The influence of phytoestrogens or estrogens on the proliferation of the rat endocervical mucosa

SUMMARY INTRODUCTION Although estrogen therapy is widely used against post-menopausal symptoms, it can present adverse effects, including endometrial cancer. Soy isoflavones are considered a possible alternative to estrogen therapy. However, there are still concerns whether isoflavones exert trophic effects on the uterine cervix. OBJECTIVES To evaluate the histomorphometric and immunohistochemical alterations in the uterine cervix of ovariectomized rats treated with soy isoflavones (Iso). METHODS Fifteen adult Wistar rats were ovariectomized (Ovx) and divided into three groups: Group I (Ovx), administered with vehicle solution; Group II (OVX-Iso), administered with concentrated extract of Iso (150 mg/kg) by gavage; and Group III (OVX-E2), treated with 17β-estradiol (10 µg/kg), subcutaneously. After 30 days of treatments, the uterine cervix was fixed in 10% formaldehyde and processed for paraffin-embedding. Sections were stained with Hematoxylin and eosin for morphological and morphometric studies or subjected to immunohistochemistry for detections of Ki-67 and vascular endothelial growth factor-A (Vegf-A). The data obtained were subjected to statistical analysis (p ≤ 0.05). RESULTS We noted an atrophic uterine cervix in GI, whereas it was more voluminous in GII and even more voluminous in GIII. The thickness of the cervical mucosa was significantly higher in GIII, as compared to GI and GII. The cell proliferation (Ki-67) was significantly elevated in the estradiol and isoflavones treated groups, whereas Vegf-A immunoexpression was significantly higher in GIII, as compared to groups GII and GI. CONCLUSIONS Soy isoflavones cause less trophic and proliferative effects in the uterine cervix of rats as compared to estrogen.

RESUMO INTRODUÇÃO Embora a terapia estrogênica seja amplamente utilizada contra sintomas pós-menopausais, ela pode apresentar efeitos adversos, incluindo câncer de mama e endometrial. Assim, as isoflavonas da soja são consideradas uma alternativa possível à terapia estrogênica. No entanto, ainda há controvérsias se estes compostos exercem efeitos tróficos significativos no colo do útero. OBJETIVOS Avaliar as alterações histomorfométricas e imuno-histoquímicas no colo do útero de ratas ovariectomizadas tratadas com isoflavonas da soja (iso). MÉTODOS Quinze ratas Wistar adultas foram ovariectomizadas bilateralmente (Ovx) e separadas em três grupos: Grupo I (Ovx) - veículo (propilenoglicol); Grupo II (Ovx-Iso) - receberam extrato concentrado de Iso (150 mg/kg) e Grupo III (Ovx-E2) - tratado com 17β-estradiol (10 µg/kg); as soluções foram administradas via gavagem por 30 dias consecutivos. Posteriormente, os colos uterinos foram retirados, fixados em formaldeído a 10% tamponado e processados para inclusão em parafina. Cortes (4 µm) foram coradas com hematoxilina e eosina para estudo morfológico e morfométricos, enquanto outros foram submetidos à imuno-histoquímica para detecção de Ki-67 e do fator de crescimento endotelial vascular-A (Vegf-A). Os dados obtidos foram submetidos à análise estatística (p≤0,05). RESULTADOS Observamos a presença de colo uterino atrófico no GI (Ovx), sendo este mais volumoso no GII (Ovx+Iso) e ainda mais volumoso no GIII (Ovx+E2). A espessura da mucosa cervical foi significativamente maior no GIII (Ovx-E2), em comparação ao GI (Ovx) e ao GII (Ovx-Iso). A proliferação celular (Ki-67) foi significativamente mais elevada nos grupos tratados com estradiol e isoflavonas, enquanto a imunoexpressão de Vegf-A foi significativamente maior no GIII (Ovx-E2), em comparação ao GII (Ovx-Iso) e ao GI (Ovx-E2). CONCLUSÕES As isoflavonas da soja causam menos efeitos tróficos e proliferativos no colo do útero de ratas em comparação ao estrogênio.

