Publications by authors named "Antonietta Messina"

71 Publications

[Hepatic organoids: What are the challenges?]

Med Sci (Paris) 2021 Oct 14;37(10):902-909. Epub 2021 Oct 14.

Inserm UMRS 1193, Université Paris-Saclay, 12-14 avenue Paul Vaillant Couturier, F-94800 Villejuif, France - Fédération hospitalo-universitaire Hépatinov, hôpital Paul Brousse, F-94800 Villejuif, France - Institut français de BioFabrication, hôpital Paul Brousse, F-94800 Villejuif, France.

The study and understanding of liver organogenesis have allowed the development of protocols for pluripotent stem cells differentiation to overcome the lack of primary cells, providing an almost unlimited source of liver cells. However, as their differentiation in conventional 2D culture systems has shown serious limits, hepatic organoids derived from human pluripotent stem cells represent a promising alternative. These complex and organized structures, containing one or more cell types, make it possible to recapitulate in vitro some of the organ functions, thus enabling numerous applications such as the study of the liver development, the mass production of functional liver cells for transplantation or the development of bioartificial livers, as well as the in vitro modeling of hepatic pathologies allowing high throughput applications in drug screening or toxicity studies. Economic and ethical issues must also be taken into account before using these organoids in therapeutic applications.
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http://dx.doi.org/10.1051/medsci/2021119DOI Listing
October 2021

The Role of Very Low Calorie Ketogenic Diet in Sympathetic Activation through Cortisol Secretion in Male Obese Population.

J Clin Med 2021 Sep 18;10(18). Epub 2021 Sep 18.

Department of Experimental Medicine, Section of Human Physiology and Unit of Dietetics and Sports Medicine, Università degli Studi della Campania "Luigi Vanvitelli", 80138 Naples, Italy.

Adipose tissue is considered an endocrine organ, and its excess compromises the immune response and metabolism of hormones and nutrients. Furthermore, the accumulation of visceral fat helps to increase the synthesis of cortisol. The hypothalamus-pituitary-adrenal (HPA) axis is a neuroendocrine system involved in maintaining homeostasis in humans under physiological conditions and stress, and cortisol is the main hormone of the HPA axis. It is known that a stress-induced diet and cortisol reactivity to acute stress factors may be related to dietary behavior. In obesity, to reduce visceral adipose tissue, caloric restriction is a valid strategy. In light of this fact, the aim of this study was to assess the effects of a commercial dietary ketosis program for weight loss on the sympathetic nervous system and HPA axis, through evaluation of salivary cortisol and GSR levels. Thirty obese subjects were recruited and assessed before and after 8 weeks of Very Low Calorie Ketogenic Diet (VLCKD) intervention to evaluate body composition and biochemical parameters. Salivary cortisol levels and GSR significantly decreased after dietary treatment; in addition, body composition and biochemical features were ameliorated. The VLCKD had a short-term positive effect on the SNS and HPA axes regulating salivary cortisol levels. Finally, the effects of the VLCKD on the SNS and HPA axis may lead to more individualized treatment strategies that integrate obesity and stress and support the usefulness of such therapeutic interventions in promoting the reduction of the individual disease burden.
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http://dx.doi.org/10.3390/jcm10184230DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8470486PMC
September 2021

Obese Subjects without Eating Disorders Experience Binge Episodes Also Independently of Emotional Eating and Personality Traits among University Students of Southern Italy.

Brain Sci 2021 Aug 29;11(9). Epub 2021 Aug 29.

Department of Experimental Medicine, University of Campania "Luigi Vanvitelli", 80138 Naples, Italy.

It is widely acknowledged that obesity is a growing public clinical issue involving both physical and psychological well-being. Nevertheless, the relationship between psychological features and weight gain is still unclear. Although emotional eating (EE) and personality traits are considered significant predictors of eating disorders, their role in obesity without eating disorders (OB-wed) is far from proven. The present study aimed at investigating the cumulative effect of EE and personality traits on overeating behavior in a sample of 266 university students (169 female; mean age = 21.85, SD = 2.39) stratified based on their body mass index (BMI; normal weight, overweight, obese). They were enrolled during free screening days promoted by the Human Dietetic and Sport Service of a Southern Italian university. The results show a psychological pattern of increasing overeating behavior and lower Self-Directedness combined with higher Sadness and Anger. However, OB-wed subjects overate regardless of this emotional/personological configuration.
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http://dx.doi.org/10.3390/brainsci11091145DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8465169PMC
August 2021

Very Low-Calorie Ketogenic Diet Modulates the Autonomic Nervous System Activity through Salivary Amylase in Obese Population Subjects.

Int J Environ Res Public Health 2021 08 11;18(16). Epub 2021 Aug 11.

Section of Human Physiology and Unit of Dietetics and Sports Medicine, Department of Experimental Medicine, Università degli Studi della Campania "Luigi Vanvitelli", 80138 Naples, Italy.

In obesity, to reduce visceral adipose tissue (VAT), caloric restriction is a valid strategy. Salivary amylase is an enzyme that cleaves large starch carbohydrates molecules and its production is modulated by the central nervous system. In addition, heart rate variability (HRV) is simply a measure of the variation in time between each heartbeat. This variation is controlled by the autonomic nervous system. In the light of this evidence, the aim of this study is to characterize the effect of a very low-calorie ketogenic diet (VLCKD) on the autonomic nervous system in obese patients. Twenty subjects affected by obesity were recruited before and after 8 weeks of VLCKD intervention to evaluate salivary amylase by the ELISA test and HRV analysis. These parameters significantly increased after dietary treatment, and positively correlate to each other. VLCKD exerts a positive effect on salivary amylase and HRV, ameliorating body composition and biochemical features. In brief, this dietary intervention improves the autonomic nervous system activity. This is the first study about the effects of VLCKD upon the autonomic nervous system, but further studies are needed to elucidate the mechanism undergone VLCKD effects.
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http://dx.doi.org/10.3390/ijerph18168475DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8393849PMC
August 2021

Role of Vitamin E and the Orexin System in Neuroprotection.

