Effect of fish oil on oxidative stress markers in patients with probable Alzheimer´s disease

High intake of omega-3 fatty acids has been associated with synaptic plasticity, neurogenesis and memory in several experimental models. To assess the efficacy of fish oil supplementation on oxidative stress markers in patients diagnosed with probable Alzheimer´s disease (AD) we conducted a double blind, randomized, placebo controlled clinical trial. AD patients who met the inclusive criteria were given fish oil (containing 0.45 g eicosapentaenoic acid and 1 g docosahexaenoic acid) or placebo daily for 12 months. Oxidative stress markers [lipoperoxides, nitric oxide catabolites levels, oxidized/reduced glutathione ratio, and membrane fluidity] and fatty acid profile in erythrocytes were assessed at enrollment, and 6 and 12 months after the start of the testing period. At the end of the trial, in patients who received fish oil, we detected a decrease in the omega 6/omega 3 ratio in erythrocyte membrane phospholipids. This change was parallel with decreases in plasma levels of lipoperoxides and nitric oxide catabolites. Conversely, the ratio of reduced to oxidized glutathione was significantly increased. In addition, membrane fluidity was increased significantly in plasma membrane samples. In conclusion fish oil administration has a beneficial effect in decreasing the levels of oxidative stress markers and improving the membrane fluidity in plasma(AU)

El alto consumo de ácidos grasos omega-3 se asocia con la plasticidad sináptica, neurogénesis y memoria en varios modelos experimentales. Para evaluar la eficacia de la suplementación con aceite de pescado en los marcadores de estrés oxidativo en pacientes con diagnóstico de la enfermedad de Alzheimer (EA) probable realizamos un ensayo clínico doble ciego, aleatorizado, controlado con placebo. A los pacientes con la EA que cumplían los criterios de inclusión se les administró aceite de pescado (que contenía 0,45 g de ácido eicosapentaenoico y 1 g de ácido docosahexaenoico) o placebo diariamente durante 12 meses. Los marcadores de estrés oxidativo plasmático [niveles de lipoperóxidos y catabolitos del óxido nítrico, cociente de glutatión reducido a glutatiónoxidado) y fluidez de la membrana] y el perfil de ácidos grasos en los eritrocitos se evaluaron al inicio, 6 meses y alos 12 meses. Al final del ensayo, en pacientes que recibieron aceite de pescado detectamos una disminución en el cociente de ácidos grasos omega 6/omega 3 en los fosfolípidos de la membrana eritrocitaria. Este cambio ocurrió en paralelo a la disminución de los niveles plasmáticos de lipoperóxidos y catabolitos del óxido nítrico. Por el contrario, el cociente de glutatión reducido a glutatión oxidado se incrementó significativamente. Además, la fluidez de la membrana aumentó significativamente en las muestras analizadas. En conclusión, la administración de aceite de pescado tiene un efecto beneficioso al disminuir los niveles de marcadores de estrés oxidativo plasmático y mejorar la fluidez de la membrana plasmática(AU)

Marcadores de estrés oxidativo en pacientes con esclerosis múltiple durante un brote y su remisión / Oxidative stress markers in patients with multiple sclerosis during an outbreak and its remission / Marcadores de estresse oxidativo em pacientes com esclerose múltipla durante um surto e sua remissão

La esclerosis múltiple remitente-recurrente (EM-RR) es una enfermedad desmielinizante del sistema nervioso central. A fin de entender la asociación del estrés oxidativo a nivel periférico con la recaída de la enfermedad se determinaron los niveles de marcadores de estrés oxidativo en plasma de pacientes en la recaída o brote y una semana después de la misma. Se analizaron muestras de 60 personas (20 pacientes con recaída, 20 pacientes sin recaída y 20 controles sanos). Se cuantificaron mediante métodos espectrofotométricos las actividades enzimáticas de óxido nítrico sintasa (ONS), glutatión peroxidasa (GPx), los niveles de lipoperóxidos y nitritos-nitratos y la fluidez de membrana. En el brote de la enfermedad aumentan significativamente los niveles de las actividades enzimáticas de ONS y GPx y los niveles de nitritos-nitratos y lipoperóxidos (p<0,01 en todos los casos), al ser comparados con los de individuos sanos. Dichos parámetros disminuyeron significativamente una semana después de iniciado el brote. Además, los parámetros evaluados se mantuvieron elevados en pacientes que no experimentaron un brote de la enfermedad cuando se los comparó con individuos sanos. La fluidez de membrana en los pacientes con y sin brote fue similar a la de los controles. En conclusión, el estrés oxidativo es un componente importante en los pacientes con esclerosis múltiple.

