Ricardo Santos Simões

Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, San Paulo, São Paulo, Brazil

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Publications (145)139.77 Total impact

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    ABSTRACT: The aim of this study was to evaluate the effects of metoclopramide-induced hyperprolactinemia on the tibial epiphyseal plate of hormone-treated oophorectomized mice. For this purpose, 18 animals with intact ovaries were allocated to two groups, M (metoclopramide) and V (vehicle). One hundred and eight oophorectomized animals were allocated to 12 subgroups: Oophx/V (vehicle); Ooph/M (metoclopramide); Oophx/V + E (vehicle + estradiol); Oophx/M + E (metoclopramide + estradiol); Oophx/V + P (vehicle + progesterone); Oophx/M + P (metoclopramide + progesterone); Oophx/V + T (vehicle + testosterone); Oophx/M + T (metoclopramide + testosterone); Oophx/V + E + P (Vehicle + estradiol + progesterone); Oophx/M + E + P (metoclopramide + estradiol + progesterone); Oophx/V + E + P + T (vehicle + estradiol + progesterone + testosterone); Oophx/M + E + P + T (metoclopramide + estradiol + progesterone + testosterone). After a 50-day treatment was performed histomorphometric and immunohistochemical cell death analysis. In the epiphyseal plate of the hyperprolactinemic and/or oophorectomized animals, cell proliferation and bone formation decreased, inducing intensified cell death. In the sex steroid-treated animals, estrogen boosted cell proliferation; progesterone, bone formation and testosterone, both cell proliferation and bone formation. These findings suggest that oophorectomy and hyperprolactinemia changed epiphyseal plate morphology causing cartilage degeneration. Treatment with combined sex steroids may diminish such deleterious effects.
    Gynecological Endocrinology 07/2015; DOI:10.3109/09513590.2015.1068753 · 1.14 Impact Factor
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    ABSTRACT: To evaluate the sex steroid profile and histomorphometry of the adrenal cortical zones of androgenized rats (wistar) with polycystic ovary syndrome treated with metformin. Thirty animals were divided into three groups: GC (regular estrous cycle), GPE (permanent estrus), and GPEM (permanent estrus + metformin 28 mg/kg for 50 days). At the end of this period, blood was collected for hormone measurement. The width of the adrenal cortical zones and the nuclear volumes were analyzed by histomorphometry. The ANOVA test was used in the statistical analysis. The adrenal glands of the androgenized animals were larger and more intensely vascularized than those of the other groups. The concentration of androstenedione in GPE was higher than that in the other groups (0.4 ± 0.1*>= 0.2 ± 0.1 = 0.2 ± 01, *p < 0.05). The width of the zona glomerulosa and of the zona reticularis and their nuclear volumes were greater in GPE compared to those of the other groups (GPE* > GPEM = GC, *p < 0.05). Metformin treatment may decrease the serum levels of androstenedione as well as the width and the nuclear volumes of the zona glomerulosa and of the zona reticularis in androgenized animals.
    Gynecological Endocrinology 06/2015; DOI:10.3109/09513590.2015.1019342 · 1.14 Impact Factor
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    ABSTRACT: To evaluate the effects of angico bark extract (Anadenanthera colubrina var. cebil) in the healing process of the skin of rats. Twenty adult male rats were divided into four groups of five animals each, according to the respective postoperative days, as follow: G4, G7, G14 and G21. Each group received two incisions on skin and subcutaneous tissue in the right and left antimere of the thoracic region, separated by a distance of 2 cm. The right lesion was treated daily with saline and the left with the angico alcoholic extract (5%). At the end of each experimental period, the animals were euthanized and fragments of the wound area with the edges were removed, fixed in 10% formaldehyde solution and processed for paraffin embedding. Histological sections (5 μm of thickness) were stained with hematoxylin and eosin (HE), Gomori trichromic and picrosisirus red for morphological and morphometric analyses. Statistical analysis was done by ANOVA and Tukey-Kramer test (p<0.05). Morphological analysis showed larger fibroblasts and a higher concentration of collagen fibers in skyn wounds treated with the angico extract. Morphometric analysis demonstrated a significant increase in the number of fibroblasts at 7th and collagen in 7th and 14th days (p<0.01) in wounds treated with the angico extract. The angico alcoholic extract (Anadenanthera colubrina var. cebil) induces the acceleration of wound healing in skin wounds of rats.
