Infection with a human-derived enteroinvasive Escherichia coli strain altered intestinal barrier function in guinea pigs / La infección con una cepa enteroinvasiva de Escherichia coli de origen humano alteró la función de la barrera intestinal en cobayos

Background/aims: The aim was to characterize a bacterium causing intestinal mucosal barrier damage and to identify the possible invasion mechanism. Materials and methods: The intestinal permeability and tight junction protein levels were detected in guinea pigs infected with Escherichia coli D-09 via immunofluorescence analysis and western blotting. In order to explain this invasion mechanism at the gene level, whole genome sequencing analysis was performed on this bacterium. Results: The results showed an increased intestinal permeability and upregulated expression of the leaky protein claudin-2 in both the colon and liver of the infected animals. In addition, the draft genome of E. coli D-09 comprised 42 scaffolds (size, > 645 bp) with a total size of 4,679,567 bp. A total of 4379 protein coding genes were identified, which contained 45 antibiotic resistance and 86 virulence-related genes and covered 88.0% of the whole genome. Conclusions: This study verified that the human-derived enteroinvasive E. coli strain could destroy intestinal barrier function in guinea pigs. Additionally, our data first characterized the genome features of E. coli O124:K72 D-09, which may provide new insights into the possible invasion mechanism.(AU)

Trichophyton erinacei: an emergent pathogen of pediatric dermatophytosis / Trichophyton erinacei: un patógeno emergente en las dermatofitosis en niños

BACKGROUND: Dermatophytoses in children are common pathologies worldwide caused mainly by Trichophyton rubrum. However, due to the globalization and the atypical pets that people nowadays own, some zoonotic species are also involved in these lesions. CASE REPORT: We present two cases of tinea faciei caused by the zoonotic mould Trichophyton erinacei in two children that owned a guinea pig and a hedgehog, respectively. Mycological diagnosis was performed inoculating skin scales on Sabouraud-glucose agar plates supplemented with chloramphenicol, with and without gentamicin, and on Sabouraud-glucose agar tubes, with and without cycloheximide. Microscopical examination in both cases and ITS region sequencing to confirm the identification (performed in one of them) were compatible with T. erinacei. Multiple treatments like corticosteroids and antibiotics were prescribed prior to the accurate diagnosis. Finally, both patients received topical and oral terbinafine, respectively, the lesions being resolved entirely. CONCLUSIONS: Zoonotic fungi must be considered in the diagnosis of skin lesions. An accurate medical record, with a guided anamnesis about possible risk factors and an ongoing and open dialogue between health professionals, are essential to improve both the management of these exotic and zoophilic dermatophytoses

ANTECEDENTES: Las dermatofitosis son patologías comunes en niños y son causadas principalmente por Trichophyton rubrum. Sin embargo, debido a la globalización y a la presencia cada vez más frecuente de animales exóticos como mascotas, algunas especies zoonóticas menos habituales pueden convertirse en agentes causales. CASO CLÍNICO: Nuestro objetivo es describir dos casos de Tinea faciei causados por Trichophyton erinacei en dos niños que poseían, respectivamente, una cobaya y un erizo como mascotas. Se tomó muestra de escamas cutáneas que fueron inoculadas en placas de agar Sabouraud-glucosa suplementado con cloranfenicol, con y sin gentamicina, y en tubos de agar Sabouraud-glucosa con y sin cicloheximida. El examen microscópico fue compatible con Trichophyton erinacei, cuya identificación pudo ser confirmada por secuenciación de la región ITS en uno de los casos. Antes del correcto diagnóstico los pacientes habían recibido múltiples tratamientos (corticosteroides, antibióticos). Finalmente, los dos pacientes recibieron terbinafina tópica y oral, respectivamente, lo que llevó a la resolución completa de las lesiones. CONCLUSIONES: Los hongos zoonóticos deben ser considerados en el diagnóstico diferencial de las lesiones cutáneas. Una historia clínica con anamnesis guiada sobre posibles factores de riesgo, junto con una comunicación multidisciplinar fluida, es indispensable para mejorar el manejo de estas dermatofitosis

Arthroderma benhamiae en pacientes con cobayas / Arthroderma benhamiae in patients with guinea pigs

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Estudio comparativo de insectos asociados a cadáveres de cobayas en dos formas de muerte en Castilla, Piura (Perú) / Comparative study of insects associated with guinea pig corpses in two forms of death in Castilla, Piura (Peru)

Se determinaron los insectos asociados a cadáveres de cobayas, en las dos formas de muerte con mayor incidencia en Piura: envenenamiento (raticida) y arma blanca (cuchillo); utilizando como testigo una muerte por parada cardiorrespiratoria. Para este fin, se sacrificaron cobayas hembras, de pesos similares y procedentes de la misma granja, en tres repeticiones (una por mes), expuestos en un área de bosque seco en el distrito de Castilla, dentro de jaulas de malla metálica, y separadas 60 metros entre sí. La colecta de dípteros adultos se realizó mediante una red entomológica, y se les sacrificó con cianuro en un frasco mortal. Los coleópteros se colectaron por muestreo manual alrededor del cadáver, y se sacrificaron en un frasco mortal con alcohol al 70%. Todos los individuos fueron determinados y cuantificados con un estereoscopio y claves taxonómicas, siempre procurando llegar al nivel taxonómico más bajo. Se utilizó el programa SPSS Vs.22 para calcular las diferencias en la entomofauna entre las formas de muerte, mediante el análisis de varianzas (ANOVA); encontrándose un total de 24 especies, correspondientes a 22 especies para el testigo, 17 para envenenamiento y 19 para arma blanca, a una temperatura y humedad promedio de 25,94 °C y 63,19%, respectivamente. Estadísticamente, no existían diferencias significativas entre las formas de muerte con un nivel de significancia de 0,05

