Anticarcinogenic activity of methanol extract of Melastoma malabathricum leaves is attributed to the presence of phenolics compounds and the activation of endogenous antioxidant system / Actividad anticancerígena del extracto metanólico de hojas de Melastoma malabathricum atribuida a la presencia de compuestos fenólicos y a la activación del sistema antioxidante endógeno

Melastoma malabathricum (M. malabathricum) extracts have been reported to exert various pharmacological activities including antioxidants, anti-inflammatory and antiproliferative activities. The objective of the present study was to determine the anticarcinogenic activity of its methanol extract (MEMM) against the azoxymethane (AOM)-induced early colon carcinogenesis in rats. Rats were randomly assigned to five groups (n=6) namely normal control, negative control, and treatment (50, 250 or 500 mg/kg of MEMM) groups. Colon tissues were harvested for histopathological analysis and endogenous antioxidant system determination. MEMM was also subjected to HPLC analysis. Findings showed that MEMM significantly (p<0.05) reversed the AOM-induced carcinogenicity by: i) reducing the formation of aberrant crypt foci (ACF) in colon tissues, and; ii) enhancing the endogenous antioxidant activity (catalase, superoxide dismutase and glutathione peroxidase). Moreover, various phenolics has been identified in MEMM. In conclusion, MEMM exerts the in vivo anticarcinogenic activity via the activation of endogenous antioxidant system and synergistic action of phenolics.

Se ha informado que los extractos de Melastoma malabathricum (M. malabathricum) ejercen diversas actividades farmacológicas, incluidas actividades antioxidantes, antiinflamatorias y antiproliferativas. El objetivo del presente estudio fue determinar la actividad anticancerígena de su extracto de metanol (MEMM) contra la carcinogénesis de colon temprana inducida por azoximetano (AOM) en ratas. Las ratas se asignaron al azar a cinco grupos (n=6), a saber, los grupos de control normal, control negativo y tratamiento (50, 250 o 500 mg/kg de MEMM). Tejidos de colon fueron recolectados para análisis histopatológico y determinación del sistema antioxidante endógeno. MEMM también se sometió a análisis de HPLC. Los hallazgos mostraron que MEMM invirtió significativamente (p<0.05) la carcinogenicidad inducida por AOM al: i) reducir la formación de focos de criptas aberrantes (ACF) en los tejidos del colon, y; ii) potenciar la actividad antioxidante endógena (catalasa, superóxido dismutasa y glutatión peroxidasa). Además, se han identificado varios fenólicos en MEMM. En conclusión, MEMM ejerce la actividad anticancerígena in vivo mediante la activación del sistema antioxidante endógeno y la acción sinérgica de los fenólicos.

Efecto de la cáscara o pulpa de Solanum Tuberosum sobre el peso de órganos y estrés oxidativo hepático en ratas obesas / Effect of Solanum Tuberosum peel or pulp on organ weight and hepatic oxidative stress in obese rats

RESUMEN Con el objetivo de determinar el efecto del consumo de harina de cáscara o harina de pulpa de dos variedades de Solanum tuberosum (papa Yungay y papa Canchán) sobre la acumulación de tejido adiposo, peso de órganos y estrés oxidativo en hígado de ratas realizamos un estudio experimental en 24 ratas Holtzman obesas, divididos en cuatro grupos y, sometidas a dietas que contenían 10% de harina de las dos variedades de papa. Los grupos fueron T1: cáscara Yungay, T2: pulpa Yungay; T3: cáscara Canchán; y T4: pulpa Canchán. Al finalizar, se sacrificaron todos los animales para registrar los pesos de órganos y tejido adiposo, y extraer muestras para determinar la actividad enzimática de superóxido dismutasa y catalasa en el hígado. El grupo de ratas obesas que consumió pulpa de variedad Yungay tuvo menor estrés oxidativo en el hígado; además, independientemente de la parte de tubérculo consumido, esta variedad redujo el peso de los riñones.

ABSTRACT This study aimed to determine the effect of the consumption of peel flour or pulp flour from two varieties of Solanum tuberosum (Yungay potato and Canchán potato) on the accumulation of adipose tissue, organ weight, and oxidative stress in the liver of rats. We carried out an experimental study in 24 obese Holtzman rats, divided into four groups and subjected to diets containing 10% flour from both varieties of potato. The groups were T1: Yungay peel; T2: Yungay pulp; T3: Canchán peel; and T4: Canchán pulp. When the study was completed, all the animals were slaughtered to record the weights of organs and adipose tissue and to extract samples to determine the enzyme activity of superoxide dismutase and catalase in the liver. The group of obese rats that consumed the pulp of the Yungay variety had less oxidative stress in the liver. Also, regardless of the tuber part consumed, this variety reduced the weight of the kidneys.

Agonistic activity of tamoxifen, a selective estrogen-receptor modulator (SERM), on arthritic ovariectomized mice

Arthritis is positively associated with the decline of sex hormones, especially estrogen. Tamoxifen (TMX) is a selective estrogen receptor modulator, possessing agonist or antagonistic activity in different tissues. Thus, the objective of this study was to investigate the effect of TMX on the zymosan-induced arthritis model. Female Swiss normal and ovariectomized (OVX) mice were divided into groups and treated for five days with TMX (0.3, 0.9 or 2.7 mg/kg) or 17-β-estradiol (E2, 50 µg/kg). On the fifth day, arthritis was induced and 4 h later, leukocyte migration into joint cavities was evaluated. The neutrophil migration in OVX animals, but not in normal mice, treated with TMX (all tested doses) was significantly decreased compared with mice that received the vehicle (P≤0.05). Similarly, this effect was also demonstrated in the E2-treated group. Therefore, the present study demonstrates that TMX presented agonist effects in inhibiting neutrophil migration and preventing arthritis progression in OVX mice.