Recurrent-remitting multiple sclerosis (RR-MS) is a demyelinating disease of the central nervous system. In order to understand the association of oxidative stress at the peripheral level with the relapse of the disease, the levels of oxidative stress markers in plasma of patients in the relapse or outbreak and one week after relapse were determined. Samples of 60 subjects were analyzed (20 patients in relapse, 20 patients without relapse, and 20 healthy controls). The enzymatic activities of nitric oxide synthase (NOS), glutathione peroxidase (GPx), lipoperoxides and nitrite-nitrate levels and membrane fluidity were quantified by spectrophotometric methods. In relapse, the levels of enzymatic activities of NOS and GPx, and the levels of lipoperoxides and nitrites-nitrates were significantly increased (p<0.01, in all cases), compared with healthy individuals. These parameters decreased significantly 1 week after the start of the outbreak. In addition, the parameters evaluated remained high in patients who did not experience an outbreak of the disease compared to healthy subjects. The membrane fluidity in the patients with and without outbreak was similar to that of the controls. In conclusion, oxidative stress is an important component in patients with multiple sclerosis.

A esclerose múltipla recorrente-remitente (EM-RR) é uma doença desmielinizante do sistema nervoso central. Para compreender a associação do estresse oxidativo a nível periférico com a recaída da doença foram determinados os níveis de marcadores de estresse oxidativo em plasma de doentes na recaída ou surto e uma semana após a recaída. Foram analisadas a amostras de 60 pessoas (20 pacientes com recaída, 20 pacientes sem recaída e 20 controles saudáveis). As atividades enzimáticas de óxido nítrico sintase (ONS), glutationa peroxidase (GPX), os níveis de lipoperóxidos e nitritos-nitratos e a fluidez de membrana foram quantificadas por métodos espectrofotométricos. No surto da doença aumentam em forma significativa os níveis da atividade enzimática de ONS e GPX, e os níveis de nitritos-nitratos e lipoperóxidos (p<0,01 em todos os casos), em comparação com os indivíduos saudáveis. Esses parâmetros diminuíram significativamente uma semana após o início do surto. Além disso, os parâmetros avaliados permaneceram elevados em pacientes que não experimentaram um surto da doença quando comparados com indivíduos saudáveis. A fluência de membrana nos pacientes com e sem surto foi semelhante à dos controles. Em conclusão, o estresse oxidativo é um componente importante nos pacientes com esclerose múltipla.

Mecanismos patogénicos en el desarrollo de la esclerosis múltiple: ambiente, genes, sistema inmune y estrés oxidativo / Pathogenic mechanisms of neuronal damage in multiple sclerosis

La esclerosis múltiple (EM) es la principal causa de discapacidad neurológica de origen no traumático en adultos jóvenes. EM es una enfermedad crónica inflamatoria que se caracteriza por daño a las fibras nerviosas y la cubierta de mielina. Esto produce una gran variedad de síntomas una vez que nervios específicos muestran inflamación y pérdida de su función. Estudios epidemiológicos y experimentales han identificado alteraciones genéticas, anormalidades en enzimas antioxidantes y autoinmunidad como algunos de los factores de riesgo para el desarrollo de la enfermedad. Evidencia reciente sugiere que la inflamación y el estrés oxidativo en el sistema nervioso central contribuyen al daño del tejido cerebral. Las células residentes en el sistema nervioso central así como las células inflamatorias invasivas liberan una gran cantidad de especies reactivas de oxígeno y nitrógeno, las cuales causan desmielinización y destrucción de los axones: los hallazgos histopatológicos de la esclerosis múltiple. La interacción entre los procesos inflamatorios y neurodegenerativos producen perturbaciones neurológicas intermitentes seguidas por la acumulación progresiva de la discapacidad. Para tratar de limitar o disminuir la progresión de la enfermedad es necesario reducir la inflamación y el estrés oxidativo como estrategia terapéutica importante. Con la finalidad de mejorar la sobrevivencia y la calidad de vida de los pacientes, se están desarrollando ensayos clínicos con suplementos alimenticios tales como los antioxidantes y los ácidos grasos poliinsaturados omega-3.