Reactional changes in short-term levonorgestrel-releasing intrauterine system (lng-ius) use

SUMMARY OBJECTIVE: To evaluate endocervical and vaginal environment changes in women using a levonorgestrel-releasing intrauterine system (LNG-IUS). METHODS: A quasi-experimental study included sixty women who had an LNG-IUS inserted in the Family Planning Clinic of UNICAMP between April and November of 2016. Women in reproductive age, non-pregnant, without the use of antibiotics and contraceptives seeking for LNG-IUS insertion were selected for this study. All women were evaluated with regard to vaginal and endocervical pH, vaginal and endocervical Gram-stained bacterioscopy, and Pap-smear before and two months after LNG-IUS insertion. Clinical aspects such as cervical mucus, vaginal discharge, and cervical ectopy were also observed. RESULTS: After LNG-IUS insertion, there was an increase in the following parameters: endocervical pH>4.5 (p=0.02), endocervical neutrophil amount (p<0.0001), vaginal cytolysis (p=0.04). There was a decrease in vaginal discharge (p=0.01). No statistically significant changes were found in vaginal pH, neutrophils amount in the vaginal mucosa, vaginal discharge appearance, vaginal candidiasis, bacterial vaginosis, vaginal coccobacillary microbiota, cervical mucus appearance, or cervical ectopy size. CONCLUSIONS: Short-term LNG-IUS use did not increase vulvovaginal candidiasis or bacterial vaginosis, and led to diminished vaginal discharge. Notwithstanding, this device promoted reactional changes in the vaginal and endocervical environment, without modification on cervical ectopy size.

RESUMO OBJETIVO: Avaliar as alterações do ambiente endocervical e vaginal em mulheres usuárias de sistema intrauterino liberador de levonorgestrel (SIU-LNG). MÉTODOS: Um estudo quase-experimental incluiu 60 mulheres que inseriram o SIU-LNG na Clínica de Planejamento Familiar da UNICAMP entre abril e novembro de 2016. Mulheres em idade reprodutiva, não gestantes, sem uso de antibióticos e contraceptivos, em busca pela inserção do SIU-LNG, foram selecionadas para este estudo. Todas as mulheres foram avaliadas quanto ao pH vaginal e endocervical, bacterioscopia vaginal e endocervical por coloração de Gram, exame de Papanicolau antes e dois meses após a inserção de SIU-LNG. Aspectos clínicos como muco cervical, corrimento vaginal e ectopia cervical também foram observados. RESULTADOS: Após a inserção do SIU-LNG houve aumento nos seguintes parâmetros: pH endocervical >4,5 (p=0,02), quantidade de neutrófilos endocervicais (p<0,0001), citolise vaginal (p=0,04). Houve diminuição do conteúdo vaginal (p=0,01). Não foram encontradas alterações estatisticamente significativas no pH vaginal, na quantidade de neutrófilos na mucosa vaginal, apecto do corrimento vaginal, candidíase vaginal, vaginose bacteriana, microbiota cocobacilar vaginal, aparência de muco cervical ou tamanho da ectopia cervical. CONCLUSÃO: O uso do SIU-LNG em curto prazo não aumentou a candidíase vulvovaginal ou a vaginose bacteriana, levou à diminuição do conteúdo vaginal. No entanto, este dispositivo promoveu mudanças reacionais no ambiente vaginal e endocervical, sem modificação no tamanho da ectopia cervical.

Immunohistochemistry of the uterine cervix of rats bearing the Walker 256 tumor treated with copaiba balsam

PURPOSE: To investigate the immunohistochemistry of the uterine cervix of 20 Wistar rats (Rattus norvegicus) bearing the Walker 256 tumor, treated with copaiba oil (Copaifera officinalis). METHODS: The animals were grouped into four subgroups, with five rats each: the GCT and GCopT received distilled water and topically copaiba, respectively, while the GCG and GCopG received distilled water and copaiba by gavage, respectively. The substances were administered for nine days. On the 12th day, after euthanasia, the tumor pieces were sent to the identification of T CD4+, T CD8+ and Natural Killer cells. RESULTS: It was found that the pattern of expression for specific markers of phenotypes of cells involved in tumor immune response was similar in all groups, regardless the administration way of copaiba oil (topical or gavage). CONCLUSION: Copaiba balsam, administered either topically or by gavage, did not alter the pattern of tumor immune response in rats bearing Walker 256 Tumor.

