Anastrozole promotes implantation by altering the expression of paxillin and fak in rat luminal uterine epithelium / El anastrozol promueve la implantación alterando la expresión de paxilina y fak en el epitelio uterino luminal de rata

An alternative hyper-ovulator inducer to replace clomiphene citrate (CC) is needed as it is unsuitable for women with polycystic ovarian syndrome and is associated with low pregnancy rates. Anastrozole is an effective hyper-ovulator inducer, but has not been well researched. In order to determine the effectiveness of anastrozole as a hyper-ovulator inducer and to an extent compare it with CC in similar situations, this study ascertained the effects of these drugs on the expression of the focal adhesion proteins, paxillin and FAK, which are uterine receptivity markers in the surface luminal uterine epithelial cells of day 1 and day 6 pregnant Wistar rats. The results show that paxillin is localized in focal adhesions at the base of the uterine epithelial cells at day 1 of pregnancy whereas at day 6, paxillin disassembles from the basal focal adhesions and localizes and increases its expression apically. FAK is faintly expressed at the basal aspect of the uterine epithelial cells while moderately expressed at the cell-to-cell contact at day 1 in all groups from where it disassembles and relocates apically and becomes more intensely expressed at day 6 of pregnancy in untreated and anastrozole treated rats. Although paxillin is localized apically at day 6, its expression is significantly down-regulated with CC treatment suggesting its interference with the implantation process. These findings seem to suggest that anastrozole could favor implantation.

Para reemplazar el citrato de clomifeno (CC) es necesario un inductor de hiperovulación alternativo, ya que no es adecuado para mujeres con síndrome de ovario poliquístico y está asociado con tasas bajas de embarazo. El anastrozol es un inductor eficaz del hiper-ovulador, pero no se ha investigado adecuadamente. Con el fin de determinar la efectividad del anastrozol como inductor del hiper-ovulador y, en cierta medida, compararlo con CC en situaciones similares, este estudio determinó los efectos de estos fármacos en la expresión de las proteínas de adhesión focal, paxillin y FAK, uterinas marcadores de receptividad en la superficie luminal de células uterinas epiteliales, del día 1 y día 6 en ratas Wistar preñadas. Los resultados muestran que la paxilina se localiza en adherencias focales en la base de las células epiteliales uterinas en el día 1 del embarazo, mientras que en el día 6, la paxilina se desmonta de las adherencias focales basales y localiza y aumenta su expresión apicalmente. FAK se expresa débilmente en el aspecto basal de las células epiteliales uterinas, mientras que se expresa moderadamente en el contacto de célula a célula en el día 1 en todos los grupos, donde se separa y se reubica apicalmente y se expresa con mayor intensidad el día 6 de la preñez, en pacientes no tratados y tratados. ratas tratadas con anastrozol. Aunque la paxillina se localiza apicalmente en el día 6, su expresión está significativamente disminuida con el tratamiento con CC, lo que sugiere su interferencia con el proceso de implantación. Estos hallazgos sugieren que el anastrozol podría favorecer el proceso de implantación.

Pharmacological treatment for symptomatic adenomyosis: a systematic review / Tratamento farmacológico para adenomiose sintomática: revisão sistemática

Abstract Objective To assess the efficacy of non-surgical treatment for adenomyosis. Data Sources A search was performed by two authors in the Pubmed, Scopus, and Scielo databases and in the grey literature from inception to March 2018, with no language restriction. Selection of Studies We have included prospective randomized studies for treating symptomaticwomen with adenomyosis (abnormal uterine bleeding and/or pelvic pain) diagnosed by ultrasound or magnetic resonance imaging. Data Collection Studies were primarily selected by title and abstract. The articles that were eligible for inclusion were evaluated in their entirety, and their data was extracted for further processing and analysis. Data Synthesis From567retrieved records only 5 remained for analysis. The intervention groups were: levonorgestrel intrauterine system (LNG-IUS)(n= 2), dienogest (n= 2), and letrozole (n= 1). Levonorgestrel intrauterine system was effective to control bleeding when compared to hysterectomy or combined oral contraceptives (COCs). One study assessed chronic pelvic pain and reported that LNG-IUS was superior to COC to reduce symptoms. Regarding dienogest, it was efficient to reduce pelvic pain when compared to placebo or goserelin, but less effective to control bleeding than gonadotropin-releasing hormone (GnRH) analog. Letrozolewas as efficient asGnRHanalog to relieve dysmenorrhea and dyspareunia, but not for chronic pelvic pain. Reduction of uterine volumewas seen with aromatase inhibitors, GnRH analog, and LGN-IUD. Conclusion Levonorgestrel intrauterine system and dienogest have significantly improved the control of bleeding and pelvic pain, respectively, in women with adenomyosis. However, there is insufficient data from the retrieved studies to endorse eachmedication for this disease. Further randomized control tests (RCTs) are needed to address pharmacological treatment of adenomyosis.

