Original article
Ex vivo evaluation of adhesive strength and barrier effect of a novel treatment for esophagitis
Evaluación ex vivo de la fuerza adhesiva y el efecto barrera de un nuevo tratamiento para la esofagitis
Yeray Brito-Casillasa,b,
, María José Caballeroc, Luisa Hernández-Barazaa, Rosa María Sánchez-Hernándeza,d, Juan Carmelo Betancort-Acostad, Ana M. Wägnera,b,d
Corresponding author
a Instituto Universitario de Investigaciones Biomédicas y Sanitarias, Universidad de Las Palmas de Gran Canaria, Las Palmas de Gran Canaria, Spain
b Strategos BioTech SL, Teide, Spain
c Instituto Universitario de Sanidad Animal, Universidad de Las Palmas de Gran Canaria, Las Palmas de Gran Canaria, Spain
d Servicio de Endocrinología y Nutrición, Complejo Hospitalario Universitario Insular Materno-Infantil de Gran Canaria, Las Palmas de Gran Canaria, Spain
Read
367
Timeswas read the article
104
Total PDF
263
Total HTML
Share statistics
array:23 [ "pii" => "S0210570522002540" "issn" => "02105705" "doi" => "10.1016/j.gastrohep.2022.10.013" "estado" => "S300" "fechaPublicacion" => "2023-06-01" "aid" => "2006" "copyright" => "Elsevier España, S.L.U.. All rights reserved" "copyrightAnyo" => "2022" "documento" => "article" "crossmark" => 1 "subdocumento" => "fla" "cita" => "Gastroenterol Hepatol. 2023;46:455-61" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "itemSiguiente" => array:19 [ "pii" => "S0210570522001443" "issn" => "02105705" "doi" => "10.1016/j.gastrohep.2022.04.003" "estado" => "S300" "fechaPublicacion" => "2023-06-01" "aid" => "1939" "copyright" => "Elsevier España, S.L.U." "documento" => "simple-article" "crossmark" => 1 "subdocumento" => "crp" "cita" => "Gastroenterol Hepatol. 2023;46:462-6" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "es" => array:11 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Carta científica</span>" "titulo" => "Colangitis esclerosante secundaria: una complicación tras la infección severa por COVID-19" "tienePdf" => "es" "tieneTextoCompleto" => "es" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "462" "paginaFinal" => "466" ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "Secondary sclerosing cholangitis: A complication after severe COVID-19 infection" ] ] "contieneTextoCompleto" => array:1 [ "es" => true ] "contienePdf" => array:1 [ "es" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figura 1 Valores de GGT en la evolución de los casos" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1037 "Ancho" => 1675 "Tamanyo" => 133049 ] ] "descripcion" => array:1 [ "es" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Nazaret María Pizarro Vega, Paz Valer Lopez-Fando, Gema de la Poza Gómez, Belén Piqueras Alcol, Marina Gil Santana, Paloma Ruiz Fuentes, Marcos Alfredo Rodríguez Amado, Fernando Bermejo San José" "autores" => array:8 [ 0 => array:2 [ "nombre" => "Nazaret María" "apellidos" => "Pizarro Vega" ] 1 => array:2 [ "nombre" => "Paz" "apellidos" => "Valer Lopez-Fando" ] 2 => array:2 [ "nombre" => "Gema" "apellidos" => "de la Poza Gómez" ] 3 => array:2 [ "nombre" => "Belén" "apellidos" => "Piqueras Alcol" ] 4 => array:2 [ "nombre" => "Marina" "apellidos" => "Gil Santana" ] 5 => array:2 [ "nombre" => "Paloma" "apellidos" => "Ruiz Fuentes" ] 6 => array:2 [ "nombre" => "Marcos Alfredo" "apellidos" => "Rodríguez Amado" ] 7 => array:2 [ "nombre" => "Fernando" "apellidos" => "Bermejo San José" ] ] ] ] ] "idiomaDefecto" => "es" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S2444382423000895" "doi" => "10.1016/j.gastre.2022.04.011" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2444382423000895?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0210570522001443?idApp=UINPBA00004N" "url" => "/02105705/0000004600000006/v2_202306121247/S0210570522001443/v2_202306121247/es/main.assets" ] "itemAnterior" => array:18 [ "pii" => "S0210570522002527" "issn" => "02105705" "doi" => "10.1016/j.gastrohep.2022.10.011" "estado" => "S300" "fechaPublicacion" => "2023-06-01" "aid" => "2004" "copyright" => "Elsevier España, S.L.U." "documento" => "article" "crossmark" => 1 "subdocumento" => "fla" "cita" => "Gastroenterol Hepatol. 2023;46:446-54" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original article</span>" "titulo" => "Prognostic implications of systolic function in patients with cirrhosis" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "446" "paginaFinal" => "454" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Implicaciones pronósticas de la función sistólica en pacientes con cirrosis" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1490 "Ancho" => 1508 "Tamanyo" => 84674 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Primary endpoint of the study. Kaplan–Meier survival analysis for the incidence of the primary endpoint (any-cause mortality or liver transplantation).</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Ana González-Mansilla, Irene Castellote-Domínguez, Sara Fernández-Quintanilla, Pablo Martínez-Legazpi, Cristina Ripoll, Maria Vega Catalina, Diego Rincón, Francisco Fernández-Avilés, Rafael Bañares, Javier Bermejo" "autores" => array:10 [ 0 => array:2 [ "nombre" => "Ana" "apellidos" => "González-Mansilla" ] 1 => array:2 [ "nombre" => "Irene" "apellidos" => "Castellote-Domínguez" ] 2 => array:2 [ "nombre" => "Sara" "apellidos" => "Fernández-Quintanilla" ] 3 => array:2 [ "nombre" => "Pablo" "apellidos" => "Martínez-Legazpi" ] 4 => array:2 [ "nombre" => "Cristina" "apellidos" => "Ripoll" ] 5 => array:2 [ "nombre" => "Maria" "apellidos" => "Vega Catalina" ] 6 => array:2 [ "nombre" => "Diego" "apellidos" => "Rincón" ] 7 => array:2 [ "nombre" => "Francisco" "apellidos" => "Fernández-Avilés" ] 8 => array:2 [ "nombre" => "Rafael" "apellidos" => "Bañares" ] 9 => array:2 [ "nombre" => "Javier" "apellidos" => "Bermejo" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0210570522002527?idApp=UINPBA00004N" "url" => "/02105705/0000004600000006/v2_202306121247/S0210570522002527/v2_202306121247/en/main.assets" ] "en" => array:20 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original article</span>" "titulo" => "<span class="elsevierStyleItalic">Ex vivo</span> evaluation of adhesive strength and barrier effect of a novel treatment for esophagitis" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "455" "paginaFinal" => "461" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Yeray Brito-Casillas, María José Caballero, Luisa Hernández-Baraza, Rosa María Sánchez-Hernández, Juan Carmelo Betancort-Acosta, Ana M. Wägner" "autores" => array:6 [ 0 => array:4 [ "nombre" => "Yeray" "apellidos" => "Brito-Casillas" "email" => array:1 [ 0 => "yeray.brito@ulpgc.es" ] "referencia" => array:3 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] 2 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "María José" "apellidos" => "Caballero" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] 2 => array:3 [ "nombre" => "Luisa" "apellidos" => "Hernández-Baraza" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 3 => array:3 [ "nombre" => "Rosa María" "apellidos" => "Sánchez-Hernández" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">d</span>" "identificador" => "aff0020" ] ] ] 4 => array:3 [ "nombre" => "Juan Carmelo" "apellidos" => "Betancort-Acosta" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">d</span>" "identificador" => "aff0020" ] ] ] 5 => array:3 [ "nombre" => "Ana M." "apellidos" => "Wägner" "referencia" => array:3 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] 2 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">d</span>" "identificador" => "aff0020" ] ] ] ] "afiliaciones" => array:4 [ 0 => array:3 [ "entidad" => "Instituto Universitario de Investigaciones Biomédicas y Sanitarias, Universidad de Las Palmas de Gran Canaria, Las Palmas de Gran Canaria, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Strategos BioTech SL, Teide, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Instituto Universitario de Sanidad Animal, Universidad de Las Palmas de Gran Canaria, Las Palmas de Gran Canaria, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Servicio de Endocrinología y Nutrición, Complejo Hospitalario Universitario Insular Materno-Infantil de Gran Canaria, Las Palmas de Gran Canaria, Spain" "etiqueta" => "d" "identificador" => "aff0020" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Evaluación <span class="elsevierStyleItalic">ex vivo</span> de la fuerza adhesiva y el efecto barrera de un nuevo tratamiento para la esofagitis" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 447 "Ancho" => 1340 "Tamanyo" => 85114 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Cranial oesophageal sections. Tissue sections from the cranial oesophageal mucosa (haematoxylin–eosin). (A) 4× magnification and (B) 10× magnification. Both images show a focal loss of epithelium and the damage of the remaining fractions.