Biomarcadores del metabolismo y nutrición de hierro / Biomarkers of metabolism and iron nutrition

La anemia por deficiencia de hierro continúa siendo la deficiencia nutricional más abundante en el mundo, y son los lactantes, preescolares, mujeres en edad fértil y embarazadas los grupos de mayor susceptibilidad. Debido a esto es que se hace necesario el conocer los mecanismos de regulación de captación, transporte y absorción del metal a nivel celular, principalmente a nivel del enterocito y, una vez que el hierro entra a la circulación, conocer cuáles son los biomarcadores que permiten realizar un seguimiento del estatus del hierro corporal. En esta revisión mostramos, en primer lugar, cómo se regula la entrada de hierro a nivel de la célula del epitelio intestinal, mostrando las principales proteínas involucradas (transportadores de entrada y salida de hierro, oxido-reductasas, proteína de almacenamiento) y, para finalizar, hacemos un recuento de los principales biomarcadores del metabolismo de hierro una vez que este ha entrado y circula por el organismo.

Iron deficiency anemia is the most common nutritional deficiency worldwide, and the most susceptible groups are infants, preschoolers, women of childbearing age, and pregnant women. It is therefore essential to understand the mechanisms of regulation of iron uptake, transport, and absorption at the cellular level, particularly in enterocytes, and to identify blood biomarkers that allow the evaluation of iron status. This review describes how iron absorption is regulated by intestinal epithelial cells, the main proteins involved (iron transporters, oxidoreductases, storage proteins), and the main blood biomarkers of iron metabolism.

Efecto de metformina sobre la expresión del factor de necrosis tumoral-α, los receptores Toll-like 2/4 y la PCR ultra sensible en sujetos obesos con diabetes tipo 2 / Effect of metformin on the expression of tumor necrosis factor-α, Toll like receptors 2/4 and C reactive protein in obese type-2 diabetic patients

Background: The pharmacological action of metformin goes beyond mere glycemic control, decreasing markers of inflammation and contributing to the reduction of oxidative stress. Aim: To evaluate biochemical, anthropometric and pro-inflammatory markers in obese type 2 diabetic patients treated or not with metformin. Patients and Methods: Obese patients with type 2 diabetes were invited to participate in the study if they were aged more than 40 years, were not receiving insulin, did not have cardiovascular diseases and were not taking anti-inflammatory drugs. A pharmacological history was taken and patients were stratified in two groups whether they were using metformin or not. A fasting blood sample was obtained to measure blood glucose, insulin, lipid levels, C reactive protein (hsCRP) and to isolate peripheral blood mononuclear cells. RNA was isolated from these cells to measure expression of tumor necrosis factor-α (TNF-α), Interleukin-6 (IL-6), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB), Toll-Like Receptor 2/4 (TLR 2/4) and beta-2-microglobulin (B2M). Results: Thirty participants were studied. Of these, 16 subjects aged 54.4 ± 5.5years were treated with metformin and 14 subjects aged 54.9 ± 6.4 years did not receive the drug. Participants receiving metformin had lower levels of hsCRP and lower mRNA relative abundance of TNF-α and TLR 2/4. There were no differences in glucose levels or lipid profile between both groups. Conclusions: Obese diabetic patients treated with metformin had lower levels of hsCRP expression of TNF-α and TLR 2/4, than their counterparts not receiving the drug.

Inhibidores de la integrasa y raltegravir en el manejo de la infección por vírus de la inmunodeficiencia humana en la era de la resistencia a múltiples medicamentos: [revisión] / Integrase Inhibitors and raltegravir use in the management of HIV infection in the era of multidrug resistance: [review]

La infección por el virus de la inmunodeficiencia humana ha generado un impacto mundial que ha sobrepasado los cálculos iniciales previstos para esta enfermedad. En la actualidad, se hace necesaria la búsqueda de nuevos medicamentos antirretrovirales dentro de las familias de medicamentos conocidas, pero, aún más importante, es la búsqueda de nuevos blancos terapéuticos sobre los cuales incidan los fármacos a los que no ha estado expuesto el virus y, asimismo, ante los cuales no presentan resistencia natural. Los inhibidores de la integrasa constituyen la familia de medicamentos antirretrovirales más recientemente aprobada para uso clínico. El raltegravir es un medicamento nuevo, con atributos importantes que lo hacen una herramienta que se debe tener en cuenta en esquemas de rescate, terapia de cambio y acorde con la consideración de paciente naive, es decir, sin tratamiento previo con este fármaco.

Immunodeficiency virus infection in humans (HIV) has generated a worldwide impact exceeding initial estimates for this disease. At present, it is necessary to search for new antiretroviral drugs within the families of known medication, but the search for new therapeutic objectives under the effect of medication which has not been exposed to the virus and, therefore without natural resistance to it, is even more important. Integrase inhibitors are the family of antiretroviral medication most recently approved for clinical use; raltegravir is a new drug with important attributes that make it a tool to be considered in rescue regimens, change therapies, and naïve patient particular cases.

