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Sample records for rat ovary interactions

  1. Cryopreservation and orthotopic transplantation of rat ovaries.

    PubMed

    Dorsch, Martina; Wedekind, Dirk

    2010-01-01

    The number of rat strains increased considerably in the last decade and will increase continuously during the next years. This requires enough space for maintaining vital strains and techniques for cryobanking, which can be applied not only in specialised rat resource centres but also in regular animal houses. Here we describe an easy and fast method for the cryopreservation and transplantation of frozen-thawed ovaries of the rat. With dimethyl sulfoxide as cryoprotectant rat ovaries can be stored at -196 degrees C for unlimited time. For revitalisation thawed ovaries have to be orthotopically transplanted into appropriate ovarectomised recipients. Reestablishment of the reproductive cycle in the recipients can be confirmed by vaginal cytology shortly after transplantation. The recipients are able to produce 2-3 litters after mating with males of an appropriate strain. Cyropreservation of ovaries thus can be considered a reliable method to preserve scientifically and economically important stocks and strains of rats that are currently not required.

  2. Periovulatory leukocyte infiltration in the rat ovary.

    PubMed

    Oakley, Oliver R; Kim, HeyYoung; El-Amouri, Ismail; Lin, Po-Ching Patrick; Cho, Jongki; Bani-Ahmad, Mohammad; Ko, Chemyong

    2010-09-01

    Ovulation is preceded by intraovarian inflammatory reactions that occur in response to the preovulatory gonadotropin surge. As a main inflammatory event, leukocytes infiltrate the ovary and release proteolytic enzymes that degrade the extracellular matrix weakening the follicular wall, a required step for follicle rupture. This study aimed to quantitatively measure the infiltrating leukocytes, determine their cell types, and localize infiltration sites in the periovulatory rat ovary. Cycling adult and gonadotropin-stimulated immature rats were used as animal models. Ovaries were collected at five different stages of estrous cycle in the adult rats (diestrus, 1700 h; proestrus, 1500 h; proestrus, 2400 h; estrus, 0600 h; and metestrus, 1700 h) and at five different time points after superovulation induction in the immature rats (pregnant mare's serum gonadotrophin, 0 h; pregnant mare's serum gonadotrophin, 48 h; human chorionic gonadotropin, 6 h; human chorionic gonadotropin, 12 h; and human chorionic gonadotropin, 24 h). The ovaries were either dissociated into a single cell suspension for flow cytometric analysis or fixed for immunohistochemical localization of the leukocytes. Similar numbers of leukocytes were seen throughout the estrous cycle (approximately 500,000/ovary), except proestrus 2400 when 2-fold higher numbers of leukocytes were found (approximately 1.1 million/ovary). A similar trend of periovulatory rise of leukocyte numbers was seen in the superovulation-induced immature rat model, recapitulating a dramatic increase in leukocyte numbers upon gonadotropin stimulation. Both macrophage/granulocytes and lymphocytes were among the infiltrating leukocytes and were localized in the theca and interstitial tissues, where platelet-endothelial cell adhesion molecule-1 and intercellular adhesion molecule-1 may play roles in the transmigration of leukocytes, because their expressions correlates spatiotemporally with the infiltrating leukocytes. In addition, a

  3. Effects of talc on the rat ovary.

    PubMed Central

    Hamilton, T. C.; Fox, H.; Buckley, C. H.; Henderson, W. J.; Griffiths, K.

    1984-01-01

    Exposure of rat ovaries to talc was accomplished by intrabursal injection. As early as 1 and up to 18 months after treatment, the ovaries and associated tissue were cystic in appearance; these changes were the result of bursal distention. Histologically the ovarian tissue was decreased in amount and spread as a remnant on the inner wall of the bursa. In four to 10 treated animals but in no controls, focal areas of papillary change were noted in the surface epithelium of the ovary. Polarized light and electron microscope microanalysis confirmed the presence of talc in the surface epithelium, ovarian cortex, and connective tissue matrix of the bursa. Although the changes in the ovarian surface may be related to direct effects of talc exposure, it is postulated that these changes might also be related to constant exposure to the high concentrations of steroid hormones which have undoubtedly accumulated in the intrabursal space. Images Fig. 1 Fig. 2 Fig. 3 PMID:6696826

  4. Leptin regulates gonadotropins and steroid receptors in the rats ovary.

    PubMed

    Silveira Cavalcante, Fernanda; Aiceles, Verónica; da Fonte Ramos, Cristiane

    2013-01-01

    The leptin hormone is important to satiety and an important link between the nutritional status and reproductive processes. Owing to the contradictory effects of leptin on the ovary and the failure to clarify the precise mechanism by which leptin affects the ovary, our aim was to contribute to evaluation if leptin can directly regulate the gene expression of leptin itself and its receptors, and the expression of several genes related to the ovary function by a model of tissue culture. Ovaries from Wistar dams were used at 90 days of age and were submitted to medium with presence and absence of leptin. The results can demonstrate that leptin regulates gonadotropins and steroid receptors, which could suggest that the ovarian leptin role could be secondary to the changes in these receptors expression in rats.

  5. CONFOCAL LASER SCANNING MICROSCOPY OF APOPTOSIS IN WHOLE MOUSE AND RAT OVARIES

    EPA Science Inventory

    Confocal Laser Scanning Microscopy of Apoptosis in Whole Mouse and Rat Ovaries. Robert M. Zucker Susan C. Jeffay and Sally D. Perreault Reproductive Toxicology Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research ...

  6. CONFOCAL LASER SCANNING MICROSCOPY OF APOPTOSIS IN WHOLE MOUSE AND RAT OVARIES

    EPA Science Inventory

    Confocal Laser Scanning Microscopy of Apoptosis in Whole Mouse and Rat Ovaries. Robert M. Zucker Susan C. Jeffay and Sally D. Perreault Reproductive Toxicology Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research ...

  7. Expression of cystic fibrosis transmembrane conductance regulator in rat ovary.

    PubMed

    Jin, Lei; Tang, Ruiling

    2008-10-01

    The protein expression of cystic fibrosis transmembrane conductance regulator (CFTR), a cAMP-activated Cl(-) channel, in ovarian stimulated premature female rat ovary during a cycle of follicle development and corpus luteum formation was investigated. Animals were injected with 10 U pregnant Mare's serum gonadotropin (PMSG) and subsequently 10 U hCG 48 h later. Time-dependent immunohistochemistry and Western blotting experiments were performed before and 24, 48, 72 h after hCG treatment. The immunohistochemistry revealed that administration of PMSG stimulated the CFTR expression in thecal cell layer and granulosa cell layer of mature follicles 48 h post injection, coincident with the PMSG-induced peak in follicular estradiol. However, the expression of CFTR in the granulose lutein cell layer and thecal lutein cell layer was time-dependently reduced following hCG injection, in accordance with the gradually increased progestogen level during luteum corpus formation. Western blotting analysis demonstrated that rat ovarian tissue expressed the special CFTR band at 170 kD. It is concluded that cAMP-dependent Cl(-) channels are involved in regulation of follicle development and luteum formation.

  8. Regulation of 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4 isomerase expression and activity in the hypophysectomized rat ovary: Interactions between the stimulatory effect of human chorionic gonadotropin and the luteolytic effect of prolactin

    SciTech Connect

    Martel, C.; Labrie, C.; Dupont, E.; Couet, J.; Trudel, C.; Rheaume, E.; Simard, J.; Luu-The, V.; Pelletier, G.; Labrie, F. )

    1990-12-01

    The enzyme 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4 isomerase (3 beta-HSD) catalyzes an obligatory step in the conversion of pregnenolone and other 5-ene-3 beta-hydroxysteroids into progesterone as well as precursors of all androgens and estrogens in the ovary. Since 3 beta-HSD is likely to be an important target for regulation by pituitary hormones, we have studied the effect of chronic treatment with LH (hCG), FSH, and PRL on ovarian 3 beta-HSD expression and activity in hypophysectomized adult female rats. Human CG (hCG) (10 IU, twice a day (bid)), ovine FSH (0.5 microgram, bid), and ovine PRL (1 mg, bid) were administered, singly or in combination, for a period of 10 days starting 15 days after hypophysectomy. In hypophysectomized rats, PRL exerted a potent inhibitory effect on all the parameters studied. In fact, PRL caused a 81% decrease in ovarian 3 beta-HSD mRNA content accompanied by a similar decrease in 3 beta-HSD activity and protein levels. In addition, ovarian weight decreased by 40% whereas serum progesterone fell dramatically from 1.92 nmol/liter to undetectable levels after treatment with PRL. Whereas hCG alone had only slight stimulatory effects on 3 beta-HSD mRNA, protein content and activity levels, treatment with the gonadotropin partially or completely reversed the potent inhibitory effects of oPRL on all the parameters measured. FSH, on the other hand, had no significant effect on 3 beta-HSD expression and activity. In situ hybridization experiments using the 35S-labeled rat ovary 3 beta-HSD cDNA probe show that the inhibitory effect of PRL is exerted primarily on luteal cell 3 beta-HSD expression and activity. On the other hand, it can be seen that hCG stimulates 3 beta-HSD mRNA accumulation in interstitial cells.

  9. Histological assessment of ovaries and uterus of rats subjected to nandrolone decanoate treatment.

    PubMed

    Gerez, Juliana Rubira; Frei, Fernando; Camargo, Isabel Cristina Cherici

    2005-07-01

    This study aimed to analyze the effects of nandrolone decanoate on the ovaries and uterus of adult females rats. This drug was administered intraperitoneally, at one, two and three doses of 3 mg nandrolone decanoate/kg of body weight, respectively, in the first, second and third week of treatment. The females of the control group received a physiological solution. The rats treated with nandrolone decanoate showed estral acyclicity and there was destruction of follicular units and an absence of corpus luteum in the ovaries. In the uterus, the drug promoted morphological alterations, characterized by vacuolated epithelium and endometrial stroma fibrosis. Ovary, uterus and pituitary weights were not affected by the steroid treatment. Nandrolone decanoate affects the sexual cycle and promotes histological alterations in the ovaries and uterus of adult female rats.

  10. Hyberbaric oxygen increases atresia in normal & steroid induced PCO rat ovaries

    PubMed Central

    2012-01-01

    Background In this study, we investigated the effect of hyperbaric oxygen therapy (HBOT) on the morphology of estradiol valerate (EV) induced polycystic ovary (PCO) to find a new treatment modality for improvement of PCO. Methods The rats were divided into four groups. Group1, control; group 2, PCO group; group 3, PCO with HBOT group and group 4, normal ovary with HBOT. PCO was induced by a single intramuscular injection of 4 mg EV in adult cycling rats. Other rats with normal ovaries had oil injection as placebo. HBOT was applied to third and fourth groups for six weeks. Histopathologic evaluation of ovaries of all groups were performed & compared. Results Six weeks of HBOT was resulted in increase in follicular atresia, decrease in the number of primary, secondary, tertiary follicles and decrease in the number of fresh corpus luteum in normal rat ovary. HBOT on polycystic rat ovary, resulted in significant increase in atretic follicles which were already present. Conclusions HBOT of six weeks itself, changed ovarian morphology in favor of atresia both in PCO group and control group. This result of aggravated follicular atresia after HBOT on EV induced PCO may be due to long-term exposure in our protocol which with this state seems to be inapplicable in the improvement of PCO morphology. PMID:22309835

  11. Lateralization of the connections of the ovary to the celiac ganglia in juvenile rats

    PubMed Central

    Morán, Carolina; Zarate, Fabiola; Morán, José Luis; Handal, Anabella; Domínguez, Roberto

    2009-01-01

    During the development of the female rat, a maturing process of the factors that regulate the functioning of the ovaries takes place, resulting in different responses according to the age of the animal. Studies show that peripheral innervation is one relevant factor involved. In the present study we analyzed the anatomical relationship between the neurons in the celiac-superior mesenteric ganglia (CSMG), and the right or left ovary in 24 or 28 days old female pre-pubertal rats. The participation of the superior ovarian nerve (SON) in the communication between the CSMG and the ovaries was analyzed in animals with unilateral section of the SON, previous to injecting true blue (TB) into the ovarian bursa. The animals were killed seven days after treatment. TB stained neurons were quantified at the superior mesenteric-celiac ganglia. The number of labeled neurons in the CSMG of rats treated at 28 days of age was significantly higher than those treated on day 24. At age 24 days, injecting TB into the right ovary resulted in neuron stains on both sides of the celiac ganglia; whereas, injecting the left side the stains were exclusively ipsilateral. Such asymmetry was not observed when the rats were treated at age of 28 days. In younger rats, sectioning the left SON resulted in significantly lower number of stained neurons in the left ganglia while sectioning the right SON did not modify the number of stained neurons. When sectioning of the SON was performed to 28 days old rats, no staining was observed. Present results show that the number and connectivity of post-ganglionic neurons of the CSMG connected to the ovary of juvenile female rats change as the animal mature; that the SON plays a role in this communication process as puberty approaches; and that this maturing process is different for the right or the left ovary. PMID:19460167

  12. Afferent fibers involved in the bradykinin-induced cardiovascular reflexes from the ovary in rats.

    PubMed

    Uchida, Sae; Kagitani, Fusako; Hotta, Harumi

    2015-12-01

    Bleeding or rupture of the ovary often accompanies ovarian cysts and causes severe pain and autonomic responses such as hypotension. It would be expected that ovarian afferents contribute to cardiovascular responses induced by ovarian failure. The present study examined cardiovascular responses to noxious chemical stimulation of the ovary by bradykinin, an algesic substance released by tissue damage, and explored the role of ovarian afferents in the ovarian-cardiovascular responses in anesthetized rats. Non-pregnant adult rats were anesthetized with pentobarbital and artificially ventilated. The carotid artery was cannulated to monitor blood pressure and heart rate. Noxious chemical stimulation was achieved by applying a small piece of cotton soaked with bradykinin to the surface of the ovary for 30s. Application of bradykinin (10(-4) M) to the ovary decreased heart rate and blood pressure. These cardiovascular responses were not significantly influenced by severance of the vagal nerves or the superior ovarian nerve, but were abolished by severance of the ovarian nerve plexus (ONP). Application of bradykinin (10(-4) M) to the ovary evoked afferent activity of the ONP both in vivo and in vitro preparations. These results indicate that the decreases in heart rate and blood pressure following chemical noxious stimulation of the ovary with bradykinin are reflex responses, whose afferent nerve pathway is mainly through afferent fibers in the ONP.

