Actividad y tratamiento de la artritis reumatoide / Rheumatoid Arthritis Activity and Treatment

El diagnóstico y el tratamiento de la artritis reumatoide temprana en el curso de la enfermedad proporcionan alivio de los síntomas y también previene el daño estructural a largo plazo y el deterioro funcional, con una mejora concomitante en la calidad de vida. El propósito de este estudio es exponer algunos enfoques de la artritis reumatoide en cuanto al tratamiento y comportamiento de la actividad de la enfermedad. El reconocimiento de los pacientes de que su enfermedad progresa rápidamente es fundamental para identificar candidatos en los cuales la terapia intensiva puede tener el mayor impacto, en términos de prevenir la progresión de la enfermedad. Los datos acumulados muestran que las estrategias de tratamiento intensivo con agentes biológicos, especialmente los inhibidores del factor de necrosis tumoral, son más eficaces que la monoterapia secuencial o la terapia de combinación progresiva. Estos muestran una eficacia sustancial en combinación con el metotrexato, ya que proporcionan beneficios y mejoras rápidas y sustanciales a los pacientes(AU)

The diagnosis and treatment of rheumatoid arthritis early in the course of the disease provides relief of symptoms and also prevents long-term structural damage and functional deterioration, with a concomitant improvement in quality of life. To expose approaches to rheumatoid arthritis in terms of the treatment and behavior of the activity of said disease. Recognition of patients with rapidly progressing disease is essential to identify candidates in whom intensive therapy can have the greatest impact, in terms of preventing disease progression. The accumulated data shows that intensive treatment strategies with biological agents, especially TNF inhibitors, are more effective than sequential monotherapy or progressive combination therapy. These show substantial efficacy in combination with methotrexate, providing rapid and substantial benefits and improvements in patient outcomes(AU)

Cuidados en los primeros mil días de vida. Armenta, San Pedro Sula / Care in the first thousand days of life, Armenta. San Pedro Sula

Los mil días de vida van desde la concep- cion hasta los 2 años de edad, etapa donde se determina el desarrollo básico del niño; la falta de una alimentación y cuidados adecua- dos produce daños físicos y cognitivos irreversibles para el resto de su vida. Objeti- vo Identificar los cuidados ofrecidos por la madre/encargado en los primeros mil días de vida, en los niños del programa de Atencion Integral de la niñez en la comunidad (AIN-C) de Armenta, San Pedro Sula, I Semestre aca- démico del 2016. Pacientes y Método: Investigación cuantitativa, transversal, des- criptivo, instrumento tipo cuestionario aplica- do a madres/encargados del cuidado de niños menores de dos años monitoreados por el programa AIN-C, estrategia de la secretaria de salud (SESAL) Población: 69 madres/encargados, muestra: 60 que acce- dieron a participar. Resultados: 83.4% de los niños menores de 2 años son cuidados por la madre, 83.3% asistieron a control prenatal, 66.6% de las madres asistió a un control puerperal, 93.4% de los menores recibieron lactancia materna/mixta, 100% de las madres/encargados vacunaron a los meno- res y 56.6% integraron los alimentos antes de los 6 meses. Conclusiones Los resultados señalan que las madres/encargados no reali- zan todos los cuidados que se deben ofrecer al niño en los primeros mil días de vida y los que se ofrecen no reúnen los requerimientos necesarios que le garanticen un desarrollo físico y cognitivo adecuado que le permita estar saludable en las siguientes etapas de su vida...(AU)

HPLC separation of human serum albumin isoforms based on their isoelectric points.

Human serum albumin (HSA) is the most abundant protein in plasma. Cys34, the only free Cys residue, is the predominant plasma thiol and a relevant sacrificial antioxidant. Both in vivo circulating HSA and pharmaceutical preparations are heterogeneous with respect to the oxidation state of Cys34. In this work, we developed an external pH gradient chromatofocusing procedure that allows the analysis of the oxidation status of HSA in human plasma and biopharmaceutical products based on the different apparent isoelectric points and chemical properties of the redox isoforms. Specifically, reduced-mercury blocked HSA (HSA-SHg(+)), HSA with Cys34 oxidized to sulfenic acid (HSA-SOH) and HSA oxidized to sulfinate anion (HSA-SO2(-)) can be separated with resolutions of 1.4 and 3.1 (first and last pair) and hence quantified and purified. In addition, an N-terminally degraded isoform (HSA3-585) in different redox states can be resolved as well. Confirmation of the identity of the chromatofocusing isolated isoforms was achieved by high resolution whole protein MS. It is proposed that the chromatofocusing procedure can be used to produce more exact and complete descriptions of the redox status of HSA in vivo and in vitro. Finally, the scalability capabilities of the chromatofocusing procedure allow for the preparation of highly pure standards of several redox isoforms of HSA.