The insects associated with corpses of guinea pigs were determined, in the two forms of death with the highest incidence in Piura: poisoning (rat poison) and white weapon (knife); using as a witness, a death due to cardiorespiratory arrest. For this purpose, female guinea pigs, of similar weights and from the same farm, were slaughtered in three repetitions (one per month), exposed in an area of dry forest in the district of Castilla, in metal mesh cages, and separated 60 meters between them. The collection of adult diptera was carried out with an entomological network, and the sacrifice of these, in a deadly vial with cyanide. Coleoptera were collected by manual sampling around the body, and sacrificed in a deadly vial with 70% alcohol. All individuals were determined and quantified with a stereoscope and taxonomic keys, always trying to reach the lowest taxonomic level. The SPSS program Vs.22 was used to calculate the differences in the entomofauna between the forms of death, through the analysis of variances (ANOVA). There were a total of 24 species, corresponding to 22 species for the control, 17 for poisoning and 19 for weaponry, at an average temperature and humidity of 25.94 °C and 63.19% respectively, there being no statistically significant differences between the forms of death at a significance level of 0.05

Efectos producidos por diferentes tipos de láser en córnea de cobayos: identificación de un láser capaz de provocar lesiones superficiales sin dejar cicatrices / Effects produced by different types of laser in córnea of Guinea pigs: identification of a laser capable of producing superficial lesions without leaving scars

OBJETIVO: La queratopatía climática esferoidea (QCE) está íntimamente asociada a erosiones corneales superficiales y a carencia de mecanismos protectores contra los efectos nocivos de la radiación ultravioleta (RUV) durante muchos años. Debido a que una de las dificultades en el estudio de los mecanismos patogénicos de esta enfermedad humana es la ausencia de un modelo experimental, en este trabajo quisimos identificar cuál es el mejor método para estudiar una de las variables involucradas en su génesis (erosiones superficiales de la córnea). A tal fin investigamos los efectos producidos por 4 tipos de láser con diferentes condiciones de potencia y tiempo en la córnea de cobayos normales con el fin de seleccionar un láser y condición que lesione solamente el epitelio y estroma superficial, de manera reversible, sin dejar cicatrices. MÉTODOS: Se indujeron daños en la córnea de cobayos utilizando distintas potencias y tiempos con 4 tipos de láser: argón, CO2, diodo y Nd-Yag en distintos grupos de animales y se evaluaron dichas lesiones por biomicroscopia (BM) y microscopia óptica. Córneas de otros animales normales fueron expuestas a láser de argón (350 mW, 0,3 s, 50μm de diámetro) y las alteraciones inducidas se estudiaron en diferentes tiempos utilizando BM, tomografía de coherencia óptica (TCO) y microscopia electrónica (ME). RESULTADOS: Solo el láser argón a una potencia de 350 mW, 0,3 s, 50μm de diámetro produjo lesiones de epitelio y estroma superficial, manteniéndose indemne el endotelio. Por BM se observaron algunos leucomas que desaparecieron hacia el día 15. Mediante TCO se observó un adelgazamiento del espesor corneal en los ojos tratados con esas condiciones de láser argón durante la primera semana. Mediante ME, se observaron diferentes alteraciones ultraestructurales en epitelio y estroma corneal durante los primeros días, las cuales desaparecieron hacia el día 15. CONCLUSIONES: Fue posible desarrollar lesiones corneales en epitelio y estroma anterior de cobayos de manera reproducible mediante el uso de láser argón. Los estudios in vivo e in vitro demostraron que las córneas lesionadas con este láser y en esas condiciones no dejaron alteraciones microscópicas ni ultraestructurales irreversibles. Este modo de erosión corneal combinado con exposición a RUV y déficit parcial de ascorbato en la dieta de los animales durante un período prolongado de tiempo está siendo utilizado con el fin de intentar desarrollar un modelo experimental de QCE

PURPOSE: Climatic droplets keratopathy (CDK) is closely associated with superficial corneal erosions and lack of protective mechanisms against the harmful effects of ultraviolet radiation (UVR) during a prolonged period of time. One of the difficulties in studying the pathogenic mechanisms involved in this human disease is the lack of an experimental animal model. In this paper, a study is conducted on the effects of 4 types of lasers at various powers and time conditions on the normal guinea pig corneas in order to select only one laser condition that reversibly injures the epithelium and superficial stroma, without leaving scarring. METHODS: Damage was induced in the cornea of Guinea pigs using different powers and exposure times of 4 types of laser: argon, CO2, diode and Nd-Yag, and any injuries were evaluated by biomicroscopy (BM) and optical microscopy. Corneas from other normal animals were exposed to argon laser (350 mW, 0.3s, 50μm of diameter), and the induced alterations were studied at different times using BM, optical coherence tomography (OCT) and transmission electron microscopy (TEM). RESULTS: Only argon laser at 350 mW, 0.3s, 50μm of diameter produced epithelium and superficial stroma lesions. Some leukomas were observed by BM, and they disappeared by day 15. Corneal thickness measured by OCT decreased in the eyes treated with argon laser during the first week. Using TEM, different ultra structural alterations in corneal epithelium and stroma were observed during the early days, which disappeared by day 15. CONCLUSIONS: It was possible to develop reproducible corneal epithelium and anterior stroma injuries using Argon laser at 350 mW, 0.3s, 50μm of diameter. In vivo and in vitro studies showed that injured corneas with these laser conditions did not leave irreversible microscopic or ultra structural alterations. This protocol of corneal erosion combined with exposure to UVR and partial deficiency of ascorbate in the diets of the animals for an extended period of time has been used in order to try to develop an experimental model of CDK

