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Revista Brasileira de Ginecologia e Obstetrícia. 2015;37(5):233-240
DOI 10.1590/SO100-720320150005333
To assess the effect of tibolone on mammary tissue of castrated rats over 3
different periods of time.
Sixty virgin female Wistar rats were submitted to oophorectomy. Twenty-one days
after surgery, with hypoestrogenism confirmed, the experimental rats were randomly
assigned to six groups: Tibolone 1 (n=10) received tibolone 1 mg/day for 23 days,
tibolone 2 (n=10) for 59 days and tibolone 3 (n=10) for 118 days. The groups
control 1 (n=8), control 2 (n=7) and control 2 (n=10) received distilled water for
23, 59 and 118 days, respectively. After treatment, all six pairs of mammary
glands were removed and stained with hematoxylin and eosin (HE) for histological
analysis after euthanasia. The histological parameters evaluated were: epithelial
cell proliferation and secretory activity. The variables were analyzed
statistically, with the level of significance set at 0.05.
Histological changes were observed in 20/55 rats, mild epithelial hyperplasia in
7/55, moderate epithelial hyperplasia in 5/55, alveolar-nodular hyperplasia in
7/55, atypia without epithelial proliferation in 1/55, and no cases of severe
epithelial hyperplasia were found. Secretory activity was observed in 31/55 rats.
The secretory activity was significantly higher in the tibolone groups compared to
control at all the time points assessed (p=0,001). The histological changes were
did not show significance when the control and tibolone groups were compared. The
time of exposure to tibolone did not show significance when the three different
periods of evaluation were compared.
No relation between histological modification and tibolone treatment was verified
after short-, medium- and long-term treatment.
Summary
Revista Brasileira de Ginecologia e Obstetrícia. 2015;37(5):233-240
DOI 10.1590/SO100-720320150005333
To assess the effect of tibolone on mammary tissue of castrated rats over 3
different periods of time.
Sixty virgin female Wistar rats were submitted to oophorectomy. Twenty-one days
after surgery, with hypoestrogenism confirmed, the experimental rats were randomly
assigned to six groups: Tibolone 1 (n=10) received tibolone 1 mg/day for 23 days,
tibolone 2 (n=10) for 59 days and tibolone 3 (n=10) for 118 days. The groups
control 1 (n=8), control 2 (n=7) and control 2 (n=10) received distilled water for
23, 59 and 118 days, respectively. After treatment, all six pairs of mammary
glands were removed and stained with hematoxylin and eosin (HE) for histological
analysis after euthanasia. The histological parameters evaluated were: epithelial
cell proliferation and secretory activity. The variables were analyzed
statistically, with the level of significance set at 0.05.
Histological changes were observed in 20/55 rats, mild epithelial hyperplasia in
7/55, moderate epithelial hyperplasia in 5/55, alveolar-nodular hyperplasia in
7/55, atypia without epithelial proliferation in 1/55, and no cases of severe
epithelial hyperplasia were found. Secretory activity was observed in 31/55 rats.
The secretory activity was significantly higher in the tibolone groups compared to
control at all the time points assessed (p=0,001). The histological changes were
did not show significance when the control and tibolone groups were compared. The
time of exposure to tibolone did not show significance when the three different
periods of evaluation were compared.
No relation between histological modification and tibolone treatment was verified
after short-, medium- and long-term treatment.