Brain Sci 2021 Aug 20;11(8). Epub 2021 Aug 20.

Department of Clinical and Experimental Medicine, University of Foggia, 71122 Foggia, Italy.

Microglia are the first line of defense at the level of the central nervous system (CNS). Phenotypic change in microglia can be regulated by various factors, including the orexin system. Neuroinflammation is an inflammatory process mediated by cytokines, by the lack of interaction of specific receptors such as the OX2-OX2R complex, caused by systemic tissue damage or, more often, associated with direct damage to the CNS. Chronic activation of microglia could lead to long-term neurodegenerative diseases. This review aims to explore how tocopherol (vitamin E) and the orexin system may play a role in the prevention and treatment of microglia inflammation and, consequently, in neurodegenerative diseases thanks to its antioxidant properties. The results of animal and in vitro studies provide evidence to support the use of tocopherol for a reduction in microglia inflammation as well as a greater activation of the orexinergic system. Although there is much in vivo and in vitro evidence of vitamin E antioxidant and protective abilities, there are still conflicting results for its use as a treatment for neurodegenerative diseases that speculate that vitamin E, under certain conditions or genetic predispositions, can be pro-oxidant and harmful.
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http://dx.doi.org/10.3390/brainsci11081098DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8394512PMC
August 2021

A versatile microfluidic tool for the 3D culture of HepaRG cells seeded at various stages of differentiation.

Sci Rep 2021 07 7;11(1):14075. Epub 2021 Jul 7.

Université Paris Saclay, ENS Paris Saclay, CNRS LUMIN, 91190, Gif-sur-Yvette, France.

The development of livers-on-a-chip aims to provide pharmaceutical companies with reliable systems to perform drug screening and toxicological studies. To that end, microfluidic systems are engineered to mimic the functions and architecture of this organ. In this context we have designed a device that reproduces series of liver microarchitectures, each permitting the 3D culture of hepatocytes by confining them to a chamber that is separated from the medium conveying channel by very thin slits. We modified the structure to ensure its compatibility with the culture of hepatocytes from different sources. Our device was adapted to the migratory and adhesion properties of the human HepaRG cell line at various stages of differentiation. Using this device, it was possible to keep the cells alive for more than 14 days, during which they achieved a 3D organisation and acquired or maintained their differentiation into hepatocytes. Albumin secretion as well as functional bile canaliculi were confirmed on the liver-on-a-chip. Finally, an acetaminophen toxicological assay was performed. With its multiple micro-chambers for hepatocyte culture, this microfluidic device architecture offers a promising opportunity to provide new tools for drug screening applications.
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http://dx.doi.org/10.1038/s41598-021-92011-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8263583PMC
July 2021

COVID-19: Role of Nutrition and Supplementation.

Nutrients 2021 Mar 17;13(3). Epub 2021 Mar 17.

Department of Experimental Medicine, Section of Human Physiology and Unit of Dietetics and Sports Medicine, Università degli Studi della Campania "Luigi Vanvitelli", 80131 Naples, Italy.

At the end of 2019, a new coronavirus (COVID-19) appeared on the world scene, which mainly affects the respiratory system, causing pneumonia and multi-organ failure, and, although it starts with common symptoms such as shortness of breath and fever, in about 2-3% of cases it leads to death. Unfortunately, to date, no specific treatments have been found for the cure of this virus and, therefore, it is advisable to implement all possible strategies in order to prevent infection. In this context, it is important to better define the role of all behaviors, in particular nutrition, in order to establish whether these can both prevent infection and improve the outcome of the disease in patients with COVID-19. In the literature, it is widely shown that states of malnutrition, overweight, and obesity negatively affect the immune system, leading to viral infections, and several studies have shown that nutritional interventions can act as immunostimulators, helping to prevent viral infections. Even if several measures, such as the assumption of a specific diet regimen, the use of dietary supplements, and other similar interventions, are promising for the prevention, management, and recovery of COVID-19 patients, it is important to highlight that strong data from randomized clinical trials are needed to support any such assumption. Considering this particular scenario, we present a literature review addressing several important aspects related to diet and SARS-CoV-2 infection, in order to highlight the importance of diet and supplementation in prevention and management of, as well as recovery from COVID-19.
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http://dx.doi.org/10.3390/nu13030976DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8002713PMC
March 2021

Transcranial Magnetic Stimulation as a Tool to Investigate Motor Cortex Excitability in Sport.

Brain Sci 2021 Mar 28;11(4). Epub 2021 Mar 28.

Deparment of Clinical and Experimental Medicine, University of Foggia, 71122 Foggia, Italy.

Transcranial magnetic stimulation, since its introduction in 1985, has brought important innovations to the study of cortical excitability as it is a non-invasive method and, therefore, can be used both in healthy and sick subjects. Since the introduction of this cortical stimulation technique, it has been possible to deepen the neurophysiological aspects of motor activation and control. In this narrative review, we want to provide a brief overview regarding TMS as a tool to investigate changes in cortex excitability in athletes and highlight how this tool can be used to investigate the acute and chronic responses of the motor cortex in sport science. The parameters that could be used for the evaluation of cortical excitability and the relative relationship with motor coordination and muscle fatigue, will be also analyzed. Repetitive physical training is generally considered as a principal strategy for acquiring a motor skill, and this process can elicit cortical motor representational changes referred to as use-dependent plasticity. In training settings, physical practice combined with the observation of target movements can enhance cortical excitability and facilitate the process of learning. The data to date suggest that TMS is a valid technique to investigate the changes in motor cortex excitability in trained and untrained subjects. Recently, interest in the possible ergogenic effect of non-invasive brain stimulation in sport is growing and therefore in the future it could be useful to conduct new experiments to evaluate the impact on learning and motor performance of these techniques.
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http://dx.doi.org/10.3390/brainsci11040432DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8065474PMC
March 2021

Advanced Techniques and Awaited Clinical Applications for Human Pluripotent Stem Cell Differentiation into Hepatocytes.