Colonización por dermatofitos en cuyes (Cavia porcellus) mantenidos en tiendas de mascotas. Primer reporte en Santiago de Chile / Dermatophyte colonization on guinea pigs (Cavia porcellus) kept in pet stores. First report from Santiago, Chile

Antecedentes: Los dermatofitos son hongos patógenos que pueden formar parte de la microbiota de mamíferos como perros, gatos y roedores, que pueden ser fuente y vehículo de transmisión a otros hospederos, incluyendo al hombre. En nuestro medio, existe un aumento sostenido en la incorporación de cuyes (Cavia porcellus) como mascota, sin contar con estudios locales que evidencien la colonización de dermatofitos. Objetivos: Determinar la presencia de dermatofitos en cuyes clínicamente sanos, mantenidos en tiendas de mascotas en la ciudad de Santiago de Chile. Métodos: Se incluyeron en el estudio 52 animales clínicamente sanos, muestreados mediante el método de Mariat y Tapia (1966). Para el cultivo de las muestras y la identificación de los agentes aislados se siguieron los procedimientos micológicos clásicos. Resultados: Del total de cuyes, 4 (7,7%) presentaron colonización por dermatofitos; las especies aisladas fueronTrichophyton mentagrophytes (3 casos) y Trichophyton verrucosum (un caso). Conclusiones: Este estudio evidencia, por primera vez en Chile, que los cuyes pueden ser colonizados por dermatofitos, lo cual debe alertar a los administradores de las tiendas de mascotas y a los médicos veterinarios y humanos, para tenerlo presente en el momento de adquirir o atender a este tipo de mascota en la clínica veterinaria (AU)

Background: Dermatophytes are pathogenic fungi that can be present in the flora of mammals, such as dogs, cats and rodents, which can be a source and transmission vehicle to other hosts, including humans. In Chile, there is a steady increase of acquiring guinea pigs (Cavia porcellus) as pets, with no local studies on their colonization by dermatophytes. Objective: To determine the presence of dermatophytes on clinically healthy guinea pigs, kept in pet stores in Santiago, Chile. Methods: A total of 52 clinically healthy animals were studied using the method by Mariat and Tapia (1966). The specimen culture and identification of the dermatophytes were performed using classical mycological procedures. Results: Four guinea pigs (7.7%) out of 52 were colonized by dermatophytes, and were identified as Trichophyton mentagrophytes (3 cases) and Trichophyton verrucosum (one case). Conclusion: This study shows, for the first time in Chile, that guinea pigs can be colonized by dermatophytes, which should alert administrators of pet stores, veterinarians and physicians, to keep this in mind when purchasing or looking after this type of pet in a veterinary office (AU)

Modelos animales de enfermedad pulmonar obstructiva crónica / Animal Models of Chronic Obstructive Pulmonary Disease

El desarrollo de modelos animales de una enfermedad ha sido siempre bien acogido por la comunidad científica porque permite realizar una aproximación a la investigación de determinados aspectos de la misma. Los modelos animales de la EPOC no pueden llegar a reproducir la heterogeneidad de esta enfermedad y generalmente solo llegan a representar los estadios más leves de la misma. Además, la obstrucción al flujo aéreo, variable que determina el diagnóstico en un paciente, no siempre se tiene en cuenta en los modelos. Por este motivo, los modelos se han centrado en el desarrollo de enfisema, fácilmente detectable por morfometría pulmonar, sin prestar atención a otros componentes de la enfermedad, como la lesión de las vías aéreas o las alteraciones vasculares asociadas. La exposición continua y prolongada al humo de tabaco se considera el principal factor de riesgo de esta enfermedad, lo que justifica que sea el modelo de exposición al humo de tabaco el más ampliamente utilizado. Sobre esta base de modelo podemos encontrar algunas variantes relacionadas con el tiempo de exposición, la asociación de otros inductores o inhibidores, las exacerbaciones o el uso de animales transgénicos que facilitan la identificación de las vías patogénicas. Es posible, por tanto, reproducir algunas variantes o heterogeneidades de esta enfermedad y diseñar uno u otro modelo que sea capaz de responder a una u otra pregunta de investigación, dirigida bien a una identificación patogénica y/o bien a una respuesta terapéutica

Animal models of disease have always been welcomed by the scientific community because they provide an approach to the investigation of certain aspects of the disease in question. Animal models of COPD cannot reproduce the heterogeneity of the disease and usually only manage to represent the disease in its milder stages. Moreover, airflow obstruction, the variable that determines patient diagnosis, not always taken into account in the models. For this reason, models have focused on the development of emphysema, easily detectable by lung morphometry, and have disregarded other components of the disease, such as airway injury or associated vascular changes. Continuous, long-term exposure to cigarette smoke is considered the main risk factor for this disease, justifying the fact that the cigarette smoke exposure model is the most widely used. Some variations on this basic model, related to exposure time,the association of other inducers or inhibitors, exacerbations or the use oftransgenic animals to facilitate the identification of pathogenic pathways have been developed. Some variations or heterogeneity of this disease, then, can be reproduced and models can be designed for resolving researchers’ questions on disease identification or treatment responses

Morphology of female guinea pig Harderian gland during postnatal development - secretory endpieces

