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Extra-intestinal manifestations of non-celiac gluten sensitivity: an expanding paradigm

World Journal of Gastroenterology 2018年第14期24卷 1521-1530页

作者： giuseppe Losurdo Mariabeatrice Principi Andrea Iannone Annacinzia Amoruso Enzo Ierardi Alfredo di Leo Michele Barone Section of Gastroenterology Department of Emergency and Organ Transplantation University "Aldo Moro" of Bari

Non celiac gluten sensitivity(NCGS) is a syndrome characterized by a cohort of symptoms related to the ingestion of gluten-containing food in subjects who are not affected by celiac disease(CD) or wheat allergy. The possibility of systemic manifestations in this condition has been suggested by some reports. In most cases they are characterized by vague symptoms such as ‘foggy mind', headache, fatigue, joint and muscle pain, leg or arm numbness even if more specific complaints have been described. NCGS has an immune-related background. Indeed there is a strong evidence that a selective activation of innate immunity may be the trigger for NCGS inflammatory response. The most commonly autoimmune disorders associated to NCGS are Hashimoto thyroiditis, dermatitis herpetiformis, psoriasis and rheumatologic diseases. The predominance of Hashimoto thyroiditis represents an interesting finding, since it has been indirectly confirmed by an Italian study, showing that autoimmune thyroid disease is a risk factor for the evolution towards NCGS in a group of patients with minimal duodenal inflammation. On these bases, an autoimmune stigma in NCGS is strongly supported; it could be a characteristic feature that could help the diagnosis and be simultaneously managed. A possible neurological involvement has been underlined by NCGS association with gluten ataxia, gluten neuropathy and gluten encephalopathy. NCGS patients may show even psychiatric diseases such as depression, anxiety and psychosis. Finally, a link with functional disorders(irritable bowel syndrome and fibromyalgia) is a topic under discussion. In conclusion, the novelty of this matter has generated an expansion of literature data with the unavoidable consequence that some reports are often based on low levels of evidence. Therefore, only studies performed on large samples with the inclusion of control groups will be able to clearly establish whether the large information from the literature regarding extra-intestinal

关键词： Non celiac gluten sensitivity celiac disease gluten gluten ataxia autoimmunity gluten-related disorders thyroiditis extra-intestinal

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Optimizing proton pump inhibitors in Helicobacter pylori treatment:Old and new tricks to improve effectiveness

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World Journal of Gastroenterology 2019年第34期25卷 5097-5104页

作者： Enzo Ierardi giuseppe Losurdo Rosa Federica La Fortezza Mariabeatrice Principi Michele Barone Alfredo di Leo Section of Gastroenterology Department of Emergency and Organ Transplantation University of Bari

The survival and replication cycle of Helicobacter pylori(***)is strictly dependant on intragastric pH,since *** enters replicative phase at an almost neutral pH(6-7),while at acid pH(3-6)it turns into its coccoid form,which is resistant to *** these bases,it is crucial to increase intragastric pH by proton pump inhibitors(PPIs)when an antibiotic-based eradicating therapy needs to be ***,several tricks need to be used to optimize eradication rate of different *** administration of the highest dose as possible of PPI,by doubling or increasing the number of pills/day,has shown to be able to improve therapeutic outcome and has often proposed in rescue therapies,even if specific trials have not been performed.A pre-treatment with PPI before starting antibiotics does not seem to be effective,therefore it is ***,the choice of PPI molecule could have a certain weight,since second-generation substances(esomeprazole,rabeprazole)are likely more effective than those of first generation(omeprazole,lansoprazole).A possible explanation is due to their metabolism,which has been proven to be less dependent on cytochrome P450(CYP)2C19 genetic ***,vonoprazan,a competitive inhibitor of H+/K+-ATPase present on luminal membrane of gastric parietal cells has shown the highest efficacy,due to both its highest acid inhibition power and rapid pharmacologic *** current data come only from Eastern Asia,therefore its strong power needs to be confirmed outside this geographic area in Western countries as well as related to the local different antibiotic resistance rates.

关键词： Helicobacter pylori Proton pump inhibitors Eradication Cytochrome P450 Optimization

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How to choose the most appropriate technique for the single-stage treatment of cholecysto-choledocolithiasis?

