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Introducción. Alrededor de 3700 millones menores de 50 años con infección por VHS-1 y 491 millones de personas de 15 a 49 años cursan con infección por VHS-2 en el mundo; sus síntomas, vesículas o ulceras dolorosas reaparecen periódicamente. El tratamiento convencional disminuyó su efectividad en cepas resistentes e inmunodeprimidos. Alternativas terapéuticas con extractos de plantas medicinales y potencial antiviral, como Opuntia soehrensii Brito conocida como "ayrampù" en Bolivia, utiliza infusión de sus semillas como analgésico, antidiabético, hipotensor y febrífugo. En vapores por inhalación para afecciones respiratorias; como tintura tópica en lesiones dérmicas de viruela, sarampión y herpes labial. Objetivo. Evaluar la seguridad preclínica de un gel que contiene el extracto hidro-alcohólico de semillas de Opuntia soehrensii en diferentes dosis, aplicado en la mucosa vaginal de ratas Sprague Dawley. Material y métodos. Se ejecutaron protocolos de toxicidad aguda y subaguda para evaluar la respuesta sistémica, a través de marcadores bioquímicos y de comportamiento, y la respuesta local en mucosa vaginal, mediante estudios histopatológicos, en grupos de animales a los que se aplicó el gel con diferentes concentraciones del extracto de Opuntia soehrensii, comparados con un grupo control y otro que recibió solo el vehículo. Resultados. Se encontró que los indicadores sistémicos de comportamiento y ganancia de peso no mostraron diferencias entre grupos. Los indicadores hematológicos y bioquímicos mostraron resultados fisiológicamente esperados y sin cambios en los grupos de estudio. La citología expuso conservación del fenotipo celular para las fases del ciclo estral en todos los grupos. Los indicadores histológicos de reacción local e integridad celular se distribuyeron de igual manera en los todos los grupos. Conclusión. La aplicación de un gel de Opuntia soehrensii no muestra niveles apreciables de toxicidad local y sistémica, lo que permite recomendar la iniciación de estudios de aplicación clínica.

Introduction. Around 3.7 billion people under 50 years of age are infected with HSV-1 and 491 million people between the ages of 15 and 49 are infected with HSV-2 in the world; his symptoms, vesicles or painful ulcers recur periodically. Conventional treatment decreased its effectiveness in resistant and immunosuppressed strains. Therapeutic alternatives with extracts of medicinal plants and antiviral potential, such as Opuntia soehrensii Brito known as "ayrampù" in Bolivia, uses infusion of its seeds as an analgesic, antidiabetic, hypotensive and febrifuge. In vapors by inhalation for respiratory conditions; as a topical tincture in skin lesions of smallpox, measles and cold sores. Objectives . To evaluate the preclinical safety of a gel containing the hydroalcoholic extract of Opuntia soehrensii seeds in different doses, applied to the vaginal mucosa of Sprague Dawley rats. Material and Methods. Acute and sub-acute toxicity protocols were carried out to evaluate local response in the vaginal mucosa, through histo pathological studies, and systemic responses, through biochemical and behavioral markers, in groups of animals to which the gel with different concentrations of the extract of Opuntia soehrensii was applied, compared with a control group and another that received only the vehicle. Results. It was found that the histological indicators of local reaction and cell integrity were equally distributed in all groups. Cytology showed conservation of the cell phenotype for the phases of the estrous cycle in all groups. The systemic indicators of behavior and weight gain did not show differences between groups. Hematological and biochemical indicators showed results ranged in physiologic parameters, without changes in the study groups. Conclusion. The application of a gel from Opuntia soehrensii does not show appreciable levels of local and systemic toxicity, which makes it possible to recommend the initiation of clinical application studies.

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Exposure to electromagnetic radiation (EMR) from intermediate frequency sources has increased exponentially in recent years. The consequences of this exposure on biological systems are prompting scientists to study the effects on human health. This current study aimed to determine the effects of intermediate frequency (150 kHz) EMR exposure on the vital organs of female Sprague Dawley rats. The EMR group (n = 10 animals) was exposed to a frequency of 150 kHz with an intensity of 65 ± 15 µW/cm2 for two months. The control group (n = 10 animals) was exposed to an intensity of 35 ± 15 nW/cm2. Haematological, histochemical, gross, and histopathological profiles of all major organs of all animals were then performed using standard procedures. All major organs generally showed no significant detectable effects in either the control or EMR groups. However, gross and histopathological examinations revealed the effects of EMR on the liver and lungs, which showed inflammatory changes without significant biochemical/haematological manifestations. In addition, a significant increase in serum sodium level and a decrease in serum urea level were also observed in the EMR group. It can be concluded that the current frequency and duration of exposure trigger the changes in the liver and lungs but are not sufficient to cause clinical and functional manifestations. Therefore, a long-term exposure study might be helpful to determine the effects of 150 kHz IF EMR on these organs.

