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

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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

Time-expanded phase-sensitive optical time-domain reflectometry

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Light(Science & Applications) 2021年第3期10卷 443-454页

作者： Miguel Soriano-Amat Hugo F.Martins Vicente Duran Luis costa sonia Martin-Lopez Miguel Gonzalez-Herraez maria R.Fernandez-Ruiz Departamento de Electronica Universidad de AlcalaEscuela Politecnica Superior28805 MadridSpain Instituto deóptica"Daza de Valdes" IO-CSICC/Serrano 12128006 MadridSpain GROC-UJI Institute of New Imaging TechnologiesUniversity Jaume112071 CastellonSpain

Phase-sensitive optical time-domain reflectometry(CDOTDR)is a well-established technique that provides spatiotemporal measurements of an environmental variable in real *** unique capability is being leveraged in an everincreasing number of applications,from energy transportation or civil security to *** date,a wide number of different approaches have been implemented,providing a plethora of options in terms of performance(resolution,acquisition bandwidth,sensitivity or range).However,to achieve high spatial resolutions,detection bandwidths in the GHz range are typically required,substantially increasing the system cost and ***,we present a novel OOTDR approach that allows a customized time expansion of the received optical ***,the presented technique reaches cm-scale spatial resolutions over t km while requiring a remarkably low detection bandwidth in the MHz *** approach relies on the use of dual-comb spectrometry to interrogate the fibre and sample the backscattered *** phase-spectral coding is applied to the employed combs to maximize the signal-to-noise ratio of the sensing scheme.A comparison of the proposed method with alternative approaches aimed at similar operation features is provided,along with a thorough analysis of the new *** results demonstrate a radically novel high-resolution OOTDR scheme,which could promote new applications in metrology,borehole monitoring or aerospace.

关键词： optical phase expanded

Functionalization of AuMSS nanorods towards more effective cancer therapies

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Nano Research 2019年第4期12卷 719-732页

作者： Carolina F. Rodrigues Telma A. Jacinto Andre F. Moreira Elisabete C. costa sonia P. Miguel Ilidio J. Correia CICS-UBI -Centro de Investigagao em Ciencias da Saude Universidade da Beira Interior Covilhd 6200-506 Portugal CIEPQF - Departamento de Engenharia Quimica Universidade de Coimbra Rua 13 Silvio Lima Coimbra 3030-790 Portugal

The applicatio n of nano particles as selective drug delivery platforms arises as one the most promising therapeutic strategies in the biomedical field. Such systems can encapsulate drugs, prevent its premature degradation, transport and promote the drugs specific delivery to the target site. Among the different nanostructures, gold-core mesoporous silica shell (AuMSS) nanorods have been one of the most explored due to their unique physical and chemical properties. The mesoporous silica biocompatibility, high surface area that can be easily functionalized, tubular pores that can store the drugs, conjugated with the intrinsic capacity of gold nanorod to absorb near-infrared radiation, allows the combination of hyperthermia (i.e., photothermal effect) with drug delivery, making them a nanoplatforms with a huge potential for cancer therapy. Nevertheless, the successful applicati on of AuMSS nanoparticles as an effective can cer nano medicine is hindered by the uncon trolled release of the therapeutic payloads, limited blood circulation time and unfavorable pharmacokinetics. In this review, an overview of the modificati ons performed to improve the AuMSS nano rods applicati on in nanom edicine is provided, highlighting the practical approaches that enhaneed the AuMSS nanorods targeting, responsiveness to different stimuli, and blood circulation time. Further, the basics of AuMSS nano rods syn thesis procedures, gen eral properties, and its applicati on in can cer therapy are also described.

