Evolution of left ventricular mass in renal transplant recipients: the influence of glucose homeostasis and oxidative stress.

BACKGROUND: Left ventricular hypertrophy, considered an independent factor for cardiovascular mortality, is frequent among renal transplant recipients (RTR), in whom we investigated changes in left ventricular mass (LVM) after grafting and associations with possible causal factors, especially glucose metabolism and oxidative stress. METHODS: We performed a prospective study of 37 RTR without prior diabetes mellitus who were evaluated at three times after transplantation (medians of 0.6, 16 and 28 months) by means of the LVM index (LVMI, echocardiographic measure of LVM related to body surface area, g/m(2)), oral glucose tolerance test and determinations of malondialdehyde and total glutathione (GSH), as well as glomerular filtration rate (GFR) estimate by the Modification of Diet in Renal Disease formula. We calculated the overall increment (DeltaLVMI) and percent change of LVMI. Patients were diagnosed to be prediabetic (PD) or new-onset diabetes after transplant (NODAT) according to ADA criteria. RESULTS: The mean LVMI decreased significantly over time among whole group baseline = 108.34 ± 27.71 g/m(2) versus middle: 100.03 ± 27.53 g/m(2) versus final: 90.62 ± 24.06 g/m(2) (P = .000). However, 13.5% of subjects showed an increased LVMI and 59.5%, a decrease less than 20%. Patients with NODAT at the end of the study showed a positive DeltaLVMI, which was negative in nondiabetics (0.24 ± 16.14 versus -19.86 ± 12.61 g/m(2), P = .018). Compared with DeltaLVMI(-) recipients, patients with DeltaLVMI(+) showed a greater proportion of PD and NODAT at baseline (60% and 40% versus 18.8% and 12.5%, P = .017), and significantly higher all-time fasting glycemia, lower estimated GFR, and greater increments of malondialdehyde and GSH over time. Those with a <20% LVMI decrease experienced progressive GFR impairment over time, as opposed to those with an LVMI decrease > 20%, who showed greater and improving GFR over the whole study. CONCLUSIONS: LVMI does not always improve in RTR; the evolution of ventricular mass after renal transplantation is influenced by glucose metabolism disorders, oxidative stress, and graft function.

Function and expression of renal epithelial sodium transporters in rats with thyroid dysfunction.

Thyroid disorders are accompanied by major changes in renal sodium handling and blood pressure. Sodium transporters play a crucial role in regulating sodium excretion. We determined the function and expression of type 3 Na/H (NHE3) exchanger, type 2 Na+K+2Cl co-transporter (NKCC2) co-transporter, NaCl co-transporter (NCC) cotransporter, and epithelial sodium channel (ENaC) in hypoand hyperthyroid rats at 6 weeks after each thyroid disorder induction. We measured the renal response to functional blockade of the tubular sodium transporters, using acetazolamide to inhibit the activity of NHE3, furosemide for NKCC2, hydrochlorotiazide for NCC, and amiloride for ENaC. Expression of sodium transporters was analyzed by measuring the protein abundance by Western blot. The responsiveness to NHE3 inhibition and NHE3 protein was lower in hypothyroid rats and higher in hyperthyroid rats vs controls. Hypothyroid rats showed greater diuretic and natriuretic responses to NKCC2 and ENaC blockade and higher protein abundance of NKCC2 vs controls. Hyperthyroid rats showed greater protein expression of NKCC2 and NCC vs controls. Groups did not differ in responsiveness to NCC blockade. The expression and activity of ENaC were lower in hyperthyroid rats. In conclusion, reduced NHE3 activity may participate in the low blood pressure of hypothyroid rats and elevated NHE3 activity in the high blood pressure of hyperthyroid rats. These proximal alterations are counter-balanced by functional upregulation of NKCC2 and ENaC in downstream nephron segments of hypothyroid rats and by downregulation of αENaC activity and expression in hyperthyroid rats.

Mechanisms of hydrogen peroxide-induced vasoconstriction in the isolated perfused rat kidney.