Resumo Objetivo: Avaliar a eficácia de tratamento não cirúrgico para adenomiose. Fontes de dados: Uma pesquisa foi realizada por dois autores nas bases de dados Pubmed, Scopus, Scielo e na literatura cinzenta desde o início de cada base de dados até março de 2018, sem restrição de idioma. Seleção de estudos: Incluímos estudos prospectivos randomizados para tratamento de mulheres sintomáticas com adenomiose (sangramento uterino anormal e/ou dor pélvica) diagnosticadas por ultrassonografia ou ressonância magnética. Coleta de dados: Os estudos foram selecionados principalmente por título e resumo. Os artigos que preencheram os critérios de inclusão foram avaliados na íntegra, e seus dados foram extraídos para posterior processamento e análise. Síntese dos dados: De 567 registros recuperados, somente 5 permaneceram para análise. Os grupos de intervenção foram: sistema intrauterino de levonorgestrel (SIU-LNG) (n= 2), dienogest (n= 2), e letrozol (n= 1). O SIU-LNG foi efetivo no controle do sangramento quando comparado à histerectomia ou aos contraceptivos orais combinados (COCs).Umestudo avaliou a dor pélvica crônica e relatou que o SIU-LNGfoi superior ao COC para reduzir os sintomas.Emrelação ao dienogest, este foi eficienteemreduzir a dor pélvica quando comparado ao placebo ou à goserelina, mas foi menos eficaz no controle do sangramento do que o análogo do hormônio liberador de gonadotropina (GnRH). O letrozol foi tão eficiente quanto o análogo do GnRH para aliviar a dismenorreia e a dispareunia, mas não para a dor pélvica crônica. Redução do volume uterino foi observada com inibidores de aromatase, análogo de GnRH, e SIU-LNG. Conclusão: O SIU-LNG e dienogest apresentaram bons resultados para o controle de sangramento e dor pélvica, respectivamente, em mulheres com adenomiose. No entanto, não há dados suficientes para endossar cada medicação para tratar essa doença. Futuros estudos randomizados são necessários para avaliar o tratamento farmacológico da adenomiose.

Traditional knowledge and uses of medicinal plants by the inhabitants of the islands of the São Francisco river, Brazil and preliminary analysis of Rhaphiodon echinus (Lamiaceae) / Conhecimento tradicional e usos de plantas medicinais por habitantes das ilhas do rio São Francisco, Brasil e análise preliminar de Rhaphiodon echinus (Lamiaceae)

Abstract This study aimed to carry out an ethnobotanical survey of medicinal plants used by inhabitants of the Rodeadouro Island, Jatoba Island and Massangano Island, located in The Submedium São Francisco River Valley. Also phytochemicals and preliminary pharmacological tests were performed to species most cited by the community. Ethnobotanical data were collected through observation visits and semi-structured interviews with 12 key informants. We calculated the relative importance (RI), the percentage of agreement related to the main uses (cAMU) and use value (UV). The aerial parts of Rhaphiodon echinus (Ness & Mart.) Schauer were used to obtain the lyophilizate (LYO-Re), crude ethanol extract (CEE-Re) and their hexanic (HEX-Re), chloroform (CLO-Re) and ethyl acetate (EA-Re) fractions. The microdilution technique was used for determining Minimum inhibitory concentration (MIC) for selected microorganisms. Already the spasmolytic effect was evaluated in isolated uterus fragments of Wistar rats, pre contracted with KCl 60 mM. We found 34 species cited, belonging to 22 families. The most plants were grown by locals. There were 51 different diseases, but the main indication was infectious and parasitic diseases. The species R. echinus was the most reported and it was indicated for urinary tract infection and dysmenorrhea. The screening revealed a higher prevalence of flavonoids, tannins, lignans and saponins in LYO-Re and AE-Re. Already terpene compounds were more present in HEX-Re and CLO-Re. The RE-Re fraction stood out with strong effect against E. coli and S. aureus while CEE-Re has moderate effect against gram-negative bacteria. The evaluation of the spasmolytic activity showed that LYO-Re, CEE-Re and HEX-Re fractions have similar activity, with partial effect and concentration-dependent response. This work brought about knowledge and use of medicinal plants by the riparian of the São Francisco River. It also revealed the importance of other methodologies for scientific evidence for the popular use of R. echinus.

Resumo Objetivou-se realizar um levantamento etnobotânico de plantas medicinais utilizadas nas ilhas do Massangano, Jatobá II e Rodeadouro, localizadas entre Petrolina-PE e Juazeiro-BA, no submédio do rio São Francisco e posterior investigação fitoquímica e farmacológica da espécie mais citada, conforme a indicação da comunidade. Realizaram-se visitas de observação nas ilhas e os dados etnobotânicos foram coletados por entrevistas semiestruturadas com 12 informantes-chave. Calculou-se a Importância Relativa (IR), a Porcentagem Corrigida de Concordância quanto ao Uso Principal (CUPc) e o Valor de Uso (VU). Utilizaram-se as partes aéreas da espécie mais citada para obtenção do extrato etanólico bruto (EEB-Re), suas frações hexânica (HEX-Re), clorofórmica (CLO-Re) e acetato de etila (AE-Re); o produto liofilizado (LIO-Re) e o óleo essencial (OE-Re). A técnica de microdiluição foi usada para determinar a Concentração Inibitória Mínima (CIM) para microorganismos selecionados. A atividade espasmolítica foi avaliada em fragmentos isolados de útero de ratas Wistar pré-contraídos com KCl 60 mM. Foram relatadas 34 espécies, contidas em 22 famílias diferentes. A maioria das plantas era cultivada pelos moradores. Registraram-se 51 enfermidades diferentes, mas a principal indicação foi doenças parasitárias e infecciosas. A espécie Rhaphiodon echinus (Ness & Mart.) Schauer foi a mais citada, com principal indicação para tratar infecção do trato urinário e dismenorreia. O screening fitoquímico revelou prevalência de flavonoides, taninos, lignanas e saponinas em LIO-Re e AE-Re e compostos terpênicos em HEX-Re e CLO-Re. Os testes antibacterianos mostraram que AE-Re é mais atuante contra E. coli e S. aureus do que para P. aeruginosa. O EEB-Re tem efeito parcial contra bactérias gram-negativas e OE-Re possui moderada resposta para todos microorganismos testados. LIO-Re, EEB-Re e HEX-Re possuem atividade espasmolítica dependente da concentração, sem diferença significativa e sem relaxamento total. Este trabalho trouxe conhecimento sobre o uso de plantas medicinais pelos ribeirinhos do rio São Francisco e revela a importância de estudos mais aprofundados para a comprovação científica do uso popular da R. echinus.

