Oral glucose lowering drugs in type 2 diabetic patients with chronic kidney disease

Chronic kidney disease (CKD) represents a challenge in the treatment of type 2 diabetic patients. Renal impairment may affect drug clearance and other pharmacokinetic processes which can increase toxicity and drug to drug interactions or cause ineffective therapy. There are many oral glucose lowering drugs available for the treatment of type 2 diabetes mellitus (T2DM) with different mechanisms of action and different pharmacokinetic profiles. While all classes may be used in patients with mild renal impairment, therapeutic options for patients with moderate to severe CKD are still limited. This review focuses on the pharmacokinetics, metabolism, and safety of oral glucose lowering drugs in patients with T2DM and CKD

Mangal communities of the "Salgado Paraense": Ecological heterogeneity along the Bragança peninsula assessed through soil and leaf analyses

Mangroves in the Bragança peninsula occur in a variety of environmental settings differing in tidal influence and fresh water run-off. The construction of a paved road running through the middle of the peninsula modified the transversal flow of water. Five sites were sampled along this road: I. Coastal site near the village of Ajuruteua, II. Tidal creeks flowing into the lower Caeté river, III. Central lagoons, IV. Avicennia basin forest, and V. Upper Caeté estuary near the village of Acarajó. All but site III, harbored the three common mangroves species Rhizophora mangle, Laguncularia racemosa and Avicennia germinans. Monospecific communities of shrub-like Avicennia germinans stands characterized site III. Soils were highly organic therefore bulk density was inversely correlated to the concentrations of C and N. Sites I and V had the lowest salinity values. The highest salinity was measured ii the Avicennia dominated sites III and IV. Nitrogen showed similar values in all sites, but S was clearly more abundant in sites II and V. Leaf dimensions varied significantly between sites. Considering leaf area expansion as indicator ofstress and δ 13C values as indicator of water use efficiency, site V was more favorable for Rhizophora and Laguncularia while site IV was so for Avicennia. Leaf shape measured as the length/width ratio was more variable in Avicennia and least variable in Rhizophora. Leaf nutrients were not correlated with soil nutrient content. Sodium and Mg were more concentrated in Avicennia leaves while Fe was more concentrated in Laguncularia and Mn in Rhizophora leaves. Avicennia showed the highest N and the lowest Ca concentrations as expected for being a glycinbetaine accumulator and an oxalate-former. δ 15N values indicate that N source for mangroves is essentially the mineralization of organic matter

Aplicação prática da Norma NP EN ISO/IEC 17025: apresentação de dois casos de estudo

A qualidade tornou-se, ao longo dos tempos, uma ferramenta de diferenciação de produtos e serviços, ajudando a consolidar posições no mercado. Se de início a motivação para a qualidade residia na satisfação do cliente ao nível das suas exigências mais básicas, como seja o paladar ou a estética, hoje a motivação está muito mais apoiada na segurança e higiene dos produtos, mantendo, contudo, o vector de satisfação básica do consumidor. Para que a Qualidade fosse uma certeza e fosse possível a sua garantia, foi necessário criar um sistema de certificação e acreditação de produtos e serviços. Assim, ao nível da acreditação de laboratórios de ensaio e/ou calibração, surgiu a Norma NP EN ISO/IEC 17025, que veio garantir a diferenciação entre uma qualidade controlada, verificada e validada e a qualidade aparente, que pode ou não ser comprovada. Dada a complexidade da implementação dos processos de acreditação de laboratórios e as dificuldades provenientes da livre interpretação da Norma, foi criado um guia interpretativo da mesma. Ainda assim, as dúvidas persistem, nomeadamente quanto à adequação dos requisitos a cada caso concreto. O confronto com esta realidade conduziu à realização do presente trabalho