The vasoconstrictor effect of hydrogen peroxide (H(2)O(2)) on isolated perfused rat kidney was investigated. H(2)O(2) induced vasoconstriction in the isolated rat kidney in a concentration-dependent manner. The vasoconstrictor effects of H(2)O(2) were completely inhibited by 1200 U/ml catalase. Endothelium-removal potentiated the renal response to H(2)O(2). The H(2)O(2) dose-response curve was not significantly modified by administration of the NO inhibitor L-NAME (10(-4) mol/l), whereas it was increased by the non-specific inhibitor of K+-channels, tetraethylammonium (3.10(-3) mol/l). Separately, removal of extracellular Ca(2+), administration of a mixture of calcium desensitizing agents (nitroprusside, papaverine, and diazoxide), and administration of a protein kinase C (PKC) inhibitor (chelerythrine, 10(-5) mol/l) each significantly attenuated the vasoconstrictor response to H(2)O(2), which was virtually suppressed when they were performed together. The pressor response to H(2)O(2) was not affected by: dimethyl sulfoxide (7.10(-5) mol/l) plus mannitol (3.10(-5) mol/l); intracellular Ca(2+) chelation using BAPTA (10(-5) mol/l); calcium store depletion after repeated doses of phenylephrine (10(-5) g/g kidney); or the presence of indomethacin (10(-5) mol/l), ODYA (2.10(-6) mol/l) or genistein (10(-5) mol/l). We conclude that the vasoconstrictor response to H(2)O(2) in the rat renal vasculature comprises the following components: 1) extracellular calcium influx, 2) activation of PKC, and 3) stimulation of pathways leading to sensitization of contractile elements to calcium. Moreover, a reduced pressor responsiveness to H(2)O(2) in female kidneys was observed.

[Effects of thermo-oxidised oils on lipid peroxidation in experimental animals]. / Efectos del consumo de aceites termo-oxidados sobre la peroxidación lipídica en animales de laboratorio.

INTRODUCTION: The quality of fats and oils used for frying is as important as the quality of the final product since during the frying process oxidization by-products are formed and become part of the diet, being potentially harmful for the consumers' health. OBJECTIVE: To determine the effects of thermo-oxidised fats and oils on the oxidization of plasma lipoproteins inexperimental rats. METHODS: Determination by means of spectrophotometric techniques of those substances reacting with thiobarbituric acid and total cholesterol (enzymatic method) in the sera of 40 Wistar rats that consumed crude thermooxidised oils and fats with different levels of malonil aldehyde(MDA) for 30 days. RESULTS: The group of rats receiving a diet with thermooxidised oils and fats experienced significant increases in MDA plasma levels throughout the study period, lipid peroxidation being higher with increasing MDA content (p < 0.05) regardless the type of fat compound consumed. However, those rats receiving crude oils and fats kept plasma levels of lipidic peroxides without significant changes throughout the experimental period (p > 0.05). By contrast, cholesterol levels increased towards the end of the experimental period in both the rats consuming crude fats and those consuming thermo-oxidised fats (p < 0.05). CONCLUSIONS: Consumption of oils and fats submitted to repeat thermal heating has an influence on plasma lipidic peroxidation, which becomes higher with increasing number of heating processes applied, so that it would advisable not to abuse of reheating the oils used for frying foods.

Efectos del consumo de aceites termo-oxidados sobre la peroxidación lipídica en animales de laboratorio / Effects of thermo-oxidised oils on lipid peroxidation in experimental animals