Multiple sclerosis is the most common cause of progressive neurological disability in young adults. This disease involves damage to the myelin sheath that normally insulates the electrical activity of nerve fibers. This leads to a wide range of symptoms as specific nerves become injured and lose their function. Epidemiological and experimental studies show that genetic alterations, antioxidant enzyme abnormalities and autoimmunity are risk factors for developing the disease. Recent evidence suggests that inflammation and oxidative stress within the central nervous system are major causes of ongoing tissue damage. Resident central nervous system cells and invading inflammatory cells release several reactive oxygen and nitrogen species which cause the histopathological features of multiple sclerosis: demyelization and axonal damage. The interplay between inflammatory and neurodegenerative processes results in an intermittent neurological disturbance followed by progressive accumulation of disability. Reductions in inflammation and oxidative stress status are important therapeutic strategies to slow or halt the disease processes. Therefore, several drugs are currently in trial in clinical practice to target this mechanism; particularly the use of supplements such as antioxidants and omega-3 polyunsaturated fatty acids, in order to improve the survival and quality of patients’ lives.

Mitochondrial ATPase activity and membrane fluidity changes in rat liver in response to intoxication with Buckthorn (Karwinskia humboldtiana)

BACKGROUND: Karwinskia humboldtiana (Kh) is a poisonous plant of the rhamnacea family. To elucidate some of the subcellular effects of Kh toxicity, membrane fluidity and ATPase activities as hydrolytic and as proton-pumping activity were assessed in rat liver submitochondrial particles. Rats were randomly assigned into control non-treated group and groups that received 1,1.5 and 2 g/Kg body weight of dry powder of Kh fruit, respectively. Rats were euthanized at day 1 and 7 after treatment. RESULTS: Rats under Kh treatment at all dose levels tested, does not developed any neurologic symptoms. However, we detected alterations in membrane fluidity and ATPase activity. Lower dose of Kh on day 1 after treatment induced higher mitochondrial membrane fluidity than control group. This change was strongly correlated with increased ATPase activity and pH gradient driven by ATP hydrolysis. On the other hand, membrane fluidity was hardly affected on day 7 after treatment with Kh. Surprisingly, the pH gradient driven by ATPase activity was significantly higher than controls despite an diminution of the hydrolytic activity of ATPase. CONCLUSIONS: The changes in ATPase activity and pH gradient driven by ATPase activity suggest an adaptive condition whereby the fluidity of the membrane is altered.

Epidemiological Characteristics of Surgical Wound- Infections in Cancer Patients from Jalisciense Institute of Cancerology. México.

Background: The surgical wound infections (SWI) are common in hospitals, depending on the type of surgery and the presence of risk factors, cancer patients have a higher prevalence of infection, (immune-compromised state in which it is located). A low rate of infection is one parameter to measure the quality of surgical services. The aim of the present work was to determine the epidemiological characteristics of SWI in cancer patients in the Jaliscience institute of cancerology. Study Design: A descriptive, retrospective study. Methodology: 46 patients were studied with SWI. Centers of disease control and prevention criteria for surgical wound infection were considered. Information was obtained from the Jaliscience Institute of Cancerology epidemiological department, using the hospital network for epidemiological surveillance (HNES) format record´s, included microbiological results and clinical data. The statistical analysis were performed with the SPSS-20 program. Results: There were 2637 major surgeries from April 2008 thru December 2010. 46 had SWI. Frequency of service per 100 infected surgeries was: Gastroenterology 58.6%, Gynecology 32.6%, Urology 4.4, Head and Neck 2.2% and Traumatology 2.2%. Incidence by gender: men (1.1), women (0.83), with no significant difference. Average age of 51 years. The surgical-wound infected (SWI) were detected between 7.4±4.2 days. Average days stay 19 days. The results of microbiology cultures exhibited: Escherichia coli 53.3%, Pseudomonas aeruginosa 11.9%, Morganella morganii 4.8%, Enterococcus faecium 11.9%, Enterococcus faecalis 23.8%, Staphylococcus-coagulase-negative 7.1%, Streptococcus ß-hemolytic 4.8%. Conclusion: Surgical wound infection rates were similar to that reported in other countries and below the rates reported in oncology hospitals in México. It is important to note that a proper preventive approach and epidemiological surveillance are critical to avoid mortality of patients.

Effect of Combined Aerobic and Anaerobic Training on Hemodynamic Response, Serum Oxidative Stress Markers and Platelet ATP Synthase Activities in Patients with Coronary Heart Disease: A Pilot Study.