The main objective of this study was to investigate the morphological aspects of the development of the Harderian gland (HG) in the female guinea pig. A total number of thirty animals were used and divided according to age into groups, five animals each. Specimens were taken at the following ages; birth, one week, two weeks, three weeks, four weeks and two months postnatal. Histological, histochemical and immunohistochemical techniques were used. The gland was constituted of secretory end pieces and a duct system formed of intra- and extra-parenchymal ducts. At birth, the female guinea pig HG was active in the secretion of lipid and neutral mucin and the differentiation of several populations of cells (light and dark) was possible. However, its histological structure was still incomplete. The lining cells revealed many free ribosomes, a few and small organelles and large irregularly shaped nuclei and numerous mitotic figures. The secretory cells reached maturity by the age of three weeks, but growth in size continued up to the age of two months. They were light or dark; the light cells presented three forms that exhibited different morphological features. All modes of secretion (apocrine, merocrine and holocrine) were detected

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Historia de la heparina / History of heparin

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Ascorbic acid is superior to silymarin in the recovery of ethanol-induced inflammatory reactions in hepatocytes of guinea pigs

Both oxidative stress and inflammatory reactions play a major role in alcoholic liver fibrosis. We evaluated the efficacy of ascorbic acid (AA) and silymarin in the regression of alcohol-induced inflammation in hepatocytes of guinea pigs (Cavia porcellus). Animals were administered with ethanol at a daily dose of 4 g/kg body weight (b.wt) for 90 days. On the ninety-first day, ethanol administration was stopped and animals were divided into alcohol abstention group and silymarin- (25 mg/100 g b.wt) and AA- (25 mg/100 g b.wt) supplemented groups and maintained for 30 days. There was a significant increase in the activities of alanine aminotransferase, aspartate aminotransferase, and Gamma-glutamyl transpeptidase in the serum of the ethanol group. The intracellular reactive oxygen species (ROS) and expressions of cytochrome P4502E1 and nuclear factor KappaB1, tumor necrosis factor-Alpha, and transforming growth factor-Beta(1) in hepatocytes were significantly increased in ethanol group. The fibrotic markers Alpha -smooth muscle actin and Alpha(1)(I) collagen and activity of cytotoxicity marker caspase-3 were significantly increased and AA content was significantly reduced in hepatocytes of alcohol-treated guinea pigs. But the AA and silymarin supplementation significantly reduced these changes in comparison with alcohol abstention group. AA could induce greater reduction of inflammatory and fibrotic markers in hepatocytes than silymarin. This indicates that AA is superior to silymarin in inhibiting intracellular ROS generation and thereby reducing the ethanol-induced inflammation in hepatocytes

New drugs for tuberculosis treatment

Los datos disponibles en el proceso de investigación de nuevos fármacos antituberculosos han descubiertodiferentes propiedades de los compuestos que permiten crear expectativas acerca de sus futuras indicaciones.Modelos terapéuticos que incluyan altas dosis de rifamicinas y pautas que asocien rifapentina conmoxifloxacino o gatifloxacino podrían acortar el tratamiento de la tuberculosis, mientras que SQ109 incrementaríala actividad de las combinaciones basadas en esta rifamicina. Por otra parte, la tuberculosis latentepodría tratarse adecuadamente con la asociación de moxifloxacino y PA-824, y la tuberculosis multirresistentey extensamente resistente con linezolid, PA-824 y TMC207, en pautas sin rifampicina.Desgraciadamente, tratamientos más cortos que los existentes, basados en asociaciones de los fármacosque se comentan en este trabajo, llevarán al menos otra década para ser completamente desarrollados eintroducidos en la práctica clínica (AU)

AbstractAvailable data on anti-tuberculosis drug research reveal different properties of the agents and provoke speculation about future directions. Higher doses of the rifamycins are promising and are currently being evaluated in regimens of shorter duration that the isoniazid plus rifampin-based, six-to-nine month-course therapy. Moxifloxacin and gatifloxacin might shorten tuberculosis treatment as well, possibly in combination with rifapentine, while SQ109 could enhance the activity of rifampin-containing regimens. On the other hand, co-administration of moxifloxacin and PA-824 could be active against latent tuberculosis, whereas linezolid, PA-824 and TMC207 are candidates for a rifampin-free regimen in multidrug-resistant and extensively-resistant tuberculosis. Unfortunately, shorter than existent treatment regimens based on the new agents discussed here are likely to take at least another decade to be fully developed and implemented in clinical practice (AU)

Tratamiento combinado de la aspergilosis invasora. ¿Una oportunidad para micafungina? / Combination therapy for invasive aspergillosis

Las infecciones fúngicas invasoras, y en concreto la aspergilosis invasora, han aumentado en frecuencia en las últimas décadas, y pese a la aparición de nuevos antifúngicos se asocian a una elevada mortalidad que oscila entre el 40 y el 80%, dependiendo del paciente en el que incida y de la localización de ésta. Para intentar disminuir esta elevada tasa, se han planteado nuevas estrategias terapéuticas, entre las que se encuentra la terapia combinada. La mayoría de los datos disponibles sobre la eficacia de las combinaciones proceden de modelos experimentales, datos in vitro y estudios observacionales retrospectivos o con un número reducido de pacientes donde además mezclan pacientes en tratamiento de primera línea con pacientes en rescate, y hay muchas aspergilosis posibles y pocas probadas o probables. De momento, no se ha demostrado que el tratamiento combinado tenga una eficacia significativamente superior a la monoterapia; sin embargo, podría estar indicado en formas de aspergilosis grave, que cursen con afectación del sistema nervioso central o afectación pulmonar extensa con insuficiencia respiratoria, etc. Entre las combinaciones, la asociación de una equinocandina, grupo al que pertenece la micafungina, con voriconazol o anfotericina B liposomal parece mostrar sinergia y ha sido la más ensayada en estudios clínicos y, por tanto, aunque con escaso grado de evidencia, es la recomendada por las diferentes sociedades científicas (AU)