Introducción: La calidad de las grasas y aceites utilizados para frituras es tan importante como la calidad del producto final, ya que durante el proceso de fritura se desarrollan productos de oxidación que pasan a formar parte de la dieta pudiendo ser nocivos para la salud de los consumidores. Objetivo: determinar los efectos del consumo de grasas y aceites termo-oxidados sobre la oxidación de lipoproteínas plasmáticas en ratas de laboratorio. Métodos: determinación, mediante técnicas espectrofotométricas, de sustancias que reaccionan con el ácido tiobarbitúrico y colesterol total (método enzimático) en el suero de 40 ratas de la cepa wistar que consumieron aceites y grasas crudas y termo-oxidadas con diferentes niveles de malonilaldehido (MDA) durante 30 días. Resultados: El grupo de animales que recibió dieta con aceites y grasa termo-oxidados experimentaron aumentos significativos en la concentración plasmática de MDA a lo largo del período de estudio, siendo la peroxidación lipídica mayor cuanto mayor fue el contenido de MDA (p < 0,05), independientemente del tipo de materia grasa consumida. Sin embargo aquellos que recibieron aceites y grasas en estado crudo mantuvieron los niveles plasmáticos de peróxidos lipídicos sin cambios significativos durante el período de experimentación (p > 0,05). En cambio, la colesterolemia aumentó hacia el final del período experimental tanto en aquellos animales que consumieron materias grasas crudas como las que las tomaron termo-oxidadas (p < 0,05). Conclusiones: el consumo de aceites y grasa sometidos a sucesivos calentamientos térmicos influye sobre la peroxidación lipídica plasmática y es mayor cuanto mayor sea el número de calentamientos aplicados, por lo que sería recomendable no abusar del recalentamiento de los aceites utilizados en la frituras (AU)

Introduction: The quality of fats and oils used for frying is as important as the quality of the final product since during the frying process oxidization by-products are formed and become part of the diet, being potentially harmful for the consumers' health. Objective: To determine the effects of thermo-oxidised fats and oils on the oxidization of plasma lipoproteins inexperimental rats. Methods: Determination by means of spectrophotometric techniques of those substances reacting with thiobarbituric acid and total cholesterol (enzymatic method) in the sera of 40 Wistar rats that consumed crude thermooxidised oils and fats with different levels of malonil aldehyde(MDA) for 30 days. Results: The group of rats receiving a diet with thermooxidised oils and fats experienced significant increases in MDA plasma levels throughout the study period, lipid peroxidation being higher with increasing MDA content (p < 0.05) regardless the type of fat compound consumed. However, those rats receiving crude oils and fats kept plasma levels of lipidic peroxides without significant changes throughout the experimental period (p > 0.05). By contrast, cholesterol levels increased towards the end of the experimental period in both the rats consuming crude fats and those consuming thermo-oxidised fats (p < 0.05). Conclusions: Consumption of oils and fats submitted to repeat thermal heating has an influence on plasma lipidic peroxidation, which becomes higher with increasing number of heating processes applied, so that it would advisable not to abuse of reheating the oils used for frying foods (AU)

Efectos de la suplementación con glutamina sobre el sistema antioxidante y la peroxidación lipídica en pacientes críticos con nutrición parenteral / Effects of supply with glutamine on antioxidant system and lipid peroxidation in patients with parenteral nutrition

Introducción: En el paciente crítico hay una continua producción de especies reactivas de oxígeno (ERO) que necesitan se neutralizadas para evitar el estrés oxidativo (EO). Entre las defensas antioxidantes endógenas, el sistema glutatión (GSH) es cuantitativamente el más importante, pero en situaciones de estrés severo se encuentra disminuido. Para incrementarlo, la suplementación con glutamina ha demostrado ser efectiva, ejerciendo protección contra el daño oxidativo y reduciendo la morbi-mortalidad. Objetivo: Valorar el efecto de la adición de un dipéptidoal anyl-glutamina a la NP sobre la peroxidación lipídica y el metabolismo del glutatión y su relación con la morbilidad de los pacientes críticos. Métodos: Determinación, mediante técnicas espectrofo-tométricas, de glutatión peroxidasa, glutatión reductasa, glutatión total y malonil aldehído al ingreso y tras siete días de estancia en la Unidad de Cuidados Intensivos (UCI) de 20 pacientes mayores de 18 años con tratamiento nutricional parenteral. Resultados: El grupo de pacientes que recibió nutrición parenteral con adición de glutamina experimentó aumentos significativos a la semana de tratamiento nutricional en la concentración del glutatión total (42,35 ± 13 vs 55,29 ± 12 μmol/l; p < 0,05), junto a un incremento de la actividad de la enzima glutatión peroxidasa (470 ± 195 vs 705 ± 214 μmol/l; p < 0,05). En cambio, el grupo con nutrición parenteral convencional no presentó modificaciones significativas en ninguno de los parámetros estudiados (p > 0,05). Sin embargo, tanto la mortalidad como la estancia en UCI no fue diferente para los grupos estudiados, mientras que si se observó una menor gravedad, valorada por e SOFA score, en el grupo de pacientes que recibieron glutamina (SOFA 5 ± 2 vs 8 ± 1,8; p < 0,05).Conclusiones: El aporte de glutamina en pacientes críticos mejora las defensas antioxidantes, lo que repercute en una menor peroxidación lipídica y menor morbilidad durante la estancia en UCI