[Titrated oral misoprostol solution compared with oxytocin for induction of labor in women with unfavorable cervix]

Uterine contractions and an appropriate cervix are two important factors in labor contributing to good pregnancy outcomes. Oxytocin and prostaglandins, such as misoprostol, are used for the induction of labor. Misoprostol is used for cervical ripening and labor induction. The aim of this trial was to compare the efficacy and safety of titrated oral misoprostol solution with oxytocin for labor induction in pregnant women with an unfavorable cervix. In this randomized double-blind clinical trial, 140 women with a gestational age of 34-42 weeks and an unfavorable cervix were recruited. The participants had an indication for labor induction and had been referred to the Women's Hospital in Tehran, Iran between January 2010 and January 2011. The participants were randomly assigned to receive 20 micro g/hour titrated oral misoprostol plus intravenous placebo or 6 mU/min oxytocin plus oral placebo. In case contractions were inadequate, the drug doses were gradually increased. Pharmacological complications, the mean interval from the start of induction till vaginal delivery and delivery type were monitored and analyzed in both groups. The mean interval from the start of induction till vaginal delivery in misoprostol group was shorter than the oxytocin group [11.07 +/- 3.42 vs. 14.87 +/- 3.21 hours, P=0.001]. The frequency of pharmacological complications and vaginal or cesarean deliveries were similar between the two groups [P>0.05]. Use of titrated oral misoprostol is a safe and effective method for labor induction in pregnant women with unfavorable cervix. Misoprostol is associated with a shorter interval from induction to vaginal delivery than oxytocin

Sublingual misoprostol: A better choice for cervical priming before manual vacuum aspiration.

Background: Misoprostol is effective for cervical priming before manual vacuum aspiration (MVA). Aim of study was to determine whether sublingual misoprostol with a shorter interval of 2 hours before MVA would be as effective as its standard vaginal administration. Study Design: This randomized control trial included 82 women randomly assigned to receive 400 mcg of misoprostol, either sublingually or vaginally. MVA was performed 2 hours and 3 hours after in sublingual and vaginal group, respectively. Results: Cervical dilatation of 8 mm was achieved within 2 hours in sublingual group. Mean time taken for procedure (14.4 ± 5.3: sublingual group and 16.2 ± 5.7: vaginal group), and blood loss was comparable (12.2 ± 9.7 ml in sublingual group and 13.7 ± 8.5 ml in vaginal group). Conclusion: 2 hour of cervical priming with 400 mcg of sublingual misoprostol before MVA was as good as 3 hours with vaginal administration of the same dose.

Intracervical PGE2 gel for cervical ripening and induction of Labour

The objectives of the study were to evaluate the efficacy of interacervical gel as a cervical ripening agent in the unfavourable cervix. The changes in the Bishops score, onset of labour and its progress were secondary outcome measures. Fifty patients were enrolled in this prospective study conducted in Gynae "A" unit of Khyber Teaching Hospital, Peshawar from January to December 2004. Patients with singleton living fetus, cephalic presentation, gestational age of >36 weeks completed were included. Half milligram [0.5mg] of prostaglandin E2 gel intracervical was used for intracervical application. The application was repeated after 6-12 hours if the Bishop score remained unfavourable i-e < 5. The indications were postdates pregnancy [50%], PIH [18%], Diabetes Mellitus [18%] and Rh isoimmnization [6%]. The success rate in terms of vaginal delivery was 82%. The lower segment caesarean section rate was 18%. The commonest indication for caesarean section was failure to progress. The complications side effects were minimal and the neonatal outcome was good. This study showed that intracervical application of prostaglandin E2 gel is effective, safe acceptable method for ripening of cervix in women with unfavourable cervix

Comparative study of misoprostol vs dinoprostone for induction of labour.

