Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 231
Filtrar
1.
Sci Rep ; 11(1): 2216, 2021 01 26.
Artículo en Inglés | MEDLINE | ID: mdl-33500454

RESUMEN

Allantoin (ALL) is a phytochemical possessing an impressive array of biological activities. Nonetheless, developing a nanostructured delivery system targeted to augment the gastric antiulcerogenic activity of ALL has not been so far investigated. Consequently, in this survey, ALL-loaded chitosan/sodium tripolyphosphate nanoparticles (ALL-loaded CS/STPP NPs) were prepared by ionotropic gelation technique and thoroughly characterized. A full 24 factorial design was adopted using four independently controlled parameters (ICPs). Comprehensive characterization, in vitro evaluations as well as antiulcerogenic activity study against ethanol-induced gastric ulcer in rats of the optimized NPs formula were conducted. The optimized NPs formula, (CS (1.5% w/v), STPP (0.3% w/v), CS:STPP volume ratio (5:1), ALL amount (13 mg)), was the most convenient one with drug content of 6.26 mg, drug entrapment efficiency % of 48.12%, particle size of 508.3 nm, polydispersity index 0.29 and ζ-potential of + 35.70 mV. It displayed a sustained in vitro release profile and mucoadhesive strength of 45.55%. ALL-loaded CS/STPP NPs (F-9) provoked remarkable antiulcerogenic activity against ethanol-induced gastric ulceration in rats, which was accentuated by histopathological, immunohistochemical (IHC) and biochemical studies. In conclusion, the prepared ALL-loaded CS/STPP NPs could be presented to the phytomedicine field as an auspicious oral delivery system for gastric ulceration management.


Asunto(s)
Alantoína/uso terapéutico , Quitosano/química , Composición de Medicamentos , Nanopartículas/química , Úlcera Gástrica/inducido químicamente , Úlcera Gástrica/tratamiento farmacológico , Adhesividad , Alantoína/química , Alantoína/farmacología , Animales , Quitosano/análogos & derivados , Liberación de Fármacos , Etanol , Mucosa Gástrica/patología , Mediadores de Inflamación/sangre , Cinética , Malondialdehído/metabolismo , Mucinas/metabolismo , Factor 2 Relacionado con NF-E2 , Nanopartículas/ultraestructura , Estrés Oxidativo , Tamaño de la Partícula , Difracción de Polvo , Ratas , Espectroscopía Infrarroja por Transformada de Fourier , Electricidad Estática , Úlcera Gástrica/sangre , Úlcera Gástrica/patología , Temperatura , Factor de Necrosis Tumoral alfa/metabolismo
2.
Asian Pac J Cancer Prev ; 21(7): 2149-2153, 2020 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-32711444

RESUMEN

BACKGROUND AND AIM OF THE WORK: Helicobacter pylori-associated gastric ulcer (H.pylori-GU) is a serious condition, not only because H.pylori is identified as a grade 1 carcinogen but also because GU is a precancerous condition. Identification and treatment of H.pylori-GU may prevent the sequential progression of dysplasia to carcinoma. Trefoil factor 3 (Tf3) has been implicated in gastric mucosal repair. We compared serum Tf3 to gastric endoscopy in diagnosing H.pylori-GU. SUBJECTS AND METHODS: The study included eighty patients suffering from H.pylori induced gastritis, forty of which presented with GU. Gastric endoscopy with slide urease test was used to diagnose H.pylori-GU. Serum Tf3 level was determined using an enzyme immunoassay in all patients as well as thirty healthy volunteers. RESULTS: Serum Tf3 showed a significant stepwise decrease among the studied groups. It was significantly lower in patients compared to the control group (p<0.001). Furthermore, it was lower in those with GU compared to those without GU (p=0.023). Based on a receiver operating characteristic curve generated cut off value of 2.4 ng/mL, the diagnostic performance of serum Tf3 as a biomarker of H.pylori-GU revealed a diagnostic specificity of 42.5%, sensitivity of 67.5%, positive and negative predictive values of 54% and 56.67% respectively. CONCLUSION: Although serum Tf3 showed significant variation in H.pylori-GU, further studies are warranted to confirm its role in the pathogenesis of gastric ulcers.
.


Asunto(s)
Endoscopía/métodos , Infecciones por Helicobacter/complicaciones , Helicobacter pylori/aislamiento & purificación , Úlcera Gástrica/diagnóstico , Factor Trefoil-3/sangre , Adulto , Anciano , Estudios de Casos y Controles , Femenino , Estudios de Seguimiento , Infecciones por Helicobacter/microbiología , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Úlcera Gástrica/sangre , Úlcera Gástrica/diagnóstico por imagen , Úlcera Gástrica/microbiología , Adulto Joven
4.
Chem Biol Interact ; 291: 153-161, 2018 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-29944876

RESUMEN

Stress induced gastric ulcer is a serious health problem in diabetic patients. Some studies reported that hesperidin (HDN), a citrus bioflavonoid, can bind to and stimulate peroxisome proliferator-activator receptor-gamma (PPAR-γ) which may mediate its antidiabetic, anti-inflammatory and anti-oxidant effects. This work aims to study the possible protective effect of HDN against stress induced gastric ulcer in diabetic rats as well as the possible involvement of PPARγ in this effect. Type 2 diabetes was induced using streptozotocin and nicotinamide. Diabetic rats received either HDN (100 mg/kg/day, orally) & omeprazole (20 mg/kg/day, orally) or HDN (100 mg/kg/day, orally) + GW9662, PPARγ antagonist, (1 mg/kg/day, i.p.) for 8 weeks then acute gastric injury was induced by cold restraint stress technique. Glycemic controls and gastroprotective effects were evaluated by measuring serum levels of glucose and insulin, gastric free and total acidity and gastric ulcer indices. Histopathological examination of gastric mucosa was also performed. To determine the underlying mechanism of action, gastric mucosal expression of nuclear factor (erythroid-derived 2)-like 2 (Nrf2), hemeoxygenase-1 (HO-1), cluster of differentiation 45 (CD45), cyclooxygenase-2 (COX-2), nuclear factor kappa B (NFκB) and inducible nitric oxide synthase (iNOS), gastric contents of reduced glutathione (GSH), malondialdehyde (MDA), tumor necrosis factor alpha (TNF-α) and nitric oxide (NO); as well as superoxide dismutase (SOD) and catalase activities were measured. HDN significantly improved glycemic level; it also reduced gastric acidity and gastric ulcer index and histopathological changes comparable to that produced by omeprazole. Moreover, HDN reduced lipid peroxidation and inflammatory markers levels and enhanced antioxidant capacity. The use of GW9662 significantly abrogated the gastric protective effect of HDN as well as reduced the antioxidant and anti-inflammatory effects. Our work showed, for the first time that, HDN has promising protective effect against stress induced gastric ulcer in diabetic rats through activation of PPARγ.