Assessment of ovarian follicles and serum reproductive hormones in molybdenum trioxide nanoparticles treated rats / Evaluación de folículos ováricos y hormonas reproductivas en suero de ratas tratadas con nanopartículas de trióxido de molibdeno

SUMMARY: Special features of nanoparticles have resulted in their widespread use. Small molybdenum trioxide (MoO 3) nanoparticles can translocate from the entry portals into the circulatory and lymphatic systems and ultimately to body tissues and organs depending on their composition and size. In this research, sixty Wistar rats weighting 180-250 g were divided into 6 groups (n=10) randomly: Group 1 (Control) did not receive any medicine. Group 2 (Sham) received intraperitoneal normal saline for 35 days on a daily basis. Groups 3, 4, 5 and 6 received 50, 100, 200, and 300 mg/kg MoO3, respectively, the same way in the sham group and at the same interval. At the end of the experiment, the rats were weighted again and anesthetised. Then blood samples were taken from their hearts to determine the serum levels of estrogen, progesterone, and gonadotropins. Their ovaries were removed and ovarian volume, follicular diameter, number of each follicle type, and oocyte volume were determined. Results indicated that MoO3 nanoparticles strongly reduced body and ovarian weights in the rats. Moreover, a significant decrease was observed in ovarian volume, the number of follicle types, oocyte volume and follicular diameter. The nanoparticles increased the number of atretic follicles via ovarian tissue structure. MoO3 nanoparticles decreased serum estrogen level and increased serum level of FSH that was associated with disruption in the regulation of progesterone and LH secretion. The findings showed that MoO3 nanoparticles could bear negative effects on ovarian structure and function.

RESUMEN: Las características específicas de las nanopartículas han dado lugar a su uso generalizado. Las pequeñas nanopartículas de trióxido de molibdeno (MoO3) pueden penetrar los sistemas circulatorios y linfáticos y, en última instancia, dependiendo de su composición y tamaño, también los tejidos y órganos del cuerpo. En esta investigación se dividieron 60 ratas Wistar con un peso de 180-250 g en 6 grupos (n = 10) aleatoriamente: el Grupo 1 (Control) no recibió ningún medicamento. El Grupo 2 (Sham) recibió solución salina normal intraperitoneal durante 35 días diariamente. Los grupos 3, 4, 5 y 6 recibieron 50, 100, 200 y 300 mg / kg de MoO3 respectivamente, de la misma manera en el grupo simulado, y en el mismo intervalo. Concluyendo el experimento, las ratas se pesaron nuevamente y fueron anestesiadas. Luego se tomaron muestras de sangre de los corazones para determinar los niveles séricos de estrógeno, progesterona y gonadotropinas. Se retiraron los ovarios y se determinó el volumen ovárico, el diámetro folicular, el número de cada tipo de folículo y el volumen de ovocitos. Los resultados indicaron que las nanopartículas de MoO3 redujeron significativamente los pesos corporal y ovárico en las ratas. Además, se observó una disminución importante en el volumen ovárico, el número de tipos de folículos, el volumen de ovocitos y el diámetro folicular. Las nanopartículas aumentaron el número de folículos auriculares a través de la estructura del tejido ovárico. Las nanopartículas de MoO 3 disminuyeron el nivel sérico de estrógeno y aumentaron el nivel sérico de FSH que se asoció con la interrupción en la regulación de la progesterona y la secreción de LH. Los hallazgos mostraron que las nanopartículas de MoO 3 podrían tener efectos negativos sobre la estructura y la función ovárica.

La inhibición de Rho quinasa post infarto mejora el remodelado y la función ventricular: mecanismos involucrados a nivel preclínico / Rho-kinase inhibition post myocardial infarction improves remodeling and systolic function: a preclinical study of intervening factors in a pre-clinical study

Resumen: Objetivo: Determinar algunos mecanismos moleculares por los cuales la activación de ROCK cardíaca post infarto del miocardio (IAM) participa en el remodelado y en deterioro de la función sistólica. Métodos: Determinación simultánea de niveles de proteínas blanco de ROCK cardíaca, de función sistólica in vivo del ventrículo izquierdo (VI) y de fibrosis e hipertrofia cardíaca en ratas con IAM en condiciones de inhibición de ROCK con fasudil. Resultados : Siete días post IAM la masa ventricular relativa aumentó significativamente en un 30% en el grupo MI y se redujo con fasudil. La disfunción sistólica VI mejoró significativamente con fasudil mientras que la activación de ROCK cardíaca se redujo a niveles del grupo control. El inhibidor de ROCK también redujo significativamente los niveles cardíacos elevados de las isoformas ROCK1 y ROCK2, de MHC-β y del colágeno miocárdico. En el grupo con IAM aumentaron significativamente los niveles de fosforilación de ERK 42 y ERK 44 (en 2 veces y en 63%, respectivamente), mientras que en el grupo IAM tratado con fasudil estos niveles fueron similares a los del grupo control. El IAM aumentó significativamente los niveles fosforilados del factor de transcripción GATA-4, que se normalizaron con el inhibidor de ROCK. Conclusiones: La disfunción sistólica post IAM se asoció fuertemente con la activación del ROCK cardíaca y con la fosforilación de proteínas río abajo de ROCK que promueven remodelado cardíaco como β-MHC y la vía ERK / GATA-4.

