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Effect of Aspergillus niger prolyl endopeptidase in patients with celiac disease on a long-term gluten-free diet

World Journal of Gastroenterology 2024年第11期30卷 1545-1555页

作者： Juan Pablo Stefanolo Verónica Segura Martina Grizzuti Abel Heredia Isabel Comino Ana Florencia Costa Roberto Puebla María Paz Temprano Sonia Isabel Niveloni Gabriel de Diego María E Oregui edgardo Gustavo smecuol Mauricio C de Marzi Elena F Verdú Carolina Sousa Julio César Bai Small Bowel Section Department of MedicineGastroenterology Hospital of Buenos Aires“Dr.C.Bonorino Udaondo”Buenos Aires 1264Argentina Department of Microbiology and Parasitology Faculty of PharmacyUniversity of SevilleSeville 41080Spain Department of Medicine Dr.C.Bonorino Udaondo Gastroenterology HospitalBuenos Aires 1264Argentina Basic and Applied Research Group in Immunology and Bioactives(GIBAIB) Institute of Ecology and Sustainable Development(INEDES)National University of LujanLuján 6700Buenos AiresArgentina Department of Medicine Farncombe Family Digestive Health Research InstituteMcMaster UniversityHamilton L8S 4L8OntarioCanada Facultad de Medicina Universidad del SalvadorBuenos Aires C1051ABBArgentina

BACKGROUND The gluten-free diet(GFD)has limitations,and there is intense research in the development of adjuvant *** To examine the effects of orally administered Aspergillus niger prolyl endopeptidase protease(AN-PEP)on inadvertent gluten exposure and symptom prevention in adult celiac disease(CeD)patients following their usual *** This was an exploratory,double-blind,randomized,placebo-controlled trial that enrolled CeD patients on a long-term *** a 4-wk run-in period,patients were randomized to 4 wk of two AN-PEP capsules(GliadinX;AVI Research,LLC,United States)at each of three meals per day or *** endpoints were:(1)Average weekly stool gluten immunogenic peptides(GIP)between the run-in and end of treatments and between AN-PEP and placebo;(2)celiac symptom index(CSI);(3)CeD-specific serology;and(4)quality of *** samples were collected for GIP testing by ELISA every Tuesday and Friday during run-ins and *** Forty patients were randomized for the intention-to-treat analysis,and three were excluded from the per-protocol ***,628/640(98.1%)stool samples were *** was undetectable(0.32μg/g)to potentially cause mucosal *** GIP concentration in the AN-PEP arm was 44.7%lower than in the run-in ***-third of patients exhibiting GIP>0.08μg/g during run-in had lower or undetectable GIP after AN-PEP *** with the run-in period,the proportion of symptomatic patients(CSI>38)in the AN-PEP arm was significantly lower(P<0.03).AN-PEP did not result in changes in specific *** This exploratory study conducted in a real-life setting revealed high adherence to the *** AN-PEP treatment did not significantly reduce the overall GIP stool ***,given the observation of a significantly lower prevale

关键词： Celiac disease Aspergillus niger prolyl endoprotease Gluten immunogenic peptides Trial Symptoms Real-life trial

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Gluten immunogenic peptide excretion detects dietary transgressions in treated celiac disease patients

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World Journal of Gastroenterology 2019年第11期25卷 1409-1420页

作者： Ana Florencia Costa Emilia Sugai María de la Paz Temprano Sonia Isabel Niveloni Horacio Vázquez María Laura Moreno M.Remedios Domínguez-Flores Alba Mu?oz-Suano edgardo smecuol Juan Pablo Stefanolo Andrea F González Angel Cebolla-Ramirez Eduardo Mauri?o Elena F Verdú Julio César Bai Small Bowel Section Department of MedicineDr.C.Bonorino Udaondo Gastroenterology HospitalBuenos Aires 1263Argentina Department of Immunology Biomedal S.L.Sevilla 41092Spain Farncombe Family Digestive Health Research Institute McMaster UniversityHamiltonON L8S4L8Canada Research Institutes Universidad del SalvadorBuenos Aires 1050Argentina