关键词： gold nano rods silica surface modifications targeting cancer

Gastrointestinal manifestations in myotonic muscular dystrophy

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World Journal of Gastroenterology 2006年第12期12卷 1821-1828页

作者： Massimo Bellini sonia Biagi Cristina Stasi Francesco costa maria Gloria Mumolo Angelo Ricchiuti Santino Marchi Gastroenterology Unit Department of Internal MedicineUniversity of PisaItaly

Myotonic (MD ) 被肌强直的现象和进步肌肉发达的软弱描绘。胃肠道的参与是经常的并且可以发生在任何水平。临床的表明以前被归因于改变的平滑肌损坏，而是 histologic 证据引起的活动性混乱少见、冲突。一个神经因素也被假设了。，在... 详细信息

Myotonic (MD ) 被肌强直的现象和进步肌肉发达的软弱描绘。胃肠道的参与是经常的并且可以发生在任何水平。临床的表明以前被归因于改变的平滑肌损坏，而是 histologic 证据引起的活动性混乱少见、冲突。一个神经因素也被假设了。，在更低的道在上面的消化道，咽下困难，心痛，流回和消化不良是最普通的抱怨，腹的疼痛，膨胀并且在肠习惯的变化经常被报导。消化症状可以是营养不良的疾病的第一症状并且可以先于肌与骨的特征。胃肠的功能的缺陷可能有时是那么渐渐的病人与症状的很少了解适应它。不在内视镜的如此的情况常规和 ultrasonographic 评估是足够、指向的技术(胃电描记法，测压法，肌电描记法，功能的 ultrasonography， scintigraphy，等等) 被需要。而与骨胳的肌肉疾病的持续时间的积极关联被报导了，在胃肠的骚乱的骨胳的肌肉参与和存在和严厉的度之间有低关联。这些药为对待象专业版那样的胃肠的抱怨推荐了运动的、反消化不良的药和 laxatives，主要针对改正活动性混乱。自从许多重要问题仍然是未解决的，在 MD 的胃肠的参与仍然是一个复杂、吸引人的条件。专注于基因方面，早诊断的技术和新治疗学的策略的发展的进一步的研究被需要改进我们 MD 的胃肠的表明的管理。

关键词：肌肉营养不良胃肠疾病强直肌肉临床表现

Exosomal glypican-1 is elevated in pancreatic cancer precursors and can signal genetic predisposition in the absence of endoscopic ultrasound abnormalities

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World Journal of Gastroenterology 2022年第31期28卷 4310-4327页

作者： Pedro Moutinho-Ribeiro Ines A Batista Sofia T Quintas Bárbara Adem Marco Silva Rui Morais Armando Peixoto Rosa Coelho Pedro costa-Moreira Renato Medas Susana Lopes Filipe Vilas-Boas Manuela Baptista Diogo Dias-Silva Ana L Esteves Filipa Martins Joanne Lopes Helena Barroca Fátima Carneiro Guilherme Macedo sonia A Melo Serviço de Gastrenterologia Centro Hospitalar Universitário de Sao JoaoPorto 4200Portugal Faculty of Medicine University of PortoPorto 4200Portugal Instituto de Investigacao e Inovacao em Saúde(i3S) Universidade do PortoPorto 4200Portugal IPATIMUP-Institute of Molecular Pathology and Immunology University of PortoPorto 4200Portugal Instituto de Ciencias Biomédicas Abel Salazar(ICBAS) University of PortoPorto 4050Portugal Servico de Cirurgia Geral Centro Hospitalar Universitário de Sao JoaoPorto 4200Portugal Unidade de Saúde Familiar Serpa Pinto ACeS Porto OcidentalPorto 4250Portugal Serviço de Anatomia Patológica Centro Hospitalar Universitário de Sao JoaoPorto 4200Portugal