Asunto(s)
Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Experimental/patología , Hesperidina/uso terapéutico , PPAR gamma/metabolismo , Sustancias Protectoras/uso terapéutico , Úlcera Gástrica/tratamiento farmacológico , Úlcera Gástrica/metabolismo , Estrés Fisiológico , Animales , Antioxidantes/metabolismo , Biomarcadores/metabolismo , Glucemia/metabolismo , Peso Corporal/efectos de los fármacos , Ciclooxigenasa 2/metabolismo , Diabetes Mellitus Experimental/sangre , Progresión de la Enfermedad , Hesperidina/farmacología , Concentración de Iones de Hidrógeno , Insulina/sangre , Antígenos Comunes de Leucocito/metabolismo , Masculino , FN-kappa B/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa de Tipo II/metabolismo , Omeprazol/farmacología , Omeprazol/uso terapéutico , Oxidantes/metabolismo , Sustancias Protectoras/farmacología , Ratas Wistar , Estómago/efectos de los fármacos , Estómago/patología , Úlcera Gástrica/sangre , Úlcera Gástrica/patología , Factor de Necrosis Tumoral alfa/metabolismo
5.
Nutrients ; 9(9)2017 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-28878183

RESUMEN

Gastritis or peptic ulcer is believed to affect about half of people worldwide. Traditional medications can lead to adverse effects, therefore, alternative nutritional strategies are needed to prevent the development of gastric mucosal damage. A novel combination of two food-grade ingredients, wheat peptides and fucoidan (WPF), was prepared to treat male Sprague Dawley rats for 30 days before gastric mucosal damage was induced by oral administration of ethanol. The serum levels of biomarkers were determined by enzyme-linked immunosorbent assay. Biomarkers in stomach tissue were analyzed using immunohistochemistry. In addition, human gastric epithelial cell line (GES-1) was used to investigate protein expression by Western blot. WPF could attenuate ethanol-induced gastric mucosal damage in an inverse dose-dependent manner, with both ulcer index and pathological index improved. WPF increased superoxide dismutase level and decreased malondialdehyde level. WPF also decreased the levels of interleukin-8, platelet-activating factor, and Caspase 3, while increasing the levels of prostaglandin E-2, epidermal growth factor (EGF), and EGF receptor (EGFR). Furthermore, phosphorylation of EGFR and extracellular signal-regulated kinases was induced by WPF in GES-1 cells. In conclusion, the novel combination of wheat peptides and fucoidan attenuated ethanol-induced gastric mucosal damage in rats through anti-oxidant, anti-inflammatory, and pro-survival mechanisms.


Asunto(s)
Antiinflamatorios/farmacología , Antioxidantes/farmacología , Etanol , Mucosa Gástrica/efectos de los fármacos , Proteínas de Plantas/farmacología , Polisacáridos/farmacología , Hidrolisados de Proteína/farmacología , Úlcera Gástrica/prevención & control , Animales , Antiinflamatorios/aislamiento & purificación , Antioxidantes/aislamiento & purificación , Biomarcadores/sangre , Línea Celular , Supervivencia Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Receptores ErbB/metabolismo , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patología , Humanos , Masculino , Fosforilación , Proteínas de Plantas/aislamiento & purificación , Hidrolisados de Proteína/aislamiento & purificación , Ratas Sprague-Dawley , Transducción de Señal/efectos de los fármacos , Úlcera Gástrica/sangre , Úlcera Gástrica/inducido químicamente , Úlcera Gástrica/patología , Factores de Tiempo , Triticum/química
6.
Acta Vet Scand ; 59(1): 15, 2017 Mar 11.
Artículo en Inglés | MEDLINE | ID: mdl-28284214

RESUMEN

BACKGROUND: Equine gastric ulcer syndrome (EGUS) is common in adult horses, particularly those involved in performance disciplines. Currently, detection of EGUS by gastroscopy is the only reliable ante mortem method for definitive diagnosis; however it is unsuitable as a screening test because it is expensive, time consuming, and is not readily available to most veterinarians. Sucrose permeability testing represents a simple, economical alternative to gastroscopy for screening purposes, and the feasibility of this approach in the horse has been previously reported. The aim of this study was to determine the diagnostic accuracy of blood sucrose as a screening test for EGUS in a large group of adult horses with and without naturally occurring gastric disease. RESULTS: One hundred and one adult horses with or without naturally occurring gastric ulceration were studied. The diagnostic accuracy of blood sucrose for diagnosis of gastric lesions (GL), glandular lesions (GDL), squamous lesions (SQL), and clinically significant lesions (CSL) at 45 and 90 min after administration of 1 g/kg of sucrose via nasogastric intubation was assessed using receiver operator characteristics (ROC) curves and calculating the area under the curve (AUC). For each lesion type, sucrose concentration in blood was compared to gastroscopy, as the gold standard, and sensitivities (Se) and specificities (Sp) were calculated across a range of sucrose concentrations. Ulcer grading was performed blindly by one observer; and the results were validated by comparing them with that of two other observers, and calculating the level of agreement. Cut-off values were selected manually to optimize Se. The prevalence of GL, GDL, SQL, and CSL was 83, 70, 53 and 58% respectively. At the selected cut-offs, Se ranged from 51 to 79% and Sp ranged from 43 to 72%, depending upon the lesion type and time of sampling. CONCLUSIONS: Blood sucrose is neither a sensitive or specific test for detecting EGUS in this population of adult horses with naturally occurring gastric ulceration. Further studies aimed at evaluating the performance characteristics of the test in different study populations are warranted. Given the limitations of endoscopy, due consideration should also be given to alternative methods for comparison of blood sucrose with a gold standard.