Hepatology 2021 Aug 22;74(2):1101-1116. Epub 2021 Aug 22.

INSERM, Université Paris-Saclay, Unité Mixte de Recherche (UMR_S) 1193, Villejuif, France.

Liver transplantation is currently the only curative treatment for several liver diseases such as acute liver failure, end-stage liver disorders, primary liver cancers, and certain genetic conditions. Unfortunately, despite improvements to transplantation techniques, including live donor transplantation, the number of organs available remains insufficient to meet patient needs. Hepatocyte transplantation has enabled some encouraging results as an alternative to organ transplantation, but primary hepatocytes are little available and cannot be amplified using traditional two-dimensional culture systems. Indeed, although recent studies have tended to show that three-dimensional culture enables long-term hepatocyte culture, it is still agreed that, like most adult primary cell types, hepatocytes remain refractory to in vitro expansion. Because of their exceptional properties, human pluripotent stem cells (hPSCs) can be amplified indefinitely and differentiated into any cell type, including liver cells. While many teams have worked on hepatocyte differentiation, there has been a consensus that cells obtained after hPSC differentiation have more fetal than adult hepatocyte characteristics. New technologies have been used to improve the differentiation process in recent years. This review discusses the technical improvements made to hepatocyte differentiation protocols and the clinical approaches developed to date and anticipated in the near future.
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http://dx.doi.org/10.1002/hep.31705DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8457237PMC
August 2021

The Social Brain and Emotional Contagion: COVID-19 Effects.

Medicina (Kaunas) 2020 Nov 25;56(12). Epub 2020 Nov 25.

Department of Clinical and Experimental Medicine, University of Foggia, 71122 Foggia, Italy.

Background And Objectives: Coronavirus disease 2019 (COVID-19) is a highly contagious infectious disease, responsible for a global pandemic that began in January 2020. Human/COVID-19 interactions cause different outcomes ranging from minor health consequences to death. Since social interaction is the default mode by which individuals communicate with their surroundings, different modes of contagion can play a role in determining the long-term consequences for mental health and emotional well-being. We examined some basic aspects of human social interaction, emphasizing some particular features of the emotional contagion. Moreover, we analyzed the main report that described brain damage related to the COVID-19 infection. Indeed, the goal of this review is to suggest a possible explanation for the relationships among emotionally impaired people, brain damage, and COVID-19 infection.

Results: COVID-19 can cause several significant neurological disorders and the pandemic has been linked to a rise in people reporting mental health problems, such as depression and anxiety. Neurocognitive symptoms associated with COVID-19 include delirium, both acute and chronic attention and memory impairment related to hippocampal and cortical damage, as well as learning deficits in both adults and children.

Conclusions: Although our knowledge on the biology and long-term clinical outcomes of the COVID-19 infection is largely limited, approaching the pandemic based on lessons learnt from previous outbreaks of infectious diseases and the biology of other coronaviruses will provide a suitable pathway for developing public mental health strategies, which could be positively translated into therapeutic approaches, attempting to improve stress coping responses, thus contributing to alleviate the burden driven by the pandemic.
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http://dx.doi.org/10.3390/medicina56120640DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7760735PMC
November 2020

Neurodevelopmental Disorders: Effect of High-Fat Diet on Synaptic Plasticity and Mitochondrial Functions.

Brain Sci 2020 Oct 31;10(11). Epub 2020 Oct 31.

Department of Biology, University of Naples Federico II, 80126 Naples, Italy.

Neurodevelopmental disorders (NDDs) include diverse neuropathologies characterized by abnormal brain development leading to impaired cognition, communication and social skills. A common feature of NDDs is defective synaptic plasticity, but the underlying molecular mechanisms are only partially known. Several studies have indicated that people's lifestyles such as diet pattern and physical exercise have significant influence on synaptic plasticity of the brain. Indeed, it has been reported that a high-fat diet (HFD, with 30-50% fat content), which leads to systemic low-grade inflammation, has also a detrimental effect on synaptic efficiency. Interestingly, metabolic alterations associated with obesity in pregnant woman may represent a risk factor for NDDs in the offspring. In this review, we have discussed the potential molecular mechanisms linking the HFD-induced metabolic dysfunctions to altered synaptic plasticity underlying NDDs, with a special emphasis on the roles played by synaptic protein synthesis and mitochondrial functions.
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http://dx.doi.org/10.3390/brainsci10110805DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7694125PMC
October 2020

The Metabolic Rearrangements of Bariatric Surgery: Focus on Orexin-A and the Adiponectin System.

J Clin Med 2020 Oct 16;9(10). Epub 2020 Oct 16.

Department of Clinical and Experimental Medicine, University of Foggia, 71100 Foggia, Italy.

The accumulation of adipose tissue represents one of the characteristics of obesity, increasing the risk of developing correlated obesity diseases such as cardiovascular disease, type 2 diabetes, cancer, and immune diseases. Visceral adipose tissue accumulation leads to chronic low inflammation inducing an imbalanced adipokine secretion. Among these adipokines, Adiponectin is an important metabolic and inflammatory mediator. It is also known that adipose tissue is influenced by Orexin-A levels, a neuropeptide produced in the lateral hypothalamus. Adiponectin and Orexin-A are strongly decreased in obesity and are associated with metabolic and inflammatory pathways. The aim of this review was to investigate the involvement of the autonomic nervous system focusing on Adiponectin and Orexin-A after bariatric surgery. After bariatric surgery, Adiponectin and Orexin-A levels are strongly increased independently of weight loss showing that hormone increases are also attributable to a rearrangement of metabolic and inflammatory mediators. The restriction of food intake and malabsorption are not sufficient to clarify the clinical effects of bariatric surgery suggesting the involvement of neuro-hormonal feedback loops and also of mediators such as Adiponectin and Orexin-A.
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http://dx.doi.org/10.3390/jcm9103327DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7602946PMC
October 2020

The endothelium, a key actor in organ development and hPSC-derived organoid vascularization.

