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  • Original Article

    Effects of combined estrogen and raloxifene therapy on rat endometrium

    Rev Bras Ginecol Obstet. 2006;28(2):101-106

    Summary

    Original Article

    Effects of combined estrogen and raloxifene therapy on rat endometrium

    Rev Bras Ginecol Obstet. 2006;28(2):101-106

    DOI 10.1590/S0100-72032006000200005

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    PURPOSE: to evaluate the effects of conjugated equine estrogens (CEE) and raloxifene (Ral), alone or combined, on the rat endometrium. METHODS: fifty-six adult rats were ovariectomized and randomly divided into seven groups: GCont (control); GCEE (CEE 50 µg/kg); GCEE/25 (CEE 25 µg/kg); GRal/0.75 (Ral 0.75 mg/kg); GRal/0.4 (Ral 0.4 mg/kg); GCEERal (50/0.75) - (CEE 50 µg/kg + Ral 0.75 mg/kg), and GCEE-Ral (25/0.4) - (CEE 25 µg/kg + Ral 0.4 mg/kg). The drugs were orally administered (gavage) for 21 consecutive days. At the end of the experiment, all animals were anesthetized and sacrificed. Fragments of uterus were removed, fixed in 10% formaldehyde and processed for paraffin inclusion. The histological sections were stained by HE and submitted to histomorphometric evaluation. The following parameters were analyzed: thickness of superficial epithelium and number of endometrial glands/mm² and of blood vessels/mm². The data were evaluated using ANOVA followed by the Turkey-Kramer test. RESULTS: in the GCont and only Ral treatment (GRal/0.75 and GRal/0.4) the endometrium showed signals of atrophy. In the groups treated with only CEE signs of endometrial proliferation were observed, mainly in group GCEE/50. Also, there was endometrial proliferation in the groups that received combined CEE and Ral (Ral GCEE (50/0.75) and GCEE-Ral (25/0.4)), but it was more intensive in the animals treated with isolated estrogen than in those that received combined estrogen and raloxifene. CONCLUSION: raloxifene may partially block the action of estrogen on the castrated adult rat endometrium.

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    Effects of combined estrogen and raloxifene therapy on rat endometrium
  • Original Article

    Effects of Domperidone on Pregnant Albino Rats Pregnancy

    Rev Bras Ginecol Obstet. 2000;22(2):107-111

    Summary

    Original Article

    Effects of Domperidone on Pregnant Albino Rats Pregnancy

    Rev Bras Ginecol Obstet. 2000;22(2):107-111

    DOI 10.1590/S0100-72032000000200008

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    Purpose: the aim of the present work was to study the chronic action of the antiemetic domperidone on the pregnancy of albino rats. Methods: fifty albino, pregnant Wistar rats were randomly allocated to five groups: GI (control I) = intact rats; GII (control II) = rats receiving the drug vehicle (distilled water) by gavage at the same schedule of the experimental groups; rats in groups GIII, GIV and GV were treated with domperidone by gavage, 2, 6 and 12 mg/kg per day, respectively, divided into 4 daily doses, always in 1 ml of distilled water, from time zero up to the 20th day of pregnancy. The evolution of body weight gain was followed throughout and the animals were sacrificed at term (20th day) by deep ether anesthesia. Number of fetuses, placenta and implantation sites, placenta and fetus weight, fetal malformations and maternal and fetal mortality were evaluated. Results: we observed only intrauterine fetal mortality with 14, 26 and 32 in 74, 60 and 57 newborns of the groups III, IV and V, respectively. Conclusion: though the results of animal experimentation cannot directly be transposed to human conditions, this paper calls attention to the need for a safe judgement when prescribing domperidone to a first-trimester pregnant patient in order to reduce her emetic crises.