BACKGROUND Life-long removal of gluten from the diet is currently the only way to manage celiac disease(CeD). Until now, no objective test has proven useful to objectively detect ingested gluten in clinical practice. Recently, tests that determine consumption of gluten by assessing excretion of gluten immunogenic peptides(GIP) in stool and urine have been developed. Their utility, in comparison with conventional dietary and analytical follow-up strategies, has not been fully *** To assess the performance of enzyme-linked immunosorbent assay(ELISA) and point-of-care tests(PoCTs) for GIP excretion in CeD patients on gluten-free diet(GFD).METHODS We conducted an observational, prospective, cross-sectional study in patients following a GFD for at least two years. Using the Gastrointestinal Symptom Rating Scale questionnaire, patients were classified at enrollment as asymptomatic or symptomatic. Gluten consumption was assessed twice by 3-d dietary recall and GIP excretion(by ELISA in stool and PoCTs(commercial kits for stool and urine) in two consecutive samples. These samples and dietary reports were obtained 10 day apart one from the other. Patients were encouraged to follow their usual GFD during the study *** Forty-four patients were enrolled, of which 19(43.2%) were symptomatic despite being on a GFD. Overall, 83 sets of stool and/or urine samples were *** out of 44 patients(25.0%) had at least one positive GIP test. The occurrence of at least one positive test was 32% in asymptomatic patients compared with 15.8% in symptomatic patients. GIP was concordant with dietary reports in 65.9% of cases(Cohen′s kappa: 0.317). PoCT detected dietary indiscretions. Both ELISA and PoCT in stool were concordant(concomitantly positive or negative) in 67 out of 74(90.5%) samples. Excretion of GIP was detected in 7(8.4%) stool and/or urine samples from patients considered to be strictly compliant with the GFD by dietary *** GIP dete

关键词： Celiac disease Follow-up Gluten-free diet Gluten immunogenic peptide excretion Rapid tests

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Celiac disease serology in patients with different pretest probabilities: Is biopsy avoidable?

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World Journal of Gastroenterology 2010年第25期16卷 3144-3152页

作者： Emilia Sugai María L Moreno Hui J Hwang Ana Cabanne Adriana Crivelli Fabio Nach-man Horacio Vázquez Sonia Niveloni Julio Argonz Roberto Mazure Graciela La Motta María E Caniggia edgardo smecuol Néstor Chopita Juan C Gómez Eduardo Maurińo Julio C Bai Small Bowel Section Department of Medicine Gastroenterology Hospital "Dr. C. Bonorino Udaondo" Caseros 2061 Ciudad de Buenos Aires Argentina Pathology Service Hospital de Gastroenter-ología "Dr. C. Bonorino Udaondo" Av. Caseros 2061 Ciudad de Buenos Aires Argentina USNMA HIGA "San Martín" La Plata B1900 Provincia de Buenos Aires Argentina Endoscopy Service Hospital de Gastroenter-ología "Dr. C. Bonorino Udaondo" Av. Caseros 2061 Ciudad de Buenos Aires Argentina Endoscopy Service HIGA "San Martín" La Plata

AIM: To establish the diagnostic performance of sev-eral serological tests, individually and in combination, for diagnosing celiac disease (CD) in patients with different pretest probabilities, and to explore potential se- rological algorithms to reduce the necessity for biopsy. METHODS: We prospectively performed duodenal biopsy and serology in 679 adults who had either high risk (n = 161) or low risk (n = 518) for CD. Blood samples were tested using six assays (enzyme-linked immunosorbent assay) that detected antibodies to tissue transglutaminase (tTG) and deamidated gliadin peptide (DGP). RESULTS: CD prevalence was 39.1% in the high-risk population and 3.3% in the low-risk group. In high-risk patients, all individual assays had a high diagnostic efficacy [area under receiving operator characteristic curves (AU ROC): 0.968 to 0.999]. In contrast, assays had a lower diagnostic efficacy (AU ROC: 0.835 to 0.972) in the low-risk group. Using assay combinations, it would be possible to reach or rule out diagnosis of CD without biopsy in 92% of cases in both pretest populations. We observed that the new DGP/tTG Screen assay resulted in a surplus compared to more conventional assays in any clinical situation. CONCLUSION: The DGP/tTG Screen assay could be considered as the best initial test for CD. Combinations of two tests, including a DGP/tTG Screen, might be able to diagnose CD accurately in different clinical scenarios making biopsy avoidable in a high proportion of subjects.

