Lucia Marseglia

Oxidative Stress in Obesity: A Critical Component in Human Diseases

Obesity, a social problem worldwide, is characterized by an increase in body weight that results in excessive fat accumulation. Obesity is a major cause of morbidity and mortality and leads to several diseases, including metabolic syndrome, diabetes mellitus, cardiovascular, fatty liver diseases, and cancer. Growing evidence allows us to understand the critical role of adipose tissue in controlling the physic-pathological mechanisms of obesity and related comorbidities. Recently, adipose tissue, especially in the visceral compartment, has been considered not only as a simple energy depository tissue, but also as an active endocrine organ releasing a variety of biologically active molecules known as adipocytokines or adipokines. Based on the complex interplay between adipokines, obesity is also characterized by chronic low grade inflammation with permanently increased oxidative stress (OS). Over-expression of oxidative stress damages cellular structures together with under-production of anti-oxidant mechanisms, leading to the development of obesity-related complications. The aim of this review is to summarize what is known in the relationship between OS in obesity and obesity-related diseases.

Protective Role of Melatonin in Neonatal Diseases

Oxidative stress contributes to the severity of several newborn conditions to the extent that Saugstad coined the phrase “oxygen radical diseases of neonatology.” In order to counteract free radicals damage many strategies to augment antioxidant status in ill-term and preterm infants have been proposed and several medications have been experimented with mixed results. Several studies have tested the efficacy of melatonin to counteract oxidative damage in diseases of newborns such as chronic lung disease, perinatal brain injury, necrotizing enterocolitis, and retinopathy of prematurity, giving promising results. The peculiar perinatal susceptibility to oxidative stress indicates that prophylactic use of antioxidants as melatonin could help to prevent or at least reduce oxidative stress related diseases in newborns. However, more studies are needed to confirm these beneficial effects.

Oxidative Stress-Mediated Aging during the Fetal and Perinatal Periods

Oxidative stress is worldwide recognized as a fundamental component of the aging, a process that begins before birth. There is a critical balance between free radical generation and antioxidant defenses. Oxidative stress is caused by an imbalance between the production of free radicals and the ability of antioxidant system to detoxify them. Oxidative stress can occur early in pregnancy and continue in the postnatal period; this damage is implicated in the pathophysiology of pregnancy-related disorders, including recurrent pregnancy loss, preeclampsia and preterm premature rupture of membranes. Moreover, diseases of the neonatal period such as bronchopulmonary dysplasia, retinopathy of prematurity, necrotizing enterocolitis, and periventricular leukomalacia are related to free radical damage. The specific contribution of oxidative stress to the pathogenesis and progression of these neonatal diseases is only partially understood. This review summarizes what is known about the role of oxidative stress in pregnancy and in the pathogenesis of common disorders of the newborn, as a component of the early aging process.

Melatonin and atopy: role in atopic dermatitis and asthma.

Melatonin may have important immunostimulatory actions in allergic diseases, in addition to its well-known antioxidant and cytoprotective effects in several inflammatory conditions. The activation of the immune system leads to free radical production associated with decreased melatonin levels and depressed antioxidant enzyme activities in several inflammatory diseases. Many skin disorders, including atopic dermatitis, are accompanied by infiltration and activation of mast cells, which release vasoactive and proinflammatory mediators. Experimental data suggest that melatonin inhibits development of atopic eczema and reduces serum total IgE and IL-4. Allergic asthma is a condition characterized by bronchial hyperresponsiveness and the presence of IgE antibodies in response to inhaled allergens; often there is also enhanced total serum IgE levels. Melatonin regulates smooth muscle tone and influences the immune response. Melatonin may, however, act as a pro-inflammatory agent in asthma leading to bronchial constriction. The safety of melatonin as a sleep-inducing agent has been confirmed in asthmatic subjects, but its routine use is not recommended in bronchial asthma. This review summarizes what is known about the role of melatonin as an immunomodulatory agent in asthma and atopic eczema.

Analgesic, Anxiolytic and Anaesthetic Effects of Melatonin: New Potential Uses in Pediatrics

Exogenous melatonin is used in a number of situations, first and foremost in the treatment of sleep disorders and jet leg. However, the hypnotic, antinociceptive, and anticonvulsant properties of melatonin endow this neurohormone with the profile of a drug that modulates effects of anesthetic agents, supporting its potential use at different stages during anesthetic procedures, in both adults and children. In light of these properties, melatonin has been administered to children undergoing diagnostic procedures requiring sedation or general anesthesia, such as magnetic resonance imaging, auditory brainstem response tests and electroencephalogram. Controversial data support the use of melatonin as anxiolytic and antinociceptive agents in pediatric patients undergoing surgery. The aim of this review was to evaluate available evidence relating to efficacy and safety of melatonin as an analgesic and as a sedative agent in children. Melatonin and its analogs may have a role in antinociceptive therapies and as an alternative to midazolam in premedication of adults and children, although its effectiveness is still controversial and available data are clearly incomplete.