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0155" class="elsevierStylePara elsevierViewall">Gastro-oesophageal reflux disease (GERD) is a frequent clinical problem, associated with a negative impact on quality of life.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,2</span></a> GERD is defined as gastro-esophageal reflux that results in disturbing symptoms, like pyrosis or regurgitation, or complications like esophagitis.<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3,4</span></a> The symptoms of GERD are common, and its growing prevalence can reach 30% according to some reports, and the presence of esophagitis, erosion or ulceration is detected in at least one-third of the patients suffering from this condition.<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3–6</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Among the different pharmacological treatments for GERD, surface agents act by protecting the mucosal surface of the stomach and oesophagus from the acidic environment and can be indicated for the alleviation of symptoms.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Esophacare (Atika Pharma SL) is a drinkable liquid formula designed to exert a protective and restorative action in patients with esophagitis. Esophacare is composed by water, aloe vera gel (AVG) (<span class="elsevierStyleItalic">Aloe barbandesis</span>, Miller), hyaluronic acid (HA), chondroitin sulfate (CS), vitamin C and arabic gum. AVG has shown anti-inflammatory and wound healing activities<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> and appropriate physical properties.<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8–10</span></a> HA is effective against oral ulcers,<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> and with CS, are natural glycosaminoglycans involved in wound healing.<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">12–15</span></a> Vitamin C (<span class="elsevierStyleSmallCaps">l</span>-ascorbic acid) stimulates collagen synthesis and enhances the production of barrier lipids against physical abrasion <span class="elsevierStyleItalic">in vitro</span>.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">The <span class="elsevierStyleItalic">ex vivo</span> model Falling Liquide Film Technique (FLFT) on animal esophagi, is an accepted model of GERD that allows the mucoadhesion and the barrier effect evaluations, with similar tissue damaging characteristics.<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">12–18</span></a> Therefore, we evaluated Esophacare following the FLFT in porcine esophagi.</p><p id="par0025" class="elsevierStylePara elsevierViewall">The aim of this study was to assess the efficacy of Esophacare in an <span class="elsevierStyleItalic">ex vivo</span> model of esophagitis.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Material and methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Tested formulations</span><p id="par0030" class="elsevierStylePara elsevierViewall">The studied formulations were Esophacare® (E), Ziverel® (Z) as positive control, and distilled water (C) as negative control. Z was bought in a local pharmacy; E was provided by the manufacturer. Ziverel® is an oral treatment solution for GERD, developed by Norgine B.V., and mainly composed by HA, CS and poloxamer 407, a thickener. To overcome their lack of colour, products were stained with methylene blue for macroscopic evaluation (5<span class="elsevierStyleHsp" style=""></span>mg:2<span class="elsevierStyleHsp" style=""></span>g) (Panreac-Applichem).<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">12–18</span></a></p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Tissue specimens</span><p id="par0035" class="elsevierStylePara elsevierViewall">Porcine esophagi were obtained from freshly sacrificed pigs (Landrace, 20–30<span class="elsevierStyleHsp" style=""></span>kg) and transported on ice in a humidity chamber. Some were used directly and the rest frozen (−20<span class="elsevierStyleHsp" style=""></span>°C).<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> These latter were defrosted overnight (4<span class="elsevierStyleHsp" style=""></span>°C). The mucous layer was briefly clean with refrigerated saline (Fisiovet; B-Braun-VetCare) of gross materials (rest of food and blood) and were examined for injuries that could interfere in the evaluations. The muscular part and annexes were dissected. The mucous was briefly rinsed with refrigerated saline.<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">12–18</span></a> For each experimental replicate, three adjacent specimens from the same oesophagus (1–1.5<span class="elsevierStyleHsp" style=""></span>cm<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>15–25<span class="elsevierStyleHsp" style=""></span>cm) were included, one per treatment.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Falling Liquide Film Technique experiments</span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Research conditions</span><p id="par0040" class="elsevierStylePara elsevierViewall">Treatments (E, Z, C) were distributed over specimens and simultaneously washed in triplicate (one experiment: three triplicates) (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>). Specimens were set in cranio-caudal orientation, at 35° above the horizontal, 37<span class="elsevierStyleHsp" style=""></span>°C, 90% RH and 100<span class="elsevierStyleHsp" style=""></span>rpm.<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">12–25</span></a> Products were washed (2<span class="elsevierStyleHsp" style=""></span>mL/min) for 30 or 60<span class="elsevierStyleHsp" style=""></span>min, depending on the procedure, with saline (Fisiovet; B-Braun-VetCare), acid-solution (HCl) (acidified saline 0.1<span class="elsevierStyleHsp" style=""></span>M HCl,pH = 1.2-1.5; HCl 35–38%, LabKem-Labbox) or acid-solution with pepsin (HCl<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>pepsin) (acidified saline with pepsin 2000<span class="elsevierStyleHsp" style=""></span>U/mL; 0.7<span class="elsevierStyleHsp" style=""></span>FIP-U/mg; Panreac-Applichem).<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">12–18</span></a> After optimization, 1<span class="elsevierStyleHsp" style=""></span>μL was established as optimal to evaluate the adhesive strength and 1<span class="elsevierStyleHsp" style=""></span>mL to measure the persistence area and barrier effect.</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Procedure A: mucoadhesive adhesive strength</span><p id="par0045" class="elsevierStylePara elsevierViewall">Twenty-five product samples (1<span class="elsevierStyleHsp" style=""></span>μL) were arranged over the mucosa (25<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">N</span><span class="elsevierStyleInf">0</span>). After washing, the remaining samples were counted (<span class="elsevierStyleItalic">N</span><span class="elsevierStyleInf">s</span>). The mucoadhesive strength (%) was calculated: <span class="elsevierStyleItalic">N</span><span class="elsevierStyleInf">0</span>/<span class="elsevierStyleItalic">N</span><span class="elsevierStyleInf">s</span><span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>100.