Abstracts: Objective: to determine some molecular mechanisms by which cardiac ROCK activation after myocardial infarction (MI) intervene in cardiac systolic function decline and remodeling. Methods: simultaneous measurement of different cardiac ROCK target proteins levels, in vivo left ventricular (LV) systolic function, myocardial fibrosis, and hypertrophy in rats with MI under ROCK inhibition with fasudil were performed. Results: seven days after MI the relative ventricular mass increased significantly by 30% in the MI groupand was reduced with fasudil. LV systolic dysfunction improved significantly with fasudil whereas at the same time cardiac ROCK activation was reduced to sham levels. The ROCK inhibitor also reduced increased cardiac levels of both ROCK1 and ROCK2 isoforms, β-MHC levels and myocardial collagen volume fraction decline. MI significantly increased phosphorylation levels of ERK 42 and ERK 44 by 2-fold and 63% respectively whereas in the fasudil-treated MI group these levels were similar to those in the sham group. MI significantly increased phosphorylated levels of the transcription factor GATA-4 which were normalyzed by the ROCK inhibitor. Conclusion: LV systolic dysfunction after MI was strongly associated to cardiac ROCK activation and subsequent phosphorylation of ROCK target proteins that promote ventricular remodeling, such as β-MHC and the ERK/GATA-4 pathway. ROCK inhibition with fasudil significantly improved systolic function, diminished myocardial fibrosis, and normalized β-MHC and ERK/GATA-4 phosphorylation levels.

Protective effect of alcoholic extract of garden cress seeds on the histopathological changes of the ventral prostate in streptozotocin diabetic rats / Efecto protectivo de extracto alcohólico de garden cress seeds en los cambios histopatológicos de la próstata ventral en ratas diabéticas por streptozotocina

Diabetes mellitus is a common serious metabolic illness occurring worldwide that may lead to male infertility. Various plants have been used in the treatment of diabetes. In this study, the effect of garden cress (Lepidium sativum) seed extract on fasting blood sugar is assessed for its protective effect on histopathological changes in the ventral prostate gland of streptozotocine-induced diabetic rats. Fifty adult male Wistar rats were randomly selected into five groups. Group 1 was the control placebo group where rats received only 0.1 mL normal saline via gastric gavages. Rats in Group 2 received an intraperitoneal injection of STZ 60 mg/kg body weight and those with FBS >250 mg/dL were considered diabetic. In Group 3, diabetic rats received insulin (3 U/100 g body weight) while in Groups 4 and 5 diabetic rats received 0.1 ml of 200 and 400 mg/kg respectively of an ethanol extract of Lepidium sativum seeds by gavage daily. The prostate was removed and weighed before transfer to Bouin’s solution for histological studies. Administration of the 200 and 400 mg/kg doses of Lepidium sativum seed extract increased epithelium height and decreased interstitial volume density and fibromuscular thickness of the prostate significantly. Also, the volume density of the epithelium, fibro muscular, lumen, and interstitial tissues were changed significantly. The results suggest that Lepidium sativum seed extract has beneficial effects as a protective agent against the detrimental effects of diabetes on the reproductive system of diabetic male rats.

La diabetes mellitus es una enfermedad metabólica común y grave que ocurre en todo el mundo y que puede conducir a la infertilidad masculina. Se han utilizado varias plantas en el tratamiento de la diabetes. En este estudio se evalúa el efecto del extracto de semilla de Lepidium sativum sobre los niveles de azúcar en sangre, en ayunas, por su efecto protector sobre los cambios histopatológicos en la próstata ventral, de ratas diabéticas inducidas por estreptozotocina (STZ). Cincuenta ratas Wistar adultas fueron divididas aleatoriamente en cinco grupos. El grupo 1 fue el grupo placebo, de control, en el que las ratas recibieron sólo 0,1 ml de solución salina normal mediante sondas gástricas. Las ratas del grupo 2 recibieron una inyección intraperitoneal de 60 mg / kg de peso corporal de STZ y aquellas con FBS> 250 mg / dl se consideraron diabéticas. En el grupo 3, las ratas diabéticas recibieron insulina (3 U / 100 g de peso corporal) mientras que en los grupos 4 y 5 las ratas diabéticas recibieron 0,1 ml de 200 y 400 mg / kg respectivamente de un extracto etanólico de semillas de Lepidium sativum por gavage diariamente. La próstata se retiró y se pesó antes de transferir a una solución de Bouin para realizar estudios histológicos. La administración de las dosis de 200 y 400 mg / kg de extracto de semilla de Lepidium sativum aumentó la altura del epitelio y disminuyó la densidad volumétrica intersticial y el espesor fibromuscular de la próstata, significativamente. Además, la densidad volumétrica del epitelio fibromuscular, del lumen y el intersticio de los tejidos sufrieron modificaciones significativas. Los resultados sugieren que el extracto de semilla de Lepidium sativum posee efectos beneficiosos como agente protector contra los efectos perjudiciales de la diabetes en el sistema reproductivo de las ratas macho diabéticas.

Organophosphorous pesticides: their effects on biosentinel species and humans: control and application in Chile / Pesticidas organofosforados: sus efectos en especies biosentinelas y humanos: control y aplicación en Chile

The environment is negatively affected by the increasing accumulation of both natural and man-made waste and by-products. Organophosphorous pesticides -malathion, diazinon and methamidophos- are used worldwide in pest control. The aim of this report is to review the effects of organophosphates on the male reproductive tract of mice, rats and earthworms, and to evaluate their projection into the human population. Assessing failures in the male reproductive system is an excellent in vivo biomarker to determine the level of toxicity of suspected pollutants. In rodents organophosphates cause decreased testicular weight and sperm density, abnormal tubular plugging and increased teratozoospermia. In earthworms they cause a significant decrease in body weight and alter the spermatheca, with an initial significant increase in immature sperm followed by a significant decrease in sperm count with high frequency of metachromasia. Given the environmental impact of these pesticides -and their potential effects on human health-, international and regional organizations are warning about the correct handling and managing of these substances during work-related and domestic exposures and about their relation to water sources and food, placing a greater emphasis on the school children population due to its higher vulnerability, reduced detoxification capacity, and their endocrine and physiological effects.