BACKGROUND Individuals within specific risk groups for pancreatic ductal adenocarcinoma(PDAC)[mucinous cystic lesions(MCLs),hereditary risk(HR),and new-late onset diabetes mellitus(NLOD)]represent an opportunity for early cancer *** ultrasound(EUS)is a premium image modality for PDAC screening and precursor lesion *** no specific biomarker is currently clinically available for this purpose,glypican-1(GPC1)is overexpressed in the circulating exosomes(crExos)of patients with PDAC compared with healthy subjects or those harboring benign pancreatic *** To evaluate the capacity of GPC1+crExos to identify individuals at higher risk within these specific groups,all characterized by *** This cross-sectional study with a prospective unicentric cohort included 88 subjects:40 patients with MCL,20 individuals with HR,and 20 patients with NLOD.A control group(CG)was submitted to EUS for other reasons than pancreatic pathology,with normal pancreas and absence of hereditary risk factors(n=8).The inclusion period was between October 2016 and January 2019,and the study was approved by the Ethics Committee of Centro Hospitalar Universitário de São João,Porto,*** patients provided written informed *** and blood tests for quantification of GPC1+crExos by flow cytometry and carbohydrate antigen 19-9(CA 19-9)levels by ELISA were performed in all ***-guided tissue acquisition was done whenever *** statistical analysis,SPSS®27.0(IBM Corp.,Armonk,NY,United States)version was *** graphs were created using GraphPad Prism 7.00(GraphPad Software,San Diego,CA,United States).RESULTS Half of MCLs harbored worrisome features(WF)or high-risk stigmata(HRS).Pancreatic abnormalities were detected by EUS in 10.0%and 35.0%in HR and NLOD individuals,respectively,all considered non-malignant and“harmless.”Median levels of GPC1+crExos were statistically different:MCL[99.4%,interquartile range(IQR):94.9%-99.8%],HR(8

关键词： Glypican-1 Circulating exosomes Endoscopic ultrasound Pancreatic cancer risk groups Pancreatic cancer precursor lesions Genetic predisposition

Whey Protein-Carboxymethylcellulose Obtained by Complex Coacervation as an Ingredient in Probiotic Fermented Milk

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Food and Nutrition Sciences 2015年第6期6卷 571-580页

作者： maria Elisa Caetano-Silva Caroline Dá rio Capitani Adriane Elisabete costa Antunes Erna Vougt Vera sonia Nunes da Silva maria Teresa Bertoldo Pacheco Faculty of Food Engineering University of Campinas Campinas Brazil School of Applied Sciences University of Campinas Limeira Brazil Food Science and Technology Institute Federal University of Rio Grande do Sul Porto Alegre Brazil Chemistry Center of Food and Applied Nutrition Institute of Food Technology (ITAL) Campinas Brazil

Discharge of whey proteins is still a current practice by small cheese producers. The development of low-cost alternatives for recovery of these proteins is fundamental for small producers who cannot apply expensive techniques. The present study investigated the complex coacervation technique as a cheap technology to recover proteins from sweet whey using carboxymethylcellulose, and the coacervate used as an ingredient in the formulation of probiotic fermented milk. The nutritional properties of whey-carboxymethylcellulose coacervates (WP-CMC) were evaluated in trials with animals (rats) using casein as a reference. All these parameters—the coefficient of feed efficiency (CEA), protein digestibility-corrected amino acid score (PDCAAS), and net protein ratio (NPR), as well as weight gain—were determined to evaluate protein quality. A sensory acceptance test was applied to evaluate the sensory characteristics of the product. The complex coacervation technique recovered 86% of the protein from sweet whey. No significant (p > 0.05) differences were observed in the biological tests for both groups (WP-CMC and Casein groups) when NPR (4.98 to 5.04), digestibility (92.35 to 90.64), and CEA (0.40 to 0.42) were evaluated. Probiotic fermented milk beverage containing WP-CMC (0.78%) and guar gum (0.68%) presented good acceptability as determined by sensory evaluation. WP-CMC can be considered an ingredient with high nutritional and biological value that could be applied in probiotic fermented milk as an alternative to small producers to allocate the residual whey from cheese manufacture.

关键词： Nutritional Value Whey Proteins Complex Coacervation Probiotic Fermented Milk Environmental Impact

Abnormal Linguistic Lateralization and Sensory Processing in High Functioning Children with Autism Spectrum Conditions

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Journal of Behavioral and Brain Science 2014年第9期4卷 432-442页

作者： sonia Martínez-Sanchis María Consuelo Bernal Ana costa Marien Gadea Department of Psychobiology University of Valencia Valencia Spain Neurodevelopmental Disorders Research Unit University of Valencia Valencia Spain Department of Social Psychology University of Valencia Valencia Spain IDOCAL University of Valencia Valencia Spain Pediatric Neurorehabilitation Unit Hospital of Manises Valencia Spain