The frequency of invasive fungal infections, and specifically invasive aspergillosis, has increased in the lastfew decades. Despite the development of new antifungal agents, these infections are associated with highmortality, ranging from 40% to 80%, depending on the patient and the localization of the infection. Toreduce these figures, several therapeutic strategies have been proposed, including combination therapy.Most of the available data on the efficacy of these combinations are from experimental models, in vitrodata and retrospective observational studies or studies with a small number of patients that have includedboth patients in first-line treatment and those receiving rescue therapy; in addition there are many patientswith possible forms of aspergillosis and few with demonstrated or probable forms. To date, there is noevidence that combination therapy has significantly higher efficacy than monotherapy; however,combination therapy could be indicated in severe forms of aspergillosis, or forms with central nervousinvolvement or extensive pulmonary involvement with respiratory insufficiency, etc. Among thecombinations, the association of an echinocandin – the group that includes micafungin – with voriconazoleor liposomal amphotericin B seems to show synergy. These combinations are those most extensivelystudied in clinical trials and therefore, although the grade of evidence is low, are recommended by thevarious scientific societies (AU)

Levosulpirida en el manejo de la dispepsia funcional y la gastroparesia / Levosulpiride in the management of functional dyspepsia and delayed gastric emptying

Levosulpirida es un isómero de la sulpirida que ejerce su acción procinética mediante un mecanismo dual: 1) antagonista de los receptores dopaminérgicos D2, y 2) agonista de los receptores serotoninérgicos 5HT4, lo que le confiere una acción facilitadora colinérgica. A una dosis de 25mg tres veces al día levosulpirida acelera el vaciamiento gástrico y de la vesícula biliar. Ensayos clínicos han mostrado que levosulpirida es más eficaz que placebo en la reducción de los síntomas dispépticos, y estudios comparativos han mostrado que levosulpirida posee un efecto similar o superior al de otros fármacos antagonistas dopaminérgicos. El perfil de seguridad de levosulpirida es bueno, y la frecuencia de acontecimientos adversos similar a la de otros fármacos antagonistas D2. Por ello, este fármaco constituye una opción terapéutica útil en el manejo de los pacientes con dispepsia funcional, así como en pacientes con retraso del vaciamiento gástrico como la gastroparesia (AU)

Levosulpiride is a sulpiride isomer that exerts its prokinetic action through a dual mechanism: 1) as a D2 dopamine receptor antagonist and 2) as a serotonin 5HT4 receptor agonist, conferring this drug with a cholinergic effect. At a dosage of 25mg three times daily, levosulpiride accelerates gastric and gallbladder emptying. Clinical trials have shown that this agent is more effective than placebo in reducing the symptoms of dyspepsia, while comparative studies have demonstrated that its effect is similar or superior to that of other dopamine antagonists. The safety profile of levosulpiride is good and the frequency of adverse events is similar to that of other D2 dopamine antagonists. Therefore, this drug is a useful therapeutic option in the management of patients with functional dyspepsia, as well as in those with delayed gastric emptying (AU)

The 1.3 isoform of Na+–Ca2+ exchanger expressed in guinea pig tracheal smooth muscle is less sensitive to KB-R7943

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The sodium–calcium exchanger (NCX) plays a major role in the regulation of cytosolic Ca2+ in muscle cells. In this work, we performed force experiments to explore the role of NCX during contraction and relaxation of Cch-stimulated guinea pig tracheal smooth muscle strips. This tissue showed low sensitivity to NCX inhibitor KB-R7943 (IC50, 57 ± 2 µM), although a complete relaxation was obtained by NCX inhibition at 100 µM. Interestingly, relaxation after washing the agonist was prolonged in the absence of external Na+, whereas washing without Na+ and in the presence of KB-R7943 resembled control conditions with physiological solution. Altogether, this suggests the reversal of NCX to a Ca2+ influx mode by the manipulation on the Na+ gradient, which can be inhibited by KB-R7943. In order to understand the low sensitivity to KB-R7943, we studied the molecular aspects of the NCX expressed in this tissue and found that the isoform of NCX expressed is 1.3, similar to that described in human tracheal smooth muscle. Sequencing revealed that amino acid 19 in exon B is phenylalanine, whereas in its human counterpart is leucine, and that the first amino acid after exon D is aspartate instead of glutamate in humans. Results herein presented are discussed in term of their possible functional implications in the exchanger activity and thus in airway physiology (AU)

Tempol protects the gallbladder against ischemia/reperfusion

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Impairment in gallbladder emptying, increase in residual volume, and reduced smooth muscle contractility are hallmarks of acute acalculous cholecystitis and seem to be related to ischemia/reperfusion (I/R). This study was designed to determine the effects of tempol, a general antioxidant, on I/R-induced changes in gallbladder contractile capacity, the mechanisms involved in the contractile process, and the level of inflammatory mediators. Experimental gallbladder I/R was induced in male guinea pigs by common bile duct ligation for 2 days, then a deligation of the duct was performed and after 2 days the animals were sacrificed. A group of animals was treated with tempol, administered in the drinking water at 1 mmol/l for 10 days prior the bile duct ligation and until animal sacrifice. Isometric tension recordings showed that KCl and cholecystokinin-induced contractions were impaired by I/R, which correlated with decreased F-actin content and detrimental effects on Ca2+ influx. In addition, I/R depolarized mitochondrial membrane potential, as indicated by the reduction of the heterogeneity of the rhodamine123 fluorescence signal, and increased the expression of NF-êB, COX-2, and iNOS. Tempol treatment improved contractility via normalization of Ca2+ handling and improvement of F-actin content. Moreover, the antioxidant ameliorated mitochondrial polarity and normalized the expression levels of the inflammatory mediators. These results show that antioxidant treatment protects the gallbladder from I/R, indicating the potential therapeutic benefits of tempol in I/R injury (AU)