Introduction: In the critically ill patient, there is a continuous production of reactive oxygen species (ROS) that need to be neutralized to prevent oxidative stress (OS). Quantitatively speaking, the glutathionesystem (GSH) is the most important anti-oxidant endogenous defense. To increase it, glutamine supplementation has been shown to be effective by protecting against the oxidative damage and reducing the morbimortality. Objective: To assess the effect of adding an alanylglutamine dipeptide to PN on lipid peroxidation lipidica and glutathione metabolism, as well as its relationship with morbidity in critically ill patients. Methods: Determination through spectrophotometry techniques of glutathione peroxidase, glutathione reductase, total glutathione, and maloniladdehyde at admission and after seven days of hospitalization at the Intensive Care Unit (ICU) in 20 patients older than 18 years on parenteral nutrition therapy. Results: The group of patients receiving parenteral nutrition with glutamine supplementation had significant increases in total glutathione (42.35 ± 13 vs 55.29 ±12 μmol/l; p < 0.05) and the enzymatic activity of glutathione peroxidasa (470 ± 195 vs 705 ± 214 μmol/l; p < 0.05) within one week of nutritional therapy, where as the group on conventional parenteral nutrition did not show significant changes of any of the parameters studied(p > 0.05). However, both mortality and ICU stay were not different between the study group, whereas the severity (assessed by the SOFA score) was lower in the group of patients receiving glutamine (SOFA 5 ± 2 vs 8 ±1.8; p < 0.05).Conclusions: Glutamine intake in critically ill patients improves the antioxidant defenses, which leads to lower lipid peroxidation and lower morbidity during admission at the ICU

[Effects of supply with glutamine on antioxidant system and lipid peroxidation in patients with parenteral nutrition]. / Efectos de la suplementación con glutamina sobre el sistema antioxidante y la peroxidación lipídica en pacientes críticos con nutrición parenteral.

INTRODUCTION: In the critically ill patient, there is a continuous production of reactive oxygen species (ROS) that need to be neutralized to prevent oxidative stress (OS). Quantitatively speaking, the glutathione system (GSH) is the most important anti-oxidant endogenous defense. To increase it, glutamine supplementation has been shown to be effective by protecting against the oxidative damage and reducing the morbimortality. OBJECTIVE: To assess the effect of adding an alanylglutamine dipeptide to PN on lipid peroxidation lipidica and glutathione metabolism, as well as its relationship with morbidity in critically ill patients. METHODS: Determination through spectrophotometry techniques of glutathione peroxidase, glutathione reductase, total glutathione, and maloniladdehyde at admission adn after seven days of hospitalization at the Intensive Care Unit (ICU) in 20 patients older than 18 years on parenteral nutrition therapy. RESULTS: The group of patients receiving parenteral nutrition with glutamine supplementation had significant increases in total glutathione (42.35+/-13 vs 55.29+/-12 micromol/l; p<0.05) and the enzymatic activity of glutathione peroxidasa (470+/-195 vs 705+/-214 micromol/l; p<0.05) within one week of nutritional therapy, whereas the group on conventional parenteral nutrition did not show significant changes of any of the parameters studied (p>0.05). However, both mortality and ICU stay were not different between the study group, whereas the severity (assessed by the SOFA score) was lower in the group of patients receiving glutamine (SOFA 5+/-2 vs 8+/-1.8; p<0.05). CONCLUSIONS: Glutamine intake in critically ill patients improves the antioxidant defenses, which leads to lower lipid peroxidation and lower morbidity during admission at the ICU.

Perspectives in the design and development of new products for enteral nutrition.