Obesity and breastfeeding: The strength of association

UNLABELLED Obesity and attendant co-morbidities are an emergent problem in public health. Much attention has focused on prevention, especially during the perinatal period. Breastfeeding is considered a possible protective factor for obesity in childhood, influencing gene-neuroendocrine-environment-lifestyle interaction. Therefore, breastfeeding and its longer duration are probably associated with lower development of childhood obesity. Through human milk, but not formula, the child assumes greater bioactive factors contributing to immunological, endocrine, development, neural and psychological benefits. Contrarily, other studies did not confirm a critical role of breast milk. Confounding factors, especially maternal pre-pregnancy overweight, may influence breastfeeding effects. This review summarises what is known about the possible relationship between breastfeeding and prevention of obesity development. CONCLUSION Breastfeeding appears to represent a protective factor for obesity in childhood, although evidence is still controversial and underlying mechanisms unclear. Further research is needed to improve knowledge on overweight/obesity and breastfeeding.

Serum levels of resistin and its correlation with adiponectin and insulin in healthy full term neonates

UNLABELLED Resistin and adiponectin are two adipokines involved in the regulation of insulin sensitivity, and have been suggested as mediators of adult metabolic syndrome. AIM The aim of this study was to investigate cord blood levels of resistin, and their postnatal changes in full-term appropriate for gestational age (AGA) neonates. Interrelations between resistin, adiponectin, and insulin, and between resistin and neonatal and maternal anthropometric parameters were also assessed. DESIGN Blood samples were obtained from 30 full term AGA neonates at birth and on the 4th day of life. Anthropometric variables studied included birth weight, length, body mass index (BMI), neonatal weight loss, and mothers BMI. Resistin and adiponectin were determined by ELISA, and insulin by radioimmunoassay method. Data were analyzed using Wilcoxon test and Spearmans correlation coefficient. RESULTS Resistin levels were high at birth and did not change on the 4th day of life. Resistin levels were not correlated to insulin, nor adiponectin levels, nor any anthropometric parameter of neonates or their mothers. Instead, adiponectin levels increased on the 4th day of life, and were correlated to insulin levels. CONCLUSION High levels of resistin in full-term AGA neonates suggest that this hormone may play a role in maintenance of metabolic neonatal homeostasis, but its physiological significance needs further investigation.

Oxidative Stress-Mediated Damage in Newborns with Necrotizing Enterocolitis: A Possible Role of Melatonin.

BACKGROUND Necrotizing enterocolitis is a gastrointestinal surgical emergency in premature neonates. Free radicals have been linked to the development of the disease in infants. Ischemia, hypoxia-reperfusion, infection, and inflammation produce elevated levels of reactive oxygen species, impairing the redox balance and shifting cells into a state of oxidative stress. Melatonin, an effective direct free-radical scavenger and indirect antioxidant agent, exerts pleiotropic action on the human body. Several studies have tested the efficacy of melatonin in counteracting oxidative injury in diseases of newborns. Melatonin has been widely used in newborns including cases of asphyxia, respiratory distress syndrome, and sepsis, and no significant toxicity or treatment-related side effects with long-term melatonin therapy have been reported. CONCLUSION Therefore, melatonin, besides standard therapies, could be considered as a potentially safe approach to prevent and treat necrotizing enterocolitis in premature infants. This review summarizes what is known about the role of oxidative stress, and potentially beneficial effects of antioxidants, such as melatonin, in necrotizing enterocolitis.

Menstrual cycle pattern during the first gynaecological years in girls with precocious puberty following gonadotropin-releasing hormone analogue treatment

Keywords Menarchetiming.Menstrualcycle.Centralprecociouspuberty.GnRHaOur aim was to longitudinally investigate menarche timingand menstrual cycle (MC) pattern during the first fivegynaecological years in 101 girls with idiopathic centralprecocious puberty (CPP) who had been treated withgonadotropin-releasing hormone agonists (GnRHa) for atleast two years. Our girls received Decapeptyl Depot(60

Potential Utility of Melatonin in Preeclampsia, Intrauterine Fetal Growth Retardation, and Perinatal Asphyxia

Aim: Reactive oxygen species play an important role in the pathogenesis of several diseases during gestation and the perinatal period. During pregnancy, increased oxygen demand augments the rate of production of free radicals. Oxidative stress is involved in pregnancy disorders including preeclampsia and intrauterine fetal growth retardation (IUGR). Moreover, increased levels of oxidative stress and reduced antioxidative capacities may contribute to the pathogenesis of perinatal asphyxia. Melatonin, an efficient antioxidant agent, diffuses through biological membranes easily and exerts pleiotropic actions on every cell and appears to be essential for successful gestation. This narrative review summarizes current knowledge concerning the role of melatonin in reducing complications during human pregnancy and in the perinatal period. Results: Melatonin levels are altered in women with abnormally functioning placentae during preeclampsia and IUGR. Short-term melatonin therapy is highly effective and safe in reducing complications during pregnancy and in the perinatal period. Because melatonin has been shown to be safe for both mother and fetus, it could be an attractive therapy in pregnancy and is considered a promising neuroprotective agent in perinatal asphyxia. Conclusion: We believe that the use of melatonin treatment during the late fetal and early neonatal period might result in a wide range of health benefits, improved quality of life, and may help limit complications during the critical periods prior to, and shortly after, delivery.