Nitro-fatty acids: formation, redox signaling, and therapeutic potential.

SIGNIFICANCE: Nitrated derivatives of unsaturated fatty acids (nitro-fatty acids) are being formed and detected in human plasma, cell membranes, and tissue, triggering signaling cascades via covalent and reversible post-translational modifications of susceptible nucleophilic amino acids in transcriptional regulatory proteins and enzymes. RECENT ADVANCES: Nitro-fatty acids modulate metabolic as well as inflammatory signaling pathways, including the p65 subunit of nuclear factor κB and the transcription factor peroxisome proliferator-activated receptor-γ. Moreover, nitro-fatty acids can activate heat shock as well as phase II antioxidant responses. As electrophiles, they also activate the Nuclear factor erythroid 2-related factor 2 pathway. CRITICAL ISSUES: We first discuss the mechanisms of nitro-fatty acid formation as well as their key chemical and biochemical properties, including their capacity to release nitric oxide and exert antioxidant actions. The electrophilic properties of nitro-fatty acids to activate anti-inflammatory signaling pathways are discussed in detail. A critical issue is the influence of nitroarachidonic acid on prostaglandin endoperoxide H synthases, modulating inflammatory processes through redirection of arachidonic acid metabolism and signaling. FUTURE DIRECTIONS: Based on this information, we analyze in vivo data supporting nitro-fatty acids as promising pharmacological tools to prevent inflammatory diseases associated with oxidative and nitrative stress conditions. A key future issue is to evaluate whether nitro-fatty acid supplementation would be useful for human diseases linked to inflammation as well as their potential toxicity when administered by long periods of time.

Nitroarachidonic acid, a novel peroxidase inhibitor of prostaglandin endoperoxide H synthases 1 and 2.

Prostaglandin endoperoxide H synthase (PGHS) catalyzes the oxidation of arachidonate to prostaglandin H(2). We have previously synthesized and chemically characterized nitroarachidonic acid (AANO(2)), a novel anti-inflammatory signaling mediator. Herein, the interaction of AANO(2) with PGHS was analyzed. AANO(2) inhibited oxygenase activity of PGHS-1 but not PGHS-2. AANO(2) exhibited time- and concentration-dependent inhibition of peroxidase activity in both PGHS-1 and -2. The plot of k(obs) versus AANO(2) concentrations showed a hyperbolic function with k(inact) = 0.045 s(-1) and K(i)(*app) = 0.019 µM for PGHS-1 and k(inact) = 0.057 s(-1) and K(i)(*app) = 0.020 µM for PGHS-2. Kinetic analysis suggests that inactivation of PGHS by AANO(2) involves two sequential steps: an initial reversible binding event (described by K(i)) followed by a practically irreversible event (K(i)(*app)) leading to an inactivated enzyme. Inactivation was associated with irreversible disruption of heme binding to the protein. The inhibitory effects of AANO(2) were selective because other nitro-fatty acids tested, such as nitrooleic acid and nitrolinoleic acid, were unable to inhibit enzyme activity. In activated human platelets, AANO(2) significantly decreased PGHS-1-dependent thromboxane B(2) formation in parallel with a decrease in platelet aggregation, thus confirming the biological relevance of this novel inhibitory pathway.

6-Methylnitroarachidonate: a novel esterified nitroalkene that potently inhibits platelet aggregation and exerts cGMP-mediated vascular relaxation.

Nitro-fatty acids represent endogenously occurring products of oxidant-induced nitration reactions. We have previously synthesized a mixture of four isomers of nitroarachidonic acid, a novel anti-inflammatory signaling mediator. In this study, we synthesized and chemically and biologically characterized for the first time an esterified nitroalkene derived from the nitration of methylarachidonate (AAMet): 6-methylnitroarachidonate (6-AAMetNO(2)). Synthesis was performed by reacting AAMet with sodium nitrite under acidic conditions. Analysis by mass spectrometry (positive-ion ESI-MS) showed an [M+H](+) ion of m/z 364, characteristic of AAMetNO(2). Fragmentation of this ion yielded a daughter ion at m/z 317, corresponding to the neutral loss of the nitro group ([M+H-HNO(2)](+)). Furthermore, IR signal at 1378 cm(-1) and NMR data confirmed the structure of a 6-nitro-positional isomer. This novel esterified nitroalkene was capable of promoting vascular protective actions including: (a) the induction of vasorelaxation via endothelium-independent mechanisms, associated with an increase in smooth muscle cell cGMP levels, and (b) a potent dose-dependent inhibition of human platelet aggregation. We postulate that 6-AAMetNO(2) could be a potential drug for the prevention of vascular and inflammatory diseases, and the presence of the methyl group may increase its pharmacological potential.