  13. Metformin Ameliorates Uterine Defects in a Rat Model of Polycystic Ovary Syndrome.

    PubMed

    Zhang, Yuehui; Hu, Min; Meng, Fanci; Sun, Xiaoyan; Xu, Hongfei; Zhang, Jiao; Cui, Peng; Morina, Njomeza; Li, Xin; Li, Wei; Wu, Xiao-Ke; Brännström, Mats; Shao, Ruijin; Billig, Håkan

    2017-03-18

    Adult rats treated concomitantly with insulin and human chorionic gonadotropin exhibit endocrine, metabolic, and reproductive abnormalities that are very similar to those observed in polycystic ovary syndrome (PCOS) patients. In this study, we used this rat model to assess the effects of metformin on PCOS-related uterine dysfunction. In addition to reducing androgen levels, improving insulin sensitivity, and correcting the reproductive cycle, metformin treatment induced morphological changes in the PCOS-like uterus. At the molecular and cellular levels, metformin normalized the androgen receptor-mediated transcriptional program and restored epithelial-stromal interactions. In contrast to glucose transport, uterine inflammatory gene expression was suppressed through the PI3K-Akt-NFκB network, but without affecting apoptosis. These effects appeared to be independent of AMPK subunit and autophagy-related protein regulation. We found that when metformin treatment partially restored implantation, several implantation-related genes were normalized in the PCOS-like rat uterus. These results improve our understanding of how metformin rescues the disruption of the implantation process due to the uterine defects that result from hyperandrogenism and insulin resistance. Our data provide insights into the molecular and functional clues that might help explain, at least in part, the potential therapeutic options of metformin in PCOS patients with uterine dysfunction.

  14. Effects of jnk inhibitor on inflammation and fibrosis in the ovary tissue of a rat model of polycystic ovary syndrome

    PubMed Central

    Bulut, Gulay; Kurdoglu, Zehra; Dönmez, Yeliz Bozdemir; Kurdoglu, Mertihan; Erten, Remzi

    2015-01-01

    Objective: In our study, we aimed to investigate the effects of Jun N-terminal kinase inhibitor (SP600125) on fibrosis and inflammation in rats with polycystic ovary syndrome (PCOS). Method: 50 Wistar-albino rats were divided into five groups (n=10 each): control group, sham group, PCOS group, SP600125+ PCOS group and SP600125 group. In the estradiol valerate (EV)-treated group in which PCOS was injected with a single 4 mg/kg i.p. of EV in 0.2 ml sesame oil and the rats were sacrificed on day 60. The estradiol valerate (EV)-treated + SP600125-treated group was injected with a single 4 mg/kg i.p. of EV in 0.2 ml sesame oil. As of day 60, the treatment group was additionally given 15 mg/kg i.p. of SP600125 once daily for 4 consecutive days and the rats were sacrificed on day 65. Histopathological findings (ovarian morphology, edema, inflammatory cell infiltration, vascular congestion and hyperemia) and collagen type IV immunoexpression were assessed. Results: The SP600125+ PCOS group showed a significant level of improvement in ovarian follicle morphology, edema, inflammatory infiltrate, vascular congestion and hyperemia as compared with the PCOS group. Furthermore, collagen type IV immunoexpression showed a significant reduction in staining intensity on the theca cell layer and ovary stroma as compared to the PCOS group. Conclusion: This study demonstrates the therapeutic effect of SP600125 in the prevention of PCOS in an experimental model. PMID:26464620

  15. Unilateral or bilateral vagotomy induces ovulation in both ovaries of rats with polycystic ovarian syndrome

    PubMed Central

    2013-01-01

    Background Injecting estradiol valerate (EV) to pre-pubertal or adult female rat results in effects similar to those observed in women with polycystic ovarian syndrome (PCOS). One of the mechanisms involved in PCOS development is the hyperactivity of the sympathetic nervous system. In EV-induced PCOS rats, the unilateral sectioning of the superior ovarian nerve (SON) restores ovulation of the innervated ovary. This suggests that, in addition to the sympathetic innervation, other neural mechanisms are involved in the development/maintenance of PCOS. The aims of present study were analyze if the vagus nerve is one of the neural pathways participating in PCOS development. Methods Ten-day old rats were injected with EV dissolved in corn oil. At 24-days of age sham-surgery, unilateral, or bilateral sectioning of the vagus nerve (vagotomy) was performed on these rats. The animals were sacrificed at 90–92 days of age, when they presented vaginal estrous preceded by a pro-estrus smear. Results In EV-induced PCOS rats, unilateral or bilateral vagotomy restored ovulation in both ovaries. Follicle-stimulating hormone (FSH) levels in PCOS rats with unilateral or bilateral vagotomy were lower than in control rats. Conclusions This result suggests that in EV-induced PCOS rats the vagus nerve is a neural pathway participating in maintaining PCOS. The vagus nerve innervates the ovaries directly and indirectly through its synapsis in the celiac-superior-mesenteric ganglion, where the somas of neurons originating in the SON are located. Then, it is possible that vagotomy effects in EV-induced PCOS rats may be explained as a lack of communication between the central nervous system and the ovaries. PMID:23866168

  16. A neuroimmune regulation at peripheral level on the steroidogenesis of polycystic ovary in rats.

    PubMed

    Forneris, M L; Aguado, L I; Oliveros, L B

    2003-09-01

    It is known that noradrenergic sympathetic nerve fibers connect the ovary and the spleen from the celiac ganglion. The modulation of the ovarian steroidogenesis in rats with polycystic ovary (PCO) by secretions of culture splenocytes from control (non PCO), PCO and PCO rats with superior ovarian nerve transection (PCO+SON-t) is investigated. Splenocytes from PCO rats increased progesterone (P) and decreasing estradiol (E) and androstenedione (A) release, a steroidogenic response different from that obtained with splenocytes of control rats. PCO also decreased the number of splenocyte beta-adrenergic receptors (betaR). SON transection reverted the effect of PCO on splenocytes betaR numbers and secretions of these splenocytes also reverted the stimulatory effect of PCO on P release, while norepinephrine (NE) treatment to PCO+SON-t splenocytes decreased their betaR number and their secretions restored the stimulation on progesterone release. Inversely, PCO+SON-t splenocyte secretions intensified the inhibition in estradiol with no effect on A. Treatment of PCO+SON-t splenocytes with NE or neuropeptide Y partially reverted the effects of PCO and SON-t The P and E-A response of PCO ovary might be differentially regulated by the splenocyte secretions through the neural connection involving ovary, SON, celiac ganglion and spleen and the neurotransmitter NE.

  17. Postnatal Ovary Development in the Rat: Morphologic Study and Correlation of Morphology to Neuroendocrine Parameters

    PubMed Central

    Picut, Catherine A.; Dixon, Darlene; Simons, Michelle L.; Stump, Donald G.; Parker, George A.; Remick, Amera K.

    2014-01-01

    Histopathologic examination of the immature ovary is a required end point on juvenile toxicity studies and female pubertal and thyroid function assays. To aid in this evaluation and interpretation of the immature ovary, the characteristic histologic features of rat ovary through the developmental periods are described. These histologic features are correlated with published changes in neuroendocrine profiles as the hypothalamic–pituitary–gonadal axis matures. During the neonatal stage (postnatal day [PND] 0–7), ovarian follicle development is independent of pituitary gonadotropins (luteinizing hormone [LH] or follicle-stimulating hormone [FSH]), and follicles remain preantral. Antral development of “atypical” follicles occurs in the early infantile period (PND 8–14) when the ovary becomes responsive to pituitary gonadotropins. In the late infantile period (PND 15–20), the zona pellucida appears, the hilus forms, and antral follicles mature by losing their “atypical” appearance. The juvenile stage (PND 21–32) is the stage when atresia of medullary follicles occurs corresponding to a nadir in FSH levels. In the peripubertal period (PND 33–37), atresia subsides as FSH levels rebound, and LH begins its bimodal surge pattern leading to ovulation. This report will provide pathologists with baseline morphologic and endocrinologic information to aid in identification and interpretation of xenobiotic effects in the ovary of the prepubertal rat. PMID:25107574

  18. Postnatal ovary development in the rat: morphologic study and correlation of morphology to neuroendocrine parameters.

    PubMed

    Picut, Catherine A; Dixon, Darlene; Simons, Michelle L; Stump, Donald G; Parker, George A; Remick, Amera K

    2015-04-01

    Histopathologic examination of the immature ovary is a required end point on juvenile toxicity studies and female pubertal and thyroid function assays. To aid in this evaluation and interpretation of the immature ovary, the characteristic histologic features of rat ovary through the developmental periods are described. These histologic features are correlated with published changes in neuroendocrine profiles as the hypothalamic-pituitary-gonadal axis matures. During the neonatal stage (postnatal day [PND] 0-7), ovarian follicle development is independent of pituitary gonadotropins (luteinizing hormone [LH] or follicle-stimulating hormone [FSH]), and follicles remain preantral. Antral development of "atypical" follicles occurs in the early infantile period (PND 8-14) when the ovary becomes responsive to pituitary gonadotropins. In the late infantile period (PND 15-20), the zona pellucida appears, the hilus forms, and antral follicles mature by losing their "atypical" appearance. The juvenile stage (PND 21-32) is the stage when atresia of medullary follicles occurs corresponding to a nadir in FSH levels. In the peripubertal period (PND 33-37), atresia subsides as FSH levels rebound, and LH begins its bimodal surge pattern leading to ovulation. This report will provide pathologists with baseline morphologic and endocrinologic information to aid in identification and interpretation of xenobiotic effects in the ovary of the prepubertal rat.

  19. The effects of unilateral varicose ovarian vein on antioxidant capacity and oocyte quality in rat ovary

    PubMed Central

    Kehinde, Babatunde Adebayo; Abolhassani, Farid; Yazdekhasti, Hossein; Abbasi, Niloufar; Heydari, Leyla; Daneshi, Erfan; Rajabi, Zahra; Hamada, Alaa; Agarwal, Ashok; Abbasi, Mehdi

    2016-01-01

    Objective(s): Several researchers have reported the relationship between infertility in male and varicocele for so many years but the implication of varicocele in female patients is remains elusive. Here, we aim to examine the effects of unilateral varicose ovarian vein on antioxidant capacity and oocyte quality of rat ovary after the experimental creation of varicocele in female rats. Materials and Methods: In this study, thirty adult female albino rats were divided into three equal groups: Group 1 as the control group has 10 rats, Group 2 as the sham group has 10 rats and they underwent a sham operation and finally Group 3 has the varicocele group has 10 rats. Antioxidant assays for superoxide dismutase, glutathione peroxidase and catalase were performed using specific assay kits and gene expression for Bax, Bmp-15, Hsp-27 and Gdf-9 was done via real time PCR. Results: The adverse effects of the experimentally induced varicocele were reported and recorded on the left ovary compared to the right sided ovary (no varicocele induction) in the varicocele group. Real time PCR data shows that the expression of Gdf-9, Hsp-27 and Bmp-15 genes were all significantly reduced at p≤ 0.05. Conclusion: The results of this study show that reduced gene expression of Bmp-15, Gdf-9 and Hsp-27, increased gene expression of bax and an imbalance between pro-oxidant/antioxidant ratio are few of the several mechanisms by which varicocele may lead to infertility in female. PMID:27746868

  20. Phosphodiesterases in the rat ovary: effect of cAMP in primordial follicles.

    PubMed

    Petersen, Tonny Studsgaard; Stahlhut, Martin; Andersen, Claus Yding

    2015-07-01

    Phosphodiesterases (PDEs) are important regulators of the intracellular cAMP concentration, which is a central second messenger that affects a multitude of intracellular functions. In the ovaries, cAMP exerts diverse functions, including regulation of ovulation and it has been suggested that augmented cAMP levels stimulate primordial follicle growth. The present study examined the gene expression, enzyme activity and immunolocalization of the different cAMP hydrolysing PDEs families in the rat ovary. Further, the effect of PDE4 inhibition on primordial follicle activation in cultured neonatal rat ovaries was also evaluated. We found varied expression of all eight families in the ovary with Pde7b and Pde8a having the highest expression each accounting for more than 20% of the total PDE mRNA. PDE4 accounted for 15-26% of the total PDE activity. Immunoreactive PDE11A was found in the oocytes and PDE2A in the corpora lutea. Incubating neonatal rat ovaries with PDE4 inhibitors did not increase primordial follicle activation or change the expression of the developing follicle markers Gdf9, Amh, Inha, the proliferation marker Mki67 or the primordial follicle marker Tmeff2. In addition, the cAMP analogue 8-bromo-cAMP did not increase AKT1 or FOXO3A phosphorylation associated with follicle activation or increase the expression of Kitlg known to be associated with follicle differentiation but did increase the Tmeff2, Mki67 and Inha expression in a dose-dependent manner. In conclusion, this study shows that both Pde7b and Pde8a are highly expressed in the rodent ovary and that PDE4 inhibition does not cause an increase in primordial follicle activation. © 2015 Society for Reproduction and Fertility.

  1. Effects of sub-chronic aluminum chloride exposure on rat ovaries.

    PubMed

    Fu, Y; Jia, F B; Wang, J; Song, M; Liu, S M; Li, Y F; Liu, S Z; Bu, Q W

    2014-03-28

    This experiment investigated the effects of sub-chronic aluminum chloride (AlCl3) exposure on rat ovaries. Eighty female Wistar (5weeks old) rats, weighed 110-120g, were randomly divided into four treatment groups: control group (CG), low-dose group (LG, 64mg/kg BW AlCl3), mid-dose group (MG, 128mg/kg BW AlCl3) and high-dose group (HG, 256mg/kg BW AlCl3). The AlCl3 was administered in drinking water for 120days. The ovarian ultrastructure was observed. The activities of acid phosphatase (ACP), alkaline phosphatase (ALP), succinate dehydrogenase (SDH), Na(+)-K(+)-ATPase, Mg(2+)-ATPase and Ca(2+)-ATPase, the contents of Fe, Cu and Zn, and the protein expression of follicle-stimulating hormone receptor (FSHR) and luteinizing hormone receptor (LHR) in the ovary were determined. The results showed that the structure of the ovary was disrupted, the activities of ALP, ACP, SDH, Na(+)-K(+)-ATPase, Mg(2+)-ATPase and Ca(2+)-ATPase, the contents of Zn, Fe and the protein expression of FSHR and LHR were lowered, and the content of Cu was increased in AlCl3-treated rats than those in control. The results indicate that sub-chronic AlCl3 exposure caused the damage of the ovarian structure, the disturbed metabolism of Fe, Zn and Cu and the decreased activities of Na(+)-K(+)-ATPase, Mg(2+)-ATPase and Ca(2+)-ATPase in the ovary, which could result in suppressed energy supply in the ovary. A combination of suppression of energy supply and reduction of expression of FSHR and LHR could inhibit ovulation and corpus luteum development, leading to infertility in female rats. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Role of macrophage secretions on rat polycystic ovary: its effect on apoptosis.

    PubMed

    Figueroa, Florencia; Motta, Alicia; Acosta, Mariano; Mohamed, Fabian; Oliveros, Liliana; Forneris, Myriam

    2015-11-01

    Polycystic ovarian syndrome is the most common endocrine disorder among women of reproductive age. Little is known about its etiology, although the evidence suggests an intrinsic ovarian abnormality in which endocrine, metabolic, neural and immune factors would be involved. In this work, the effects of macrophage (MO) secretion on ovarian apoptosis in a polycystic ovary syndrome rat model (PCO rat) induced by estradiol valerate are studied. Spleen MO secretions were used to stimulate ovaries and ovarian interstitial and granulosa cells from both PCO and control rats. Ovarian hormones and prostaglandin E2 (PGE2) were measured by RIA; ovarian mRNA levels of Bax, Bcl2 and NFkB by RT-PCR; and ovarian inducible nitric oxide synthase (iNOS) by western blot. The number of apoptotic cells was evaluated by TUNEL. In the PCO ovary, the MO secretions from PCO rats increased the Bax and NFkB mRNA expressions and increased TUNEL staining in both granulosa and theca cells. In addition, the PCO MO secretions produced a decrease of nitric oxide release, iNOS protein level and PGE2 content in the PCO ovary, and it also induced an increase of androstenedione production by PCO interstitial cells, in comparison with control MO secretions. Considering these results and knowing that testosterone stimulates tumour necrosis factor-α production by PCO MO modifying ovarian response by increasing androstenedione, it is reasonable to suggest that the increase of androgens stimulated in ovarian cells by PCO MO secretions could in turn stimulate the cytokine production from MO, thus maintaining an apoptotic vicious cycle in the PCO ovary. © 2015 Society for Reproduction and Fertility.