Estado actual del trasplante cardíaco en Nuevo León: primeros 33 casos / Heart transplant in Nuevo Leon: the first 33 cases

Heart failure is one of the most important causes of death worldwide. Heart transplant is the last effective alternative when the medical and surgical treatments have failed in patients with end stage heart failure, giving them an 80% one year survival rate. Unfortunately, during the outcome, the heart transplant patients can develop complications such as graft rejection and opportunistic infections because of the use of immunosuppressive therapy. In the present article we report the experience with 33 heart transplant patients. Our program not only has successfully transplanted patients with advanced age but, for the first time in Latin America we have transplanted patients assisted with the ambulatory Thoratec TLC II system. Even with limited resources, we have managed the same complications than other heart transplant programs, our 82% one year survival rate is similar than reports in medical literature.

Inhibition of iron and copper uptake by iron, copper and zinc

Interactions of micronutrients can affect absorption and bioavailability of other nutrients by a number of mechanisms. In aqueous solutions, and at higher uptake levels, competition between elements with similar chemical characteristics and uptake process can take place. The consequences of these interactions may depend on the relative concentrations of the nutrients. In this work, we measure the effects of increasing concentrations of iron, zinc, and copper on iron and copper uptake in Caco-2 cells. Intracellular Fe or Cu levels were affected by incubating with increased concentrations of metals. However, when the cells already had different intracellular metal concentration, the uptake of Fe or Cu was nor affected. In competition studies, we showed that Cu and Zn inhibited Fe uptake, and while Fe inhibited Cu uptake, Zn did not. When the three metals were given together (1: 1: 1 ratio), Fe or Cu uptake was inhibited 40 percent. These results point to a potential risk in the absorption and bioavailability of these minerals by the presence of other minerals in the diet. This aspect must be considered in food supplementation and fortification programs.

Antioxidant responses of cortex neurons to iron loading

Brain cells have a highly active oxidative metabolism, yet they contain only low to moderate superoxide dismutase and catalase activities. Thus, their antioxidant defenses rely mainly on cellular reduced glutathione levels. In this work, in cortical neurons we characterized viability and changes in reduced and oxidized glutathione levels in response to a protocol of iron accumulation. We found that massive death occurred after 2 days in culture with 10 mM Fe. Surviving cells developed an adaptative response that included increased synthesis of GSH and the maintenance of a glutathione-based reduction potential. These results highlight the fundamental role of glutathione homeostasis in the antioxidant response and provide novel insights into the adaptative mechanisms of neurons subjected to progressive iron loads.

Heme oxygenase 1 overexpression increases iron fluxes in Caco-2 cells

Heme oxygenase-1 is a microsomal enzyme that, when induced by stress, protects the cells from oxidative injury. Heme oxygenase-1 participates in the cleavage of the heme ring producing biliverdin, CO and ferrous Fe. The released Fe becomes part of intracellular Fe pool and can be stored in ferritin or released by an iron exporter. The mechanism by which heme enters cells is not completely understood, although it had been suggested that it might be internalized by an endocytosis process. In this study, we expressed a full-length Heme oxygenase-1 cDNA in Caco-2 cells and measured intracellular iron content, heme-iron uptake and transport and immunolocalization of heme oxygenase-1 in these cells. We found that heme oxygenase-1 expressing cells showed increased apical heme iron uptake and transepithelial transport when compared to control cells. These results suggested that heme oxygenase-1 mediates heme iron influx and efflux in intestinal cells.

Determinación de ferritina sérica por ELISA / Serum ferritin determination by ELISA

Se montó un ELISA para la determinación de ferritina sérica, para ello se purificó ferritina a partir de bazo humano con Sephrosa 6B. Con la ferritina obtenida se inocularon conejos adultos para la obtención del antisuero. El antisuero fue conjugado con peroxidasa de rábano y para realizar la fase sólida se agregó a las placas antiferritina tipo Ig G en buffer carbonato. Se obtuvo una sensibilidad de 1,8 *g/L de ferritina sérica. una reproducibilidad intradía de 1,6ñ0,5% e interdía de 4,9ñ2,5%. una recuperabilidad de 81,5ñ3,2%. Para evaluar la exactitud, se comparó nuestro ELISA con un ELISA monoclonal de referencia y con Ferrizyme (Abbott MR.), estudiándose 117 muestras (rango entre 2,2 y 83,4 *g/L), no hubo diferencia significativa entre los promedios geométricos del ELISA monoclonal y el ELISA INTA (10,5 *g/L vs 10,2 *g/L respectivamente) y se obtuvo una correlación de 0,83 entre ellas