Asunto(s)
Enfermedades de los Caballos/sangre , Enfermedades de los Caballos/diagnóstico , Úlcera Gástrica/veterinaria , Sacarosa/sangre , Animales , Femenino , Gastroscopía/veterinaria , Caballos , Masculino , Sensibilidad y Especificidad , Úlcera Gástrica/sangre , Úlcera Gástrica/diagnóstico
7.
Klin Khir ; (4): 9-11, 2016 Apr.
Artículo en Ucraniano | MEDLINE | ID: mdl-27434945

RESUMEN

Pathophysiological mechanisms of the vitamin K impact, including those in the gut with ulcerative affection, are studied still insufficiently. Investigations of pharmacogenomics of the vitamin K gives a new approach to therapy in patients, suffering gastro-intestinal hemorrhage. Possibilities of titration of the vitamin K3 (menadione) doses, depending on level of estrogenemia and genetic constitution, concerning genes-candidates ESR1 (rs2234693) and VKORC1 (rs9923231), were studied. There were examined 36 patients, who were treated for the ulcer hemorrhage. The blood serum concentration of estradiol was investigated in accordance to method of solid phase enzyme immunoassay, the genotyping procedure was performed in accordance to indices of polymerase chain reaction with analysis of the restrictional fragments length. The initial daily dose of menadione have constituted 20 mg. After a genotype determination made (first-second day after admittance to hospital) in patients with normoestrogenemia in genotypes CC/GG, CC/GA, CT/GG, CT/GA a vitaminotherapy was prolonged in daily dose of 20 mg, and in a conditionally-pathological variant of genotype the dose of vitamin K was enhanced up to 30 mg. Determination of hormones and the patients' genetic constitution makes possible to apply a personified approach for the vitamin K3 application in the ulcerative hemorrhage.


Asunto(s)
Anticoagulantes/uso terapéutico , Úlcera Duodenal/tratamiento farmacológico , Receptor alfa de Estrógeno/genética , Hemorragia Gastrointestinal/tratamiento farmacológico , Úlcera Gástrica/tratamiento farmacológico , Vitamina K Epóxido Reductasas/genética , Vitamina K/uso terapéutico , Adulto , Cálculo de Dosificación de Drogas , Úlcera Duodenal/sangre , Úlcera Duodenal/genética , Úlcera Duodenal/patología , Estradiol/sangre , Receptor alfa de Estrógeno/sangre , Femenino , Hemorragia Gastrointestinal/sangre , Hemorragia Gastrointestinal/genética , Hemorragia Gastrointestinal/patología , Expresión Génica , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Polimorfismo de Longitud del Fragmento de Restricción , Polimorfismo de Nucleótido Simple , Medicina de Precisión , Úlcera Gástrica/sangre , Úlcera Gástrica/genética , Úlcera Gástrica/patología , Vitamina K Epóxido Reductasas/sangre
8.
J Physiol Pharmacol ; 67(2): 261-75, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-27226186

RESUMEN

The antioxidizing properties of curcumin, a highly pleiotropic substance used for centuries in traditional medicine has been confirmed by numerous experimental and clinical studies. Curcumin exhibits anti-inflammatory, antiproliferative and anti-angiogenic actions inhibiting the development and progression of tumors but the efficacy of this compound to influence gastric acid secretion n in the stomach and to affect the gastric mucosal damage induced by non-topical ulcerogenes such as stress has been little studied. We determined the effect of curcumin on basal and pentagastrin- or histamine-stimulated gastric secretion, in rats with surgically implemented gastric fistulas and we assessed the contribution of gastric secretion, endogenous prostaglandin (PG), endogenous nitric oxide (NO), as well as sensory afferent nerves in the mechanisms underlying the potential gastroprotective effects of curcumin against stress-induced gastric mucosal lesions. Rats exposed to water immersion and restraint stress (WRS) for 3.5 h were pretreated either with: 1) vehicle (saline); 2) curcumin (2.5 - 100 mg/kg i.g.) or 3) curcumin (50 mg/kg i.g.) combined with or without indomethacin (5 mg/kg i.p.), SC-560 (5 mg/kg i.g.) or rofecoxib (10 mg/kg i.g.); 4) curcumin (50 mg/kg i.g.) co-administered with (L-NNA (20 mg/kg i.p.) with or without L-arginine (200 mg/kg i.g.), a substrate for NO-synthase; 5) curcumin (50 mg/kg i.g.) administered in rats with intact or capsaicin-induced functional ablation of sensory nerve fibers, and 6) curcumin (50 mg/kg i.g.) administered with capsazepine (5 mg/kg i.g.), the antagonist of vanilloid TRPV1 receptor. The number of gastric lesions was determined by planimetry, the gastric blood flow (GBF) was assessed by H2-gas clearance technique, the plasma gastrin concentrations were measured using the radioimmunoassay (RIA) and the expression of mRNA for tumor necrosis factor-α (TNF-α), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in gastric mucosa was evaluated by reverse transcription polymerase chain reaction (RT-PCR). Curcumin dose-dependently reduced the WRS-induced gastric lesions, the dose inhibiting these lesions by 50% being about 50 mg/kg. These effects of curcumin were accompanied by an increase in GBF and the reduction in basal and histamine- or pentagastrin-stimulated gastric acid secretion. The protective and hyperemic activities of curcumin (50 mg/kg i.g.) against WRS lesions were significantly attenuated (P < 0.05) in rats pretreated with rofecoxib and SC-560 and completely reversed (P < 0.01) by indomethacin. L-NNA significantly reduced (P < 0.05) the decrease in WRS-induced lesions and the accompanying rise in GBF caused by curcumin and these effects were restored by concurrent treatment with L-arginine (200 mg/kg i.g.). The curcumin-induced decrease in the number of WRS-induced gastric lesions and accompanying increase in the GBF were significantly attenuated (P < 0.05) in capsaicin-denervated rats and in those pretreated with capsazepine. These effects of curcumin in rats with capsaicin denervation were restored by concomitant treatment with exogenous calcitonin gene related pepetide (CGRP) combined with curcumin and subsequently exposed to WRS. The expression of mRNA for TNF-α, COX-2 and iNOS was significantly increased (P < 0.05) in vehicle-pretreated control rats exposed to WRS and significantly attenuated (P < 0.05) by curcumin administered in graded dosages. We conclude that curcumin exerts gastroprotective and hyperemic activities against experimental stress-induced gastric lesions by mechanism involving endogenous prostaglandins, NO, the neuropeptides such as CGRP released from capsaicin-sensitive afferent nerves and the activation of vanilloid TRPV1 receptors located on these sensory nerve terminals.