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Abstract Biological activity of boron-containing compounds (BCCs) has been well-known. Growing interest and numerous applications for BCCs have been reported. Boron and boron-containing acids show low acute toxicity in mammals but data on halogenated boroxine (HB) - dipotassium-trioxohydroxytetrafluorotriborate, K2(B3O3F4OH) acute toxicity have not been reported before. This compound, characterized as a potential therapeutic for skin changes, exhibits no observable genotoxicity in doses lower that 0.1 mg/ml in vitro and 55 mg/kg in vivo. It has also been confirmed as an antitumour agent both in vitro and in vivo as well as an inhibitor of enzymes involved in antioxidant mechanisms. The aim of this study was to assess the acute toxicity of HB and to determine the maximum tolerated dose as well as a dose free of any signs of toxicity in different test organisms. Acute toxicity of HB was tested in Sprague-Dawley and Wistar rats and BALB/c mice after single parenteral application of different doses. We determined doses free of any sign of toxicity and LD50 after single dose administration. LD50 of HB ranges from 63 to 75 mg/kg in different test models, meaning that HB shows moderate toxicity

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This study aimed to evaluate whether aluminum chloride (AlCl3) causes hematological changes in the peripheral blood of Sprague-Dawley (SD) rats. Five groups of female SD rats were intragastrically administered with 4 different concentrations of AlCl3 for 5 days a week for a total of 90 days. The aluminum concentration was determined via graphite furnace atomic absorption spectroscopy. Analysis of serum iron-kinetic profiles, blood cytometry outcomes, and blood smears of the blood samples. Scanning electron microscopy (SEM) and Raman spectroscopy were used to search for structural and ultrastructural changes, respectively. Blood aluminum concentration ranged 12.38-16.24 µg/L with no significant difference between experimental treatments. At the AlCl3 concentration of 40 mg Al/kg bw of rats/day, the mean ferritin value in the serum iron kinetic profile was 29.81±6.1 ng/mL, and this value showed a significant difference between experimental treatments. Blood cytometry revealed that there were 6.45-7.11×106 cells/µL erythrocytes, 8.91-9.32×103 cells/µL leukocytes, and 477.2-736.3×103 cells/µL platelets along with a hemoglobin of 37.38-41.93 g/dL and hematocrit level of 37.38-41.93%; the experimental treatments showed no significant differences. Erythrocyte structural analysis using SEM showed no differences between experimental treatments, whereas ultrastructural evaluation using Raman spectroscopy made it possible to identify the following bands: 741, 1123, 1350, 1578, and 1618 cm-1, which were respectively associated with the following vibrational modes and compounds: vibration of the tryptophan ring, asymmetric C-O-C stretching of glucose, C-H curve of tryptophan, C=C stretching of the heme group, and C-N stretching of the heme group, with no significant differences between experimental treatments. Therefore, AlCl3 administration does not induce ultrastructural changes in the erythrocyte membrane. This study revealed that serum ferritin concentration was the only parameter affected by AlCl3 exposure at 40 mg of Al/kg bw of rats/day.

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Para el control y prevención del cólera humano se han llevado a cabo diferentes estrategias, entre las cuales, la vacunación es una de las medidas más eficaces. La evaluación preclínica de candidatos vacunales requiere de la demostración de la seguridad de los mismos, para lo cual los estudios toxicológicos son determinantes, al ser obligatorios y altamente regulados. Este estudio tuvo como objetivo demostrar la relevancia de las ratas Sprague Dawley como biomodelo a través de su respuesta inmunológica al candidato vacunal contra el cólera, vax-COLER®, utilizando la técnica de determinación de anticuerpos vibriocidas. Además, evaluar los efectos toxicológicos locales y sistémicos por la administración de una dosis de vax-COLER® a través de la evaluación de síntomas, del consumo de agua y alimentos, el peso corporal y estudios anatomopatológicos. La vacuna vax-COLER® resultó inmunogénica y no evidenció síntomas ni muertes, no hubo cambios en el peso corporal y los consumos de agua y alimentos se comportaron de forma similar entre todos los grupos. Los estudios anatomopatológicos solo mostraron cambios a nivel histológico en los ganglios linfáticos mesentéricos y placas de Peyer de los animales vacunados, con presencia de hiperplasia de los folículos secundarios subcapsulares, hallazgo que difirió significativamente con el resto de los grupos. Se concluye que la vacuna vax-COLER® es inmunogénica en ratas Sprague Dawley, demostrando la relevancia del biomodelo para la evaluación de la seguridad preclínica y que la aplicación de una dosis no produjo efectos tóxicos agudos generales ni locales(AU)

