Hyperprolactinemia modifies extracellular matrix components associated with collagen fibrillogenesis in harderian glands of non- and pregnant female mice.

The harderian gland (HG) is a gland located at the base of the nictating membrane and fills the inferomedial aspect of the orbit in rodents. It is under the influence of the hypothalamic-pituitary-gonadal axis and, because of its hormone receptors, it is a target tissue for prolactin (PRL) and sex steroid hormones (estrogen and progesterone). In humans and murine, the anterior surface of the eyes is protected by a tear film synthesized by glands associated with the eye. In order to understand the endocrine changes caused by hyperprolactinemia in the glands responsible for the formation of the tear film, we used an animal model with metoclopramide-induced hyperprolactinemia (HPRL). Given the evidences that HPRL can lead to a process of cell death and tissue fibrosis, the protein expression of small leucine-rich proteoglycans (SLRPs) was analyzed through immunohistochemistry in the HG of the non- and the pregnant female mice with hyperprolactinemia. The SRLPs are related to collagen fibrillogenesis and they participate in pro-apoptotic signals. Our data revealed that high prolactin levels and changes in steroid hormones (estrogen and progesterone) can lead to an alteration in the amount of collagen, and in the structure of type I and III collagen fibers through changes in the amounts of lumican and decorin, which are responsible for collagen fibrillogenesis. This fact can lead to the impaired functioning of the HG by excessive apoptosis in the HG of the non- and the pregnant female mice with HPRL and especially in the HG of pregnancy-associated hyperprolactinemia.

Hormonal and Metabolic Factors Influence the Action of Progesterone on the Endometrium of Women with Polycystic Ovary Syndrome.

Hormonal and metabolic factors may influence endometrial quality and interfere with the action of progesterone. Therefore, the aim of our study was to address this issue. Participants were recruited from an outpatient reproductive endocrinology clinic at an academic tertiary medical care centre. All subjects underwent endometrial biopsy (EB) in the follicular phase of the cycle prior to treatment. Thereafter, they were treated with micronized progesterone (400 mg/day × 10 days intravaginally) from days 14-28 of the next cycle. A second EB was performed between days 21-24 of the cycle (the second phase). The metabolic and hormonal serum levels were evaluated during the implantation window. EB samples were analysed using light microscopy for histomorphometric analysis. The endometrium of women with Polycystic Ovarian Syndrome (PCOS) in the second phase demonstrated a uniform surface epithelium with less leukocyte infiltration and an absence of apoptotic figures compared to the control group. (p < 0.021). The thickness of the surface epithelium in the second phase of the PCOS group correlated positively with free and bioavailable testosterone values. The number of stromal cells increases with increasing insulin levels. Our results suggest that histomorphometric abnormalities of the endometrium persist and are linked to androgen and insulin levels despite progesterone supplementation in PCOS.

Impact of the prolactin levels in breast cancer: a systematic review and meta-analysis.

Prolactin (PRL) acts stimulating the mammary glands development, and its deregulation has been associated to the emergence of several types of tumors, including breast cancer. Breast cancer represents the most prevalent malignancy in women, and the second cause of death in several countries. This tumor can be arise due to several molecular alterations, among them PRL has been the object of increasing interest from researchers worldwide. OBJECTIVE: To assess the association between elevated levels of plasma prolactin and breast cancer development. METHODS: A total of 158 studies were found in search databases (48 from PubMed, 69 from Scopus, 88 from Cochrane, 25 from Embase and 10 retrieved from the gray literature) after removing duplicates. Of these, 104 studies were excluded after title and abstract reading, and 54 studies were then read in full, of which only 14 were selected for this review because they had evaluated the association between PRL and breast cancer. Meta-analysis was carried out using the relative risk (RR), mean and standard deviation, confidence interval (95% CI), and the total number of patients for each study. Fixed- and random-effect models were used as applicable and, for the analysis. RESULTS: The meta-analysis showed a positive association between elevated levels of PRL and breast cancer occurrence (RR 1.26; 95%CI 1.15-1.37). Additionally, the patient sub-group analyses showed a positive association between PRL and invasive breast cancer (1.42; 1.24-1.60), ER+/PR+ (1.49; 1.23-1.75), and post-menopausal status (1.29; 1.16-1.43). CONCLUSION: The results showed a positive association between plasma prolactin levels and breast cancer, especially in women with ER+/PR + tumors, of post-menopausal age and those with invasive cancer.