Asunto(s)
Antiulcerosos/farmacología , Curcumina/farmacología , Mucosa Gástrica/efectos de los fármacos , Animales , Antiulcerosos/uso terapéutico , Capsaicina/análogos & derivados , Capsaicina/farmacología , Curcumina/uso terapéutico , Ciclooxigenasa 2/genética , Femenino , Ácido Gástrico/metabolismo , Mucosa Gástrica/metabolismo , Gastrinas/sangre , Inmersión , Masculino , Óxido Nítrico Sintasa de Tipo II/genética , ARN Mensajero/metabolismo , Ratas Wistar , Restricción Física , Úlcera Gástrica/sangre , Úlcera Gástrica/tratamiento farmacológico , Úlcera Gástrica/metabolismo , Estrés Psicológico , Canales Catiónicos TRPV/antagonistas & inhibidores , Factor de Necrosis Tumoral alfa/genética , Agua
9.
Cell Mol Neurobiol ; 36(4): 621-35, 2016 May.
Artículo en Inglés | MEDLINE | ID: mdl-26215054

RESUMEN

Results of the very first experiments conducted to evaluate therapeutic potentials of a fumarate containing Fumaria indica extract and of fairly low daily oral doses of monomethyl fumarate for prevention of chronic unavoidable foot-shock stress-induced gastric ulcers, and possible involvement of diverse neuro-hormonal and oxidative process in their stress response desensitizing effects are reported and discussed in this article. Preventive effects of 21 daily oral 60, 120, and 240 mg/kg doses of a standardized 50 % methanolic F. indica extract (MFI) and 1.25, 2.50, and 5.00 mg/kg/day of pure monomethyl fumarate (MMF) were compared in rats subjected to one hour daily unavoidable foot-shocks. A pharmaceutically well-standardized Withania somnifera (WS) root extract was used as a reference herbal anti-stress agent in all experiments. Effects of the treatments on stress-induced alterations in body weight, adrenal and spleen weights, gastric ulcer and ulcer index, weight of glandular stomach, protective mucosal glycoprotein content, cellular proliferation, oxidative stress on stomach fundus, and brain tissues of male rats were quantified. Other parameters quantified were plasma corticosterone levels, brain monoamine levels, and expressions of the cytokines TNF-α, IL-10, and IL-1ß in blood and brain of stressed and treated rats. Most but not every observed stress-induced anomalies were suppressed or completely prevented by both MFI and pure MMF treatments in dose-dependent manner. Qualitatively, the observed activity profiles of both of them were similar to those of WS dose tested. These results reveal that both MFI and MMF are potent gastro-protective agents against chronic unavoidable stress-induced ulcers and strongly suggest that they act as regulators or modulators of monoamine, corticosterone, and cytokine homeostasis.


Asunto(s)
Fumaratos/uso terapéutico , Fumaria/química , Maleatos/uso terapéutico , Extractos Vegetales/uso terapéutico , Sustancias Protectoras/uso terapéutico , Estómago/patología , Estrés Psicológico/tratamiento farmacológico , Animales , Peso Corporal/efectos de los fármacos , Encéfalo/efectos de los fármacos , Encéfalo/patología , Enfermedad Crónica , Corticosterona/sangre , Citocinas/metabolismo , Fumaratos/farmacología , Masculino , Maleatos/farmacología , Metanol/química , Tamaño de los Órganos/efectos de los fármacos , Extractos Vegetales/farmacología , Sustancias Protectoras/farmacología , Ratas , Reacción en Cadena en Tiempo Real de la Polimerasa , Estómago/efectos de los fármacos , Úlcera Gástrica/sangre , Úlcera Gástrica/tratamiento farmacológico , Úlcera Gástrica/patología , Estrés Psicológico/sangre , Estrés Psicológico/patología
10.
Klin Lab Diagn ; 61(4): 233-7, 2016 Apr.
Artículo en Ruso | MEDLINE | ID: mdl-30586244

RESUMEN

The stomach ulcer is widely spread and is characterized by dangerous and now and then lethal complications. The study was carried out to develop mode of prognosis of course of stomach ulcer. The complex examination of 40 healthy volunteers (control group) and 42 patients with stomach ulcer (main group)was implemented. All participants gave informed consent. In blood serum of examined persons using immune enzyme technique the concentration of secretory immunoglobulin A (sIgA), pepsinogen-II (PG-II) and cancer antigen 72-4 (CA 72-4) were detected. The results were statistically processed. In patients levels of sIgA and PG-II exceeded upper limits of normal values in 90.5% and 61.9% of cases correspondingly and depended on course of disease. The level CA 72-4 was higher of upper limit of normal values in all patients with severe course and frequent exacerbations of stomach ulcer. The detected in patients significant alterations of sIgA, PG-II, CA 72-4 permit to recommend detection of the given combination of indices for prognosis of course of stomach ulcer.