Different strategies have been carried out for the control and prevention of human cholera. Vaccination is one of the most effective strategies. Preclinical evaluation of vaccines needs to prove their safety; whereby toxicological studies are decisive. They are mandatory and highly regulated. This study was aimed to demonstrate the relevance of Sprague Dawley rats as a biomodel, through the immunological response to vax-COLER® cholera vaccine, using the technique of determination of vibriocidal antibodies. In addition, local and systemic toxicological effects were evaluated after administration of a dose of vax-COLER®; through the evaluation of symptoms, water and food consumption, body weight and anatomopathological studies. The vax-COLER® vaccine was immunogenic and showed no symptoms or deaths. No changes in body weight were detected, and food and water consumption were similar among all groups. The anatomopathological studies showed histological changes in the mesenteric lymph nodes and Peyer's patches of the vaccinated animals, with hyperplasia of the subcapsular secondary follicles, finding that differed significantly from the rest of the groups. It is concluded that vax-COLER® vaccine is immunogenic in Sprague-Dawley rats, demonstrating the relevance of the biomodel for the evaluation of preclinical safety, as well as that the application of a single dose did not produce acute general or local toxic effects(AU)

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Este estudio se realizó con el propósito de analizar el efecto de la aplicación de ondas de USBI sobre la velocidad y distancia de movimiento dentario, y su efecto a nivel histológico en ratas Sprague-Dawley. Veintitrés ratas macho Sprague-Dawley fueron parte del experimento, las que fueron divididas aleatoriamente en tres grupos. Cinco ratas fueron utilizadas como control sin movimiento dentario ortodóncico (MDO), nueve ratas fueron sometidas a una aplicación de fuerza ortodóncica sin aplicación de USBI y nueve fueron sometidas a una aplicación de fuerza ortodóncica con USBI. Estas fuerzas ortodóncicas fueron realizadas entre el aspecto mesio vestibular del primer molar superior izquierdo y el incisivo central superior, traccionando el molar hacia mesial, aplicando una fuerza aproximada de 50 gramos durante 21 días, debido a problemas con la sedación estos dos últimos grupos quedaron compuestos de seis y ocho ratas respectivamente. En el grupo MDO sin USBI, se registró una reducción del espacio entre molares e incisivos de 2 mm. En el grupo MDO con USBI dicha reducción fue de 3.4 mm, siendo esta diferencia estadísticamente significativa. Histológicamente el grupo MDO c/USBI mostró un perímetro vascular y espacios medulares aumentados respecto de los otros grupos, no obstante, no se encontraron diferencias significativas en la cantidad de osteoclastos. Fue posible observar y demostrar cuantitativamente que el USBI es una forma de estimulación mecánica eficiente para la aceleración del MDO sobre un período experimental de 21 días, donde se observaron diferencias significativas entre el grupo control, el grupo MDO sin USBI y el grupo MDO con USBI en la magnitud del movimiento dentario. Se observó una mayor vascularidad en el grupo con USBI, expresando perímetros vasculares de mayor tamaño, esto pudo deberse al efecto estimulatorio del ultrasonido sobre la angiogénesis.

The objective of this study was to analyze the effect of USBI wave application on the speed and distance of dental movement, and its effect at histological level in SpragueDawley rats. In this study twenty-three male Sprague-Dawley rats were randomly divided into three groups. Five rats were used as control without orthodontic tooth movement (MDO), nine rats were subjected to an orthodontic force application without USBI application, and nine were subjected to an orthodontic force application with USBI. The orthodontic forces were performed between the vestibular mesio aspect of the first upper left molar and upper central incisor, pulling the molar mesially, applying an approximate force of 50 grams for 21 days. In light of sedation problems these last two groups were composed of six and eight rats respectively. In the MDO group without USBI, there was a reduction in the space between molars and incisors of 2 mm. In the MDO group with USBI this reduction was 3.4mm, this difference being statistically significant. Histologically, the MDO c / USBI group showed a vascular perimeter and enlarged spinal spaces with respect to the other groups, however, no significant differences were found in the amount of osteoclasts. It was possible to quantitatively demonstrate that USBI is a form of efficient mechanical stimulation for MDO acceleration over an experimental 21-day period, where significant differences were observed in tooth movement between the control group, the group without USBI and the group with USBI. A greater vascularity was observed in the group with USBI, expressing larger vascular perimeters, which could be due to the stimulatory effect of ultrasound on angiogenesis.

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Combined vaccines for childhood are a strategy in the prevention of several diseases. These can maximize protection and decrease immunization schedules in children. New candidates are getting closer to being able to meet these needs, but they raise numerous strategic questions related to formulation and regulatory aspects. In addition to being immunogenic and protective must have low reactogenicity when combined with other antigens. Adjuvants are important components in achieving these combinations. Therefore, a reactogenicity study was designed for two Bordetella pertussis formulations containing hydroxide or aluminum phosphate in Sprague Dawley rats. Both formulations dose were administered in 0.2 mL intramuscularly. Clinical evaluations, body weight, water consumption, food, temperature, muscle volume, dermal irritability and pathological studies with special interest at the inoculation site were carried out. Only differences in body temperature and muscle volume were found with a slight increase in values with return to normal. The macroscopic study showed lesions at the site of inoculation, consid­ered characteristics of aluminum adjuvants, such as granulomatous abscesses and the increase in regional lymph nodes near the inoculation site. As conclusion, there are no differences between the formulations of B. pertussis with hydroxide or aluminum phosphate resulted in low reactogenicity.