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Gastroenterology Report 2019年第4期7卷 258-262,I0001,I0002页

作者： Aldo Bove Paolo Panaccio Raffaella di Renzo Gino Palone Marco Ricciardiello Sara Ciuffreda giuseppe Bongarzoni Department of Medicine Dentistry and BiotechnologyUniversity‘G.D’Annunzio’Via dei VestiniChietiItaly

Background:We utilized transcystic clearance and intra-operative papillotomy through a rendezvous technique for the treatment of *** goal of this study was to evaluate the reliability of pre-operative parameters to address the most suitable surgical ***:A total of 180 patients affected by calculi of the gallbladder and bile duct underwent the single-stage *** to several pre-operative parameters,141 patients had to supposedly undergo transcystic clearance of the bile duct,while 39 patients had to be treated with the rendezvous *** patients were treated with the sequential procedure:first,we tried the transcystic procedure and,if there was a failure,we used a rendezvous *** prospectively analysed each group based on a series of variables such as sex,age,operative time,success rate of proposed treatment,conversion rate,post-operative complications and hospital ***:Transcystic clearance was successful in 134 out of 141 patients(95.0%),while 2 patients needed to undergo a laparo-endoscopy procedure(failure).Thirty-five out of 39 patients(89.7%)obtained common bile-duct(CBD)clearance through the rendezvous technique,while 1 patient obtained clean-up through the simple transcystic procedure(failure).Five out of 141 patients with transcystic clearance and 3 out of 39 patients with the rendezvous technique underwent laparotomy CBD clearance with conversion rates of 3.5%and 7.7%,***-operative complications showed similar percentages for both ***,the surgical time turned out to be longer for the rendezvous ***:The one-stage procedure for the treatment of cholecysto-choledocolithiasis was possible in 94%of the cases utilizing a surgical technique selected according to the patient’s case *** pre-operative parameters,such as jaundice,CBD diameters and stone diameters,have certified their reliability as good predictors of the most suitable

关键词： Common bile-duct stone transcystic laparoscopic bile-duct clearance laparoscopic common bile-duct exploration rendezvous intra-operative endoscopic retrograde cholangiography

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Probiotic monotherapy and Helicobacter pylori eradication: A systematic review with pooled-data analysis

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World Journal of Gastroenterology 2018年第1期24卷 139-149页

作者： giuseppe Losurdo Rossella Cubisino Michele Barone Mariabeatrice Principi Gioacchino Leandro Enzo Ierardi Alfredo di Leo Section of Gastroenterology Department of Emergency and Organ TransplantationUniversity "Aldo Moro"Piazza Giulio Cesare National Institute of Gastroenterology "S De Bellis" Research Hospital

AIM To define probiotic monotherapy effect on Helicobacter pylori(H. pylori) status by performing a systematic *** Methods of analysis and inclusion criteria were based on PRISMA recommendations. Relevant publications were identified by searching Pub Med, MEDLINE, Science direct, and EMBASE. The end-point was to estimate eradication rate and urea breath test delta value before and after probiotic monotherapy across all studies and, overall, with a pooled data analysis. Adverse events of probiotic therapy were evaluated. The data were expressed as proportions/percentages, and 95%CIs were calculated. For continuous variables, we evaluated the weighted mean difference. Odd ratios(ORs) were calculated according to the Peto method for the comparison of eradication rates between probiotics and *** Eleven studies were selected. Probiotics eradicated H. pylori in 50 out of 403 cases. The mean weighted eradication rate was 14%(95%CI: 2%-25%, P =0.02). Lactobacilli eradicated the bacterium in 30 out of 235 patients, with a mean weighted rate of 16%(95%CI: 1%-31%). Saccharomyces boulardii achieved eradication in 6 out of 63 patients, with a pooled eradication rate of 12%(95%CI: 0%-29%). Multistrain combinations were effective in 14 out of 105 patients, with a pooled eradication rate of 14%(95%CI: 0%-43%). In the comparison of probiotics vs placebo, we found an OR of 7.91 in favor of probiotics(95%CI: 2.97-21.05, P difference in adverse events was found between probiotics and placebo(OR = 1, 95%CI: 0.06-18.08).CONCLUSION Probiotics alone show a minimal effect on H. pylori clearance, thus suggesting a likely direct role.

关键词： Helicobacter pylori probiotics eradication meta-analysis breath test

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A new therapeutic approach to erectile dysfunction： urotensin-II receptor high affinity agonist ligands

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Asian Journal of Andrology 2015年第1期17卷 81-85,I0008,I0009页

作者： Roberta d'Emmanuele di Villa Bianca Emma Mitidieri Erminia Donnarumma Ferdinando Fusco Nicola Longo giuseppe De Rosa Ettore Novellino Paolo Grieco Vincenzo Mirone giuseppe Cirino Raffaella Sorrentino Department of Pharmacy University of Naples Federico II Via D. Montesano 49 Naples Italy Interdepartmental Centre for Sexual Medicine University of Naples Federico II Via S. Pansini 5 Naples Italy Department of Neurosciences Human Reproduction and Odontostomatology University of Naples Federico II Via S. Pansini 5 Naples Italy.