关键词： Celiac disease Serology Gliadin peptide antibodies Tissue transglutaminase Antigliadin antibodies Small bowel biopsy Diagnostic accuracy

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Risk perception and knowledge of COVID-19 in patients with celiac disease

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World Journal of Gastroenterology 2021年第12期27卷 1213-1225页

作者： Jamie Zhen Juan Pablo Stefanolo María de la Paz Temprano Caroline L Seiler Alberto Caminero Enrique de-Madaria Miguel Montoro Huguet Vivas Santiago Sonia Isabel Niveloni edgardo Gustavo smecuol Luis Uzcanga Dominguez Elena Trucco Virginia Lopez Carolina Olano Pasquale Mansueto Antonio Carroccio Peter H Green Donald Duerksen Andrew S Day Jason A Tye-Din Julio César Bai Carolina Ciacci Elena F Verdú Benjamin Lebwohl M Ines Pinto-Sanchez Department of Medicine Farncombe Family Digestive Health Research InstituteMcMaster University Medical CenterHamilton Health SciencesHamilton L8S4K1ONCanada Department of Medicine Dr.C.Bonorino Udaondo Gastroenterology HospitalBuenos Aires 1264Argentina Department of Pancreatic Unit Hospital General Universitario de AlicanteAlicante 03010Spain Department of Medicine Instituto Aragonés de Ciencias de la Salud(IACS)Zaragoza 50009Spain Department of Medicine Hospital Universitario San Jorge.HuescaZaragoza 50004Spain Department of Gastroenterology Univ Hosp LeonGastroenterol UnitAltos de Nava S-NLeon 24071Spain Department of Medicine Instituto Nacional de Ciencias Médicas y Nutrición Salvador ZubiránMexico DF 14080Mexico Department of Medicine Universidad de la RepublicMontevideo 11800Uruguay Department of Internal Medicine PROMISE DepartmentUniversity of PalermoPalermo 90127Italy Department of Internal Medicine V.Cervello HospitalPROMISE DepartmentUniversity of PalermoPalermo 90127Italy Celiac Disease Center Columbia University Medical CenterColumbia UnivCeliac Dis CtrDiv Digest and Liver DisNew YorkNY 10032United States Department of Medicine St Boniface Gen HospUniversity of ManitobaWinnipeg R2H 2A6Canada Department of Paediatrics University of Otago ChristchurchChristchurch 8041New Zealand Department of Gastroenterology Royal Melbourne HospitalImmunology DivisionWalter and Eliza Hall InstituteMelbourne 3052Australia Department of Medicine Surgery and DentryScuola Medica SalernitanaUniversity of SalernoCeliac Center at the University Hospital San Giovanni di Dio e Ruggi di AragonaSalerno 84131Italy Department of Medicine Farncombe Family Digestive Research InstituteMcMaster UniversityHamilton L8S4K1ONCanada The Celiac Disease Center Columbia UniversityNew YorkNY 10032United States

BACKGROUND We recently demonstrated that the odds of contracting coronavirus disease 2019(COVID-19)in patients with celiac disease(CeD)is similar to that of the general ***,how patients with CeD perceive their COVID-19 risk may differ from their actual *** To investigate risk perceptions of contracting COVID-19 in patients with CeD and determine the factors that may influence their *** We distributed a survey throughout 10 countries between March and June 2020 and collected data on demographics,diet,COVID-19 testing,and risk perceptions of COVID-19 in patients with *** were recruited through various celiac associations,clinic visits,and social *** perception was assessed by asking individuals whether they believe patients with CeD are at an increased risk of contracting COVID-19 when compared to the general *** regression was used to determine the influencing factors associated with COVID-19 risk perception,such as age,sex,adherence to a gluten-free diet(GFD),and comorbidities such as cardiac conditions,respiratory conditions,and *** was presented as adjusted odds ratios(aORs)RESULTS A total of 10737 participants with CeD completed the *** them,6019(56.1%)patients with CeD perceived they were at a higher risk or were unsure if they were at a higher risk of contracting COVID-19 compared to the non-CeD population.A greater proportion of patients with CeD perceived an increased risk of contracting COVID-19 when compared to infections in general due to their CeD(56.1%vs 26.7%,P<0.0001).Consequently,34.8%reported taking extra COVID-19 precautions as a result of their *** of celiac associations were less likely to perceive an increased risk of COVID-19 when compared to non-members(49.5%vs 57.4%,P<0.0001).Older age(aOR:0.99;95%CI:0.99 to 0.99,P<0.001),male sex(aOR:0.84;95%CI:0.76 to 0.93,P=0.001),and strict adherence to a GFD(aOR:0.89;95%CI:0.82 to 0.96,P=0.007)were associated

关键词： Celiac disease Gluten Risk Infection Knowledge Perception Coronavirus COVID-19

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Risk of fracture in celiac disease:Gender,dietary compliance,or both?

