Clinical oxidative stress during leprosy multidrug therapy:impact of dapsone oxidation

This study aims to assess the oxidative stress in leprosy patients under multidrug therapy (MDT; dapsone, clofazimine and rifampicin), evaluating the nitric oxide (NO) concentration, catalase (CAT) and superoxide dismutase (SOD) activities, glutathione (GSH) levels, total antioxidant capacity, lipid peroxidation, and methemoglobin formation. For this, we analyzed 23 leprosy patients and 20 healthy individuals from the Amazon region, Brazil, aged between 20 and 45 years. Blood sampling enabled the evaluation of leprosy patients prior to starting multidrug therapy (called MDT 0) and until the third month of multidrug therapy (MDT 3). With regard to dapsone (DDS) plasma levels, we showed that there was no statistical difference in drug plasma levels between multibacillary (0.518±0.029 μg/mL) and paucibacillary (0.662±0.123 μg/mL) patients. The methemoglobin levels and numbers of Heinz bodies were significantly enhanced after the third MDTsupervised dose, but this treatment did not significantly change the lipid peroxidation and NO levels in these leprosy patients. In addition, CAT activity was significantly reduced in MDT-treated leprosy patients, while GSH content was increased in these patients. However, SOD and Trolox equivalent antioxidant capacity levels were similar in patients with and without treatment. These data suggest that MDT can reduce the activity of some antioxidant enzyme and influence ROS accumulation, which may induce hematological changes, such as methemoglobinemia in patients with leprosy. We also explored some redox mechanisms associated with DDS and its main oxidative metabolite DDS-NHOH and we explored the possible binding of DDS to the active site of CYP2C19 with the aid of molecular modeling software