  3. Inhibition of serotonin reuptake in the prepubertal rat ovary by fluoxetine and effects on ovarian functions.

    PubMed

    Romero-Reyes, Jessica; Cárdenas, Mario; Damián-Matsumura, Pablo; Domínguez, Roberto; Ayala, María Elena

    2016-01-01

    Fluoxetine (FLX), a selective serotonin reuptake inhibitor is an antidepressant in the treatment of mood disorders. Its impact on reproductive processes is incompletely known. The present study analyzed the reproductive effects of FLX in prepubertal female rats. Two experiments were conducted. First (acute administration), 30-day-old female rats were injected intraperitoneally with 5mg/kg of fluoxetine-hydrochloride, and were terminated 24, 48 or 72h after the treatment. Second (subchronic administration), FLX was injected on days 30-33 of age, and the animals were terminated the day of first estrus. In acute treatment estradiol concentration increased to 72h. In subchronic treatment increased serotonin concentration in ovaries and decreased the number of ova shed. An increase in number of atretic follicles and oocyte fragmentation was observed in these animals. The results suggest that FLX acts on the ovary or hypothalamus-pituitary axis resulting in modifications of the follicular development and ovulation.

  4. The celiac ganglion modulates LH-induced inhibition of androstenedione release in late pregnant rat ovaries

    PubMed Central

    Casais, Marilina; Delgado, Silvia M; Sosa, Zulema; Telleria, Carlos M; Rastrilla, Ana M

    2006-01-01

    Background Although the control of ovarian production of steroid hormones is mainly of endocrine nature, there is increasing evidence that the nervous system also influences ovarian steroidogenic output. The purpose of this work was to study whether the celiac ganglion modulates, via the superior ovarian nerve, the anti-steroidogenic effect of LH in the rat ovary. Using mid- and late-pregnant rats, we set up to study: 1) the influence of the noradrenergic stimulation of the celiac ganglion on the ovarian production of the luteotropic hormone androstenedione; 2) the modulatory effect of noradrenaline at the celiac ganglion on the anti-steroidogenic effect of LH in the ovary; and 3) the involvement of catecholaminergic neurotransmitters released in the ovary upon the combination of noradrenergic stimulation of the celiac ganglion and LH treatment of the ovary. Methods The ex vivo celiac ganglion-superior ovarian nerve-ovary integrated system was used. This model allows studying in vitro how direct neural connections from the celiac ganglion regulate ovarian steroidogenic output. The system was incubated in buffer solution with the ganglion and the ovary located in different compartments and linked by the superior ovarian nerve. Three experiments were designed with the addition of: 1) noradrenaline in the ganglion compartment; 2) LH in the ovarian compartment; and 3) noradrenaline and LH in the ganglion and ovarian compartments, respectively. Rats of 15, 19, 20 and 21 days of pregnancy were used, and, as an end point, the concentration of the luteotropic hormone androstenedione was measured in the ovarian compartment by RIA at various times of incubation. For some of the experimental paradigms the concentration of various catecholamines (dihydroxyphenylalanine, dopamine, noradrenaline and adrenaline) was also measured in the ovarian compartment by HPLC. Results The most relevant result concerning the action of noradrenaline in the celiac ganglion was found on day 21

  5. Triazophos-induced oxidative stress and histomorphological changes in ovary of female Wistar rats.

    PubMed

    Sharma, Dharmender; Sangha, Gurinder Kaur; Khera, Kuldeep Singh

    2015-01-01

    Triazophos (TZ), a non-systemic broad spectrum organophosphate (OP), is being extensively used against a wide range of pests in agricultural practices. The present study was carried out to investigate the toxic effects of triazophos (TZ) in female Wistar rats. Three sub-chronic dose levels of TZ corresponding to 1/10th, 1/20th and 1/40th of LD50 were given for 30 days to adult female Wistar rats through oral intubation. During the treatment period estrous cycle was significantly altered. Activity levels of different oxidative stress (OS) parameters viz. catalase (CAT), superoxide dismutase (SOD), glutathione-S-transferase (GST), glutathione reductase (GR), glutathione peroxidase (GPx) and lipid peroxidation (LPO) were differentially altered in the ovary of treated rats. Estradiol levels were significantly high while progesterone levels were significantly reduced in plasma of 1/10th and 1/20th of LD50 TZ-treated rats. Histomorphological studies of ovary revealed increased follicular atresia and increased ovarian surface epithelial height in 1/10th and 1/20th of LD50 TZ-treated rats. Enhanced apoptosis and necrosis were also observed in ovarian granulosa cells at dose-dependent manner. Results infer that TZ exposure may lead to the number of pathophysiological conditions in female rats and severity increases at high doses.

  6. Coconut water solutions for the preservation of spleen, ovary, and skin autotransplants in rats.

    PubMed

    Schettino César, J M; Petroianu, A; de Souza Vasconcelos, L; Cardoso, V N; das Graças Mota, L; Barbosa, A J A; Vianna Soares, C D; Lima de Oliveira, A

    2015-03-01

    The purpose of this study was to evaluate the efficacy of coconut water in the preservation of spleen, ovary, and skin autotransplantations in rats. Fifty female Wistar rats were divided randomly into 5 groups on the basis of the following tissue graft preservation solutions: group 1, lactated Ringer's; group 2, Belzer's solution; group 3, mature coconut water; group 4, green coconut water; and group 5, modified green coconut water. In group 5, the green coconut water solution was modified to obtain the same electrolyte composition as Belzer's solution. The spleen, ovaries, and a skin fragment were removed from each animal, stored for 6 hours in one of the solutions, and then re-implanted. The recoveries of tissue functions were assessed 90 days after surgery by means of spleen scintigraphy and blood tests. The implanted tissues were collected for histological analyses. Higher immunoglobulin G levels were observed in the animals of group 5 than in the animals of group 1. Differences in follicle-stimulating hormone levels were observed between groups 1 and 2 (P < .001), between groups 4 and 2 (P = .03), and between groups 5 and 2 (P = .01). The spleen scintigraphy results did not differ among the groups. The ovarian tissue was better preserved in the mature coconut water group (P < .007). Solutions containing coconut water allowed for the preservation of the spleen, ovaries, and skin for 6 hours, and the normal functions of these tissues were maintained in rats. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Dual protective role for glutathione S-transferase class pi against VCD-induced ovotoxicity in the rat ovary.

    PubMed

    Keating, Aileen F; Sen, Nivedita; Sipes, I Glenn; Hoyer, Patricia B

    2010-09-01

    The occupational chemical 4-vinylcyclohexene diepoxide (VCD) selectively destroys ovarian small pre-antral follicles in rats and mice via apoptosis. Detoxification of VCD can occur through glutathione conjugation, catalyzed by glutathione S-transferase (GST) enzymes. Further, GST class pi (GSTp) can negatively regulate JNK activity through protein:protein interactions in extra-ovarian tissues. Dissociation of this protein complex in the face of chemical exposure releases the inhibition of pro-apoptotic JNK. Increased JNK activity during VCD-induced ovotoxicity has been shown in isolated ovarian small pre-antral follicles following in vivo dosing of rats (80mg/kg/day; 15days, i.p.). The present study investigated the pattern of ovarian GSTp expression during VCD exposure. Additionally, the effect of VCD on an ovarian GSTp:JNK protein complex was investigated. PND4 F344 rat ovaries were incubated in control medium+/-VCD (30muM) for 2-8days. VCD increased ovarian GSTp mRNA (P <0.05) relative to control on d4-d8; whereas GSTp protein was increased (P<0.05) on d6-d8. A GSTp:JNK protein complex was detected by immunoprecipitation and Western blotting in ovarian tissues. Relative to control, the amount of GSTp-bound JNK was increased (P=0.09), while unbound JNK was decreased (P<0.05) on d6 of VCD exposure. The VCD-induced decrease in unbound JNK was preceded by a decrease in phosphorylated c-Jun which occurred on d4. These findings are in support of a possible dual protective role for GSTp in the rat ovary, consisting of metabolism of VCD and inhibition of JNK-initiated apoptosis.

  8. Dual protective role for Glutathione S-transferase class pi against VCD-induced ovotoxicity in the rat ovary

    SciTech Connect

    Keating, Aileen F.; Sen, Nivedita; Sipes, I. Glenn; Hoyer, Patricia B.

    2010-09-01

    The occupational chemical 4-vinylcyclohexene diepoxide (VCD) selectively destroys ovarian small pre-antral follicles in rats and mice via apoptosis. Detoxification of VCD can occur through glutathione conjugation, catalyzed by glutathione S-transferase (GST) enzymes. Further, GST class pi (GSTp) can negatively regulate JNK activity through protein:protein interactions in extra-ovarian tissues. Dissociation of this protein complex in the face of chemical exposure releases the inhibition of pro-apoptotic JNK. Increased JNK activity during VCD-induced ovotoxicity has been shown in isolated ovarian small pre-antral follicles following in vivo dosing of rats (80 mg/kg/day; 15 days, i.p.). The present study investigated the pattern of ovarian GSTp expression during VCD exposure. Additionally, the effect of VCD on an ovarian GSTp:JNK protein complex was investigated. PND4 F344 rat ovaries were incubated in control medium {+-} VCD (30 {mu}M) for 2-8 days. VCD increased ovarian GSTp mRNA (P < 0.05) relative to control on d4-d8; whereas GSTp protein was increased (P < 0.05) on d6-d8. A GSTp:JNK protein complex was detected by immunoprecipitation and Western blotting in ovarian tissues. Relative to control, the amount of GSTp-bound JNK was increased (P = 0.09), while unbound JNK was decreased (P < 0.05) on d6 of VCD exposure. The VCD-induced decrease in unbound JNK was preceded by a decrease in phosphorylated c-Jun which occurred on d4. These findings are in support of a possible dual protective role for GSTp in the rat ovary, consisting of metabolism of VCD and inhibition of JNK-initiated apoptosis.

  9. Recovery of ovary function impaired by chemotherapy using Chinese herbal medicine in a rat model.

    PubMed

    Xia, Tian; Fu, Yu; Gao, Hui; Zhao, Zhimei; Zhao, Liying; Han, Bing

    2014-10-01

    The ovary is not only involved in female germ cell development and maturation, but also adjusts female endocrinology. Its function is severely impaired during chemotherapy, and premature ovarian failure may be induced. Chinese herbal medicine (CHM) has displayed significant potential in the treatment of female endocrine disorders; however, it is unknown whether it can recover ovarian function impaired by chemotherapy. In the present study, CHM was used to treat rat models of ovarian dysfunction impaired by chemotherapeutic drugs. Three groups were included in this study: a prevention group, a treatment group, and a prevention-treatment group. Routine gonadotropin-releasing hormone agonists (GnRHa) treatment was used as a control. The results showed that body weight, fertility, estrus days, hormone levels, and ovary weight were restored when CHM was administered in these rat models. Moreover, in the prevention-treatment group, the number of follicles at each developmental stage significantly increased compared with the prevention or treatment group. Furthermore, the number of apoptotic cells significantly decreased, and the relative mRNA expression of caspase-3 significantly decreased, in the prevention-treatment group. The results of gene expression analysis indicated that the expression of anti-Müllerianhormone (AMH) which indicates ovarian preservation was significantly up-regulated in the prevention-treatment group and was similar to normal rats. The expression of growth differentiation factor 9 (GDF9) was significantly enhanced in both the prevention-treatment group and the GnRHa group, which suggested that the oocytes were of better quality. Finally, we found that there were no differences in body weight and fertility in the offspring conceived by the drug-treated rats, which partly indicated the safety of the medicine. In conclusion, Chinese herbal medicine showed a beneficial role in the recovery of ovary function in these rat models and has significant

  10. PDGFR Inhibition Results in Pericyte Depletion and Hemorrhage into the Corpus Luteum of the Rat Ovary.

    PubMed

    Hall, Anthony P; Ashton, Susan; Horner, Judith; Wilson, Zena; Reens, Jaimini; Richmond, Graham H P; Barry, Simon T; Wedge, Steve R

    2016-01-01

    The growth plate, ovary, adrenal gland, and rodent incisor tooth are sentinel organs for antiangiogenic effects since they respond reliably, quantitatively, and sensitively to inhibition of the vascular endothelial growth factor receptor (VEGFR). Here we report that treatment of rats with platelet-derived growth factor receptor beta (PDGFRβ) inhibitors that target pericytes results in severe ovarian hemorrhage with degeneration and eventual rupture of the corpus luteum. Evaluation of the growth plate, adrenal gland, and incisor tooth that are typical target organs for antiangiogenic treatment in the rodent revealed no abnormalities. Histologically, the changes in the ovary were characterized by sinusoidal dilatation, increased vessel fragility, and hemorrhage into the corpus luteum. Immunocytochemical staining of vessels with alpha smooth muscle actin and CD31 that recognize pericytes and vascular endothelium, respectively, demonstrated that this effect was due to selective pericyte deficiency within corpora lutea. Further experiments in which rats were treated concurrently with both PDGFRβ and VEGFR inhibitors ablated the hemorrhagic response, resulting instead in corpus luteum necrosis. These changes are consistent with the notion that selective pericyte loss in the primitive capillary network resulted in increased vessel fragility and hemorrhage, whereas concomitant VEGFR inhibition resulted in vessel regression and reduced vascular perfusion that restricted development of the hemorrhagic vessels. These results also highlight the utility of the rodent ovary to respond differentially to VEGFR and PDGFR inhibitors, which may provide useful information during routine safety assessment for determining target organ toxicity.

  11. Studies on gonadotropin receptor of rat ovary and testis

    SciTech Connect

    Zhang, Q.

    1989-01-01

    The subunit structure of the testicular LH/hCG receptor was studied by a chemical cross-linking technique. Leydig cells isolated from rat testis were incubated with {sup 125}I-hCG, following which the bound {sup 125}I-hCG was covalently cross-linked to the receptor on the cell surface with a cleavable or a non-cleavable cross-linking reagent. The hormone-receptor complex was extracted and then either subjected to gel permeation chromatography under nondenaturing conditions, or resolved by SDS-polyacrylamide gel electrophoresis, followed by autoradiographic analysis. The ovarian LH/hCG receptor was studied with luteal cells from pseudopregnant rats. Purification of the receptor was achieved by ligand affinity chromatography following detergent solubilization of the plasma membrane. The purified hCG receptor displayed properties identical to the membrane bound receptor with regard to binding specificity and affinity, and exhibited a molecular weight of approximately 130,000 dalton.

