A new experimental model for inducing interstitial cystitis by oxidative stress using bladder instillation of a nitric oxide donor gel | Actas Urológicas Españolas (English Edition)

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Incisión de la piel. B. Disección de la capa muscular. C. Apertura de la pared abdominal. D. Identificación y extracción de la vejiga. E. Apertura de la vejiga. F. La vejiga se coloca en un bastoncillo para su fijación en formol." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "T.F. Palma, A. Seabra, S.C. Souto, L. Maciel, M. Alvarenga, R. Siniscalchi, M. Ganzarolli, C. Ricetto" "autores" => array:8 [ 0 => array:2 [ "nombre" => "T.F." "apellidos" => "Palma" ] 1 => array:2 [ "nombre" => "A." "apellidos" => "Seabra" ] 2 => array:2 [ "nombre" => "S.C." "apellidos" => "Souto" ] 3 => array:2 [ "nombre" => "L." "apellidos" => "Maciel" ] 4 => array:2 [ "nombre" => "M." "apellidos" => "Alvarenga" ] 5 => array:2 [ "nombre" => "R." "apellidos" => "Siniscalchi" ] 6 => array:2 [ "nombre" => "M." "apellidos" => "Ganzarolli" ] 7 => array:2 [ "nombre" => "C." 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Cleffi, A.S. Neto, L.O. Reis, Priscila Maia, F. Fonseca, M.L. Wroclawski, M. Neves, A.C.L. Pompeo, A. Del Giglio, E.F. Faria, M. Tobias-Machado" "autores" => array:11 [ 0 => array:2 [ "nombre" => "S." "apellidos" => "Cleffi" ] 1 => array:2 [ "nombre" => "A.S." "apellidos" => "Neto" ] 2 => array:2 [ "nombre" => "L.O." "apellidos" => "Reis" ] 3 => array:2 [ "nombre" => "Priscila" "apellidos" => "Maia" ] 4 => array:2 [ "nombre" => "F." "apellidos" => "Fonseca" ] 5 => array:2 [ "nombre" => "M.L." "apellidos" => "Wroclawski" ] 6 => array:2 [ "nombre" => "M." "apellidos" => "Neves" ] 7 => array:2 [ "nombre" => "A.C.L." "apellidos" => "Pompeo" ] 8 => array:2 [ "nombre" => "A." "apellidos" => "Del Giglio" ] 9 => array:2 [ "nombre" => "E.F." "apellidos" => "Faria" ] 10 => array:2 [ "nombre" => "M." 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Palma, A. Seabra, S.C. Souto, L. Maciel, M. Alvarenga, R. Siniscalchi, M. Ganzarolli, C. Ricetto" "autores" => array:8 [ 0 => array:4 [ "nombre" => "T.F." "apellidos" => "Palma" "email" => array:1 [ 0 => "thais.palma@gmail.com" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "¿" "identificador" => "cor0005" ] ] ] 1 => array:2 [ "nombre" => "A." "apellidos" => "Seabra" ] 2 => array:2 [ "nombre" => "S.C." "apellidos" => "Souto" ] 3 => array:2 [ "nombre" => "L." "apellidos" => "Maciel" ] 4 => array:2 [ "nombre" => "M." "apellidos" => "Alvarenga" ] 5 => array:2 [ "nombre" => "R." "apellidos" => "Siniscalchi" ] 6 => array:2 [ "nombre" => "M." "apellidos" => "Ganzarolli" ] 7 => array:2 [ "nombre" => "C." "apellidos" => "Ricetto" ] ] "afiliaciones" => array:1 [ 0 => array:1 [ "entidad" => "Hospital Clínico Universitario de la Universidad Estatal de Campinas, Brazil" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Un nuevo modelo experimental de inducción de cistitis intersticial mediante estrés oxidativo empleando instilación vesical de un gel donante de óxido nítrico" ] ] "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" => 1494 "Ancho" => 2084 "Tamanyo" => 316165 ] ] "descripcion" => array:1 [ "en" => "The rats undergo tricotomy and asepsis (A). The urethra is shown with tweezers (B). The catheter is inserted carefully (C). Instillation of the liquid according to each group (D)." ] ] ] "textoCompleto" => "IntroductionInterstitial cystitis (IC) is a condition characterized by bladder pain, urinary urgency, frequency and nocturia. The International Continence Society (ICS) prefers the term painful bladder syndrome defined as the supra-pubic pain related to the bladder filling, and with other symptoms such as increased frequency (day and night) in the absence of urinary tract infection or some other obvious disease.<a class="elsevierStyleCrossRef" href="#bib0005">1</a> It is known that IC affects both men and women, but it is predominantly present in women (around 90% of all the patients).<a class="elsevierStyleCrossRef" href="#bib0010">2</a> The main problem for the patients is how disease impacts their quality of life.<a class="elsevierStyleCrossRef" href="#bib0015">3</a>The regulation of the nitric oxide synthase enzyme (NOS) in the urine was suggested as an important factor in the immune response of IC. Other theories include a possible infectious origin, neurogenic inflammation and histamine-induced generalized visceral hypersensitivity caused by abnormalities in the immune or neuroendocrine system.<a class="elsevierStyleCrossRef" href="#bib0020">4</a>A new experimental model using oxidative stress would be a major advantage for understanding this idiopathic condition. Moreover, it would allow for the experimental evaluation of new treatments. The objective of this study is to present a new experimental model of IC induction by oxidative stress using a nitric oxide donor gel.Materials and methodsWe studied the effects of a polymeric aqueous solution of the copolymer poly(ethylene oxide)–poly(propylene oxide)–poly(ethylene oxide) (PEO–PPO–PEO) Pluronic F127, containing S-nitrousglutathione (GSNO) as a nitric oxide donor on the bladder wall of Wistar rats. GSNO is an endogenous S-nitrousthiol that acts as a carrier and donor of NO, increasing its half-life. This project was developed at our institution, after approval by the Research Ethics Committee, protocol 1296-1. The rats were accommodated in cages containing five animals each, under ideal feeding, temperature, humidity and light conditions.A pilot study including 20 Wistar rats was carried out as a training process for bladder catheterization in the animals. The sample size included 40 female Wistar rats aged 3 months. The nitric oxide donor chosen for this experiment was the S-nitrousglutathione (GSNO), produced and donated by the Institute of Chemistry of the State University of Campinas. GSNO was synthesized by reacting equimolar amounts of glutathione with sodium nitrite in aqueous hydrochloric acid (HCl 0.5M), stirring it in an ice bath for 40min. The final solution was precipitated with acetone, filtered and washed with cold water and acetone. The precipitate formed was dried for 24h. The GSNO obtained was stored in the freezer (−20°C) and protected from light.Preparation of the solution containing NO Gel Pluronic F-127 (25wt%) in water containing GSNO (100μM) was prepared as described previously. Pluronic F-127 solid was added to cold water (5°C). This solution was left at 5°C for 12h to reach equilibrium dissolution of the polymer. Appropriate volume of aqueous solution of GSNO (0.35mM) was added to the solution of Pluronic F-127 by stirring in an ice bath to complete homogenization of the solution. The animals were anesthetized by injection of sodium thiopental in the dorsal vein of the tail and then placed in the supine position, so that antisepsis could be performed with PVPI-lode.Group distributionInstillation was performed according to animal division in four groups, as shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>. In all groups, the substances were infused intravesically (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>), until bladder overflow was achieved (mean of 1mL). The substances were kept in the bladder until the next micturition of the animals.<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005">–Group 1. Ten rats underwent two sessions of bladder instillation of saline solution 0.9% at 0.04ml/min, with a 24-h interval between them, until bladder overflow was achieved and they were then injected with GSNO solution in 3 doses, with a 2-day interval between each dose; after that they were euthanized.</li><li class="elsevierStyleListItem" id="lsti0010">–Group 2. Ten rats underwent two sessions of bladder instillation of saline solution 0.9% at 0.04ml/min, with a 24-h interval between them until bladder overflow was achieved; they were then injected with excipient solution (only the polymeric solution, without the GSNO) in 3 doses, 2 days between each dose and after that they were euthanized.</li><li class="elsevierStyleListItem" id="lsti0015">–Group 3. Ten rats underwent two sessions of bladder catheterization using protamine solution (30mg/ml) and KCl 300mM 0.04ml/min, with a 24-h interval between them until bladder overflow (when the maximum bladder capacity was obtained); they were then injected with excipient solution (only polymeric solution without GSNO) in 3 doses, with a 2-day between each dose; after that they were euthanized.</li><li class="elsevierStyleListItem" id="lsti0020">–Group 4. Ten rats underwent two sessions of bladder catheterization using protamine solution (30mg/ml) and KCl 300mM 0.04ml/min, until bladder overflow with a 24-h interval between them (when the maximum bladder capacity was obtained); they were then injected with GSNO solution in 3 doses, with a 2-day interval between each dose; after that they were euthanized.</li></ul><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="fig0005"></elsevierMultimedia>AnalysisHalf of the rats of each group were euthanized with a lethal dose of anesthetic on day 6, and the other half after 9 days. Skin and muscle layers were dissected and the abdominal wall was opened. The bladder was identified and removed (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>). After opening the bladder, it was put on a stick to be fixated in formaldehyde for 24h and then in ethylic alcohol 70%, before being embedded in paraffin and analyzed for the presence of IC. Histological slides were made with histological cuts 3–4μm wide and HE stained. The pathological study was based on the following classification according to the therapeutic groups (<a class="elsevierStyleCrossRefs" href="#tbl0010">Tables 2 and 3</a>).<elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0015"></elsevierMultimedia>The histological slides were analyzed by a pathologist, who received them identified only by numbers, with no indication of the groups. All the parameters of the table were analyzed and the data were analyzed statistically. Statistical analysis was performed with assistance of the Department of Statistics of the Research Board of the Faculty of Medical Sciences of the State University of Campinas. A descriptive analysis was conducted using frequency tables for categorical variables. For comparison of proportions, the Fisher exact test was used and the level of significance was 5%.ResultsMacroscopically we observed edema and hyperemia of the mucosa in 2 (22%) of the animals in group 1, in 0 (0%) of the animals in group 2, in 10 (100%) of the animals in group 3, and in 5 (50%) of the animals in group 4. In the protamine+KCl group and in saline+GSNO group, similar effects were observed on the bladder wall. A pathologist performed the microscopic evaluation following the parameters cited in <a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>.Microscopically, there was no significant difference between the groups regarding vascular congestion in the animals on day 6 (p=0.6329). After 9 days, vascular congestion was significantly reduced in group 2 (saline solution+excipient) when compared to groups 1, 3 and 4 (p=0.0035) (<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>). No difference was observed between the groups regarding fibrosis on day 6 (p=0.3781). After 9 days, fibrosis was significantly higher in group 4 (protamine+GSNO) when compared to groups 1 and 2 (p=0.0035) (<a class="elsevierStyleCrossRef" href="#tbl0025">Table 5</a>).<elsevierMultimedia ident="tbl0020"></elsevierMultimedia><elsevierMultimedia ident="tbl0025"></elsevierMultimedia>Neutrophilic infiltrate of variable intensity was observed in all groups after 6 days (p=0.7277). A tendency towards regression was observed after 9 days, without reaching differences of statistical significance between groups (p=0.2301). A tendency towards regression was also observed in all groups regarding edema, without significant differences either (p=0.8096 at 6 days; p=0.2478 at 9 days). The animals euthanized on day 6 did not present any significant differences regarding lymphomonocitary infiltrate (p=0.7253); however, on day 9 there was a significant difference between the groups (p=0.0459). In the group treated with GSNO+saline solution, infiltrate was more extensive than in the rest. Differential presence of mast cells in the infiltrate was not observed among groups.DiscussionInterstitial cystitis is a condition that deserves clinician attention, especially due to the lack of reliable criteria for diagnosis. Classically reported models do not reproduce the inflammation status properly, mostly because its cause is unknown.<a class="elsevierStyleCrossRef" href="#bib0025">5</a> Previous studies found higher levels of NO in these patients<a class="elsevierStyleCrossRef" href="#bib0030">6</a>; however, it is very difficult to collect material from patients in clinical trials because it causes great discomfort. A study was performed on patients in which 25mL of air were introduced in the bladder by means of a catheter and the level of NO was compared to that in the air in the room. The study found significant differences, proving that the patients with cystitis presented more NO than healthy individuals.<a class="elsevierStyleCrossRef" href="#bib0035">7</a>Experimental models of IC described in the literature are scarce. The first projects to develop interstitial cystitis in animals used acetic acid, cyclophosphamide, lipopolysaccharides, protamine sulphate and vanilloid receptor agonists. These substances did not produce the effects intended, either because they damaged the bladder too much, or because they were not reliable. Fraser et al. sought to develop a model that would reliably mimic the acute phase of this debilitating disease.<a class="elsevierStyleCrossRef" href="#bib0040">8</a> To this end, they combined protamine sulphate (PS) treatment, thought to breakdown urothelial umbrella cell barrier function, and physiologic concentrations of potassium chloride (KCl) in an open cystometrogram animal model. Female Sprague-Dawley rats were anesthetized and transurethral continuous cystometry was performed with normal saline and 100mmol/L KCl or 0mmol/L KCl as control. Either 10 or 30mg/mL PS was then added to the control solution for a 30-min period (for modest and severe urothelial barrier breakdown, respectively), after which the control solution was continued for 1–2h. Bladder contraction amplitudes, durations, frequency and intercontractile intervals were recorded and analyzed. There were no differences between the saline 100mmol/L KCl or 500mmol/L KCl control periods, indicating that barrier function in these animals was not affected by the physical preparation. Of the treatments tested, 100mmol/L KCl with 30mg/mL PS and 500mmol/L KCl (the physiologic concentration of rat urine) with either 10 or 30mg/mL PS produced reliable irritation, which continued up to 2h after cessation of PS administration. These results indicate that the historical use of normal saline, instead of the more physiologic 500mmol/L KCl for cystometry, greatly biases our understanding of the function of the lower urinary tract in animal models of IC; and modest, non-cytotoxic insults to urothelial barrier function can result in dramatic irritative responses, given the proper physiological conditions.<a class="elsevierStyleCrossRef" href="#bib0040">8</a>In 2007, an experimental model of IC with intraperitoneal administration of cyclophosphamide (CP) was described. This anti-tumor agent is metabolized into acrolein in the kidney and accumulates in the bladder to produce toxic effects, ultimately resulting in visceral pain. This substance produces histological damage only in the urothelium when dissolved in 0.9% saline and administered intraperitoneally (i.p.). Vehicle or CP was administered (200–400mg/kg, i.p.), and spontaneous and evoked pain behaviors were evaluated simultaneously in the same mice.<a class="elsevierStyleCrossRef" href="#bib0045">9</a>Another experimental study was performed in cats that already presented idiopathic IC. In some cats there is naturally an idiopathic form of IC that provokes all the characteristics of human IC, including symptoms. The animals had history of pollakiuria, hematuria and micturition in inadequate locations. After the study of NO levels in both control and IC bladders, it was observed that the NO levels in the IC bladders were higher.<a class="elsevierStyleCrossRef" href="#bib0050">10</a> Other experimental models of IC include the use of attenuated pseudorabies virus (Bartha PRV), an α-herpes virus that is taken up by neurons and undergoes retrograde transport and viral replication within the central nervous system<a class="elsevierStyleCrossRefs" href="#bib0045">9,10</a> and IC induction with substance P and lipopolysaccharides that induce the release of histamine and cytokine by the bladder. The probable relation between NO and the inflammatory process related to IC brings an experimental model that is closer to reality with the use of a NO donor gel to start up the inflammatory process. The inflammatory response to bladder instillation of an aqueous solution of S-nitrousglutathione (GSNO) was very similar to that induced by bladder instillation of PS and KCl. Therefore, instillation of GSNO can be considered a new model for experimental induction of interstitial cystitis in rats.Conflict of interestThe authors declare to have no conflict of interest." "textoCompletoSecciones" => array:1 [ "secciones" => array:10 [ 0 => array:2 [ "identificador" => "xres98361" "titulo" => array:5 [ 0 => "Summary" 1 => "Purpose" 2 => "Materials and methods" 3 => "Results" 4 => "Conclusion" ] ] 1 => array:2 [ "identificador" => "xpalclavsec85522" "titulo" => "Keywords" ] 2 => array:2 [ "identificador" => "xres98362" "titulo" => array:5 [ 0 => "Resumen" 1 => "Objetivo" 2 => "Material y métodos" 3 => "Resultados" 4 => "Conclusión" ] ] 3 => array:2 [ "identificador" => "xpalclavsec85521" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Materials and methods" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Group distribution" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Analysis" ] ] ] 6 => array:2 [ "identificador" => "sec0025" "titulo" => "Results" ] 7 => array:2 [ "identificador" => "sec0030" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0035" "titulo" => "Conflict of interest" ] 9 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2010-05-25" "fechaAceptado" => "2010-05-27" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec85522" "palabras" => array:3 [ 0 => "Interstitial cystitis" 1 => "Nitric oxide" 2 => "In vivo model" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec85521" "palabras" => array:3 [ 0 => "Cistitis intersticial" 1 => "Óxido nítrico" 2 => "Modelo in vivo" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Summary" "resumen" => "PurposeThe aim of this study is to develop a new experimental model of inducing interstitial cystitis (IC) through vesical instillation of a polymeric solution containing the NO donor S-nitrousglutathione (GSNO) and to compare it to the experimental interstitial cystitis induced by vesical instillation of protamine and potassium chloride. Materials and methodsFor that purpose 40 female Wistar rats were used, divided into four groups: (1) saline solution+GSNO; (2) saline solution+polymeric solution (without GNSO); (3) protamine sulphate+KCl; (4) protamine sulphate+GSNO. The rats received one application (5 animals) or 3 applications (5 animals) of the corresponding substance through intravesical instillation, and after 6days (5 animals) or 9days (5 animals) they were euthanized and their bladders were removed for macroscopic evaluation and histological study. ResultsIn the macroscopic evaluation we observed edema and hyperemia of the mucosa in 2 (22%) of the animals in group 1, in 0 (0%) of the animals in group 2, in 10 (100%) of the animals in group 3, and in 5 (50%) of the animals in group 4. In the protamine+KCl group and in saline+GSNO similar effects were observed on the bladder wall. The animals in group 2 (saline+polymeric) showed vascular congestion, significantly smaller than the rest after 9days instillations (p=0.0035). Significant increased fibrosis was observed after instillations in groups 3 and 4, after 6days (p=0.3781) and 9days (p=0.0459), respectively, when compared to control (group 2). All groups presented neutrophilic infiltrate of variable intensity 6days after instillations (p=0.7277). After 9days, there was a regression of the infiltrate, with no evidence of accentuated neutrophilic reaction in all the groups (p=0.2301). ConclusionThe inflammatory response to bladder instillation of an aqueous solution of S-nitrousglutathione was very similar to that induced by bladder instillation of protamine and KCl. Instillation of an aqueous solution of GSNO can be considered a new model for experimental induction of interstitial cystitis." ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "ObjetivoLa principal finalidad de este estudio es el desarrollo de un nuevo modelo experimental para la inducción de cistitis intersticial (CI) mediante la instilación vesical de una solución polimérica que contiene el S-nitrosoglutatión donante de óxido nítrico (GSNO), y su comparación con la cistitis intersticial experimental inducida por instilación vesical de protamina y cloruro potásico. Material y métodosPara la consecución de nuestro objetivo utilizamos 40 hembras de rata Wistar divididas en cuatro grupos: (a) solución salina+GSNO; (b) solución salina+solución polimérica (sin GNSO); (c) sulfato de protamina+KCl; y (d) sulfato de protamina+GSNO. Se realizó bien una aplicación a las ratas (5 animales), bien 3 aplicaciones (5 animales) de la sustancia correspondiente mediante instilación vesical, y al cabo de 6 días (5 animales) o 9 días (5 animales) se les practicó la eutanasia y se les extrajeron las vejigas para su evaluación macroscópica y estudio histológico. ResultadosEn términos de evaluación macroscópica observamos edema e hiperemia de la mucosa en dos (22%) de los animales del grupo 1, en 0 (0%) de los del grupo 2, en 10 (100%) de los del 3 y en 5 (50%) de los animales del grupo 4. En el grupo de protamina+KCl y en solución salina+GSNO se observaron efectos similares en la pared vesical. Los animales del grupo 2 (solución salina+polimérica) mostraban congestión vascular, bastante menos significativa que en el resto después de 9 días de instilaciones (p=0.0035). Se observó un aumento de la fibrosis tras las instilaciones en los grupos 3 y 4 a los 6 días (p=0.3781) y a los 9 días (p=0.0459) respectivamente, en comparación con los controles (grupo 2). En todos los grupos aparecía un infiltrado de neutrófilos con intensidad variable a los 6 días de las instilaciones (p=0.7277). Al cabo de 9 días se producía una regresión del infiltrado, y sin evidencias de reacción neutrofílica marcada en todos los grupos (p=0.2301). ConclusiónLa respuesta inflamatoria a la instilación vesical de una solución acuosa de S-nitrosoglutatión fue muy parecida a la inducida por la instilación vesical de protamina y KCl. La instilación de una solución acuosa de GSNO puede considerarse un nuevo modelo para la inducción experimental de cistitis intersticial." ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Palma TF, et al. Un nuevo modelo experimental de inducción de cistitis intersticial mediante estrés oxidativo empleando instilación vesical de un gel donante de óxido nítrico. Actas Urol Esp 2011;35:253–8." ] ] "multimedia" => array:7 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1494 "Ancho" => 2084 "Tamanyo" => 316165 ] ] "descripcion" => array:1 [ "en" => "The rats undergo tricotomy and asepsis (A). The urethra is shown with tweezers (B). The catheter is inserted carefully (C). Instillation of the liquid according to each group (D)." ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1771 "Ancho" => 2501 "Tamanyo" => 412399 ] ] "descripcion" => array:1 [ "en" => "Skin is incised (A). Muscle layer is dissected (B). Opening of the abdominal wall (C). Identification and removal of the bladder (D). Opening the bladder (E). The bladder is put on a stick to be fixated in formaldehyde (F)." ] ] 2 => array:7 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "In T=6, five animals were euthanized." "tablatextoimagen" => array:1 [ 0 => array:2 [ "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"><td 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" style="border-bottom: 2px solid black">Time \t\t\t\t\t\t\n \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">T=1 \t\t\t\t\t\t\n \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">T=2 \t\t\t\t\t\t\n \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">T=3 \t\t\t\t\t\t\n \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">T=6 \t\t\t\t\t\t\n \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">T=9 \t\t\t\t\t\t\n \t\t\t\t</td></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 " colspan="6" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Group 1. Saline solution+GSNO</td></tr><tr title="table-row"><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">Day \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">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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 \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">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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9 \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 " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Instillation \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">Saline solution \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">Saline solution \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">GSNO \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">GSNO \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">GSNO \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="6" align="left" valign="\n \t\t\t\t\ttop\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="6" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Group 2. Saline solution+polymeric solution</td></tr><tr title="table-row"><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">Day \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">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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 \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">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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9 \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 " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Instillation \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">Saline solution \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">Saline solution \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">Polymeric solution \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">Polymeric solution \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">Polymeric solution \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="6" align="left" valign="\n \t\t\t\t\ttop\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="6" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Group 3. Saline solution+protamine and KCl</td></tr><tr title="table-row"><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">Day \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">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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 \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">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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9 \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 " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Instillation \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">Saline solution \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">Saline solution \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">Protamine \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">Protamine \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">Protamine \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="6" align="left" valign="\n \t\t\t\t\ttop\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="6" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Group 4. Protamine and KCl+GSNO</td></tr><tr title="table-row"><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">Day \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">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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 \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">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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9 \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 " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Instillation \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">Protamine \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">Protamine \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">GSNO \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">GSNO \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">GSNO \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab183631.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Time table of groups 1–4." ] ] 3 => array:7 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "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"><td 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" style="border-bottom: 2px solid black">Group \t\t\t\t\t\t\n \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">Treatment \t\t\t\t\t\t\n \t\t\t\t</td></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 " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Saline+GSNO \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 " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 \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">Saline+excipient \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 " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Protamine+excipient \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 " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Protamine+GSNO \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab183634.