Immunoexpression of vascular endothelial growth factor and B-cell lymphoma 2 in the uterine tissue of rats treated with melatonin in the estrus phase

Abstract Purpose: To investigate the effect of melatonin on uterine tissue in the ovariectomized rat model. Methods: Fourty Wistar albino rats were divided into four groups for histologic and immunohistochemical examination. The rats were first numbered randomly and then randomly divided into 4 equal groups: control (group 1), torsion (group 2), torsion+detorsion (group 3) and torsion+detorsion+melatonin (group 4) groups. In addition, four Wistar albino rats were used for western blot analysis in each group. And also, malondialdehyde (MDA) levels were measured biochemically in all rats. Results: The histopathological examination of the uterine tissue in rats ovarectomized showed a degeneration in uterine glands, dilation of blood vessels in the internal layer with a thrombosis and bleeding, abnormal nucleuses and vacuolated cytoplasm above and below the nucleus. In torsion group, the apoptotic cells increased in luminal epithelium and gland cells. In the melatonin group showed that the Bcl2 negative effect on the uterine epithelium and did not lead to apoptotic cells. Conclusion: The increase in vascular endothelial growth factor expression resulted in the rearrangement of endothelial cell growth and the induction of angiogenesis.

The therapeutic effects of curcumin and capsaicin against cyclophosphamide side effects on the uterus in rats

Abstract Purpose: To evaluate the impact of systemic cyclophosphamide treatment on the rat uterus and investigate the potential therapeutic effects of natural antioxidant preparations curcumin and capsaicin against cyclophosphamide side effects. Methods: A 40 healthy adult female Wistar albino rats were used in this study. Rats were randomly divided into four groups to determine the effects of curcumin and capsaicin against Cyclophosphamide side effects on the uterus (n=10 in each group); Group 1 was the control group (sham-operated), Group 2 was the cyclophosphamide group, Group 3 was the cyclophosphamide + curcumin (100mg/kg) group, and Group 4 was the cyclophosphamide + capsaicin (0.5 mg/kg) group. Results: Increased tissue oxidative stress and histological damage in the rat uterus were demonstrated due to the treatment of systemic cyclophosphamide chemotherapy alone. The level of tissue oxidant and antioxidant markers and histopathological changes were improved by the treatment of curcumin and capsaicin. Conclusion: Cytotoxic effects of natural alkylating chemotherapeutic agents like cyclophosphamide on the uterus can be prevented by curcumin and capsaicin.

Effects on the female reproductive system of air pollution produced by the use of wood combustion for residential heating: challenges and perspectives of morphological studies / Efectos sobre el sistema reproductivo femenino de la contaminación del aire producido por el uso de la combustión de madera para calefacción residencial: retos y perspectivas de los estudios morfológicos

Previous studies have shown that air pollution affects cardio-respiratory function, but its role regarding reproductive processes is unknown. There are few experimental background studies on its effects on the morpho-function in the reproductive system. The use of wood combustion for residential heating (WCRH) in the cities of south-central Chile has increased significantly. As a result, it has become a source of significant emissions of particulate matter suspended (PM) in the air. The possible association between exposure to PM and reproductive problems has been suggested only on the basis of epidemiological studies, most of them carried out in environments where the main source of PM emission is the combustion of oil by motorized vehicles and industries, ignoring the effects produced by the smoke of WCRH. For example, in the city of Temuco-Padre Las Casas, Chile, 93 % of PM emissions correspond to WCRH smoke, thus being considered an urban area with a single PM emission source and the factors that contribute to this type of contamination are reasonably representative of most of the cities in south-central Chile. We therefore suggest this as an adequate setting to evaluate the real effect of the environmental contamination produced by the smoke of WCRH in the reproductive system. The limited number of studies reported on the effects of this type of emission on the female reproductive system, present a challenge for the morphological sciences and also for those who make decisions that affect public health.

Estudios previos han demostrado que la polución del aire afecta la función cardio-respiratoria, pero el rol que tiene ésta respecto a los procesos reproductivos es desconocida. Existen escasos antecedentes experimentales sobre sus efectos sobre la morfo-función en el sistema reproductivo. El uso de la combustión de madera para calefacción residencial (WCRH) en las ciudades del centro-sur de Chile ha aumentado significativamente. Como resultado, se ha convertido en una fuente de emisión importante de material particulado en suspensión (PM) en el aire ambiental. La posible asociación entre exposición a PM y problemas reproductivos ha sido sugerida solo en base a estudios epidemiológicos, la mayoría de ellos realizados en ambientes donde la principal fuente de emisión de PM es la combustión del petróleo por vehículos motorizados e industrias, ignorando los efectos producidos por el humo de WCRH. Por ejemplo, en la ciudad de Temuco-Padre Las Casas, Chile, el 93 % de las emisiones de PM corresponden al humo de WCRH, por lo tanto, es considerada como un área urbana con una fuente de emisión de PM única y los factores que contribuyen a este tipo de contaminación son razonablemente representativos a la mayoría de las ciudades en el centro-sur de Chile, lo que permite sugerirla como un ambiente adecuado para evaluar el efecto de la contaminación ambiental producida por el humo de la WCRH en el sistema reproductivo. Los escasos estudios reportados sobre los efectos de este tipo de emisión sobre el sistema reproductivo femenino constituyen un desafío no tan solo para las ciencias morfológicas, sino que además, para quienes toman decisiones que afectan la salud pública.