Efecto de la fluticasona inhalada sobre la inflamaci¨®n pulmonar administrada durante y despu¨¦s de la sensibilizaci¨®n de cobayas / Effect of Inhaled Fluticasone on Lung Inflammation Administered During and After Guinea Pig Sensitization

ObjetivoSe examin¨® el efecto de un corticoesteroide inhalado, el propionato de fluticasona (PF), sobre la inflamaci¨®n pulmonar de cobayas sensibilizados.Material y m¨¦todosSe sensibiliz¨® con ovoalb¨²mina (OA) a 4 grupos de cobayas (n=8). El grupo de control recibi¨® soluciones similares sin OA. Durante un periodo de 18 d¨ªas, un grupo sensibilizado fue tratado con 250¦Ìg de PF inhalado 2 veces al d¨ªa durante la sensibilizaci¨®n; el otro grupo despu¨¦s de ella y los otros 2 grupos fueron tratados con placebo, uno durante la sensibilizaci¨®n y otro despu¨¦s de ella. A las 24h del ¨²ltimo tratamiento, se examinaron las respuestas traqueales de todos los grupos de animales a metacolina y OA. Tambi¨¦n se examinaron el recuento total de leucocitos y la f¨®rmula leucocitaria del l¨ªquido de lavado pulmonar y la anatom¨ªa patol¨®gica pulmonar.ResultadosEn ambos grupos placebo la reactividad traqueal tanto a metacolina como a OA y el recuento de leucocitos fueron significativamente mayores que los del grupo de control (p<0,001 para todos los casos). En los grupos placebo se demostraron cambios anatomopatol¨®gicos variables de los pulmones (no significativos hasta p<0,001), comparado con los grupos de control. En los 2 grupos tratados con PF la reactividad traqueal tanto a metacolina como a OA disminuy¨® significativamente comparado con los grupos placebo (p<0,01 hasta p<0,001). El tratamiento con PF da lugar a una mejora del recuento de leucocitos (p<0,001) y de la f¨®rmula leucocitaria (no significativo p<0,001) al igual que del desprendimiento mucoso (p<0,001), pero no otros cambios anatomopatol¨®gicos(AU)

ConclusionesEstos resultados demuestran un efecto protector del PF sobre la reactividad traqueal y la inflamaci¨®n pulmonar. Adem¨¢s, el presente estudio demostr¨® que el tratamiento con propionato de fluticasona inhalado durante la sensibilizaci¨®n (desarrollo de inflamaci¨®n y cambios anatomopatol¨®gicos) fue m¨¢s eficaz que despu¨¦s de ella (establecimiento de inflamaci¨®n y cambios anatomopatol¨®gicos)(AU)

ObjectiveThe effect of an inhaled corticosteroid, fluticasone propionate (FP) lung inflammation of sensitized guinea pig was examined.Material and methodsFour groups of guinea pigs (n=8) were sensitized (S) with ovalbumin (OA). Control group was given similar solutions without OA. One S group was treated with inhaled 250¦Ìg inhaled FP twice/day during, other group after sensitization for 18 days and two groups were treated with placebo, one during, and the other after sensitization. One day after the last treatment, tracheal responses of all animal groups to methacholine and OA were examined. Total and differential white blood cell (WBC) counts of lung lavage and lung pathology were also examined.ResultsTracheal responsiveness to both methacholine and OA and WBC of both placebo groups were significantly higher than those of control group (P<0.001 for all cases). The lungs of placebo groups showed variable pathological changes (non significant to P<0.001) compared to control group. Tracheal responsiveness in two treated groups with FP to both methacholine and OA were significantly decreased compared to placebo groups (P<0.01 to P<0.001). Treatment with FP leads to improvement in total (P<0.001) and differential WBC counts (non significant to P<0.001) as well as mucosal detachment (P<0.001), but not other pathological changes.ConclusionsThese results showed a protective effect of FP on tracheal responsiveness and lung inflammation. In addition, this study showed that treatment with inhaled fluticasone propionate, during sensitization (development of inflammation and pathological changes) was more effective than after sensitization (establishment of inflammation and pathological changes)(AU)

Estudio comparativo de la aplicación del hidrocarburo aromático policíclico 7, 12-dimetil-1, 2-benzatraceno (DMBA) sobre la mucosa oral del hámster y del cobaya / A comparative study of the effect of applying polycyclic aromatic hydrocarbon, 7,12-dimethyl-1,2-benzanthracene (DMBA), to the oral mucosa of hamsters and guinea-pigs