Las vacunas combinadas resultan una estrategia importante en la obtención de vacunas múltiples para la infancia y el uso de adyuvantes es un componente de gran valor en lograr estas combinaciones, además de ser inmunogénicas y protectoras deben tener baja reactogenicidad, cuando se combinan con diferentes antígenos. Por esta razón, se diseñó un estudio de reactogenicidad a dos formulaciones que contenían hidróxido y fosfato de aluminio con antígenos de Bordetella pertussis en ratas Sprague Dawley. Se administró a cada grupo de ensayo una dosis correspondiente de ambas formulaciones en 0,2 mL por vía intramuscular. Se realizaron observaciones clínicas, comportamiento del peso corporal, consumo de agua, alimentos, temperatura corporal, volumen muscular, irritabilidad dérmica y estudios anatomopatológicos macroscópicos, con especial interés en el sitio de inoculación. No se observaron síntomas, ni muertes en los animales durante el estudio. Tampoco se encontraron diferencias entre los grupos experimentales en cuanto al peso corporal, el consumo de agua y de alimentos; los estudios de temperatura corporal y volumetría muscular evidenciaron un ligero incremento en los valores, los cuales involucionaron rápidamente a la normalidad. En el estudio anatomopatológico macroscópico se observaron lesiones a nivel del punto de inoculación, consideradas propias de los adyuvantes que contienen aluminio, tales como formaciones abscedadas de tipo granulomatosas y el aumento de los ganglios linfáticos regionales cercanos al punto de inoculación. Se concluye que las formulaciones en hidróxido y fosfato de aluminio con antígenos de B.pertussis resultaron ser de baja reactogenicidad.

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Situs inversus totalis is a condition where there is a transposition of all internal organs from their normal anatomical location. This infrequent and rare congenital condition has been described in several species of mammals. Dextorcardia is a series of conditions associated with an abnormal congenital positioning of the heart, and is often associated with situs inversus totalis. Here we report a case of situs inversus totalis and two cases of dextrocardia identified in Sprague Dawley rats during gross necropsy evaluations at both the Health Sciences North Research Institute (HSNRI) in Canada and Finlay Institute of Vaccine Research and Production in Cuba. The intent of this report is to share our findings and aid in the accumulation of data on these rare conditions.

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OBJECTIVE: This study investigated the effects of D-ribose and L-cysteine on aluminum-induced testicular damage in male Sprague-Dawley rats. METHOD: A total number of thirty-five (35) adult male Sprague-Dawley rats were divided into four groups (AD). Group A (comprised five (5) rats) was designated the Control Group that received Physiological Saline; while groups B, C, and D (comprised ten (10) rats) were given 75 mg/kg, 150 mg/kg and 300 mg/kg of body weight of aluminum chloride respectively for 39 days. At day 40, the aluminum-treated groups were subdivided into sub-groups (B1, C1, D1) comprising of five (5) rats each, and 30 mg/kg body weight of Riboceine were administered for twenty (20) days. Groups B, C and D remained on the normal dosage of aluminum chloride for three more weeks (59 days). RESULTS: Andrological parameters (Sperm count, motility, morphology and testosterone) in the aluminum-treated Groups B and C showed no significant difference in their mean values when compared with their control counterparts, whereas there was a significant reduction in the andrological parameters in Group D rats when compared with the Control animals. Histoarchitecture of the testes "stain with H&E" of Group A, B and C rats appeared normal while Group D rats showed testicular damages with several abnormal seminiferous tubules with incomplete maturation of germinal cell layers and absence of spermatozoa in their lumen; Leydig cells appear hyperplastic. Group B1, C1 and D1 andrological and histological parameters appeared normal. CONCLUSION: Riboceine treatment significantly attenuates aluminum-induced testicular toxicity in male Sprague-Dawley in rats.

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Zinc deficiency during pregnancy and postnatal life can adversely increase risk of developing human diseases at adulthood. The present study was designed to evaluate whether dietary zinc deficiency or supplementation during the pregnancy, lactation and juvenile stages interferes in the development of mammary tumors induced by 7,12-dimethylbenzanthracene (DMBA) in female Sprague-Dawley (SD) rats. Pregnant female SD rats were allocated into three groups: zinc-adequate diet (ZnA - 35-mg/kg chow), zinc-deficient diet (ZnD - 3-mg/kg chow) or zinc-supplemented diet (ZnS - 180-mg/kg chow) during gestational day 10 (GD 10) until the litters' weaning. Female offspring received the same diets as their dams until postnatal day (PND) 51. At PND 51, the animals received a single dose of DMBA (50 mg/kg, ig) and zinc-adequate diets. At PND 180, female were euthanized, and tumor samples were processed for histological evaluation and gene expression microarray analysis. The ZnD induced a significant reduction in female offspring body weight evolution and in mammary gland development. At late in life, the ZnD or ZnS did not alter the latency, incidence, multiplicity, volume or histological types of mammary tumors in relation to the ZnA group. However, the total tumor number in ZnS group was higher than in ZnA group, accompanied by distinct expression of 4 genes up- and 15 genes down-regulated. The present findings indicate that early-in-life dietary zinc supplementation, differently to zinc deficiency, has a potential to modify the susceptibility to the development of mammary tumors induced by DMBA.