BRS Sarandi: A New Andropogon Gayanus Cultivar for Tropical Pastures

BRS Sarandi is adapted to low and medium fertility soils. It has a medium-high height, with a semi-erect growth habit and a high total number of tillers. The annual productivity of dry matter is 11 t ha-1, concentrated in the rainy season (90%). Of the total DM produced, 60% are leaves. The levels of crude protein (CP), in vitro dry matter digestibility (IVDMD), neutral detergent fiber (NDF) and acid detergent fiber (ADF) are, on average, 8.7, 56.5, 66.7 and 38.2%, respectively. . The average daily weight gain was 0.7 kg/head/day, the gain per was and 1.7 kg ha-1 day with no supplementation except for mineral salt. The weight gain per area (AG) reached 15 @/ha/year with an average stocking rate of 2.5 AU. BRS Sarandi was registered in the Brazilian Cultivar Registry (Registro Nacional de Cultivares - RNC/MAPA) and is protected in the National Cultivar Protection System (Sistema Nacional de Proteção de Cultivares - SNPC/MAPA)

Apresentação clínica de SCA2 como uma síndrome ataxia-parkinsonismo-doença do neurônio motor

Universidade Federal de São Paulo (UNIFESP) Department of Neurology and Neurosurgery Division of General Neurology and AtaxiasUNIFESP, Department of Neurology and Neurosurgery Division of General Neurology and AtaxiasSciEL

Repeatability, number of harvests, and phenotypic stability of dry matter yield and quality traits of Panicum maximum jacq.

Selection of superior forage genotypes is based on agronomic traits assayed in repeated measures. The questions are how repeatable the performance of individual genotypes is and how many harvests are needed to select the best genotypes. The objectives were to estimate repeatability coefficients of dry matter yield (DMY) and forage quality, their phenotypic stability and the number of harvests needed for an accurate selection. Two randomized complete block design experiments data with 24 genotypes each, undergoing 12 and 16 harvests, over a period of 2 and 3 years, respectively, were used. The DMY repeatability estimates ranged from 0.42 to 0.55, suggesting a low heritability. The mean numbers of repeated measures were 5 and 7 harvests for 0.80 and 0.85 accuracy, respectively. The inclusion of the first two harvests negatively affects the estimates. Repeatability for quality traits ranged from 0.30 to 0.69, indicating low to moderate heritability.Título em português: Repetibilidade, número de colheitas e estabilidade fenotípica da produção de matéria seca e de características de qualidade de Panicum maximum jacq

Tuberculose em área endêmica na Bahia, Brasil: análise de tendência de uma década

Objetivo: Descrever os casos de tuberculose, com base no perfil clínico-epidemiológico e na distribuição geográfica, no período de 2010 a 2020, em uma área endêmica da Bahia, Brasil. Método: Estudo realizado a partir de dados secundários obtidos mediante consulta às fichas de notificação de tuberculose de um centro de referência no município de Paulo Afonso, Bahia, Brasil. Os casos notificados de tuberculose entre 2010 e 2020 foram incluídos e submetidos à análise estatística e distribuição espacial. Resultados: Dos 391 casos, 90,8% foram diagnosticados como tuberculose pulmonar, com média de 25,9 casos por 100.000 habitantes na série histórica. Do total de casos, 69,8% eram do sexo masculino, 49,6% tinham idade entre 31 e 59 anos, média de idade 43,4 ± 17.7 anos, 62,1% eram bacilíferos e a maioria dos pacientes foram categorizados como casos novos (81,6%). Ao final do tratamento da TB, 75,7% apresentaram um resultado bem-sucedido (curado) e 48,8% dos casos receberam terapia diretamente observada. Na distribuição espacial, observou-se aglomerados nas macrozonas insular e sul no município de Paulo Afonso. Conclusão: A tuberculose persiste como significativo problema de saúde pública no município e medidas para melhorar o diagnóstico precoce e o tratamento são essenciais, principalmente após a pandemia da COVID-19, considerando o perfil epidemiológico e a distribuição espacial da doença.Objective: To describe the tuberculosis cases, based on clinical-epidemiological profile and geographic distribution, from 2010 to 2020 in an endemic area in Bahia, Brazil. Method: It was a study based on secondary data obtained of individual tuberculosis reporting forms from a reference center in Paulo Afonso municipality, Bahia, Brazil. Reported tuberculosis cases between 2010 and 2020 were included and submitted to statistical analysis and spatial distribution. Results: Among the 391 cases, 90.8% had a pulmonary form with a mean of 25.9 cases per 100,000 inhabitants in the historical series. Of all cases, 69.8% were male, 49.6% were aged between 31 and 59 years, mean age 43.4 ± 17.7 years, 62.1% were smear-positive and most of the cases were new (81.6%). At the end of TB treatment, 75.7% had a successful outcome (cured) and 48.8% patients received directly observed therapy. In the spatial distribution, we observed agglomerates in the insular and south macrozones in Paulo Afonso municipality. Conclusion: Tuberculosis remains a significant public health problem in the municipality, and measures to improve early diagnosis and treatment are crucial, especially following the onset of the COVID-19 pandemic, considering the epidemiological profile and spatial distribution of the disease

