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Cytotoxic synergism of Clostridioides difficile toxin B with proinflammatory cytokines in subjects with inflammatory bowel diseases

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World Journal of Gastroenterology 2023年第4期29卷 582-596页

作者： gabrio bassotti Alessandro Fruganti Fabrizio Stracci Pierfrancesco Marconi Katia Fettucciari Department of Medicine and Surgery GastroenterologyHepatology&Digestive Endoscopy Section University of Perugia Medical SchoolPiazza Lucio SeveriPerugia 06132Italyand Santa Maria della Misericordia HospitalGastroenterology&Hepatology Unit Perugia 06156Italy School of Biosciences and Veterinary Medicine University of CamerinoMatelica 62024Italy Medicine and Surgery Hygiene and Public Health SectionUniversity of PerugiaPerugia 06123Italy Medicine and Surgery Biosciences&Medical Embryology SectionUniversity of PerugiaPerugia 06132Italy

Clostridioides difficile(***)is progressively colonizing humans and animals living with *** this process,hypervirulent strains and mutated toxin A and B of ***(TcdA and TcdB)are originating and *** in healthy subjects colonization by *** becomes a risk after the use of antibiotics that alter the microbiome,other categories of people are more susceptible to infection and at risk of relapse,such as those with inflammatory bowel disease(IBD).Recent in vitro studies suggest that this increased susceptibility could be due to the strong cytotoxic synergism between TcdB and proinflammatory cytokines the tumor necrosis factor-alpha and interferon-gamma(CKs).Therefore,in subjects with IBD the presence of an inflammatory state in the colon could be the driver that increases the susceptibility to *** infection and its progression and *** is internalized in the cell via three receptors:chondroitin sulphate proteoglycan 4;poliovirus receptor-like 3;and Wnt receptor frizzled *** sulphate proteoglycan 4 and Wnt receptor frizzled family are involved in cell death by apoptosis or necrosis depending on the concentration of TcdB and cell types,while poliovirus receptor-like 3 induces only *** is possible that cytokines could also induce a greater expression of receptors for TcdB that are more involved in necrosis than in ***,in subjects with IBD there are the conditions:(1)For greater susceptibility to *** infection,such as the inflammatory state,and abnormalities of the microbiome and of the immune system;(2)for the enhancement of the cytotoxic activity of TcdB+Cks;and(3)for a greater expression of TcdB receptors stimulated by cytokines that induce cell death by necrosis rather than *** only therapeutic approach currently possible in IBD patients is monitoring of *** colonization for interventions aimed at reducing tumor necrosis factor-alpha and interfero

关键词： Inflammatory bowel diseases Clostridioides difficile infection Cytokines Tumor necrosis factor-alpha Interferon-gamma Necrosis Apoptosis Cytotoxic synergism

Cellular and molecular basis of chronic constipation: Taking the functional/idiopathic label out

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World Journal of Gastroenterology 2013年第26期19卷 4099-4105页

作者： gabrio bassotti Vincenzo Villanacci Dragos Cretoiu Sanda Maria Cretoiu Gabriel Becheanu Gastroenterology and Hepatology Section Department of Clinical and Experimental Medicine University of Perugia Second Pathology Section Spedali Civili Division of Cellular and Molecular Medicine Department of Morphological Sciences "Carol Davila" University of Medicine and Pharmacy Department of Molecular Medicine "Victor Babes" National Institute of Pathology Department of Ultrastructural Pathology "Victor Babes" National Institute of Pathology Department of Gastroenterology and Hepatology Fundeni Clinical Institute

In recent years, the improvement of technology and the increase in knowledge have shifted several strongly held paradigms. This is particularly true in gastroenterology, and specifically in the field of the so-called "functional" or "idiopathic" disease, where conditions thought for decades to be based mainly on alterations of visceral perception or aberrant psychosomatic mechanisms have, in fact, be reconducted to an organic basis (or, at the very least, have shown one or more demonstrable abnormalities). This is particularly true, for instance, for irritable bowel syndrome, the prototype entity of "functional" gastrointestinal disorders, where low-grade inflammation of both mucosa and myenteric plexus has been repeatedly demonstrated. Thus, researchers have also investigated other functional/idiopathic gastrointestinal disorders, and found that some organic ground is present, such as abnormal neurotransmission and myenteric plexitis in esophageal achalasia and mucosal immune activation and mild eosinophilia in functional dyspepsia. Here we show evidence, based on our own and other authors' work, that chronic constipation has several abnormalities reconductable to alterations in the enteric nervous system, abnormalities mainly characterized by a constant decrease of enteric glial cells and interstitial cells of Cajal (and, sometimes, of enteric neurons). Thus, we feel that (at least some forms of) chronic constipation should no more be considered as a functional/idiopathic gastrointestinal disorder, but instead as a true enteric neuropathic abnormality.