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    Effects of Domperidone on Pregnant Albino Rats Pregnancy
  • Original Article

    Effects of chronic use of tramadol on pregnant albino rats

    Rev Bras Ginecol Obstet. 2001;23(2):113-117

    Summary

    Original Article

    Effects of chronic use of tramadol on pregnant albino rats

    Rev Bras Ginecol Obstet. 2001;23(2):113-117

    DOI 10.1590/S0100-72032001000200009

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    Purpose: to examine the effects of tramadol hydrochloride on rat pregnancy. Methods: five groups of 10 pregnant albino rats each were treated from the 1st up to the 20th day of pregnancy as follows: GI = intact controls; GII = controls which received 0.5 ml of distilled water (drug vehicle) once a day by gavage; GIII, GIV and GV = groups treated respectively with 6.7, 20.1 or 45.6 mg/kg of tramadol hydrochloride once a day by gavage in a final volume of 0.5 mL. Body weight gain was monitored by weighing at the beginning and on the 7th, 14th and 20th day of pregnancy. At term the animals were killed under deep ether anesthesia and the following parameters were evaluated: number of implantations, of resorptions, of viable fetuses and of placentae; presence of major malformations; maternal and fetal mortality and weights of fetuses and placentae. Results: tramadol significantly affected maternal body weight gain, this effect being more apparent in groups IV and V (mean reductions of weight gain of 41 and 56%, respectively). In group III the weight gain was affected more at days 7 and 14 (33% mean gain reductions) than at day 20 (19%). Drug treatment affected significantly and in a dose-dependent fashion the following parameters: individual weight of fetuses (GV = -39.2%), offspring weight (GIV = -51.7%; GV = -44.2%), number of placentae (GIV = -28.4%; GV = -11.6%), individual weight of placentae (GV = -10%) and the total weight of placentae (GIV = -28.4%; GV = -16.8%). Though among the treated animals there was an increase in resorptions and deaths at birth, these events were not significantly different from those found in controls. Conclusions: Tramadol showed definite deleterious effects on albino rat pregnancy, and these effects were exerted not only on the maternal but also the on fetal organisms. Overall, the effects were more pronounced at the 14th than at the 20th day of pregnancy, thus suggesting that the organogenic phase of the fetus is more susceptible than its initial (embryogenic) or final (term) phases. The results call attention to the care which is to be taken when the use of this opioid is considered during pregnancy.

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    Effects of chronic use of tramadol on pregnant albino rats
  • Original Article

    Effects of chronic nelfinavir treatment on rat pregnancy: biological assay

    Rev Bras Ginecol Obstet. 2006;28(3):184-189

    Summary

    Original Article

    Effects of chronic nelfinavir treatment on rat pregnancy: biological assay

    Rev Bras Ginecol Obstet. 2006;28(3):184-189

    DOI 10.1590/S0100-72032006000300008

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    PURPOSE: to evaluate the chronic effects of nelfinavir on body weight gain of pregnant albino rats and their concepts, as well as on the number of implantations, reabsorptions, fetuses, placentae, and maternal and fetal mortality. METHODS: fifty pregnant EPM-1 Wistar albino rats were randomly divided into five groups: two controls, Contr1 (control of stress) and Contr2 (drug vehicle control), and 3 experimental groups, Exp40, Exp120, Exp360, which received 40, 120 or 360 mg/kg per day of oral solution of nelfinavir, respectively. The drug and the vehicle (distilled water) were administered twice a day (12/12 h) by gavage from the first up to the 20th day of pregnancy. After sacrifice under deep anesthesia, the following parameters were evaluated: number of implantations and reabsorptions, the weight of fetuses and placentae, and the number of intrauterine deaths as well as inspection for major malformations. Data were evaluated by ANOVA followed by the Kruskal-Wallis multiple comparison test. RESULTS: body weight gain during pregnancy was normal for all the groups, and no significant differences were detected between them. ANOVA did not reveal any significant effect of nelfinavir on the studied parameters. The means of number of fetuses were: control = 9.7±0.50; nelfinavir-treated groups = 9.7±0.81. Regarding the means of number of placentae and implantations, controls = 9.7±0.50; nelfinavir-treated groups = 9.6±0.78. The mean fetal weights were as follows: controls = 4.04±0.50; nelfinavir-treated groups = 3.91±0.33 g. Finally, control placental weights averaged 0.64±0.02; nelfinavir-treated groups = 0.67±0.02 g. CONCLUSION: nelfinavir was well tolerated at all the administered doses; no damage was produced on the fetuses.