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Groups of treatment." ] ] 4 => array:7 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "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"><td 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">Parameters \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="4" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Severity</td></tr><tr title="table-row"><td 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" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">Acute \t\t\t\t\t\t\n \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">Moderate \t\t\t\t\t\t\n \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">Mild \t\t\t\t\t\t\n \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">Not Present \t\t\t\t\t\t\n \t\t\t\t</td></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 " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Neutrophils \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 \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 \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 \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">0 \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 " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Edema \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 \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 \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 \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">0 \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 " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Vascular congestion \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 \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 \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 \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">0 \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 " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Monomorphonuclear \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 \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 \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 \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">0 \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 " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Granulation tissue \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 \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 \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 \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">0 \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 " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Fibrosis \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 \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 \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 \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">0 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab183632.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Classifications of histological findings of HE." ] ] 5 => array:7 [ "identificador" => "tbl0020" "etiqueta" => "Table 4" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "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"><td 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" style="border-bottom: 2px solid black">Group \t\t\t\t\t\t\n \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">N \t\t\t\t\t\t\n \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">Acute \t\t\t\t\t\t\n \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">Moderate \t\t\t\t\t\t\n \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">Mild \t\t\t\t\t\t\n \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">Not present \t\t\t\t\t\t\n \t\t\t\t</td></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 " colspan="6" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">T=6</td></tr><tr title="table-row"><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">Saline+GSNO \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 \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">33.3 \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">66.67 \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">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">0 \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 " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Saline+excipient \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">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">75 \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">25 \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">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">0 \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 " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Protamine \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">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">50 \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">50 \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">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">0 \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 " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Protamine+GSNO \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">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">80 \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 \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">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">0 \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="6" align="left" valign="\n \t\t\t\t\ttop\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="6" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">T=9</td></tr><tr title="table-row"><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">Saline+GSNO \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">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">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">80 \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 \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">0 \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 " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Saline+excipient \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">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">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">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">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">100<a class="elsevierStyleCrossRef" href="#tblfn0005">a</a> \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 " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Protamine \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 \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">33.3 \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">66.67 \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">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">0 \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 " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Protamine+GSNO \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">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">40 \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">60 \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">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">0 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab183635.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "a" "nota" => "Reduced in group 2 (saline solution+excipient) when compared to groups 1, 3 and 4 (p=0.0035)." ] ] ] "descripcion" => array:1 [ "en" => "Descriptive analysis and comparison of vascular congestion among groups (%)." ] ] 6 => array:7 [ "identificador" => "tbl0025" "etiqueta" => "Table 5" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "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"><td 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" style="border-bottom: 2px solid black">Group \t\t\t\t\t\t\n \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">N \t\t\t\t\t\t\n \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">Not present \t\t\t\t\t\t\n \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">Mild \t\t\t\t\t\t\n \t\t\t\t</td></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 " colspan="4" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">T=6</td></tr><tr title="table-row"><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">Saline+GSNO \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 \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">33.33 \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">66.67 \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 " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Saline+excipient \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">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">100 \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">0 \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 " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Protamine \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">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">50 \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">50 \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 " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Protamine+GSNO \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">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">60 \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">40 \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="4" align="left" valign="\n \t\t\t\t\ttop\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="4" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">T=9</td></tr><tr title="table-row"><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">Saline+GSNO \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">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">100 \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">0 \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 " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Saline+excipient \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">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">100 \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">0 \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 " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Protamine \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 \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">33.3 \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">66.67 \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 " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Protamine+GSNO \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">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">40 \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">60<a class="elsevierStyleCrossRef" href="#tblfn0010">a</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab183633.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0010" "etiqueta" => "a" "nota" => "Increased in group 4 (protamine+GSNO) when compared to groups 1 and 2 (p=0.0035)." ] ] ] "descripcion" => array:1 [ "en" => "Descriptive analysis and comparison of fibrosis among groups (%)." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 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A new experimental model for inducing interstitial cystitis by oxidative stress using bladder instillation of a nitric oxide donor gel

Un nuevo modelo experimental de inducción de cistitis intersticial mediante estrés oxidativo empleando instilación vesical de un gel donante de óxido nítrico

T.F. Palma

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thais.palma@gmail.com

Corresponding author.