关键词： Constipation Enteric glia Enteric nervous system Enteric neurons Interstitial cells of Cajap Neurogastroenterology

Gastrointestinal motility disorders in inflammatory bowel diseases

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World Journal of Gastroenterology 2014年第1期20卷 37-44页

作者： gabrio bassotti Elisabetta Antonelli Vincenzo Villanacci Marianna Salemme Manuela Coppola Vito Annese Gastroenterology and Hepatology Section Department of Clinical and Experimental MedicineUniversity of Perugia06156 PerugiaItaly Second Pathology Section Spedali Civili of Brescia25100 BresciaItaly Gastroenterology Unit Careggi University Hospital50134 FlorenceItaly

The relationship between motility and inflammatory gastrointestinal disorders is at the same time complex and intriguing since these conditions might share some genetic, environmental, immunological and microbial predisposing factors. In addition, significant symptom overlapping may occur, muddling the waters within the clinical context. Although on one hand this represents a challenge for the clinician for a potential under- or over-treatment and diagnostic delay, on the other hand it possibly represents an opportunity for the researcher to better disclose the intimate relationship between chronic (often low-grade) inflammation, motor disorders and deranged sensory function. The best example is probably represented by Crohn’s disease and ulcerative colitis. In fact, a number of gastrointestinal motor disorders have been described in association with these diseases, disorders which span from the esophagus to the anorectum, and which will be extensively covered in this review. It is conceivable that at least part of this derangement is strictly related to inflammatory cytokine trafficking and neuromuscular changes; however, given the high prevalence of functional gastrointestinal disorders in the general population, this overlap might also be serendipitous. However, it is worth noting that literature data on this topic are relatively scarce, sometimes quite outdated, and mostly focused on the interplay between irritable bowel syndrome and inflammatory bowel disease. Nevertheless, both researchers and clinicians must be aware that symptoms related to gastrointestinal motility disorders may be highly prevalent in both active and inactive inflammatory bowel disease, correlate with greater psychological comorbidity and poorer quality of life, and may negatively influence the therapeutic approaches.

关键词： Crohn’ s disease, Gastrointestinal motility disorders, Gut, Inflammatory bowel diseases, Perception, Ulcerative colitis

Gastroparesis:New insights into an old disease

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World Journal of Gastroenterology 2020年第19期26卷 2333-2348页

作者： Paolo Usai-Satta Massimo Bellini Olivia Morelli Francesca Geri Mariantonia Lai gabrio bassotti Department of Internal Medicine Division of GastroenterologyBrotzu HospitalCagliari 09124Italy Gastrointestinal Unit Department of Translational Research and New Technologies in Medicine and SurgeryUniversity of PisaPisa 56122Italy Gastroenterology and Hepatology Section Department of MedicineUniversity of Perugia Medical SchoolPerugia 06123Italy Gastroenterology Unit University of CagliariMonserrato 09042Italy

Gastroparesis(Gp)is a chronic disease characterized by a delayed gastric emptying in the absence of mechanical *** this condition has been reported in the literature since the mid-1900s,only recently has there been renewed clinical and scientific interest in this disease,which has a potentially great impact on the quality of *** aim of this review is to explore the pathophysiological,diagnostic and therapeutical aspects of Gp according to the most recent evidence.A comprehensive online search for Gp was carried out using MEDLINE and *** is the result of neuromuscular abnormalities of the gastric motor *** is evidence that patients with idiopathic and diabetic Gp may display a reduction in nitrergic inhibitory neurons and in interstitial cells of Cajal and/or *** regards diagnostic approach,99-Technetium scintigraphy is currently considered to be the gold standard for *** limits are a lack of standardization and a mild risk of radiation *** C13 breath testing is a valid and safe alternative method.13C acid octanoic and the 13C Spirulina platensis recently approved by the Food and Drug Administration are the most commonly used diagnostic *** wireless motility capsule is a promising technique,but its use is limited by costs and scarce availability in many ***,therapeutic strategies are related to the clinical severity of *** mild and moderate Gp,dietary modification and prokinetic agents are generally *** is the only drug approved by the Food and Drug Administration for ***,other older and new prokinetics and antiemetics can be *** a second-line therapy,tricyclic antidepressants and cannabinoids have been *** severe cases the normal nutritional approach can be compromised and artificial nutrition may be *** drug-unresponsive Gp patients some alternative strategies(endoscopic,electric stimulation or surgery)are available.

关键词： Gastroparesis Delayed gastric emptying Gastric Scintigraphy 13C breath testing Wireless motility capsule Prokinetics Antiemetic drugs Gastric-per-oral endoscopic myotomy Gastric electrical stimulation

Histological healing in inflammatory bowel disease:A still unfulfilled promise

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World Journal of Gastroenterology 2013年第7期19卷 968-978页

作者： Vincenzo Villanacci Elisabetta Antonelli Karel Geboes Giovanni Casella gabrio bassotti Department of Pathology Spedali Civili of Brescia25100 BresciaItaly Gastroenterology and Hepatology Section Department of Clinical and Experimental MedicineUniversity of Perugia06156 PerugiaItaly Department of Pathology University Hospital KU Leuven and UZ Gent3000 LeuvenBelgium Division of Internal Medicine Desio General Hospital20033 DesioItaly