    Acta cirurgica brasileira / Sociedade Brasileira para Desenvolvimento Pesquisa em Cirurgia 05/2015; 30(5):353-8. DOI:10.1590/S0102-865020150050000007 · 0.48 Impact Factor
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    ABSTRACT: To evaluate wound contraction and the concentration of mast cells in skin wounds treated with 5% BPT essential oil-based ointment in rats. Twenty rats, male, of adult age, were submitted to skin surgery on the right (RA) and left antimeres (LA) of the thoracic region. They were divided into two groups: control (RA - wounds receiving daily topical application of vaseline and lanolin) and treated (LA - wounds treated daily with the topical ointment). The skin region with wounds were collected at days 4, 7, 14 and 21 after surgery. Those were fixed in 10% formaldehyde and later processed for paraffin embedding. Sections were obtained and stained by H.E for histopathology analysis. The degree of epithelial contraction was measured and mast cell concentration were also evaluated. The treated group showed higher mast cell concentrations (p<0.05) associated with increased contraction at day 7 and 14 respectively. Ointment containing 5% Brazilian pepper tree oil increases mast cell concentration and promotes skin wound contraction in rats.
    Acta cirurgica brasileira / Sociedade Brasileira para Desenvolvimento Pesquisa em Cirurgia 04/2015; 30(4):289-95. DOI:10.1590/S0102-865020150040000008 · 0.48 Impact Factor
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    ABSTRACT: To evaluate the morphology, necrotic area and collagen content in skin flaps of rats subjected to hyperbaric oxygenation (HBO). Forty adult rats were divided into four groups: GEC - epilated; GE/HBO - epilated subjected to HBO; GER - epilated submitted to skin flap (2 cm in width /8 cm length in the dorsal area) and GER/HBO - epilated, subjected to skin flap and HBO. HBO (2.4 ATA) was performed for two hours during seven consecutive days. In the eighth day, the rats were anesthetized and the skin flaps were removed and separated into three portions, relative to pedicle fixation. The material fixed in 10% formalin was processed for paraffin embedding; sections were stained by H.E and subjected to picrosirius-red method. The slides examined under light microscopy for evaluation of the collagen content in polarized light microscope and ImageLab(r) software (Bio-Rad). The data showed larger area of necrosis and lower levels of collagen in the three regions of the GER group, whereas in the GER/HBO group the collagen content was similar to the GEC and GE/HBO groups. Hyperbaric oxygenation reduced the area of necrosis and preserved the morphology and collagen content in skin flaps of rats.
    Acta cirurgica brasileira / Sociedade Brasileira para Desenvolvimento Pesquisa em Cirurgia 04/2015; 30(4):235-41. DOI:10.1590/S0102-865020150040000001 · 0.48 Impact Factor
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    ABSTRACT: To analyze steroidogenesis-related gene expression in the rat ovary exposed to melatonin supplementation. Thirty-two virgin adult female rats were randomized to two groups as follows: the control group GI received vehicle and the experimental group GII received melatonin supplementation (10 µg/night per animal) for 60 consecutive days. After the treatment, animals were anesthetized and the collected ovaries were immediately placed in liquid nitrogen for complementary deoxyribonucleic acid microarray analyses. A GeneChip¯ Kit Rat Genome 230 2.0 Affymetrix Array was used for gene analysis and the experiment was repeated three times for each group. The results were normalized with the GeneChip¯ Operating Software program and confirmed through analysis with the secondary deoxyribonucleic acid-Chip Analyzer (dChip) software. The data were confirmed by real-time reverse transcription polymerase chain reaction analysis. Genes related to ovarian function were further confirmed by immunohistochemistry. We found the upregulation of the type 9 adenylate cyclase and inhibin beta B genes and the downregulation of the cyclic adenosine monophosphate response element modulator and cytochrome P450 family 17a1 genes in the ovarian tissue of GII compared to those of the control group. Our data suggest that melatonin supplementation decreases gene expression of cyclic adenosine monophosphate, which changes ovarian steroidogenesis.
    Clinics (São Paulo, Brazil) 02/2015; 70(2):144-51. DOI:10.6061/clinics/2015(02)12 · 1.42 Impact Factor
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    ABSTRACT: Infertility associated with polycystic ovary syndrome (PCOS) could be related to many mechanisms including endometrial factors.