El medio ambiente se ve afectado negativamente por la creciente acumulación de desechos y subproductos naturales y artificiales. Los plaguicidas organofosforados malatión, diazinón y metamidofos, son usados en todo el mundo en el control de plagas. El objetivo de este trabajo fue revisar los efectos de los organofosforados en el tracto reproductivo masculino de ratones, ratas y lombrices de tierra, y evaluar su proyección en la población humana. La evaluación de fallas en el sistema reproductor masculino es un excelente biomarcador in vivo para determinar el nivel de toxicidad de los contaminantes químicos. En roedores, los organofosforados causan disminución del peso testicular y de la densidad espermática, obstrucción tubular anormal y aumento de la teratozoospermia. En lombrices de tierra causan una disminución significativa en el peso corporal y alteran la espermateca, con un aumento inicial significativo en espermatozoides inmaduros, seguido de una disminución significativa en el recuento de espermatozoides con alta frecuencia de metacromasia. Dado el impacto medioambiental de estos plaguicidas y sus efectos potenciales en la salud humana, las organizaciones internacionales y regionales advierten sobre el manejo y uso correctos de estas sustancias durante exposiciones laborales y domésticas y sobre su relación con la contaminación de las fuentes de agua y alimentos, colocando énfasis en la población de niños en edad escolar, debido a su mayor vulnerabilidad, reducción de la capacidad de desintoxicación y sus efectos a nivel endocrino y fisiológico.

Protective effect of Lepidium sativum seed extract on histopathology and morphology of epididymis in diabetic rat model / Efecto protector de extracto de semilla Lepidium sativum sobre la histopatología y morfología del epidídimo en modelo de rata diabética

Diabetes mellitus is a frequent and serious metabolic illness all over the world and plants have been a desirable source of medicine recently. Diabetes has unpleasant effect on male reproductive system and it may lead to male infertility. It causes erectile dysfunction and reduces ejaculate volume by affecting the health of small blood vessels and the small nerves that control ejaculation and also decreases libido by decreasing testosterone levels. Current study evaluated the possible protective efficiency of Lepidium sativum (Garden cress) seed extract on fasting blood sugar (FBS) and then assessed histopathological change of epididymis in streptozotocine (STZ)-induced diabetic rats. We randomly categorized 50 adult male Wistar rats into five groups (each 10 rats). Group 1 was control placebo group receiving only 0.1 ml normal saline via gastric gavages, Group 2 as control diabetic rats received an intraperitoneal (IP) injection of STZ 60 mg/kg body weight. Rats with FBS >250 mg/dl were considered as diabetic. Group 3 were diabetic rats receiving insulin in dose 3U/100 g body weight and Groups 4 and 5 were diabetic rats that received 0.1 cc of 200 and 400 mg/kg, ethanol extract of Lepidium sativum seed by gavages daily. One day after the last gavages, rats were anesthetized by chloroform. Epididymis duct was removed from abdomen and weighed with a digital scale. Afterwards, samples were putted in Bouin's solution for histological measurement. Administration of 200 and 400 mg/ml doses of Lepidium sativum seed extract increased epithelium height and decreased interstitial volume density and fibro muscular thickness significantly. Also, volume density of epithelium, fibro muscular, lumen and interstitial decreased significantly. Tubular and lumen diameter did not change significantly in different groups. It appears Lepidium sativum seed extract is a beneficial protective supplementary agent against adverse effects of diabetes on male reproductive system.

La diabetes mellitus es una enfermedad metabólica frecuente y grave que afecta a los hombres en todo el mundo. Recientemente, las plantas han sido una fuente deseable de medicina para este tipo de enfermedad. La diabetes tiene un efecto perjudicial en el sistema reproductivo masculino y puede conducir a la infertilidad. Causa disfunción eréctil y reduce el volumen de la eyaculación al afectar los pequeños vasos sanguíneos y los nervios que controlan la eyaculación. También disminuye la libido reduciendo los niveles de testosterona. El presente estudio evaluó la posible eficacia protectora del extracto de semilla de Lepidium sativum en la glucemia en ayunas y también se evaluó el cambio histopatológico del epidídimo en ratas diabéticas inducidas por estreptozotocina (STZ). Se dividieron aleatoriamente 50 ratas Wistar macho adultas en cinco grupos de 10 ratas cada uno. El grupo 1 recibió 0,1 ml de solución salina normal a través de los gavajes gástricos, el grupo 2 de ratas diabéticas control recibió una inyección intraperitoneal (IP) de STZ 60 mg / kg de peso corporal. Las ratas con FBS> 250 mg / dl se consideraron como diabéticas. El Grupo 3 eran ratas diabéticas que recibieron insulina en dosis de 3 U/ 100 g de peso corporal y los Grupos 4 y 5 estaban compuestos por ratas diabéticas que recibieron 0,1 cc con 200 y 400 mg / kg, de extracto de etanol de semillas de Lepidium sativum por gavajes diarios. Un día después de los últimos gavages, las ratas fueron anestesiadas con cloroformo. Se extrajo el epidídimo y se pesó con una pesa digital. Posteriormente, las muestras se pusieron en solución de Bouin para el estudio histológico. La administración de dosis de 200 y 400 mg / ml de extracto de semilla Lepidium sativum aumentó la altura del epitelio y disminuyó significativamente la densidad volumétrica intersticial y el grosor fibromuscular. Además, la densidad volumétrica del epitelio fibromuscular, lumen e intersticio disminuyeron significativamente. El diámetro tubular y el lumen no cambiaron significativamente en los diferentes grupos. El extracto de semilla de Lepidium sativum es un agente complementario beneficioso protector contra los efectos adversos de la diabetes en el sistema reproductor masculino.

