Efecto protector de la melatonina y del tratamiento tópico con la mezcla eutéctica de lidocaína y prilocaína en un modelo de isquemia reperfusión en el colgajo cutáneo microvascularizado en ratas / Protective effect of melatonin and the lidocaine and prilocaine eutectic mixture in an ischemia reperfusion injury model in the microvascular cutaneous flap in rats

El síndrome de isquemia reperfusión es el conjunto de sucesos desarrollados desde la instauración de la isquemia en un tejido hasta su posterior reperfusión. Se trata de una condición limitante y, hasta la fecha, inevitable, en toda cirugía que implique una revascularización tisular. En un intento por buscar medidas terapéuticas frente al estrés oxidativo desarrollado durante este síndrome en los colgajos microvascularizados, se valoró la acción del antioxidante melatonina y de los anestésicos locales lidocaína y prilocaína en un modelo de isquemia reperfusión en el colgajo epigástrico microvascularizado en ratas. Tanto el indol como los fármacos vasoactivos poseen un efecto protector en el tratamiento del síndrome de isquemia reperfusión, desde un punto de vista bioquímico e histológico, destacando su acción sinérgica manifestada principalmente como un incremento en la neovascularización tisular (AU)

Ischemia-reperfusion injury is a set of events developed since the introduction of ischemia in a tissue to subsequent reperfusion. It is a limiting condition and, to date, inevitable in any surgery involving tissue revascularization. In an attempt to find therapeutic measures against oxidative stress developed during this syndrome in microvascular flaps, we evaluated the antioxidant action of melatonin and local anesthetics lidocaine and prilocaine in a model of ischemia reperfusion in the microvascularized epigastric flap in rats. The indole and vasoactive drugs have a protective effect in the treatment of ischemia reperfusion injury, from both a biochemical and histological view, emphasizing their synergistic action mainly manifested as an increase in tissue neovascularization (AU)

Estado de los marcadores de fase aguda y estrés oxidativo en los enfermos con litiasis de la vía urinaria / State of acute phase markers and oxidative stress in patients with kidney stones in the urinary tract

Objetivo: El objetivo del presente estudio es evaluar el estado de los marcadores de fase aguda y de estrés oxidativo en enfermos con litiasis renal. Material y métodos: Estudio prospectivo en enfermos con litiasis renal. Se incluyeron100 enfermos y 25 controles sanos. Se evaluaron como marcadores de fase aguda: albúmina, beta2 microglobulina, gamma-glutamil transpepsidasa, lactato deshidrogenasa, factor de necrosistumoral alfa, interleucina 1 e interleucina 6 y como marcadores de estrés oxidativo los niveles de lipoperóxidos, superóxido dismutasa y glutatión peroxidasa. Resultados: En los enfermos estudiados se apreció un incremento de los marcadores de daño celular renal expresado por la beta2 microglobulina (p = 0,04), albúmina (p = 0,004), lactato deshidrogenasa (p = 0,001), así como gamma-glutamil transpepsidasa (p = 0,01). Existió una correlación directa entre los niveles de beta2 microglobulina con el tamaño de la litiasis (r = 0,3; p = 0,03). La asociación entre la extensión del cálculo y la activación de las citoquinas se apreció de forma más intensa en los enfermos con cálculos coraliformes en los que las cifras de factor de necrosis tumoral alfa (p = 0,011), interleucina 1 (p = 0,004) e interleucina 6 (p = 0,004) fueron significativamente mayores. Los enfermos con litiasis de la vía urinaria presentaron cifras significativamente elevadas de radicales libres en plasma, expresados como lipoperóxidos (p = 0,03), que se acompañaron de un descenso en la actividad de las enzimas antioxidantes superóxido dismutasa (p = 0.03) y glutatión peroxidasa (p = 0,002). Conclusiones: Los pacientes con litiasis urinaria presentan una elevación de los marcadores de fase aguda, asociada a un incremento de especies reactivas del oxígeno y un descenso en la actividad de las enzimas antioxidantes (AU)