<a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">18–22</span></a></p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Procedure B: persistence area quantification</span><p id="par0050" class="elsevierStylePara elsevierViewall">After each product application (1<span class="elsevierStyleHsp" style=""></span>mL), the covered area was photographed before (initial area<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">A</span><span class="elsevierStyleInf">0</span>) and after washing (final area<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">A</span><span class="elsevierStyleInf">F</span>). Images were analyzed (FIJI extension, ImageJ software)<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a> and areas were confronted (<span class="elsevierStyleItalic">A</span><span class="elsevierStyleInf">0</span><span class="elsevierStyleHsp" style=""></span>−<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">A</span><span class="elsevierStyleInf">F</span>, cm<span class="elsevierStyleSup">2</span>; 100<span class="elsevierStyleHsp" style=""></span>−<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">A</span><span class="elsevierStyleInf">F</span>, %).<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a></p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Procedure C: barrier effect estimation</span><p id="par0055" class="elsevierStylePara elsevierViewall">After HCl<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>pepsin washing (30<span class="elsevierStyleHsp" style=""></span>min), the specimens were fixed (buffered-formalin, 4%, Applichem-Panreac) maintaining their orientation. The samples were assessed in the Veterinary Pathology Service (ULPGC). Two tissue fractions were collected from each sample (cranial/caudal), paraffin embedded and haematoxylin-eosin stained.<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">27</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">Once processed, the histological sections were randomly chosen and blindly evaluated, by an experienced pathologist (MJC). Initially, the area of interest was defined (cranial or caudal) to determine the barrier effect. Secondly, the severity and the extension of the injuries were estimated, and images were acquired (5× magnification; BX51, Olympus-Corp.).</p></span></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Statistical analysis</span><p id="par0065" class="elsevierStylePara elsevierViewall">Results were presented as mean (SD) or median [min-max], depending on whether normal or non-normal distribution. Student's-<span class="elsevierStyleItalic">t</span> or Mann–Whitney's <span class="elsevierStyleItalic">U</span> tests were used for comparisons (two tailed <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.05 considered significant) (IBM-SPSS Statistics 20, SPSS Inc.).</p></span></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Results</span><p id="par0070" class="elsevierStylePara elsevierViewall">Sixty-three tissue specimens were evaluated, 27 per procedures A and B, and 9 in procedure C.</p><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Procedure A: mucoadhesive adhesive strength</span><p id="par0075" class="elsevierStylePara elsevierViewall">E shows an overall adhesive strength of 94.7% (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>). The global strength of E did not differ between both acid solutions (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.37), but was higher after saline washing, reaching 100% of adhesive strength (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.046). No statistical differences were found for the strength between cranial and caudal oesophagus (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.69).</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0080" class="elsevierStylePara elsevierViewall">In contrast, Z shows a lower global adhesive strength of 27.6% (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.001), for all the washings and oesophageal regions (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.05), compared to E (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>).</p><p id="par0085" class="elsevierStylePara elsevierViewall">Regarding the negative control, instead of reflecting adherence, it stained the mucosa. This control was included in agreement to previous authors’ methodology.<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> However, to avoid misinterpretation, it was excluded from the analysis (procedures A and B). Besides, a specific evaluation was performed to clarify this, where a staining of the tissue (not adherence) by the negative control was confirmed (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Procedure B: persistence area quantification</span><p id="par0090" class="elsevierStylePara elsevierViewall">No differences were found among the initial surface covered by any of the products (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>0.96). Globally, E shows higher persistence than Z, under all conditions (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>).</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Procedure C: barrier effect estimation</span><p id="par0095" class="elsevierStylePara elsevierViewall">Initially when the area of interest was defined, two very divergent histological scenarios between the cranial and caudal sections were observed. The first, exposed to the initial fall of the washing (HCl<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>pepsin) showed multifocal areas with disappeared epithelium (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>). In the caudal region, the epithelium was more preserved but nonetheless showed injuries (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>): detachment of the epithelium, separated apical layers of epidermis, disintegration of the epithelium outer layers, and thickness of epithelium. Besides, focal cavitated areas and loss of epithelial cell cohesion is observed in lower layers of mucosa. This could be attributed to varied degree of a permeabilization. A descriptive evaluation of severity and extension of the lesions was performed, and representative images of the histological sections were obtained (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>).</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0100" class="elsevierStylePara elsevierViewall">The disintegration of the outer layer of the epithelium was the greatest injury to illustrate this analysis. Tissue sections showed a largely homogeneous response between product replicates. In general, the tissues treated with Z and C showed more injuries and lost their normal architecture. Those with E were not exempt from damage, but the epithelium was thicker and more preserved. The superficial layers remained united among replicates and the cavitary areas were more superficial and less extensive (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>).</p></span></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Discussion</span><p id="par0105" class="elsevierStylePara elsevierViewall">Using an <span class="elsevierStyleItalic">ex vivo</span> model of GERD, the present study shows that E displays high adhesive strength and persistence, as well as a barrier effect on the mucosa. In contrast, the positive control exhibited worse performance.</p><p id="par0110" class="elsevierStylePara elsevierViewall">The strength of this study is the minimization of the interferences on each procedure, performed in triplicate, with adjoining sections of the same organ, to test products simultaneously under similar conditions. In each triplicate, the treatments were applied in rotating order for the three specimens. The <span class="elsevierStyleItalic">ex vivo</span> conditions were adapted aiming to approach them to those of the clinical application.<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">12–23</span></a> In line with this, previous studies left the product acting on the mucosa to adhere for variable periods (5–30<span class="elsevierStyleHsp" style=""></span>min). The present procedures were assessed immediately. In addition, previous authors determine adhesive strength only for saline washing,<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> here, acidified solutions were included, and have expressed a mean global value for this strength for more realistic determinations. For the persistence area, a quantification through image analysis software was also included to increase accuracy.<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">17,26</span></a> Finally, the histological assessment was blinded for the different treatments and washing solutions.