Environmental-dependent proline accumulation in plants living on gypsum soils

[EN] Biosynthesis of proline¿or other compatible solutes¿is a conserved response of all organisms to different abiotic stress conditions leading to cellular dehydration. However, the biological relevance of this reaction for plant stress tolerance mechanisms remains largely unknown, since there are very few available data on proline levels in stress-tolerant plants under natural conditions. The aim of this work was to establish the relationship between proline levels and different environmental stress factors in plants living on gypsum soils. During the 2-year study (2009¿2010), soil parameters and climatic data were monitored, and proline contents were determined, in six successive samplings, in ten taxa present in selected experimental plots, three in a gypsum area and one in a semiarid zone, both located in the province of Valencia, in south-east Spain. Mean proline values varied significantly between species; however, seasonal variations within species were in many cases even wider, with the most extreme differences registered in Helianthemum syriacum (almost 30 lmol g-1 of DW in summer 2009, as compared to ca. 0.5 in spring, in one of the plots of the gypsum zone). Higher proline contents in plants were generally observed under lower soil humidity conditions, especially in the 2009 summer sampling preceded by a severe drought period. Our results clearly show a positive correlation between the degree of environmental stress and the proline level in most of the taxa included in this study, supporting a functional role of proline in stress tolerance mechanisms of plants adapted to gypsum. However, the main trigger of proline biosynthesis in this type of habitat, as in arid or semiarid zones, is water deficit, while the component of ¿salt stress¿ due to the presence of gypsum in the soil only plays a secondary role.This work has been supported by the Spanish Ministry of Science and Innovation (Project CGL2008-00438/BOS), with contribution from the European Regional Development Fund.Boscaiu, M.; Bautista Carrascosa, I.; Lidón Cerezuela, AL.; Llinares Palacios, JV.; Lull, C.; Donat-Torres, M.; Mayoral García-Berlanga, O.... (2013). Environmental-dependent proline accumulation in plants living on gypsum soils. Acta Physiologiae Plantarum. 35:2193-2204. https://doi.org/10.1007/s11738-013-1256-3S2193220435Alvarado JJ, Ruiz JM, López-Cantarero I, Molero J, Romero L (2000) Nitrogen metabolism in five plant species characteristic of gypsiferous soils. J Plant Physiol 156:612–616Ashraf M, Foolad MR (2007) Roles of glycine betaine and proline in improving plant abiotic stress resistance. Environ Exp Bot 59:206–216Bates LS, Waldren RP, Teare ID (1973) Rapid determination of free proline for water stress studies. Plant Soil 39:205–207Briens M, Larher F (1982) Osmoregulation in halophytic higher plants: a comparative study of soluble carbohydrates, polyols, betaines and free proline. Plant, Cell Environ 5:287–292Burriel F, Hernando V (1947) Nuevo método para determinar el fósforo asimilable en los suelos. Anales de Edafología y Fisiología Vegetal 9:611–622Caballero I, Olano JM, Loidi J, Escudero A (2003) Seed bank structure along a semi-arid gypsum gradient in Central Spain. J Arid Environ 55:287–299Escudero A, Carnes LF, Pérez García F (1997) Seed germination of gypsophytes and gypsovags in semi-arid central Spain. J Arid Environ 36:487–497Escudero A, Somolinos RC, Olano JM, Rubio A (1999) Factors controlling the establishment of Helianthemum squamatum, an endemic gypsophite of semi-arid Spain. J Ecol 87:290–302FAO (1990) Management of gypsiferous soils. FAO Soils Bull 62Ferriol M, Pérez I, Merle H, Boira H (2006) Ecological germination requirements of the aggregate species Teucrium pumilum (Labiatae) endemic to Spain. Plant Soil 284:205–216Flowers TJ, Colmer TD (2008) Salinity tolerance in halophytes. New Phytol 179:945–963Flowers TJ, Troke PF, Yeo AR (1977) The mechanism of salt tolerance in halophytes. Ann Rev Plant Physiol 28:89–121Gil R, Lull C, Boscaiu M, Bautista I, Lidón A, Vicente O (2011) Soluble carbohydrates as osmolytes in several halophytes from a Mediterranean salt marsh. Not Bot Horti Agrobo 39(2):9–17Grigore MN, Boscaiu M, Vicente O (2011) Assessment of the relevance of osmolyte biosynthesis for salt tolerance of halophytes under natural conditions. Eur J Plant Sci Biotech 5:12–19Hare PD, Cress WA, Van Standen J (1998) Dissecting the roles of osmolyte accumulation during stress. Plant Cell Environ 21:535–553Keeney DR, Nelson DW (1982) Nitrogen inorganic forms. In: Page AL et al (eds) Methods of soil analysis, part 2: chemical and microbiological properties. Soil Science Society of America, Madison, pp 643–698Knudsen D, Peterson GA, Pratt PF (1982) Lithium, Sodium and Potassium. In: Page AL et al (eds) Methods of soil analysis, part 2: chemical and microbiological properties. Soil Science Society of America, Madison, pp 225–246Kuo S (1996) Phosphorus. In: Spark DL (ed) Methods of soil analysis: chemical methods, part 3. Soil Science Society of America, Madison, pp 869–919Martens H, Maes T (1989) Multivariate calibration. Wiley, New York, pp 97–108Martínez-Duro E, Ferrandis P, Escudero A, Luzuriaga AL, Herranz JM (2010) Secondary old-field succession in an ecosystem with restrictive soils: does time from abandonment matter? 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Not Bot Horti Agrobo 39(1):18–23Mota JF, Sánchez Gómez P, Merlo Calvente ME, Catalán Rodríguez P, Laguna Lumbreras E, de la Cruz Rot M, Navarro Reyes FB, Marchal Gallardo F, Bartolomé Esteban C, Martínez Labarga JM, Sainz Ollero H, Valle Tendero F, Serra Laliga L, Martínez Hernández F, Garrido Becerra JA, Pérez García FJ (2009) Aproximación a la checklist de los gipsófitos ibéricos. Anales de Biología 31:71–80Murakeözy ÉP, Nagy Z, Duhazé C, Bouchereau A, Tuba Z (2003) Seasonal changes in the levels of compatible osmolytes in three halophytic species of inland saline vegetation in Hungary. J Plant Physiol 160:395–401Nelson DW, Sommers LE (1982) Total carbon, organic carbon, and organic matter. In: Page AL et al (eds) Methods of soil analysis, part 2: chemical and microbiological properties. Soil Science Society of America, Madison, pp 539–577Palacio S, Escudero A, Montserrat-Martí G, Maestro M, Milla R, Albert M (2007) Plants living on gypsum: beyond the specialist model. Ann Bot 99:333–343Parsons RF (1977) Gypsophily in plants—a review. Am Midl Nat 96:1–20Pueyo Y, Alados CL, Maestro M, Komac B (2007) Gypsophile vegetation patterns under a range of soil properties induced by topographical position. Plant Ecol 189:301–311Rivas-Martínez S, Rivas-Sáenz S (2009) Worldwide Bioclimatic Classification System. Phytosociological Research Center, Complutense University of Madrid, Spain. http://www.globalbioclimatics.org/ . Accessed 15 Nov 2012Romão RL, Escudero A (2005) Gypsum physical soil crusts and the existence of gypsophytes in semi-arid central Spain. Plant Ecol 181:127–137Rubio A, Escudero A (2000) Small-scale spatial soil-plant relationship in semi-arid gypsum environment. Plant Soil 220:139–150Ruíz JM, López-Cantarero I, Rivero RM, Romero L (2003) Sulphur phytoaccumulation in plant species characteristic of gypsiferous soils. Int J Phytorem 5:203–210Szabados L, Savouré A (2010) Proline: a multifunctional amino acid. Trends Plant Sci 15:89–97Szabados L, Kovács H, Zilberstein A, Bouchereau A (2011) Plants in extreme environments: importance of protective compounds in stress tolerance. Adv Bot Res 57:105–150Tecator Application Note (1984) AN 5226: Determination of ammonium in 2 M KCl soil extracts by FIAstar 5000. AN 5201: Determination of the sum of nitrate and nitrite in water by FIAstar 5000. (Adapted for 2 M KCl soil extracts)Tipirdamaz R, Gagneul D, Duhazé C, Aïnouche A, Monnier C, Özkum D, Larher F (2006) Clustering of halophytes from an inland salt marsh in Turkey according to their ability to accumulate sodium and nitrogenous osmolytes. Environ Exp Bot 57:139–153Verheye WH, Boyadgiev TG (1997) Evaluating the land use potential of gypsiferous soils from field pedogenic characteristics. Soil Use Manage 13:97–103Vicente O, Boscaiu M, Naranjo MA, Estrelles E, Bellés JM, Soriano P (2004) Responses to salt stress in the halophyte Plantago crassifolia (Plantaginaceae). 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Portuguese recommendations for the use of biological and targeted synthetic diseasemodifying antirheumatic drugs in patients with rheumatoid arthritis – 2020 update