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    Effects of chronic nelfinavir treatment on rat pregnancy: biological assay
  • Original Article

    Morphological and molecular effects of isoflavone and estrogens on the rat mammary gland

    Rev Bras Ginecol Obstet. 2005;27(4):204-209

    Summary

    Original Article

    Morphological and molecular effects of isoflavone and estrogens on the rat mammary gland

    Rev Bras Ginecol Obstet. 2005;27(4):204-209

    DOI 10.1590/S0100-72032005000400007

    Views2

    PURPOSE: to analyze the effects of isoflavones and estrogens on the morphology, morphometry and VEGF expression of the adult female rat mammary gland. METHODS: Forty-five adult female rats were oophorectomized; 28 days after surgery they were divided into 3 groups of 15 animals each: CON - control (treated with propylenoglycol); ISO - isoflavones (100 mg/kg) and CEE - conjugated equine estrogens (50 µg/Kg). Drugs or vehicle were given orally once a day for 60 days. After this, the animals were killed and the first pair of inguinal mammary glands was immediately removed; part of the material was processed for routine histological study and the remaining tissue was frozen for further analyses of the expression of VEGF mRNA by means of the RT-PCR technique. RESULTS: We observed that mammary ducts were atrophic in the control (CON) and isoflavone-treated (ISO) groups. In these groups the mammary glands were composed of a large concentration of adipose tissue with some ducts and rare alveolar structures. In the CEE group the ducts were well developed with many buds and alveolar structures. The number of mammary gland alveoli was higher in CEE than in the other groups (CON = 1.4 ± 2.1; ISO = 1.6 ± 3.8; CEE = 12.3 ± 7.1 alveoli/mm²; p<0.05%); also, the cell volume was higher (CON = 14.9 ± 4.9; ISO = 11.4 ± 6.9; CEE = 27.4 ± 9.7 µm³, p< 0.05%). The same was observed with regard to the number of blood vessels (CON = 16.4 ± 1.5; ISO = 18.4 ± 2.1; CEE = 37.1 ± 4.1 vessels/mm², p< 0.05). The expression of VEGF in the CEE group was higher than in the other groups, which did not significantly differ from each other in this respect. CONCLUSION: Our data did not show any proliferation effect in the mammary tissue of adult oophorectomized rats treated with isoflavones (100 mg/kg) during 60 days.

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    Morphological and molecular effects of isoflavone and estrogens on the rat mammary gland
  • Original Article

    Effects of chronic amprenavir treatment on rat pregnancy

    Rev Bras Ginecol Obstet. 2004;26(3):207-211

    Summary

    Original Article

    Effects of chronic amprenavir treatment on rat pregnancy

    Rev Bras Ginecol Obstet. 2004;26(3):207-211

    DOI 10.1590/S0100-72032004000300006

    Views2

    OBJECTIVE: to evaluate the chronic effects of amprenavir on implantations, reabsorptions, fetuses, placentae, and maternal and fetal mortality in the albino rat. METHODS: five groups of EPM-1 Wistar pregnant rats were used: two controls: Contr1 (control of stress) and Contr2 (drug vehicle control), and 3 experimental groups that were treated once a day throughout gestation with 46mg/kg (Exper1), 138mg/kg (Exper2) and 414mg/kg (Exper3) of oral solution of amprenavir. The drug and the vehicle (propyleneglycol) were administered by gavage. The evaluations included maternal body weight gain, number of implantations, reabsorptions, fetuses, placentae and of intrauterine deaths as well as fetal and placental mean weight and major malformations. Fragments of lungs, kidneys, liver and intestines were collected and prepared for histopathological evaluation. RESULTS: Exper3 group tended to show lesser maternal body weight gain during gestation (P = 0.07), but amprenavir did not affect the intrauterine contents. The cytotoxic effect of the drug was observed with regard to the histopathological analyses of pregnant rat viscerae and to the maternal mortality rate: 50% in Exper1 and Exper2 groups, and 70% in Exper3 group. CONCLUSION: amprenavir exerted adverse side effects on maternal lung, gut, kidney and liver, and significantly increased maternal mortality rates in all administered doses and especially at 414 mg/kg.