J Biomed Sci 2020 May 22;27(1):67. Epub 2020 May 22.

INSERM UMRS-MD 1197, Université Paris Sud-Université Paris-Saclay. Hôpital Paul Brousse, Villejuif, France.

Over the last 4 decades, cell culture techniques have evolved towards the creation of in vitro multicellular entities that incorporate the three-dimensional complexity of in vivo tissues and organs. As a result, stem cells and adult progenitor cells have been used to derive self-organized 3D cell aggregates that mimic the morphological and functional traits of organs in vitro. These so-called organoids were first generated from primary animal and human tissues, then human pluripotent stem cells (hPSCs) arose as a new tool for organoid generation. Due to their self-renewal capacity and differentiation potential, hPSCs are an unlimited source of cells used for organoids. Today, hPSC-derived small intestinal, kidney, brain, liver, and pancreas organoids, among others, have been produced and are promising in vitro human models for diverse applications, including fundamental research, drug development and regenerative medicine. However, achieving in vivo-like organ complexity and maturation in vitro remains a challenge. Current hPSC-derived organoids are often limited in size and developmental state, resembling embryonic or fetal organs rather than adult organs. The use of endothelial cells to vascularize hPSC-derived organoids may represent a key to ensuring oxygen and nutrient distribution in large organoids, thus contributing to the maturation of adult-like organoids through paracrine signaling.Here, we review the current state of the art regarding vascularized hPSC-derived organoids (vhPSC-Orgs). We analyze the progress achieved in the generation of organoids derived from the three primary germ layers (endoderm, mesoderm and ectoderm) exemplified by the pancreas, liver, kidneys and brain. Special attention will be given to the role of the endothelium in the organogenesis of the aforementioned organs, the sources of endothelial cells employed in vhPSC-Org protocols and the remaining challenges preventing the creation of ex vivo functional and vascularized organs.
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http://dx.doi.org/10.1186/s12929-020-00661-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7245026PMC
May 2020

The Important Role of Adiponectin and Orexin-A, Two Key Proteins Improving Healthy Status: Focus on Physical Activity.

Front Physiol 2020 22;11:356. Epub 2020 Apr 22.

Department of Clinical and Experimental Medicine, University of Foggia, Foggia, Italy.

Exercise represents the most important integrative therapy in metabolic, immunologic and chronic diseases; it represents a valid strategy in the non-pharmacological intervention of lifestyle linked diseases. A large body of evidence indicates physical exercise as an effective measure against chronic non-communicable diseases. The worldwide general evidence for health benefits are both for all ages and skill levels. In a dysregulated lifestyle such as in the obesity, there is an imbalance in the production of different cytokines. In particular, we focused on Adiponectin, an adipokine producted by adipose tissue, and on Orexin-A, a neuropeptide synthesized in the lateral hypothalamus. The production of both Adiponectin and Orexin-A increases following regular and structured physical activity and both these hormones have similar actions. Indeed, they improve energy and glucose metabolism, and also modulate energy expenditure and thermogenesis. In addition, a relevant biological role of Adiponectin and Orexin A has been recently highlighted in the immune system, where they function as immune-suppressor factors. The strong connection between these two cytokines and healthy status is mediated by physical activity and candidates these hormones as potential biomarkers of the beneficial effects induced by physical activity. For these reasons, this review aims to underly the interconnections among Adiponectin, Orexin-A, physical activity and healthy status. Furthermore, it is analyzed the involvement of Adiponectin and Orexin-A in physical activity as physiological factors improving healthy status through physical exercise.
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http://dx.doi.org/10.3389/fphys.2020.00356DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7188914PMC
April 2020

Functional Role of Dietary Intervention to Improve the Outcome of COVID-19: A Hypothesis of Work.

Int J Mol Sci 2020 Apr 28;21(9). Epub 2020 Apr 28.

Department of Clinical and Experimental Medicine, University of Foggia, 71122 Foggia, Italy.

Background: On the 31 December 2019, the World Health Organization (WHO) was informed of a cluster of cases of pneumonia of unknown origin detected in Wuhan City, Hubei Province, China. The infection spread first in China and then in the rest of the world, and on the 11th of March, the WHO declared that COVID-19 was a pandemic. Taking into consideration the mortality rate of COVID-19, about 5-7%, and the percentage of positive patients admitted to intensive care units being 9-11%, it should be mandatory to consider and take all necessary measures to contain the COVID-19 infection. Moreover, given the recent evidence in different hospitals suggesting IL-6 and TNF-α inhibitor drugs as a possible therapy for COVID-19, we aimed to highlight that a dietary intervention could be useful to prevent the infection and/or to ameliorate the outcomes during therapy. Considering that the COVID-19 infection can generate a mild or highly acute respiratory syndrome with a consequent release of pro-inflammatory cytokines, including IL-6 and TNF-α, a dietary regimen modification in order to improve the levels of adiponectin could be very useful both to prevent the infection and to take care of patients, improving their outcomes.
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http://dx.doi.org/10.3390/ijms21093104DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7247152PMC
April 2020

Neuropeptides' Hypothalamic Regulation of Sleep Control in Children Affected by Functional Non-Retentive Fecal Incontinence.

Brain Sci 2020 Feb 25;10(3). Epub 2020 Feb 25.

Department of Psychology, Educational and Science and Human Movement, University of Palermo, 90133 Palermo PA, Italy.