Focal adhesion proteins, vinculin and integrin ß5, during early pregnancy in rat uterine epithelial cells: anastrozole favors their normal distribution / Proteínas de adhesión focales, vinculina e integrina ß5, durante el embarazo temprano en células epiteliales uterinas de rata: anastrozol favorece su distribución normal

SUMMARY: An alternative superovulator to replace clomiphene citrate is needed as clomiphene citrate is associated with low pregnancy rates. Anastrozole is an effective superovulator, but it has not been well researched. In order to determine the effectiveness of anastrozole as a superovulator and to compare it with clomiphene citrate in similar situations, this study ascertained the effects of these drugs on the expression of the focal adhesion proteins, vinculin and integrin β5, which are uterine receptivity markers, in the uterine epithelial cells of day 1 and day 6 pregnant Wistar rats. The results show that vinculin and integrin β5 are co-localized at the base of the uterine epithelium at day 1 of pregnancy whereas at day 6, they disassemble from the basal focal adhesions and co-localize and significantly increase their expression apically (p≤0.0001). Moreover, there is a significant difference in the protein expression levels of vinculin and integrin b5 in uterine luminal epithelial cells between untreated (control) and chlomiphene citrate treated rats (p≤0.0001), anastrozole and chlomiphene citrate treated rats at day 6 (p≤0.0001) suggesting the interpretation that anastrozole seems to enhance their expression in order to perhaps assist in the implantation process of the blastocyst. The immunofluorescence experiments agree with the vinculin and integrin β5 gene expression findings in which at day 6 of pregnancy, vinculin and integrin β5 gene expression are significantly upregulated in uterine luminal epithelial cells in the anastrozole treated group relative to the calibrator sample (p≤0.0001). These findings suggest that anastrozole is implantation friendly.

RESUMEN: Es necesario un superovulador alternativo para reemplazar el citrato de clomifeno, debido a que está asociado con bajas tasas de preñez. El anastrozol es un superovulador eficaz, sin embargo es poca su investigación. Con el fin de determinar la efectividad del anastrozol como superovulador y compararlo con citrato de clomifeno en situaciones similares, se determinaron los efectos de estos fármacos sobre la expresión de las proteínas de adhesión focal, vinculina e integrina β5, en marcadores de receptividad uterina en días 1 y 6, en las células epiteliales uterinas de ratas Wistar preñadas. Los resultados muestran que la vinculina y la integrina β5 se co-localizan en la base del epitelio uterino al día 1 de la gravidez mientras que al día 6 se desmontan de las adherencias focales basales, co-localizan y aumentan significativamente su expresión apicalmente (p≤0.0001). Además, existe una diferencia significativa en los niveles de expresión de proteína de vinculina e integrina β5 en células epiteliales luminales uterinas entre ratas no tratadas (control) y tratadas con citrato declomifeno (p≤0.0001), ratas tratadas con anastrozol y citrato declomifeno al día 6 (p≤0,0001) sugiriendo la interpretación de que el anastrozol parece mejorar su expresión con el fin de ayudar en el proceso de implantación del blastocisto. Los experimentos de inmunofluorescencia coinciden con los resultados de la expresión de los genes vinculina e integrina β5 en los cuales al día 6 de la preñez, la vinculina y la integrina β5 están significativamente reguladas en células epiteliales luminales uterinas en el grupo tratado con anastrozol con respecto a la muestra del calibrador (p<0,0001). Estos hallazgos sugieren que el anastrozol es favorable para la implantación.

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.

Quantitative analysis of collagen fibrillar structure in canine uterus exposed to acetate of medroxyprogesterone using second harmonic generation microscopy / Análisis cuantitativo de la estructura de fibras colágenas en útero canino expuesto a acetato de medroxiprogesterona utilizando generación microscópica de un segundo harmónico

Collagen is the most abundant structural protein found in organs and is responsible for providing tissues with structure and function. In order to investigate in canine uteri the potential effect of medroxyprogesterone acetate (MPA) on the changes in collagen deposition were grouped as nulliparous (n=11), multiparous (n=11) and treated with MPA (n=11; nulliparous with two treatments; 5 mg/kg; i.m.). The amount of collagen was studied in the fold and basal regions of the endometrium and myometrium using second harmonic generation with a two-photon spectral confocal microscope, quantified using ImageJ software with a color segmentation plugin, was expressed as fraction area (%) and analyzed by ANOVA (p<0,05). No differences were observed between groups in the fold (p=0,3995) or base (p=0,7392) of the endometrium and myometrium (p=0,1781). In conclusion, our data demonstrate that two doses of MPA (5 mg/kg; i.m.) do not affect the total collagen deposition in canine uteri undergoing contraceptive treatment.

El colágeno es la proteína estructural más abundante presente en órganos y es responsable de proporcionar la sostén y función a los tejidos. Para investigar en caninos el efecto potencial del acetato de medroxiprogesterona (MPA) sobre cambios en el depósito de colágeno en útero, éstos fueron agrupados como nulíparos (n = 11), multíparos (n = 11) y tratados con MPA (n = 11, nulíparos con dos tratamientos 5 mg/kg, im). El colágeno fue evaluado en el pliegue y regiones basales del endometrio y en miometrio utilizando la Generación de un Segundo Harmónico con un microscopio confocal espectral y dos fotones y cuantificado utilizando el software ImageJ a partir de la segmentación de colores. Los resultados fueron expresados y analizados como fracción de área (%; ANOVA; p<0,05). No se observaron diferencias entre los grupos en el pliegue (p = 0,3995) y base (p=0,7392) del endometrio y tampoco en miometrio (p=0,1781). En conclusión, nuestra evidencia demuestra que dos dosis de MPA (5 mg/kg, i.m.) no afectan el depósito total de colágeno en úteros caninos expuestos a tratamiento anticonceptivo.