</p><p id="par0115" class="elsevierStylePara elsevierViewall">Despite the methodological aspects considered, we acknowledge that the main limitation is the lack of an adequate negative control. This limitation was not detected during the performance, until subsequent analysis, as procedures A and B were performed at once in a short period of time. However, previous studies have not reported this issue (in text or photo), though the addition of methylene blue to the negative control is common.</p><p id="par0120" class="elsevierStylePara elsevierViewall">The preclinical soundness of the present <span class="elsevierStyleItalic">ex vivo</span> model has been validated in subsequent clinical trials<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">12–28</span></a> and many of the main components of surface agents for GERD, have been evaluated by FLFT.<a class="elsevierStyleCrossRefs" href="#bib0095"><span class="elsevierStyleSup">19–22</span></a> In the present study, the effectiveness and superiority of E <span class="elsevierStyleItalic">versus</span> Z was evidenced during the FLFT, for all the conditions, what was also confirmed histologically.</p><p id="par0125" class="elsevierStylePara elsevierViewall">Z is used as a liquid treatment in patients with GERD, that shares components of similar formulations, as HA and CS, and its adherence capacity is based on the use of poloxamer 407. Z was utilized as positive control due to the shared components, indication and availability. In the case of E, the main differentiating ingredients with respect to the Z formula are AVG, vitamin C and Arabic gum. The superior adhesive capacity in the case of E might be explained by individual or by the joint interaction of the described ingredients, however specific studies are needed.</p><p id="par0130" class="elsevierStylePara elsevierViewall">The histological findings provide an idea of the protection exerted by E. If used in patients with oesophagitis, mucosal healing could be facilitated by the protection exerted by this product. However, this <span class="elsevierStyleItalic">ex vivo</span> evaluation do not consider the full effects of the products assessed and is focused on some mechanisms. These experiments aim to mimic what happens <span class="elsevierStyleItalic">in vivo</span> but cannot replace randomized clinical trials.</p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Conclusions</span><p id="par0135" class="elsevierStylePara elsevierViewall">Based on the results obtained, E shows an adhesive strength close to 100%, irrespective of the washing solution applied or the oesophageal region studied. Furthermore, the persistence area after the washing solutions, was also high (74.29% of the initially covered area), and this value was not affected by the different washing solutions used. Finally, histologically, E reduces the abrasive effects of the acidic solution on the oesophageal epithelium, preserving its thickness and the integrity of its apical layers, as well as reducing permeability to the washing solution. The results in this <span class="elsevierStyleItalic">ex vivo</span> model of GERD support the potential of E as a treatment for this disease.</p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Funding</span><p id="par0140" class="elsevierStylePara elsevierViewall">This work was requested and funded by Atika Pharma SL.</p></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0150">Conflict of interest</span><p id="par0145" class="elsevierStylePara elsevierViewall">The authors designed and performed the experiments, analysed the results and wrote the manuscript. The funders approved the study protocol and participated in the decision to publish the results. They had no role in the performance of the experiments, the analysis of the results or the preparation of the manuscript.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:13 [ 0 => array:3 [ "identificador" => "xres1911798" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Aim" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1651085" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1911797" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Objetivo" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1651084" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Material and methods" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Tested formulations" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Tissue specimens" ] 2 => array:3 [ "identificador" => "sec0025" "titulo" => "Falling Liquide Film Technique experiments" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0030" "titulo" => "Research conditions" ] 1 => array:2 [ "identificador" => "sec0035" "titulo" => "Procedure A: mucoadhesive adhesive strength" ] 2 => array:2 [ "identificador" => "sec0040" "titulo" => "Procedure B: persistence area quantification" ] 3 => array:2 [ "identificador" => "sec0045" "titulo" => "Procedure C: barrier effect estimation" ] ] ] 3 => array:2 [ "identificador" => "sec0050" "titulo" => "Statistical analysis" ] ] ] 6 => array:3 [ "identificador" => "sec0055" "titulo" => "Results" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0060" "titulo" => "Procedure A: mucoadhesive adhesive strength" ] 1 => array:2 [ "identificador" => "sec0065" "titulo" => "Procedure B: persistence area quantification" ] 2 => array:2 [ "identificador" => "sec0070" "titulo" => "Procedure C: barrier effect estimation" ] ] ] 7 => array:2 [ "identificador" => "sec0075" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0080" "titulo" => "Conclusions" ] 9 => array:2 [ "identificador" => "sec0085" "titulo" => "Funding" ] 10 => array:2 [ "identificador" => "sec0090" "titulo" => "Conflict of interest" ] 11 => array:2 [ "identificador" => "xack670714" "titulo" => "Acknowledgements" ] 12 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2022-06-14" "fechaAceptado" => "2022-10-14" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1651085" "palabras" => array:4 [ 0 => "Gastro-oesophageal reflux disease (GERD)" 1 => "Falling Liquide Film Technique (FLFT)" 2 => "Adhesive strength" 3 => "Aloe vera" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1651084" "palabras" => array:4 [ 0 => "Enfermedad por reflujo gastroesofágico (ERGE)" 1 => "<span class="elsevierStyleItalic">Falling liquide film technique</span> (FLFT)" 2 => "Fuerza adhesiva" 3 => "Aloe vera" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Aim</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">To investigate the mucoadhesive strength and barrier effect of Esophacare® (Atika Pharma SL, Las Palmas de Gran Canaria) in an <span class="elsevierStyleItalic">ex vivo</span> model of gastro-oesophageal reflux.</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">An <span class="elsevierStyleItalic">ex vivo</span> evaluation through the Falling Liquide Film Technique with porcine esophagi was performed, compared to a positive control (Ziverel®; Norgine, Amsterdam), after different washing periods with saline, acidified saline (pH 1.2) and acidified saline with pepsin (2000<span class="elsevierStyleHsp" style=""></span>U/mL).</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">The adhesive mean strength on the oesophageal mucosa of Esophacare was 94.7 (6.0)%, compared to 27.6 (19.1)% of the positive control (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.05). These results were homogeneous across the different washes and throughout the tissue. The area covered by 1<span class="elsevierStyleHsp" style=""></span>mL of Esophacare, and its respective persistence after washing was also assessed, yielding a mean global persistence of 74.29 (19.7)% <span class="elsevierStyleItalic">vs.</span> 18.9 (12.3)% for the control (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.05). In addition, after 30<span class="elsevierStyleHsp" style=""></span>min exposure to acidified saline with pepsin, Esophacare shows a protective effect on the oesophageal mucosa, detectable histologically: preserved integrity and structure of the apical layers was observed, as well as reduced permeability to the washing solution.