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Se tiene evidencia que la exposición a una dieta alta en grasa puede ser perjudicial para la cognición a lo largo de la vida. Hemos demostrado previamente que el aprendizaje contexto-estímulo es sensible a los efectos de una dieta alta en grasas durante la adolescencia, pero no la edad adulta. En el presente estudio se determinó si la exposición a una dieta alta en grasa en la pre y peri adolescencia interfiere con la capacidad de respuesta de inhibición, el aprendizaje de reglas, y la memoria en la edad adulta. Las ratas fueron alimentadas con una grasa alta o dieta baja en grasa durante la pre y periadolescencia y se completaron las pruebas de comportamiento como adultos para evaluar la capacidad de respuesta de inhibición y eficacia reforzador regla-aprendizaje y la memoria a corto plazo. Los resultados indican que la dieta rica en grasas durante la pre y periadolescencia puede tener efectos a largo plazo sobre la eficacia del refuerzo y la atención sostenida. Sin embargo, los resultados indican que o bien el periodo de pre y periadolescencia es demasiado corto para que una dieta alta en grasas pueda inducir déficits a largo plazo en la respuesta de inhibición, regla de aprendizaje o la memoria, o que la maduración en ausencia de una dieta alta en grasas rescate a los individuos de estos déficits.

Several lines of evidence demonstrate that high fat diet exposure can be detrimental to cognition across the lifespan. We have previously shown that context-stimulus learning is sensitive to high fat diet effects during adolescence but not adulthood. In the present study we determined if pre and periadolescent high fat diet exposure interferes with response -inhibition capacity, rule - learning, and memory during adulthood. Rats were fed a high fat or low fat diet during pre and periadolescence and completed behavioral testing as adults to assess response -inhibition capacity and reinforcer efficacy rule-learning and short-term memory. Results indicate pre and periadolescent high fat diet may have long-term effects on reinforcer efficacy and sustained attention. However, results indicate that either the pre and periadolescence period is too short for a high fat diet to induce long-term deficits in response-inhibition, rule -learning, or memory, or that maturation in the absence of a high fat diet rescued these deficits.

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Se efectuó un estudio preclínico, experimental y analítico en 100 ratas Sprague-Dawley para determinar los efectos del limo de la salina de Guantánamo en la cicatrización por segunda intención en un modelo de herida incisional, mediante el control simultáneo a dichas ratas. Estas fueron distribuidas en 4 grupos: uno de estudio y 3 controles; a los primeros se les aplicó limo y los segundos fueron tratados con NaCl al 0,9 %; NaCl al 4,0 % y Hebermin®, respectivamente. Se constató que las heridas cicatrizaron más rápido con limo y que hubo una reacción inflamatoria aguda efectiva al reducir el edema y el tejido desvitalizado, además de estimular la angiogénesis, la fibroplasia y la reepitelización. Se concluyó que el limo de la salina de Guantánamo posee propiedades cicatrizantes más efectivas que el Hebermin® y el NaCl al 4,0 %.

A preclinical, experimental and analytical study was carried out, in 100 Sprague-Dawley rats to determine the effects of the saline slime from Guantánamo in the scaring for second intention in a model of incisional wound, by means of the simultaneous control to them. They were distributed in 4 groups: a study group and 3 control groups; the first ones were treated with slime and the second ones were treated with 0,9% NaCl; 4,0% NaCl and Hebermin®, respectively. It was verified that the wounds healed quicker with slime and that there was an effective acute inflammatory reaction when reducing the edema and the devitalized tissue, besides stimulating the angiogenesis, fibroplasia and reepitelization. It was concluded that the saline slime from Guantánamo has more effective healing properties than Hebermin® and 4,0% NaCl.

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Introducción: la enfermedad hepática tóxica es un problema desconcertante debido al amplio número de sustancias capaces de inducir este tipo de reacciones. Datos epidemiológicos y estadísticos demuestran que la Mimosa púdica conocida como moriviví, sensitiva, adormidera es una de las plantas (objeto de abuso) más empleadas como adulterante en los pitillos de marihuana en pacientes drogadictos. Objetivos: evaluar el comportamiento de los parámetros bioquímicos y describir los hallazgos anatopatológicos en el hígado de ratas por efecto de la planta Mimosa púdica. Métodos: se realizó un estudio preclínico de hepatotoxicidad aguda con la planta Mimosa púdica en animales de experimentación. Se seleccionaron 25 ratas Sprague Dawley, cinco por cada grupo (control positivo, control y tres grupos experimentales) de experimentación. Se administró una dosis de 500, 1000 y 2000 miligramos por kilogramo de peso corporal de la decocción de la planta a los grupos experimentales respectivamente; tetracloruro de carbono a dosis de 3 mililitros por kilogramo de peso corporal al control positivo y agua estéril al control. Resultados: aumento de los niveles de transaminasas (TGP y TGO) en los grupos experimentales con respecto al grupo control. Las alteraciones anatomopatológicos observadas fueron: necrosis focal periportal, congestión de venas centrolobulillares y degeneración acidófila del hígado. Conclusiones: el consumo de la decocción de la planta Mimosa púdica afecta el hígado, lo que provoca alteraciones bioquímicas y anatomopatológicas, de probable importancia en pacientes drogadictos, aunque se requieren más estudios.