    International Journal of Gynecology & Obstetrics 12/2014; 129(1). DOI:10.1016/j.ijgo.2014.10.022 · 1.56 Impact Factor
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    ABSTRACT: Abstract The aim of this study was to quantify the sulfated glycosaminoglycans in the endometria of women with polycystic ovary syndrome (PCOS). Of the 18 patients recruited for this study, 10 patients with PCOS comprised the PCOS group (PCOSG), and eight patients with regular and ovulatory menstrual cycles comprised the control group (CG). The clinical, biochemical, morphological and endometrial data from both groups were analyzed. Biopsies were performed during the proliferative phase of the menstrual cycle for the CG and during the persistent proliferative phase for the PCOSG (all women were amenorrheic). In the PCOSG, there was a significant increase in the endometrial concentration levels of heparan sulfate (p = 0.03), but no difference in the concentrations of chondroitin sulfate was determined between the two groups (p = 0.77). Period of time without menstruation (p = 0.001) and body mass index (BMI) (p = 0.04) correlated directly and positively with heparan sulfate concentration. There was no association between heparan sulfate levels and basal insulin values (p = 0.08). High levels of endometrial heparan sulfate in women with PCOS indicate an interference with maternal-fetal recognition, which contributes to infertility; thus, endometrial heparan sulfate may be a predictive marker of future neoplasia risk.
    Gynecological Endocrinology 12/2014; DOI:10.3109/09513590.2014.989980 · 1.14 Impact Factor
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    ABSTRACT: ABSTRACT Objective: We evaluated whether genistein or oestrogen treatment has the same effect when administered immediately or late to rats induced with menopause using ovariectomy (OVx). Methods: Sixty adult female rats were divided into six treatment groups: GI= vehicle immediately after OVx; GII= vehicle 30 days after Ovx; GIII= genistein immediately after OVx; GIV= genistein 30 days after OVx; GV= oestrogen immediately after OVx; and GVI= oestrogen 30 days after OVx. All animals were treated for 30 consecutive days. At the end of the treatment, part of the uteri was removed for subsequent histological studies and another part was used to evaluate oestrogen receptor (Esr1, Esr2), cell proliferation (Ccna1, Ccna2, Ccnd1, Cdkn1a, Cdkn1b, Cdkn2a, Mki67) and angiogenesis (Vegfa) gene expression. Results: Late treatment after castration in rats results in more developed endometrium, enhanced cell proliferation and oestrogen-signalling pathways, particularly the cyclin-related genes Ki67 and VEGF-A, compared to early treatment. Interestingly, these same effects were less intense to genistein compared to those induced by oestrogen, especially when genistein was late administered. Conclusion: Our data show that isoflavone renders a lower risk of cancer when compared to oestrogen in treatments.
    Climacteric 09/2014; DOI:10.3109/13697137.2014.964671 · 2.24 Impact Factor
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    ABSTRACT: To develop this guideline the following primary and secondary electronic databases were consulted: Medline (1966-2009), Cochrane, Cochrane Central Register of Controlled Trials - Central, Embase (1980-2010) and Lilacs (1982-2010). The search for evidence came from actual clinical scenarios and used keywords (MeSH terms) grouped in the following syntax: surgical procedures, operative, nonsurgical,therapy, lumbosacral region, lumbosacral, degenerative, spondylolisthesis, spondylolisthesis. The articles were selected after critical evaluation of the strength of scientific evidence by specialists from the participating Medical Associations, and publications of greatest strength were used for recommendation. The recommendations were drawn from group discussion. The entire guideline was reviewed by an independent group specializing in evidence-based clinical guidelines.