Treatment of inflammatory bowel disease(IBD) is traditionally based on several drugs,including salicylates,corticosteroids,and antibiotics;in addition,the therapeutic armamentarium has considerably evolved with the advent of newer,effective therapeutic measures(such as the biological agents) that are able to improve in a considerable manner both the clinical and endoscopic ***,mucosal healing,at least considered from an endoscopic point of view,is today regarded as the ultimate endpoint for treatment of these ***,it is also increasingly clear that endoscopic healing is not necessarily paralleled by histological healing;There are few doubts that the latter should be considered as a true,objective healing and the ultimate goal to reach when treating patients with ***,and surprisingly,only a few,incomplete,and somewhat conflicting data exist on this topic,especially because there is still the need to standardize both histological assessment and the severity grading of these disorders;Issues that have not been yet been resolved for clinical practice and therapeutic ***,with the help of an increased awareness on the clinical researchers' side,and the availability of dedicated pathologists on the other side,this matter will be effectively faced and resolved in the near future.

关键词： Crohn’s disease Healing Histology Inflammatory bowel diseases Ulcerative colitis

Inflammatory bowel disease in the dog:Differences and similarities with humans

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World Journal of Gastroenterology 2010年第9期16卷 1050-1056页

作者： Matteo Cerquetella Andrea Spaterna Fulvio Laus Beniamino Tesei Giacomo Rossi Elisabetta Antonelli Vincenzo Villanacci gabrio bassotti School of Medical Veterinary Sciences University of CamerinoVia Circonvallazione Gastroenterology and Hepatology Section Department of Clinical and Experimental MedicineSanta Maria della Misericordia Hospital 2nd Department of Pathology Spedali Civili of BresciaPiazza Spedali Civili

Inflammatory bowel diseases (IBD) represent important chronic conditions affecting the gastrointestinal tract in ***,similar disorders are found in several animal species and the IBD affecting dogs are particularly *** are encompassed by an umbrella of probably several different entities with common symptoms,some of which seem to share striking similarities with human *** review will focus on the actual knowledge of IBD in dogs,and attempt to identify differences and similarities with human IBD conditions.

关键词： Colitis Dog Inflammatory bowel diseases

Non-surgical treatment of esophageal achalasia

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World Journal of Gastroenterology 2006年第36期12卷 5763-5766页

作者： Vito Annese gabrio bassotti Dipartimento di Medicina Generale e Specialistica Unità Operativa di Gastroenterologia ed Endoscopia Ospedale "Casa Sollievo della Sofferenza"-I.R.C.C.S. San Giovanni Rotondo Italy Dipartimento di Medicina Clinica e Speri-mentale Sezione di Gastroenterologia ed Epatologia Università di Perugia Italy

Esophageal achalasia is an infrequent motility disorder characterized by a progressive stasis and dilation of the oesophagus; with subsequent risk of aspiration, weight loss, and malnutrition. Although the treatment of achalasia has been traditionally based on a surgical approach, especially with the introduction of laparoscopic techniques, there is still some space for a medical approach. The present article reviews the non-surgical therapeutic options for achalasia.

关键词： Achalasia Botulinum toxin Pneumatic dilatation

Slow transit constipation: A functional disorder becomes an enteric neuropathy

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World Journal of Gastroenterology 2006年第29期12卷 4609-4613页

作者： gabrio bassotti Vincenzo Villanacci Gastroenterology and Hepatology Section Department of Clinical and Experimental Medicine University of PerugiaItaly 2~(nd) Pathology Section Spedali Civili BresciaItaly

Slow transit constipation has been traditionally considered and classified as a functional disorder. However, clinical and manometric evidence has been accumulating that suggests how most of the motility alterations in STC might be considered of neuropathic *** addition, further investigations showed that subtle alterations of the enteric nervous system, not evident to conventional histological examination, may be present in these patients. In the present article we will discuss these evidences, and will try to put them in relation with the abnormal motor function of the large bowel documented in this pathological condition.

关键词： Constipation Enteric neuropathy Functionaldisorders Slow transit

Pathophysiological aspects of diverticular disease of colon and role of large bowel motility

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World Journal of Gastroenterology 2003年第10期9卷 2140-2142页

作者： gabrio bassotti Fabio Chistolini Antonio Morelli Clinica di Gastroenterologia ed Epatologia Dipartimento di Medicina Clinica e SperimentaleUniversità di PerugiaItaly

Colonic diverticular disease (diverticulosis) is one of the most common gastrointestinal disorders in Western countries. This disorder is strictly related to aging and fibre intake, and still bears a discrete amount of morbidity. Numerous etiological co-factors have to date been implicated in the pathogenesis of the disease, yet the supporting evidence is still far from absolute. The present review considers the pathophysiology of colonic diverticular disease, with a special emphasis on factors related to abnormal colonic motility.

关键词： Colon Diverticulosis, Colonic Gastrointestinal Motility Humans