Introducción: El carcinoma oral de células escamosases una neoplasia maligna con mal pronóstico y baja tasa desupervivencia, en cuya etiología están fuertemente implicadosel tabaco y el alcohol, entre otros factores. En 1954,Salley describió un modelo experimental de carcinogénesisen la mucosa yugal del hámster mediante la aplicación delagente DMBA. Métodos: Hemos desarrollado dos modelosexperimentales diferenciados, basados en la aplicación delDMBA sobre cobayas y hámster respectivamente. Resultados:En el primer modelo (cobayas) no ocurrió el fenómenode la carcinogénesis con el tiempo y las dosis administradas.Solamente observamos áreas de displasia epitelial,que era más severa en los animales que, además del tratamientocon DMBA, ingerían etanol. En el segundo modelo(hámster), se desarrollaron neoplasias malignas, que eranmás numerosas y con un comportamiento biológico másagresivo cuando se administraba el DMBA combinado conel etanol. Conclusiones: El etanol se ha comportado comoagente promotor de la carcinogénesis(AU)

Introduction: Oral squamous cell carcinoma is a malignantneoplasm with a bad prognosis and low survival rate.Tobacco and alcohol are among the most important causativefactors. In 1954, Salley described an experimental modelof carcinogenesis, applying the agent DMBA to the jugalmucosa of hamsters. Methods: we have developed two differentexperimental models based on the application ofDMBA to guinea pigs and hamsters. Results: No carcinogenesiswas seen in the guinea pigs at the administereddoses of DMBA, only areas of epithelial dysplasia, whichwere more severe in the animals that were also given alcohol.Malignant neoplasias developed in the hamsters andwere more numerous and more aggressive when DMBAwas administered together with ethanol. Conclusions: Inthe present study, ethanol acted as an enhancer of carcinogenesis(AU)

The Effects of Agonists of Ionotropic GABA A and Metabotropic GABA B Receptors on Learning

The research described here investigates the role played by inhibitory processes in the discriminations made by the nervous system of humans and animals between familiar and unfamiliar and significant and nonsignificant events. This research compared the effects of two inhibitory mediators of gamma-aminobutyric acid (GABA): 1) phenibut, a nonselective agonist of ionotropic GABAA and metabotropic GABAB receptors and 2) gaboxadol a selective agonist of ionotropic GABAA receptors on the process of developing active defensive and inhibitory conditioned reflexes in alert non-immobilized rabbits. It was found that phenibut, but not gaboxadol, accelerates the development of defensive reflexes at an early stage of conditioning. Both phenibut and gaboxadol facilitate the development of conditioned inhibition, but the effect of gaboxadol occurs at later stages of conditioning and is less stable than that of phenibut. The earlier and more stable effects of phenibut, as compared to gaboxadol, on storage in memory of the inhibitory significance of a stimulus may occur because GABAB receptors play the dominant role in the development of internal inhibition during an early stage of conditioning. On the other hand this may occur because the participation of both GABAA and GABAB receptors are essential to the process. We discuss the polyfunctionality of GABA receptors as a function of their structure and the positions of the relevant neurons in the brain as this factor can affect regulation of various types of psychological processes (AU)

Este trabajo investiga el papel de los procesos inhibitorios en la discriminación realizada por el sistema nervioso de los humanos y los animales entre sucesos familiares y no familiares y significativos y no significativos. Se comparó los efectos de dos mediadores inhibitorios del ácido gamma-aminobutírico (GABA): 1) Phenibut, un agonista no selectivo de los receptores del GABAA ionotrópico y del GABAB metabotrópico y 2) gaboxadol, un agonista selectivo de los receptores del GABAA ionotrópico, sobre el desarrollo de reflejos condicionados de defensa activa e inhibitorios en conejos en alerta y no inmovilizados. Se encontró que el phenibut, pero no el gaboxadol, acelera el desarrollo de reflejos defensivos en una etapa temprana del condicionamiento. Tanto el phenibut como el Gaboxadol facilitaron el desarrollo de la inhibición condicionada, pero el efecto del gaboxadol ocurre en etapas tardías del condicionamiento y es menos estable que el del phenibut. Los efectos más estables y más tempranos del phenibut, en comparación con el gaboxadol, sobre el almacenaje en la memoria de la significación inhibitoria de un estímulo pueden deberse a que los receptores del GABAB tienen el papel dominante en el desarrollo de la inhibición interna durante la fase inicial del condicionamiento. Por otro lado esto puede deberse a que la participación de los receptores tanto del GABAA como del GABAB son esenciales para el proceso. Comentamos la multifuncionalidad de los receptores del GABA como función de su estructura y de las posiciones de las neuronas relevantes en el cerebro, dado que este factor puede afectar la regulación de varios tipos de procesos psicológicos (AU)

Efecto de amoxapina en preparaciones de órgano aislado de cobaya y de rata "in vitro" / Effect of amoxapine on severa preparations of isolated guinea-pig and rat organ "in vitro"

OBJETIVO. Estudiar las modificaciones inducidas por amoxapina en las respuestas del íleon aislado de cobaya a acetilcolina e histamina, conducto deferente de rata a noradrenalina y dopamina y útero aislado de rata a histamina. MATERIAL Y MÉTODOS. Se utilizó ileon aislado de cobaya incubado en solución de Tyrode, conducto deferente de rata incubado en solución de Krebs-Henseleit y útero aislado de rata incubado en solución de Jalón. Se realizaron curvas dosis-efecto a acetilcolina, histamina, noradrenalina y dopamina en ausencia y en presencia de amoxapina y se calcularon los valores de pA2 y pD'2. RESULTADOS. La amoxapina se comporta como antagonista de los neurotransmisores estudiados. CONCLUSIONES. La amoxapina se comporta como estabilizador inespecífico de membrana (AU)