Various methods of induction of labour may be associated with risk and complications. Therefore, this study has been undertaken to compare the safety and efficacy of intra-vaginal misoprostol (PGE1 analogue) with intra-cervical dinoprostone (PGE2) in progress and induction of labour, the maternal side effects and the foetal outcome. 40 pregnant women aged between 16-35 years with indication of induction of labour participated in the study. Twenty patients (control) were administered 0.5 mg dinoprostone intra-cervically, 12 hourly while 20 patients (study group) were given misoprostol 100 microg, 4 hourly, intravaginally. The mean induction of labour initiation interval was 2.08 +/- 1.46 hours in study group and 2.21 +/- 1.20 hours in dinoprostone group. The Induction delivery interval was 6.92 +/- 4.01 hours in misoprostol group and 12.54 +/- 7.73 in dinoprostone group, whereas vaginal route of delivery was 95% in misoprostol group and 85% in dinoprostone group. Average dosages required were 1.55 +/- 1.02 in misoprostol group and 1.30 +/- 0.46 in dinoprostone group. All these result were statistically significant. Very few maternal side effects were reported in study group. There was no significant difference in foetal out come in either group. Therefore, it can be concluded that misoprostol is easy to administer and is cheap, effective, safe and convenient drug for induction of labour.

Use of misoprostol for induction of labour in unfavorable cervix in eclampsia

To find out safety and efficacy of Misoprostol in cervical ripening and induction of labour to achieve vaginal delivery Design: Prospective observational study Setting: Dept. of Obstetrics and Gynecology, Khulna Medical College, Bangladesh Patients Et From January 2002 to December 2003, 5197 obstetric patients were received for delivery. This included 251 eclampsia patients. Out of the 251 Eclampsia patients, 81 patients [Primigravida 49 and multigravida 32] with unripe cervix were selected for induction of labour using Misoprostol tablet 1/4 th mixed with K-Y Jelly. Misoprostol application was stopped after third dose if there was no progress in cervical dilatation or effective uterine contractions and patients were taken for caesarean operation. From Misoprostol insertion to delivery time was 4-24 hours. Vaginal delivery was achieved in 80.2%, which included spontaneous, forceps and vacuum extraction. Caesarean section rate was 19.7%. Indications for C. Section included Misoprostol unresponsiveness 11% and fetal distress in 8.6%. Oxytocin augmentation was required in 32% of cases. Term babies were 58%. Intrauterine death and neonatal deaths were 9.8% and 8.6% respectively. Hyper stimulation and postpartum haemorrhage was seen in 2.4% and 3.7% of patients respectively Conclusions: Intravaginal Misoprostol is well tolerated and is very effective for the induction of labour in eclampsia. It helps vaginal delivery in toxemic patients, reduces maternal morbidity, mortality and hospital stay

In vitro study of biosynthesis of protoporphyrin IX induced by Ù-Aminolevulinic acid in normal and cancerous cells of the human cervix

Bxkground. Ù-Aminolevulinic acid (ALA) is recognized as the starter in the biosynthesis of the heme group, the structural basis of cytochromes, chlorophylls, biliary pigments, and other porphyrins. It is the first intermediary in the biosynthesis of protoporphyrin IX (PpIX), and of ther heme group. PpIX is present in low concentration in normal cells, and in high concentration in tumor cells. Methods. The accumulation of protoporhyrin IX (PpIX) induced by Ù-aminolevulinic acid (ALA) was tested in two cervico-uterine cancer cell lines (HeLa and CaLo), and in normal human cervical epithelial (NHCE) cells. Results. The optimal concentration of ALA that induced maximum levels of intra- and extracellular accumulation of PpIX in both HeLa and NHCE cells was 300 µg of ALA/mL, and for CaLo cells, 150 µg/mL. The viability of HeLa, CaLo, and NHCE cells exposed to ALA measured 81, 98 and 84 percent, respectively. The optimale time for accumulation of PpIX, both intra- and extracellular, was 4 h for HeLa and NHCE cells and 5 h for CaLo cells per 24 h of expusure to optimal concentrations of ALA. After the maximum level of PpIX accumulation was reached, there was a gradual decrease until there was only a small quantity. A statistically significant difference (p <0.0001) was foundf in the accumulation of PpIX, depending on the concentrations of ALA used as well as between cervical cancer cell lines and 1:7, and for NHCE and CaLo cells. 1:5. Conclusions. These results are important for determining the usefulness of the sensitizer (PpIX)