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World Journal of Gastroenterology 2011年第25期17卷 3035-3042页

作者： María Inés Pinto Sánchez Adriana Mohaidle Andrea Baistrocchi Dolores Matoso Horacio Vázquez Andrea González Roberto Mazure Evangelina Maffei Guillermina Ferrari edgardo smecuol Adriana Crivelli Juan Andrés de Paula Juan C Gómez Silvia Pedreira Eduardo Maurio Julio César Bai Small Bowel Section Department of Medicine"Dr.C.Bonorino Udaondo" Gastroenterology Hospital Department of Gastroenterology German Hospital Nutritional Support Unit and Malabsortion "San Martin" HIGA1900 La PlataArgentina Department of Gastroenterology Italian Hospital

AIM:To determine the incidence of peripheral fractures in patients with celiac disease (CD) and the effect of treatment on fracture ***:We compared the incidence and risk of peripheral fractures before and after diagnosis between a cohort of 265 patients who had been diagnosed with CD at least 5 years before study entry and a cohort of 530 age-and sex-matched controls who had been diagnosed with functional gastrointestinal *** were collected through in-person interviews with an *** overall assessment window for patients was 9843 patient-years (2815 patient-years after diagnosis).RESULTS:Compared with the control group,the CD cohort showed significantly higher incidence rate and risk of first peripheral fracture before diagnosis [adjusted hazard ratio (HR):1.78,95% CI:1.23-2.56,P < 0.002] and in men (HR:2.67,95% CI:1.37-5.22,P < 0.004).Fracture risk was significantly associated with the classic CD presentation with gastrointestinal symptoms (P < 0.003).In the time period after diagnosis,the risk of fractures was comparable between the CD cohort and controls in both sexes (HR:1.08,95% CI:0.55-2.10 for women;HR:1.57,95% CI:0.57-4.26 for men).CONCLUSION:CD patients have higher prevalence of fractures in the peripheral skeleton before *** is associated with male sex and classic clinical *** fracture risk was reduced after the treatment.

关键词： Celiac disease Fracture risk Peripheralfractures Gluten-free diet Sex difference

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After having changed the treatment of heart failure with reduced ejection fraction: what are the latest evidences with sacubitril valsartan?

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Journal of Geriatric Cardiology 2019年第2期16卷 151-155页

作者： edgardo Kaplinsky Cardiology Unit Department of Medicine Hospital Municipal de Badalona

1 Introduction Sacubitril/valsartan(SV)is a first in class dual action molecule of the neprilysin(NEP)inhibitor prodrug sacubitril(AHU377)and the angiotensin II receptor(Ang-II)type 1 antagonist valsartanJ11 It is the first angiotensin receptor-neprilysin inhibitor(ARNI)whose pharmacodynamic effects are consistent with a simultaneous stimulation of the natriuretic peptides system(via NEP inhibition)and the blockade of the renin-angiotensin-aldosterone system(valsartan effect)that finally results in systemic vasodilation,increased diuresis and natriuresis,reduction of plasmatic volume and diminution of peripheral vascular resistance.

关键词： Heart failure Sacubitril/Valsartan

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Seamount chains and hotspot tracks:Superficially similar,deeply different

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Geoscience Frontiers 2023年第6期14卷 307-326页

作者： edgardo Cañón-Tapia División de Ciencias de la Tierra CICESE.Carretera Ensenada-Tijuana#3985Ensenada Baja CaliforniaCP 22860Mexico

Nearly 80%of the seafloor extension has not been covered by high-resolution bathymetry,impeding direct observation of ***,lists of seamount location and height at a global scale have been produced using different *** this work four of such databases(publicly available)are compared with each other to assess their *** identify large differences among databases that could have exerted strong influences on models of seamount production and associated geodynamic *** those differences,it is shown that all databases allow the identification of seamount lines both along the present-day Mid Ocean Ridge(MOR)system and on intraplate ***,those seamount lines do not coincide with the so-called hotspot tracks that commonly were defined by selectively focusing attention on the larger *** of all the databases also shows that distinction based only on seamount size between seamounts produced at Mid-Ocean Ridge(MOR)environments from those associated with mantle-plum fed-hotspot activity has been ***,combined with the fact that most seamount lines defined by the available databases can be traced back to past locations of MOR indicates that most of the present-day intraplate linear arrays of seamounts,which include some large seamounts,were not produced by the action of underlying mantle anomalies envisaged in the form of mantle *** evidence presented here calls for a reassessment of the form in which volcanic and tectonic activities are conceptually related to each other.