  12. The Characterization of Obese Polycystic Ovary Syndrome Rat Model Suitable for Exercise Intervention

    PubMed Central

    Qiu, Shuwei; Jiang, Zhongli

    2014-01-01

    Objective To develop a new polycystic ovary syndrome (PCOS) rat model suitable for exercise intervention. Method Thirty six rats were randomly divided into three experimental groups: PCOS rats with high-fat diet (PF, n = 24), PCOS rats with ordinary diet (PO, n = 6), and control rats with ordinary diet (CO, n = 6). Two kinds of PCOS rat model were made by adjustment diet structure and testosterone injection for 28 days. After a successful animal model, PF model rats were randomly assigned to three groups: exercise with a continuation of high-fat diet (PF-EF, n = 6), sedentary with a continuation of high-fat diet (PF-SF, n = 6), exercise with an ordinary diet (PF-EO, n = 6). Fasting blood glucose (FBG) and insulin (FINS), estrogen (E2), progesterone (P), and testosterone (T) in serum were determined by RIA, and ovarian morphology was evaluated by Image-Pro plus 6.0. Results Body weight, Lee index, FINS increased significantly in PF rat model. Serum levels of E2 and T were significantly higher in PF and PO than in CO. Ovary organ index and ovarian areas were significant lower in PF than in CO. After intervention for 2 weeks, the levels of 1 h postprandial blood glucose (PBG1), 2 h postprandial blood glucose (PBG2), FINS and the serum levels of T decreased significantly in PF-EF rats and PF-EO rats. The ratio of FBG/FINS was significant higher in PF-EO rats than in PF-SF rats. Ovarian morphology showed that the numbers of preantral follicles and atretic follicles decreased significantly, and the numbers of antral follicles and corpora lutea increased significantly in the rats of PF-EF and PF-EO. Conclusion By combination of high-fat diet and testosterone injection, the obese PCOS rat model is conformable with the lifestyle habits of fatty foods and insufficient exercise, and has metabolic and reproductive characteristics of human PCOS. This model can be applied to study exercise intervention. PMID:24905232

  13. Brown adipose tissue activation by rutin ameliorates polycystic ovary syndrome in rat.

    PubMed

    Hu, Tao; Yuan, Xiaoxue; Ye, Rongcai; Zhou, Huiqiao; Lin, Jun; Zhang, Chuanhai; Zhang, Hanlin; Wei, Gang; Dong, Meng; Huang, Yuanyuan; Lim, Wonchung; Liu, Qingsong; Lee, Hyuek Jong; Jin, Wanzhu

    2017-09-01

    Polycystic ovary syndrome (PCOS) is a complex endocrinopathy that is characterized by anovulation, hyperandrogenism and polycystic ovary. However, there is a lack of effective treatment for PCOS at present because the pathologic cause of PCOS has not been elucidated. Although it has been known that brown adipose tissue transplantation ameliorates PCOS by activating endogenous BAT, BAT transplantation is not applicable in clinic. Therefore, BAT activation with natural compound could be an effective treatment strategy for PCOS patients. Here, we found that 3 weeks of rutin (a novel compound for BAT activation) treatment increased BAT activation, thereby it improved thermogenesis and systemic insulin sensitivity in dehydroepiandrosterone (DHEA)-induced PCOS rat. In addition, the expression levels of ovarian steroidogenic enzymes such as P450C17, aromatase, 3β-HSD, 17β-HSD and STAR were up-regulated in rutin-treated PCOS rat. Furthermore, acyclicity and the serum level of luteinizing hormone were normalized, and a large number of mature ovulated follicle with a reduction of cystic formation were observed in PCOS rat after rutin treatment. Finally, rutin treatment surprisingly improved fertility and birth defect in PCOS rat. Collectively, our results indicate that rutin treatment significantly improves systemic insulin resistance and ovarian malfunction in PCOS, and our findings in this study provide a novel therapeutic option for the treatment of PCOS by activating BAT with rutin. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Unilateral sectioning of the superior ovarian nerve of rats with polycystic ovarian syndrome restores ovulation in the innervated ovary

    PubMed Central

    2010-01-01

    The present study tested the hypothesis that if polycystic ovary syndrome (PCOS) results from activating the noradrenergic outflow to the ovary, unilaterally sectioning the superior ovarian nerve (SON) will result in ovulation by the denervated ovary, and the restoration of progesterone (P4), testosterone (T) and estradiol (E2) normal serum level. A single 2 mg dose of estradiol valerate (EV) to adult rats results in the development of a syndrome similar to the human PCOS. Ten-day old rats were injected with EV or vehicle solution (Vh) and were submitted to sham surgery, unilateral or bilateral sectioning of the SON at 24-days of age. The animals were sacrificed at 90 to 92 days of age, when they presented vaginal estrus preceded by a pro-estrus smear. In EV-treated animals, unilateral sectioning of the SON restored ovulation by the innervated ovary and unilateral or bilateral sectioning of the SON normalized testosterone and estradiol levels. These results suggest that aside from an increase in ovarian noradrenergic tone in the ovaries, in the pathogenesis of the PCOS participate other neural influences arriving to the ovaries via the SON, regulating spontaneous ovulation. Changes in P4, T and E2 serum levels induced by EV treatment seem to be controlled by neural signals arising from the abdominal wall and other signals arriving to the ovaries through the SON, and presents asymmetry. PMID:20723258

  15. Quercetin Decreases Insulin Resistance in a Polycystic Ovary Syndrome Rat Model by Improving Inflammatory Microenvironment.

    PubMed

    Wang, Zhenzhi; Zhai, Dongxia; Zhang, Danying; Bai, Lingling; Yao, Ruipin; Yu, Jin; Cheng, Wen; Yu, Chaoqin

    2017-05-01

    Insulin resistance (IR) is a clinical feature of polycystic ovary syndrome (PCOS). Quercetin, derived from Chinese medicinal herbs such as hawthorn, has been proven practical in the management of IR in diabetes. However, whether quercetin could decrease IR in PCOS is unknown. This study aims to observe the therapeutic effect of quercetin on IR in a PCOS rat model and explore the underlying mechanism. An IR PCOS rat model was established by subcutaneous injection with dehydroepiandrosterone. The body weight, estrous cycle, and ovary morphology of the quercetin-treated rats were observed. Serum inflammatory cytokines were analyzed using enzyme-linked immunosorbent assay. In ovarian tissues, the expression of key genes involved in the inflammatory signaling pathway was detected through Western blot, real-time polymerase chain reaction, or immunohistochemistry. The nuclear translocation of nuclear factor κB (NF-κB) was also observed by immunofluorescence. The estrous cycle recovery rate of the insulin-resistant PCOS model after quercetin treatment was 58.33%. Quercetin significantly reduced the levels of blood insulin, interleukin 1β, IL-6, and tumor necrosis factor α. Quercetin also significantly decreased the granulosa cell nuclear translocation of NF-κB in the insulin-resistant PCOS rat model. The treatment inhibited the expression of inflammation-related genes, including the nicotinamide adenine dinucleotide phosphate oxidase subunit p22phox, oxidized low-density lipoprotein, and Toll-like receptor 4, in ovarian tissue. Quercetin improved IR and demonstrated a favorable therapeutic effect on the PCOS rats. The underlying mechanism of quercetin potentially involves the inhibition of the Toll-like receptor/NF-κB signaling pathway and the improvement in the inflammatory microenvironment of the ovarian tissue of the PCOS rat model.

  16. Alphafetoprotein and atretic follicles in the ovary of the pregnant rat.

    PubMed

    Seralini, G E; Lafaurie, M; Krebs, B; Stora, C

    1986-01-01

    Previous experiments have been conducted concerning the role of alphafetoprotein in genital system blockade in several cases: during adult rat N2-fluorenylacetamide hepatocarcinogenesis, after alphafetoprotein injections into normal adult female rats, during fetal life, and during postnatal and prepuberal development. In these conditions, alphafetoprotein is present at high plasma levels, and the normal cyclic ovarian function is stopped or nonexistent. The degenerating oocytes observed in the ovaries are often AFP-positive by histo-immunolocalization. Pregnancy corresponds to a physiological state in which alphafetoprotein levels are high while the gonadal activity is not characterized by ovulatory cycles. In order to assess our hypothesis, alpha-fetoprotein was studied in the ovary of pregnant rats from day 18 to 21 of gestation by an immunofluorescent technique, and alpha-fetoprotein was assayed in plasma samples. The results of this work show that, during pregnancy, follicular maturation is blocked at the antral stage, and the follicles contain degenerating oocytes that are AFP-positive in immunofluorescence. In conclusion, we suggest that the alpha-fetoprotein produced by the fetal liver and the yolk sac is disseminated in the amniotic fluid and passes through the placenta, and then reaches the ovarian follicles and the oocytes. The possible role of alphafetoprotein in follicular atresia is discussed.

  17. Effect of prenatal and neonatal exposure to lead on gonadotropin receptors and steroidogenesis in rat ovaries

    SciTech Connect

    Wiebe, J.P.; Barr, K.J.; Buckingham, K.D.

    1988-01-01

    Sprague-Dawley rats were treated with lead chloride (20 or 200 ppm) or sodium chloride (controls) in their drinking water, either prior to pregnancy or during pregnancy and lactation, and female offspring were examined at weaning (21 d) or at 150 d. Other female rats were treated from d 21 to 35. Tissue (blood, kidney, bone) lead levels, body, ovary, and uterus weights, ovarian steroidogenesis, and gonadotropin (luteinizing hormone and follicle-stimulating hormone) levels, and gonadotropin-receptor binding were determined. Prenatal and/or postnatal exposure to lead at these levels (20 and 200 ppm) did not affect tissue weights but did cause a significant decrease in gonadotropin-receptor binding in the prepubertal, pubertal and adult females. Conversion of progesterone to androstenedione and dihydrotestosterone was significantly decreased in 21-d-old rats; in 150-d-old females, the prenatal and/or postnatal exposure to lead resulted in significantly increased conversion to the 5-alpha-reduced steroid, normally high during puberty. The results demonstrate that lead exposure prior to mating may affect gonadotropin-receptor binding in the offspring and that lead exposure (in utero, via mother's milk, or post weaning) may significantly alter steroid production and gonadotropin binding in ovaries of the prepubertal, pubertal, and adult female.

  18. The Stage- and Cell Type-Specific Localization of Fragile X Mental Retardation Protein in Rat Ovaries.

    PubMed

    Takahashi, Noriyuki; Tarumi, Wataru; Itoh, Masanori T; Ishizuka, Bunpei

    2015-12-01

    Premutations of the fragile X mental retardation 1 (FMR1) gene are associated with increased risk of primary ovarian insufficiency. Here we examined the localization of the Fmr1 gene protein product, fragile X mental retardation protein (FMRP), in rat ovaries at different stages, including fetus, neonate, and old age. In ovaries dissected from 19 days postcoitum embryos, the germ cells were divided into 2 types: one with decondensed chromatin in the nucleus was FMRP positive in the cytoplasm, but the other with strongly condensed chromatin in the nucleus was FMRP negative in the cytoplasm. The FMRP was predominantly localized to the cytoplasm of oocytes in growing ovarian follicles. Levels of FMRP in oocytes from elderly (9 or 14 months of age) ovaries were lower than in those from younger ovaries. These results suggest that FMRP is associated with the activation of oogenesis and oocyte function. Especially, FMRP is likely to be implicated in germline development during oogenesis.

  19. Regulation of HGF and c-MET Interaction in Normal Ovary and Ovarian Cancer.

    PubMed

    Kwon, Youngjoo; Godwin, Andrew K

    2017-04-01

    Binding of hepatocyte growth factor (HGF) to the c-MET receptor has mitogenic, motogenic, and morphogenic effects on cells. The versatile biological effects of HGF and c-MET interactions make them important contributors to the development of malignant tumors. We and others have demonstrated a therapeutic value in targeting the interaction of c-MET and HGF in epithelial ovarian cancer (EOC). However, both HGF and c-MET are expressed in the normal ovary as well. Therefore, it is important to understand the differences in mechanisms that control HGF signaling activation and its functional role in the normal ovary and EOC. In the normal ovary, HGF signaling may be under hormonal regulation. During ovulation, HGF-converting proteases are secreted and the subsequent activation of HGF signaling enhances the proliferation of ovarian surface epithelium in order to replenish the area damaged due to expulsion of the ovum. In contrast, EOC cells that exhibit epithelial characteristics constitutively express both c-MET and HGF-converting proteases such as urokinase-type plasminogen activator. In EOC, mechanisms to control the activation of HGF signaling are absent since HGF is provided locally from the tissue microenvironment as well as remotely throughout the body. Potential incessant HGF signaling in EOC may lead to an increase in proliferation, invasion through the stroma, and migration to other tissues of cancer cells. Therefore, targeting the interaction of c-MET and HGF would be beneficial in treating EOC.

  20. The role of nesfatin-1 expression in letrozole-induced polycystic ovaries in the rat.

    PubMed

    Xu, Yingqiao; Zhang, Hua; Li, Qingchun; Lao, Kaixue; Wang, Yanlin

    2017-02-21

    Polycystic ovary syndrome (PCOS) is a complex and heterogeneous endocrine disorder, generally exhibiting the characteristic features of hyperandrogenemia, insulin resistance (IR) and obesity. Nesfatin-1 is derived from the precursor nucleobindin2 (NUCB2), and plays an active role in energy balance, glucose metabolism and most likely gonadal function. In order to explore the role of nesfatin-1, we employed a rat model that uses letrozole to induce PCOS. The PCOS rats exhibited increased body weight, irregular cycles, polycystic ovaries characterized by cysts formed from atretic follicles, and a diminished granulosa layer. The expression of both nesfatin-1 mRNA and protein in the ovarian tissues of PCOS group decreased significantly compared to the control group (p < 0.05). Nesfatin-1 expression in peripheral blood also decreased in the PCOS group, in contrast with the control group. Furthermore, we found that nesfatin-1 had a positive correlation with FSH, E2 and P, whereas it had a negative correlation with LH, and total T (p < 0.05). When taken together, these data indicated that the decrease in nesfatin-1 may contribute to the mechanism governing PCOS, and might provide a new potential target for therapies aimed at treating PCOS.

  1. Remote ischemic preconditioning on neovascularization and follicle viability on ovary autotransplantation in rats.

    PubMed

    Damous, L L; Silva, S M; Simões, R S; Morello, R J; Carbonel, A P F; Simões, M J; Montero, E F S

    2008-04-01

    Verify the optimum remote vascular occlusion time to reduce ovarian injury in autologous transplants in rats. Twenty-four adult female rats were assigned to four groups: GC (control group): bilateral oophorectomy followed by ovary transplant; GIPC (ischemic preconditioning group): remote ischemic preconditioning at the iliac artery for 5, 10, and 15 minutes (GIPC-5, GIPC-20, and GIPC-15) previous to bilateral oophorectomy and ovarian transplantation. The right ovary was fixed in the retroperitoneum. Euthanasia was performed 4 days after the surgical procedure. The follicles were counted and classified as developing versus atretic. The immunohistochemical assay identified vascular factor of endothelial growth (VEGF) in the ovarian stroma and assessed the proliferation capacity by means of the Ki-67 in the ovarian follicles. Every group showed an inflammatory infiltrate, luteous body, and ovarian follicles in several phases of development. The ischemic preconditioning groups displayed greater amounts of viable ovarian follicles and increased vascularization and vasodilatation than the control group. GIPC-15 showed the highest amount of viable follicles compared to the others (P < .05 GIPC-15 vs GC; GIPC-15 vs GIPC-5). More VEGF-labeled cells were observed in GIPC-10 than the control group (P < .05, GIPC-10 vs GC). The proliferation index assessed by Ki-67 marking showed GC: 80%; GIPC-5: 76%; GIPC-10: 67%; and GIPC-15: 64% (P > .05). The PCI-15 cohort seem to be the most adequate timing to achieve functional support and preservation of a greater number of viable ovarian follicles.

