Gabriella D’Angelo

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.

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.

Role of the diet as a link between oxidative stress and liver diseases

Oxidative stress is caused by an imbalance between the production of reactive oxygen (free radicals) and the bodys ability (antioxidant capacity) to readily detoxify the reactive intermediates or easily repair the resulting damage. An adequate diet, characterized by daily intake of foods associated with improvements in the total antioxidant capacity of individuals and reduced incidence of diseases related to oxidation, can modulate the degree of oxidative stress. In fact, diet-derived micronutrients may be direct antioxidants, or are components of antioxidant enzymes, leading to improvement of some indicators of hepatic function. However, although their increased dietary intake might be beneficial, literature data are still controversial. This review summarizes what is known about the effects of diet nutrients on oxidative stress, inflammation and liver function. Moreover, we have analyzed: (1) the main nutritional components involved in the production and/or removal of free radicals; and (2) the role of free radicals in the pathogenesis of several hepatic diseases and related comorbidities.

Gastroesophageal reflux and congenital gastrointestinal malformations

Although the outcome of newborns with surgical congenital diseases (e.g., diaphragmatic hernia; esophageal atresia; omphalocele; gastroschisis) has improved rapidly with recent advances in perinatal intensive care and surgery, infant survivors often require intensive treatment after birth, have prolonged hospitalizations, and, after discharge, may have long-term sequelae including gastro-intestinal comorbidities, above all, gastroesophageal reflux (GER). This condition involves the involuntary retrograde passage of gastric contents into the esophagus, with or without regurgitation or vomiting. It is a well-recognized condition, typical of infants, with an incidence of 85%, which usually resolves after physiological maturation of the lower esophageal sphincter and lengthening of the intra-abdominal esophagus, in the first few months after birth. Although the exact cause of abnormal esophageal function in congenital defects is not clearly understood, it has been hypothesized that common (increased intra-abdominal pressure after closure of the abdominal defect) and/or specific (e.g., motility disturbance of the upper gastrointestinal tract, damage of esophageal peristaltic pump) pathological mechanisms may play a role in the etiology of GER in patients with birth defects. Improvement of knowledge could positively impact the long-term prognosis of patients with surgical congenital diseases. The present manuscript provides a literature review focused on pathological and clinical characteristics of GER in patients who have undergone surgical treatment for congenital abdominal malformations.

Visfatin: New marker of oxidative stress in preterm newborns

Background: Oxidative stress is involved in several neonatal conditions characterized by an upregulation in the production of oxidative or nitrative free radicals and a concomitant decrease in the availability of antioxidant species. Oxygen, which is obviously vital to survival, can be highly damaging to neonatal tissue which is known to be poorly equipped to neutralize toxic derivatives. Thus, exposure of the newborn infant to high oxygen concentrations during resuscitation at birth increases oxidative damage. Visfatin is an adipocytokine involved in oxidative stress and an important mediator of inflammation that induces dose-dependent production of both pro-inflammatory and anti-inflammatory cytokines. To our knowledge, the diagnostic value of visfatin as a marker of oxidative stress in preterm newborns has not been investigated. Objective: The aim of this study was to evaluate visfatin levels in preterm neonates resuscitated with different concentrations of oxygen in the delivery room. Patients: Fifty-two preterm newborns with gestational age less than 32 weeks, resuscitated randomly with different oxygen concentrations (40%, 60%, or 100%) were enrolled at the University Hospital of Messina, over a 12-month period to evaluate serum visfatin levels at T0 (within 1 h after birth), T24 h, T72 h, and T168 h of life. Results: At T72 h and T168 h, higher serum visfatin values in the high-oxygen group compared to the low- and mild-oxygen subjects (P = 0.002 and P <0.001, respectively) were noted. Conclusion: The results of this study suggest that visfatin could be a new marker of oxidative stress in preterm newborns.

Ventilation strategies for preventing oxidative stress-induced injury in preterm infants with respiratory disease: an update

Reactive oxygen and nitrogen species are produced by several inflammatory and structural cells of the airways. The lungs of preterm newborns are susceptible to oxidative injury induced by both reactive oxygen and nitrogen species. Increased oxidative stress and imbalance in antioxidant enzymes may play a role in the pathogenesis of inflammatory pulmonary diseases. Preterm infants are frequently exposed to high oxygen concentrations, infections or inflammation; they have reduced antioxidant defense and high free iron levels which enhance toxic radical generation. Multiple ventilation strategies have been studied to reduce injury and improve outcomes in preterm infants. Using lung protective strategies, there is the need to reach a compromise between satisfaction of gas exchange and potential toxicities related to over-distension, derecruitment of lung units and high oxygen concentrations. In this review, the authors summarize scientific evidence concerning oxidative stress as it relates to resuscitation in the delivery room and to the strategies of ventilation.

