Melatonin Preserves Fluidity in Cell and Mitochondrial Membranes against Hepatic Ischemia-Reperfusion.

We evaluated the in vivo effects of melatonin treatment on oxidative damage in the liver in an experimental model of ischemia-reperfusion. A total of 37 male Sprague-Dawley rats were randomly divided into four groups: control, ischemia, ischemia + reperfusion, and ischemia + reperfusion + melatonin. Hepatic ischemia was maintained for 20 min, and the clamp was removed to initiate vascular reperfusion for 30 min. Melatonin (50 mg/kg body weight) was intraperitoneally administered. Fluidity was measured by polarization changes in 1-(4-trimethylammoniumphenyl)-6-phenyl-1,3,5-hexatriene-p-toluene sulfonate). After 20 min of ischemia, no significant changes were observed in cell and mitochondrial membrane fluidity levels, lipid peroxidation, and protein carbonylation. However, after 30 min of reperfusion, membrane fluidity decreased compared to controls. Increases in lipid and protein oxidation were also seen in hepatic homogenates of animals exposed to reperfusion. Melatonin injected 30 min before ischemia and reperfusion fully prevented membrane rigidity and both lipid and protein oxidation. Livers from ischemia-reperfusion showed histopathological alterations and positive labeling with antibodies to oxidized lipids and proteins. Melatonin reduced the severity of these morphological changes and protected against in vivo ischemia-reperfusion-induced toxicity in the liver. Therefore, melatonin might be a candidate for co-treatment for patients with hepatic vascular occlusion followed by reperfusion.

Role of Oxidative Stress on the Etiology and Pathophysiology of Amyotrophic Lateral Sclerosis (ALS) and Its Relation with the Enteric Nervous System.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease affecting motor neurons in the spinal cord, cerebral cortex, and medulla oblongata. Most patients present a clinical phenotype of classic ALS-with predominant atrophy, muscle weakness, and fasciculations-and survival of 3 to 5 years following diagnosis. In the present review, we performed a literature search to provide an update on the etiology and pathophysiological mechanisms involved in ALS. There are two types of ALS: the familial form with genetic involvement, and the sporadic form with a multifactorial origin. ALS pathophysiology is characterized by involvement of multiple processes, including oxidative stress, glutamate excitotoxicity, and neuroinflammation. Moreover, it is proposed that conditioning risk factors affect ALS development, such as susceptibility to neurodegeneration in motor neurons, the intensity of performed physical activity, and intestinal dysbiosis with involvement of the enteric nervous system, which supports the existing theories of disease generation. To improve patients' prognosis and survival, it is necessary to further deepen our understanding of the etiopathogenesis of ALS.

Interstitial Cells of Cajal and Enteric Nervous System in Gastrointestinal and Neurological Pathology, Relation to Oxidative Stress.

The enteric nervous system (ENS) is organized into two plexuses-submucosal and myenteric-which regulate smooth muscle contraction, secretion, and blood flow along the gastrointestinal tract under the influence of the rest of the autonomic nervous system (ANS). Interstitial cells of Cajal (ICCs) are mainly located in the submucosa between the two muscle layers and at the intramuscular level. They communicate with neurons of the enteric nerve plexuses and smooth muscle fibers and generate slow waves that contribute to the control of gastrointestinal motility. They are also involved in enteric neurotransmission and exhibit mechanoreceptor activity. A close relationship appears to exist between oxidative stress and gastrointestinal diseases, in which ICCs can play a prominent role. Thus, gastrointestinal motility disorders in patients with neurological diseases may have a common ENS and central nervous system (CNS) nexus. In fact, the deleterious effects of free radicals could affect the fine interactions between ICCs and the ENS, as well as between the ENS and the CNS. In this review, we discuss possible disturbances in enteric neurotransmission and ICC function that may cause anomalous motility in the gut.

Performance of Bayesian Area Under the Concentration-Time Curve-Based Pharmacokinetic Dosing Based on a One-Compartment Model and Trough-Only Monitoring for Vancomycin.