Uterine transplantation: a systematic review

Up to 15% of the reproductive population is infertile, and 3 to 5% of these cases are caused by uterine dysfunction. This abnormality generally leads women to consider surrogacy or adoption. Uterine transplantation, although still experimental, may be an option in these cases. This systematic review will outline the recommendations, surgical aspects, immunosuppressive drugs and reproductive aspects related to experimental uterine transplantation in women.

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.

The effect of visfatin on inflammatory reaction in uterus of LPS-induced rats / Efecto de visfatina en la reacción inflamatoria en el útero de ratas inducidas por LPS

The present study was to investigate the effects of visfatin on the morphological structure and function of the rat uterus during inflammation. The expression and distribution of visfatin, morphological structure, eosinophils (EOS), myeloperoxidase (MPO) and cytokines in the uterus of the LPS-induced rat were studied using hematoxylin-eosin staining (HE), immunohistochemical methods, western blots and enzyme-linked immunosorbent assay (ELISA). The present study showed that visfatin positive cells dispersed widely in the uterus, and strong positive staining was observed mainly in the cell cytoplasm. Compared with saline group, in visfatin group, more uterine glands were found, EOS increased, and the difference was significant (P<0.05), MPO reduced, and the difference was significant (P<0.01). In addition, visfatin was able to increase the secretion of IL-1b, IL-6, and TNF-a (P<0.01). Compared with LPS group, in vifatin+LPS group, the uterine glands of the lamina propria increased, the myometrium became thinner, the number of EOS and MPO reduced obviously, but the difference was not significant (P>0.05), and after LPS stimulated body, visfatin decrease the level of IL-1b, IL-6, TNF-a (P<0.01). The above results suggest that visfatin could affect the morphological structure of rat uterus; Visfatin could modulate the inflammatory response in rats' uterus by regulating the quantity of inflammatory cells, such as EOS and MPO, and the level of inflammatory cytokines, such as IL-1b, IL-6, TNF-a.

El objetivo del presente estudio fue investigar los efectos de la visfatina sobre la estructura morfológica y la función del útero de la rata durante la inflamación. Se estudiaron la expresión y distribución de la visfatina, la estructura morfológica, eosinófilos, mieloperoxidasa y citoquinas en el útero de rata mediante la tinción de H&E, métodos inmunohistoquímicos, Western blots y ELISA. El estudio mostró que las células visfatina positivas se dispersan ampliamente en el útero, junto a una fuerte tinción positiva, principalmente en el citoplasma de la célula. En comparación con el grupo control, en el grupo visfatina, se encontraron más glándulas uterinas, se observó un aumento de EOS y la diferencia fue significativa (p<0,05), MPO reducida siendo esta diferencia también significativa (p<0,01). Además, la visfatina fue capaz de aumentar la secreción de IL-1b, IL-6 y TNF-a (P<0,01). En comparación con el grupo LPS, visfatina+grupo LPS, las glándulas uterinas de la lámina propia aumentaron, se observó un miometrio más delgado, y número reducido de EOS y MPO, sin embargo, la diferencia no fue significativa (P>0,05). Después de estímulo LPS en el cuerpo, se registró un nivel menor de visfatina en IL-1b, IL-6, TNF-a (P<0,01). Los resultados anteriores sugieren que visfatina podría afectar a la estructura morfológica del útero de rata. Además, podría modular la respuesta inflamatoria en el útero mediante la regulación de la cantidad de células inflamatorias, tales como EOS y MPO.

Genistein-induced fluid accumulation in ovariectomised rats' uteri is associated with increased cystic fibrosis transmembrane regulator expression

OBJECTIVE: High genistein doses have been reported to induce fluid accumulation in the uteri of ovariectomised rats, although the mechanism underlying this effect remains unknown. Because genistein binds to the oestrogen receptor and the cystic fibrosis transmembrane regulator mediates uterine fluid secretion, we hypothesised that this genistein effect involves both the oestrogen receptor and cystic fibrosis transmembrane regulator. METHODS: Ovariectomised adult female Sprague-Dawley rats were treated with 25, 50, or 100 mg/kg/day genistein for three consecutive days with and without the ER antagonist ICI 182780. One day after the final drug injection, the animals were humanely sacrificed, and the uteri were removed for histology and cystic fibrosis transmembrane regulator mRNA and protein expression analysis using real-time polymerase chain reaction and Western blotting, respectively. The cystic fibrosis transmembrane regulator protein distribution was analysed visually by immunohistochemistry. RESULTS: The histological analysis revealed an increase in the circumference of the uterine lumen with increasing doses of genistein, which was suggestive of fluid accumulation. Moreover, genistein stimulated a dose-dependent increase in the expression of cystic fibrosis transmembrane regulator protein and mRNA, and high-intensity cystic fibrosis transmembrane regulator immunostaining was observed at the apical membrane of the luminal epithelium following 50 and 100 mg/kg/day genistein treatment. The genistein-induced increase in uterine luminal circumference and cystic fibrosis transmembrane regulator expression was antagonised by treatment with ICI 182780. CONCLUSION: Genistein-induced luminal fluid accumulation in ovariectomised rats' uteri involves the oestrogen receptor and up-regulation of cystic fibrosis transmembrane regulator expression, and these findings reveal the mechanism underlying the effect of this compound on changes in ...