  2. Preliminary results of orthotopic en bloc uterus and ovary transplantation in the laboratory rat.

    PubMed

    Motoc, A; Jiga, L; Ionac, M; Raica, M; Motoc, M; Chiovschi, S

    2003-01-01

    A new experimental model of whole uterus and ovary transplantation in the laboratory rat was achieved. The main goals of this study were concerned with developing and standardizing the microsurgical technique of uterus transplantation in rats and observing the particular cellular patterns of acute allograft rejection at the level of the transplanted graft. Thirty-five orthotopic uterus transplantations were performed. An additional 20 female rats were used for dissection training sessions. Recipients were euthanasied at 24 hours, 48 hours and 72 hours. Immediate postoperative survival was 100%. Patency of the microsurgical anastomoses, checked at 24 hours, was 100%. At 72 hours thrombosis occurred in all anastomoses. The explanted uterine grafts were fixed in formaline and analyzed under light microscopy and specific imunohistochemical analysis. The acute allograft rejection has a particular cellular reaction pattern, probably due to the unique diversity of the tissues that compose it. Inflammatory cells like LTCD8+, LBCD20+ and mastocytes tend to agglomerate in the vicinity of nervous and vascular structures, showing no signs of lymphoid tissue disposition like in typical acute rejection. Uterus transplantation in rats has proven to be a valid experiment that allows us to express hope that by further research on transplantation of the uterus gynecologists will be able to introduce an adapted technique in the treatment of specific cases of human female infertility.

  3. Parabens inhibit the early phase of folliculogenesis and steroidogenesis in the ovaries of neonatal rats.

    PubMed

    Ahn, Hyo-Jin; An, Beum-Soo; Jung, Eui-Man; Yang, Hyun; Choi, Kyung-Chul; Jeung, Eui-Bae

    2012-09-01

    Parabens are widely used as anti-microbial agents in the cosmetic and pharmaceutical industries. Recently, parabens have been shown to act as xenoestrogens, a class of endocrine disruptors. In the present study, 55 female pups were given daily subcutaneous injections of methyl-, propyl-, and butyl-paraben or 17beta-estradiol (E2) during neonatal Day 1-7. The ovaries were excised on postnatal Day 8, then fixed and stained with hematoxylin and eosin for histological analysis. The follicles were counted and classified as being in the primordial, early primary, or primary stages. The number of primordial follicles increased while early primary follicles decreased at the high doses of propyl- and butyl-paraben. The levels of anti-Mullerian hormone (AMH) and Foxl2 mRNA increased by propyl- and butyl-parabens whereas kit ligand/stem cell factor (KITL) expression was up regulated only by butyl-paraben. The mRNA levels of StAR and Cyp11a1 were significantly decreased after treatment with methyl-, propyl-, and butyl-parabens. Consistent with its use as a positive control, E2 regulated the expression of KITL, StAR, and Cyp11a1 genes, but surprisingly did not affect AMH and Foxl2 levels. Thus, E2 and parabens had different effects on the regulation of folliculogenic and steroidogenic genes, demonstrating the estrogenic and nonestrogenic properties of parabens in the ovary. Taken together, our data show that parabens stimulated AMH mRNA expression and consequently inhibited the early phase of folliculogenesis in the ovaries of neonatal female rat. The levels of steroidogenic enzymes, indicators of follicle differentiation, appeared to be regulated by parabens through inhibition of their transcriptional repressor, Foxl2. Copyright © 2012 Wiley Periodicals, Inc.

  4. Effects of methoxychlor on IGF-I signaling pathway in rat ovary.

    PubMed

    Ozden-Akkaya, O; Altunbas, K; Yagcı, A

    2017-01-01

    Follicular development and other ovarian functions are regulated by growth factors that can be affected by exogenous agents. Methoxychlor (MXC) is an organochloride pesticide that causes female infertility. We investigated how MXC affects the distribution of developing ovarian follicles in adult rats after treatment between embryonic day (E) 18 and postnatal day (PND) 7. We also measured insulin-like growth factor-I (IGF-I) and its receptor, IGF-IR, expressions in ovarian follicles and investigated whether MXC changed the levels of IGF-I and IGF-IR in the ovary. Using immunohistochemical (IHC) staining, we detected IGF-I expression in oocytes and granulosa cells of the follicles, luteal cells, interstitial cells, theca externa and theca interna, and the smooth muscle of ovarian vessels. IGF-IR was co-localized with IGF-I in the ovary except for the theca externa. IGF-I expression was decreased in granulosa cells of preantral and antral follicles after treatment with MXC compared to granulosa cells of preantral and antral follicles of the control group. We also observed that oocytes of secondary follicles and granulosa cells of secondary and preantral follicles of the MXC treated groups showed increased IGF-IR expression compared to oocytes of secondary follicles and granulosa cells of secondary and preantral follicles of the control group. We also detected more secondary and preantral follicles, and fewer primordial and antral follicles after MXC administration compared to controls. Therefore, the IGF signaling pathway may participate in MXC induced ovary dysfunction and female infertility.

  5. Study origin of germ cells and formation of new primary follicles in adult human and rat ovaries.

    PubMed

    Bukovsky, Antonin; Gupta, Satish K; Virant-Klun, Irma; Upadhyaya, Nirmala B; Copas, Pleas; Van Meter, Stuart E; Svetlikova, Marta; Ayala, Maria E; Dominguez, Roberto

    2008-01-01

    The central thesis regarding the human ovaries is that, although primordial germ cells in embryonal ovaries are of extraovarian origin, those generated during the fetal period and in postnatal life are derived from the ovarian surface epithelium (OSE) bipotent cells. With the assistance of immune system-related cells, secondary germ cells and primitive granulosa cells originate from OSE stem cells in the fetal and adult human gonads. Fetal primary follicles are formed during the second trimester of intrauterine life, prior to the end of immune adaptation, possibly to be recognized as self-structures and renewed later. With the onset of menarche, a periodical oocyte and follicular renewal emerges to replace aging primary follicles and ensure that fresh eggs for healthy babies are always available during the prime reproductive period. The periodical follicular renewal ceases between 35 and 40 yr of age, and the remaining primary follicles are utilized during the premenopausal period until exhausted. However, the persisting oocytes accumulate genetic alterations and may become unsuitable for ovulation and fertilization. The human OSE stem cells preserve the character of embryonic stem cells, and they may produce distinct cell types, including new eggs in vitro, particularly when derived from patients with premature ovarian failure or aging and postmenopausal ovaries. Our observations also indicate that there are substantial differences in follicular renewal between adult human and rat ovaries. As part of this chapter, we present in detail protocols utilized to analyze oogenesis in humans and to study interspecies differences when compared to the ovaries of rat females.

  6. Effects of Exercise Intervention on Preventing Letrozole-Exposed Rats From Polycystic Ovary Syndrome.

    PubMed

    Cao, Si-Fan; Hu, Wen-Long; Wu, Min-Min; Jiang, Li-Yan

    2017-03-01

    Polycystic ovary syndrome (PCOS) is a prevalent endocrinological disorder in reproductive-age women and is often associated with a metabolic syndrome. To investigate whether exercise intervention promotes PCOS prevention, a rat model was used. Polycystic ovary syndrome was induced by letrozole administration, and animals presented with obesity, sex hormone disorder, no ovulation, large cystic follicles, and increasing fasting insulin (FINS) and leptin levels. The intervention was set at 3 different intensities of swimming exercise: low (0.5 h/d), moderate (1 h/d), and high (2 h/d), and compared with a PCOS model group (letrozole administration without exercise intervention) and a control group. The exercise intervention in the low-intensity group did not produce changes in obesity, testosterone, progesterone (P), and follicle-stimulating hormone (FSH) levels. Moderate-intensity exercise reduced body weight, retained ovulation, and P levels were increased but remained lower than those in the control group. The FSH levels were significantly higher, and FINS and leptin levels were lower than in the model group ( P < 0.05) but not in the control group. The high-intensity group demonstrated the greatest effect of PCOS prevention. Testosterone, luteinizing hormone, FINS, and leptin levels were significantly lower in the high-intensity group, and FSH and P levels were higher compared with the model group. These results suggest that high-intensity exercise intervention can effectively prevent PCOS development.

  7. Morphometry and immunohistochemistry of follicles growth and steroidogenesis in saharian wild sand rat, Psammomys obesus, ovary.

    PubMed

    Boubekri, Amina; Gernigon-Spychalowicz, Thérese; Khammar, Farida; Exbrayat, Jean-Marie

    2009-01-01

    The sand rat (Psammomys obesus) constitutes a model to study seasonal changes and several metabolic disorders. In order to perform breeding laboratory conditions, the reproductive function of this species living in North Occidental Algerian Sahara was studied. The aim of this work was to investigate the follicular growth changes and the steroidogenic associated aspects. The study was performed using morphometrical and immunohistochemical methods. From primordial to preantral states, the follicle diameter increased progressively from 17-20 mum to 192-225 mum. The preovulatory follicles reached about 500 mum in diameter. Immunoreactivity to progesterone, androstenediol and estradiol, varied in the different parts of the ovary and follicular cells. The progesterone antibody appeared clearly labelled in the theca interna of the growing follicle and increased in the granulosa; the androgen antibody was continuously weak and diffuses in all follicles; the estradiol labelling appeared weak and diffuse in preantral follicles then increased in antral follicles in both theca and granulosa or only in granulosa. In antral follicles, estradiol label was clearly localized in granulosa cells and totally devoid in theca cells. In Psammomys ovary, labels of hormone were diffuse or localized, weak or intense in the theca and or in the granulosa according to the follicle size.

  8. Protective effects of honokiol on ischemia/reperfusion injury of rat ovary: an experimental study.

    PubMed

    Yaman Tunc, Senem; Agacayak, Elif; Goruk, Neval Yaman; Icen, Mehmet Sait; Turgut, Abdulkadir; Alabalik, Ulas; Togrul, Cihan; Ekinci, Cenap; Ekinci, Aysun; Gul, Talip

    2016-01-01

    The purpose of this study was to investigate the protective effect of honokiol on experimental ischemia/reperfusion injury of rat ovary. A total of 40 female Wistar albino rats were used in this study. The rats were divided into five groups as follows: sham (Group I), torsion (Group II), torsion + detorsion (Group III), torsion + detorsion + saline (Group IV), and torsion + detorsion + honokiol (Group V). Bilateral adnexa in all the rats except for those in the sham group were exposed to torsion for 3 hours. The rats in Group IV were administered saline, whereas the rats in Group V were administered honokiol by intraperitoneal route 30 minutes before detorsion. Tissue and plasma concentrations of malondialdehyde and nitric oxide were determined. Ovarian tissue was histologically evaluated. Data analyses were performed by means of Kruskal-Wallis test and Mann-Whitney U-test (Bonferroni correction) in SPSS 15.0 (Statistical Package for Social Sciences; SPSS Inc., Chicago, IL, USA). The torsion and detorsion groups had higher scores in vascular congestion, hemorrhage, and inflammatory cell infiltration compared with the sham group (P<0.005). In addition, total histopathological scores were significantly higher in the torsion and detorsion groups compared with the sham group (P<0.005). A significant reduction was observed in hemorrhage, inflammatory cell infiltration, and cellular degeneration scores, of all histopathological scores, in the honokiol group (P<0.005). Ovarian tissue concentrations of malondialdehyde were significantly higher in the torsion and detorsion groups compared with the sham and honokiol groups (P<0.005). Ovarian tissue concentrations of nitric oxide, on the other hand, were significantly higher in the torsion group compared with the sham, saline, and honokiol groups (P<0.005). Honokiol has a beneficial effect on ovarian torsion-related ischemia/reperfusion injury.

  9. Protective effects of honokiol on ischemia/reperfusion injury of rat ovary: an experimental study

    PubMed Central

    Yaman Tunc, Senem; Agacayak, Elif; Goruk, Neval Yaman; Icen, Mehmet Sait; Turgut, Abdulkadir; Alabalik, Ulas; Togrul, Cihan; Ekinci, Cenap; Ekinci, Aysun; Gul, Talip

    2016-01-01

    Aim The purpose of this study was to investigate the protective effect of honokiol on experimental ischemia/reperfusion injury of rat ovary. Materials and methods A total of 40 female Wistar albino rats were used in this study. The rats were divided into five groups as follows: sham (Group I), torsion (Group II), torsion + detorsion (Group III), torsion + detorsion + saline (Group IV), and torsion + detorsion + honokiol (Group V). Bilateral adnexa in all the rats except for those in the sham group were exposed to torsion for 3 hours. The rats in Group IV were administered saline, whereas the rats in Group V were administered honokiol by intraperitoneal route 30 minutes before detorsion. Tissue and plasma concentrations of malondialdehyde and nitric oxide were determined. Ovarian tissue was histologically evaluated. Data analyses were performed by means of Kruskal–Wallis test and Mann–Whitney U-test (Bonferroni correction) in SPSS 15.0 (Statistical Package for Social Sciences; SPSS Inc., Chicago, IL, USA). Results The torsion and detorsion groups had higher scores in vascular congestion, hemorrhage, and inflammatory cell infiltration compared with the sham group (P<0.005). In addition, total histopathological scores were significantly higher in the torsion and detorsion groups compared with the sham group (P<0.005). A significant reduction was observed in hemorrhage, inflammatory cell infiltration, and cellular degeneration scores, of all histopathological scores, in the honokiol group (P<0.005). Ovarian tissue concentrations of malondialdehyde were significantly higher in the torsion and detorsion groups compared with the sham and honokiol groups (P<0.005). Ovarian tissue concentrations of nitric oxide, on the other hand, were significantly higher in the torsion group compared with the sham, saline, and honokiol groups (P<0.005). Conclusion Honokiol has a beneficial effect on ovarian torsion-related ischemia/reperfusion injury. PMID:27022246

  10. Expression and regulation of scavenger receptor class B type 1 in the rat ovary and uterus during the estrous cycle.

    PubMed

    Wang, Yalei; Meng, Chenling; Wei, Quanwei; Shi, Fangxiong; Mao, Dagan

    2015-04-01

    Scavenger receptor class B type 1 (SR-B1) preferentially mediates the selective uptake of high density lipoprotein-cholesterol ester and the delivery of cholesterol for steroidogenesis. Although multiple analyses have investigated the function of SR-B1 in the liver, adrenal and ovary, its expression in rat ovary and uterus during the estrous cycle is lacking. In the present study, real-time PCR, western blot and immunohistochemistry (IHC) were used to investigate SR-B1 expression in the rat ovary and uterus during the estrous cycle. The results demonstrated that ovarian SR-B1 expression was in a stage-dependent manner, continuously increased from proestrus and kept elevated during metoestrus, while uterine SR-B1 expression decreased from proestrus to diestrus. To determine whether ovarian and uterine SR-B1 expression were affected by sex steroid hormones, immature rats were treated with 17 β-estradiol (E2), progesterone (P4), or their antagonists from postnatal days 24-26. Results showed that the levels of SR-B1 mRNA and protein were significantly up-regulated by E2 in both the ovary and uterus. IHC results showed that SR-B1 was primarily localized in the oocytes, theca internal cells (T-I) of follicles, interstitial cells (IC) as well as corpus luteum (CL), but not granulosa cells (GC) in the ovary during the estrous cycle. Uterine SR-B1 was highly expressed in the endometrial luminal epithelial cells (LEC) and glandular epithelial cells (GEC) as well as in the circular muscle (CM) cells, and weak staining in stromal cells (SC) through estrous cycle. Taken together, SR-B1 expression in the ovary and uterus across the estrous cycle demonstrate that SR-B1 may be involved in uterine function, follicular development as well as luteal function. Copyright © 2015 Elsevier GmbH. All rights reserved.