A novel Bayesian method was developed to interpret serum vancomycin concentrations (SVCs) following the administration of one or more vancomycin doses with potential varying doses and intervals based on superposition principles. The method was evaluated using retrospective data from 442 subjects from three hospitals. The patients were required to receive vancomycin for more than 3 days, have stable renal function (fluctuation in serum creatinine of ≤0.3 mg/dL), and have at least 2 trough concentrations reported. Pharmacokinetic parameters were predicted using the first SVC, and the fitted parameters were then used to predict subsequent SVCs. Using only covariate-adjusted population prior estimates, the first two SVC prediction errors were 47.3 to 54.7% for the scaled mean absolute error (sMAE) and 62.1 to 67.8% for the scaled root mean squared error (sRMSE). "Scaled" refers to the division of the MAE or RMSE by the mean value. The Bayesian method had minimal errors for the first SVC (by design), and for the second SVC, the sMAE was 8.95%, and the sRMSE was 36.5%. The predictive performance of the Bayesian method did degrade with subsequent SVCs, which we attributed to time-dependent pharmacokinetics. The 24-h area under the concentration-time curve (AUC) was determined from simulated concentrations before and after the first SVC was reported. Prior to the first SVC, 170 (38.4%) patients had a 24-h AUC of <400 mg · h/L, 186 (42.1%) had a 24-h AUC within the target range, and 86 (19.5%) had a 24-h AUC of >600 mg · h/L. After the first SVC was reported, 322 (72.9%) had a 24-h AUC within the target range, 68 (15.4%) had low values, and 52 (11.8%) had high values based on the model simulation. Target attainments were 38% before the first SVC and 73% after the first SVC. The hospitals had no policies or procedures in place for targeting 24-h AUCs, although the trough target was typically 13 to 17 mg/L. Our data provide evidence of time-dependent pharmacokinetics, which will require regular therapeutic drug monitoring regardless of the method used to interpret SVCs.

Tumor trofoblástico de sitio placentario secundario a mola parcial. Reporte de un caso / Placental site trophoblastic tumor secondary to partial mole. Report of a case

Resumen ANTECEDENTES: La enfermedad trofoblástica gestacional es un padecimiento que incluye un grupo de tumores placentarios, consecuencia de una proliferación anormal del tejido del trofoblasto. Se caracteriza por una excesiva elevación de la gonadotrofina coriónica humana que se considera diagnóstica y un predictor pronóstico. CASO CLÍNICO: Paciente de 23 años con hiperémesis gravídica y aumento del tamaño del útero mayor para las siete semanas de gestación y cuantificación de las concentraciones de HGC anormalmente elevadas en comparación con su valor basal. Se descartaron los diagnósticos diferenciales de mola parcial hidatiforme, mola completa y embarazo múltiple. Se concluyó que se trataba de enfermedad trofoblástica gestacional. Se procedió a la evacuación de la cavidad uterina de la que se extrajeron abundantes porciones de tejido ovoconformacional y molariforme. El informe de Patología fue: útero arcuato con tumor de sitio placentario, endometritis crónica, cervicitis con metaplasia escamosa, quiste de Nabot y endometrio proliferativo tardío. CONCLUSIÓN: Puesto que las pacientes con enfermedad trofoblástica gestacional suelen tener un pronóstico sombrío se sugiere la histerectomía simple para llegar a la curación. Por la agresividad del tumor y resistencia a otros tratamientos es indispensable el monitoreo riguroso semanal de la cuantificación de la HCG.

Abstract BACKGROUND: Gestational trophoblastic disease is a condition that includes a group of placental tumors resulting from abnormal proliferation of trophoblast tissue. It is characterized by an excessive elevation of human chorionic gonadotropin which is considered diagnostic and a prognostic predictor. CLINICAL CASE: 23-year-old patient with hyperemesis gravidarum and uterine enlargement greater than 7 weeks' gestation and abnormally elevated HGC levels compared to baseline. The differential diagnoses of hydatidiform partial mole, complete mole and multiple pregnancy were ruled out. It was concluded that it was gestational trophoblastic disease. The uterine cavity was evacuated and abundant portions of ovoconformal and molariform tissue were extracted. The pathology report was: arcuate uterus with placental site tumor, chronic endometritis, cervicitis with squamous metaplasia, Nabot's cyst and late proliferative endometrium. CONCLUSION: Since patients with gestational trophoblastic disease usually have a dismal prognosis simple hysterectomy is suggested to reach cure. Because of the aggressiveness of the tumor and resistance to other treatments, rigorous weekly monitoring of HCG quantification is indispensable.

Melatonin's role in preventing toxin-related and sepsis-mediated hepatic damage: A review.