Introduction: toxic liver disease is a concerning problem due to the large number of substances that cause such reactions. Epidemiological and statistical data show that Mimosa (Moriviví), known as sensitive and opium poppy is one of the most used plants by drug-addict patients, as an adulterant in marihuana cigarettes drug. Objectives: to evaluate the behavior of biochemical parameters and describe pathological findings in the liver of rats as a result of Mimosa pudica plant. Methods: a preclinical study of acute hepatotoxicity with Mimosa pudica plant in experimental animals was performed. Twenty five Sprague Dawley rats, five per group (positive control, group control and three experimental) were selected for the study. A dose of 500, 1000 and 2000 mg administered per kilogram of body weight of the decoction of the plant to the experimental groups respectively; carbon tetrachloride at doses of 3 milliliters per kilogram of body weight to the positive control and sterile water to control. Results: the results showed an increase of levels of transaminases (SGOT and SGPT) in the experimental groups compared to the control group. The pathological changes observed were focal periportal necrosis, congestion and centrilobular veins acidophilic degeneration of the liver. Conclusions: the consumption of the decoction of the plant Mimosa pudica affects the liver, causing biochemical and pathological alteration of likely importance in drug patients, although further studies are required.

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Introducción: el D-004, un extracto lipídico del fruto de la palma real, Roystonea regia, constituido por una mezcla reproducible de ácidos grasos, principalmente oleico, palmítico, láurico y mirístico, ha mostrado prevenir la hiperplasia prostática (HP) inducida con T en roedores y actúa mediante un mecanismo multifactorial que implica la inhibición de 5a-reductasa prostática, el antagonismo de las respuestas mediadas por los a1-ADR, efectos anti-inflamatorios y antioxidantes. Objetivo: el presente trabajo tiene como propósito resumir los resultados parciales (18 meses) del estudio de carcinogenicidad a largo plazo del D-004 en ratas, el cual culminará con el tiempo establecido de 24 meses. Métodos: se distribuyeron ratas Sprague Dawley (SD) de ambos sexos aleatoriamente, en cuatro grupos (50 ratas/sexo/grupo): un grupo como control de vehículo, y tres tratados con D-004 (500, 1 000 y 1 500 mg/kg, respectivamente). Los tratamientos se administraron por intubación gástrica. Este reporte incluye los resultados de peso corporal, observaciones clínicas, mortalidad y frecuencia de aparición de tumores hasta ese momento. Resultados: la frecuencia de mortalidad es baja, en los grupos tratados fue de un 8.3 por ciento por un 9 por ciento en los controles, no se evidencia disminución en el tiempo de supervivencia y las observaciones diarias no revelaron signos indicativos de toxicidad atribuibles al tratamiento. Además, el momento de aparición y la frecuencia de tumores en animales tratados y controles fueron estadísticamente similares en ambos sexos. Conclusiones: en conclusión, la administración de D-004 (5001500 mg/kg) a ratas durante los primeros 18 meses del estudio, no mostró evidencias de toxicidad o carcinogenicidad temprana relacionadas con el tratamiento

Introduction: D-004, a lipid extract from royal palm (Roystonea regia) fruit made up of a reproducible mixture of fatty acids, mainly oleic, palmitic, lauric and myristic, has shown to prevent prostate hyperplasia (PH) induced by T in rodents. It acts through a multifactorial mechanism involving prostatic 5a-reductase inhibition, antagonism of a1-ADR-mediated responses, and antiinflammatory and antioxidant effects. Objective: the paper is aimed at summarizing the partial results (18 months) of the long-term carcinogenicity study of D-004 in rats, which is set to conclude in the established 24-month period. Method: Sprague Dawley (SD) rats of both sexes were randomly distributed into four groups (50 rats/sex/group): one group as vehicle control and three treated with D-004 (500, 1 000 and 1 500 mg/kg, respectively). Treatments were administered by gastric intubation. This report presents the results obtained so far concerning body weight, clinical observations, mortality and frequency of appearance of tumors. Results: mortality rate is low: 8.3 percent in the treated groups and 9 percent among controls. No evidence was found of survival time reduction, and daily observations did not reveal any signs of toxicity attributable to the treatment. The time of appearance and the frequency of tumors in treated animals and controls were statistically similar in both sexes. Conclusions: administration of D-004 (5001 500 mg/kg) to rats during the first 18 months of the study did not show any evidence of early carcinogenicity or toxicity associated with the treatment