Functional non-retentive fecal incontinence (FNRFI) is a common problem in pediatric age. FNRFI is defined as unintended loss of stool in a 4-year-old or older child after organic causes have been excluded. FNRFI tends to affects up to 3% of children older than 4 years, with males being affected more frequently than females. Clinically, children affected by FNRFI have normal intestinal movements and stool consistency. Literature data show that children with fecal incontinence have increased levels of separation anxiety, specific phobias, general anxiety, attention-deficit/hyperactivity disorder (ADHD), and oppositional defiant disorder. In terms of possible relationship between incontinence and sleep, disorders of sleep organization have been observed in the pathogenesis of enuresis so generating the hypothesis that the orexinergic system may have a crucial role not only for the sleep organization but also for the sphincterial control in general. This study aimed to focus on specific neurophysiological aspects to investigate on the possible relationship between sleep organizational abnormalities and FNRFI. Specifically, we aimed to measure orexin serum levels in children with FNRFI and assess their polysomnographic sleep macrostructure patterns. Two study groups were considered: FNFRI ( = 45) and typically developed (TD) ( = 45) group. In both groups, sleep patterns and respiratory events were assessed by polysomnographic recordings (PSG) during a period of two nights at least, and plasma levels of Orexin-A were measured in each participant. The findings of this initial investigation seem to support a major role of Orexin-A in sleep organization alterations in children with FNFRI. Also, our data suggest that sleep habits evaluation should be considered as screening and complementary tool for the diagnosis of fecal incontinence in children.
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http://dx.doi.org/10.3390/brainsci10030129DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7139357PMC
February 2020

Pluripotent-Stem-Cell-Derived Hepatic Cells: Hepatocytes and Organoids for Liver Therapy and Regeneration.

Cells 2020 02 12;9(2). Epub 2020 Feb 12.

INSERM unité mixte de recherche (UMR_S) 1193, F-94800 Villejuif, France.

The liver is a very complex organ that ensures numerous functions; it is thus susceptible to multiple types of damage and dysfunction. Since 1983, orthotopic liver transplantation (OLT) has been considered the only medical solution available to patients when most of their liver function is lost. Unfortunately, the number of patients waiting for OLT is worryingly increasing, and extracorporeal liver support devices are not yet able to counteract the problem. In this review, the current and expected methodologies in liver regeneration are briefly analyzed. In particular, human pluripotent stem cells (hPSCs) as a source of hepatic cells for liver therapy and regeneration are discussed. Principles of hPSC differentiation into hepatocytes are explored, along with the current limitations that have led to the development of 3D culture systems and organoid production. Expected applications of these organoids are discussed with particular attention paid to bio artificial liver (BAL) devices and liver bio-fabrication.
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http://dx.doi.org/10.3390/cells9020420DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7072243PMC
February 2020

What Does Personality Mean in the Context of Mental Health? A Topic Modeling Approach Based on Abstracts Published in Pubmed Over the Last 5 Years.

Front Psychiatry 2019 9;10:938. Epub 2020 Jan 9.

7 Department of Neurosciences and Reproductive and Odontostomatological Sciences, University of Naples Federico II, Naples, Italy.

Personality disorders (PDs) are one of the major problems for the organization of public health systems. Deepening the link between personality traits and psychopathological drifts, it seems increasingly essential for the often dramatic repercussions that PDs have on social contexts. Some of these disorders, such as borderline PD, antisocial PD, in their most tragic expression, are the basis of problems related to crime, sexual violence, abuse, and mistreatment of minors. Many authors propose a dimensional classification of personality pathology, which has received empirical support from numerous studies over the last 20 years based on more robust theoretical principles than those applied to current nosography. The present study investigates the nature of the research carried out in the last years on the personality in the clinical field exploring the contents of current research on personality relapses, evaluating, on the one hand, the emerging areas of greatest interest and others, those that they stopped generating sufficient motivations in scholars. This study evaluates text patterns regarding how the terms "personality" and "mental health" are used in titles and abstracts published in PubMed in the last 5 years. We use a topic analysis: Latent Dirichlet Allocation that expresses every report as a probabilistic distribution of latent topics that are represented as a probabilistic distribution of words. A total of 7,572 abstracts (from 2012 to 2017) were retrieved from PubMed for the query on "mental health" and "personality." The study found 30 topics organized in eight hierarchical clusters that describe the type of current research carried out on personality and its clinical relapse. The hierarchical clusters latent themes were the following: social dimensions, clinical aspects, biological issues, clinical history of PD, internalization and externalization symptoms, impulsive behaviors, comorbidities, criminal behaviors. The results indicate that the concept of personality is associated with a wide range of conditions. The study of personality and mental health still proceeds, mainly, according to a practical-clinical approach; too little moves, however, according to an innovative research approach, but the work shows the common commitment of scholars to a new way of dealing with the study of personality.
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http://dx.doi.org/10.3389/fpsyt.2019.00938DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6962292PMC
January 2020

HepaRG Self-Assembled Spheroids in Alginate Beads Meet the Clinical Needs for Bioartificial Liver.

Tissue Eng Part A 2020 06 12;26(11-12):613-622. Epub 2020 Feb 12.

UMR CNRS 7338 Biomechanics & Bioengineering, Université de Technologie de Compiègne, Alliance Sorbonne Université, Compiègne, France.