Hyaluronic acid and proliferation/cellular death amount in the female rats mammary gland after estroprogestative therapy.

AIMS: To evaluate the concentration of hyaluronan acid and proliferation/cellular death in mammary gland of ovariectomized female rat after estroprogestative therapy. MATERIALS AND METHODS: Forty ovariectomized female rats were divided into four groups with 10 animals/each: OG (vehicle); EG: (Estradiol, 7 days of treatment), PG (Progesterone acetate, 23 days of treatment), and EPG: (Estradiol, 7 days of treatment, and next Progesterone acetate, 23 days of treatment). Twenty-four hours after the last treatment, all animals were euthanized, the mammary gland removed, then, a fragment was immersed in acetone to quantifying of the hyaluronan acid biochemical method (ELISA-Like fluorometric assay), and a fragment fixed for 24 h in 10% formaldehyde in phosphate-buffered saline (PBS) processed for immunohistochemistry method for detection of the cell marker proliferation (Ki67) and cellular marker death by DNA fragmentation the TUNEL method. RESULTS: The estradiol-treatment alone (EG) or associated with progesterone (EPG) affected the concentration of hyaluronan acid, increased cell proliferation, and decreased cell death compared to OG and PG (p < .05) in the mammary tissue. CONCLUSIONS: Our results suggest that the excessive reduction of HA in mammary tissue, as occurred with progesterone treatment, can lead to a breakdown of the extracellular matrix. These changes may be indicative of mammary pathology such as the development of tumor.

Prior exercise training and experimental myocardial infarction: A systematic review and meta-analysis.

Exercising prior to experimental infarction may have beneficial effects on the heart. The objective of this study was to analyze studies on animals that had exercised prior to myocardial infarction and to examine any benefits through a systematic review and meta-analysis. The databases MEDLINE, Google Scholar, and Cochrane were consulted. We analyzed articles published between January 1978 and November 2018. From a total of 858 articles, 13 manuscripts were selected in this review. When animals exercised before experimental infarction, there was a reduction in mortality, a reduction in infarct size, improvements in cardiac function, and a better molecular balance between genes and proteins that exhibit cardiac protective effects. Analyzing heart weight/body weight, we observed the following results - Mean difference 95% CI - -0.02 [-0.61,0.57]. Meta-analysis of the infarct size (% of the left ventricle) revealed a statistically significant decrease in the size of the infarction in animals that exercised before myocardial infarction, in comparison with the sedentary animals -5.05 [-7.68, -2.40]. Analysis of the ejection fraction, measured by echo (%), revealed that animals that exercised before myocardial infarction exhibited higher and statistically significant measures, compared with sedentary animals 8.77 [3.87,13.66]. We conclude that exercise performed prior to experimental myocardial infarction confers cardiac benefits to animals.

Prior exercise training and experimental myocardial infarction: A systematic review and meta-analysis

Exercising prior to experimental infarction may have beneficial effects on the heart. The objective of this study was to analyze studies on animals that had exercised prior to myocardial infarction and to examine any benefits through a systematic review and meta-analysis. The databases MEDLINE, Google Scholar, and Cochrane were consulted. We analyzed articles published between January 1978 and November 2018. From a total of 858 articles, 13 manuscripts were selected in this review. When animals exercised before experimental infarction, there was a reduction in mortality, a reduction in infarct size, improvements in cardiac function, and a better molecular balance between genes and proteins that exhibit cardiac protective effects. Analyzing heart weight/body weight, we observed the following results - Mean difference 95% CI - -0.02 [-0.61,0.57]. Meta-analysis of the infarct size (% of the left ventricle) revealed a statistically significant decrease in the size of the infarction in animals that exercised before myocardial infarction, in comparison with the sedentary animals -5.05 [-7.68, -2.40]. Analysis of the ejection fraction, measured by echo (%), revealed that animals that exercised before myocardial infarction exhibited higher and statistically significant measures, compared with sedentary animals 8.77 [3.87,13.66]. We conclude that exercise performed prior to experimental myocardial infarction confers cardiac benefits to animals.