Urotensin-II （U-II） is a cyclic peptide that acts through a G protein-coupled receptor （urotensin-II receptor [UTR]） mainly involved in cardiovascular function in humans. The urotensinergic system is also implicated in the urogenital tract. Indeed, U-II relaxes human corpus cavernosum strips and causes an increase in intracavernous pressure （ICP） in rats. In light of this, the U-II/UTR pathway can be considered a new target for the treatment of erectile dysfunction. On this hypothesis, herein we report on two new UTR high affinity-agonists, P5U （H-Asp-c[Pen-Phe-Trp-Lys-Tyr-Cys]-Val-OH） and UPG84（H-Asp-c[Pen-Phe-DTrp-Orn-（pNH2） Phe-Cys]-Val-OH）. The effects of P5U and UPG84 were each compared separately with U-II by monitoring the ICP in anesthetized rats. Intracavernous injection of U-II （0.03-1 nmol）, P5U （0.03-1 nmol） or UPG84 （0.03-1 nmol） caused an increase in ICP. P5U, in particular, elicited a significant increase in ICP as compared to U-II. The observed effect by using P5U at a dose of 0.1 nmol per rat was comparable to the effect elicited by U-II at a dose of 0.3 nmol. Moreover, UPG84 at the lowest dose （0.03 nmol） showed an effect similar to the highest dose of U-II （1 nmol）. Furthermore, UPG84 was found to be more effective than P5U. Indeed, while the lowest dose of P5U （0.03 nmol） did not affect the ICP, UPG84, at the same dose, induced a prominent penile erection in rat. These compounds did not modify the blood pressure, which indicates a good safety profile. In conclusion, UPG84 and P5U may open new perspectives for the management of erectile dysfunction.

关键词： erectile dysfunction intracavernous pressure rat urotensin-II urotensin-II ligands

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Novel four-wing and eight-wing attractors using coupled chaotic Lorenz systems

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Chinese Physics B 2008年第9期17卷 3247-3251页

作者： giuseppe Grassi dipartimento di Ingegneria dell’Innovazione Università del Salento

This paper presents the problem of generating four-wing （eight-wing） chaotic attractors. The adopted method consists in suitably coupling two （three） identical Lorenz systems. In analogy with the original Lorenz system, where the two wings of the butterfly attractor are located around the two equilibria with the unstable pair of complex-conjugate eigenvalues, this paper shows that the four wings （eight wings） of these novel attractors axe located around the four （eight） equilibria with two （three） pairs of unstable complex-conjugate eigenvalues.

关键词： chaotic attractors multi-wing attractor coupled Lorenz systems dynamical behaviours

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Propulsion tests on ultra-high-temperature ceramic matrix composites for reusable rocket nozzles

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Journal of Advanced Ceramics 2023年第7期12卷 1345-1360页

作者： diletta Sciti Antonio Vinci Luca Zoli Pietro Galizia Simone Failla Stefano Mungiguerra giuseppe D.di Martino Anselmo Cecere Raffaele Savino Institute of Science Technology and Sustainability for Ceramics-National Research CouncilFaenza 48018Italy Department of Industrial Engineering University of Naples Federico IINaples 80125Italy

Ultra-high-temperature ceramic matrix composites(UHTCMCs)based on a ZrB_(2)/SiC matrix have been investigated for the fabrication of reusable nozzles for *** de Laval nozzle prototypes,obtained by sintering with either hot pressing(HP)or spark plasma sintering(SPS),were tested 2-3 times in a hybrid rocket motor for proving *** were extracted after oxidation tests to study the microstructural changes and oxidative and thermomechanical stresses induced by the repeated *** to a reference graphite nozzle,no measurable erosion was observed for the UHTCMC-based *** oxidation mechanism consisted in the formation of a ZrO_(2)intermediate layer,with a liquid silicon oxide(SiO_(2))layer on the surface that was displaced by the action of the gas flux towards the divergent part of the nozzle,protecting it from further *** specimens obtained by HP and SPS displayed similar performance,with very slight differences,which were attributed to small changes in *** tests demonstrated the capability of complex-shaped prototypes made of the developed UHTCMCs to survive repeated exposure to environments representative of a realistic space propulsion application,for overall operating time up to 30 s,without any failure nor measurable erosion,making a promising step towards the development of reusable rocket components.

关键词： ultra-high-temperature ceramics(UHTCs) ceramic matrix composites(CMCs) propulsion oxidation resistance nozzle prototypes

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direct oral anticoagulant administration in cirrhotic patients with portal vein thrombosis:What is the evidence?