Enteral nutrition is a technique that even though it was used in times immemorial, in the last 25 years has suffered a considerable development, from being considered a secondary therapeutic weapon destined only to feed the patient, to occupying an important status that goes beyond the single act of nourishing. The quantitative composition but overall the qualitative one, is object of an interesting argument in which a profile allowing the modulation of certain aspects of the organism response through the supplementation with different nutrients is searched. That includes from the keeping of the intestinal trophism and of the anti-bacteria intestinal barrier, so important to avoid the frightening multiple organ dysfunction, up to the lessening of the Systemic Response Inflammatory Syndrome (SRIS), going through the immuno-modulative feeding concepts, specific-feeding, pharmaco-nutrient or eco-nutrition. In this new dynamic not only certain nutrients such as glutamine, arginine, nucleotides, omega-3 fatty acids and many antioxidants have acquired importance, but also the manipulation of other molecules of a non- nutritional nature, such as hormones, cytokines and blockers. These aspects that imply passionate ways of investigation for the future are born from the better knowledge that is being acquired from such a severe pathophysiology processes such as sepsis and the organism response before fast and severe aggression; therefore, the modulation of that response through changes in the quantitative and qualitative formulas composition is being attempted.

Perspectivas en el diseño y desarrollo de productos para nutrición enteral / Perspectives in the design and development of new products for enteral nutrition

La Nutrición Enteral es una técnica que aunque utilizada desde tiempos inmemoriales, ha sido en los últimos 25 años cuando ha experimentado un desarrollo considerable, pasando de ser un elemento terapéutico secundario, destinado exclusivamente a alimentar al paciente, a ocupar en la actualidad un papel importante que va mucho más allá del simple acto de nutrir. La composición cuantitativa pero sobre todo la cualitativa, es objeto de un interesante debate en el que se busca un perfil que permita modular determinados aspectos de la respuesta del organismo mediante el enriquecimiento con distintos nutrientes. Ello incluye desde el mantenimiento del trofismo intestinal y de la "barrera intestinal" antibacteriana, tan importante para prevenir el temido fracaso multiórgánico, hasta la atenuación del Síndrome de la Respuesta Inflamatoria Sistémica, pasando por los conceptos de alimentación inmunomoduladora, alimentación organoespecífica, farmaconutrientes o econutrición. En ésta nueva dinámica han adquirido importancia determinados nutrientes como la glutamina, arginina, nucleótidos, ácidos grasos de la serie ω-3 y antioxidantes diversos, así como la manipulación de otras moléculas de naturaleza no nutricional, como hormonas, factores de crecimiento, citoquinas y bloqueantes. Estos aspectos que suponen para el futuro unas apasionantes vías de investigación, nacen del mejor conocimiento que se va teniendo de la fisiopatología de procesos tan graves como la sepsis, y de la reacción del organismo ante el ayuno y la agresión grave, de modo que se está intentando modular dicha respuesta a través de cambios en la composición cuantitativa y cualitativa de las fórmulas (AU)

Enteral nutrition is a technique that even though it was used in times immemorial, in the last 25 years has suffered a considerable development, from being considered a secondary therapeutic weapon destined only to feed the patient, to occupying an important status that goes beyond the single act of nourishing. The quantitative composition but overall the qualitative one, is object of an interesting argument in which a profile allowing the modulation of certain aspects of the organism response through the supplementation with different nutrients is searched. That includes from the keeping of the intestinal trophism and of the anti-bacteria intestinal barrier, so important to avoid the frightening multiple organ dysfunction, up to the lessening of the Systemic Response Inflammatory Syndrome (SRIS), going through the immuno-modulative feeding concepts, specific- feeding, pharmaco-nutrient or eco-nutrition. In this new dynamic not only certain nutrients such as glutamine, arginine, nucleotides, ω-3 fatty acids and many antioxidants have acquired importance, but also the manipulation of other molecules of a non- nutritional nature, such as hormones, cytokines and blockers. These aspects that imply passionate ways of investigation for the future are born from the better knowledge that is being acquired from such a severe pathophysiology processes such as sepsis and the organism response before fast and severe aggression; therefore, the modulation of that response through changes in the quantitative and qualitative formulas composition is being attempted (AU)