Asunto(s)
Antígenos de Carbohidratos Asociados a Tumores/sangre , Inmunoglobulina A Secretora/sangre , Pepsinógeno C/sangre , Úlcera Gástrica/sangre , Adulto , Progresión de la Enfermedad , Femenino , Mucosa Gástrica/patología , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Úlcera Gástrica/fisiopatología
11.
Molecules ; 20(12): 22553-64, 2015 Dec 16.
Artículo en Inglés | MEDLINE | ID: mdl-26694339

RESUMEN

The objective of this study was to explore the gastroprotective properties of the aerial part of Lycium chinense Mill (LCA) against ethanol-induced gastric mucosa lesions in mice models. Administration of LCA at doses of 50, 100, 200 and 400 mg/kg body weight prior to ethanol consumption dose dependently inhibited gastric ulcers. The gastric mucosal injury was analyzed by gastric juice acidity, glutathione (GSH), superoxide dismutase (SOD), malondialdehyde (MDA), myeloperoxidase (MPO) activities. Furthermore, the levels of the inflammatory mediators, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1ß (IL-1ß) in serum were also analyzed using ELISA. Pathological changes were also observed with the aid of hematoxylin-eosin (HE) staining. Our results indicated that LCA significantly reduced the levels of MPO, MDA and increased SOD and GSH activities. Furthermore, LCA also significantly inhibited the levels of TNF-α, IL-6, and IL-1ß in the serum of ulcerated mice in a dose dependent manner. Immunohistological analysis indicated that LCA also significantly attenuated the overexpression of nuclear factor-κB in pretreated mice models. This findings suggests Lycium chinense Mill possesses gastroprotective properties against ethanol-induced gastric injury and could be a possible therapeutic intervention in the treatment and management of gastric ulcers.


Asunto(s)
Antiulcerosos/uso terapéutico , Lycium/química , Extractos Vegetales/uso terapéutico , Úlcera Gástrica/tratamiento farmacológico , Animales , Antiulcerosos/farmacología , Citocinas/sangre , Modelos Animales de Enfermedad , Evaluación Preclínica de Medicamentos , Etanol , Jugo Gástrico/metabolismo , Glutatión/sangre , Concentración de Iones de Hidrógeno , Masculino , Malondialdehído/sangre , Ratones Endogámicos ICR , Estrés Oxidativo , Peroxidasa/metabolismo , Extractos Vegetales/farmacología , Estómago/efectos de los fármacos , Estómago/patología , Úlcera Gástrica/sangre , Úlcera Gástrica/inducido químicamente , Superóxido Dismutasa/sangre , Factor de Transcripción ReIA/metabolismo
12.
J Ethnopharmacol ; 173: 459-67, 2015 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-25959443

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Zuojin Pill (ZJP), a traditional Chinese medicinal decoction, contains two herbal drugs: Coptis chinensis Franch. and Tetradium ruticarpum (A. Juss.) Hartley in the ratio of 6:1 (w/w). In this study, ZJP was evaluated for its gastroprotective potential against mucosal lesions induced by ethanol in mice. MATERIALS AND METHODS: 50 mice were assigned to 5 groups: groups 1 and 2 were given distilled water orally. Group 3 was administered omeprazole 20mg/kg, groups 4 and 5 were given ZJP (1g/kg, 2g/kg, respectively). After an additional hour, the mice in groups 2-5 received ethanol (0.2ml/kg) orally while group 1 received distilled water instead. Mice were killed after 4h and their serum and stomachs subjected to further studies. The superoxidase dismutase (SOD) activities and malondialdehyde (MDA) level in serum were assayed by SOD and MDA kits, respectively. The myeloperoxidase (MPO) activities in stomachs were assayed by MPO kit. The levels of inflammatory mediators including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1ß (IL-1ß) in serum were assayed by enzyme-linked immunosorbent assay method (ELISA). Pathological changes were observed by hematoxylin-eosin (HE) staining. The levels of nuclear factor-кBp65 (NF-кBp65), P-NF-кBp65, P-IкBα, IкBα, P-IKKα, IKKα, P-IKKß, IKKß in stomachs were assayed by western blot. RESULTS: The data showed that treatment with the ZJP markedly attenuated MPO, MDA, TNF-α, IL-6, IL-1ßand increased SOD; and ZJP also decreased protein levels of P-NF-кBp65, P-IкBα, P-IKKαand P-IKKßin gastric stomachs. CONCLUSION: It was concluded that ZJP may represents a potential therapeutic option to reduce the risk of gastric ulceration and the gastroprotective activity of ZJP might contribute in adjusting the inflammatory cytokine by regulating the NF-кB signaling pathway.


Asunto(s)
Antiulcerosos/uso terapéutico , Medicamentos Herbarios Chinos/uso terapéutico , Úlcera Gástrica/tratamiento farmacológico , Animales , Antiulcerosos/farmacología , Coptis , Citocinas/sangre , Modelos Animales de Enfermedad , Medicamentos Herbarios Chinos/farmacología , Etanol , Evodia , Masculino , Malondialdehído/sangre , Ratones Endogámicos ICR , Peroxidasa/sangre , Fitoterapia , Estómago/efectos de los fármacos , Estómago/patología , Úlcera Gástrica/sangre , Úlcera Gástrica/inducido químicamente , Úlcera Gástrica/patología , Superóxido Dismutasa/sangre
13.
Klin Med (Mosk) ; 93(11): 35-41, 2015.
Artículo en Ruso | MEDLINE | ID: mdl-26987137

RESUMEN

AIM: To study the role of the vascular endothelial growth factor (VEGF), Ki-67, BCL-2, and endocrine cells (EC) of gastric mucosa producing somatostatin (SS), glucagon (GL), and pancreatic polypeptide (PP) in diseases associated with Helicobacter pylori. To use the data obtained to develop early diagnostic criteria for the progress of structural changes in gastric mucosa of the patients with stomach ulcer disease [SUD), chronic atrophic gastritis (CAG), gastric adenomatous polyps (GAP), and gastric cancer (GC) before and after surgical intervention and eradication of H. pylori. MATERIALS AND METHODS: We examined 104 patients with gastric pathology associated with Helicobacter pylori including 30 with SUD, 30 with CAG, 20 with GAP and CAG, 24 with stage II noncardia GC. The effectiveness of the treatment was evaluated 2 months after alleviation of inflammation in the stomachfollowing polypectomy in case of GAP or gastrectomy in case of GC. Material for immunohistochemical studies was taken from the fundus. Monoclonal antibodies against VEGF SS, GL, PP Ki-67, BCL-2 (1:100, Novocastra) were used. Histobacterioscopy was conducted using antral mucosal smears stained by the Romanowsky-Giemsa procedure. RESULTS: Exacerbation of SUD was accompanied by a decrease in the number of epithelial cells and EC producing VEGF glucagon (GL), and pancreatic polypeptide (PP) with the increase in the number of SS-secreting EC along with intensification of proliferative processes determined from the number of Ki-67 and BCL-2 immunopositive epithelial cells. CAG and GC were associated with persistence of H. pylori, hyperplasia of EC producing VEGF glucagon (GL), pancreatic polypeptide (PP) and hypoplasia of SS-secreting EC along with high proliferative activity of epitheliocytes expressed via Ki-67 and BCL-2. CONCLUSION: Endothelial growth factor (VEGF), somatostatin (SS), glucagon (GL), and pancreatic polypeptide (PP) are of importance for the prognostication of development and clinical course of diseases associated with Helicobacter pylori since their pathological properties are realized either directly or indirectly through H. pylori, Ki-67 and BCL-2. Eradication of H. pylori does not result in the disappearance of intestinal metaplasia.