Lumbar herniated disc treatment with percutaneous hydrodiscectomy

SUMMARY Lumbar herniated disc are common manifestations of degenerative spine diseases, the main cause of radiated lower back pain. This guideline followed standard of a systematic review with recovery of evidence based on the movement of evidence-based medicine. We used the structured method for formulating the question synthesized by the acronym p.I.C.O., In which the p corresponds to the lumbar herniated disc, i to the treatment intervention with percutaneous hydrodiscectomy, c comparing with other treatment modalities, o the outcome of clinical evolution and complications. From the structured question, we identify the descriptors which constituted the evidence search base in the medline-pubmed databases (636 papers) and therefore, after the eligibility criteria (inclusion and exclusion), eight papers were selected to answer to clinical question. The details of the methodology and the results of this guideline are exposed in annex i.

RESUMO Hérnias discais lombares são manifestações comuns das doenças degenerativas da coluna, sendo a principal causa de dor lombar irradiada. Esta diretriz seguiu padrão de uma revisão sistemática com recuperação de evidências com base no movimento da Medicina Baseada em Evidências. Utilizamos a forma estruturada de formular a pergunta sintetizada pelo acrônimo P.I.C.O., em que o P corresponde à Hérnia de disco lombar, I à intervenção Tratamento com hidrodiscectomia percutânea, C comparando com Outras modalidades de tratamento, O de desfecho de Evolução clínica e complicações. A partir da pergunta estruturada, identificamos os descritores que constituíram a base da busca da evidência nas bases de dados Medline-PubMed (636 trabalhos) e, assim, após os critérios de elegibilidade (inclusão e exclusão), oito trabalhos foram selecionados para responder à dúvida clínica. Os detalhes da metodologia e dos resultados desta diretriz estão expostos no Anexo I.

Concentration of sulfated glycosaminoglycans in the mammary tissue of female rats with the aging and about hormonal influence.

It was to evaluate the concentration of sulfate glycosaminoglycans (GAG) in mammary tissue of the young and adult female rats and ovariectomized females rats after hormonal stimulation. For this purpose, 60 female rats were divided into six groups with 10 animals/each: nonovariectomized groups: G1 (5 months), and G2 (15 months) and ovariectomized groups: OG (vehicle); EG: (estradiol, 7 days of treatment), PG (progesterone acetate, 23 days of treatment) and EPG: (estradiol (7 days of treatment) and next progesterone acetate (23 days of treatment). Twenty-four hours after the last treatment, all animals were euthanized, the mammary tissue removed, processed for biochemical evaluation and quantification of the GAG. The comparison between groups showed that the concentration dermatan sulfate (DS) G1 was lower compared to G2, OG, EG (p < .05) and G2 was lower compared to OG (p < .05), and OG was higher compared to EG, GP, EPG (p < .05); and heparan sulfate (HS) G1 was higher compared to G2 (p < .05), and G2 was higher compared to OG, EP, PG and EPG (p < .05). These changes in the extracellular matrix might explain, at least in part, hormonal influence about sulfated glycosaminoglycans in response to physiological state/age, and in response to hormonal treatment in the mammary tissues.

Lumbar herniated disc treatment with percutaneous hydrodiscectomy.

Lumbar herniated disc are common manifestations of degenerative spine diseases, the main cause of radiated lower back pain. This guideline followed standard of a systematic review with recovery of evidence based on the movement of evidence-based medicine. We used the structured method for formulating the question synthesized by the acronym p.I.C.O., In which the p corresponds to the lumbar herniated disc, i to the treatment intervention with percutaneous hydrodiscectomy, c comparing with other treatment modalities, o the outcome of clinical evolution and complications. From the structured question, we identify the descriptors which constituted the evidence search base in the medline-pubmed databases (636 papers) and therefore, after the eligibility criteria (inclusion and exclusion), eight papers were selected to answer to clinical question. The details of the methodology and the results of this guideline are exposed in annex i.

Collagen concentration on the facial skin of postmenopausal women after topical treatment with estradiol and genistein: a randomized double-blind controlled trial.