, A. Seabra, S.C. Souto, L. Maciel, M. Alvarenga, R. Siniscalchi, M. Ganzarolli, C. Ricetto

Hospital Clínico Universitario de la Universidad Estatal de Campinas, Brazil

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    "titulo" => "A new experimental model for inducing interstitial cystitis by oxidative stress using bladder instillation of a nitric oxide donor gel"
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          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">The rats undergo tricotomy and asepsis &#40;A&#41;&#46; The urethra is shown with tweezers &#40;B&#41;&#46; The catheter is inserted carefully &#40;C&#41;&#46; Instillation of the liquid according to each group &#40;D&#41;&#46;</p>"
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Interstitial cystitis &#40;IC&#41; is a condition characterized by bladder pain&#44; urinary urgency&#44; frequency and nocturia&#46; The International Continence Society &#40;ICS&#41; prefers the term painful bladder syndrome defined as the supra-pubic pain related to the bladder filling&#44; and with other symptoms such as increased frequency &#40;day and night&#41; in the absence of urinary tract infection or some other obvious disease&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> It is known that IC affects both men and women&#44; but it is predominantly present in women &#40;around 90&#37; of all the patients&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> The main problem for the patients is how disease impacts their quality of life&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">The regulation of the nitric oxide synthase enzyme &#40;NOS&#41; in the urine was suggested as an important factor in the immune response of IC&#46; Other theories include a possible infectious origin&#44; neurogenic inflammation and histamine-induced generalized visceral hypersensitivity caused by abnormalities in the immune or neuroendocrine system&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">A new experimental model using oxidative stress would be a major advantage for understanding this idiopathic condition&#46; Moreover&#44; it would allow for the experimental evaluation of new treatments&#46; The objective of this study is to present a new experimental model of IC induction by oxidative stress using a nitric oxide donor gel&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Materials and methods</span><p id="par0020" class="elsevierStylePara elsevierViewall">We studied the effects of a polymeric aqueous solution of the copolymer poly&#40;ethylene oxide&#41;&#8211;poly&#40;propylene oxide&#41;&#8211;poly&#40;ethylene oxide&#41; &#40;PEO&#8211;PPO&#8211;PEO&#41; Pluronic F127&#44; containing <span class="elsevierStyleItalic">S</span>-nitrousglutathione &#40;GSNO&#41; as a nitric oxide donor on the bladder wall of Wistar rats&#46; GSNO is an endogenous <span class="elsevierStyleItalic">S</span>-nitrousthiol that acts as a carrier and donor of NO&#44; increasing its half-life&#46; This project was developed at our institution&#44; after approval by the Research Ethics Committee&#44; protocol 1296-1&#46; The rats were accommodated in cages containing five animals each&#44; under ideal feeding&#44; temperature&#44; humidity and light conditions&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">A pilot study including 20 Wistar rats was carried out as a training process for bladder catheterization in the animals&#46; The sample size included 40 female Wistar rats aged 3 months&#46; The nitric oxide donor chosen for this experiment was the <span class="elsevierStyleItalic">S</span>-nitrousglutathione &#40;GSNO&#41;&#44; produced and donated by the Institute of Chemistry of the State University of Campinas&#46; GSNO was synthesized by reacting equimolar amounts of glutathione with sodium nitrite in aqueous hydrochloric acid &#40;HCl 0&#46;5<span class="elsevierStyleHsp" style=""></span>M&#41;&#44; stirring it in an ice bath for 40<span class="elsevierStyleHsp" style=""></span>min&#46; The final solution was precipitated with acetone&#44; filtered and washed with cold water and acetone&#46; The precipitate formed was dried for 24<span class="elsevierStyleHsp" style=""></span>h&#46; The GSNO obtained was stored in the freezer &#40;&#8722;20<span class="elsevierStyleHsp" style=""></span>&#176;C&#41; and protected from light&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Preparation of the solution containing NO Gel Pluronic F-127 &#40;25<span class="elsevierStyleHsp" style=""></span>wt&#37;&#41; in water containing GSNO &#40;100<span class="elsevierStyleHsp" style=""></span>&#956;M&#41; was prepared as described previously&#46; Pluronic F-127 solid was added to cold water &#40;5<span class="elsevierStyleHsp" style=""></span>&#176;C&#41;&#46; This solution was left at 5<span class="elsevierStyleHsp" style=""></span>&#176;C for 12<span class="elsevierStyleHsp" style=""></span>h to reach equilibrium dissolution of the polymer&#46; Appropriate volume of aqueous solution of GSNO &#40;0&#46;35<span class="elsevierStyleHsp" style=""></span>mM&#41; was added to the solution of Pluronic F-127 by stirring in an ice bath to complete homogenization of the solution&#46; The animals were anesthetized by injection of sodium thiopental in the dorsal vein of the tail and then placed in the supine position&#44; so that antisepsis could be performed with PVPI-lode&#46;</p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Group distribution</span><p id="par0035" class="elsevierStylePara elsevierViewall">Instillation was performed according to animal division in four groups&#44; as shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46; In all groups&#44; the substances were infused intravesically &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#44; until bladder overflow was achieved &#40;mean of 1<span class="elsevierStyleHsp" style=""></span>mL&#41;&#46; The substances were kept in the bladder until the next micturition of the animals&#46;<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">&#8211;</span><p id="par0040" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Group 1</span>&#46; Ten rats underwent two sessions of bladder instillation of saline solution 0&#46;9&#37; at 0&#46;04<span class="elsevierStyleHsp" style=""></span>ml&#47;min&#44; with a 24-h interval between them&#44; until bladder overflow was achieved and they were then injected with GSNO solution in 3 doses&#44; with a 2-day interval between each dose&#59; after that they were euthanized&#46;</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">&#8211;</span><p id="par0045" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Group 2</span>&#46; Ten rats underwent two sessions of bladder instillation of saline solution 0&#46;9&#37; at 0&#46;04<span class="elsevierStyleHsp" style=""></span>ml&#47;min&#44; with a 24-h interval between them until bladder overflow was achieved&#59; they were then injected with excipient solution &#40;only the polymeric solution&#44; without the GSNO&#41; in 3 doses&#44; 2 days between each dose and after that they were euthanized&#46;</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">&#8211;</span><p id="par0050" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Group 3</span>&#46; Ten rats underwent two sessions of bladder catheterization using protamine solution &#40;30<span class="elsevierStyleHsp" style=""></span>mg&#47;ml&#41; and KCl 300<span class="elsevierStyleHsp" style=""></span>mM 0&#46;04<span class="elsevierStyleHsp" style=""></span>ml&#47;min&#44; with a 24-h interval between them until bladder overflow &#40;when the maximum bladder capacity was obtained&#41;&#59; they were then injected with excipient solution &#40;only polymeric solution without GSNO&#41; in 3 doses&#44; with a 2-day between each dose&#59; after that they were euthanized&#46;</p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">&#8211;</span><p id="par0055" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Group 4</span>&#46; Ten rats underwent two sessions of bladder catheterization using protamine solution &#40;30<span class="elsevierStyleHsp" style=""></span>mg&#47;ml&#41; and KCl 300<span class="elsevierStyleHsp" style=""></span>mM 0&#46;04<span class="elsevierStyleHsp" style=""></span>ml&#47;min&#44; until bladder overflow with a 24-h interval between them &#40;when the maximum bladder capacity was obtained&#41;&#59; they were then injected with GSNO solution in 3 doses&#44; with a 2-day interval between each dose&#59; after that they were euthanized&#46;</p></li></ul></p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Analysis</span><p id="par0060" class="elsevierStylePara elsevierViewall">Half of the rats of each group were euthanized with a lethal dose of anesthetic on day 6&#44; and the other half after 9 days&#46; Skin and muscle layers were dissected and the abdominal wall was opened&#46; The bladder was identified and removed &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46; After opening the bladder&#44; it was put on a stick to be fixated in formaldehyde for 24<span class="elsevierStyleHsp" style=""></span>h and then in ethylic alcohol 70&#37;&#44; before being embedded in paraffin and analyzed for the presence of IC&#46; Histological slides were made with histological cuts 3&#8211;4<span class="elsevierStyleHsp" style=""></span>&#956;m wide and HE stained&#46; The pathological study was based on the following classification according to the therapeutic groups &#40;<a class="elsevierStyleCrossRefs" href="#tbl0010">Tables 2 and 3</a>&#41;&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0065" class="elsevierStylePara elsevierViewall">The histological slides were analyzed by a pathologist&#44; who received them identified only by numbers&#44; with no indication of the groups&#46; All the parameters of the table were analyzed and the data were analyzed statistically&#46; Statistical analysis was performed with assistance of the Department of Statistics of the Research Board of the Faculty of Medical Sciences of the State University of Campinas&#46; A descriptive analysis was conducted using frequency tables for categorical variables&#46; For comparison of proportions&#44; the Fisher exact test was used and the level of significance was 5&#37;&#46;</p></span></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Results</span><p id="par0070" class="elsevierStylePara elsevierViewall">Macroscopically we observed edema and hyperemia of the mucosa in 2 &#40;22&#37;&#41; of the animals in group 1&#44; in 0 &#40;0&#37;&#41; of the animals in group 2&#44; in 10 &#40;100&#37;&#41; of the animals in group 3&#44; and in 5 &#40;50&#37;&#41; of the animals in group 4&#46; In the protamine<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>KCl group and in saline<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>GSNO group&#44; similar effects were observed on the bladder wall&#46; A pathologist performed the microscopic evaluation following the parameters cited in <a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">Microscopically&#44; there was no significant difference between the groups regarding vascular congestion in the animals on day 6 &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;6329&#41;&#46; After 9 days&#44; vascular congestion was significantly reduced in group 2 &#40;saline solution<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>excipient&#41; when compared to groups 1&#44; 3 and 4 &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;0035&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>&#41;&#46; No difference was observed between the groups regarding fibrosis on day 6 &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;3781&#41;&#46; After 9 days&#44; fibrosis was significantly higher in group 4 &#40;protamine<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>GSNO&#41; when compared to groups 1 and 2 &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;0035&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0025">Table 5</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia><elsevierMultimedia ident="tbl0025"></elsevierMultimedia><p id="par0080" class="elsevierStylePara elsevierViewall">Neutrophilic infiltrate of variable intensity was observed in all groups after 6 days &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;7277&#41;&#46; A tendency towards regression was observed after 9 days&#44; without reaching differences of statistical significance between groups &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;2301&#41;&#46; A tendency towards regression was also observed in all groups regarding edema&#44; without significant differences either &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;8096 at 6 days&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;2478 at 9 days&#41;&#46; The animals euthanized on day 6 did not present any significant differences regarding lymphomonocitary infiltrate &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;7253&#41;&#59; however&#44; on day 9 there was a significant difference between the groups &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;0459&#41;&#46; In the group treated with GSNO<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>saline solution&#44; infiltrate was more extensive than in the rest&#46; Differential presence of mast cells in the infiltrate was not observed among groups&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Discussion</span><p id="par0085" class="elsevierStylePara elsevierViewall">Interstitial cystitis is a condition that deserves clinician attention&#44; especially due to the lack of reliable criteria for diagnosis&#46; Classically reported models do not reproduce the inflammation status properly&#44; mostly because its cause is unknown&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> Previous studies found higher levels of NO in these patients<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a>&#59; however&#44; it is very difficult to collect material from patients in clinical trials because it causes great discomfort&#46; A study was performed on patients in which 25<span class="elsevierStyleHsp" style=""></span>mL of air were introduced in the bladder by means of a catheter and the level of NO was compared to that in the air in the room&#46; The study found significant differences&#44; proving that the patients with cystitis presented more NO than healthy individuals&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a></p><p id="par0090" class="elsevierStylePara elsevierViewall">Experimental models of IC described in the literature are scarce&#46; The first projects to develop interstitial cystitis in animals used acetic acid&#44; cyclophosphamide&#44; lipopolysaccharides&#44; protamine sulphate and vanilloid receptor agonists&#46; These substances did not produce the effects intended&#44; either because they damaged the bladder too much&#44; or because they were not reliable&#46; Fraser et al&#46; sought to develop a model that would reliably mimic the acute phase of this debilitating disease&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> To this end&#44; they combined protamine sulphate &#40;PS&#41; treatment&#44; thought to breakdown urothelial umbrella cell barrier function&#44; and physiologic concentrations of potassium chloride &#40;KCl&#41; in an open cystometrogram animal model&#46; Female Sprague-Dawley rats were anesthetized and transurethral continuous cystometry was performed with normal saline and 100<span class="elsevierStyleHsp" style=""></span>mmol&#47;L KCl or 0<span class="elsevierStyleHsp" style=""></span>mmol&#47;L KCl as control&#46; Either 10 or 30<span class="elsevierStyleHsp" style=""></span>mg&#47;mL PS was then added to the control solution for a 30-min period &#40;for modest and severe urothelial barrier breakdown&#44; respectively&#41;&#44; after which the control solution was continued for 1&#8211;2<span class="elsevierStyleHsp" style=""></span>h&#46; Bladder contraction amplitudes&#44; durations&#44; frequency and intercontractile intervals were recorded and analyzed&#46; There were no differences between the saline 100<span class="elsevierStyleHsp" style=""></span>mmol&#47;L KCl or 500<span class="elsevierStyleHsp" style=""></span>mmol&#47;L KCl control periods&#44; indicating that barrier function in these animals was not affected by the physical preparation&#46; Of the treatments tested&#44; 100<span class="elsevierStyleHsp" style=""></span>mmol&#47;L KCl with 30<span class="elsevierStyleHsp" style=""></span>mg&#47;mL PS and 500<span class="elsevierStyleHsp" style=""></span>mmol&#47;L KCl &#40;the physiologic concentration of rat urine&#41; with either 10 or 30<span class="elsevierStyleHsp" style=""></span>mg&#47;mL PS produced reliable irritation&#44; which continued up to 2<span class="elsevierStyleHsp" style=""></span>h after cessation of PS administration&#46; These results indicate that the historical use of normal saline&#44; instead of the more physiologic 500<span class="elsevierStyleHsp" style=""></span>mmol&#47;L KCl for cystometry&#44; greatly biases our understanding of the function of the lower urinary tract in animal models of IC&#59; and modest&#44; non-cytotoxic insults to urothelial barrier function can result in dramatic irritative responses&#44; given the proper physiological conditions&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a></p><p id="par0095" class="elsevierStylePara elsevierViewall">In 2007&#44; an experimental model of IC with intraperitoneal administration of cyclophosphamide &#40;CP&#41; was described&#46; This anti-tumor agent is metabolized into acrolein in the kidney and accumulates in the bladder to produce toxic effects&#44; ultimately resulting in visceral pain&#46; This substance produces histological damage only in the urothelium when dissolved in 0&#46;9&#37; saline and administered intraperitoneally &#40;i&#46;p&#46;&#41;&#46; Vehicle or CP was administered &#40;200&#8211;400<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#44; i&#46;p&#46;&#41;&#44; and spontaneous and evoked pain behaviors were evaluated simultaneously in the same mice&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a></p><p id="par0100" class="elsevierStylePara elsevierViewall">Another experimental study was performed in cats that already presented idiopathic IC&#46; In some cats there is naturally an idiopathic form of IC that provokes all the characteristics of human IC&#44; including symptoms&#46; The animals had history of pollakiuria&#44; hematuria and micturition in inadequate locations&#46; After the study of NO levels in both control and IC bladders&#44; it was observed that the NO levels in the IC bladders were higher&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> Other experimental models of IC include the use of attenuated pseudorabies virus &#40;Bartha PRV&#41;&#44; an &#945;-herpes virus that is taken up by neurons and undergoes retrograde transport and viral replication within the central nervous system<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9&#44;10</span></a> and IC induction with substance P and lipopolysaccharides that induce the release of histamine and cytokine by the bladder&#46; The probable relation between NO and the inflammatory process related to IC brings an experimental model that is closer to reality with the use of a NO donor gel to start up the inflammatory process&#46; The inflammatory response to bladder instillation of an aqueous solution of <span class="elsevierStyleItalic">S</span>-nitrousglutathione &#40;GSNO&#41; was very similar to that induced by bladder instillation of PS and KCl&#46; Therefore&#44; instillation of GSNO can be considered a new model for experimental induction of interstitial cystitis in rats&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Conflict of interest</span><p id="par0105" class="elsevierStylePara elsevierViewall">The authors declare to have no conflict of interest&#46;</p></span></span>"
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          "identificador" => "sec0025"
          "titulo" => "Results"
        ]
        7 => array:2 [
          "identificador" => "sec0030"
          "titulo" => "Discussion"
        ]
        8 => array:2 [
          "identificador" => "sec0035"
          "titulo" => "Conflict of interest"
        ]
        9 => array:1 [
          "titulo" => "References"
        ]
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2010-05-25"
    "fechaAceptado" => "2010-05-27"
    "PalabrasClave" => array:2 [
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec85522"
          "palabras" => array:3 [
            0 => "Interstitial cystitis"
            1 => "Nitric oxide"
            2 => "<span class="elsevierStyleItalic">In vivo</span> model"
          ]
        ]
      ]
      "es" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec85521"
          "palabras" => array:3 [
            0 => "Cistitis intersticial"
            1 => "&#211;xido n&#237;trico"
            2 => "Modelo <span class="elsevierStyleItalic">in vivo</span>"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:2 [
      "en" => array:2 [
        "titulo" => "Summary"