Asunto(s)
Gastritis Atrófica , Infecciones por Helicobacter , Helicobacter pylori/patogenicidad , Sistemas Neurosecretores , Pólipos , Neoplasias Gástricas , Úlcera Gástrica , Adulto , Gastritis Atrófica/sangre , Gastritis Atrófica/etiología , Gastritis Atrófica/patología , Infecciones por Helicobacter/sangre , Infecciones por Helicobacter/complicaciones , Infecciones por Helicobacter/patología , Humanos , Pólipos/sangre , Pólipos/etiología , Pólipos/patología , Neoplasias Gástricas/sangre , Neoplasias Gástricas/etiología , Neoplasias Gástricas/patología , Úlcera Gástrica/sangre , Úlcera Gástrica/etiología , Úlcera Gástrica/patología
14.
J Ethnopharmacol ; 160: 211-8, 2015 Feb 03.
Artículo en Inglés | MEDLINE | ID: mdl-25481080

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: The rhizome of Atractylodes lancea (AL, Compositae, Chinese name: Cangzhu; Japanese name: Sou-ju-tsu) has been used traditionally for the treatment of various diseases such as digestive disorders, rheumatic diseases, and influenza in China, Korea and Japan. The crude AL and AL bran-processed are both listed in the Chinese Pharmacopoeia. However, the differences between the effects of the crude and AL bran-processed on gastric ulcer were poorly understood, and the mechanisms for the treatment of gastric ulcer were not clear. This study aimed at comparing the anti-ulcer effects between the crude AL and AL processed in acetic acid induced model in rats and evaluating the mechanisms of action involved in the anti-ulcer properties of AL. MATERIALS AND METHODS: The model of gastric ulcer was imitated by acetic acid in rats, and AL was gavaged. The serum and gastric tissues were collected. The levels of epidermal growth factor (EGF), trefoil factor2 (TFF2), tumor necrosis factor-α (TNF-α), interleukin 6, 8 (IL-6, 8) and prostaglandin E2 (PGE2) in serum and gastric tissues were determined by the double-antibody sandwich enzyme-linked immunosorbent assay (ELISA), and the mRNA expressions of EGF, TFF2, TNF-α, and IL-8 in stomach were analyzed by quantitative real-time reverse transcription polymerase chain reaction (RT-PCR). Meanwhile, histopathological changes were evaluated by hematoxylin and eosin (HE) stain. The protein expressions of EGF, TFF2, TNF-α, and IL-8 were examined by immunohistochemistry in stomach. RESULTS: The results demonstrated that the damage of gastric tissue was obviously alleviated and the productions of TNF-α, IL-8, IL-6, and PGE2 and the mRNA expressions of TNF-α, and IL-8 were notably inhibited. Furthermore, the productions of EGF and TFF2 and the mRNA expressions of EGF and TFF2 were significantly stimulated by both crude AL and AL processed in a dose-dependent manner. Compared with the crude AL, the processed AL was more effective. CONCLUSION: The AL processed had more satisfactory effects in treatment of gastric-ulcer than the crude AL. The anti-ulcer effects of AL could be attributed to the anti-inflammatory properties via down-regulating TNF-α, IL-8, IL-6 and PGE2 and to the gastroprotective effects via up-regulating EGF and TFF2.


Asunto(s)
Ácido Acético , Antiinflamatorios/uso terapéutico , Atractylodes/química , Fibras de la Dieta , Medicamentos Herbarios Chinos/uso terapéutico , Úlcera Gástrica/inducido químicamente , Úlcera Gástrica/tratamiento farmacológico , Animales , Antiinflamatorios/química , Dinoprostona/sangre , Dinoprostona/metabolismo , Modelos Animales de Enfermedad , Medicamentos Herbarios Chinos/química , Factor de Crecimiento Epidérmico/sangre , Factor de Crecimiento Epidérmico/metabolismo , Femenino , Interleucina-6/sangre , Interleucina-6/metabolismo , Interleucina-8/sangre , Interleucina-8/metabolismo , Masculino , Péptidos/sangre , Péptidos/metabolismo , Polvos , Ratas , Úlcera Gástrica/sangre , Úlcera Gástrica/metabolismo , Úlcera Gástrica/patología , Factor Trefoil-2 , Factor de Necrosis Tumoral alfa/sangre , Factor de Necrosis Tumoral alfa/metabolismo
15.
World J Gastroenterol ; 20(44): 16782-5, 2014 Nov 28.
Artículo en Inglés | MEDLINE | ID: mdl-25469052

RESUMEN

IgG4-related disease is a recently recognized entity linked initially to autoimmune pancreatitis and has been subsequently described in nearly every organ system. Men over the age of 50 represent the most affected demographic group and a comprehensive set of diagnostic criteria has been developed to aid treating clinicians. Though elevated levels of IgG4 in the serum are suggestive of the disease, definitive diagnosis is made on histopathology. Treatment is tailored to the clinical presentation with corticosteroid therapy known to have proven efficacy. Gastric manifestations of the IgG4-related disease primarily come in two varieties, notably chronic ulceration or pseudotumor formation. Autoimmune pancreatitis conveys increased risk for IgG4-related disease of the stomach, which is independent of Helicobacter pylori status. In this case report, we present an acute gastric-pericardial fistula secondary to IgG4-related disease that required urgent operative management. To our knowledge, this is the first report in the medical literature describing this complication of IgG4-related disease.