    Revista da Associação Médica Brasileira 09/2014; 60(5):400. DOI:10.1590/1806-9282.60.05.004 · 0.92 Impact Factor
  • Microscopy and Microanalysis 08/2014; 20:1424. DOI:10.1017/S143192761400885X · 1.76 Impact Factor
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    ABSTRACT: Abstract Objective: To evaluate the effects of soy isoflavones extract (ISO) in the prooxidant/antioxidant balance in the uterus of ovariectomized (OVX) rats. Methods: Twenty 3-month-old adult female Wistar rats were equally divided into four groups: GI- Sham-operated (estrous phase); GII- control OVX; GIII- OVX treated with genistein (50 µg/kg/day) by gavage; GIV- OVX subcutaneously treated with estrogen (E2) (10µg/Kg/day). After thirty consecutive days of treatment, the rats were euthanized and the uterus removed. The distal third of the uterine horns were processed for histomorphometric analyses of endometrial and myometrial thickness and glandular area. Other uteri regions were kept in liquid nitrogen and subsequently processed for analysis of reactive species quantification (DCF), total antioxidant capacity (TAC) and lipid oxidation status (TBARS). Data were statistically analyzed by one-way ANOVA, complemented by Tukey-Kramer test (p<0.05). Results: GII and GIII exhibited lower endometrial thickness, glandular area and myometrial thickness than GI and GIV, while a higher myometrial thickness was observed in GIV compared to the other groups. Moreover, ISO treated group showed lower DCF and TBARS compared to GII, and also an improvement of TAC compared to GI and GIV. Despite the significant decrease in TBARS, no significant difference in DCF or a decrease in TAC were observed in GIV when compared to GII. Conclusion: Our data show that isoflavones improve antioxidant status and counteract oxidative stress, without promoting trophic effect in the uterus of rats.
    Climacteric 08/2014; DOI:10.3109/13697137.2013.856402 · 2.24 Impact Factor
  • Microscopy and Microanalysis 08/2014; 20(S3):1390-1391. DOI:10.1017/S143192761400868X · 1.76 Impact Factor
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    Revista da Associação Médica Brasileira 07/2014; 60(4):302-304. DOI:10.1590/1806-9282.60.04.006 · 0.92 Impact Factor
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    ABSTRACT: Objective: to evaluate the immunohistochemical expression of proliferative, apoptotic and steroidogenic enzyme markers in the ovaries of rats with polycystic ovary syndrome (PCOS). Methods: twenty rats were divided into two groups: GCtrl - estrous phase, and PCOS - with polycystic ovaries. The GCtrl animals were subjected to a lighting period from 7 am to 7 pm, while the animals with PCOS group remained with continuous lighting for 60 days. Subsequently, the animals were anesthetized, the ovaries were removed and fixed in 10% formaldehyde, prior to paraffin embedding. Sections were stained using H.E. or subjected to immunohistochemical methods for the detection of Ki-67, cleaved caspase-3, CYP11A1, CYP17A1 and CYP19A1. The results were analyzed using Student's t-test (p < 0,05). Results: morphological results showed evidence of interstitial cells originating from the inner theca cells of degenerating ovarian cysts in PCOS. Immunoexpression of Ki-67 was higher in the granulosa cells in GCtrl, and the theca interna cells in PCOS, while cleaved caspase-3 was higher in granulosa cells of ovarian cysts from PCOS and in the theca interna cells of GCtrl. Immunoreactivity of CYP11A1 in the theca interna, granulosa and interstitial cells was similar between the two groups, while CYP17A1 and CYP19A1 were higher in the granulosa and interstitial cells in the PCOS group. Conclusion: the results indicate that the interstitial cells are derived from the theca interna and that enzymatic changes occur in the theca interna and interstitial cells in ovaries of rats with PCOS, responsible for the high levels of androgens and estradiol.
    Revista da Associação Médica Brasileira 07/2014; 60(4):349-356. DOI:10.1590/1806-9282.60.04.0014 · 0.92 Impact Factor
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    Revista da Associação Médica Brasileira 07/2014; 60(4):295-297. DOI:10.1590/1806-9282.60.04.004 · 0.92 Impact Factor
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    Revista da Associação Médica Brasileira 06/2014; 60(3):192-195. DOI:10.1590/1806-9282.60.04.002 · 0.92 Impact Factor
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    ABSTRACT: To analyze the expression of genes related to steroidogenesis in the ovary of pinealectomized rats. Experimental research. University research laboratory. Thirty female adult rats. Administration of vehicle (GI), pinealectomy with vehicle (GII), or pinealectomy with melatonin replacement (10 μg/night) for 60 consecutive days (GIII), then euthanasia after 2 months of treatment, ovary collection complementary DNA microarray analyses, confirmatory quantitative reverse-transcriptase polymerase chain reaction analyses, and immunohistochemical analyses for localizing steroidogenesis changes in the ovary. Biologic molecular study followed by immunohistochemical analysis. The changes in the expression of CYP11A1, CYP17A1, and CYP19A1 after pinealectomy (GII) compared with control (GI) showed the Cyp17a1 expression level increased in the theca interna and interstitial cells in the GII rats compared with the other groups. Melatonin deprivation (pinealectomy) or administration may influence the ovarian CYP17A1 expression and steroidogenesis.