Effects of cabergoline administration on uterine perfusion in women with polycystic ovary syndrome

The aim of this study was to determine the effects of Cabergoline administration on uterine blood flow in women suffering from polycystic ovary syndrome [PCOS]. This study is a randomized, controlled, triple-blind trial which is tested on 40 women who were randomly divided into two groups of 20 people and using a randomized block design during which the subjects were assessed and included. They were suffering from polycystic ovarian syndrome. Inclusion criteria were classically defined PCOS criteria including: oligomenorrhea or amenorrhea, clinical or Laboratory findings based on increase in blood level androgen [testosterone] and ultrasound confirmation of PCOS. Exclusion criteria were Pregnancy, lactation, Dopamine Agonist Therapy. After selection of intervention and placebo groups, primary control Doppler ultrasound was done for both groups. Then a weekly dose of Cabergoline 0.5 mg was administered to intervention group for duration of 12 weeks. Placebo group were administered placebo in the same fashion. At the end of 12 weeks, Doppler ultrasound was performed and the results were recorded in the check lists. No significant difference was noticed in both groups with respect to their age, employment, level of education, type of infertility, duration of marriage, and results of RI and PI before intervention. Later PCOS patients under the treatment of Cabergoline showed a significant increase in uterine blood flow Pulsatility Index [PI] before 2.65 +/- 0.52 and after 1.98 +/- 0.52 and RI before 0.85 and after intervention 0.77], yet no significant difference were found in PCOS patient under the treatment of placebo. PCOS patients were shown to have more resistance in uterine blood flow than healthy people; however, Cabergoline administration proved to increase uterine blood perfusion and regulate menstruation cycle

Effects of the phytoestrogen genistein on the development of the reproductive system of Sprague Dawley rats

OBJECTIVES: Genistein is known to influence reproductive system development through its binding affinity for estrogen receptors. The present study aimed to further explore the effect of Genistein on the development of the reproductive system of experimental rats. METHODS: Eighteen post-weaning female Sprague Dawley rats were divided into the following groups: (i) a control group that received vehicle (distilled water and Tween 80); (ii) a group treated with 10 mg/kg body weight (BW) of Genistein (Gen 10); and (iii) a group treated with a higher dose of Genistein (Gen 100). The rats were treated daily for three weeks from postnatal day 22 (P22) to P42. After the animals were sacrificed, blood samples were collected, and the uteri and ovaries were harvested and subjected to light microscopy and immunohistochemical study. RESULTS: A reduction of the mean weekly BW gain and organ weights (uteri and ovaries) were observed in the Gen 10 group compared to the control group; these findings were reversed in the Gen 100 group. Follicle stimulating hormone and estrogen levels were increased in the Gen 10 group and reduced in the Gen 100 group. Luteinizing hormone was reduced in both groups of Genistein-treated animals, and there was a significant difference between the Gen 10 and control groups (p<0.05). These findings were consistent with increased atretic follicular count, a decreased number of corpus luteum and down-regulation of estrogen receptors-a in the uterine tissues of the Genistein-treated animals compared to the control animals. CONCLUSION: Post-weaning exposure to Genistein could affect the development of the reproductive system of ovarian-intact experimental rats because of its action on the hypothalamic-pituitary-gonadal axis by regulating hormones and estrogen receptors.

Efeitos de misoprostol sublingual pré-operatório no tônus uterino durante anestesia com isoflurano para cesariana / Effects of preoperative sublingual misoprostol on uterine tone during isoflurane anesthesia for cesarean section / Efectos del misoprostol sublingual preoperatorio en el tono uterino durante la anestesia con isoflurano para cesárea

JUSTIFICATIVA E OBJETIVOS: Misoprostol reduz o sangramento uterino após o parto cesáreo sem efeitos prejudiciais para a mãe ou o bebê. Nosso objetivo foi avaliar os efeitos de misoprostol pré-operatório no sangramento materno e no tônus uterino e a necessidade de ocitocina após cesariana sob anestesia com isoflurano. MÉTODOS: Depois da aprovação pelo Comitê de Ética, 366 pacientes programadas para cesariana eletiva foram randomicamente designadas para receber 400 µg de misoprostol sublingual (n = 179) ou um comprimido de placebo (n = 187) após intubação. A anestesia foi mantida com CAM de isoflurano a 0,5-0,7 e óxido nitroso. Todas as pacientes receberam infusão de ocitocina (10 UI) após expulsão da placenta. A estimativa de perda sanguínea, do tônus uterino, da necessidade de ocitocina complementar, da contagem de hematócrito, dos escores de Apgar no 1º e aos 5 minutos e os efeitos adversos foram registrados. RESULTADOS: Após a indução, as pacientes que receberam misoprostol sublingual tiveram perda sanguínea perioperatória (202 ± 383,1 vs 708 ± 204,3 mL, p < 0,001), necessidade de ocitocina (p < 0,001), níveis mais elevados de hematócrito (p < 0,001) e tônus uterino (p < 0,02) menos significativos. A incidência de tremores foi maior no grupo misoprostol (p = 0,04). Não houve diferenças entre os dois grupos quanto aos índices de Apgar, náusea e vômito, distúrbios gastrointestinais e febre. CONCLUSÃO: A administração pré-operatória de misoprostol sublingual (400 µg) é segura e eficaz para atenuar o sangramento materno e o efeito no tônus uterino da anestesia com isoflurano em parto cesário.

BACKGROUND AND OBJECTIVES: Misoprostol would reduce the uterine bleeding after cesarean delivery without harmful effects on either mother or baby. We aimed to evaluate the effects of preoperative misoprostol on maternal blood loss, uterine tone, and the need for additional oxytocin after cesarean delivery under isoflurane anesthesia. METHODS: After ethical approval, 366 patients scheduled for elective cesarean delivery were randomly allocated to receive either sublingual misoprostol 400 µg (n = 179) or placebo tablet (n = 187) after intubation. Anesthesia was maintained with 0.5-0.7 MAC isoflurane with nitrous oxide. All patients received intravenous infusion of 10 IU of oxytocin after placental delivery. Perioperative estimated blood loss, uterine tone, need for supplementary oxytocin, hematocrit, Apgar scores at 1 and 5 min and adverse effects were recorded. RESULTS: After induction, patients receiving sublingual misoprostol had significant less perioperative estimated blood loss (202 ± 383.1 vs. 708 ± 204.3 mL, p < 0.001), need for oxytocin (p < 0.001), higher hematocrit levels (p < 0.001) and uterine tone (p < 0.02). The incidence of shivering was higher in the misoprostol group (p = 0.04). There were no differences between the two groups as regarding Apgar scores, nausea and vomiting, gastrointestinal disturbances and pyrexia. CONCLUSION: Preoperative administration of sublingual misoprostol 400 µg is safe and effective in attenuating the maternal bleeding and uterine atony from isoflurane anesthesia for cesarean delivery.