Background: The overall aim of this work was to study the impact of combined aerobic and anaerobic training in relation to hemodynamic response (heart rate, systolic blood pressure, and double product), serum oxidative stress markers (lipoperoxides, nitrites-nitrates) and platelet ATP synthase activities in patients with coronary heart disease. Materials and Methods: Ten subjects, 9 male and 1 female, (mean age 57.7±7.2 years) with coronary heart disease participated in this study. Patients performed combined aerobic and anaerobic exercise for 24 sessions (three times a week). Results: The results suggest myocardium adaptations, manifested in the reduction of heart rate with increased workloads and increased double product [(heart rate) x (systolic blood pressure)] according to the intensity, frequency and duration of training. The ATP synthesis rate was significantly increased at session 3 (post-exercise) compared to session 1 (pre exercise). Furthermore, rate of ATP hydrolysis was significantly decreased at session 24 (post-exercise 3) compared to session 1 (post-exercise 1). Serum lipid peroxidation products and nitric oxide catabolites were significantly diminished at session 24 (pre-exercise). Conclusion: In some patients hemodynamic responses showed improvements in response to exercise. The exercise sessions induced lower levels of lipid peroxidation products, nitric oxide catabolites and ATPase activity. Conversely, ATP synthase activity showed higher values at the end of the experiment. These results confirm the beneficial effect of combined aerobic and anaerobic exercise.

Spinal Muscular Atrophy: Review of a Child Onset Disease.

Spinal Muscular Atrophy (SMA) is a group of inherited disorders that involve mainly bulbar and spinal motor neurons; causing muscle weakness and atrophy of proximal and symmetrical predominantly in lower extremities, without affecting the facial muscles and the intellectual ability. It is also unclear if SMA is a developmental or a neurodegenerative disease and occurs predominantly in childhood. The continuous clinical spectrum of SMA has been divided into 3 types based on the age at onset and highest motor milestones achieved. SMA type I was described by Hoffman in 1894 and in 1900 was reported as a disease characterized by hypotonia during the first 3 months of life, as well, is considered as the leading cause of death in children under two years of age among genetic diseases worldwide. SMA type II patients can achieve sitting but not walking. While SMA type III patients achieve full milestones with a progressive loss of walking ability. Deterioration in muscle strength and motor function eventually occurs in SMA type II and III. SMA occurs due to depletion of SMN, a ubiquitously expressed protein, which in all cells regulates RNA biogenesis and splicing through its role in the assembly of small nuclear ribonucleoprotein (snRNP) complexes.

Envejecimiento y metabolismo: cambios y regulación

Los estudios sobre los efectos del envejecimiento en la fisiología y el metabolismo cada vez son más, uno de sus objetivos es contribuir a instrumentar programas para mejorar la calidad de vida y prevenir discapacidades en la vejez. Es de gran importancia mencionar que durante el envejecimiento se presenta una desaceleración natural del metabolismo, se produce una serie de cambios en la regulación de la energía, lo que contribuye a la pérdida de peso y grasa; estos cambios en la regulación de la ingesta calórica contribuyen en un aumento de la susceptibilidad al desequilibrio energético tanto positivo como negativo, lo cual va asociado a un deterioro en la salud. Sin embargo, el llegar a la vejez, no es una sentencia de muerte para el metabolismo, por el contrario, éste puede ser controlado mediante el mantenimiento de un estilo de vida activo, aunado a esto investigaciones han demostrado que el metabolismo puede ser regulado mediante el papel que desempeña un sistema de reloj sincronizado (ritmos biológicos), el cual a su vez es modulado por varias proteínas reguladoras; esta relación garantiza que las células funcionen correctamente y por tanto el mantenerse saludables. El objetivo de esta revisión es aportar información actualizada sobre la regulación metabolismo-energía y su relación con la gran variedad de componentes involucrados en el gasto energético que acompañan al envejecimiento; analizar la regulación de este sistema para mejorar la calidad de vida y mantener la salud en la vejez.

Aging and metabolism: changes and regulation. Studies about the effects of aging in the physiology and metabolism are increasingly, one of its objectives is to help implement programs to improve the quality of life and prevent disability in elderly. It is relevant to mention that, during aging, there is a natural metabolic deceleration, a series of changes in the regulation of energy are produced, which contributes to loss of weight and fat; the changes in the regulation of caloric intake contribute to increase the susceptibility to energy imbalance both positive and negative, which is associated with a deterioration in health. However, to grow old, is not a death sentence for metabolism, on the other hand, it can be controlled by maintaining an active lifestyle, coupled with this, research has shown that the metabolism can be regulated by a synchronized clock (circadian rhythms), which is mediated by regulatory proteins, this relationship ensures the proper functioning of the cells and therefore good health. The aim of this review is to provide updated information on the energy- metabolism-regulation and its relationship with the great variety of components involved in energy expenditure that accompany aging, to analyze the regulation of this system to improve the quality of life and maintenance of health in old age.