</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Esophacare shows an adhesive strength close to 100%, irrespective of the washing solution applied or the oesophageal region studied. Histologically, it reduces the abrasive effects of the acidic solution on the oesophageal epithelium, reducing permeability to the washing solution. The results in this <span class="elsevierStyleItalic">ex vivo</span> model of gastro-oesophageal reflux disease (GERD) support its therapeutic potential.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Aim" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Objetivo</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Investigar la fuerza mucoadhesiva y el efecto barrera de Esophacare® (Atika Pharma SL, Las Palmas de Gran Canaria) en un modelo <span class="elsevierStyleItalic">ex vivo</span> con reflujo gastroesofágico.</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Métodos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Se realizó una evaluación <span class="elsevierStyleItalic">ex vivo</span> mediante la técnica <span class="elsevierStyleItalic">falling liquide film</span> con esófagos porcinos, en comparación con un control positivo (Ziverel®, Norgine, Ámsterdam, Países Bajos), después de diferentes periodos de lavado con solución salina, solución salina acidificada (pH 1,2) y solución salina acidificada con pepsina (2.000 U/mL).</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">La fuerza media de adhesión en la mucosa esofágica de Esophacare fue del 94,7% (6,0%), en comparación con el 27,6% (19,1%) del control positivo (<span class="elsevierStyleItalic">p</span> < 0,05). Estos resultados fueron homogéneos en los diferentes lavados y en todo el tejido. También se evaluó el área cubierta por 1<span class="elsevierStyleHsp" style=""></span>mL de Esophacare y su respectiva persistencia tras el lavado: se obtuvo una persistencia global media del 74,29% (19,7%) frente al 18,9% (12,3)% del control (<span class="elsevierStyleItalic">p</span> < 0,05). Además, tras 30 minutos de exposición a una solución salina acidificada con pepsina, Esophacare muestra un efecto protector sobre la mucosa esofágica, detectable histológicamente, con la conservación de la integridad y la estructura de las capas apicales, así como con reducción de la permeabilidad a la solución de lavado.</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Esophacare muestra una fuerza adhesiva cercana al 100%, independientemente de la solución de lavado aplicada o de la región esofágica estudiada. Histológicamente, reduce los efectos abrasivos de la solución ácida sobre el epitelio esofágico y reduce la permeabilidad a la solución de lavado. Los resultados en este modelo <span class="elsevierStyleItalic">ex vivo</span> de enfermedad de reflujo gastroesofágico apoyan su potencial terapéutico.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Objetivo" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] ] "multimedia" => array:6 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 996 "Ancho" => 1340 "Tamanyo" => 137228 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Macroscopic evaluation during adhesive strength determination. (5×; saline washing, 30<span class="elsevierStyleHsp" style=""></span>min). (A) Mucosa stained. After 1<span class="elsevierStyleHsp" style=""></span>μL application of control solution (distilled water with methylene blue), dye diffused between the application spots and margins are lost. (B) Esophacare adherence. A defined oval is seen, apparently protruding from the surface, with undissolved methylene blue crystals. Its location shows the area of application.</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 447 "Ancho" => 1340 "Tamanyo" => 85114 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Cranial oesophageal sections. Tissue sections from the cranial oesophageal mucosa (haematoxylin–eosin). (A) 4× magnification and (B) 10× magnification. Both images show a focal loss of epithelium and the damage of the remaining fractions.</p>" ] ] 2 => array:7 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 2192 "Ancho" => 2925 "Tamanyo" => 872862 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Histological evaluation for the barrier effect estimation <span class="elsevierStyleItalic">ex vivo</span>. Haematoxylin–eosin staining of the oesophageal mucosa after 30<span class="elsevierStyleHsp" style=""></span>min washing with acidified solution and pepsin (10× magnification). Columns 1–3: Esophacare, Ziverel, Control (distilled water). Rows A–H, (experimental replicates): A–C, D–F, G–H. Cell damage in the apical layers of the epithelium was observed with varying affection degrees, as consequence of the abrasive process. The most evident lesion was the disintegration and disorganization of the apical and intermediate epithelial layers (detached layers forming convolutions, losing their dense longitudinal structure) present in B, C, F, H and I, (Ziverel, Control) with complete or partial detachment in some cases (C and E), injury that may decrease the thickness of epithelium (E and H). In contrast, the less affected tissues are A, D, G, (Esophacare), with more preserved architecture and compact appearance at superficial layers. Another remarkable lesion is the cavitated areas due to the epithelial cell cohesion loss (spaces within the flat keratinized stratified epithelium), of variable depth, extent and frequency. In this sense, this lesion was more evident in E, F, H, I, (Ziverel, Control) and slightly evident in D and G (Esophacare). The depth of this lesion is also greater in the same cases, reaching the germinative strata in E, F, H and I, where it seems that this phenomenon spreads linearly, causing group detachments of the upper strata.</p>" ] ] 3 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Falling Liquid Film Technique (FLFT) procedures, products, washing solutions and replicates. Washing solutions: Saline (NaCl 0.9%); HCl: acidified saline; HCl<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>pepsin: acidified saline with pepsin. Products: C<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>control (distilled water); Z<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>Ziverel; E<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>Esophacare.</p><p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">FLFT procedures A and B: 27 specimens were used, in 9 triplicates. FLFT procedure C: 9 specimens were used, in three triplicates.</p>" "tablatextoimagen" => array:1 [ 0 => array:1 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">FLFT \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Washing solutions \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Replicates \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="9" align="left" valign="middle">A (adhesive strength)B (persistence area)</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="3" align="left" valign="middle">Saline</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3×C \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3×Z \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3×E \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="3" align="left" valign="middle">HCl</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3×C \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3×Z \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3×E \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="3" align="left" valign="middle">HCl<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>pepsin</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3×C \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3×Z \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3×E \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="3" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="3" align="left" valign="middle">C (barrier effect)</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="3" align="left" valign="middle">HCl<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>pepsin</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3×C \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3×Z \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3×E \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Falling Liquide Film Technique procedures.