Optimal fractions of phosphorus fertilizer applied in preplanting and in drip fertigation of tomato crop

O objetivo deste trabalho foi estabelecer frações ótimas da dosagem total de fósforo, a serem aplicadas no pré‑plantio e na fertirrigação do tomateiro de crescimento determinado, bem como determinar o efeito das diferentes formas de aplicação do nutriente sobre sua distribuição espacial no solo. Os tratamentos consistiram de cinco esquemas de aplicação do fertilizante: 100, 75, 50, 25 e 0% da dose total de P, dividida entre o pré‑plantio (superfosfato triplo incorporado ao solo) e a fertirrigação (ácido fosfórico). O experimento foi realizado em Latossolo Vermelho argiloso com duas classes de disponibilidade de P – 7,5 e 32,9 mg dm-3 (Mehlich‑1). Os tratamentos não apresentaram efeito sobre as variáveis de produção do tomateiro cultivado no solo com alta disponibilidade de P. Entretanto, no solo com menor disponibilidade do nutriente, a fertirrigação com P apresentou efeito quadrático sobre a produtividade de frutos, a receita líquida e a taxa líquida de retorno. Os melhores resultados foram obtidos com a aplicação de metade da dose total de P pela fertirrigação. A fertirrigação possibilitou movimento vertical do nutriente no solo para até 30 cm de profundidade, e movimento horizontal de até 15 cm.The objective of this work was to establish the optimal fractions of the total amount of phosphorus to be applied in preplanting and in drip fertigation of determinate‑growth tomato, as well as to determine the effect of the different forms of nutrient application on their soil spatial distribution. Treatments consisted of five schemes of fertilizer application: 100, 75, 50, 25, and 0% of P total dose divided between the pre‑planting (triple superphosphate in band placement) and the fertigation (phosphoric acid). The experiment was carried out in a clayed Oxisol with two P availability classes – 7.5 and 32.9 mg dm-3 (Mehlich‑1). The treatments showed no effect on tomato production variables in the soil with high P availability. However, in the soil with smaller availability of the nutrient, P fertigation showed a quadratic effect on fruit yield, net income, and net rate of return. The best results were obtained with half of the P total dose applied by fertigation. The fertigation allowed P movement in the soil up to 30 cm deep, and horizontal movement up to 15 cm

Targeting MAGE-C1/CT7 Expression Increases Cell Sensitivity to the Proteasome Inhibitor Bortezomib in Multiple Myeloma Cell Lines