Propolis protective role against morphological, hormonal biochemical and histological alterations induced by sildenafil overdoses / Rol protector del propóleo contra las alteraciones morfológicas, hormonales, bioquímicas e histológicas inducidas por sobredosis de sildenafil

Sildenafil is widely used for the treatment of erectile dysfunction with few studies are available on the protective role of propolis against its reproductive toxicity. The present study aims to investigate the hormonal biochemical and histomorphometric alterations induced in the testicular tissues by sildenafil overdoses. Four groups of rabbits were exposed to sildenafil with or without propolis as follows: Group I received the formulated vehicle, Group II received sildenafil (3 mg/kg), Group III received propolis (50 mg/kg), Group IV received sildenafil plus propolis. Sildenafil lowered body weight gain, testosterone and follicular stimulating hormone concentration but increased testis index while luteinizing hormone was almost not affected. Moreover, sildenafil treated rabbits showed degenerative seminiferous tubules and disturbance of spermatogenesis together with spermatocytes sloughing and nuclear alterations. Exposure to sildenafil plus propolis ameliorated tubular alterations, spermatogenesis disturbances, hormonal levels changes and partially protected spermatocytes from morphological nuclear alterations but could not ameliorate the effect on the body weight gain and testis index. The findings of the present work may indicate that propolis can ameliorate partially the reproductive toxicity induced by sildenafil overdoses with more need for further studies on the adverse effect of these doses on the other vital organs.

El sildenafil es un medicamento ampliamente utilizado para el tratamiento de la disfunción eréctil y existen pocos estudios disponibles referente a la función protectora del propóleo contra su toxicidad reproductiva. El objetivo fue investigar las alteraciones hormonales, bioquímicas e histomorfométricas, inducidas en los tejidos testiculares por sobredosis de sildenafil. Cuatro grupos de conejos fueron expuestos a sildenafil con o sin propóleo de la siguiente manera: grupo I recibió el sildenafil formulado, grupo II recibió sildenafil (3 mg/kg), grupo III recibió propóleo (50 mg/kg) y el grupo IV recibió sildenafil más propóleo. El sildenafil redujo el peso corporal, la testosterona y la concentración de la hormona foliculoestimulante, sin embargo, se observó un aumento del índice testicular mientras que la hormona luteinizante casi no se vio afectada. Por otra parte, los conejos tratados con sildenafil mostraron degeneración de los túbulos seminíferos, trastornos de la espermatogénesis y alteraciones nucleares de los espermatocitos. Con el uso de sildenafil más propóleo fue posible disminuir las alteraciones de los túbulos seminíferos, los trastornos de la espermatogénesis y los niveles de cambios hormonales; los espermatocitos fueron protegidos parcialmente de alteraciones nucleares morfológicas, pero no pudo mejorar el efecto de aumento de peso corporal e índice testicular. Los resultados indican que el propóleo puede aliviar, en parte, la toxicidad en la reproducción inducida por sobredosis de sildenafil. No obstante, existe la necesidad de realizar más estudios sobre los efectos adversos de estas dosis en otros órganos vitales.

Postnatal exposure to a progestin does not prevent uterine adenogenesis in domestic dogs

To assess the effects of a single supraphysiological postnatal administration of a progestogen on uterine glands in dogs, 10 females were randomly assigned to a medroxyprogesterone acetate 35 mg (MPA; n = 6) or placebo (n = 4) group within the first 24 h of birth. The safety of the treatment was also evaluated. A transient mild clitoris enlargement appeared in MPA-treated females. Microscopic postpubertal uterine assessment revealed the presence of uterine glands in all cases without significant differences in the area occupied by the glands per µm2 of endometrium nor in the height of the uterine epithelium.

Should human chorionic gonadotropine treatment increase thyroid volume?

Objective Our aim was to investigate the thyroid function tests and thyroid volume differences among males with isolated hypogonadotropic hypogonadism (IHH) who take androgen replacement treatment (ART). Materials and methods Forty-four male with IHH with a mean age 33.2 (18-54), diagnosed in Endocrinology and Metabolism Department between September 2013 and September 2014 and 40 healthy male control with a mean age 27.77 (18-55) were involved to study. Patient group was divided to testosterone-treated patients (n = 19) and human chorionic gonadotropine (hCG)-treated patients (n = 25). Patient group was compared in terms of total testosterone, thyroid function tests [thyroid stimulating hormone (TSH), free thyroxine (fT4)] and thyroid volume, before and 6 months after treatment. Patient group was compared with control group as well. Results When we compared the patient group with the control group, there was no significant difference for age, Body mass index, TSH, fT4 and thyroid volume between two groups before treatment. There was no difference in terms of TSH, but fT4, testosterone levels and thyroid volume were significantly higher after treatment, when the patient group was compared before and after treatment (p < 0.05). When we compared testosterone-treated patients and hCG-treated patients; thyroid volume was higher among hCG-treated patients (p = 0.001) but there was no difference for thyroid volume before and after testosterone treatment (p > 0.05). There was no statistically significant correlation between testosterone levels with TSH, fT4 and thyroid volume (r = 0.09, p = 0.32; r = 0.14, p = 0.11; r = 0.15, p = 0.09, respectively). Conclusion Our study showed that ART increases the thyroid volume especially in hCG-treated patients. Therefore, we suggest that thyroid volume changes should be followed up in hCG-treated patients.