</p>" ] ] 4 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at2" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "<p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">Adhesive strength (percentage [mean (SD)]), by product, washing solutions and region. Washing solutions: saline (NaCl 0.9%); HCl: acidified saline (saline with HCl); HCl<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>pepsin: acidified saline with pepsin. Comparisons: *=<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.05, for Ziverel <span class="elsevierStyleItalic">vs.</span> Esophacare; <span class="elsevierStyleSup">a,b</span>=<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.05 comparisons among washing solutions within each product, <span class="elsevierStyleSup">a</span>=saline <span class="elsevierStyleItalic">vs.</span> HCl, and <span class="elsevierStyleSup">b</span>=saline <span class="elsevierStyleItalic">vs.</span> HCl<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>pepsin.</p>" "tablatextoimagen" => array:2 [ 0 => array:1 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Washing solutions \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Saline (%) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">HCl (%) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">HCl<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>pepsin (%) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Global (%) \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Esophacare® \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">100 (0)<span class="elsevierStyleSup">a,b</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">89.3 (4.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">94.7 (6.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">94.7 (6.0) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Ziverel® \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">41.3 (22.0)* \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">14.7 (4.6)* \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">26.7 (20.5)* \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">27.6 (19.1)* \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] ] 1 => array:1 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Oesophageal region \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Cranial (%) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Caudal (%) \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Esophacare® \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">94.52 (6.46) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">95.33 (7.34) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Ziverel® \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">20.29 (22.10)* \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">27.97 (17.59)* \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">Adhesive strength values.</p>" ] ] 5 => array:8 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at3" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "<p id="spar0090" class="elsevierStyleSimplePara elsevierViewall">Persistence area by product after the washing solutions (percentage or cm<span class="elsevierStyleSup">2</span>, mean (SD) or median [min–max]): Saline (NaCl 0.9%); HCl: acidified saline (saline with hydrochloric acid); HCl<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>pepsin: acidified saline with pepsin. Comparisons: *=<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.05, for Ziverel <span class="elsevierStyleItalic">vs</span> Esophacare; <span class="elsevierStyleSup">a,b</span>=<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.05 for washings within each product, <span class="elsevierStyleSup">a</span>=saline <span class="elsevierStyleItalic">vs.</span> HCl, and <span class="elsevierStyleSup">b</span>=saline <span class="elsevierStyleItalic">vs.</span> HCl<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>pepsin.</p>" "tablatextoimagen" => array:3 [ 0 => array:1 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="3" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Initial area</th></tr><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Product \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Esophacare® \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Ziverel® \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Control \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Area (cm<span class="elsevierStyleSup">2</span>) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">12.37<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>1.98 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">12.15<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>2.19 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">13.02<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>2.73 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] ] 1 => array:1 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="3" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Persistence area (%) after washing</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">Global (%) \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Saline \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">HCl \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">HCl<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>pepsin \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Esophacare® \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">93.1 [85.3–94.3] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">69.3 (21.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">62.6 (20.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">74.3 (19.7) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Ziverel® \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15.1 [14.4–38.1]* \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">20.5 (15.6)* \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">13.6 (10.8)* \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">18.9 (12.3)* \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] ] 2 => array:1 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="3" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Persistence area (cm<span class="elsevierStyleSup">2</span>) after washing</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">Global (cm<span class="elsevierStyleSup">2</span>) \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Saline \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">HCl \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">HCl<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>pepsin \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Esophacare® \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">11.9 (1.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8.7 (2.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7.64 (5.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9.4 (3.5) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Ziverel® \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3.05 (2.0)* \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2.64 (1.9)* \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.37 (1.0)* \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2.3 (1.6)* \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">Persistence area measurements.