OBJECTIVE: The objective of this study is to compare the effects of topical estrogen and genistein (a soy isoflavone) on the facial skin collagen of postmenopausal women not undergoing systemic hormonal therapy. METHODS: This is a prospective, double blind, randomized, controlled clinical trial. Volunteer women (N = 30) 45-55 year old from the Endocrine Gynecology sector of the Gynecology Department of the Federal University of São Paulo (UNIFESP). The Ethical Committee of the Federal University of São Paulo approved the study (report no. 386/2004; registration on ClinicalTrials.gov NCT01553773), were assigned to topical treatment with either estrogen or genistein for 24 weeks. We quantified and compared facial collagen concentration before and after each treatment by performing pre-auricular skin biopsies. RESULTS: Our data showed an increase in the amount of both type I and type III facial collagen by the end of both treatments. However, the outcomes of the estrogen GI (ER) group were superior to the genistein GII (GEN) group, with statistical significance p < 000.1 Conclusion: Treatment with topical estrogen is superior to genistein, but both have positive impacts on facial skin collagen. Nevertheless, it is still unclear whether prolonged use of genistein and other topical phytoestrogens could produce systemic effects and further research is needed to clarify this question.

Concentration of glycosaminoglycan in ovariectomized mice uterus after treatment with ovarian steroids.

The aim of this study was to evaluate the amount of non- and sulfated glycosaminoglycans in the ovariectomized mice uterus, after treatment with ovarian steroids. For this purpose, 50 adult female mice were divided into five groups with 10 animals/each: control group: CG (ovary intact), and ovariectomized groups: OG (vehicle), EG (estradiol), PG (progesterone) and EPG (estradiol combined to progesterone). The treatments started 30 days after ovariectomy. All the animals were treated for 50 consecutive days. These hormones were administered in a sterile oily solution via gavage. Twenty-four hours after the last treatment, all animals were euthanized, removing the uterine horn for biochemical analyses. To quantify, the hyaluronic acid (HA) used ELISA-like fluorometric assay, and the sulfated glycosaminoglycans (GAGs) used agarose gel electrophoresis. The amount of HA was significantly higher in the group treated with progesterone (PG) compared to the others groups (p < 0.05), and in the group treated with estradiol (EG), the amount of chondroitin/dermatan sulfate was significantly higher compared to the others groups (p < 0.05), and in the group treated with progesterone (PG), the amount of heparan sulfate was significantly lower compared to the others groups, except to control group (p < 0.05). Our results showed that the estroprogestative therapy after long time (50 days) profoundly affected the amount of glycosaminoglycans in uterine. These changes may be indicative of uterine pathology such as the development of tumor.

Effects of hyperprolactinemia on the tibial epiphyseal plate of mice treated with sex hormones.

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.

Melatonin influences on steroidogenic gene expression in the ovary of pinealectomized rats.

OBJECTIVE: To analyze the expression of genes related to steroidogenesis in the ovary of pinealectomized rats. DESIGN: Experimental research. SETTING: University research laboratory. ANIMAL(S): Thirty female adult rats. INTERVENTION(S): 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. MAIN OUTCOME MEASURE(S): Biologic molecular study followed by immunohistochemical analysis. RESULT(S): 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. CONCLUSION(S): Melatonin deprivation (pinealectomy) or administration may influence the ovarian CYP17A1 expression and steroidogenesis.

Effects of melatonin on histomorphology and on the expression of steroid receptors, VEGF, and PCNA in ovaries of pinealectomized female rats.

OBJECTIVE: To evaluate the effect of melatonin both on the ovaries of pinealectomized female rats through histomorphometric analysis and on steroid receptors, proliferating cell nuclear antigen (PCNA), and vascular endothelial growth factor (VEGF) expression. DESIGN: Experimental study. SETTING: Federal University of São Paulo, Brazil. ANIMAL(S): Forty female rats. INTERVENTION(S): Forty rats were divided equally into four groups: GI-vehicle without surgery; GII--surgery without removal of the pineal gland (sham); GIII--pinealectomized with vehicle; and GIV--pinealectomized with melatonin treatment. After treatment for 3 consecutive months, the animals were killed and their ovaries removed for analysis. MAIN OUTCOME MEASURE(S): Estrogen and progesterone receptors, histologic and immunohistochemical analysis. RESULT(S): The GIII samples presented signals of proliferation on ovarian surface epithelium and interstitial cells as well as high expressions of PCNA and VEGF in those structures compared with GI, GII, and GIV. Also, the levels of progesterone receptor (fmol/g) in ovaries of GIII (250.6 ± 32.4) were significantly lower than in those of GI (429.0 ± 23,8), GII (442.3 ± 30.2), and GIV (564.1 ± 78.7). The levels of progesterone in GIII were superior to those in GI, GII, and GIV. CONCLUSION(S): Our findings suggest that melatonin may attenuate proliferation in ovarian structures and increase the number of luteal bodies as well as the levels of progesterone receptor.