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World Journal of Hepatology 2022年第4期14卷 682-695页

作者： Marco Biolato Mattia Paratore Luca di Gialleonardo giuseppe Marrone Antonio Grieco Internal and Liver Transplant Medicine Unit CEMADDepartment of Medical and Surgical SciencesFondazione Policlinico Universitario Agostino Gemelli IRCCSRome 00168Italy Institute of Internal Medicine Catholic University of Sacred HeartRome 00168Italy

In recent years,the traditional concept that cirrhosis-related coagulopathy is an acquired bleeding disorder has ***,it is known that in cirrhotic patients,the hemostatic system is rebalanced,which involves coagulation factors,fibrinolysis and *** alterations disrupt homeostasis,skewing it toward a procoagulant state,which can lead to thromboembolic manifestations,especially when hemodynamic and endothelial factors co-occur,such as in the portal vein system in *** vein thrombosis is a common complication of advanced liver cirrhosis that negatively affects the course of liver disease,prognosis of cirrhotic patients and success of liver *** is still debated whether portal vein thrombosis is the cause or the consequence of worsening liver *** therapy is the mainstay treatment for acute symptomatic portal vein *** chronic portal vein thrombosis,the role of anticoagulant therapy is still *** anticoagulants,vitamin K antagonists and low-molecular-weight heparin are standard-of-care treatments for portal vein *** the last ten years,direct oral anticoagulants have been approved for the prophylaxis and treatment of many thromboembolicrelated diseases,but evidence on their use in cirrhotic patients is very *** aim of this review was to summarize the evidence about the safety and effectiveness of direct oral anticoagulants for treating portal vein thrombosis in cirrhotic patients.

关键词： Dabigatran Rivaroxaban Apixaban Edoxaban Bleeding

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Ulcerative colitis: From inflammation to cancer. Do estrogen receptors have a role?

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World Journal of Gastroenterology 2014年第33期20卷 11496-11504页

作者： Mariabeatrice Principi Michele Barone Maria Pricci Nicola De Tullio giuseppe Losurdo Enzo Ierardi Alfredo di Leo division of Gastroenterology Department of Emergency and Organ Transplantation University of Bari 70124 Bari Italy division of Gastroenterology Department of Medical and Surgical Sciences University of Foggia 71100 Foggia Italy

Ulcerative colitis(UC) is a condition at increased risk for colorectal carcinoma(CRC) development. Nowadays, screening and follow-up programs are routinely performed worldwide to promote the early detection of CRCs in subjects with well known risk factors(extent, duration and severity of the disorder). The diffusion of these procedures is presumably the main reason for the marked reduction of cancer incidence and mortality in the course of UC. In addition, chemoprevention has been widely investigated and developed in many medical fields, and aspirin has shown a preventive effect against CRC, while mesalazine has been strongly invoked as a potential chemopreventive agent in UC. However, available studies show some limitations due to the obvious ethical implications of drug withdrawal in UC in order to design a control group. The estrogenreceptors(ER) alpha/beta balance seems to have a relevant influence on colorectal carcinogenesis and ER beta appears to parallel apoptosis, and hence an anticarcinogenic effect. Phytoestrogens are compounds acting as ER beta agonists and have shown a promising chemopreventive effect on sporadic as well as genetically inherited CRC. There is evidence suggesting a role for ERs in UC-related carcinogenesis. In this perspective, since these substances can be considered as dietary supplements and are completely free from side effects, phytoestrogens could be an interesting option for CRC prevention, even when the disease is a consequence of long-term chronic inflammation, as in the course of UC. Further studies of their effects are warranted in both the basic research and clinical fields.

关键词： Ulcerative colitis Epithelial dysplasia Colorectal cancer Estrogen receptors Chemopreven-tion Phytoestrogens dietary supplementation Inflam-matory bowel disease

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Reliability based multiobjective optimization for design of structures subject to random vibrations

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Journal of Zhejiang University-Science A(Applied Physics & Engineering) 2008年第1期9卷 15-25页

作者： giuseppe Carlo MARANO Department of Environmental Engineering and Sustainable Development Technical University of Bari viale del Turismo 10-74100 Taranto Italy

Based on a multiobjective approach whose objective function (OF) vector collects stochastic reliability performance and structural cost indices, a structural optimization criterion for mechanical systems subject to random vibrations is presented for supporting engineer’s design. This criterion differs from the most commonly used conventional optimum design criterion for random vibrating structure, which is based on minimizing displacement or acceleration variance of main structure responses, without considering explicitly required performances against failure. The proposed criterion can properly take into account the design-reliability required performances, and it becomes a more efficient support for structural engineering decision making. The multiobjective optimum (MOO) design of a tuned mass damper (TMD) has been developed in a typical seismic design problem, to control structural vibration induced on a multi-storey building structure excited by nonstationary base acceleration random process. A numerical example for a three-storey building is developed and a sensitivity analysis is carried out. The results are shown in a useful manner for TMD design decision support.

关键词： Structural optimization Multiobjective optimization (MOO) Random vibration Tuned mass damper (TMD)

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