Maria Jesus Martin

EPOC y alteraciones endocrinometabólicas

Resumen La evolucion clinica y el manejo terapeutico de la enfermedad pulmonar obstructiva cronica (EPOC) pueden verse afectados por la presencia de alguna comorbilidad, lo que ademas suele contribuir a empeorar el pronostico. Entre las alteraciones endocrinometabolicas que pueden asociarse a la EPOC, se encuentran la diabetes mellitus, la osteoporosis, el sindrome metabolico o la malnutricion. Son diversos los posibles mecanismos etiopatogenicos que intervienen en la asociacion entre EPOC y diferentes trastornos endocrinometabolicos, como el tabaco y la respuesta inflamatoria sistemica con intervencion de diferentes citocinas, entre otros. Por otro lado, los glucocorticoides sistemicos a dosis altas utilizados en el tratamiento de la EPOC grave y de las agudizaciones, supone un factor importante en el riesgo de desarrollar ciertas alteraciones metabolicas, como la diabetes mellitus y la osteoporosis. En el estudio del paciente con EPOC, es importante identificar los posibles trastornos endocrinometabolicos coexistentes, para aplicar medidas de correccion y de prevencion. Por lo general, los pacientes se beneficiaran de la inclusion en un programa de rehabilitacion respiratoria con ejercicio fisico y una dieta equilibrada, ademas del tratamiento farmacologico oportuno en cada caso. Tambien resultan fundamentales ciertas medidas, como evitar el tabaquismo, el sedentarismo, y realizar el tratamiento correcto de la EPOC.The clinical course and therapeutic management of chronic obstructive pulmonary disease (COPD) may be affected by the presence of comorbid diseases, which also usually worsen prognosis. Among the endocrinological and metabolic alterations that can be associated with COPD are diabetes mellitus, osteoporosis, metabolic syndrome and malnutrition. There are several possible etiopathogenic mechanisms that intervene in the association between COPD and distinct endocrine and metabolic disorders, such as smoking and systemic inflammation, influenced by distinct cytokines among other factors. The high-dose glucocorticosteroids used in the treatment of severe COPD and exacerbations are a major risk factor for the development of some metabolic alterations such as diabetes and osteoporosis. Study of patients with COPD should identify the possible coexisting endocrinological and metabolic alterations in order to apply preventive measures and treatment. In general, patients benefit from being included in a respiratory rehabilitation program with physical exercise and a balanced diet, in addition to appropriate drug treatment in each case. Certain measures such as avoiding smoking and sedentariness are also essential in the correct treatment of COPD.

Structural Determinants of the Selectivity of 3-Benzyluracil-1-acetic Acids toward Human Enzymes Aldose Reductase and AKR1B10.

The human enzymes aldose reductase (AR) and AKR1B10 have been thoroughly explored in terms of their roles in diabetes, inflammatory disorders, and cancer. In this study we identified two new lead compounds, 2‐(3‐(4‐chloro‐3‐nitrobenzyl)‐2,4‐dioxo‐3,4‐dihydropyrimidin‐1(2H)‐yl)acetic acid (JF0048, 3) and 2‐(2,4‐dioxo‐3‐(2,3,4,5‐tetrabromo‐6‐methoxybenzyl)‐3,4‐dihydropyrimidin‐1(2H)‐yl)acetic acid (JF0049, 4), which selectively target these enzymes. Although 3 and 4 share the 3‐benzyluracil‐1‐acetic acid scaffold, they have different substituents in their aryl moieties. Inhibition studies along with thermodynamic and structural characterizations of both enzymes revealed that the chloronitrobenzyl moiety of compound 3 can open the AR specificity pocket but not that of the AKR1B10 cognate. In contrast, the larger atoms at the ortho and/or meta positions of compound 4 prevent the AR specificity pocket from opening due to steric hindrance and provide a tighter fit to the AKR1B10 inhibitor binding pocket, probably enhanced by the displacement of a disordered water molecule trapped in a hydrophobic subpocket, creating an enthalpic signature. Furthermore, this selectivity also occurs in the cell, which enables the development of a more efficient drug design strategy: compound 3 prevents sorbitol accumulation in human retinal ARPE‐19 cells, whereas 4 stops proliferation in human lung cancer NCI‐H460 cells.

Impacto de la anemia en la EPOC

The frequency of anemia may be higher than expected in patients with chronic obstructive pulmonary disease (COPD). Some studies have detected a prevalence of 33%, contrasting with the common idea that associates COPD with secondary polyglobulia. Among the risk factors associated with the development of anemia in these patients are advanced age, the severity of airflow obstruction and reduction in body mass index. In addition to being a frequent disorder in COPD, anemia is also a poor prognostic factor and leads to greater morbidity and mortality in this disease. Despite the possible clinical benefits of successfully treating anemia in these patients, the scientific evidence supporting the importance of its effect on the prognosis of COPD is scarce.