        "resumen" => "<span class="elsevierStyleSectionTitle">Purpose</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">The aim of this study is to develop a new experimental model of inducing interstitial cystitis &#40;IC&#41; through vesical instillation of a polymeric solution containing the NO donor <span class="elsevierStyleItalic">S</span>-nitrousglutathione &#40;GSNO&#41; and to compare it to the experimental interstitial cystitis induced by vesical instillation of protamine and potassium chloride&#46;</p> <span class="elsevierStyleSectionTitle">Materials and methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">For that purpose 40 female Wistar rats were used&#44; divided into four groups&#58; &#40;1&#41; saline solution<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>GSNO&#59; &#40;2&#41; saline solution<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>polymeric solution &#40;without GNSO&#41;&#59; &#40;3&#41; protamine sulphate<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>KCl&#59; &#40;4&#41; protamine sulphate<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>GSNO&#46; The rats received one application &#40;5 animals&#41; or 3 applications &#40;5 animals&#41; of the corresponding substance through intravesical instillation&#44; and after 6<span class="elsevierStyleHsp" style=""></span>days &#40;5 animals&#41; or 9<span class="elsevierStyleHsp" style=""></span>days &#40;5 animals&#41; they were euthanized and their bladders were removed for macroscopic evaluation and histological study&#46;</p> <span class="elsevierStyleSectionTitle">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">In the macroscopic evaluation we observed edema and hyperemia of the mucosa in 2 &#40;22&#37;&#41; of the animals in group 1&#44; in 0 &#40;0&#37;&#41; of the animals in group 2&#44; in 10 &#40;100&#37;&#41; of the animals in group 3&#44; and in 5 &#40;50&#37;&#41; of the animals in group 4&#46; In the protamine<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>KCl group and in saline<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>GSNO similar effects were observed on the bladder wall&#46; The animals in group 2 &#40;saline<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>polymeric&#41; showed vascular congestion&#44; significantly smaller than the rest after 9<span class="elsevierStyleHsp" style=""></span>days instillations &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;0035&#41;&#46; Significant increased fibrosis was observed after instillations in groups 3 and 4&#44; after 6<span class="elsevierStyleHsp" style=""></span>days &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;3781&#41; and 9<span class="elsevierStyleHsp" style=""></span>days &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;0459&#41;&#44; respectively&#44; when compared to control &#40;group 2&#41;&#46; All groups presented neutrophilic infiltrate of variable intensity 6<span class="elsevierStyleHsp" style=""></span>days after instillations &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;7277&#41;&#46; After 9<span class="elsevierStyleHsp" style=""></span>days&#44; there was a regression of the infiltrate&#44; with no evidence of accentuated neutrophilic reaction in all the groups &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;2301&#41;&#46;</p> <span class="elsevierStyleSectionTitle">Conclusion</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">The inflammatory response to bladder instillation of an aqueous solution of <span class="elsevierStyleItalic">S</span>-nitrousglutathione was very similar to that induced by bladder instillation of protamine and KCl&#46; Instillation of an aqueous solution of GSNO can be considered a new model for experimental induction of interstitial cystitis&#46;</p>"
      ]
      "es" => array:2 [
        "titulo" => "Resumen"
        "resumen" => "<span class="elsevierStyleSectionTitle">Objetivo</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">La principal finalidad de este estudio es el desarrollo de un nuevo modelo experimental para la inducci&#243;n de cistitis intersticial &#40;CI&#41; mediante la instilaci&#243;n vesical de una soluci&#243;n polim&#233;rica que contiene el <span class="elsevierStyleItalic">S</span>-nitrosoglutati&#243;n donante de &#243;xido n&#237;trico &#40;GSNO&#41;&#44; y su comparaci&#243;n con la cistitis intersticial experimental inducida por instilaci&#243;n vesical de protamina y cloruro pot&#225;sico&#46;</p> <span class="elsevierStyleSectionTitle">Material y m&#233;todos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Para la consecuci&#243;n de nuestro objetivo utilizamos 40 hembras de rata Wistar divididas en cuatro grupos&#58; &#40;a&#41; soluci&#243;n salina<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>GSNO&#59; &#40;b&#41; soluci&#243;n salina<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>soluci&#243;n polim&#233;rica &#40;sin GNSO&#41;&#59; &#40;c&#41; sulfato de protamina<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>KCl&#59; y &#40;d&#41; sulfato de protamina<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>GSNO&#46; Se realiz&#243; bien una aplicaci&#243;n a las ratas &#40;5 animales&#41;&#44; bien 3 aplicaciones &#40;5 animales&#41; de la sustancia correspondiente mediante instilaci&#243;n vesical&#44; y al cabo de 6 d&#237;as &#40;5 animales&#41; o 9 d&#237;as &#40;5 animales&#41; se les practic&#243; la eutanasia y se les extrajeron las vejigas para su evaluaci&#243;n macrosc&#243;pica y estudio histol&#243;gico&#46;</p> <span class="elsevierStyleSectionTitle">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">En t&#233;rminos de evaluaci&#243;n macrosc&#243;pica observamos edema e hiperemia de la mucosa en dos &#40;22&#37;&#41; de los animales del grupo 1&#44; en 0 &#40;0&#37;&#41; de los del grupo 2&#44; en 10 &#40;100&#37;&#41; de los del 3 y en 5 &#40;50&#37;&#41; de los animales del grupo 4&#46; En el grupo de protamina<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>KCl y en soluci&#243;n salina<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>GSNO se observaron efectos similares en la pared vesical&#46; Los animales del grupo 2 &#40;soluci&#243;n salina<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>polim&#233;rica&#41; mostraban congesti&#243;n vascular&#44; bastante menos significativa que en el resto despu&#233;s de 9 d&#237;as de instilaciones &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;0035&#41;&#46; Se observ&#243; un aumento de la fibrosis tras las instilaciones en los grupos 3 y 4 a los 6 d&#237;as &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;3781&#41; y a los 9 d&#237;as &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;0459&#41; respectivamente&#44; en comparaci&#243;n con los controles &#40;grupo 2&#41;&#46; En todos los grupos aparec&#237;a un infiltrado de neutr&#243;filos con intensidad variable a los 6 d&#237;as de las instilaciones &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;7277&#41;&#46; Al cabo de 9 d&#237;as se produc&#237;a una regresi&#243;n del infiltrado&#44; y sin evidencias de reacci&#243;n neutrof&#237;lica marcada en todos los grupos &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;2301&#41;&#46;</p> <span class="elsevierStyleSectionTitle">Conclusi&#243;n</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">La respuesta inflamatoria a la instilaci&#243;n vesical de una soluci&#243;n acuosa de <span class="elsevierStyleItalic">S</span>-nitrosoglutati&#243;n fue muy parecida a la inducida por la instilaci&#243;n vesical de protamina y KCl&#46; La instilaci&#243;n de una soluci&#243;n acuosa de GSNO puede considerarse un nuevo modelo para la inducci&#243;n experimental de cistitis intersticial&#46;</p>"
      ]
    ]
    "NotaPie" => array:1 [
      0 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara">Please cite this article as&#58; Palma TF&#44; et al&#46; Un nuevo modelo experimental de inducci&#243;n de cistitis intersticial mediante estr&#233;s oxidativo empleando instilaci&#243;n vesical de un gel donante de &#243;xido n&#237;trico&#46; Actas Urol Esp 2011&#59;35&#58;253&#8211;8&#46;</p>"
      ]
    ]
    "multimedia" => array:7 [
      0 => array:7 [
        "identificador" => "fig0005"
        "etiqueta" => "Figure 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 1494
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            "Tamanyo" => 316165
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        "descripcion" => array:1 [
          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">The rats undergo tricotomy and asepsis &#40;A&#41;&#46; The urethra is shown with tweezers &#40;B&#41;&#46; The catheter is inserted carefully &#40;C&#41;&#46; Instillation of the liquid according to each group &#40;D&#41;&#46;</p>"
        ]
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      1 => array:7 [
        "identificador" => "fig0010"
        "etiqueta" => "Figure 2"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr2.jpeg"
            "Alto" => 1771
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        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Skin is incised &#40;A&#41;&#46; Muscle layer is dissected &#40;B&#41;&#46; Opening of the abdominal wall &#40;C&#41;&#46; Identification and removal of the bladder &#40;D&#41;&#46; Opening the bladder &#40;E&#41;&#46; The bladder is put on a stick to be fixated in formaldehyde &#40;F&#41;&#46;</p>"
        ]
      ]
      2 => array:7 [
        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
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        "tabla" => array:2 [
          "leyenda" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">In <span class="elsevierStyleItalic">T</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>6&#44; five animals were euthanized&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" style="border-bottom: 2px solid black">Time&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">T</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">T</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td 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" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">T</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td 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" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">T</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td 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" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">T</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></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  " colspan="6" align="left" valign="\n
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                  \t\t\t\t">Group 1&#46; Saline solution<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>GSNO</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Day&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">2&nbsp;\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
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                  \t\t\t\t">3&nbsp;\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
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                  \t\t\t\t">6&nbsp;\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">9&nbsp;\t\t\t\t\t\t\n
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                  \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"><span class="elsevierStyleHsp" style=""></span>Instillation&nbsp;\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">Saline solution&nbsp;\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">Saline solution&nbsp;\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">GSNO&nbsp;\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">GSNO&nbsp;\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">GSNO&nbsp;\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="6" 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  " colspan="6" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Group 2&#46; Saline solution<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>polymeric solution</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Day&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">2&nbsp;\t\t\t\t\t\t\n
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                  \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&nbsp;\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