Ação da hialuronidase na maturação do colo uterino em gestações a termo: um estudo piloto / Cervical uterine ripening with hyaluronidase in pregnancies at term

Foi investigada a ação da injeção intracervical de hialuronidase no amadureciemnto do colo uterino em gestações de termo sem necessidade de hospitalização, com a finalidade de promover parto via vaginal em grupo de gestantes com idade gestacional de 40 e 42 semanas. Foram selecionadas 34 gestantes que apresentavam índice de Bishop menor que 5 e incluídas no estudo. Eram injetados 4 ml com 20.000 U.I. de hialuronidase no colo uterino e após 48 horas, as pacientes eram reavaliadas e uma segunda dose de hialuronidase era injetada se o indíce de Bishopera ainda menor que 5. Uma terceira avaliação era feita após 96 horas da primeira injeção. Foi considerada resposta positiva se o indíce reavaliado fosse superior a 5. Cinqüenta e oito (per cent) das nulíparas responderam positivamente nas primeiras 48 horas e 16 (per cent) entre 48 e 96 horas. Nas primíparas/multíparas essa média foi de 78 (per cent) nas primeiras 48 horas e 11 (per cent) entre 48 e 96 horas. Esses resultados sugerem que a injeção intracervical de hialuronidase, sem hospitalização pode ser um método simples, efetivo e seguro para melhorar o amadurecimento do colo uterino, reduzindo a duração do trabalho de parto (au)

Dinoprostone vs. estradiol en la inducción del parto: investigación clínica aleatorizada / Dinoprostone vs. estradiol in labor induced, randomized clinical investigation

La inducción al parto es una poderosa herramienta obstétrica de amplia aplicación, pero aún no se dispone de un procedimiento de alta eficacia para su ejecución

Estudio comparativo de misoprostol vs. dinoprostona para la inducción del trabajo de parto / Conparative study of misoprostol vs. dinoprostona for labor inducement

Objetivo. Comparar la seguridad, eficacia y costo del misoprostol intravaginal (análogo de la prostaglandina E1) y la dinoprostona intracervical (prostaglandina E2) en la inducción del trabajo del parto con cérvix inmaduro (índice de Bishop <6). Método. Ochenta y cuatro pacientes se asignaron al azar a uno de los dos grupos: 1) 43 al de misoprostol intravaginal (50 µg) y 2) 41 al de dinoprostona intracervical (0.5 mg), ambos medicamentos se administraron a intervalos de 6 horas, con un máximo de 3 dosis. Resultados. Las pacientes con misoprostol tuvieron una reducción significativa en el tiempo entre a administración del medicamento y la fase activa del trabajo de parto (500.3 ñ 310 contra 647 ñ 341 min.) (p=0.039). El tiempo de trabajo de parto se acortó significativamente con el misoprostol (652 ñ 311 contra 829.9 ñ 359 min) (p=0.022). Las complicaciones intraparto como taquisistolia, meconio y síndrome de hiperestimulación uterina ocurrieron en forma similar en los dos grupos. El porcentaje de partos vaginales, efectos adversos maternos y el seguimiento neonatal no fueron estadísticamente diferentes. Conclusiones. El misoprostol es más efectivo que la dinoprostona para alcanzar la fase activa del trabajo de parto y el parto. Tiene la misma seguridad para el feto y la madre y su costo es mínimo

Maduración cervical con prostaglandina E2 en pacientes con feto muerto / Cervical maturation with prostaglandin E2 in patient with dead fetus

El objetivo fue comparar la eficacia y eficacia de prostaglandina E2 más oxitocina versus oxitocina en la inducción de trabajo de parto y maduración cervical en pacientes con feto muerto intrauterino. Se estudiaron 30 embarazadas, 15 pacientes recibieron prostaglandina R2 más oxitocina, y 15 oxitocina únicamente. Al grupo de tratamiento se le administró prostaglandina E2 dosis única intracervical de 0.5 mg en 2.5 mL de gel más oxitocina I.V. a 2 mUI/min incrementándose a 2 mUI/min cada 30 minutos; y al grupo control se le administró oxitocina I.V. a la misma dosis. El tiempo promedio en horas para parto vaginal en el grupo de tratamiento fue 13.1 +/- 6.6 h y en el grupo de control de 30.9 +/- 9.1 h. Hubo diferencias estadísticamante significativas en la duración del trabajo de parto entre los grupos (p=0.0007). Se concluye que en pacientes con feto muerto intrauterino la utilización de prostaglandina E2 más oxitocina provoca periodos más cortos de trabajo de parto que el tratamiento con oxitocina únicamente y produce mejores resultados a corto tiempo

Comparison of intracervical and intravaginal misoprostol for cervical ripening and labour induction in patients with an unfavourable cervix.

OBJECTIVE: To compare the efficacy of intracervical versus intravaginal misoprostol for cervical ripening and labour induction at term in patients with an unfavourable cervix. METHOD: A total of 100 pregnant women with indications for induction of labour and unfavourable cervix (Bishop score < or = 4) were randomly assigned to receive either 100 ug misoprostol administered intracervically (50 cases) or intravaginally (50 cases). RESULTS: No significant differences were noted between intracervical and intravaginal misoprostol in terms of Bishop score change, (score 7.2 vs score 7.5), interval from gel insertion to vaginal delivery (17.0 hours vs 16.4 hours), meperidine as analgesic requirement (80% vs 76%), route of delivery and perinatal outcome. Uterine tachysystole occurred in 24 per cent and 32 per cent in the intracervical and intravaginal groups respectively which did not significantly differ, however, all could be rapidly resolved by terbutaline injection. No evidence of fetal distress was noted in these events. Spillage of gel out of the cervix was observed in 70 per cent of patients receiving intracervical misoprostol. Fever was observed in one patient of each group. No other serious side effects were found in both groups. One patient in the intravaginal group had postpartum hemorrhage due to delayed placental separation and uterine atony. CONCLUSION: The two routes of misoprostol gel application appear to be safe and equally effective in ripening cervix and inducing labour, however, the intravaginal application is more convenient to administer practically compared with the intracervical.

Estudio comparativo del manejo de amenaza de parto prematuro con salbutamol y óxido nítrico. Reporte preliminar / Comparative study of premature parturition menace management with salbutamol and nitric oxide. Preliminary report

El parto pretérmino constituye la principal causa de morbimortalidad neonatal, se han tratado de implementar diversas medidas terapéuticas y preventivas sin que su incidencia haya disminuido. Se realizó un estudio comparativo del uso de salbutamol y óxido nítrico en el manejo de las pacientes con amenaza de parto pretérmino en el periodo de agosto de 1995 a mayo de 1996, evaluándose variables demográficas, efectos hemodinámicos, efectos en el producto, vía de parto, complicaciones asociadas y periodo de prolongación del embarazo, sin que se encontrará diferencia estadísticamente significativa. Se concluye que el óxido nítrico puede emplearse como alternativa de tratamiento

Carboprost Metil. Parte I. Sus acciones farmacologicas / Carboprost methyl. Part I. Its pharmacological actions

Carboprost metil es una prostaglandina de actividad biologica de 10 a 20 veces superior a la PGR(2a). Es un potente estimulador de la actividad contractil del miometrio e induce dilatacion cervical. Su uso se ha sugerido desde los anos 70, a pesar de los efectos secundarios que produce. La presencia de un grupo metilo en el carbono 15 bloquea la accion de la enzima 15-hidroxi-prostaglandina dehidrogenasa, por lo cual se incrementa el tiempo de vida media: este hecho provoca que la duracion de la accion farmacologica sea de 2 a 3 veces mayor que el desarrollado por la PGF(2a)