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O câncer de mama é a neoplasia maligna mais prevalente e a principal causa de óbito entre mulheres, no mundo. A despeito de avanços substanciais no entendimento da biologia da doença, nos métodos de detecção precoce, e em sua farmacoterapia, a sobrevida geral não se modificou significantemente nas últimas décadas. Portanto, pode se dizer que um dos deveres primordiais das Universidades Públicas engajadas com pesquisa básica e aplicadas consiste em contribuir para o desenvolvimento de novas estratégias de tratamento sistêmico desta neoplasia. Nesse contexto, um dos alvos estratégicos mais promissores no desenvolvimento de novos fármacos antineoplásicos é representado pela célula-tronco neoplásica (CTN). As CTNs têm sido associadas em inúmeros estudos à capacidade de algumas neoplasias malignas de resistir às principais modalidades terapêuticas antineoplásicas, especialmente à: radio-, quimio-, hormônio- e imunoterapias. Em resumo, na atualidade, a detecção de CTNs constitui uma ferramenta clínica bastante promissora enquanto alvo terapêutico, fator prognóstico e preditivo de resposta terapêutica. O objetivo deste trabalho foi descrever e discutir as potencialidades e limitações do modelo de carcinogênese mamária pelo DMBA, após reclassificação das neoplasias mamárias segundo os critérios diagnósticos da OMS (2003, 2012), subtipagem molecular e quantificação de imunomarcadores prognósticos, preditivos e de CTN. Após a aplicação do protocolo experimental de indução química pelo DMBA e a eutanásia dos animais controle e experimental, suas linhas mamárias (contendo ou não tumores) foram ressecadas e avaliadas quanto à morfologia e a imunoexpressão para marcadores de CTNs. Após 13 semanas, 100% dos animais desenvolveram neoplasias macroscópicas e histologicamente compatíveis com os critérios de avaliação indicados pela OMS.

Breast cancer is the most common malignancy and the leading cause of death from cancer among females worldwide. Despite all the research and all the progress, methods of early detection, and its pharmacotherapy, overall survival has not changed significantly in recent decades. Therefore, the Public University has been engaged in basic and applied research is too contributed to the development of new strategies for systemic treatment of this malignancy. In this context, one of the most promising strategic targets in the development of the anticancer drugs is represented by neoplastic stem cell (NSC). Neoplastic stem cell has been linked in various studies to the capacity of some malignancies to resist major antineoplastic therapeutic modalities, especially: radio-, chemo-, hormone- and immunotherapies. In summary, the detection of NSCs is a clinical tool very promising while therapeutic target and prognostic factor predictive of therapeutic response. The aim of this study was to describe and discuss the strengths and limitations of the model of mammary carcinogenesis by DMBA, after reclassification of breast cancer according to the diagnostic criteria of the WHO (2003, 2012), and quantification of molecular subtyping prognostic immunomarkers, predictive and NSC. After application of the experimental protocol of chemical induction by DMBA and euthanasia of experimental and control animals, the mammary lines (with or without tumors) were resected and evaluated the morphology and immunostaining for markers of NSCs. After 13 weeks, 100% of the animals developed macroscopic neoplasms and histologically consistent with the evaluation criteria of evaluation indicated by WHO. Tumors were classified as ductal carcinoma, papillary carcinoma, lobular carcinoma, myoepithelial carcinoma and phyllodes tumor, being the most common type, the ductal. Few immunohistochemical markers correlated with variable behavior biological.

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Objetivo: comparar fetos de ratones Balb/c y ratas Sprague Dawley como biomodelos en el ensayo de micronúcleos transplacentarios, determinando la frecuencia espontánea e inducida, y vincular el efecto genotóxico y reproductivo. Métodos: se formaron tres grupos experimentales/especie: control negativo (simulacro), control solvente NaCl (0,9 %) y ciclofosfamida 50 mg/kg. Todos los grupos se administraron por vía intraperitoneal los días 14, 15 y 16 de la gestación, y 24 h después de la última inoculación en ratones y 48 h en ratas se procedió a realizar la eutanasia de las gestantes, para obtener las muestras de hígado fetal. Resultados: los fetos de ratas Sprague Dawley demostraron tener menores índices de citotoxicidad y de genotoxicidad, y se obtuvieron los resultados más bajos de micronúcleos endógenos. Los mejores resultados de inducción de citotoxicidad y genotoxicidad por la alta formación de micronúcleos con ciclofosfamida fueron en fetos de ratas Sprague Dawley, los que resultaron más susceptibles al daño genotóxico de este mutágeno. Se corroboró el poder clastogénico transplacentario de la ciclofosfamida, vinculando este ensayo de genotoxicidad a toxicología de la reproducción. Conclusiones: los resultados sugieren el mejor uso de fetos de ratas Sprague Dawley como biomodelo en este ensayo cuando es utilizada la ciclofosfamida como control positivo por la vía y dosis estudiada; además, se pudieran utilizar en la evaluación de nuevas drogas con carácter antigenotóxico por vía transplacentaria.