Reported shoes size during GH therapy: is foot overgrowth a myth or reality?

Objectives To describe population reference values for shoes size, and to identify possible disproportional foot growth during GH therapy.Materials and methods Construction of percentile chart based on 3,651 controls (male: 1,838; female: 1,813). The GH treated group included 13 children with idiopathic short stature (ISS) and 50 children with normal height, but with height prediction below their target height; male: 26 and female: 37 mean ± SD age 13.3 ± 1.9 and 12.9 ± 1.5 years, respectively. GH (0.05 mg/kg/day) was used for 3.2 ± 1.6 years, ranging from 1.0-10.3 years. Height expressed as SDS, target height (TH) SDS, self-reported shoes size and target shoes size (TSS) SDS were recorded.Results Reference values were established showed as a foot SDS calculator available online at www.clinicalcaselearning.com/v2. Definitive shoes size was attained in controls at mean age of 13y in girls and 14y in boys (average values 37 and 40, respectively). In the study group, shoes size was -0.15 ± 0.9 and -0.02 ± 1.3 SDS, with target feet of 0.08 ± 0.8 and -0.27 ± 0.7 SDS in males and females, respectively. There was a significant positive correlation between shoes size and familial TSS, between shoes size and height and between TSS and TH. There was no correlation between duration of GH treatment and shoes size. Our data suggest that during long-term treatment with GH, patients maintain proportional growth in shoes size and height, and the expected correlation with the familial target.Conclusions We conclude that there is no excessive increase in the size of foot as estimated by the size of shoes in individuals under long term GH therapy.

Deleterious effects of prepubertal corticosterone treatment on rat prostate

PURPOSE: To investigate the structural and functional changes induced by corticosterone (CORT) in the ventral prostrate (VP) of rats in order to study chronic stress effects in the prepubertal phase. METHODS: Wistar rats received daily saline or CORT injections during the pubertal period from the 5th to 25th day of postnatal life. The animals were distributed into four groups: 1 - Control (n=5); 2 - Control 99mTc-P (n=5); 3 - Treated with CORT (n=14); 4 - Treated with CORT and 99mTc-P (n=10). All rats were sacrificed at two months of age. Technical tissue uptakes of 99mTc-P were used to evaluate the functional and stereological methods for morphological analysis. RESULTS: Acini distribution in the group treated with CORT differed significantly (p<0.0001) from the control. The control group's epithelial average height (10.01±0.24 microns) was statistically significant (p<0.0001) from rats treated with CORT (19.27±0.73microns). The collagen distribution was lower in the treated group (2.79%) when compared to control (3.97%). The radioactivity percentage in the groups marked with 99mTc-P (%Ati/g) did not demonstrate a statistically significant difference (p=0.285897). CONCLUSION: Chronic administration of corticosterone in prepubertal rats causes changes in their acinar structure and their ventral prostate stroma, indicating possible deleterious effects of this hormone. .

Morphometric alterations induced by the toxicity of variable sizes of silver nanoparticles / Alteraciones morfométricas inducidas por la toxicidad de diferentes tamaños de nanopartículas de plata

Silver nanoprticles (SNPs) are invested in medical, industrial and environmental applications. Little if any, is known about the morphometric alterations induced by the toxicity of SNPs. The aim of the present work is to find out the effect of variable size of SNPs on different morphometric parameters. Adult healthy male mice (BAL/C) were subjected to (10 nm, 20 nm, 40 nm 60 nm and 100 nm) SNPs for 35 days. Silver NPs caused non-significant decline on the average weight, significant decline in food consumption, increase in water intake, unilateral blindness, tanning fur color and cholestasis together with a decrease in the relative ratio of the liver, kidney and spleen weight to body weight. Mice subjected to 10 nm and 20 nm were more affected than mice receiving larger nanoparticles. These findings may indicate that SNPs could induce morphometric alterations that are size related wheresmaller SNPs have more impact than the larger ones.

Poco se sabe acerca de las alteraciones morfométricas inducidas por la toxicidad de las nanopartículas de plata (NPP). El objetivo fue investigar el efecto del tamaño variable de las NPP en diferentes parámetros morfométricos. Ratones machos adultos sanos (BAL/C) fueron sometidos a diferentes NPP de diferentes tamaños durante 35 días (10 nm, 20 nm, 40 nm 60 nm y 100 nm, respectivamente). Las NPP causaron una disminución no significativa del peso promedio, una disminución significativa en el consumo de alimentos, un aumento de la ingesta de agua, ceguera unilateral, cambios en el color de piel y colestasis junto con una disminución en el tamaño promedio del hígado, riñón y el peso del bazo, en relación al peso corporal. Los ratones sometidos a 10 nm y 20 nm fueron más afectados que los ratones que recibieron las nanopartículas más grandes. Estos resultados pueden indicar que las NPP podrían inducir alteraciones morfométricas que están relacionadas con el tamaño, en las cuales las NPP más pequeñas tienen un mayor impacto que las más grandes.

Prenatal and developmental toxicity study of meclizine and caffeine combination in female albino wistar rats.