JUSTIFICATIVA Y OBJETIVOS: El Misoprostol reduce el sangramiento uterino después del parto por cesárea sin efectos perjudiciales para la madre o el bebé. Nuestro objetivo fue evaluar los efectos del misoprostol preoperatorio en el sangramiento materno y en el tono uterino, y la necesidad de ocitocina después de la cesárea bajo anestesia con isoflurano. MÉTODOS: Después de la aprobación por el Comité de Ética, 366 pacientes programadas para la cesárea electiva, fueron randómicamente designadas para recibir 400 µg de misoprostol sublingual (n = 179) o un comprimido de placebo (n = 187) después de la intubación. La anestesia se mantuvo con CAM de isoflurano a 0,5-0,7 y óxido nitroso. Todas las pacientes recibieron una infusión de ocitocina (10 UI) después de la expulsión de la placenta. La estimación de la pérdida sanguínea, del tono uterino, de la necesidad de ocitocina complementaria, del conteo de hematocrito, de los puntajes de Apgar en el 1º y a los 5 minutos y los efectos adversos fueron todos registrados. RESULTADOS: Después de la inducción, las pacientes que recibieron misoprostol sublingual tuvieron una pérdida sanguínea perioperatoria (202 ± 383,1 vs 708 ± 204,3 mL, p < 0,001), necesidad de ocitocina (p < 0,001), niveles más elevados de hematocrito (p < 0,001) y tonouterino (p < 0,02) menos significativos. La incidencia de temblores fue mayor en el grupo misoprostol (p = 0,04). No se registraron diferencias entre los dos grupos en cuanto a los índices de Apgar, náusea y vómito, trastornos gastrointestinales y fiebre. CONCLUSIONES: La administración preoperatoria de misoprostol sublingual (400 µg) es segura y eficaz para atenuar el sangramiento materno y el efecto en el tono uterino de la anestesia con isoflurano en el parto por cesárea.

Antispasmodic effects of aqueous and hydroalcoholic Punica granatum flower extracts on the uterus of non-pregnant rats

Punica granatum Linn. [PG] is native to the Mediterranean region. Its flower exhibited antioxidant activity. The present study attempt to investigate the effect of these extract on uterine contraction and its possible mechanism[s]. Thirty five female Wistar rats [200-300 g] at estrous phases of cycle was examined in this study; pieces of virgin adult rat uterus [1.5 cm] were suspended in an organ bath containing 10 ml of De Jalon solution at 29 degreeC. Tissue contractility was isometrically recorded. KCl [60 mM], BaCl[2] [4 mM] and oxytocin [10 mU/ml] were applied to the tissue in the presence and absence of aqueous and hydroalcoholic extracts of the plant [0.05, 0.1, 0.2, 0.4 and 0.8 mg/ml]. Propranolol [1 microM] and naloxane [1 microM] were added in KCl induced contractions. The results were analyzed by ANOVA and p<0.05 were considered as significant. Cumulative concentration of extracts reduced uterine contractions induced by KCl dose-dependently [p<0.01]. Extracts in a dose dependent [p<0.05] reduced uterine contractions decreased dose-dependently after of addition oxytocin. The extracts added cumulatively to the organ bath reduced contractions but they did not affect uterine contractions induced by BaCl2 except the last dose. Spasmolytic effects of the extracts were not affected by propranolol or naloxane in KCl induced contractions. Extracts diminished K[+]-induced contraction in uterus, therefore it seems that substances that decrease K[+]-induced contraction can also block voltage dependent calcium channel. The extracts did not have any effect on beta-adrenoceptors or potassium channels

Contraceptive effect of Uncaria tomentosa (cat's claw) in rats with experimental endometriosis / Efeito anticoncepcional da Uncaria tomentosa (unha-de-gato) em ratas com endometriose experimental

PURPOSE: Evaluate the histological changes in parenchyma´s epithelial layer of the uterus and ovarian of rats with induced endometriosis, treated with Uncaria tomentosa extract. METHODS: 29 rats with experimental endometriosis, were selected and divided in three groups: The uncaria group received 32mg/ml of Uncaria tomentosa extract, 1ml administered daily and the placebo group received 1ml of saline 0.9 percent per day, during for 14 days (both groups); the leuprolide group received leuprolide acetate 1mg/kg body weight applied single subcutaneous dose. In the 15th day of treatment the uterine horn and ovaries were removed for histopathological analysis. RESULTS: The uncaria group presented nine samples (90 percent) with immature ovarian follicles, whereas the placebo group did not present any case and in the leuprolide group there were eight rats (88 percent) with the same change. The placebo group showed mature corpus luteum in all animals, occurring less frequent in uncaria (10 percent) and leuprolide (22 percent) groups. The uterine epithelium showed weak proliferative in nine (90 percent) samples of the uncaria group, in two (20 percent) animals in the placebo group and seven (77.8 percent) rats in the leuprolide group. CONCLUSIONS: The findings suggest that Uncaria tomentosa has contraceptive effect.