Asunto(s)
Enfermedades Autoinmunes/inmunología , Fístula Gástrica/inmunología , Cardiopatías/inmunología , Inmunoglobulina G/sangre , Pericardio , Úlcera Gástrica/inmunología , Enfermedad Aguda , Anciano , Enfermedades Autoinmunes/sangre , Enfermedades Autoinmunes/diagnóstico , Enfermedades Autoinmunes/cirugía , Biomarcadores/sangre , Drenaje , Esofagostomía , Gastrectomía , Fístula Gástrica/sangre , Fístula Gástrica/diagnóstico , Fístula Gástrica/cirugía , Cardiopatías/sangre , Cardiopatías/diagnóstico , Cardiopatías/cirugía , Humanos , Yeyunostomía , Masculino , Pericardio/cirugía , Úlcera Gástrica/sangre , Úlcera Gástrica/diagnóstico , Úlcera Gástrica/cirugía , Tomografía Computarizada por Rayos X , Resultado del Tratamiento
16.
Eur J Pharmacol ; 740: 329-36, 2014 Oct 05.
Artículo en Inglés | MEDLINE | ID: mdl-25041839

RESUMEN

Zinc plays a key role in maintaining gastric mucosal integrity, while alcohol dependency can lead to low zinc status. Complexes containing zinc have been reported to have better ability to protect gastric mucosa than the compounds alone. In this study, taurine zinc [Zn(NH3CH2CH2SO3)2] solid dispersions (SDs) were synthesized and investigated in an ethanol-induced ulcer model in rats. Gastric ulcer index; gastric mucosa malondialdehyde (MDA) level, glutathione (GSH) content, superoxide dismutase (SOD) activity and prostaglandin E2 (PGE2) production; and serum nitric oxide (NO) were assessed and histological analysis of the gastric mucosa tissue was performed. Taurine zinc (100, 200 mg/kg) SDs protected rat gastric mucosa from ethanol-induced injury. Moreover, the gastroprotective effect of taurine zinc SDs was accompanied by a decrease in serum NO and significant increase in gastric prostaglandin E2 (PGE2). When indomethacin, a non-selective COX inhibitor was administered before the last dose of taurine zinc, the gastroprotective effect of taurine zinc was weakened. Furthermore, taurine zinc (200 mg/kg) SDs protected against ulceration more significantly than the same dose of taurine alone, suggesting a synergistic effect between taurine and zinc. These results indicate taurine zinc protects the gastric mucosa against ethanol-induced damage by elevating antioxidants, decreasing lipid peroxidation and inhibiting the production of nitric oxide. The gastroprotective effect of taurine zinc was also partially mediated by endogenous PGE2 production.


Asunto(s)
Sustancias Protectoras/farmacología , Sustancias Protectoras/uso terapéutico , Úlcera Gástrica/tratamiento farmacológico , Úlcera Gástrica/metabolismo , Taurina/farmacología , Taurina/uso terapéutico , Animales , Dinoprostona/metabolismo , Etanol , Femenino , Mucosa Gástrica/efectos de los fármacos , Mucosa Gástrica/metabolismo , Glutatión/metabolismo , Malondialdehído/metabolismo , Óxido Nítrico/sangre , Ratas Sprague-Dawley , Úlcera Gástrica/sangre , Úlcera Gástrica/inducido químicamente , Superóxido Dismutasa/metabolismo
17.
Klin Khir ; (1): 5-8, 2014 Jan.
Artículo en Ucraniano | MEDLINE | ID: mdl-24923139

RESUMEN

Dynamics of the blood serum level of serotonin in the patients, suffering gastroduodenal ulcer, Complicated by hemorrhage, was analyzed. The highest level of serotonin was observed in gastric ulcer, complicated by hemorrhage. These changes correlate with the blood loss severity enhancement, the achievement of a nonstable state of endoscopic hemostasis, high activity of inducible NO-synthase (iNOS) of periulcerative mucosa. The obtained data analysis permits to prognosticate the pathological process course and to improve the program of treatment.


Asunto(s)
Úlcera Péptica Hemorrágica/diagnóstico , Serotonina/sangre , Índice de Severidad de la Enfermedad , Úlcera Gástrica/diagnóstico , Adulto , Anciano , Estudios de Casos y Controles , Endoscopía del Sistema Digestivo , Femenino , Mucosa Gástrica/enzimología , Mucosa Gástrica/patología , Humanos , Masculino , Persona de Mediana Edad , Óxido Nítrico Sintasa de Tipo II/metabolismo , Úlcera Péptica Hemorrágica/sangre , Úlcera Péptica Hemorrágica/etiología , Úlcera Péptica Hemorrágica/patología , Valor Predictivo de las Pruebas , Pronóstico , Recurrencia , Úlcera Gástrica/sangre , Úlcera Gástrica/complicaciones , Úlcera Gástrica/patología
18.
Artículo en Inglés | MEDLINE | ID: mdl-24653572

RESUMEN

BACKGROUND: Ethno-botanical information shows that Eremomastax speciosa is used in the traditional management of various stomach complaints including gastro-duodenal ulcers. MATERIALS AND METHODS: In this study, we tested the cytoprotective potential of the whole plant methanol extract (100-200 mg/kg, p.o), against HCl/ethanol, absolute ethanol, cold/restraint stress rats, and pylorus legated rats pre-treated with indomethacin. The effects of the extract on gastric lesion inhibition, the volume of gastric juice, gastric pH, gastric acid output, mucus production and gastric peptic activity were recorded. Oxidative stress parameters were measured in blood and gastric tissue samples obtained from the animals in all the models tested. RESULTS: The extract significantly (p<0.05), reduced the formation of cold/restraint ulcers by (31-60%, inhibition), completely inhibited (100%) the formation of lesions induced by HCl/ethanol at the highest dose, but was less effective against absolute ethanol (22-46% inhibition). The extract (200 mg/kg), significantly reduced lesion formation (P<0.01), gastric acidity (P<0.01), and volume of gastric secretions (P<0.05), in the indomethacin/pylorus ligation model, and did not affect the activity of pepsin in gastric juice. Blood concentrations of antioxidant enzymes (catalase, SOD and GSH), increased significantly and MDA concentrations decreased in all models tested. CONCLUSION: Cytoprotection by E. speciosa methanol extract was attributed to its ability to reduce acid secretion, and to enhance mucosal defence and in vivo antioxidant status.