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    Effects of chronic amprenavir treatment on rat pregnancy
  • Original Article

    Effects of isoflavones on the adult rat myometrium

    Rev Bras Ginecol Obstet. 2006;28(4):227-231

    Summary

    Original Article

    Effects of isoflavones on the adult rat myometrium

    Rev Bras Ginecol Obstet. 2006;28(4):227-231

    DOI 10.1590/S0100-72032006000400004

    Views2

    PURPOSE: to evaluate histomorphometric changes in the rat myometrium upon treatment with isoflavones, as compared with estrogens, using histological and morphometric techniques. METHODS: twenty-eight oophorectomized adult rats were randomly divided into four treatment groups: GPropi = propylene glycol (control); GExtr10 - 10 mg/kg soybean extract; GExtr300 - 300 mg/kg soy bean extract; GCee - 200 µg/kg conjugated equine estrogens (Cee). Drugs or drug vehicle were administered by gavage once a day for 21 days. Upon sacrifice, the uteri were removed and weighed. Fragments of uterine horns were collected and fixed in 10% formaldehyde and processed for paraffin inclusion. The histological sections were stained by hematoxylin and eosin and evaluated microscopically by means of an image analyzer to quantify the myometrial thickness and the number of blood vessels and eosinophils. The data were studied by analysis of variance (ANOVA) followed by the Tukey-Kramer multiple comparison test. RESULTS: isoflavones in the concentration of 300 mg/kg induced a significant increase in the myometrium thickness (GExtr300=25.6±5.0 mm) compared to control (GPropi=5.5±0.5 mm). The effect of this high dose is similar to the estrogen effect (GCee=27.5±7.9 mm). In low doses (10 mg/kg), the effect was similar to control. Isoflavones (GExtr300) induced also an increase in the number of blood vessels (GPropi=3.5±1.6; GExtr300=10.2±3.6 vessels/mm²) and of eosinophils (CPropi=0.15±0.01; GExtr300=4.3±0.9 eosinophils/mm²). These effects were comparable to those produced by Cee treatment in GCee (9.2±1.1 eosinophils/mm²). CONCLUSION: a high-dose treatment with isoflavones (300 mg/kg per day, 21 days) elicited an estrogen-like, highly significant proliferative action on the rat myometrium.

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    Effects of isoflavones on the adult rat myometrium
  • Original Article

    Morphological and collagen fiber count alterations induced by hyaluronidase in the cervix of pregnant rats

    Rev Bras Ginecol Obstet. 2003;25(4):249-254

    Summary

    Original Article

    Morphological and collagen fiber count alterations induced by hyaluronidase in the cervix of pregnant rats

    Rev Bras Ginecol Obstet. 2003;25(4):249-254

    DOI 10.1590/S0100-72032003000400005

    Views1

    PURPOSE: to assess the morphological and morphometric alterations in the uterine cervix of pregnant albino rats determined by local hyaluronidase administration. METHODS: ten rats with a positive pregnancy test were randomly distributed into two equal groups. The control group consisted of rats that received a single dose of 1 mL distilled water in the uterine cervix, on gestational day 18, under anesthesia. The experimental group consisted of rats that received 0.02 mL hyaluronidase, diluted in 0.98 ml distilled water (total = 1 mL), in the same conditions as those of the control group. On day 20, the rats were anesthetized and submitted to dissection. The uterine cervix was prepared for morphological and morphometric study at light microscopy (hematoxylin and eosin, and Masson trichrome). RESULTS: in the experimental group, greater thinning of the superficial mucified epithelium was observed, with lamina propria rich in blood vessels and eosinophils. Diversely, the control group showed a large concentration of collagen fibers. The histometric analysis in the experimental group was characterized by a smaller number of collagen fibers (mean = 248 versus 552 of control; SD = 49.7 versus 31.1 of control). The parametric method (Student's t test) showed a significant difference between groups (p<0.0001). CONCLUSION: the local use of hyaluronidase in the cervix of pregnant rats determined predominance of loose connective tissue and a smaller concentration of collagen fibers.

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    Morphological and collagen fiber count alterations induced by hyaluronidase in the cervix of pregnant rats

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