Meclizine and caffeine combination is used for the treatment of morning sickness. Both compounds are teratogenic and caffeine is known to possess anti-fertility activity also. The present study was undertaken to evaluate the reproductive toxic effect of meclizine and caffeine combination. Three doses were taken for the study; low dose (LD; meclizine 3.7 mg/kg and caffeine 3 mg/kg) was selected from commercially available formulation, middle dose (MD; meclizine 37 mg/kg and caffeine 30 mg/kg) and high dose (HD; meclizine 370 mg/kg and caffeine 300 mg/kg). The mixture was administered 1-7 days and 8-14 days for fertility and embryotoxic studies respectively. Laparotomy was done on 10th day of gestation period. Number of implants and corpora lutea were counted, pre and post-implantation losses were determined. In embryo toxicity study fetuses were evaluated for external, skeletal and visceral examination. High dose was removed from both fertility and embryotoxicity studies due to its severe toxicity to the dam. Significant anti-fertility activity was observed at middle dose. Embryotoxicity study showed significant reduction in fetal body weight, body length and body mass index, dam body weight gain on gestation day 14. Absolute kidney weight in MD and absolute and relative spleen weight in both LD and MD were significantly reduced. There was no increase in external or internal congenital anomalies at both LD and MD. The, results suggest that prescription of meclizine and caffeine for morning sickness in early pregnancy should be reviewed carefully.

Difference between actual vs. pathology prostate weight in TURP and radical robotic-assisted prostatectomy specimen

Introduction To investigate and highlight the effect of formaldehyde induced weight reduction in transurethral resection of prostate (TURP) and radical robotically-assisted prostatectomy (RALP) specimen as a result of standard chemical fixation. Materials and Methods 51 patients were recruited from January 2013 to June 2013 who either underwent a TURP (n=26) or RALP (n=25). Data was collected prospectively by the operating surgeon who measured the native, unfixed histology specimen directly after operation. The specimens were fixed in 10% Formaldehyde Solution BP and sent to the pathology laboratory where after sufficient fixation period was re-weighed. Results Overall mean age 64.78 years, TURP mean age 68.31 years RALP mean age 61.12years. We found that the overall prostatic specimen (n=51) weight loss after fixation was a mean of 11.20% (3.78 grams) (p≤0.0001). Subgroup analysis of the native TURP chips mean weight was 16.15 grams and formalin treated mean weight was 14.00 grams (p≤0.0001). Therefore, TURP chips had a mean of 13.32 % (2.15 grams) weight loss during chemical fixation. RALP subgroup unfixed specimen mean weight was 52.08 grams and formalin treated mean weight was 42.60 grams (p≤0.0001), a 19.32 % (9.48grams) mean weight reduction. Conclusion It has not been known that prostatic chips and whole human radical prostatectomy specimen undergo a significant weight reduction. The practical significance of the accurate prostate weight in patient management may be limited, however, it is agreed that this should be recorded correctly, as data is potential interest for research purposes and vital for precise documentation. .

Disruption of glucose tolerance caused by glucocorticoid excess in rats is partially prevented, but not attenuated, by arjunolic acid.

Arjunolic acid (AA) obtained from plants of the Combretaceae family has shown anti-diabetic effects. Here, we analyzed whether the diabetogenic effects of dexamethasone (DEX) treatment on glucose homeostasis may be prevented or attenuated by the concomitant administration of AA. Adult Wistar rats were assigned to the following groups: vehicle-treated (Ctl), DEX-treated (1 mg/kg body weight intraperitoneally for 5 days) (Dex), AA-treated (30 mg/kg body weight by oral gavage twice per day) (Aa), AA treatment previous to and concomitant to DEX treatment (AaDex), and AA treatment after initiation of DEX treatment (DexAa). AA administration significantly ameliorated (AaDex) (P>0.05), but did not attenuate (DexAa), the glucose intolerance induced by DEX treatment. AA did not prevent or attenuate the elevation in hepatic glycogen and triacylglycerol content caused by DEX treatment. All DEX-treated rats exhibited hepatic steatosis that seemed to be more pronounced when associated with AA treatment given for a prolonged period (AaDex). Markers of liver function and oxidative stress were not significantly altered among the groups. Therefore, AA administered for a prolonged period partially prevents the glucose intolerance induced by DEX treatment, but it fails to produce this beneficial effect when given after initiation of GC treatment. Since AA may promote further hepatic steatosis when co-administered with GCs, care is required when considering this phytochemical as a hypoglycemiant and/or insulin-sensitizing agent.

Protective effect of Dillenia indica L. on acetic acid induced colitis in mice.

The inflammatory bowel disease (IBD) is an idiopathic, immune mediated and chronic inflammation of the intestine. The study aimed to elucidate the ameliorative effect of methanolic extract of Dillenia indica (DIME), hexane fraction (HFDI) and chloroform fraction (CFDI) of Dillenia indica in acetic acid induced experimental colitis in mice. Macroscopic score, colon weight, colonic catalase (CAT), superoxide dismutase (SOD), glutathione (GSH), myeloperoxidase (MPO), malondialdehyde (MDA), tumor necrosis factor (TNF-α), and histological changes were recorded after the treatment regimen of 7 days. Intra-rectal instillation of acetic acid caused enhanced macroscopic score, colon weight, colonic MPO, MDA, and TNF-α level. It caused significant decreased level of CAT, SOD and GSH. DIME (800 mg/kg), HFDI (200 mg/kg) and CFDI (200 mg/kg) treatment exhibited significant effect in lowering macroscopic score, colon weight, MPO, MDA, TNF-α levels and elevation of CAT, GSH and SOD levels. The results suggest that D. indica has ameliorating effects on experimental colitis by inhibiting the proinflammatory mediators like TNF-α production.