    Fertility and sterility 05/2014; 102(1). DOI:10.1016/j.fertnstert.2014.04.006 · 4.59 Impact Factor
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    ABSTRACT: Cryopreservation of the ovarian tissue has shown promising results. However, there remain controversial issues such as the short half-life of grafts. In this aspect, there are some evidences that preconditioning the ovarian tissue before transplantation is beneficial. To determine the effect of hypoxic preconditioning in vitro on ovarian tissue prior to transplantation. Eighteen female adult Wistar rats, were sorted into three experimental groups. Ovaries were maintained in DMEM low glucose serum free at 37[degree sign]C with 5% CO2, at atmospheric oxigen concentration (normoxia) or 1% O2 (hypoxia) for 16 hours. Oxigen concentration was determined by injection of nitrogen in the incubator. Animals submitted to ovarian transplantation immediately after oophorectomy were the Control Group (C). After this, the ovaries were implanted in the retroperitoneum with nonabsorbable suture and animals evaluated for thirty days after transplantation. Beginning on postoperative (PO) day 11, a daily collection of vaginal smear was carried out. Analyses comprised morphological, morphometric (counting ovarian follicles and corpora lutea) and immunohistochemistry for cleaved caspase-3 (apoptosis). In normoxia and control groups all animals recovered their estrous cycles, while in the hypoxia group, two animals did not ovulate but, among those which did, resumption took longer than in the other groups (p < 0.05). The number of ovarian follicles and corpora lutea decreased significantly in the hypoxia group when compared to the other two groups (p < 0.001) and apoptosis was increased in the few ovarian follicles which remained viable (p < 0.001). The hypoxic preconditioning in vitro was not beneficial to the graft and worsened their viability, compromising its functionality or delaying the return of this.
    Journal of Ovarian Research 03/2014; 7(1):34. DOI:10.1186/1757-2215-7-34 · 2.03 Impact Factor
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    ABSTRACT: Literature data indicate that the infertility in women with polycystic ovary syndrome (PCOS) is not only attributed to anovulation but also to endometrial dysfunction. Endometrial biopsies were performed in the proliferative and secretory phases of women with normal cycle and in women with PCOS before and after oral treatment with micronized progesterone. After the treatment, the endometrium of the women with PCOS exhibited a lower number of glands and thicker luminal epithelium compared to the normal women in the secretory phase. In addition, the PCOS group exhibited reduced integrin and MECA-79 immunoexpression during the secretory phase. The expression of E-cadherin was higher in the PCOS and the expression of intercellular adhesion molecule 1 was lower in PCOS, during the secretory and proliferative phases, respectively. Also, there is a negative correlation with MECA-79 and integrin expression and body mass index. Conventional doses of progesterone may not be enough to correct the changes of endometrial histomorphology and the receptive markers of PCOS-bearing women. The obesity may be a factor that interferes with this response.
    Reproductive sciences (Thousand Oaks, Calif.) 01/2014; 21(7). DOI:10.1177/1933719113519169 · 2.18 Impact Factor

Publication Stats

331 Citations
139.77 Total Impact Points

Institutions

  • 2011–2015
    • Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo
      San Paulo, São Paulo, Brazil
    • Senac São Paulo
      San Paulo, São Paulo, Brazil
    • Universidade José do Rosário Vellano – UNIFENAS
      San Paulo, São Paulo, Brazil
  • 2004–2015
    • Universidade Federal de São Paulo
      • • Escola Paulista de Medicina (EPM)
      • • Departamento de Ginecologia
      San Paulo, São Paulo, Brazil
  • 2008–2014
    • University of São Paulo
      • • Department of Obstetrics and Gynecology
      • • Faculty of Medicine (FM)
      San Paulo, São Paulo, Brazil
  • 2013
    • Federal University of Minas Gerais
      Cidade de Minas, Minas Gerais, Brazil
  • 2008–2012
    • Universidade Federal Rural de Pernambuco
      • Department of Animal Morphology and Physiology
      Arrecife, Pernambuco, Brazil
  • 2004–2012
    • UNIC - Universidade de Cuiabá
      Vila Real do Senhor Bom Jesus de Cuiabá, Mato Grosso, Brazil