  11. Differential effects of bisphenol A diglicydyl ether on bone quality and marrow adiposity in ovary-intact and ovariectomized rats.

    PubMed

    Li, Guanwu; Xu, Zheng; Hou, Lingmi; Li, Xuefeng; Li, Xin; Yuan, Wei; Polat, Maki; Chang, Shixin

    2016-12-01

    Bisphenol A diglycidyl ether (BADGE), a PPARγ2 antagonist, has been shown to inhibit marrow adipogenesis and promote bone formation in intact animals. We investigated the impact of BADGE on a new and more clinically relevant physiological model, the ovariectomized (OVX) rat model. Forty female Wistar rats were divided into four treatment groups for 12 wk (n = 10/group): sham+vehicle, sham+BADGE, OVX+vehicle, and OVX+BADGE. Postmortem analyses included MRI, micro-CT, serological test, histomorphometry, biomechanical tests, RT-PCR, and Western blot. Overall, OVX induced a sequential marrow fat expansion accompanied by bone deterioration. Compared with OVX controls, BADGE reduced fat fraction of the distal femur by 36.3%, adipocyte density by 33.0%, adipocyte size by 28.6%, adipocyte volume percentage by 57.8%, and adipogenic markers PPARγ2 and C/EBPα by ∼50% in OVX rats. Similar results were observed in sham rats vs. vehicle. BADGE could promote bone quality in sham rats; however, BADGE did not significantly improve trabecular microarchitecture, biomechanical strength, and dynamic histomorphometric parameters except for trabecular separation in OVX rats. We concluded that early BADGE treatment at a dose of 30 mg/kg attenuates marrow adiposity in ovary-intact and OVX rats and stimulates bone formation in ovary-intact rats but does not significantly rescue bone quality in OVX rats. Copyright © 2016 the American Physiological Society.

  12. Immunohistochemical expression of ghrelin in capsaicin-treated rat ovaries during the different developmental periods

    PubMed Central

    Tütüncü, Ş.; İlhan, T.; Özfiliz, N.

    2016-01-01

    Red hot pepper is a plant that belongs to the Solanaceae family and is known as Capsicum annuum. Capsaicin is the active ingredient of cayenne pepper. Ghrelin is a hormone, which consists of polypeptide structure. Ghrelin also contributes to growth hormone secretion, energy balance, food intake and body weight regulator. The aim of this study was the localization and expression of ghrelin in the ovaries of rats treated with capsaicin during the postnatal development. Ninety female Sprague-Dawley rats (21 d) were used. The rats were randomly divided into 3 groups (n=30 each) as pubertal, post pubertal and adult. Each group was subdivided into three groups. The first subgroup (control) was given no injections. The second subgroup (vehicle) received only 0.3 cc solvent and the third subgroup (experiment) received subcutaneous injection of equal volume of capsaicin (1 mg/kg/d) for 42, 56, and 70 days. Ghrelin immunoreactivity was determined in ovarian follicular granulosa cells, interstitial cells and corpus luteal cells. A ghrelin immunopositive reaction located in the cytoplasm of cells in all groups. These results indicate that prolonged administration of low dose capsaicin does not affect ghrelin expression. However, follicular atresia was seen in lower rate in capsaicin treated group in comparison to other groups. PMID:27656230

  13. Evidence for selective expression of angiotensin II receptors on atretic follicles in the rat ovary: an autoradiographic study

    SciTech Connect

    Daud, A.I.; Bumpus, F.M.; Husain, A.

    1988-06-01

    Ovarian angiotensin II (Ang II) receptors display a cyclical pattern of variation during the rat estrous cycle. Ang II receptors, estimated by the specific binding of the Ang II receptor antagonist (/sup 125/I)iodo-(Sar1,Ile8) Ang II to ovarian membranes, were lowest at estrus (binding site density (Bmax) = 35 +/- 2 fmol/mg; binding site affinity (KD) = 2.0 +/- 0.2 nM) and highest at diestrus I (Bmax = 59 +/- 3 fmol/mg; KD = 1.6 +/- 0.1 nM). We have previously shown that Ang II receptors in the rat ovary predominantly exist on the granulosa cell layer of a subpopulation of follicles. Our present studies show that the Ang II receptor-containing follicles in the rat ovary are mainly atretic (approximately 80%) or show signs of early atresia (approximately 15%) during all stages of the estrous cycle. A small number of Ang II receptor-containing follicles were healthy (approximately 5%). In contrast to the Ang II receptor-containing follicles, the FSH receptor-containing follicles were predominantly healthy (greater than 90%). Follicles which contained both Ang II receptors and FSH receptors were mainly early atretic. Since Ang II receptor-containing follicles in the rat ovary were mainly atretic these studies suggest that in the rat Ang II may be a major factor in regulating the function of atretic ovarian follicles.

  14. Hypothalamic kiss1 mRNA and kisspeptin immunoreactivity are reduced in a rat model of polycystic ovary syndrome (PCOS).

    PubMed

    Brown, Russell E; Wilkinson, Diane A; Imran, Syed A; Caraty, Alain; Wilkinson, Michael

    2012-07-27

    An intact hypothalamic kiss1/kisspeptin/kiss1r complex is a prerequisite for reproductive competence, and kisspeptin treatment could be a practical therapeutic approach to some problems of infertility. One such disorder is polycystic ovarian syndrome (PCOS), a common cause of infertility affecting more than 100 million women. A rodent model of PCOS is the prepubertal female rat treated for a prolonged period with dihydrotestosterone (DHT), which induces many of the metabolic characteristics of the syndrome. We hypothesized that hypothalamic kiss1 mRNA levels, and kisspeptin immunoreactivity (ir), would be abnormal in these rats. Prepubertal female rats were exposed to DHT for 60 days. Rats were killed in two groups: at 26 and 60 days of DHT exposure. Kiss1 mRNA was quantified in hypothalamus, pituitary, ovary and visceral adipose tissue. Separate groups of rats provided brain tissue for immunohistochemical analysis of kisspeptin-ir. At 26 days of DHT exposure, hypothalamic kiss1 mRNA was severely depleted. In contrast DHT had no effect on pituitary kiss1 expression but it significantly increased levels of kiss1 mRNA in fat (+9-fold; p<0.01) and in ovary (+3-fold; p<0.05). At 60days, kiss1 expression had reverted to normal in hypothalamus and ovary but remained elevated in fat (+4-fold; p<0.05). Immunohistochemical analysis revealed that after 26 days of exposure to DHT, kisspeptin-ir was almost completely absent in the arcuate nucleus and a large depletion in kisspeptin +ve fibers was also seen in the paraventricular nucleus, supraoptic nucleus and in the anteroventral periventricular area. At 60 days, despite restored normal levels of kiss1 mRNA, hypothalamic kisspeptin-ir remained depleted in the treated rats. In summary Kiss1 gene expression is differentially affected in various tissues by chronic exposure to dihydrotestosterone in a rat model of polycystic ovary syndrome. In hypothalamus, specifically, kiss1 mRNA, and levels of kisspeptin immunoreactivity, are

  15. [Effects of soy isoflavones on the expression of Bax mRNA and Ca(2+)-ATPase activity in ovaries of perimenopause rats].

    PubMed

    Wen, Hai-Xia; Xiao, Xiao-Hui; Zhao, Wei; Liu, Guo-Yi; Song, Hong-Zhe; Ni, Jiang

    2007-02-01

    To investigate the effects of soy isoflavones (SI) on the expression of Bax mRNA and Ca(2+) -ATPase activity in ovaries of perimenopause rats. The animal model of perimenopause rats was established by unforced aging. 12 month-old presenilins female Wistar rats were administered by intragastric (ig) with low (500 mg/kg), middle (158 mg/kg) and high (500 mg/kg) does of SI for 8 weeks. The expression of Bax mRNA in ovaries were detected by RT-PCR. Ca(2+) -ATPase activity in ovaries and MDA content and SOD activity in serum were detected by chemi-chromatometry. Intervention of SI could significantly decrease the expression of Bax mRNA in ovaries and MDA content in serum, increase Ca(2+) -ATPase activity in ovaries and SOD activity in serum of presenilins rats (P < 0.05 or P < 0.01). Soy isoflavones could down-regulate the expression of Bax mRNA and increase Ca(2+) -ATPase activity in aged ovaries. It is probably one of the mechanisms to improve the function of aged ovaries in perimenopause rats.

  16. Changes of The Uterine Tissue in Rats with Polycystic Ovary Syndrome Induced by Estradiol Valerate

    PubMed Central

    Mirabolghasemi, Ghadire; Kamyab, Zahra

    2017-01-01

    Background Polycystic ovary syndrome (PCOS) is one of the most common hormonal disorders that can lead to irregular menstrual cycles and hyperandrogenism. Reduced levels of progesterone and increased estrogen in these women can perpetually stimulate the endometrial tissue of the uterus. In this study, we assess the effect of PCOS induction by estradiol valerate (EV) in a rat model. Materials and Methods In this experimental study, adult female Wistar rats that weighed approximately 200 g were divided into control, sham, and experimental groups (n=6 per group). The experimental group received subcutaneous injections of 2 mg EV for induction of PCOS. We confirmed the presence of PCOS in the experimental group rats. Rats from all groups were subsequently killed, after which their uteri were removed and fixed for histological and cytological analyses. The uterine tissue sections were stained with hematoxylin and eosin (H&E) and iron hematoxylin (iron-H). We examined epithelium height, thickness of the uterus wall, and frequency of the mitotic cells. The data were assessed at α=0.05. Results Uterine tissue findings from the experimental group showed significant increases in the height of the uterus luminal epithelium, the thickness of the uterus wall, and the frequency of eosinophils in the endometrial stroma. We observed an increased frequency of mitotic cells in the experimental group in both luminal and glandular epithelia of the uterus. An increased rate of the glandular epithelium region was noticeable and significant. Conclusion Induction of PCOS by EV could change the proliferation rate in the endo- metrial tissue of the uterus. PMID:28367305

  17. Comparative proteomic analysis of primordial follicles from ovaries of immature and aged rats.

    PubMed

    Govindaraj, Vijayakumar; Rao, A Jagannadha

    2015-01-01

    Age related decline in reproductive performance in women is well documented and apoptosis has been considered as one of the reasons for the decline of primordial follicle reserve. Recently we observed a decline in the efficiency of DNA repair ability in aged rat primordial follicles as demonstrated by decreased mRNA levels of DNA repair genes BRCA1 and H2AX. In the present study, a two-dimensional electrophoresis (2DE) proteomic approach was employed to identify differentially expressed proteins in primordial follicles isolated from ovaries of immature (∼20 days) and aged (∼400-450 days) rats. Using MALDI-TOF/TOF MS, we identified 13 differentially expressed proteins (p < 0.05) which included seven up-regulated and six down-regulated proteins in aged primordial follicles. These proteins are involved in a wide range of biological functions including apoptosis, DNA repair, and the immune system. Interestingly, the differentially expressed proteins such as FIGNL1 (DNA repair) and BOK (apoptotic protein) have not been previously reported in the rat primordial follicles and these proteins can be related to some common features of ovarian aging such as loss of follicle reserve and genome integrity. The quantitative differences of two important proteins BOK and FIGNL1 observed by the proteomic analysis were correlated with the transcript levels, as determined by semi-quantitative RT-PCR. Our results improve the current knowledge about protein factors associated with molecular changes in rat primordial follicles as a function of aging and our understanding of the proteomic processes involved in degenerative changes observed in aging primordial follicles.

  18. Soy isoflavones exert beneficial effects on letrozole-induced rat polycystic ovary syndrome (PCOS) model through anti-androgenic mechanism.

    PubMed

    Rajan, Ravi Kumar; M, Siva Selva Kumar; Balaji, Bhaskar

    2017-12-01

    Soy is the main source of phytoestrogens, which has long been used as traditional food. One major subtype of phytoestrogens includes isoflavones and they are scientifically validated for their beneficial actions on many hormone-dependent conditions. The present study examines the effect of soy isoflavones on letrozole-induced polycystic ovary syndrome (PCOS) rat model. PCOS was induced in Sprague-Dawley rats with of 1 mg/kg letrozole, p.o. once daily for 21 consecutive days. Soy isoflavones (50 and 100 mg/kg) was administered for 14 days after PCOS induction. Physical parameters (body weight, oestrous cycle determination, ovary and uterus weight) metabolic parameters (oral glucose tolerance test, total cholesterol), steroidal hormone profile (testosterone and 17β-oestradiol), steroidogenic enzymes (3β-hydroxy steroid dehydrogenase (HSD) and 17β-HSD), oxidative stress and histopathology of ovary were studied. Soy isoflavones (100 mg/kg) treatment significantly altered the letrozole-induced PCOS symptoms as observed by decreased body weight gain (p < 0.05), percentage diestrous phase (p < 0.001), testosterone (p < 0.001), 3β-HSD (p < 0.01) and 17β-HSD (p < 0.001) enzyme activity and oxidative stress. Histological results reveal that soy isoflavones treatment in PCOS rats resulted in well-developed antral follicles and normal granulosa cell layer in rat ovary. Treatment with soy isoflavones exerts beneficial effects in PCOS rats (with decreased aromatase activity) which might be due to their ability to decrease testosterone concentration in the peripheral blood. Analysis of physical, biochemical and histological evidences shows that soy isoflavones may be beneficial in PCOS.

  19. Adrenomedullin2 (ADM2)/intermedin (IMD) in rat ovary: changes in estrous cycle and pregnancy and its role in ovulation and steroidogenesis.