Histomorphometric evaluation of soleus and lateral gastrocnemius muscles of animals submitted to pharmacological manipulation with fluoxetine / Evaluación histomorfométrica de los músculos sóleo y gastrocnemio lateral de animales sometidos a manipulación farmacológica con fluoxetina

The pharmacological manipulation with selective inhibitor of serotonin reuptake (SSRIs) can modify the operation of the serotonergic system and may facilitate or inhibit the action of this system, inducing changes in the morphology of the skeletal muscle of rats. The objective of this study was to evaluate the action of the treatment with fluoxetine during the critical period of the animal´s life on development of the soleus and lateral gastrocnemius muscles, under the aspects of weight, the number of nuclei of myocyte cells and cross-sectional area of muscle fibers. Twenty four (30 and 90-day-old) male Wistar rats were used. They were treated with saline solution (NaCl 0.9%; 1 ml/100 g of body weight) or fluoxetine (10 mg; 1 ml/100g of body weight). The animals were divided in Saline Group (GS-30 and GS-90) and Fluoxetine Group (GF-30 and GF-90). The fluoxetine group showed a reduction on weight (g) of soleus (p=0.046) and lateral gastrocnemius (p=0.02) muscles in rats with 90 days. A lesser number of myonuclei was observed in fluoxetine group than saline group of 30 days (soleus, p<0.001; lateral gastrocnemius, p0.007) and 90 days (soleus, p=0.002; lateral gastrocnemius, p0.038). The cross section area of fluoxetine groups is also smaller than the saline groups with 30 days (soleus, p=0.03; lateral gastrocnemius, p=0.041) and 90 days (soleus, p=0.042; lateral gastrocnemius, p=0.012). The treatment of fluoxetine during the critical period of development of the nervous system of rats, causes early changes in the structure of muscle fibers that seem to be related to reducing the weight of the soleus and gastrocnemius muscles only in late stage of the animal's life. Thus, the dosage used ISRS, suggests an inhibitory effect of 5-HT in relation to variables on the development of the skeletal muscle tissue of rats.

La manipulación farmacológica con inhibidores selectivos de la recaptación de la serotonina (ISRS) pueden cambiar el funcionamento del sistema serotoninérgico y facilitar o inhibir la acción de este sistema, induciendo cambios en la morfología del músculo esquelético de ratones. El objetivo fue analizar los efectos de la manipulación farmacológica neonatal con fluoxetina en el desarrollo de la masa muscular, número de núcleos y área de la sección transversa de las fibras de los músculos sóleo y gastrocnemio lateral. Se utilizaron 24 ratones Wistar machos, de 30 y 90 días de edad, tratados con solución salina (NaCl 0,9%, 1m/100 g de peso corporal) y fluoxetina (1 mg; 1 ml/100 g de peso corporal). Los animales fueron divididos en grupos con solución salina (GS-30 y GS-90) y fluoxetina (GF-30 y GF-90). El grupo tratado con fluoxetina mostró una reducción de peso (g) de los músculos sóleo (p=0,0046) y gastrocnemio lateral (p=0,02) en 90 días. Además, se observó en este mismo grupo una reducción de núcleos en 30 días (M. sóleo, p<0,001; M. gastrocnemio lateral, p0,007) así como en el período de 90 días (M. sóleo, p=0,002; M. gastrocnemio lateral, p0,038). También se observó reducción del área de la sección transversal en los animales tratados con fluoxetina durante el período de 30 días (M. sóleo, p=0,03; M. gastrocnemio lateral, p= 0,041;) y 90 días (M. sóleo, p=0,042; M. gastrocnemio lateral, p=0,012). El tratamiento con fluoxetina durante el período crítico del desarrollo del sistema nervioso de ratones, induce cambios prematuros en la estructura de la fibra muscular, los que parecen estar relacionados con la reducción de peso de los músculos sóleo y gastrocnemio en una fase tardía de vida del animal. En consecuencia, la dosis utilizada de ISRS, sugiere un efecto inhibidor de la 5-HT, en relación a las variables estudiadas sobre el desarrollo del tejido muscular esquelético de ratones.

Protective effect of curcumin against nicotine-induced damage on reproductive parameters in male mice / Efecto protector de la curcumina contra el daño inducido por la nicotina sobre los parámetros reproductivos en ratones machos

Nicotine consumption can decrease fertility drive in males through inducing oxidative stress and DNA damage. The color of turmeric is because of a substance called curcumin for which some anti-oxidative and anti-inflammatory properties have been identified. In this study, various doses of curcumin (10, 30 and 60 mg/kg) and curcumin plus nicotine (10, 30 and 60 mg/kg) were administered intraperitoneally to male mice for 28 consequent days and reproductive parameters were determined. The results indicated that nicotine administration (0.5 mg/kg) significantly decreased testosterone level, count and motility of sperms, and testis weight compared to control group. However, increasing the dose of curcumin significantly increased reproductive indices in most of the groups. Thus, it seems that curcumin inhibits nicotine-induced adverse effects on reproductive parameters.

El consumo de nicotina puede disminuir la fertilidad en los hombres mediante la inducción de estrés oxidativo y daño del ADN. El color de la cúrcuma se debe a una sustancia llamada curcumina en la cual se han identificado algunas propiedades anti-oxidantes y anti-inflamatorias. En este estudio se administraron diferentes dosis de curcumina (10, 30 y 60 mg/kg) y de curcumina más nicotina (10, 30 y 60 mg/kg) por vía intraperitoneal a ratones machos durante 28 días consecutivos y se determinaron los parámetros reproductivos. La administración de nicotina (0,5 mg/kg) disminuyó significativamente el nivel de testosterona, el número y motilidad de los espermatozoides, y peso de los testículos en comparación con el grupo control. Sin embargo, el incremento de la dosis de curcumina aumentó significativamente los índices reproductivos en la mayoría de los grupos. Este estudio sugiere que la curcumina inhibe los efectos adversos inducidos por la nicotina sobre los parámetros reproductivos.