关键词： Seamount origin Chains of seamounts Spatial distribution of volcanism Intraplate volcanism Mid Ocean Ridge volcanism

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Biosorption of mercury by Macrocystis pyrifera and Undaria pinnatifida:Influence of zinc,cadmium and nickel

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Journal of Environmental Sciences 2011年第11期23卷 1778-1786页

作者： Josefina Plaza Marisa Viera edgardo Donati Eric Guibal Centro de Investigacióny Desarrollo en Fermentaciones Industriales CINDEFI (CCT La Plata-CONICET UNLP)Facultad de Ciencias Exactas50 y 115(1900) La PlataArgentina Ecole des Mines d'Ale`s Laboratoire Ge'nie de l'Environnement Industriel6avenue de Clavie`resF-30319 Ale`s cedexFrance Ecole des Mines d‘Ale`s Laboratoire Ge'nie de l‘Environnement Industriel6avenue de Clavie`resF-30319 Ale`s cedexFrance

This study investigated the adsorption of Hg（Ⅱ） on Macrocystis pyrifera and Undaria pinnatifida in monometallic system in the presence of Zn（II）,Cd（Ⅱ） and Ni（II）.The two biosorbents reached the same maximum sorption capacity （q m = 0.8 mmol/g） for *** showed a greater affinity （given by the coefficient b of the Langmuir equation） for mercury compared to *** （4.4 versus 2.7 L/mmol）.Mercury uptake was significantly reduced （by more than 50%） in the presence of competitor heavy metals such as Zn（II）,Cd（II） and Ni（Ⅱ）.Samples analysis using an environmental scanning electron microscopy equipped with an energy dispersive X-ray microanalysis showed that mercury was heterogeneously adsorbed on the surface of both biomaterials,while the other heavy metals were homogeneous *** analysis of biosorbents by Fourier transform infrared spectrometry indicated that Hg（Ⅱ） binding occurred on S=O （sulfonate） and N-H （amine） functional groups.

关键词： mercury isotherm sorption M.pyrifera U.pinnatifida ESEM-EDX FT-IR spectrometry

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Changing the treatment of heart failure with reduced ejection fraction： clinical use of sacubitril-valsartan combination

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Journal of Geriatric Cardiology 2016年第11期13卷 914-923页

作者： edgardo Kaplinsky Cardiology Unit Medicine Department Hospital Municipal de Badalona. Via Augusta Av. 9-13 (08911) Badalona Spain

Despite significant therapeutic advances, patients with chronic heart failure （HF） remain at high risk of morbidity and mortality. Sacubitill valsartan （previously known as LCZ696） is a new oral agent approved for the treatment of symptomatic chronic heart failure in adults with reduced ejection fraction. It is described as the fast in class angiotensin receptor neprilysin inhibitor （ARNI） since it incorporates the neprilysin inhibitor, sacubitril and the angiotensin Ⅱ receptor antagonist, valsartan. Neprilysin is an endopeptidase that breaks down several vasoactive peptides including natriuretic peptides （NPs）, bradykinin, endothelin and angiotensin II （Ang-II）. Therefore, a natural consequence of its inhibition is an increase of plasmatic levels of both, NPs and Ang-Ⅱ （with opposite biological actions）. So, a combined inhibition of these both systems （Sacubitril / valsartan） may enhance the benefits of NPs effects in HF （natriuresis, diuresis, etc） while Ang-Ⅱ receptor is inhibited （reducing vasoconstriction and aldosterone release）. In a large clinical trial （PARADIGM-HF with 8442 patients）, this new agent was found to significantly reduce cardiovascular and all cause mortality as well as hospitalizations due to HF （compared to enalapril）. This manuscript reviews clinical evidence for sacubitril valsartan, dosing and cautions, future directions and its considered place in the therapy of HF with reduced ejection fraction.

关键词： Heart failure LCZ696 Neprilysin PARADIGM-HF Sacubitril Valsartan

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PARADIGM-HF trial： will LCZ696 change the current treatment of systolic heart failure？

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Journal of Geriatric Cardiology 2015年第5期12卷 470-473页

作者： edgardo Kaplinsky Cardiology Unit Medicine Department Hospital Municipal de Badalona Spain

1 Introduction Heart failure （HF） is a global health problem with an estimated prevalence of over 5.8 million in the USA and over 23 million *** represents the most common cause of hospitalization in elderly patients （〉 65 years） and its incidence has a growing trend mainly due to the aging of the population. Neurohumoral activation plays a major role in the pathophysiology. So in consequence, the cornerstone of its medical treatment is based on the inhibition of the renin-angiotensin-aldosterone system （RAAS） and the sympathetic nervous system, According to this, all patients with HF and reduced ejection fraction should be treated with an angiotensin converting enzyme inhibitor （ACEI） or an angiotensin receptor blocker （ARB） plus a beta blocker （BB） and if needed, a mineralocorticoid recep- tor antagonist （MRA）.

关键词： Angiotensin receptor blocker Heart failure LCZ696

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