Objectives: to compare fetuses from Balb/c mice and Sprague Dawley rats as biomodels in transplacental micronuclei assay and to determine the spontaneous and induced frequency to link the genotoxic and reproductive effect. Methods: three experimental groups by species were formed: a negative control (simulation), NaCl (0.9 %) solvent control and 50 mg/kg cyclophosphamide. All the groups were intraperitoneally administered at 14th, 15th and 16th days of gestation, and 24 h after the last inoculation in mice and 48 h in rats, it proceeded to perform euthanasia in the pregnant animals to obtain the fetal liver samples. Results: the fetuses from Sprague Dawley exhibited smaller cytotoxicity and genotoxicity indexes, and the lowest endogenous micronucleus results. The best results of the cytotoxicity and genotoxicity induction for the high micronucleus formation with cyclophosphamide were found in Sprague Dawley rat fetuses, being more susceptible to the genotoxic damage by this mutagen. The clastogenic transplacental power of cyclophosphamide was confirmed whereas this genotoxicity assay was linked to reproduction toxicology. Conclusions: these results suggest that the Sprague Dawley rats fetuses could be better used as biomodels in this assay when cyclophosphamide is employed as positive control through the way of administration and the studied dosage. It could be similarly used in the evaluation of new antigenotoxic drugs with antigenotoxic effect through transplacental administration.

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INTRODUCCIÓN: El hígado graso no alcohólico puede abarcar desde una simple esteatosis hasta una cirrosis hepática. Los mecanismos fisiopatológicos que modulan el estrés oxidativo, la actividad inflamatoria y profibrótica, deberían ser cruciales en su mayor o menor agresividad hepática y vascular. Un compuesto derivado de la Cúrcuma longa L, la curcumina, poseería propiedades vasoprotectoras. OBJETIVO: Comparar en situaciones de dieta hipercolesterolémica los cambios vasculares entre ratas macho Sprague Dawley que consumen curcumina y las que no consumen. MATERIAL Y MÉTODO: Estudio analítico, experimental, longitudinal y prospectivo en ratas macho Sprague-Dawley expuestas a condiciones de hígado graso no alcohólico e hígado graso no alcohólico adicionando curcumina, durante 4 meses. Sacrificadas, se realizó protocolo de función vascular en arteria mesentérica superior aislada (respuesta a acetilcolina, N nitro-L-arginina metil éster y nitroprusiato) y medición de presión portal por punción directa. Los resultados fueron expresados en promedios junto a la desviación estándar de la media. Lasdiferencias entre los grupos fueron probadas mediante t de Studenty test de Mann-Whitney. RESULTADOS: La medición de presión portal no mostró diferencias significativas entre ambos grupos. No hubo diferencias significativas en las pruebas con Nnitro-L-arginina metil éster ni nitroprusiato; diferencia que sí existió con acetilcolina entre la dilatación de la arteria mesentérica superior de hígado graso no alcohólico y las de hígado graso no alcohólico más curcumina. DISCUSIÓN: La curcumina mejoró la respuesta vasodilatadora a acetilcolina, lo que sugiere que el posible efecto antioxidante sería mejorando la función endotelial. Se sugiere su futuro uso terapéutico.

INTRODUCTION: Nonalcoholic fatty liver disease can range from simple steatosis to cirrhosis. The pathophysiological mechanisms that modulate oxidative stress, inflammatory and profibrotic activity should be crucial in the liver injury and vascular aggressiveness. Curcumin, a compound derived from Curcuma longa L, possesses vasoprotectives properties. OBJECTIVE: To compare in hypercholesterolemic diet situations the vascular changes between Sprague-Dawley male rats who consume curcumin and who do not consume. MATERIAL AND METHOD: Analytical, experimental, prospective and longitudinal study in Sprague-Dawley male rats exposed to conditions of Nonalcoholic fatty liver with and without curcumin, for four months. After the sacrifice, a vascular function protocol was performed on an isolated superior mesenteric artery (response to acetylcholine, L-NGNitroarginine Methyl Ester and nitroprusside) and measurement of portal pressure by direct puncture. The results were expressed as average and the standard deviation of the central tendency. The differences between the groups were tested using Student's t-test and Mann-Whitney test. RESULTS: The portal pressure measurement showed no significant differences between groups. There was no significant difference in the nitroprusside test, in the other hand, exist a difference with acetylcholine between arteries of nonalcoholic fatty liver group against nonalcoholic fatty liver plus curcumin group. DISCUSSION: Curcumin improved the vasodilator response in response to acetylcholine, suggesting a possible antioxidant effect which improves endothelial function. It is suggested for future therapeutic use.

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