Objective: This present study has aimed to assess the state of acute phase markers and oxidative stress in patients with kidney stones. Material and methods: A prospective study was carried out on 100 patients with kidney stones and 25 healthy controls. Albumin, beta2 microglobulin, Gamma-glutamyl transpepsidase, Lactatede hydrogenase, Tumor necrosis factor alpha, Interleukin 1 and Interleukin-6 were evaluated as acute phase markers and lipid peroxidation products, Superoxide dismutase and Glutathione peroxidase levels acted as oxidative stress markers. Results: An increase in renal cell damage markers as expressed by the beta2 microglobulin (p = 0.04), albumin (p = 0.004), Lactate dehydrogenase (p = 0.001) and Gamma glutamyl transpepsidasa (p = 0.01) was observed in the patient group. There was a direct correlation between levels of beta2 microglobulin and stone size (r = 0.3, p = 0.03). The association between stone size and cytokine activation was observed to be stronger in patients with staghorn calculi. In these patients, Tumor necrosis factor alpha (p = 0.011), Interleukin 1 (p = 0.004) and Interleukin6 (p = 0.004) were significantly higher. Patients with stones in the urinary tract showed data of significantly higher oxidative stress, expressed as an increase in levels of lipid peroxidation products (p = 0.03) and a decrease in the antioxidant activity of Superoxide dismutase (p = 0.03)and Glutathione peroxidase (p = 0.002).Conclusions: Patients undergoing urolithiasis showed an elevation of acute phase markers, associated with oxidative stress as expressed by an increase in lipid peroxidation products and a decrease in the antioxidant enzyme activity (AU)

[State of acute phase markers and oxidative stress in patients with kidney stones in the urinary tract]. / Estado de los marcadores de fase aguda y estrés oxidativo en los enfermos con litiasis de la vía urinaria.

OBJECTIVE: This present study has aimed to assess the state of acute phase markers and oxidative stress in patients with kidney stones. MATERIAL AND METHODS: A prospective study was carried out on 100 patients with kidney stones and 25 healthy controls. Albumin, ß2 microglobulin, Gamma-glutamyl transpepsidase, Lactate dehydrogenase, Tumor necrosis factor alpha, Interleukin 1 and Interleukin-6 were evaluated as acute phase markers and lipid peroxidation products, Superoxide dismutase and Glutathione peroxidase levels acted as oxidative stress markers. RESULTS: An increase in renal cell damage markers as expressed by the ß2 microglobulin (p=0.04), albumin (p=0.004), Lactate dehydrogenase (p=0.001) and Gamma glutamyl transpepsidasa (p=0.01) was observed in the patient group. There was a direct correlation between levels of ß2 microglobulin and stone size (r=0.3, p=0.03). The association between stone size and cytokine activation was observed to be stronger in patients with staghorn calculi. In these patients, Tumor necrosis factor alpha (p=0.011), Interleukin 1 (p=0.004) and Interleukin 6 (p=0.004) were significantly higher. Patients with stones in the urinary tract showed data of significantly higher oxidative stress, expressed as an increase in levels of lipid peroxidation products (p=0.03) and a decrease in the antioxidant activity of Superoxide dismutase (p=0.03) and Glutathione peroxidase (p=0.002). CONCLUSIONS: Patients undergoing urolithiasis showed an elevation of acute phase markers, associated with oxidative stress as expressed by an increase in lipid peroxidation products and a decrease in the antioxidant enzyme activity.

Effects of nitric oxide synthase-3 overexpression on post-translational modifications and cell survival in HepG2 cells.

Hepatocarcinoma is the fifth most common neoplasm and the third cause of cancer-related death. The development of genetic- and/or molecular-based therapies is urgently required. The administration of high doses of nitric oxide (NO) promotes cell death in hepatocytes. NO contributes to cell signaling by inducing oxidative/nitrosative-dependent post-translational modifications. The aim of the present study was to investigate protein modifications and its relation with alteration of cell proliferation and death in hepatoma cells. Increased intracellular NO production was achieved by stable nitric oxide synthase-3 (NOS-3) overexpression in HepG2 cells. We assessed the pattern of nitration, nitrosylation and carbonylation of proteins by proteomic analysis. The results showed that NOS-3 cell overexpression increased oxidative stress, which affected proteins mainly involved in cell protein folding. Carbonylation also altered metabolism, as well as immune and antioxidant responses. The interaction of nitrosative and oxidative stress generated tyrosine nitration, which affected the tumor marker Serpin B3, ATP synthesis and cytoskeleton. All these effects were associated with a decrease in chaperone activity, a reduction in cell proliferation and an increased cell death. Our study showed that alteration of nitration, nitrosylation and carbonylation pattern of proteins by NO-dependent oxidative/nitrosative stress was related to a reduction of cell survival in a hepatoma cell line.