Objective: To update the recommendations for the treatment of rheumatoid arthritis (RA) with biological and targeted synthetic disease-modifying antirheumatic drugs (bDMARDs and tsDMARDs), endorsed by the Portuguese Society of Rheumatology (SPR). Methods: These treatment recommendations were formulated by Portuguese rheumatologists taking into account previous recommendations, new literature evidence and consensus opinion. At a national meeting, in a virtual format, three of the ten previous recommendations were re-addressed and discussed after a more focused literature review. A first draft of the updated recommendations was elaborated by a team of SPR rheumatologists from the SPR rheumatoid arthritis study group, GEAR. The resulting document circulated among all SPR rheumatologists for discussion and input. The level of agreement with each of all the recommendations was anonymously voted online by all SPR rheumatologists. Results: These recommendations cover general aspects such as shared decision, treatment objectives, systematic assessment of disease activity and burden and its registry in Reuma.pt. Consensus was also achieved regarding specific aspects such as initiation of bDMARDs and tsDMARDs, assessment of treatment response, switching and definition of persistent remission. Conclusion: These recommendations may be used for guidance of treatment with bDMARDs and tsDMARDs in patients with RA. As more evidence becomes available and more therapies are licensed, these recommendations will be updated.info:eu-repo/semantics/publishedVersio

Força muscular respiratória e capacidade funcional na insuficiência renal terminal

OBJETIVO: Verificar a associação da força muscular respiratória com a capacidade funcional, força proximal de membros inferiores e variáveis bioquímicas em pacientes em hemodiálise (HD). MÉTODOS: Participaram deste estudo 30 indivíduos (18 homens), com 53,4 ± 12,9 anos e tempo de HD de 41,1 ± 55,7 meses. Foram avaliados pressão inspiratória máxima (PImax), pressão expiratória máxima (PEmax), distância percorrida no teste de caminhada de seis minutos (6MWT), número de repetições no teste de sentar-e-levantar em 30 segundos (TSL) e registrados os exames bioquímicos de rotina no serviço. RESULTADOS: Houve diminuição da PEmax em relação aos valores preditos (p = 0,015) e redução na distância percorrida no 6MWT quando comparados com equações de predição (p < 0,001). O logPImax e o logPEmax correlacionaram-se com o número de repetições no TSL (r = 0,476, p = 0,008; r = 0,540, p = 0,002, respectivamente), e com os níveis séricos de fósforo (r = 0,422, p = 0,020; r = 0,639, p < 0,001, respectivamente). A distância no 6MWT correlacionou-se com o logPEmax (r = 0,511; p = 0,004) e com o número de repetições no TSL (r = 0,561; p = 0,001). CONCLUSÃO: A redução da PEmax em pacientes com IRT em HD está associada à capacidade funcional, força proximal de membros inferiores e níveis de fósforo sérico, podendo representar, pelo menos em parte, o baixo desempenho físico-funcional desses pacientes.OBJECTIVE: to evaluate the association of respiratory muscle strength with functional capacity, lower limb strength and biochemical variables in hemodialysis (HD) patients. METHODS: a cross-sectional study involving 30 patients (18 male), 53.4 ± 12.9 years, 41.1 ± 55.7 months on HD therapy. Maximal inspiratory pressure (PImax),maximal expiratory pressure (PEmax),distance completed in a six-minute walk test (6MWT) and number of repetitions in sit-and-stand test (STST) were evaluated. The biochemical variables were recorded in the database routine work service. RESULTS: LogEPmax and 6MWT values were significantly lower than the predicted values (p = 0.015; p < 0.001, respectively). logPImax and logPEmax were correlated with number of repetitions in STST (r = 0.476, p = 0.008; r = 0.540, p = 0.002, respectively) and with phosphorus blood levels (r = 0.422, p = 0.020; r = 0.639, p < 0.001, respectively). 6MWT was correlated with logPEmax (r = 0.511; p = 0.004) and with number of repetitions in STST (r = 0.561; p = 0.001). CONCLUSION: PEmax reduction in patients with ESRD on HD is associated with functional capacity, lower limb strength and phosphorus blood levels, and may at least partly represent the low physical and functional performance of these patients