Melatonin Secretion Is Increased in Children with Severe Traumatic Brain Injury

Background: Traumatic brain injury (TBI) is a leading cause of death and disability in children. Oxidative stress plays a significant role in brain damage and melatonin exhibits both direct and indirect antioxidant effects. The primary aim of the present study was to evaluate serum melatonin levels in children with severe TBI in comparison to critically ill children admitted to the Pediatric Intensive Care Unit for conditions other than TBI. Methods: Twenty-four children were evaluated, equally divided into severe TBI and no-TBI. Blood samples for serum melatonin analysis were collected at 22:00, 01:00, 03:00, 05:00, 08:00, and 12:00. Results: Mean serum melatonin peaks in children of the TBI group were higher compared to the values of no-TBI critically ill children (495 ± 102 vs. 294 ± 119 pg/mL, p = 0.0002). Furthermore, the difference was even more significant in comparison to values reported in literature for healthy age-matched children (495 ± 102 vs. 197 ± 71 pg/mL, p < 0.0001). Conclusion: This study has shown that endogenous serum melatonin levels dramatically increase in children after severe TBI. This elevation is likely to represent a response to oxidative stress and/or inflammation due to severe head injury.

“Cumulative Stress”: The Effects of Maternal and Neonatal Oxidative Stress and Oxidative Stress-Inducible Genes on Programming of Atopy

Although extensive epidemiological and laboratory studies have been performed to identify the environmental and immunological causes of atopy, genetic predisposition seems to be the biggest risk factor for allergic diseases. The onset of atopic diseases may be the result of heritable changes of gene expression, without any alteration in DNA sequences occurring in response to early environmental stimuli. Findings suggest that the establishment of a peculiar epigenetic pattern may also be generated by oxidative stress (OS) and perpetuated by the activation of OS-related genes. Analyzing the role of maternal and neonatal oxidative stress and oxidative stress-inducible genes, the purpose of this review was to summarize what is known about the relationship between maternal and neonatal OS-related genes and the development of atopic diseases.

Atopy and autoimmune thyroid diseases: melatonin can be useful?

Recently, there has been growing interest in the relationship between allergic and autoimmune diseases. Allergy and autoimmunity can be considered two potential outcomes of dysregulated immunity and analysis of literature data shows a strong positive association between a history of Th2-mediated allergic disorders and Th1-mediated autoimmune disorders.Autoimmune thyroid diseases are the most common of all autoimmune pathological conditions.Currently, the mechanisms explaining an association among atopy, autoimmunity, and thyroid diseases are not fully understood.There are data in literature pointing to the relationship between melatonin and thyroid activity. Several studies have suggested a paracrine role for this molecule in the regulation of thyroid activity, documenting that administration, as an antioxidant, in thyroid tissues under conditions of increased oxidative stress, could be helpful to reduce the oxidative processes involved in autoimmune thyroid diseases.Although thyroid autoimmunity has been regularly associated with atopic conditions in children, the possible protective role of melatonin has not yet been investigated.This review summarizes what is known regarding the connection between atopy and autoimmune thyroid diseases, and analyses the probable beneficial action of melatonin.

Oxidative Stress of Newborn

Free radicals are highly reactive molecules containing one or more unpaired electrons. They donate or abstract electrons from other molecules in an attempt to pair their electrons and generate a more stable species. Oxygen-derived reactants collectively termed reactive oxygen species (ROS) as well as reactive nitrogen species (RNS) are normally produced in living organisms. When produced in excess, they are important mediators of cell and tissue injury [Halliwell, B. (1999), Fridovich, I. (1998), Gitto, E. et al. (2002)]. The resulting damage is referred to as oxidative stress. Free radicals are highly unstable and several enzymes and small-molecular-weight molecules with antioxidant capabilities protect against them [Halliwell, B. (1992)]; these protective molecules are part of the antioxidative defence system. There is a critical balance between free radical generation and antioxidant defences. Free radical reactions lead to the oxidation of lipids, proteins, polysaccharides and to DNA damage (fragmentation, base modifications and strand breaks); as a consequence, radicals have a wide range of biologically toxic effects [Saugstad, OD. (1996), Sarker, AH. et al. (1995)]. The generation of both ROS and RNS are summarised in figure 1.