD. Despite recent advances in understanding the disease at the molecular level, few therapeutic strategies are available. Hydroxyurea is the only drug currently approved by the U.S. Food and Drug Administration for the disease, and it has serious adverse effects and lack of efficacy in some patients. However, new therapeutic approaches are under investigation in the hope of discovering new drugs to treat SCD. These include agents that: a) increase nitric oxide bioavailability; b) modify the rheological properties of the blood; c) bind covalently to hemoglobin; d) prevent hemoglobin dehydration; e) reduce iron overload; and f) induce the expression of gamma globin and fetal hemoglobin. In this chapter, we discuss the current treatment of SCD and the advances made in medicinal chemistry to find new drugs to treat this neglected hematological disease

Avaliação tridimensional de carcinoma mucoepidermoide em palato duro: relato de caso clínico

Mucoepidermoid carcinoma is of unknown aetiopathology, but it may be related to genetic factors, exposure to ionizing radiation and smoking habits as well. Mucoepidermoid carcinoma is considered the most common malignant neoplasm of salivary glands found in the oral cavity, with its clinical characteristics (e.g., size and shape) favoring the diagnosis and treatment planning. This report describes a case of mucoepidermoid carcinoma which infiltrates into the maxillary sinus and nasal fossa through the palate and highlights the importance of obtaining three-dimensional (3D) images of the tumor for volumetric analysis, thus improving the chances of a successful surgery. We have described the use of the segmentation technique in which the tumor’s volume was calculated to help in predicting surgical outcomes. A 50-year-old patient sought dental treatment because of a purplish swelling in the hard palate region on the left side. Computed tomography examination was performed for visualization of the lesion and incisional biopsy for obtaining a sample, which was sent to anatomopathological study. Histological characteristics of the lesion and presence of neoplastic cells showed positive immunohistochemical reactions for cytokeratin 7 antibody, leading to a diagnosis of mucoepidermoid carcinoma. In view of the malignant characteristics of the lesion, the patient was referred to a head and neck surgeon for treatment.O carcinoma mucoepidermoide possui etiopatogenia desconhecida, porém, pode ser relacionado a fatores genéticos, exposição à radiação ionizante e também ao hábito de fumar. Há a possibilidade de crescer de forma assintomática. É considerado a neoplasia maligna de glândulas salivares mais comum encontrada na cavidade oral e as suas características clínicas (por exemplo, sítio de predileção e forma como se apresenta) favorecem um melhor diagnóstico e planejamento de intervenção. Este relato apresenta um caso de carcinoma mucoepidermoide que se infiltra no seio maxilar e fossa nasal através do palato e destaca a importância da obtenção de imagens tridimensionais (3-D) do tumor para análise volumétrica e melhoria das chances de sucesso cirúrgico. Descrevemos o uso de uma técnica pictórica em que o volume do tumor foi calculado para ajudar a prever os resultados cirúrgicos. A paciente de 50 anos procurou atendimento odontológico devido ao aumento de volume com coloração arroxeada em região de palato duro do lado esquerdo, foi realizado o exame de Tomografia Computadorizada onde se verificou a lesão. A partir da biópsia incisional e o encaminhamento para avaliação anatomopatológica, suas características histológicas e as células neoplásicas mostraram-se positivas para as reações de imunohistoquímica contra anticorpo citoqueratina sete, o que concluiu o diagnóstico de carcinoma mucoepidermoide. Diante das características malignas da lesão, a paciente foi encaminhada para médico cirurgião de cabeça e pescoço para tratamento