The liver is a central organ in detoxifying molecules and would otherwise cause molecular damage throughout the organism. Numerous toxic agents including aflatoxin, heavy metals, nicotine, carbon tetrachloride, thioacetamide, and toxins derived during septic processes, generate reactive oxygen species followed by molecular damage to lipids, proteins and DNA, which culminates in hepatic cell death. As a result, the identification of protective agents capable of ameliorating the damage at the cellular level is an urgent need. Melatonin is a powerful endogenous antioxidant produced by the pineal gland and a variety of other organs and many studies confirm its benefits against oxidative stress including lipid peroxidation, protein mutilation and molecular degeneration in various organs, including the liver. Recent studies confirm the benefits of melatonin in reducing the cellular damage generated as a result of the metabolism of toxic agents. These protective effects are apparent when melatonin is given as a sole therapy or in conjunction with other potentially protective agents. This review summarizes the published reports that document melatonin's ability to protect hepatocytes from molecular damage due to a wide variety of substances (aflatoxin, heavy metals, nicotine, carbon tetrachloride, chemotherapeutics, and endotoxins involved in the septic process), and explains the potential mechanisms by which melatonin provides these benefits. Melatonin is an endogenously-produced molecule which has a very high safety profile that should find utility as a protective molecule against a host of agents that are known to cause molecular mutilation at the level of the liver.

Improved prenatal detection of congenital heart disease in an integrated health care system.

The reported prenatal detection rates (PDRs) for significant congenital heart disease (sCHD) have been suboptimal, even in the current era. Changes in prenatal ultrasound policy and training may lead to improved prenatal detection of sCHD. This study analyzed the results of a policy to assess fetal cardiac outflow tracts shown by screening prenatal ultrasound using the electronic medical record (EMR). During a 6-year period, fetuses and patients younger than 1 year with sCHD were identified. The EMR was used to gather detection and outcome data. As an internal control within the same health care system, the PDR of only the surgical cases was compared with that of a similar group in which documentation of the fetal cardiac outflow tracts was not standard policy. Among 25,666 births, sCHD was identified in 93 fetuses or patients, yielding an incidence of 3.6 per 1,000 births. The PDR was 74.1%. Detection after birth but before discharge was 20.4%, and detection after discharge was 5.4%. A significant improvement in the PDR of sCHD was found when a concerted effort was made to obtain fetal cardiac outflow tract views during pregnancy screening (59.3 vs. 28%). Within an integrated health care system and with the use of an EMR, a PDR of 74% can be obtained, and 94% of sCHD can be detected before discharge. A concerted program that includes documentation of fetal cardiac outflow tracts in the pregnancy screening can result in improved PDR of sCHD.

Melatonin reduces lipid and protein oxidative damage in synaptosomes due to aluminium.

Prolonged exposure to excessive aluminium (Al) concentrations is involved in the ethiopathology of certain dementias and neurological disorders. Melatonin is a well-known antioxidant that efficiently reduces lipid peroxidation due to oxidative stress. Herein, we investigated in synaptosomal membranes the effect of melatonin in preventing Al promotion of lipid and protein oxidation when the metal was combined with FeCl(3) and ascorbic acid. Lipid peroxidation was estimated by quantifying malondialdehyde (MDA) and 4-hydroxyalkenals (4-HDA) concentrations in the membrane suspension and protein carbonyls were measured in the synaptosomes as an index of oxidative damage. Under our experimental conditions, the addition of Al (0.0001-1mmol/L) enhanced MDA+4-HDA formation in the synaptosomes. In addition, Al (1mmol/L) raised protein carbonyl contents. Melatonin reduced, in a concentration-dependent manner, lipid and protein oxidation due to Al, FeCl(3) and ascorbic acid in the synaptosomal membranes. These results show that melatonin confers protection against Al-induced oxidative damage in synaptosomes and suggest that this indoleamine may be considered as a neuroprotective agent in Al toxicity because of its antioxidant activity.

Detection of single clone deletions using array CGH: identification of submicroscopic deletions in the 22q11.2 deletion syndrome as a model system.

Constitutional submicroscopic DNA copy number alterations have been shown to cause numerous medical genetic syndromes, and are suspected to occur in a portion of cases for which the causal events remain undiscovered. Array comparative genomic hybridization (array CGH) allows high-throughput, high-resolution genome scanning for DNA dosage aberrations and thus offers an attractive approach for both clinical diagnosis and discovery efforts. Here we assess this capability by applying array CGH to the analysis of copy number alterations in 44 patients with a phenotype of the 22q11.2 deletion syndrome. Twenty-five patients had the deletion on chromosome 22 characteristic of this syndrome as determined by fluorescence in situ hybridization (FISH). The array measurements were in complete concordance with the FISH analysis, supporting their diagnostic utility. These data show that a genome-scanning microarray has the level of sensitivity and specificity required to prospectively interrogate and identify single copy number aberrations in a clinical setting. We demonstrate that such technology is ideally suited for microdeletion syndromes such as 22q11.2.

Fisiología del envejecimiento y del estrés oxidativo (B40) / No disponible

No disponible