In liver tissue engineering, cell culture in spheroids is now well recognized to promote the maintenance of hepatic functions. However, the process leading to spheroids formation is time consuming, costly, and not easy to scale-up for further use in human bioartificial liver (BAL) applications. In this study, we encapsulated HepaRG cells (precursors of hepatocyte-like cells) in 1.5% alginate beads without preforming spheroids. Starting from a given hepatic biomass, we analyzed cell differentiation and metabolic performance for further use in a fluidized-bed BAL. We observed that cells self-rearranged as aggregates within the beads and adequately differentiated over time, in the absence of any differentiating factors classically used. On day 14 postencapsulation, cells displayed a wide range of hepatic features necessary for the treatment of a patient in acute liver failure. These activities include albumin synthesis, ammonia and lactate detoxification, and the efficacy of the enzymes involved in the xenobiotic metabolism (such as CYP1A1/2). Impact statement It has been recognized that culturing cells in spheroids (SPHs) is advantageous as they better reproduce the three-dimensional physiological microenvironment. This approach can be exploited in bioartificial liver applications, where obtaining a functional hepatic biomass is the major challenge. Our study describes an original method for culturing hepatic cells in alginate beads that makes possible the autonomous formation of SPHs after 3 days of culture. In turn, the cells differentiate adequately and display a wide range of hepatic features. They are also capable of treating a pathological plasma model. Finally, this setup can easily be scaled-up to treat acute liver failure.
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http://dx.doi.org/10.1089/ten.TEA.2019.0262DOI Listing
June 2020

Telmisartan cardioprotects from the ischaemic/hypoxic damage through a miR-1-dependent pathway.

J Cell Mol Med 2019 10 1;23(10):6635-6645. Epub 2019 Aug 1.

Multidisciplinary Department of Surgical and Dental Specialties, University of Campania 'Luigi Vanvitelli', Naples, Italy.

The aim of this study was to investigate whether telmisartan protects the heart from the ischaemia/reperfusion damage through a local microRNA-1 modulation. Studies on the myocardial ischaemia/reperfusion injury in vivo and on the cardiomyocyte hypoxia/reoxygenation damage in vitro were done. In vivo, male Sprague-Dawley rats administered for 3 weeks with telmisartan 12 mg/kg/d by gastric gavage underwent ischaemia/reperfusion of the left descending coronary artery. In these rats, infarct size measurement, ELISA, immunohistochemistry (IHC) and reverse transcriptase real-time polymerase chain reaction showed that expressions of connexin 43, potassium voltage-gated channel subfamily Q member 1 and the protein Bcl-2 were significantly increased by telmisartan in the reperfused myocardium, paralleled by microRNA-1 down-regulation. In vitro, the transfection of cardiomyocytes with microRNA-1 reduced the expressions of connexin 43, potassium voltage-gated channel subfamily Q member 1 and Bcl-2 in the cells. Telmisartan (50 µmol/L) 60 minutes before hypoxia/reoxygenation, while not affecting the levels of miR-1 in transfected cells in normoxic condition, almost abolished the increment of miR-1 induced by the hypoxia/reoxygenation to transfected cells. All together, telmisartan cardioprotected against the myocardial damage through the microRNA-1 modulation, and consequent modifications of its downstream target connexin 43, potassium voltage-gated channel subfamily Q member 1 and Bcl-2.
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http://dx.doi.org/10.1111/jcmm.14534DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6787508PMC
October 2019

Attentional bias in the radial and vertical dimensions of space.

C R Biol 2019 Mar - May;342(3-4):97-100. Epub 2019 Apr 27.

Dipartimento di Medicina Sperimentale, Università degli Studi della Campania "Luigi Vanvitelli", 80128 Napoli, Italy.

Under visual guidance, healthy subjects usually misbisect radial lines farther than, and vertical lines above the true center. It was suggested that radial and vertical misbisection depended on the presence of an attentional bias toward far/upper space. The aim of the present study was to investigate whether such attentional bias depends on a single mechanism or on separate mechanisms. Ninety participants were asked to bisect lines radially and vertically oriented. The results confirmed the presence of a consistent bisection bias farther than (radial lines), and above (vertical lines) the true center. Furthermore, there was a significant correlation between radial and vertical bisection errors. These findings suggest that a single neural mechanism is involved in producing the attentional bias toward far/upper space.
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http://dx.doi.org/10.1016/j.crvi.2019.03.003DOI Listing
July 2019

Hemispheric Asymmetries in Radial Line Bisection: Role of Retinotopic and Spatiotopic Factors.

Front Psychol 2018 12;9:2200. Epub 2018 Nov 12.

Department of Experimental Medicine, Section of Human Physiology and Unit of Dietetics and Sports Medicine, Università degli Studi della Campania Luigi Vanvitelli, Naples, Italy.

Previous studies showed that healthy individuals bisect radial lines oriented along the midsagittal plane farther than the true center (distal bisection bias). It was proposed that the distal bisection bias depended on the presence of an attention bias directed toward far space (distal attention bias) and that this bias is related to the activity of the occipitotemporal visual processing stream. Other studies have also suggested that a similar distal attention bias is linked to the activity of the right hemisphere. In the present experiment we investigated whether distal bisection bias increased when radial lines were placed in the left hemispace. Furthermore, we also examined whether the bisection bias was enhanced by the use of the left hand, as left hand movements are mainly controlled by the right hemisphere. Right-handed participants were asked to bisect radial lines presented below eye level along the midsagittal plane (central lines), or laterally and parallel to the midsagittal plane, in the left or right hemispace (left and right lines, respectively). Participants used their right or left hand. The results showed that participants consistently bisected left and central radial lines farther than (i) the true center and (ii) the subjective midpoint of right radial lines. Conversely, they bisected accurately right radial lines. The hand did not influence bisection error. The present study suggests that the distal bisection bias found in the bisection of left radial lines might depend on the presence of a distal attention bias related to right hemisphere activity. The relative contribution of retinotopic and spatiotopic factors in producing the distal bisection bias is discussed.
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http://dx.doi.org/10.3389/fpsyg.2018.02200DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6240617PMC
November 2018

Modafinil and orexin system: interactions and medico-legal considerations.

Front Biosci (Landmark Ed) 2019 01 1;24:564-575. Epub 2019 Jan 1.

Clinic of Child and Adolescent Neuropsychiatry, Department of Mental Health, Physical and Preventive Medicine, Università degli Studi della Campania,Luigi Vanvitelli, Naples, Italy.

Modafinil (Mo) is increasingly being used as an enhancement drug rather than for its therapeutic effects. The effects of this drug have been examined in attention deficit disorders, depression, mental fatigue, and in enhancing concentration. The drug possesses wakefulness-promoting properties which are mediated through the interaction of orexinergic system with the activated sympathetic nervous system. Mo exerts a synergistic effect on the orexin system, controls energy expenditure and strengthens the ability of the individual to exercise. Some view Mo as a drug that enhances sports performance, since it induces a prolonged wakefulness and decreasing the sense of fatigue. These characteristics being similar to conventional stimulants have allowed Mo to emerge as a novel stimulant requiring medico-legal considerations. However, more studies are needed to better understand the mid and long-term effects of the drug on user/abuser.
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http://dx.doi.org/10.2741/4736DOI Listing
January 2019

Autoalgometry: An Important Tool for Pressure Pain Threshold Evaluation.

J Clin Med 2018 Sep 12;7(9). Epub 2018 Sep 12.

Department of Medicine, Surgery and Dentistry "Scuola Medica Salernitana", University of Salerno, 84081 Baronissi, Italy.

The term "pain threshold" refers to the measurement of the intensity of a physical stimulus that evokes pain. To estimate the pain threshold, a mechanical or electrical stimulus with increasing intensity is usually applied until the subject under evaluation refers to a pain sensation. This study aims to evaluate the autoalgometric pain threshold as a perfect technique to determine the effects of stimulation rate in relation to both gender and the site of stimulation. In this experimental model, pressure algometry was applied: the subject under evaluation pushed a finger against a small round metal tip, producing and at the same time controlling the intensity of the noxious stimulus. Through autoalgometry, the stimulus intensity was recorded over time, measuring the force change rate applied and studying the subject's behavior on approaching pain. This test was performed with 50 healthy volunteers on two days, applying a fast or slow rate of stimulation. The results described demonstrate that there is a positive correlation between the pressure increase rate and the pressure threshold evaluation. In light of these findings, autoalgometry can be proposed as an objective measure of pressure pain threshold for clinical and research use.
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http://dx.doi.org/10.3390/jcm7090273DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6162811PMC
September 2018

Adiponectin and Orexin-A as a Potential Immunity Link Between Adipose Tissue and Central Nervous System.

Front Physiol 2018 24;9:982. Epub 2018 Jul 24.

Department of Clinical and Experimental Medicine, University of Foggia, Foggia, Italy.

Adipose tissue (AT) is strongly associated with development and progression of immune disorders through adipokines secretion, such as adiponectin. This protein has beneficial energetic properties and is involved in inflammation and immunity processes. Three oligomers of circulating adiponectin with different molecular weight are described: High (HMW), Medium (MMW), and Low (LMW). The HMW is the most biologically active oligomers. On binding to its receptors AdipoR1, AdipoR2, and T-cadherin, adiponectin acts on both innate and acquired immunity. The suppression of NF-κB activation and pro-inflammatory cytokine expression in macrophages is mediated by AdipoR1. AdipoR2 mediates polarization of anti-inflammatory M2 macrophages T-cadherin is essential for the M2 macrophage proliferation. Furthermore, adiponectin reduces T cells responsiveness and B cells lymphopoiesis. The immune system is very sensitive to environmental changes and it is not only interconnected with AT but also with the central nervous system (CNS). Cytokines, which are mediators of the immune system, exercise control over mediators of the CNS. Microglia, which are immunity cells belonging to the macrophage family, are present within the CNS. The nervous system is also involved in immunity through the production of neuropeptides such as orexin-A/hypocretin-1. This neuropeptide is involved in metabolic disorders, inflammation and in the immune response. The relationship between adipokines, immunity, and the nervous system is validated by both the role of orexin-A on fat, food intake, and energy expenditure, as well as by role of adiponectin on the CNS. In this review, we focused on the functions of adiponectin and orexin-A as a potential immunity link between AT and CNS.
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http://dx.doi.org/10.3389/fphys.2018.00982DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6094989PMC
July 2018

Long Feeding High-Fat Diet Induces Hypothalamic Oxidative Stress and Inflammation, and Prolonged Hypothalamic AMPK Activation in Rat Animal Model.

Front Physiol 2018 6;9:818. Epub 2018 Jul 6.

Department of Biology, University of Naples Federico II, Naples, Italy.

The hypothalamus is a key brain region involved in the control of feeding and energy expenditure. Hypothalamic inflammation and oxidative stress are landmarks of both obesity and aging processes, although the molecular mechanisms are still unknown. Therefore, with the aim to understand the neurobiological mechanisms of energy homeostasis during aging, we evaluate the effects of long feeding high-fat diet (HFD) in rats, at different age, on modulation of hypothalamic molecular pathway, oxidative stress, and inflammation. Male Wistar rats were divided into two groups: control group, receiving standard diet (CD), and treated group, receiving HFD. Both groups were treated with the appropriate diet for 1, 3, 6, 12, or 18 weeks. We investigated energy balance and body composition, as well as lipid profile, homeostatic model assessment index, and inflammatory state in serum. Furthermore, we also analyzed, at hypothalamic level, inflammation and oxidative stress, and adenosine monophosphate-dependent kinase (AMPK) and pAMPK expression levels. Our data showed that aging and HFD induce increased energy intake and energy efficiency and decreased energy expenditure associated, at hypothalamic level, with inflammation and oxidative stress and activation of AMPK. Our results indicate that the age at which HFD feeding starts and the diet duration are critical in obesity development. The prolonged activation of hypothalamic AMPK may be related to the alterations in energy homeostasis.
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http://dx.doi.org/10.3389/fphys.2018.00818DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6043859PMC
July 2018

Stress Profile in Remotely Piloted Aircraft Crewmembers During 2 h Operating Mission.

Front Physiol 2018 7;9:461. Epub 2018 May 7.

Department of Clinical and Experimental Medicine, University of Foggia, Foggia, Italy.

Emotional stability plays a key role in individual and team performance during both routine activities and management of unexpected emergencies. Using a psycho-physiological approach, the stress response was investigated in drone operators in service. Salivary α-amylase (sAA), galvanic skin response (GSR) and anxiety were assessed over a 2-h operating flight. Compared to baseline values, GSR and sAA values increased in operating conditions. Moreover, these values were higher in Pilots than in Sensor Operators, indicating that their stress response was greater. These results were associated with an increase in anxiety level, highlighting a relationship between autonomic reactivity and anxiety. This is the first report providing experimental evidences of the stress response related to Remotely Piloted Aircraft operations.
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http://dx.doi.org/10.3389/fphys.2018.00461DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5949534PMC
May 2018

Anabolic androgenic steroids and carcinogenicity focusing on Leydig cell: a literature review.

Oncotarget 2018 Apr 10;9(27):19415-19426. Epub 2018 Apr 10.

University of Catania, Department of Medical, Surgical and Advanced Technologies, "G.F. Ingrassia", Catania, Italy.

Anabolic androgenic steroids (AAS) are some of the most common drugs used among athletes, frequently in combination with resistance training, to improve physical performance or for aesthetic purpose. A great number of scientific reports showed the detrimental effects of anabolic androgenic steroids on different organs and tissues. In this literature review, we analyzed the AAS-mediated carcinogenicity, focusing on Leydig cell tumor. AAS-induced carcinogenicity can affect DNA transcription through two pathways. It can act directly via the androgen receptor, by means of dihydrotestosterone (DHT) produced by the action of 5-a-reductase. It can also work through the estrogen receptor, by means of estradiol produced by CYP19 aromatase. In addition, nandrolone and stanazolol can activate the PI3K/AKT and PLC/PKC pathways via . This would result in cell proliferation in Leydig cell cancer, or magnify cyclin D1 concentration inducing breast cell proliferation. AAS abuse is becoming a serious public health concern in view of the severe health consequences secondary to AAS abuse. The negative role of AAS in supraphysiological dosage impairs the expression of enzymes involved in testosterone biosynthesis. Abnormal synthesis of testosterone plays has a negative effect on the hormonal changes/regulation, and might be involved in certain carcinogenic mechanisms. At the light of this review, it could become very interesting to perform an information campaign more strengthened in gyms and schools in order to prevent male fertility impairment and other tissues damage.
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http://dx.doi.org/10.18632/oncotarget.24767DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5922407PMC
April 2018

Inhibition of aldose-reductase-2 by a benzofuroxane derivative bf-5m increases the expression of kcne1, kcnq1 in high glucose cultured H9c2 cardiac cells and sudden cardiac death.

Oncotarget 2018 Apr 14;9(25):17257-17269. Epub 2017 Dec 14.

Department of Experimental Medicine, Division of Pharmacology, University of Campania L. Vanvitelli, Naples, Italy.

Long QT syndrome (LQTS) is characterized by prolonged QT interval, leading to sudden cardiac death. Hyperglycemia is an important risk factor for LQTS, inhibiting the cardiac rapid component delayed rectifier K+ current (Iks), responsible for QT interval. We previously showed that the new ALR2 inhibitor BF-5m supplies cardioprotection from QT prolongation induced by high glucose concentration in the medium, reducing QT interval prolongation and preserving morphology. Here we investigated the effects of BF-5m on cell cytotoxicity and viability in H9c2 cells, and on cellular potassium ion channels expression. H9c2 cells were grown in medium with high glucose and high glucose plus the BF-5m by assessing the cytotoxic effects and the cell survival rate. In addition, KCNE1 and KCNQ1 expression in plasma and mitochondrial membranes were monitored. Also, the expression levels of miR-1 proved to suppress KCNQ1 and KCNE1, were analyzed. BF-5m treatment reduced the cytotoxic effects of high glucose on H9c2 cells by increasing cell survival rate and improving H9c2 morphology. Plasmatic KCNE1 and KCNQ1 expression levels were restored by BF-5m in H9c2 exposed to high glucose, down-regulating miR-1. These results suggest that BF-5m exerts cardioprotection from high glucose in rat heart ventricle H9c2 cells exposed to high glucose.
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http://dx.doi.org/10.18632/oncotarget.23270DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5915114PMC
April 2018

Sympathetic, Metabolic Adaptations, and Oxidative Stress in Autism Spectrum Disorders: How Far From Physiology?

Front Physiol 2018 22;9:261. Epub 2018 Mar 22.

Clinic of Child and Adolescent Neuropsychiatry, Department of Mental Health, Physical and Preventive Medicine, Università degli Studi della Campania "Luigi Vanvitelli", Naples, Italy.

Autism spectrum disorders (ASD) is a complex and multifaceted neurobehavioral syndrome with no specific cause still identified, despite the worldwide increasing (prevalence for 1,000 children from 6.7 to 14.6, between 2000 and 2012). Many biological and instrumental markers have been suggested as potential predictive factors for the precocious diagnosis during infancy and/or pediatric age. Many studies reported structural and functional abnormalities in the autonomic system in subjects with ASD. Sleep problems in ASD are a prominent feature, having an impact on the social interaction of the patient. Considering the role of orexins (A and B) in wake-sleep circadian rhythm, we could speculate that ASD subjects may present a dysregulation in orexinergic neurotransmission. Conversely, oxidative stress is implicated in the pathophysiology of many neurological disorders. Nonetheless, little is known about the linkage between oxidative stress and the occurrence or the progress of autism and autonomic functioning; some markers, such as heart rate (HR), heart rate variability (HRV), body temperature, and galvanic skin response (GSR), may be altered in the patient with this so complex disorder. In the present paper, we analyzed an autism case report, focusing on the rule of the sympathetic activity with the aim to suggest that it may be considered an important tool in ASD evaluation. The results of this case confirm our hypothesis even if further studies needed.
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http://dx.doi.org/10.3389/fphys.2018.00261DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5874307PMC
March 2018
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