Brain lateralization for language in high-functioning children with autism spectrum conditions (ASC) and sensory processing were explored as a part of a neuropsychological profile. A dichotic listening test and the Luria laterality subtest were administered to all participants (including controls) and the sensory profile test only to the ASC group. The usual right ear advantage was not exhibited by children with ASC and anomalies in auditory filtering were found. The sensory profile of 60% of the sample was characterized by hypersensitivity to auditory stimuli, hyposensitivity to vestibular information, high emotional reactions to sensory experiences, poor psychosocial coping strategies, high distractibility and inability to interpret body and facial language. Hyper-responsiveness to environmental auditory stimuli was significantly associated with impaired attention. Similarly, non-adaptive responses to sensory quotidian experiences were strongly connected to poor coping strategies. Our results, although preliminary, contribute to emphasizing the importance of including additional assessment methods such as the dichotic listening and the sensory profile questionnaire in the evaluation of cognitive profile in high-functioning children with ASC to plan an individualized psycho-educative intervention.

关键词： Children High-Functioning Autism Linguistic Lateralization Neuropsychology Sensory Profile

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

CTNS Molecular Genetics Profile in a Portuguese Cystinosis Population

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Open Journal of Genetics 2018年第4期8卷 91-100页

作者： Filipa Ferreira Ines Leal David Sousa Teresa costa Conceicao Mota Ana Marta Gomes Daniela Lopes maria do Carmo Macario Isabel Tavares Helena Pinto Joao Paulo Oliveira Rita Magrico Celia Carmona sonia Ramos Raquel Neiva Ana Marcao Laura Vilarinho Newborn Screening Metabolism and Genetics UnitHuman Genetics DepartmentNational Institute of Health Dr Ricardo JorgePortoPortugal Centro Hospitalar Lisboa Norte Hospital de Santa MariaLisboaPortugal Centro Hospitalar Universitario do Porto PortoPortugal Centro Hospitalar Vila Nova de Gaia EspinhoPortugal Centro Hospitalar Universitario de Coimbra CHUCCoimbraPortugal Servico de Genetica Medica Centro Hospitalar de Sao JoaoPortoPortugal Unidade de Genetica Faculdade de Medicina da Universidade do PortoPortoPortugal I3S—Instituto de Investigacao e Inovacao em Saude PortoPortugal Servico de Nefrologia do Hospital Garcia de Orta AlmadaPortugal Research and Development Unit Department of Human GeneticsNational Institute of Health Dr Ricardo JorgePortoPortugal

Background: Cystinosis is a multisystemic autosomal recessive deficiency of the lysosomal membrane transporter protein (cystinosin) caused by mutations in CTNS gene. Objective: This study summarizes the Portuguese experience in the diagnosis and management of patients with this rare disease over the past few years and reports recurrent mutations in the CTNS gene. Methods: Unrelated patients from different pediatric and adult hospitals all over Portugal with non-nephrotic proteinuria, hypercalciuria, hypokalemia impaired proximal reabsorption of amino acids, glycosuria and hypophosphatemia, suggestive of a Fanconi syndrome and ocular problems, were studied. Intra-leukocyte cystine levels were determined and molecular analysis was performed, to determine the presence or absence of the 57-kb deletion in CTNS, followed by direct sequencing of the coding exons of CTNS. Results: From 1998 to 2017, twenty-one cystinotic patients were biochemically diagnosed. From the remaining seventeen (four deceased), eleven were studied for CTNS gene. Five out of eleven patients were homozygous for the 57-kb deletion (10/22;45.5%), and other five were compound heterozygous for this variant (15/22;68.2%). The other mutations found were p.Q128X (c.721 C>T;2/22), p.S139F (c.755 C>T;4/22) and c.18-21delGACT (p.T7FfsX7;1/22). All of these seventeen cystinotic patients are in treatment. Approximately 84% are adults, 16% are young children, and 54.5% are kidney transplant recipient. Conclusions: The authors would like to emphasize the importance of first screening for the 57-kb deletion since it is very common in our population. This genetic study is the first in our country and it could be the basis for future genetic counseling in Portuguese population.

关键词： Cystinosis CTNS Gene Mutational Spectrum Kidney Failure 57-kb Deletion