Summary
Revista Brasileira de Ginecologia e Obstetrícia. 2011;33(7):137-142
DOI 10.1590/S0100-72032011000700004
PURPOSE: To evaluate the efect of trimegestone on the histological changes of the mammary tissue of castrated rats. METHODS: Forty-five virgin female Wistar rats were used after oophorectomy. Sixty days after surgery, with hypoestrogenisms confirmed, the experimental rats were randomly assigned to three groups of 15 animals each, when then the specific treatment for each group was started. The control group (C) and experimental groups 1 and 2 respectively received 0.9% saline solution, 17-beta-estradiol and 17-beta-estradiol in combination with trimegestone for 60 consecutive days. After the end of treatment , the inguinal mammary glands were removed, stained with hematoxylin and eosin (HE) for morphometry and examined by immunohistochemistry for the quantification of anti-PCNA antibody in the mammary tissue, followed by euthanasia. The morphometric parameters evaluated were: epithelium cell-proliferation, secretor activity and mammary stroma changes. There were nine deaths during the experiment. The variables were submitted to statistical analysis adopting the 0.05 level of significance. RESULTS:Histological changes were observed in 16/36 rats, mild epithelial hyperplasia in 13/36, moderate epithelial hyperplasia in 3/36, with no cases of severe epithelial hyperplasia. Stromal fibrosis was found in 10/36 and secretory activity in 5/36 rats. All morphometric variables were significant in the estrogen group compared to control (p=0.0361), although there were no difference between the group receiving combined treatment and the controls (p=0.405). The immunohistochemical analysis showed no difference between groups. CONCLUSIONS:The hormones administered to castrated rats, i.e., 17 beta-estradiol alone or in combination with trimegestone, increased the proliferation of breast cells, but this effect appeared to be lower in the combined treatment, the same occurring regarding fibrosis of the mammary stroma.
Summary
Revista Brasileira de Ginecologia e Obstetrícia. 2011;33(7):137-142
DOI 10.1590/S0100-72032011000700004
PURPOSE: To evaluate the efect of trimegestone on the histological changes of the mammary tissue of castrated rats. METHODS: Forty-five virgin female Wistar rats were used after oophorectomy. Sixty days after surgery, with hypoestrogenisms confirmed, the experimental rats were randomly assigned to three groups of 15 animals each, when then the specific treatment for each group was started. The control group (C) and experimental groups 1 and 2 respectively received 0.9% saline solution, 17-beta-estradiol and 17-beta-estradiol in combination with trimegestone for 60 consecutive days. After the end of treatment , the inguinal mammary glands were removed, stained with hematoxylin and eosin (HE) for morphometry and examined by immunohistochemistry for the quantification of anti-PCNA antibody in the mammary tissue, followed by euthanasia. The morphometric parameters evaluated were: epithelium cell-proliferation, secretor activity and mammary stroma changes. There were nine deaths during the experiment. The variables were submitted to statistical analysis adopting the 0.05 level of significance. RESULTS:Histological changes were observed in 16/36 rats, mild epithelial hyperplasia in 13/36, moderate epithelial hyperplasia in 3/36, with no cases of severe epithelial hyperplasia. Stromal fibrosis was found in 10/36 and secretory activity in 5/36 rats. All morphometric variables were significant in the estrogen group compared to control (p=0.0361), although there were no difference between the group receiving combined treatment and the controls (p=0.405). The immunohistochemical analysis showed no difference between groups. CONCLUSIONS:The hormones administered to castrated rats, i.e., 17 beta-estradiol alone or in combination with trimegestone, increased the proliferation of breast cells, but this effect appeared to be lower in the combined treatment, the same occurring regarding fibrosis of the mammary stroma.
Summary
Revista Brasileira de Ginecologia e Obstetrícia. 2001;23(8):507-513
DOI 10.1590/S0100-72032001000800005
Purpose: to evaluate the effect of hormone replacement therapy on breast cell proliferation and on collagen and elastic fiber formation and to analyze the changes occurring in the breast parenchyma as a whole. Method: a total of 61 adult Wistar rats were divided into 5 groups. The standard group (12 rats) represented the normal hormonal ovarian status. The remaining 49 rats were oophorectomized and, starting on the 96th P.O. day, received the specific drug for 30 days. The CEE group received 50 mg/day conjugated equine estrogens (13 rats); the MPA group, 2.0 mg/day medroxyprogesterone acetate (12 rats); the CEE + MPA group, both drugs (12 rats), and the DW group, distilled water (12 rats). On the 31st day of medication, the animals were sacrificed and the inguinal mammary glands were removed for histological analysis. Cell proliferation was assessed at the ductal and acinar levels using anti-PCNA antibody. Mature collagen (type I) and immature collagen (type III) were quantified by Sirius-Red staining, and elastic fiber formation was quantified by Weigert staining. Anatomopathological analysis was performed by hematoxylin-eosin staining, with the determination of number of acini per terminal duct, number of ducts per field, presence of intraductal secretion, and intensity of intracytoplasmic vacuolization. Results: the CEE + MPA group presented a smaller percentage of proliferating ductal cells (46.1%) (p<0.0001) and a greater proliferation of acinar cells (66.3%), similar to those detected in the MPA group (p=0.075) but differing from those detected in the remaining groups (p<0.004). The CEE group showed the largest amount of immature collagen (33.6%) (p<0.01) and the MPA group showed the highest concentration of elastic fibers (11.7%) (p<0.0001). The CEE + MPA and MPA groups showed secretory acinar hyperplasia that was intense (91.7%) in the CEE + MPA group and mild (41.7%) or moderate (58.3%) in the MPA group, but differering in both cases from the remaining groups (p<0,097). Conclusions: conjugated equine estrogens in combination with medroxyprogesterone inhibit ductal cell proliferation and stimulate acinar cell proliferation causing secretory acinar hyperplasia; conjugated horse estrogens intensify the formation of immature (type III) collagen, and medroxyprogesterone acetate increases the formation of elastic fibers.
Summary
Revista Brasileira de Ginecologia e Obstetrícia. 2001;23(8):507-513
DOI 10.1590/S0100-72032001000800005
Purpose: to evaluate the effect of hormone replacement therapy on breast cell proliferation and on collagen and elastic fiber formation and to analyze the changes occurring in the breast parenchyma as a whole. Method: a total of 61 adult Wistar rats were divided into 5 groups. The standard group (12 rats) represented the normal hormonal ovarian status. The remaining 49 rats were oophorectomized and, starting on the 96th P.O. day, received the specific drug for 30 days. The CEE group received 50 mg/day conjugated equine estrogens (13 rats); the MPA group, 2.0 mg/day medroxyprogesterone acetate (12 rats); the CEE + MPA group, both drugs (12 rats), and the DW group, distilled water (12 rats). On the 31st day of medication, the animals were sacrificed and the inguinal mammary glands were removed for histological analysis. Cell proliferation was assessed at the ductal and acinar levels using anti-PCNA antibody. Mature collagen (type I) and immature collagen (type III) were quantified by Sirius-Red staining, and elastic fiber formation was quantified by Weigert staining. Anatomopathological analysis was performed by hematoxylin-eosin staining, with the determination of number of acini per terminal duct, number of ducts per field, presence of intraductal secretion, and intensity of intracytoplasmic vacuolization. Results: the CEE + MPA group presented a smaller percentage of proliferating ductal cells (46.1%) (p<0.0001) and a greater proliferation of acinar cells (66.3%), similar to those detected in the MPA group (p=0.075) but differing from those detected in the remaining groups (p<0.004). The CEE group showed the largest amount of immature collagen (33.6%) (p<0.01) and the MPA group showed the highest concentration of elastic fibers (11.7%) (p<0.0001). The CEE + MPA and MPA groups showed secretory acinar hyperplasia that was intense (91.7%) in the CEE + MPA group and mild (41.7%) or moderate (58.3%) in the MPA group, but differering in both cases from the remaining groups (p<0,097). Conclusions: conjugated equine estrogens in combination with medroxyprogesterone inhibit ductal cell proliferation and stimulate acinar cell proliferation causing secretory acinar hyperplasia; conjugated horse estrogens intensify the formation of immature (type III) collagen, and medroxyprogesterone acetate increases the formation of elastic fibers.