The MAGE-C1/CT7 encodes a cancer/testis antigen (CTA), is located on the chromosomal region Xq26-27 and is highly polymorphic in humans. MAGE-C1/CT7 is frequently expressed in multiple myeloma (MM) that may be a potential target for immunotherapy in this still incurable disease. MAGEC1/CT7 expression is restricted to malignant plasma cells and it has been suggested that MAGE-C1/CT7 might play a pathogenic role in MM; however, the exact function this protein in the pathophysiology of MM is not yet understood. Our objectives were (1) to clarify the role of MAGE-C1/CT7 in the control of cellular proliferation and cell cycle in myeloma and (2) to evaluate the impact of silencing MAGE-C1/CT7 on myeloma cells treated with bortezomib. Myeloma cell line SKO-007 was transduced for stable expression of shRNA-MAGE-C1/CT7. Downregulation of MAGE-C1/CT7 was confirmed by real time quantitative PCR and western blot. Functional assays included cell proliferation, cell invasion, cell cycle analysis and apoptosis. Western blot showed a 70-80% decrease in MAGE-C1/CT7 protein expression in inhibited cells (shRNA-MAGE-C1/CT7) when compared with controls. Functional assays did not indicate a difference in cell proliferation and DNA synthesis when inhibited cells were compared with controls. However, we found a decreased percentage of cells in the G2/M phase of the cell cycle among inhibited cells, but not in the controls (p < 0.05). When myeloma cells were treated with bortezomib, we observed a 48% reduction of cells in the G2/M phase among inhibited cells while controls showed 13% (empty vector) and 9% (ineffective shRNA) reduction, respectively (p < 0.01). Furthermore, inhibited cells treated with bortezomib showed an increased percentage of apoptotic cells (Annexin V+/PI-) in comparison with bortezomib-treated controls (p < 0.001). We found that MAGE-C1/CT7 protects SKO-007 cells against bortezomib-induced apoptosis. Therefore, we could speculate that MAGE-C1/CT7 gene therapy could be a strategy for future therapies in MM, in particular in combination with proteasome inhibitors.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Laboratory of Molecular Biology and Genomics, Ludwig Institute for Cancer Research, São Paulo Branch, BrazilUniversidade Federal de São Paulo, Disciplina Hematol & Hemoterapia, São Paulo, BrazilLudwig Inst Canc Res, Lab Mol Biol & Genom, São Paulo, BrazilRecepta Biopharma, Ludwig Inst Canc Res, São Paulo, BrazilInCor, Fac Med, Setor Vetores Virais, Lab Genet & Cardiol Mol, São Paulo, BrazilJohns Hopkins Univ, Sch Med, Dept Neurosurg, Ludwig Collaborat Grp, Baltimore, MD 21205 USAUniv Med Ctr Hamburg Eppendorf, Dept Med 2, Hamburg, GermanyUniversidade Federal de São Paulo, Disciplina Hematol & Hemoterapia, São Paulo, BrazilWeb of Scienc

Up-scalable approaches for yeast mannan oligosaccharides (MOS) production: characterization and immunomodulatory properties

Mannan oligosaccharides (MOS) are widely used as feed additives due to their effects on gut microbiome modulation. Its application in the nutraceutical and functional food industries is also increasing. Numerous studies portraying MOS production from β-mannans can be found, but its production from yeast mannans is barely explored. Herein, two up-scalable approaches to produce yeast-derived MOS are presented: hydrothermal and acidic processing. Process efficiency was evaluated, and the resulting extracts were characterized (ATR-FT-IR, PXRD, SEM, MWD, DSC, sugar, and protein content). Extracts were also evaluated for their cytotoxicity and immunomodulatory effect; furthermore, a simulated gastrointestinal tract digestion was performed to confirm their biological potential. The hydrothermal process resulted in the highest yield, whereas the acidic process resulted in lower molecular weight populations. Immunomodulatory results indicate that MOS digested extracts do not hold anti-inflammatory activity but grant an immunostimulant effect, whereas the non-digested MOS acidic extract showed an anti-inflammatory potential. This work provides valuable contributions towards the industrial production of yeast-derived MOS extracts, highlighting their potential for applications in various fields while contributing to a circular economy approach.info:eu-repo/semantics/publishedVersio