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:28 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Simultaneous development of the Pediatric GERD Caregiver Impact Questionnaire (PGCIQ) in American English and American Spanish" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "J. Kim" 1 => "D.L. Keininger" 2 => "S. Becker" 3 => "J.A. Crawley" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1186/1477-7525-3-5" "Revista" => array:3 [ "tituloSerie" => "Health Qual Life Outcomes" "fecha" => "2005" "volumen" => "3" ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0010" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Safety of medication options for treating pediatric esophagitis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "M. Bardou" 1 => "K.J. Fortinsky" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1517/14740338.2015.1040389" "Revista" => array:6 [ "tituloSerie" => "Expert Opin Drug Saf" "fecha" => "2015" "volumen" => "14" "paginaInicial" => "1087" "paginaFinal" => "1096" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25913014" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0015" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Update on esophagitis: controversial and underdiagnosed causes" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "A.E. Noffsinger" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.5858/133.7.1087" "Revista" => array:5 [ "tituloSerie" => "Arch Pathol Lab Med" "fecha" => "2009" "volumen" => "133" "paginaInicial" => "1087" "paginaFinal" => "1095" ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0020" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "World Gastroenterology Organisation Global Guidelines" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "R. Hunt" 1 => "D. Armstrong" 2 => "P. Katelaris" 3 => "M. Afihene" 4 => "A. Bane" 5 => "S. Bhatia" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/MCG.0000000000000854" "Revista" => array:6 [ "tituloSerie" => "J Clin Gastroenterol" "fecha" => "2017" "volumen" => "51" "paginaInicial" => "467" "paginaFinal" => "478" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28591069" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0025" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Symptoms of gastro-oesophageal reflux: prevalence, severity, duration and associated factors in a Spanish population" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "M. Diaz-Rubio" 1 => "C. Moreno-Elola-Olaso" 2 => "E. Rey" 3 => "G.R. Locke" 4 => "F. Rodriguez-Artalejo" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1046/J.1365-2036.2003.01769.X" "Revista" => array:6 [ "tituloSerie" => "Aliment Pharmacol Ther" "fecha" => "2004" "volumen" => "19" "paginaInicial" => "95" "paginaFinal" => "105" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/14687171" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0030" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "How is the gastroesophageal reflux disease prevalence, incidence, and frequency of complications (stricture/esophagitis/Barrett's esophagus/carcinoma) in Turkey compared to other geographical regions globally?" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "S. Bor" 1 => "E.S. Yüksel" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.5152/TJG.201703" "Revista" => array:6 [ "tituloSerie" => "Turk J Gastroenterol" "fecha" => "2017" "volumen" => "28" "paginaInicial" => "S4" "paginaFinal" => "S9" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29199158" "web" => "Medline" ] ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0035" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Extraction, purification, structural characteristics, biological activities and pharmacological applications of Acemannan, a polysaccharide from <span class="elsevierStyleItalic">Aloe vera</span>: a review" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "C. Liu" 1 => "Y. Cui" 2 => "F. Pi" 3 => "Y. Cheng" 4 => "Y. Guo" 5 => "H. Qian" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3390/MOLECULES24081554" "Revista" => array:3 [ "tituloSerie" => "Molecules" "fecha" => "2019" "volumen" => "24" ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0040" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The effect of <span class="elsevierStyleItalic">Aloe vera</span> clinical trials on prevention and healing of skin wound: a systematic review" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "D. Hekmatpou" 1 => "F. Mehrabi" 2 => "K. Rahzani" 3 => "A. Aminiyan" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.30476/ijms.2019.40612" "Revista" => array:5 [ "tituloSerie" => "Iran J Med Sci" "fecha" => "2019" "volumen" => "44" "paginaInicial" => "1" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/30666070" "web" => "Medline" ] ] ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0045" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Processing, food applications and safety of aloe vera products: a review" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "K.S. Ahlawat" 1 => "B.S. Khatkar" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/S13197-011-0229-Z" "Revista" => array:5 [ "tituloSerie" => "J Food Sci Technol" "fecha" => "2011" "volumen" => "48" "paginaInicial" => "525" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23572784" "web" => "Medline" ] ] ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0050" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A comprehensive overview of functional and rheological properties of aloe vera and its application in foods" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "S.K. Sonawane" 1 => "J.S. Gokhale" 2 => "M.Z. Mulla" 3 => "V.R. Kandu" 4 => "S. Patil" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/S13197-020-04661-6" "Revista" => array:6 [ "tituloSerie" => "J Food Sci Technol" "fecha" => "2021" "volumen" => "58" "paginaInicial" => "1217" "paginaFinal" => "1226" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/33746250" "web" => "Medline" ] ] ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib0055" "etiqueta" => "11" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Systematic review: the efficacy of topical hyaluronic acid on oral ulcers" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M. Casale" 1 => "A. Moffa" 2 => "P. Vella" 3 => "V. Rinaldi" 4 => "M.A. Lopez" 5 => "V. Grimaldi" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Biol Regul Homeost Agents" "fecha" => "2017" "volumen" => "31" "paginaInicial" => "63" "paginaFinal" => "69" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29202564" "web" => "Medline" ] ] ] ] ] ] ] ] 11 => array:3 [ "identificador" => "bib0060" "etiqueta" => "12" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Barrier effect of Esoxx® on esophageal mucosal damage: experimental study on ex-vivo swine model" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M.P. Di Simone" 1 => "F. Baldi" 2 => "V. Vasina" 3 => "F. Scorrano" 4 => "M.L. Bacci" 5 => "A. Ferrieri" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.2147/CEG.S31404" "Revista" => array:6 [ "tituloSerie" => "Clin Exp Gastroenterol" "fecha" => "2012" "volumen" => "5" "paginaInicial" => "103" "paginaFinal" => "107" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22767997" "web" => "Medline" ] ] ] ] ] ] ] ] 12 => array:3 [ "identificador" => "bib0065" "etiqueta" => "13" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hyaluronic acid: molecular mechanisms and therapeutic trajectory" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "R.C. Gupta" 1 => "R. Lall" 2 => "A. Srivastava" 3 => "A. Sinha" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3389/FVETS.2019.00192" "Revista" => array:3 [ "tituloSerie" => "Front Vet Sci" "fecha" => "2019" "volumen" => "6" ] ] ] ] ] ] 13 => array:3 [ "identificador" => "bib0070" "etiqueta" => "14" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Chondroitin sulfate safety and quality" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "N. Volpi" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3390/MOLECULES24081447" "Revista" => array:3 [ "tituloSerie" => "Molecules" "fecha" => "2019" "volumen" => "24" ] ] ] ] ] ] 14 => array:3 [ "identificador" => "bib0075" "etiqueta" => "15" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Barrier effect of a new topical agent on damaged esophageal mucosa: experimental study on an ex vivo swine model" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "R. Salaroli" 1 => "D. Ventrella" 2 => "C. Bernardini" 3 => "A. Elmi" 4 => "A. Zannoni" 5 => "M.L. Bacci" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.2147/CEG.S269568" "Revista" => array:3 [ "tituloSerie" => "Clin Exp Gastroenterol" "fecha" => "2020" "volumen" => "13" ] ] ] ] ] ] 15 => array:3 [ "identificador" => "bib0080" "etiqueta" => "16" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The roles of vitamin C in skin health" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "J.M. Pullar" 1 => "A.C. Carr" 2 => "M.C.M. Vissers" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3390/NU9080866" "Revista" => array:3 [ "tituloSerie" => "Nutrients" "fecha" => "2017" "volumen" => "9" ] ] ] ] ] ] 16 => array:3 [ "identificador" => "bib0085" "etiqueta" => "17" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Investigations to evaluate gastric mucoadhesion of an organic product to ameliorate gastritis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "C. Winter" 1 => "S. Hartl" 2 => "D. Kolb" 3 => "G. Leitinger" 4 => "E. Roblegg" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3390/pharmaceutics12040331" "Revista" => array:3 [ "tituloSerie" => "Pharmaceutics" "fecha" => "2020" "volumen" => "12" ] ] ] ] ] ] 17 => array:3 [ "identificador" => "bib0090" "etiqueta" => "18" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A review on in vitro–in vivo mucoadhesive strength assessment" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "S. Singh" 1 => "M. Govind" 2 => "S.B. Bothara" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "PhaTechMed" "fecha" => "2013" "volumen" => "2" "paginaInicial" => "221" "paginaFinal" => "229" ] ] ] ] ] ] 18 => array:3 [ "identificador" => "bib0095" "etiqueta" => "19" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "An in vitro mucosal model for prediction of the bioadhesion of alginate solutions to the oesophagus" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "H.K. Batchelor" 1 => "D. Banning" 2 => "P.W. Dettmar" 3 => "F.C. Hampson" 4 => "I.G. Jolliffe" 5 => "D.Q.M. Craig" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S0378-5173(02)00062-5" "Revista" => array:6 [ "tituloSerie" => "Int J Pharm" "fecha" => "2002" "volumen" => "238" "paginaInicial" => "123" "paginaFinal" => "132" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11996816" "web" => "Medline" ] ] ] ] ] ] ] ] 19 => array:3 [ "identificador" => "bib0100" "etiqueta" => "20" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "An in-vitro investigation of mucosa-adhesive materials for use in controlled drug delivery" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "J.D. Smart" 1 => "I.W. Kellaway" 2 => "H.E.C. Worthington" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.2042-7158.1984.tb04377.x" "Revista" => array:6 [ "tituloSerie" => "J Pharm Pharmacol" "fecha" => "1984" "volumen" => "36" "paginaInicial" => "295" "paginaFinal" => "299" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/6145763" "web" => "Medline" ] ] ] ] ] ] ] ] 20 => array:3 [ "identificador" => "bib0105" "etiqueta" => "21" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Oesophageal bioadhesion of sodium alginate suspensions: 2. Suspension behaviour on oesophageal mucosa" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "J.C. Richardson" 1 => "P.W. Dettmar" 2 => "F.C. Hampson" 3 => "C.D. Melia" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.ejps.2004.10.001" "Revista" => array:6 [ "tituloSerie" => "Eur J Pharm Sci" "fecha" => "2005" "volumen" => "24" "paginaInicial" => "107" "paginaFinal" => "114" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15626584" "web" => "Medline" ] ] ] ] ] ] ] ] 21 => array:3 [ "identificador" => "bib0110" "etiqueta" => "22" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Formulation and evaluation of oral mucoadhesive multiparticulate system containing metoprolol tartarate: an in vitro–ex vivo characterization" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "V. Belgamwar" 1 => "V. Shah" 2 => "S. Surana" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.2174/156720109787048285" "Revista" => array:6 [ "tituloSerie" => "Curr Drug Deliv" "fecha" => "2009" "volumen" => "6" "paginaInicial" => "113" "paginaFinal" => "121" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19418963" "web" => "Medline" ] ] ] ] ] ] ] ] 22 => array:3 [ "identificador" => "bib0115" "etiqueta" => "23" "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "B. Of & T. H. E. Invention, 1. WO2010081720 – Compositions for the treatment of gastro-esofageal reflux disease (GERD) (2020) 1–7." ] ] ] 23 => array:3 [ "identificador" => "bib0120" "etiqueta" => "24" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Diseños en cuadrados latinos 7.1" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "A. García Leal" 1 => "J. Lara Porras" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Libro" => array:3 [ "fecha" => "2000" "paginaInicial" => "1" "paginaFinal" => "16" ] ] ] ] ] ] 24 => array:3 [ "identificador" => "bib0125" "etiqueta" => "25" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Análisis De Los Cuadrados Latinos Para La Optimización Del Proceso De Obtencion" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "D. Roca" 1 => "Y. Estudio" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Libro" => array:3 [ "fecha" => "2016" "paginaInicial" => "1" "paginaFinal" => "46" ] ] ] ] ] ] 25 => array:3 [ "identificador" => "bib0130" "etiqueta" => "26" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Fiji: an open-source platform for biological-image analysis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J. Schindelin" 1 => "I. Arganda-Carreras" 2 => "E. Frise" 3 => "V. Kaynig" 4 => "M. Longair" 5 => "T. Pietzsch" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/NMETH.2019" "Revista" => array:6 [ "tituloSerie" => "Nat Methods" "fecha" => "2012" "volumen" => "9" "paginaInicial" => "676" "paginaFinal" => "682" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22743772" "web" => "Medline" ] ] ] ] ] ] ] ] 26 => array:3 [ "identificador" => "bib0135" "etiqueta" => "27" "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "Bancroft's theory and practice of histological techniques. (2019). <a target="_blank" href="https://doi.org/10.1016/C2015-0-00143-5">https://doi.org/10.1016/C2015-0-00143-5</a>." ] ] ] 27 => array:3 [ "identificador" => "bib0140" "etiqueta" => "28" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Randomised clinical trial: mucosal protection combined with acid suppression in the treatment of non-erosive reflux disease – efficacy of Esoxx, a hyaluronic acid-chondroitin sulphate based bioadhesive formulation" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "V. Savarino" 1 => "F. Pace" 2 => "C. Scarpignato" 3 => "M. Astegiano" 4 => "C. Calabrese" 5 => "M. Cicala" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/APT.13914" "Revista" => array:6 [ "tituloSerie" => "Aliment Pharmacol Ther" "fecha" => "2017" "volumen" => "45" "paginaInicial" => "631" "paginaFinal" => "642" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28116754" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] "agradecimientos" => array:1 [ 0 => array:4 [ "identificador" => "xack670714" "titulo" => "Acknowledgements" "texto" => "<p id="par0150" class="elsevierStylePara elsevierViewall">We thank Laura Rodrigo for her technical support in the lab. We thank the staff of the Island Slaughter House of Gran Canaria, especially Clara Padilla and Yeray Macías for their patience, kindness and support in the provision of the oesophagi.</p>" "vista" => "all" ] ] ] "idiomaDefecto" => "en" "url" => "/02105705/0000004600000006/v2_202306121247/S0210570522002540/v2_202306121247/en/main.assets" "Apartado" => array:4 [ "identificador" => "9009" "tipo" => "SECCION" "es" => array:2 [ "titulo" => "Originales" "idiomaDefecto" => true ] "idiomaDefecto" => "es" ] "PDF" => "https://static.elsevier.es/multimedia/02105705/0000004600000006/v2_202306121247/S0210570522002540/v2_202306121247/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0210570522002540?idApp=UINPBA00004N" ]
| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 2 | 1 | 3 |
| 2024 October | 10 | 4 | 14 |
| 2024 September | 16 | 3 | 19 |
| 2024 August | 9 | 0 | 9 |
| 2024 July | 1 | 0 | 1 |
| 2024 June | 13 | 7 | 20 |
| 2024 May | 7 | 5 | 12 |
| 2024 April | 8 | 8 | 16 |
| 2024 March | 14 | 9 | 23 |
| 2024 February | 11 | 4 | 15 |
| 2024 January | 8 | 0 | 8 |
| 2023 December | 12 | 0 | 12 |
| 2023 November | 14 | 0 | 14 |
| 2023 October | 44 | 5 | 49 |
| 2023 September | 26 | 0 | 26 |
| 2023 August | 13 | 0 | 13 |
| 2023 July | 15 | 0 | 15 |
| 2023 June | 19 | 6 | 25 |
| 2023 May | 17 | 4 | 21 |
| 2023 April | 4 | 2 | 6 |
| 2023 March | 0 | 13 | 13 |
| 2023 February | 0 | 9 | 9 |
| 2023 January | 0 | 13 | 13 |
| 2022 December | 0 | 7 | 7 |
| 2022 November | 0 | 4 | 4 |
Show all