Asunto(s)
Acanthaceae , Antiulcerosos/uso terapéutico , Antioxidantes/uso terapéutico , Mucosa Gástrica/efectos de los fármacos , Fitoterapia , Extractos Vegetales/uso terapéutico , Úlcera Gástrica/tratamiento farmacológico , Animales , Antiulcerosos/farmacología , Antioxidantes/metabolismo , Antioxidantes/farmacología , Catalasa/sangre , Frío , Etanol , Ácido Gástrico/metabolismo , Mucosa Gástrica/patología , Glutatión/sangre , Ácido Clorhídrico , Indometacina , Ligadura , Masculino , Malondialdehído/metabolismo , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/farmacología , Píloro , Ratas , Ratas Wistar , Restricción Física , Úlcera Gástrica/sangre , Úlcera Gástrica/etiología , Úlcera Gástrica/patología , Superóxido Dismutasa/sangre
19.
BMC Gastroenterol ; 14: 3, 2014 Jan 03.
Artículo en Inglés | MEDLINE | ID: mdl-24383519

RESUMEN

BACKGROUND: Serum pepsinogen (PG) levels are valuable in the diagnosis of gastric diseases. However, PG levels are affected by many factors such as the area and race. This study aimed to investigate serum PG levels in patients with different gastric diseases who were Chinese Han people in Hunan Province, midsouth China. METHODS: A total of 248 gastric disease patients and 34 healthy controls were enrolled. The patients included those with non-atrophic and chronic atrophic gastritis, gastric and duodenal ulcer, early and advanced gastric cancer. Serum PG I and II levels were detected by Biohit ELISA kit (Finland), and PG I/II ratio was calculated. Differences in patients with gastric disease and healthy controls were analyzed using paired t-test. RESULTS: Compared with controls, patients with early and advanced gastric cancer had a significantly lower PG I level and PG I/II ratio (p <0.005). In contrast, patients with gastric and duodenal ulcer had a significantly higher PG I level (p <0.005). Compared with atrophic gastritis patients, patients with early and advanced carcinoma of the stomach had a significantly lower PG I/II ratio (p < 0.001). Combination of the cut-off levels of PG I (70 µg/L) and PG I/II ratio (6) provided 62.1% sensitivity of and 94.2% specificity for the diagnosis of gastric cancer. CONCLUSIONS: Decreased PG I level and PG I/II ratio are risk factors for gastric cancer. Combined use of serum PG I level and PG I/II ratio may help the early diagnosis of gastric cancer.


Asunto(s)
Carcinoma/sangre , Úlcera Duodenal/sangre , Gastritis Atrófica/sangre , Pepsinógeno A/sangre , Pepsinógeno C/sangre , Neoplasias Gástricas/sangre , Úlcera Gástrica/sangre , Adulto , Anciano , Anciano de 80 o más Años , Pueblo Asiatico , Carcinoma/diagnóstico , Carcinoma/etnología , Estudios de Casos y Controles , China/etnología , Úlcera Duodenal/diagnóstico , Úlcera Duodenal/etnología , Femenino , Gastritis Atrófica/diagnóstico , Gastritis Atrófica/etnología , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Curva ROC , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/etnología , Úlcera Gástrica/diagnóstico , Úlcera Gástrica/etnología , Adulto Joven
20.
Vopr Virusol ; 58(3): 46-8, 2013.
Artículo en Ruso | MEDLINE | ID: mdl-24006634

RESUMEN

The study included 120 patients with pre-cancer conditions of the stomach and 30 patients with gastric cancer stage II-IV. The ELISA method in the blood serum was used to determine the markers of the infection caused by Herpes simplex virus (HSV) types 1 and 2, Cytomegalovirus (CMV), and Epstein-Barr virus (EBV). The majority of the patients exhibited high titers of markers of Herpesvirus mixed infection. These data allow recommending the determination of IgG antibodies to antigens of herpesviruses in patients with the diseases of the stomach and assigning the appropriate antiviral drugs.


Asunto(s)
Anticuerpos Antivirales/sangre , Antígenos Virales/sangre , Gastritis/sangre , Herpes Simple/sangre , Lesiones Precancerosas/sangre , Neoplasias Gástricas/sangre , Úlcera Gástrica/sangre , Anticuerpos Antivirales/inmunología , Antígenos Virales/inmunología , Biomarcadores/sangre , Citomegalovirus/inmunología , Citomegalovirus/aislamiento & purificación , Infecciones por Citomegalovirus/sangre , Infecciones por Citomegalovirus/complicaciones , Infecciones por Citomegalovirus/inmunología , Infecciones por Citomegalovirus/virología , Ensayo de Inmunoadsorción Enzimática , Infecciones por Virus de Epstein-Barr/sangre , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Virus de Epstein-Barr/inmunología , Infecciones por Virus de Epstein-Barr/virología , Gastritis/complicaciones , Gastritis/inmunología , Gastritis/virología , Herpes Simple/complicaciones , Herpes Simple/inmunología , Herpes Simple/virología , Herpesvirus Humano 1/inmunología , Herpesvirus Humano 1/aislamiento & purificación , Herpesvirus Humano 2/inmunología , Herpesvirus Humano 2/aislamiento & purificación , Herpesvirus Humano 4/inmunología , Herpesvirus Humano 4/aislamiento & purificación , Humanos , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Lesiones Precancerosas/complicaciones , Lesiones Precancerosas/inmunología , Lesiones Precancerosas/virología , Federación de Rusia , Neoplasias Gástricas/complicaciones , Neoplasias Gástricas/inmunología , Neoplasias Gástricas/virología , Úlcera Gástrica/complicaciones , Úlcera Gástrica/inmunología , Úlcera Gástrica/virología
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA