Alessandra D’Alessandro - Academia.edu (original) (raw)

Papers by Alessandra D’Alessandro

PLOS ONE, 2016

Background and Aim Angiogenesis is emerging as a pivotal process in chronic inflammatory patholog... more Background and Aim Angiogenesis is emerging as a pivotal process in chronic inflammatory pathologies, promoting immune infiltration and prompting carcinogenesis. Ulcerative Colitis (UC) and Crohn's Disease (CD) represent paradigmatic examples of intestinal chronic inflammatory conditions in which the process of neovascularization correlates with the severity and progression of the diseases. Molecules able to target the angiogenesis have thus the potential to synergistically affect the disease course. Beyond its anti-inflammatory effect, palmitoylethanolamide (PEA) is able to reduce angiogenesis in several chronic inflammatory conditions, but no data about its anti-angiogenic activity in colitis have been produced, yet. Methods The effects of PEA on inflammation-associated angiogenesis in mice with dextran sulphate sodium (DSS)-induced colitis and in patients with UC were assessed. The release of Vascular Endothelial Growth Factor (VEGF), the hemoglobin tissue content, the expression of CD31 and of phosphatidylinositol 3-kinase/Akt/mammalian-target-of-rapamycin (mTOR) signaling axis were all evaluated in the presence of different concentrations of PEA and concomitant administration of PPAR-α and-γ antagonists.

International journal of immunopathology and pharmacology, 2015

In addition to the well-known involvement of macrophages and neutrophils, other cell types have b... more In addition to the well-known involvement of macrophages and neutrophils, other cell types have been recently reported to substantially contribute to the onset and progression of inflammatory bowel diseases (IBD). Enteric glial cells (EGC) are the equivalent cell type of astrocyte in the central nervous system (CNS) and share with them many neurotrophic and neuro-immunomodulatory properties. This short review highlights the role of EGC in IBD, describing the role played by these cells in the maintenance of gut homeostasis, and their modulation of enteric neuronal activities. In pathological conditions, EGC have been reported to trigger and support bowel inflammation through the specific over-secretion of S100B protein, a pivotal neurotrophic factor able to induce chronic inflammatory changes in gut mucosa. New pharmacological tools that may improve the current therapeutic strategies for inflammatory bowel diseases (IBD), lowering side effects (i.e. corticosteroids) and costs (i.e. a...

Gut, 2013

Objective Enteric glial cells (EGC) have been suggested to participate in host-bacteria cross-tal... more Objective Enteric glial cells (EGC) have been suggested to participate in host-bacteria cross-talk, playing a protective role within the gut. The way EGC interact with microorganisms is still poorly understood. We aimed to evaluate whether: EGC participate in hostbacteria interaction; S100B and Toll-like receptor (TLR) signalling converge in a common pathway leading to nitric oxide (NO) production. Design Primary cultures of human EGC were exposed to pathogenic (enteroinvasive Escherichia coli; EIEC) and probiotic (Lactobacillus paracasei F19) bacteria. Cell activation was assessed by evaluating the expression of cFos and major histocompatibility complex (MHC) class II molecules. TLR expression in EGC was evaluated at both baseline and after exposure to bacteria by real-time PCR, fluorescence microscopy and western blot analysis. S100B expression and NO release from EGC, following exposure to bacteria, were measured in the presence or absence of specific TLR and S100B pathway inhibitors. Results EIEC activated EGC by inducing the expression of cFos and MHC II. EGC expressed TLR at baseline. Pathogens and probiotics differentially modulated TLR expression in EGC. Pathogens, but not probiotics, significantly induced S100B protein overexpression and NO release from EGC. Pretreatment with specific inhibitors of TLR and S100B pathways abolished bacterial-induced NO release from EGC. Conclusions Human EGC interact with bacteria and discriminate between pathogens and probiotics via a different TLR expression and NO production. In EGC, NO release is impaired in the presence of specific inhibitors of the TLR and S100B pathways, suggesting the presence of a novel common pathway involving both TLR stimulation and S100B protein upregulation.

Surgery for Obesity and Related Diseases

Operative Techniques and Recent Advances in Acute Care and Emergency Surgery, 2019

In this chapter, we aim to highlight some of the new developments and trends in the emergency tre... more In this chapter, we aim to highlight some of the new developments and trends in the emergency treatment of the gastrointestinal emergencies. There are only four pathologic processes that occur as an emergency of the inflammatory conditions and obstruction of the gastrointestinal tract: hemorrhage, ischemia, obstruction, and infection. Most abdominal pathology involves one or a combination of these processes and may give rise to severe clinical conditions of sufficient gravity to constitute an emergency. Gastrointestinal emergencies due to an acute inflammatory diseases and acute obstruction of the abdominal viscera and their complications may be roughly classified as follows: peritonitis, intussusception, torsion, perforation with abscess formation, complications involving chronic lesions of the upper part of the digestive tract such as acute perforation of peptic ulcer, duodenal obstruction, and bleeding. Despite the new and ever-expanding array of medications for the treatment of ...

Revisiting Barrett's Esophagus

Epidemiological data indicate that Barrett’s esophagus (BE) and esophageal adenocarcinoma (EAC) h... more Epidemiological data indicate that Barrett’s esophagus (BE) and esophageal adenocarcinoma (EAC) have been increasing in incidence, particularly in developed and westernized countries. Although the pathogenesis of BE is poorly understood, evidence exists that the increasing incidence is not solely due to changes in diagnostic practice, but can most likely be attributed to temporal changes in exposure to lifestyle-related and disease-associated risk factors. This chapter will discuss risk factors for BE and will summarize possible preventive measures for development and degeneration of BE.

Gastrointestinal and Pancreatico-Biliary Diseases: Advanced Diagnostic and Therapeutic Endoscopy

Emergency Surgery in Obese Patients

Bleeding after bariatric surgery may occur during the operation or immediately after as a consequ... more Bleeding after bariatric surgery may occur during the operation or immediately after as a consequence of vascular or parenchymal injury related to laparoscopy or of failure after hemostasis at the suture line or anastomosis. Although the occurrence of bleeding is rare, it represents a true emergency and needs immediate diagnostic and therapeutic measures. Bleeding into the gastrointestinal tract causing hematemesis and/or melena is better assessed by endoscopy, whereas intraperitoneal bleeding is diagnosed by computed tomography. The first goal of treatment is to make the patient stable, whereas removal of the cause of bleeding is performed by endoscopic or radiological procedures after the diagnostic phase. When the patient remains unstable, treatment must be promptly established. Remedial surgery is the last resource of treatment. Delayed bleeding is related to peptic ulcer development and usually resolves with pharmacological and endoscopic treatment.

Cellular and Molecular Gastroenterology and Hepatology

Acta Chirurgica Belgica

Roberto Peltrini, Paola Antonella Greco, Riccardo Aurelio Nasto, Alessandra D’Alessandro, Alessan... more Roberto Peltrini, Paola Antonella Greco, Riccardo Aurelio Nasto, Alessandra D’Alessandro, Alessandro Iacobelli, Luigi Insabato and Luigi Bucci Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy; Gastroenterology and Digestive Endoscopy Unit, Pineta Grande Hospital, Caserta, Italy; Anatomic Pathology Unit, Department of Advanced Biomedical Sciences, School of Medicine, University of Naples Federico II, Naples, Italy

Journal of neuroinflammation, Jan 24, 2018

Diarrhea is a severe complication in HIV-1-infected patients with Trans-activator of transcriptio... more Diarrhea is a severe complication in HIV-1-infected patients with Trans-activator of transcription (HIV-1 Tat) protein being recognized as a major underlying cause. Beside its direct enterotoxic effects, Tat protein has been recently shown to affect enteric glial cell (EGC) activity. EGCs regulate intestinal inflammatory responses by secreting pro-inflammatory molecules; nonetheless, they might also release immune-regulatory factors, as palmytoilethanolamide (PEA), which exerts anti-inflammatory effects by activating PPARα receptors. We aimed at clarifying whether EGCs are involved in HIV-1 Tat-induced diarrhea and if PEA exerts antidiarrheal activity. Diarrhea was induced by intracolonic administration of HIV-1 Tat protein in rats at day 1. PEA alone or in the presence of peroxisome proliferator-activated receptor (PPAR) antagonists was given intraperitoneally from day 2 to day 7. S100B, iNOS, NF-kappaB, TLR4 and GFAP expression were evaluated in submucosal plexi, while S100B and N...

Journal of cellular and molecular medicine, Jan 9, 2017

The endocannabinoid system (ECS) is an endogenous signalling pathway involved in the control of s... more The endocannabinoid system (ECS) is an endogenous signalling pathway involved in the control of several gastrointestinal (GI) functions at both peripheral and central levels. In recent years, it has become apparent that the ECS is pivotal in the regulation of GI motility, secretion and sensitivity, but endocannabinoids (ECs) are also involved in the regulation of intestinal inflammation and mucosal barrier permeability, suggesting their role in the pathophysiology of both functional and organic GI disorders. Genetic studies in patients with irritable bowel syndrome (IBS) or inflammatory bowel disease have indeed shown significant associations with polymorphisms or mutation in genes encoding for cannabinoid receptor or enzyme responsible for their catabolism, respectively. Furthermore, ongoing clinical trials are testing EC agonists/antagonists in the achievement of symptomatic relief from a number of GI symptoms. Despite this evidence, there is a lack of supportive RCTs and relevant...

Digestive and Liver Disease

Scientific reports, Jan 10, 2017

Despite the effectiveness of combined anti-retroviral therapy, human immunodeficiency virus (HIV)... more Despite the effectiveness of combined anti-retroviral therapy, human immunodeficiency virus (HIV) infected-patients frequently report diarrhea and neuropsychological deficits. It is claimed that the viral HIV-1 Trans activating factor (HIV-1 Tat) protein is responsible for both diarrhea and neurotoxic effects, but the underlying mechanisms are not known. We hypothesize that colonic application of HIV-1 Tat activates glial cells of the enteric nervous system (EGCs), leading to a neuroinflammatory response able to propagate to the central nervous system. We demonstrated that HIV-1 Tat-induced diarrhea was associated with a significant activation of glial cells within the colonic wall, the spinal cord and the frontal cortex, and caused a consistent impairment of the cognitive performances. The inhibition of glial cells activity by lidocaine, completely abolished the above-described effects. These observations point out the role of glial cells as putative effectors in HIV-1 Tat-associat...

United European Gastroenterology Journal, 2017

Background: Clostridium difficile toxin A is responsible for colonic damage observed in infected ... more Background: Clostridium difficile toxin A is responsible for colonic damage observed in infected patients. Drugs able to restore Clostridium difficile toxin A-induced toxicity have the potential to improve the recovery of infected patients. Cannabidiol is a non-psychotropic component of Cannabis sativa, which has been demonstrated to protect enterocytes against chemical and/or inflammatory damage and to restore intestinal mucosa integrity. Objective: The purpose of this study was to evaluate (a) the anti-apoptotic effect and (b) the mechanisms by which cannabidiol protects mucosal integrity in Caco-2 cells exposed to Clostridium difficile toxin A. Methods: Caco-2 cells were exposed to Clostridium difficile toxin A (30 ng/ml), with or without cannabidiol (10 À7-10 À9 M), in the presence of the specific antagonist AM251 (10 À7 M). Cytotoxicity assay, transepithelial electrical resistence measurements, immunofluorescence analysis and immunoblot analysis were performed in the different experimental conditions. Results: Clostridium difficile toxin A significantly decreased Caco-2 cells' viability and reduced transepithelial electrical resistence values and RhoA guanosine triphosphate (GTP), bax, zonula occludens-1 and occludin protein expression, respectively. All these effects were significantly and concentration-dependently inhibited by cannabidiol, whose effects were completely abolished in the presence of the cannabinoid receptor type 1 (CB1) antagonist, AM251. Conclusions: Cannabidiol improved Clostridium difficile toxin A-induced damage in Caco-2 cells, by inhibiting the apoptotic process and restoring the intestinal barrier integrity, through the involvement of the CB1 receptor.

United European Gastroenterology Journal, 2016

Background: Polymorphisms of genes involved in the regulation of the immune response are risk fac... more Background: Polymorphisms of genes involved in the regulation of the immune response are risk factors for achalasia, but their contribution to disease pathogenesis is unknown. Nitric oxide is involved both in immune function and inhibitory neurotransmission. Objective: The objective of this article is to assess the association and the functional relevance of the CCTTT-inducible nitric oxide synthase (NOS2) gene promoter polymorphism in achalasia. Methods: Genomic DNA was isolated from 181 achalasia patients and 220 controls. Genotyping of the (CCTTT)n repeats was performed by PCR and capillary electrophoresis, and data analyzed by considering the frequency of the different alleles. HT29 cells were transfected with iNOS luciferase promoter-reporter plasmids containing different (CCTTT)n. Results: The alleles' distribution ranged from 7 to 18, with a peak frequency at 12 repeats. Analysis of the allele frequencies revealed that individuals carrying 10 and 13 CCTTT repeats were respectively less and more frequent in achalasia (OR 0.5, 95% CI 0.3-0.5 and OR 1.6, 95% CI 1-2.4, all p < 0.05). Long repeats were also significantly associated with an earlier onset of the disease (OR 1.69, 95% CI 1.13-2.53, p ¼ 0.01). Transfection experiments revealed a similar allele-specific iNOS transcriptional activity. Conclusion: The functional polymorphism (CCTTT) of NOS2 promoter is associated with achalasia, likely by an allele-specific modulation of nitric oxide production.