    PubMed

    Chauhan, Madhu; Balakrishnan, Meena; Blesson, Chellakkan S; Yallampalli, Chandra

    2015-02-01

    Adrenomedullin2 (ADM2) is reported to facilitate embryo implantation and placental development. Therefore, the current study was undertaken to identify if ADM2 has a functional role in ovary to facilitate its reproductive actions. This study shows that the expression of ADM2 is differentially regulated in rat estrous cycle and that ADM2 increases the synthesis and secretion of 17beta-estradiol accompanied with an increase in the expression of steroidogenic factor 1 (Sf1), estrogen receptor Esr1, and enzymes involved in steroidogenesis in equine chorionic gonadotropin (eCG)-treated rat ovaries. In addition, inhibition of endogenous ADM2 function in eCG-treated immature rats caused impaired ovulation. Furthermore, the mRNA expression of Adm2 and receptor activity modifying protein 3 is higher in the ovary on Day 18 compared to nonpregnant and pregnant rats on Day 22. ADM2-like immunoreactivity is localized in granulosa cells, blood vessels, oocytes, cumulous oophorus, and corpus luteum of pregnant ovaries, suggesting a potential role for ADM2 in the ovary. This is supported by the presence of ADM2-like immunoreactivity in the corpus luteum during pregnancy and a decline in aromatase immunoreactivity in corpus luteum on Day 9 of gestation in rats infused with ADM2 antagonist during implantation and decidualization phase. Taken together, this study suggests a potential involvement of ADM2 in the rat ovary in regulating synthesis of estradiol to support ovulation and facilitate efficient implantation and placental development for a successful pregnancy.

  20. Quantification of steroids and endocrine disrupting chemicals in rat ovaries by LC-MS/MS for reproductive toxicology assessment.

    PubMed

    Quignot, Nadia; Tournier, Mikaël; Pouech, Charlène; Cren-Olivé, Cécile; Barouki, Robert; Lemazurier, Emmanuel

    2012-06-01

    Reproductive function is controlled by a finely tuned balance of androgens and estrogens. Environmental toxicants, notably endocrine disrupting chemicals (EDCs), appear to be involved in the disruption of hormonal balance in several studies. To further describe the effects of selected EDCs on steroid secretion in female rats, we aim to simultaneously investigate the EDC concentration and the sex hormone balance in the ovaries. Therefore, an effective method has been developed for the quantification of the sex steroid hormones (testosterone, androstenedione, estradiol, and estrone) and four endocrine disrupting chemicals (bisphenol A, atrazine, and the active metabolites of methoxychlor and vinclozolin) in rat ovaries. The sample preparation procedure is based on the so-called "quick, easy, cheap, effective, rugged, and safe" approach, and an analytical method was developed to quantify these compounds with low detection limits by liquid chromatography coupled with a tandem mass spectrometer. This analytical method, applied to rat ovary samples following subacute EDC exposure, revealed some new findings for toxicological evaluation. In particular, we showed that EDCs with the same described in vitro mechanisms of action have different effects on the gonadal steroid balance. These results highlight the need to develop an integrative evaluation with the simultaneous measurement of EDCs and numerous steroids for good risk assessment.

  1. Tissue damage in rat ovaries subjected to torsion and detorsion: effects of L-carnitine and N-acetyl cysteine.

    PubMed

    Usta, Ufuk; Inan, Mustafa; Erbas, Hakan; Aydogdu, Nurettin; Oz Puyan, Fulya; Altaner, Semsi

    2008-05-01

    We aimed to evaluate histopathological changes, to detect HIF-1alpha staining intensities and to determine MDA levels in rat ovaries, which were subjected to torsion and detorsion and treated with L -carnitine or N-acetyl cysteine (NAC). Forty-eight prepubertal female Sprague-Dawley rats were divided into five groups (n = 8): 1, control; 2, ischemia; 3, reperfusion; 4, L -carnitine; and 5, NAC groups. In groups 3, 4 and 5, an ischemic period of 3 h was followed by reperfusion for 24 h. In groups 4 and 5, ischemia was performed and either L -carnitine or NAC was infused intraperitoneally 30 min before reperfusion. Ovarian tissues were examined histopathologically; tissue MDA levels and serum IL-6 levels were determined biochemically. HIF-1alpha was applied to all ovaries immunohistochemically. Total tissue damage scores, tissue MDA levels and HIF-1alpha scores, were significantly higher in group 2 (all P < 0.001) than group 4, and group 3 than group 4 (P < 0.001, P = 0.05 and P < 0.001, respectively). They were also significantly higher in group 2 (all P < 0.001) than group 5. When group 3 is compared to group 5, total tissue damage scores and tissue MDA levels were significantly higher in the former (P < 0.01 and P < 0.001, respectively). Serum IL-6 levels were significantly higher in group 2 when compared to groups 1, 4 and 5 (all P < 0.01). The degree of tissue damage of the torsioned ovaries decreased after a reperfusion period of 24 h in the torsioned ovaries. However, ovaries of both L -carnitine and NAC groups showed better recovery than the reperfusion group.

  2. The effect of oxytocin and Kisspeptin-10 in ovary and uterus of ischemia-reperfusion injured rats.

    PubMed

    Aslan, M; Erkanli Senturk, G; Akkaya, H; Sahin, S; Yılmaz, B

    2017-08-01

    Ischemia/reperfusion (I/R) injuries result in damage to endothelial and parenchymal cells. Oxytocin (OXY) stimulates uterine contraction during parturition and myoepithelial cells during suckling. OXY has been used as a protective antioxidant. Kisspeptin plays a key role in the central control of reproductive functions and onset of puberty. Recent studies show that these reproductive hormones have protective potential as antioxidant. The aim of this study is to investigate the potential protective effects of Kisspeptin and OXY as antioxidants on I/R injured ovary and uterus of female rats. Rats were separated into five groups. Group 1, is control group; Group 2, rats were subjected to ischemia followed by reperfusion. Group 3, OXY administration 30 min prior to I/R applied rats; Group 4, Kisspeptin administration 30 min prior to I/R applied rats; Group 5, OXY and Kisspeptin administration 30 min prior to I/R. Ovary and uterus were removed for histopathological and biochemical observations. Malondialdehyde, glutathione levels, and superoxide dismutase activities were analyzed in order to observe antioxidant potential of OXY and Kisspeptin. Hematoxylin and Eosin staining was applied for histopathologic scoring. Stromal and granulosa cells in ovary, endometrial cells in uterus were damaged in I/R group. The cellular damage of ovary and uterus were reduced in OXY and Kisspeptin administered I/R group when compared to only Kisspeptin injected I/R group and I/R group. There is no significant difference between OXY and OXY + Kisspeptin injected I/R groups. MDA levels were decreased in Kisspeptin and/or Oxytocin applied I/R group compared to I/R group. SOD activity and GSH levels were increased in Kisspeptin and/or OXY applied I/R group compared to I/R group. The present results suggest that exogenous application of oxytocin and kisspeptin can have antioxidant effects on the uterus and ovary. Copyright © 2017. Published by Elsevier B.V.

  3. Systems pharmacology to investigate the interaction of berberine and other drugs in treating polycystic ovary syndrome

    PubMed Central

    Wang, Yu; Fu, Xin; Xu, Jing; Wang, Qiuhong; Kuang, Haixue

    2016-01-01

    Polycystic ovary syndrome (PCOS) is a common multifactorial endocrine disorder among women of childbearing age. PCOS has various and heterogeneous clinical features apart from its indefinite pathogenesis and mechanism. Clinical drugs for PCOS are multifarious because it only treats separate symptoms. Berberine is an isoquinoline plant alkaloid with numerous biological activities, and it was testified to improve some diseases related to PCOS in animal models and in humans. Systems pharmacology was utilized to predict the potential targets of berberine related to PCOS and the potential drug-drug interaction base on the disease network. In conclusion, berberine is a promising polypharmacological drug for treating PCOS, and for enhancing the efficacy of clinical drugs. PMID:27306862

  4. Hypothalamic transcriptional expression of the kisspeptin system and sex steroid receptors differs among polycystic ovary syndrome rat models with different endocrine phenotypes.

    PubMed

    Marcondes, Rodrigo Rodrigues; Carvalho, Kátia Cândido; Giannocco, Gisele; Duarte, Daniele Coelho; Garcia, Natália; Soares-Junior, José Maria; da Silva, Ismael Dale Cotrim Guerreiro; Maliqueo, Manuel; Baracat, Edmund Chada; Maciel, Gustavo Arantes Rosa

    2017-08-01

    Polycystic ovary syndrome is a heterogeneous endocrine disorder that affects reproductive-age women. The mechanisms underlying the endocrine heterogeneity and neuroendocrinology of polycystic ovary syndrome are still unclear. In this study, we investigated the expression of the kisspeptin system and gonadotropin-releasing hormone pulse regulators in the hypothalamus as well as factors related to luteinizing hormone secretion in the pituitary of polycystic ovary syndrome rat models induced by testosterone or estradiol. A single injection of testosterone propionate (1.25 mg) (n=10) or estradiol benzoate (0.5 mg) (n=10) was administered to female rats at 2 days of age to induce experimental polycystic ovary syndrome. Controls were injected with a vehicle (n=10). Animals were euthanized at 90-94 days of age, and the hypothalamus and pituitary gland were used for gene expression analysis. Rats exposed to testosterone exhibited increased transcriptional expression of the androgen receptor and estrogen receptor-β and reduced expression of kisspeptin in the hypothalamus. However, rats exposed to estradiol did not show any significant changes in hormone levels relative to controls but exhibited hypothalamic downregulation of kisspeptin, tachykinin 3 and estrogen receptor-α genes and upregulation of the gene that encodes the kisspeptin receptor. Testosterone- and estradiol-exposed rats with different endocrine phenotypes showed differential transcriptional expression of members of the kisspeptin system and sex steroid receptors in the hypothalamus. These differences might account for the different endocrine phenotypes found in testosterone- and estradiol-induced polycystic ovary syndrome rats.

  5. Effects of Spirulina on Cyclophosphamide-Induced Ovarian Toxicity in Rats: Biochemical and Histomorphometric Evaluation of the Ovary

    PubMed Central

    Yener, Nese Arzu; Sinanoglu, Orhun; Ilter, Erdin; Celik, Aygen; Sezgin, Gulbuz; Midi, Ahmet; Aksungar, Fehime

    2013-01-01

    Cyclophosphamide (Cyc) is known to cause ovotoxicity and infertility in women. Our aim is to investigate the possible ovotoxic effects of Cyc and possible antioxidant and protective effects of blue-green algae, Spirulina (Sp), in rat ovaries. Eighteen rats were given: group I (n = 6, control); group II (n = 6, CP), a single dose Cyc; group III (n = 6, Sp+Cyc), 7 days Sp+single dose Cyc. Tissue malondialdehyde (MDA) levels, superoxide dismutase (SOD), and catalase (CAT) activities are assessed biochemically. Normal and atretic primordial and primary follicle counts for all sections obtained for each ovary are calculated. Mean number of follicle counts for each group are compared. In Sp+Cyc group, tissue MDA levels were significantly lower than those in the CP and higher than those in the C group (CP > Sp+Cyc > C). Tissue SOD activity was significantly higher in Sp+Cyc group than that in the CP group and lower than that in the C group (C > Sp+Cyc > C). No statistically significant difference was found between the ovarian CAT activities in any group. Histomorphometrically, there was also no significant difference between the mean numbers of normal and atretic small follicle counts. Our results suggest that single dose Cyc has adverse effects on oxidant status of the ovaries and Sp has protective effects in Cyc-induced ovotoxicity. PMID:23762559

  6. Kisspeptin mRNA expression is increased in the posterior hypothalamus in the rat model of polycystic ovary syndrome.

    PubMed

    Matsuzaki, Toshiya; Tungalagsuvd, Altankhuu; Iwasa, Takeshi; Munkhzaya, Munkhsaikhan; Yanagihara, Rie; Tokui, Takako; Yano, Kiyohito; Mayila, Yiliyasi; Kato, Takeshi; Kuwahara, Akira; Matsui, Sumika; Irahara, Minoru

    2017-01-30

    Hypersecretion of luteinizing hormone (LH) is a common endocrinological finding of polycystic ovary syndrome (PCOS). This derangement might have a close relationship with hypothalamic kisspeptin expression that is thought to be a key regulator of gonadotropin-releasing hormone (GnRH). We evaluated the relationship between the hypothalamic-pituitary-gonadal axis (HPG axis) and kisspeptin using a rat model of PCOS induced by letrozole. Letrozole pellets (0.4 mg/day) and control pellets were placed subcutaneously onto the backs of 3-week-old female Wistar rats. Body weight, vaginal opening and vaginal smear were checked daily. Blood and tissues of ovary, uterus and brain were collected at 12-weeks of age. An hypothalamic block was cut into anterior and posterior blocks, which included the anteroventral periventricular nucleus (AVPV) and the arcuate nucleus (ARC), respectively, in order to estimate hypothalamic kisspeptin expression in each area. The letrozole group showed a similar phenotype to human PCOS such as heavier body weight, heavier ovary, persistent anovulatory state, multiple enlarged follicles with no corpus luteum and higher LH and testosterone (T) levels compared to the control group. Kisspeptin mRNA expression in the posterior hypothalamic block including ARC was higher in the letrozole group than in the control group although its expression in the anterior hypothalamic block was similar between groups. These results suggest that enhanced KNDy neuron activity in ARC contributes to hypersecretion of LH in PCOS and might be a therapeutic target to rescue ovulatory disorder of PCOS in the future.

  7. Artemisinin induces hormonal imbalance and oxidative damage in the erythrocytes and uterus but not in the ovary of rats.

    PubMed

    Farombi, E O; Abolaji, A O; Adedara, I A; Maduako, I; Omodanisi, I

    2015-01-01

    Artemisinin is an antimalarial drug previously reported to induce neurotoxicity and embryotoxicity in animal models. This study investigated the erythrocytes and reproductive toxicity potentials of artemisinin in female rats. Animals were randomly divided into four study groups of eight rats each. The control group (group I) received corn oil, the vehicle, while groups II-IV were orally exposed to 7, 35 and 70 mg kg(-1) day(-1) of artemisinin, respectively, by gastric intubation for 7 consecutive days. Subsequently, we evaluated the impact of artemisinin on the endocrine environment and selected markers of oxidative damage and antioxidant status of the erythrocytes, ovary and uterus. Artemisinin significantly increased hydrogen peroxide (H2O2) and malondialdehyde (MDA) levels and decreased catalase, glutathione peroxidase and superoxide dismutase activities in erythrocytes and uterus of rats compared with control group (p < 0.05). However, artemisinin did not alter ovarian MDA, H2O2, glutathione levels and catalase activity, while ovarian and uterine histological assessment revealed absence of visible lesions. Moreover, artemisinin significantly decreased follicle-stimulating hormone and increased progesterone levels compared with control (p < 0.05). Thus, these data suggest that in the absence of malarial parasite infection, artemisinin induced hormonal imbalance and oxidative damage in the erythrocytes and uterus but spared the ovary of rats.

  8. Steroid hormone production in testis, ovary, and adrenal gland of immature rats irradiated in utero with /sup 60/Co

    SciTech Connect

    Inano, H.; Suzuki, K.; Ishii-Ohba, H.; Imada, Y.; Kumagai, R.; Kurihara, S.; Sato, A.