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                  \t\t\t\t">6&nbsp;\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">9&nbsp;\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  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Instillation&nbsp;\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">Saline solution&nbsp;\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">Saline solution&nbsp;\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">Polymeric solution&nbsp;\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">Polymeric solution&nbsp;\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">Polymeric solution&nbsp;\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="6" 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  " colspan="6" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Group 3&#46; Saline solution<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>protamine and KCl</td></tr><tr title="table-row"><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"><span class="elsevierStyleHsp" style=""></span>Day&nbsp;\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">1&nbsp;\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">2&nbsp;\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">3&nbsp;\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">6&nbsp;\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">9&nbsp;\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  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Instillation&nbsp;\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">Saline solution&nbsp;\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">Saline solution&nbsp;\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">Protamine&nbsp;\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">Protamine&nbsp;\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">Protamine&nbsp;\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="6" 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  " colspan="6" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Group 4&#46; Protamine and KCl<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>GSNO</td></tr><tr title="table-row"><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"><span class="elsevierStyleHsp" style=""></span>Day&nbsp;\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">1&nbsp;\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">2&nbsp;\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">3&nbsp;\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">6&nbsp;\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">9&nbsp;\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  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Instillation&nbsp;\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">Protamine&nbsp;\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">Protamine&nbsp;\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">GSNO&nbsp;\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">GSNO&nbsp;\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">GSNO&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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                0 => "xTab183631.png"
              ]
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        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Time table of groups 1&#8211;4&#46;</p>"
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      3 => array:7 [
        "identificador" => "tbl0010"
        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:1 [
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "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"><td 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" style="border-bottom: 2px solid black">Group&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">Treatment&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></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  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&nbsp;\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">Saline<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>GSNO&nbsp;\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  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&nbsp;\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">Saline<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>excipient&nbsp;\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  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&nbsp;\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">Protamine<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>excipient&nbsp;\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  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&nbsp;\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">Protamine<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>GSNO&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "en" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Groups of treatment&#46;</p>"
        ]
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      4 => array:7 [
        "identificador" => "tbl0015"
        "etiqueta" => "Table 3"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:1 [
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "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"><td 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">Parameters&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Severity</td></tr><tr title="table-row"><td 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" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">Acute&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">Moderate&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">Mild&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td 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" style="border-bottom: 2px solid black">Not Present&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></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  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Neutrophils&nbsp;\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&nbsp;\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&nbsp;\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&nbsp;\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">0&nbsp;\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  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Edema&nbsp;\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&nbsp;\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&nbsp;\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&nbsp;\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">0&nbsp;\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  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Vascular congestion&nbsp;\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&nbsp;\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&nbsp;\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&nbsp;\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">0&nbsp;\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  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Monomorphonuclear&nbsp;\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&nbsp;\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&nbsp;\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&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">Fibrosis&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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                0 => "xTab183632.png"
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        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Classifications of histological findings of HE&#46;</p>"
        ]
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      5 => array:7 [
        "identificador" => "tbl0020"
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Protamine<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>GSNO&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Saline<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>excipient&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Protamine&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Protamine<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>GSNO&nbsp;\t\t\t\t\t\t\n
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                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab183635.png"
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Saline<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>excipient&nbsp;\t\t\t\t\t\t\n
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                      "titulo" => "Determination of nitric oxide synthase activity and apoptosis of germ cells in different obstruction models"
                      "autores" => array:1 [
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                          "etal" => true
                          "autores" => array:6 [
                            0 => "G&#46; Oktem"
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                        "tituloSerie" => "Acta Histochem"
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                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18614207"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The standardisation of terminology in lower urinary tract function&#58; report from the standardisation sub-committee of the International Continence Society"
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                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
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                            2 => "M&#46; Fall"
                            3 => "D&#46; Griffiths"
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                      "titulo" => "DMSO&#58; effect on bladder afferent neurons and nitric oxide release"
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                          "autores" => array:3 [
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                      "Revista" => array:6 [
                        "tituloSerie" => "J Urol"
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                        "paginaFinal" => "1995"
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Article information

ISSN: 21735786
Original language: English

DOI:10.1016/j.acuroe.2011.06.006

The statistics are updated each day

Year/Month	Html	Pdf	Total

2023 March	1	0	1
2018 February	10	0	10
2018 January	10	1	11
2017 December	5	3	8
2017 November	7	0	7
2017 October	16	2	18
2017 September	11	3	14
2017 August	6	5	11
2017 July	13	1	14
2017 June	18	3	21
2017 May	12	2	14
2017 April	11	0	11
2017 March	15	3	18
2017 February	7	0	7
2017 January	17	0	17
2016 December	15	3	18
2016 November	24	3	27
2016 October	24	4	28
2016 September	15	4	19
2016 August	19	2	21
2016 July	25	3	28
2016 June	32	11	43
2016 May	29	22	51
2016 April	32	17	49
2016 March	33	6	39
2016 February	38	17	55
2016 January	34	10	44
2015 December	23	12	35
2015 November	29	14	43
2015 October	38	20	58
2015 September	29	7	36
2015 August	15	5	20
2015 July	11	4	15
2015 June	15	5	20
2015 May	15	1	16
2015 April	28	7	35
2015 March	23	10	33
2015 February	19	4	23
2015 January	37	8	45
2014 December	35	15	50
2014 November	20	11	31
2014 October	39	10	49
2014 September	46	10	56
2014 August	31	14	45
2014 July	35	6	41
2014 June	21	9	30
2014 May	16	8	24
2014 April	17	8	25
2014 March	27	7	34
2014 February	13	5	18
2014 January	19	9	28
2013 December	21	8	29
2013 November	23	5	28
2013 October	27	6	33
2013 September	21	7	28
2013 August	14	5	19
2013 July	9	3	12

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