OBJETIVE. Study the modifications produced by amoxapine in the responses of isolated guinea-pig to acetylcholine and histamine, rat vas deferens to noradrenaline and dopamine and rat uterus to histamine. MATERIAL AND METHODS. Guinea-pig incubated in Tyrode solution were used. Dose-effect curves to acetylcholine and histamine were made in absence and in the presence of amoxapine. Rat vas deferens incubated in Krebs-Henseleit solution were used. Dose-effect to noradrenaline and dopamine were made in the absence and in the presence of amoxapine. Uterus of rat incubated in Jalon solution were used. Dose-effect curves to histamine were made in the absence and in the presence of amoxapine. pA2 and pD'2 were calculated. RESULTS. Amoxapine behave as antagonist of acetylcholine, histamine and dopamine. CONCLUSIONS. Amoxapine acts as unspecific membrane stabilizer (AU)

Efectos de citalopram, reboxetina y nefazondona sobre diversas preparaciones de órgano aislado de cobaya y de rata "in vitro" / Effectos of citalopram, reboxetine and nefazodone in differentes tissues form guinea-pig and rat "in vitro"

El citalopram, la reboxetina y la nefazodona son fármacos antidepresivos que fundamentalmente inhiben la recaptación neuronal de serotonina, aunque se han descrito otras interacciones. Se estudian los efectos de citalopram, reboxetina y nefazodona sobre noradrenalina (NA), dopamina (DA) o potasio (K+) en conducto deferente de rata; histamina (H), acetilcolina (Ach), 4-aminopiridina (4-AP) y potasio en ileon aislado de cobaya y serotonina (5-HT), oxitocina y potasio en útero aislado de rata. Se utilizó solución de Krebs-Henseleit con o sin adición de cocaína, 17-beta estradiol y propranolol, para el conducto deferente aislado de rata, solución de Jalón para el útero de rata y solución de Tyrode para el ileon aislado de cobaya. Cuando fue posible se calcularon los valores de pD'2. CONCLUSIONES: El citalopram inhibe las contracciones inducidas por Ach (pD'2 = 4.3 ± 0.3), H (pD'2 = 5.3 ± 0.4), 4-AP (pD'2 = 5.4 ± 0.4) y potasio (pD'2 = 4.3 ± 0.3) en ileon aislado de cobaya; 5-HT (pD'2 = 3.5 ± 0.3), oxitocina (pD'2= 4.8 ± 0.3) y potasio (pD'2= 4.2 ± 0.3) en útero de rata. La reboxetina inhibe las contracciones inducidas por 5-HT (pD'2= 5.1 ± 0.4), oxitocina (pD'2= 4.9 ± 0.3) y potasio (pD'2= 5.1 ± 0.4) en útero de rata y DA (pD'2= 4.6 ± 0.4 en conducto deferente aislado de rata. La nefazodona inhibe las contracciones inducidas por Ach (pD'2= 5.3 ± 0.3), H (pD'2 = 5.3 ± 0.4), 4-AP (pD'2 = 5.2 ± 0.3) y potasio (pD'2 = 5.2 ± 0.4) en ileon aislado de cobaya; 5-HT (pD'2 = 7.0 ± 0.5), oxitocina (pD'2 = 5.2 ± 0.4) y potasio (pD'2 = 5.2 ± 0.4) en útero de rata; NA (pD'2 = 2.4 ± 0.1), DA (pD'2 = 5.2 ± 0.4) y potasio (pD'2 = 4.4 ± 0.4) en conducto deferente aislado de rata. Otras interacciones no son estadísticamente significativas (AU)

Citalopram, reboxetine and nefazodone are antidepressants which mainly inhibit serotonin (5-HT) reuptake, other interactions have been described. Therefore, the effects of citalopram, reboxetine and nefazodone on noradrenaline (NA), dopamine (DA), or K+ - contracted rat vas deferens have studied. The effects on 5-HT, oxytocin and K+-induced contractions in rat uterus and those on histamine (H), acetylcholine (Ach), 4-aminopyridine (4-AP) and K+-contractions in guinea-pig ileum were also studied. Krebs-Henseleit solution with and without adding cocaine, 17 beta estradiol and propranolol was used for rat vas deferens tissues. Jalon solution for rat uterus and Tyrode solution for guinea-pig ileum. When possible pD'2 values were calculated. CONCLUSIONS: Citalopram inhibited contractions induced by Ach (pD'2 = 4.3 ± 0.3), H (pD'2 = 5.3 ± 0.4), 4-AP (pD'2 = 5.4 ± 0.4), and potassium (pD'2 = 4.3 ± 0.3) in guinea-pig ileum; 5-HT (pD'2 = 3.5 ± 0.3), oxytocin (pD'2 = 4.8 ± 0.3) and potassium (pD'2 = 4.2 ± 0.3) in rat uterus. Reboxetine inhibited contractions induced by 5-HT (pD'2 = 5.1 ± 0.4), oxytocin (pD'2 = 4.9 ± 0.3) and potassium (pD'2 = 5.1 ± 0.4) in rat uterus; DA (pD'2 = 4.6 ± 0.4) in rat vas deferens. Nefazodone inhibited contractions induced by Ach (pD'2 = 5.3 ± 0.3), H (pD'2 = 5.3 ± 0.4), 4-AP (pD'2 = 5.2 ± 0.3) and potassium (pD'2 = 5.2 ± 0.4) in guinea-pig ileum; 5-HT (pD'2 = 7.0 ± 0.5), oxytocin (pD'2 = 5.2 ± 0.4), and potassium (pD'2 = 5.2 ± 0.4) in rat uterus; NA pD'2 = 2.4 ± 0.1), DA (pD'2 = 5.2 ± 0.4) and potassium (pD'2 = 4.4 ± 0.4) in rat vas deferens. Other interactions were not statistically significant (AU)