Hyperbaric oxygen therapy protects the liver from apoptosis caused by ischemia-reperfusion injury in rats.

PURPOSE: : The present paper aimed to investigate the role of hyperbaric oxygen treatment (HBO) and the apoptosis in rat liver ischemia-reperfusion injury (IRI). METHODS: : Thirty-seven male Wistar rats were subjected to 30 minutes of hepatic ischemia and 30 minutes of reperfusion and randomly distributed into six groups: G-I/R (n = 8), control without HBO; G-HBO/I (n = 8), HBO only during the ischemia period; G-HBO/R (n = 8), HBO only during the reperfusion period; G-HBO-I/R (n = 8), HBO during both the ischemia and reperfusion periods; G-Sh (n = 3), HBO without ischemia or reperfusion as sham group; G-C (n = 2) for control of current apoptosis expression on the normal liver tissue. HBO was carried out using a transparent, cylindrical acrylic chamber with a pressure of 2.0 ATA. Hepatic samples were stained for caspase-3 cleavage. RESULTS: : Apoptotic cells were identified in all groups. In the hepatic specimens of animals HBO-treated during ischemia (GHBO-I), there was a significant decrease (P < 0.001) in the number of cells undergoing apoptosis (1.62 +/- 0.91). The apoptotic index showed no significant difference in the animals HBO-treated during ischemia/reperfusion (5.75 +/- 1.28) compared with the G-I/R (3.5 +/- 0.75), which had no HBO treatment. The apoptosis index (11.25 +/- 1.90) was significantly higher (P < 0.01) in HBO-treated animals during the reperfusion period when compared with any of the other groups. CONCLUSION: : A favorable effect was obtained when hyperbaric oxygen was administered early during ischemia. The hyperbaric oxygen in later periods of reperfusion was associated with a more severe apoptosis index. (c) 2009 Wiley-Liss, Inc. Microsurgery 2009.

[Melatonin effects on the female genital system: a brief review]. / Efeitos da melatonina no sistema genital feminino: breve revisão.

Melatonin is secreted by the pineal gland and this is linked to the day/night cycle. It is an antioxidant and plays a fundamental role in the regulation of the jet-lag stage, in several physiological reactions and in control of the biologic rhythm. Human melatonin has an important influence on the female genital system. In fact, melatonin may influence production and action of steroids, modifying cellular signalization on the target tissue. There are many evidences that the melatonin therapy may be interfering with neoplasia development, mainly of the estrogen-dependent tumor. This paper aims to analyze the actions of melatonin on the neuroendocrine, immunological and cardiovascular systems, as well as on the reproductive function.

Efeitos da melatonina no sistema genital feminino: breve revisão / Melatonin effects on the female genital system: a brief review

A melatonina é um hormônio produzido pela glândula pineal, cuja secreção está diretamente relacionada ao ciclo claro-escuro. É um poderoso antioxidante e tem papel fundamental na regulação do estado sono/vigília, do ritmo de vários processos fisiológicos, participando do controle do relógio biológico, inclusive nos seres humanos. Ressalta-se que há evidências da sua ação no sistema genital feminino, influenciando a função ovariana e a fertilidade. De fato, este hormônio interage com esteróides sexuais, como o estrogênio, modificando a sinalização celular e a resposta no tecido alvo. Estudos clínicos sugerem que o tratamento com a melatonina interviria com a evolução de neoplasia-dependente do estrogênio. O objetivo dessa revisão é analisar as principais ações da melatonina no sistema neuroendócrino, no ciclo sono-vigília, no sistema imunológico, no sistema cardiovascular, bem como no sistema reprodutor.

Melatonin is secreted by the pineal gland and this is linked to the day/night cycle. It is an antioxidant and plays a fundamental role in the regulation of the jet-lag stage, in several physiological reactions and in control of the biologic rhythm. Human melatonin has an important influence on the female genital system. In fact, melatonin may influence production and action of steroids, modifying cellular signalization on the target tissue. There are many evidences that the melatonin therapy may be interfering with neoplasia development, mainly of the estrogen-dependent tumor. This paper aims to analyze the actions of melatonin on the neuroendocrine, immunological and cardiovascular systems, as well as on the reproductive function.