OBJETIVO: Avaliação histológica do útero e parênquima ovariano de ratas com endometriose induzida tratadas com extrato de Uncaria tomentosa. MÉTODOS: Foram selecionadas 29 ratas com endometriose experimental e formados três grupos: O grupo uncaria recebeu extrato de Uncaria tomentosa com 32mg/ml, administrado 1ml ao dia e o grupo placebo recebeu 1ml de solução salina a 0,9 por cento, ambos por 14 dias; o grupo leuprolida recebeu acetato de leuprolida 1mg/kg de peso corporal aplicado via subcutânea dose única. No 15° dia de tratamento realizou-se retirada de corno uterino e ovários para análise histopatológica. RESULTADOS: O grupo uncaria apresentou nove amostras (90 por cento) com maturação incompleta dos folículos ovarianos, já o grupo placebo não apresentou nenhum caso e no grupo leuprolida houve oito ratas (88 por cento) com a mesma alteração. O grupo placebo apresentou corpo lúteo maduro em todos os animais, acontecendo de forma menos freqüente nos grupos uncaria (10 por cento) e leuprolida (22 por cento). O epitélio uterino se mostrou fracamente proliferativo em nove (90 por cento) das amostras do grupo unacaria, em dois (20 por cento) casos do grupo placebo e sete (77.8 por cento) casos no grupo leuprolida. CONCLUSÃO: Os achados sugerem que a Uncaria tomentosa tem efeito anticoncepcional.

Changes in the volume and histology of endometriosis foci in rats treated with copaiba oil (Copaiferalangsdorffii) / Mudanças no volume e histologia do foco de endometriose em ratas tratadas com óleo de Copaíba (Copaiferalangsdorffii)

PURPOSE: The aim of this study was to analyze the changes that occur in rats with experimental endometriosis after treatment with copaiba oil. METHODS: Experimental endometriosis was induced in rats. The experimental group received copaiba oil (Copaiferalangsdorffii) orally (0.63 mg/day), and the control group received a 0.9 percent sodium chloride solution orally (1 ml/100 g of body weight/day). Both groups were treated with gavage for 14 days. After this period, the animals were euthanized, and the implant volume was calculated. The autologous transplants were removed, dyed with hematoxylin-eosin, and analyzed by light microscopy. RESULTS: The average final volumes were significantly different between the groups (p=0.007). There was a significant increase (p=0.012) between the initial and final volumes in the control group, whereas treatment with Copaiferalangsdorffii caused a marked reduction in endometrial growth over time (p=0.016). Histologically, 6/11 (55.00 percent) rats in the experimental group had a well-preserved epithelial layer, and 3 (45.00 percent) had mildly preserved epithelium. The control group had seven cases (58.30 percent) of well-preserved epithelial cells and five cases (41.70 percent) of mildly preserved epithelial cells (p>0.05). CONCLUSION: Copaiba oil (Copaiferalangsdorffii) appears to be a promising alternative treatment for endometriosis.

OBJETIVO: O objetivo deste estudo foi analisar as mudanças que ocorreram em ratas com endometrioses experimental tratadas com óleo de copaíba. MÉTODOS: Foi induzida a endometriose experimental nas ratas. O grupo experimental recebeu óleo de copaíba (Copaiferalangsdorffii) oralmente (0,63mg/dia) e o grupo controle recebeu oralmente solução salina 0,9 por cento (1mL/100g/dia). Ambos grupos foram tratados por gavagem por 14 dias. Depois desse período, foi realizada a eutanásia dos animais e calculado o volume do implante. Os transplantes autólogos foram removidos, corados com Hematoxilina-eosina e realizada a microscopia óptica. RESULTADOS: A média final dos volumes foi significativamente diferente entre os grupos (p=0,007). Houve um aumente significante (p=0,12) entre o volume inicial e final do grupo controle, enquanto no grupo tratado com Copaiferalangsdorffii causou uma redução acentuada no crescimento endometrial ao longo durante o período (p=0,016). Histologicamente,6 das 11 (55 por cento) ratas do grupo experimental tinha uma camada epitelial bem preservada e 3 (45 por cento) apresentaram epitélio levemente preservado. O grupo controle apresentou sete casos (58,3 por cento) de células epiteliais bem preservadas e cinco casos (41,7 por cento) de células epiteliais levemente preservadas (p>0,05). CONCLUSÃO: O óleo de copaíba (Copaiferalangsdorffii) parece ser um tratamento alternativo promissor para endometriose.

Contraceptive, estrogenic and anti-estrogenic potentials of methanolic root extract of carpolobia lutea a in rodents

Several plants are used in herbal medicine for family planning. Carpolobia lutea is a medicinal plant in South Eastern Nigeria used for family planning. The study, was designed to investigate the contraceptive, estrogenic and antiestrogenic potentials of the methanolic root extract of Carpolobia lutea in both rats and mice. The contraceptive effect of extract [7 - 21mg/kg] administered by intraperitoneal route for four days in divided doses was tested in mice and rats. Sexually-active males were introduced on day 5 at the ratio of 3F:1M and kept with these females till the end of the experiment. Investigations on the estrogenic and antiestrogenic property of the extract [7-21mg/kg] were done in immature rats that had undergone surgical removal of both ovaries. The effects of the extract [vaginal opening, vaginal cornification, uterine wet weight] were compared with 17-beta-estradiol [0.l micro g/rat/day] as standard drug. Twenty-four hours later, the animals were sacrificed following the last dose and the weights of uterus, kidney, liver and small intestine were recorded. The extract prevented conception in both mice and rats for two gestational periods. Significant changes [p<0.05-0.001] were observed in the length and weight of pups relative to control. There were no abnormalities observed in the pups over thirty days. In ovariectomized immature young rats, the extract showed estrogenic effect [vaginal opening, vaginal cornification and increased uterine wet weight] in low doses while in high doses, it showed antiestrogenic effect. These findings agree with the traditional use of Carpolobia lutea in the control of fertility. The contraceptive property of the extract may be associated with the direct effects of its chemical constituents