RESUMEN
Recent economic changes throughout the world, either development or crises and recessions, have prompted a host of nutrition related problems, including a decreased prevalence of undernutrition, an increase in the prevalence of diet related diseases, widespread food insecurity as crop prices increase, and so on. In addition, evidence is mounting that suggests that exposure to poor nutrition early in life is a predisposing factor for chronic diseases in adulthood. Thus, the role of international or community nutrition professionals is vital to not only studying and understanding the interplay between economics, food policy, and health, but also to improving the ability to intervene and prevent many problems related to food insecurity in developed and developing countries. The purpose of this review is to outline and describe these issues as a means to open discussion on how to best alleviate major nutrition problems in the world.
Asunto(s)
Adulto , Humanos , Enfermedad Crónica , Países en Desarrollo , Dieta , Abastecimiento de Alimentos , Desnutrición , Política Nutricional , PrevalenciaRESUMEN
In a 3 [1/2] year prospective, double-blind study of methotrexate used to treat RA, we examined whether methotrexate and methotrexate polyglutamates accumulation in the liver correlated with clinical efficacy or clinical/laboratory toxicity. We also validated a new histologic measure of liver histology [the Iowa Score] relative to the Roenigk grading system. Forty rheumatoid arthritis patients participated in a prospective, double-blind, 3 [1/2] year study of methotrexate treatment. Liver biopsies, liver methotrexate and methotrexate polyglutamate concentrations, laboratory tests, evaluation of disease activity and evaluation of adverse events were done prospectively at baseline, 1, 2 and 3 [1/2] years. Radiochemical ligand binding assays and HPLC methods were used to measure methotrexate and methotrexate polyglutamates. Statistical analysis included ANOVA, linear regression and logistic regression modeling. No significant changes in the mean values of AST, ALT, alkaline phosphatase, albumin or hemoglobin occurred. A surprisingly high percentage of patients had at least one abnormal alkaline phosphatase, AST or ALT [25 to 52%] although most abnormalities were small or transient. The last abnormal AST, the number of abnormal AST and ALT's plus female gender correlated with histological liver abnormalities [r[2] = 0.41] using a new histologic scoring system [the Iowa Score]. Histological abnormalities did not progress using either the Roenigk or Iowa Scores, although a slight numerical increase in fibrosis over time appeared possible. The amount of alcohol use correlated with fatty change and the methotrexate dose at biopsy was associated with liver histological abnormalities [p= 0.03 and 0.049, respectively]. Total liver methotrexate concentrations were stable from year 1 to year 3 [1/2] and the percentage of higher order polyglutamates were relatively high [38 to 56%] relative to monoglutamates. No correlation of these concentrations with clinical response or toxicity, histology or liver function tests could be documented. This analysis demonstrated the accumulation and stabilization of methotrexate concentrations in the liver and examined correlations between methotrexate liver concentrations, patient demographics, liver histology, concomitant medications and disease activity. No such correlations were found, decreasing the likelihood that methotrexate concentrations in serum would be useful measures to predict significant hepatotoxicity. This study longitudinally examines methotrexate concentrations and its polyglutamates in the liver and correlates them with histology, liver function tests, demographics and clinical efficacy and toxicity. While previously examined cross-sectional, such a study including methotrexate and metabolite concentrations has never been completed longitudinally. Correlations of histology with AST, ALT and alcohol were found, but no concentration to histology, clinical or toxicity relationships were seen. This implies a very low likelihood that serum methotrexate levels will be useful to measure or predict liver toxicity from methotrexate. In addition, this study validates a new, more sensitive [than the Roenigk score] histology liver scoring system [the Iowa Scale]