El comportamiento del factor de necrosis tumoral alfa e interleucina 6 en lesiones de vías biliares postcolecistectomía / Tumor necrosis factor-alpha and interleukin-6 levels among patients suffering a bile duct injury during cholecystectomy

Background: During cholecystectomy, the bile duct may be injured. When this complication occurs, Kupffer cells are activated and produce tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL6) to phagocyte toxic products Aim: To measure serum levels of TNF-α and IL-6 among patients that suffered a bile duct injury after a cholecystectomy. Patients and Methods: Serum levels of TNF-α and IL-6 were measured prior to the bile-enteric derivation and after one year of follow up, in 31 patients that had a complete bile duct obstruction after open or laparoscopic cholecystectomy and in 5 healthy controls. Results: At baseline TNF-α levels in healthy subjects and patients with bile duct injury were 0 and 43.9 ± 2.9 ng/mL, respectively (p < 0.01). At one year of follow up, TNF-á became undetectable among patients. At baseline, the values for IL-6 among healthy controls and patients were 3.0 ± 2.0 and 72.0 ± 94.7 pg/mL respectively, (p < 0,004). After one year of follow up, IL-6 levels decreased to 6.4 ± 0.3 pg/mL among patients. Conclusions: TNF-α and IL-6 levels were elevated before bile-enteric derivation among patients with bile duct injury and became normal one year later.

Efecto del ibuprofeno y ácido acetilsalicílico sobre el deterioro cognitivo, poder antioxidante total e isoprostanos en suero / The effect of ibuprofen and acetylsalicylic acid on cognitive impairment, total antioxidant power and isoprostane serum

Introducción: Existen estudios controvertidos sobre la prevención de la enfermedad de Alzheimer y el uso de antiinflamatorios no esteroideos. El objetivo fue evaluar el efecto del ibuprofeno y ácido acetilsalicílico sobre el deterioro cognitivo, poder antioxidante total (PAT) e isoprostanos (8-iso-PGF2á) séricos. Material y métodos: Entre abril de 2004 y febrero de 2006, a 18 mujeres mayores de 55 años de edad se les realizó escrutinio con la Prueba Mínima del Estado Mental de Folstein (MMSE); Prueba Corta para la Evaluación de la Memoria y la Atención, Syndrome Kurtz Test (SKT) y Escala de Depresión Geriátrica de Yasevage. Fueron asignadas aleatoriamente para recibir 400 mg/día de ibuprofeno (n=9) o 500 mg/día de ácido acetilsalicílico (n=9) durante un año. En la visita basal, seis meses y al año se determinó PAT y 8-iso-PGF2á séricos. Resultados: A un año de intervención, en cinco mujeres (55.6%) el MMSE aumentó cuatro puntos con ácido acetilsalicílico comparado con tres (33.3%) de ibuprofeno (p=0.028). El PAT aumentó (p=0.01) y disminuyeron los 8-iso-PGF2á (p=0.01) en ambos grupos en comparación con los valores basales. Conclusiones: Ambos medicamentos mejoraron el estado cognitivo y el perfil oxidativo en la población estudiada.

INTRODUCTION: There are controversial studies on the prevention of Alzheimer's disease with nonsteroidal antiinflammatory drugs (NSAIDs). The objective of this study was to evaluate the effect of ibuprofen and acetylsalicylic acid on cognitive impairment, serum total antioxidant power (TAP) and isoprostane (8-iso-PGF2alpha). METHODS: From April 2004 to February 2006, a Folstein mini-mental state (MMSE), Syndrome Kurtz Test (SKT) and a geriatric depression scale (Yasevage) were applied to eighteen, 55-56 years old eligible women. All women (n= 18) with normal cognitive state were randomized to ibuprofen 400 mg per day (n= 9) and acetylsalicylic acid 500 mg per day (n= 9) for one year. Serum TAP and 8-iso-PGF2alpha were performed at baseline, after six months and one year of treatment. RESULTS: After one year of treatment with acetylsalicylic acid five women (55.6%) raised their score 4 points in MMSE compared with 3 points increased (33.3%) showed by the ibuprofen group. TAP increased (p=0.01) and 8-iso-PGF2alpha reduced (p=0.01) in both groups compared with baseline. CONCLUSIONS: Both drugs improved the cognitive state andoxidative status of our population.