    1989-02-01

    Pregnant rats received whole-body irradiation at 20 days of gestation with 2.6 Gy lambda rays from a 60Co source. Endocrinological effects before maturation were studied using testes and adrenal glands obtained from male offspring and ovaries from female offspring irradiated in utero. Seminiferous tubules of the irradiated male offspring were remarkably atrophied with free germinal epithelium and containing only Sertoli cells. Female offspring also had atrophied ovaries. Testicular tissue obtained from intact and 60Co-irradiated rats was incubated with 14C-labeled pregnenolone, progesterone, 17 alpha-hydroxyprogesterone, and androstenedione as a substrate. Intermediates for androgen production and catabolic metabolites were isolated after the incubation. The amounts of these metabolites produced by the irradiated testes were low in comparison with the control. The activities of delta 5-3 beta-hydroxysteroid dehydrogenase, 17 alpha-hydroxylase, C17,20-lyase, and delta 4-5 alpha-reductase in the irradiated testes were 30-40% of those in nonirradiated testes. Also, the activities of 17 beta- and 20 alpha-hydroxysteroid dehydrogenases were 72 and 52% of the control, respectively. In adrenal glands, the 21-hydroxylase activity of the irradiated animals was 38% of the control, but the delta 5-3 beta-hydroxysteroid dehydrogenase activity was comparable to that of the control. On the other hand, the activity of delta 5-3 beta-hydroxysteroid dehydrogenase of the irradiated ovary was only 19% of the control. These results suggest that 60Co irradiation of the fetus in utero markedly affects the production of steroid hormones in testes, ovaries, and adrenal glands after birth.

  9. Transcutaneous electrical acupoint stimulation alleviates the hyperandrogenism of polycystic ovarian syndrome rats by regulating the expression of P450arom and CTGF in the ovaries

    PubMed Central

    Qu, Fan; Liang, Yi; Zhou, Jue; Ma, Rui-Jie; Zhou, Jie; Wang, Fang-Fang; Wu, Yan; Fang, Jian-Qiao

    2015-01-01

    The present study was to investigate the effects of transcutaneous electrical acupoint stimulation (TEAS) in alleviating the hyperandrogenism of polycystic ovarian syndrome (PCOS) model rats induced by testosterone propionate and the possible underlying mechanism. Thirty-six female Sprague-Dawley rats were randomly divided into normal control, PCOS model and TEAS groups with twelve rats in each group. The PCOS model rats were established by single injection of testosterone propionate at 9th day after birth, and the status of estrous cyclicity for each rat was observed. When the 8-week TEAS treatment completed, the weight of body, uterus and ovaries of the rats were respectively measured. The serum levels of total testosterone (TT), sex hormone binding globulin (SHBG), androstenedione, luteinizing hormone (LH), follicle stimulating hormone (FSH) and estradiol (E2) were detected. The mRNA and protein expression levels of aromatase cytochrome P450 (P450arom) and connective tissue growth factor (CTGF) in the ovaries of the rats were respectively measured with real-time quantitative PCR and immunohistochemistry. The TEAS treatment significantly improved the estrous cycles of the PCOS rats and the TEAS group displayed significantly lower average body and ovaries weights than the PCOS model group (P < 0.05). TEAS significantly decreased the serum TT, free androgen index (FAI), androstenedione and LH/FSH levels, and increased the serum FSH levels of the PCOS rats (P < 0.05). The TEAS treatment significantly increased the P450arom mRNA as well as protein expression levels and significantly decreased the CTGF mRNA as well as protein expression levels in the ovaries of the PCOS rats (P < 0.05). We concluded that it is through regulating the P450arom and CTGF expression levels in the ovaries that TEAS significantly alleviates the hyperandrogenism of PCOS rats induced by testosterone propionate. PMID:26221326

  10. Transcutaneous electrical acupoint stimulation alleviates the hyperandrogenism of polycystic ovarian syndrome rats by regulating the expression of P450arom and CTGF in the ovaries.

    PubMed

    Qu, Fan; Liang, Yi; Zhou, Jue; Ma, Rui-Jie; Zhou, Jie; Wang, Fang-Fang; Wu, Yan; Fang, Jian-Qiao

    2015-01-01

    The present study was to investigate the effects of transcutaneous electrical acupoint stimulation (TEAS) in alleviating the hyperandrogenism of polycystic ovarian syndrome (PCOS) model rats induced by testosterone propionate and the possible underlying mechanism. Thirty-six female Sprague-Dawley rats were randomly divided into normal control, PCOS model and TEAS groups with twelve rats in each group. The PCOS model rats were established by single injection of testosterone propionate at 9th day after birth, and the status of estrous cyclicity for each rat was observed. When the 8-week TEAS treatment completed, the weight of body, uterus and ovaries of the rats were respectively measured. The serum levels of total testosterone (TT), sex hormone binding globulin (SHBG), androstenedione, luteinizing hormone (LH), follicle stimulating hormone (FSH) and estradiol (E2) were detected. The mRNA and protein expression levels of aromatase cytochrome P450 (P450arom) and connective tissue growth factor (CTGF) in the ovaries of the rats were respectively measured with real-time quantitative PCR and immunohistochemistry. The TEAS treatment significantly improved the estrous cycles of the PCOS rats and the TEAS group displayed significantly lower average body and ovaries weights than the PCOS model group (P < 0.05). TEAS significantly decreased the serum TT, free androgen index (FAI), androstenedione and LH/FSH levels, and increased the serum FSH levels of the PCOS rats (P < 0.05). The TEAS treatment significantly increased the P450arom mRNA as well as protein expression levels and significantly decreased the CTGF mRNA as well as protein expression levels in the ovaries of the PCOS rats (P < 0.05). We concluded that it is through regulating the P450arom and CTGF expression levels in the ovaries that TEAS significantly alleviates the hyperandrogenism of PCOS rats induced by testosterone propionate.

  11. Analysis of the effects of increasing doses of ionizing radiation to the exteriorized rat ovary on follicular development, atresia, and serum gonadotropin levels

    SciTech Connect

    Jarrell, J.; YoungLai, E.V.; Barr, R.; O'Connell, G.; Belbeck, L.; McMahon, A.

    1986-02-01

    There is increasing interest in the effects of environmental and therapeutic agents on the reproductive system, in particular, the ovary. To study the effects of controlled doses of ionizing radiation to the ovary, Sprague-Dawley rats had their ovaries exteriorized and subjected to increasing doses of radiation. There was a significant increase in ovarian follicular atresia, a significant increase in serum follicle-stimulating hormone levels, but no change in serum luteinizing hormone levels. This experimental protocol may facilitate the testing putative radioprotectants.

  12. Temporal window in which exposure to estradiol permanently modifies ovarian function causing polycystic ovary morphology in rats.

    PubMed

    Cruz, Gonzalo; Barra, Rafael; González, Daniel; Sotomayor-Zárate, Ramón; Lara, Hernán E

    2012-11-01

    To investigate the developmental window in which E(2) exposure produces irreversible changes in ovarian function resulting in polycystic ovary. Basic experimental study. University animal laboratory. Thirty Sprague-Dawley rats were administered a single E(2) valerate dose (10 mg/kg of weight) at 1, 7, 14, 21, or 30 days of age. Control rats were injected with the vehicle at 1 day of age. All rats were sacrificed at 6 months of age. Observation of vaginal opening, estrous cyclicity by vaginal smears, and ovarian morphometry in the 6-month-old rat. Measurement of ovarian noradrenaline by high-performance liquid chromatography coupled with electrochemical detection, serum levels of LH by enzyme-linked immunoassay, P, androstenedione, and E(2) by enzyme immunoassay. Rats exposed to E(2) at 1, 7, or 14 days of life did not show estrual cycling activity and maintained a polycystic ovary (PCO) condition throughout the entirety of the study. However, if the exposure to E(2) occurred after postnatal day 21, the PCO-induced condition was reversible. In rats that developed a permanent PCO condition, we observed significant effects of E(2) on ovarian morphology if exposure occurred on postnatal day 1 and a presumable effect on the hypothalamus if the exposure occurred between postnatal days 1 and 14. Our findings suggest that in rats, the most sensitive period for the promotion of an irreversible PCO morphology by estrogenic compounds is during neonatal early follicular development. Copyright © 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  13. Altered expression of Bcl-2 and Bax in follicles within dehydroepiandrosterone-induced polycystic ovaries in rats.

    PubMed

    Bas, Diana; Abramovich, Dalhia; Hernandez, Fatima; Tesone, Marta

    2011-05-01

    PCOS (polycystic ovary syndrome) is a heterogeneous disease characterized by hyperandrogenaemia, hirsutism, oligo- or amenorrhea, insulin resistance and anovulation. The aim of the present study was to evaluate if the balance between the ovarian expression of Bax (proapoptotic protein) and Bcl-2 (antiapoptotic protein) is altered in a PCOS model developed in rats by DHEA (dehydroepiandrosterone) administration. In addition, the ovarian morphology and the circulating progesterone levels were evaluated. Histological studies confirmed the presence of follicular cysts, atretic follicles and the absence of corpora lutea in the ovaries from the PCOS group and a significant decrease in circulating progesterone levels. Immunohistochemical studies showed that the expression of Bcl-2 and Bax were mainly localized in granulosa cells of AFs (antral follicles) in both groups. Bax expression was greater in preantral and AFs from PCOS ovarian sections than in the controls. In contrast, intense Bcl-2 immunostaining was observed in the control AFs, while Bcl-2 protein was either absent in PFs (preantral follicles) or weakly expressed in AFs from PCOS rats. These results were partially confirmed by Western studies. Data revealed that the ovarian level of Bcl-2 protein was lower in PCOS than in the control and that there were no differences in Bax ovarian levels between groups. However, Bax/Bcl-2 ratio was significantly higher in PCOS group than in the control group. In conclusion, an increase in ovarian apoptosis through an imbalance among the Bcl-2 family members may be involved in the transformation of growing follicles in cystic follicles in the ovaries from DHEA-induced PCOS rats.

  14. Ample Evidence: Dehydroepiandrosterone (DHEA) Conversion into Activated Steroid Hormones Occurs in Adrenal and Ovary in Female Rat

    PubMed Central

    Zhou, Yingqiao; Kang, Jian; Chen, Di; Han, Ningning; Ma, Haitian

    2015-01-01

    Dehydroepiandrosterone (DHEA) is important for human health, especially for women. All estrogens and practically half of androgens are synthesized from DHEA in peripheral tissues. However, the mechanism and exact target tissues of DHEA biotransformation in the female are not fully clear. The present study showed that maximal content of androstenedione (AD) and testosterone (T) were observed at 3h after DHEA administration in female rats, which was 264% and 8000% above the control, respectively. Estradiol (E2) content significantly increased at 6h after DHEA administration, which was 113% higher than that in control group. Gavage with DHEA could significantly reduce 3β-hydroxysteroid dehydrogenase (3β-HSD) mRNA level at 3-12h and 17β-hydroxysteroid dehydrogenase (17β-HSD) mRNA level at 12h in ovary, while increasing aromatase mRNA levels at 6, 24, and 48h. It is interesting that administration of DHEA caused a significant increase of 17β-HSD, 3β-HSD and aromatase mRNA levels in adrenal. The AD and T contents also markedly increased by 537% and 2737% after DHEA administration in ovariectomised rats, in company with a significant increase in 17β-HSD and 3β-HSD mRNA levels and decreased aromatase mRNA level in adrenal. However, DHEA administration did not restore the decreased E2, estrone (E1), and progesterone (P) caused by the removal of the ovaries in females. These results clearly illustrated that exogenous DHEA is preferentially converted into androgens in adrenal, while its conversion to estrogens mainly happens in the ovary through steroidogenic enzyme in female rats. PMID:25962158

  15. Ample Evidence: Dehydroepiandrosterone (DHEA) Conversion into Activated Steroid Hormones Occurs in Adrenal and Ovary in Female Rat.

    PubMed

    Zhou, Yingqiao; Kang, Jian; Chen, Di; Han, Ningning; Ma, Haitian

    2015-01-01

    Dehydroepiandrosterone (DHEA) is important for human health, especially for women. All estrogens and practically half of androgens are synthesized from DHEA in peripheral tissues. However, the mechanism and exact target tissues of DHEA biotransformation in the female are not fully clear. The present study showed that maximal content of androstenedione (AD) and testosterone (T) were observed at 3h after DHEA administration in female rats, which was 264% and 8000% above the control, respectively. Estradiol (E2) content significantly increased at 6h after DHEA administration, which was 113% higher than that in control group. Gavage with DHEA could significantly reduce 3β-hydroxysteroid dehydrogenase (3β-HSD) mRNA level at 3-12h and 17β-hydroxysteroid dehydrogenase (17β-HSD) mRNA level at 12h in ovary, while increasing aromatase mRNA levels at 6, 24, and 48 h. It is interesting that administration of DHEA caused a significant increase of 17β-HSD, 3β-HSD and aromatase mRNA levels in adrenal. The AD and T contents also markedly increased by 537% and 2737% after DHEA administration in ovariectomised rats, in company with a significant increase in 17β-HSD and 3β-HSD mRNA levels and decreased aromatase mRNA level in adrenal. However, DHEA administration did not restore the decreased E2, estrone (E1), and progesterone (P) caused by the removal of the ovaries in females. These results clearly illustrated that exogenous DHEA is preferentially converted into androgens in adrenal, while its conversion to estrogens mainly happens in the ovary through steroidogenic enzyme in female rats.

  16. Exposure of Female Rats to an Environmentally Relevant Mixture of Brominated Flame Retardants Targets the Ovary, Affecting Folliculogenesis and Steroidogenesis.

    PubMed

    Lefèvre, Pavine L C; Berger, Robert G; Ernest, Sheila R; Gaertner, Dean W; Rawn, Dorothea F K; Wade, Michael G; Robaire, Bernard; Hales, Barbara F

    2016-01-01

    Brominated flame retardants (BFRs) are incorporated into various consumer products to prevent flame propagation. These compounds leach into the domestic environment, resulting in chronic exposure and contamination. Pregnancy failure is associated with high levels of BFRs in human follicular fluid, raising serious questions regarding their impact on female reproductive health. The goal of this study is to elucidate the effects of an environmentally relevant BFR mixture on female rat ovarian functions (i.e., folliculogenesis and steroidogenesis). A BFR dietary mixture formulated to mimic the relative BFR congener levels in North American house dust was administered to adult female Sprague-Dawley rats from 2 to 3 wk before mating until Gestational Day 20; these diets were designed to deliver nominal doses of 0, 0.06, 20, or 60 mg/kg/day of the BFR mixture. Exposure to BFRs triggered an approximately 50% increase in the numbers of preantral and antral follicles and an enlargement of the antral follicles in the ovaries of the dams. A significant reduction in the expression of catalase, an antioxidant enzyme, and downregulation of the expression of insulin-like factor 3 (Insl3) and 17alpha-hydroxylase (Cyp17a1) were observed in the ovary. In addition, BFR exposure affected steroidogenesis; we observed a significant decrease in circulating 17-hydroxypregnenolone and an increase in testosterone concentrations in BFR-exposed dams. Thus, BFRs target ovarian function in the rat, adversely affecting both folliculogenesis and steroidogenesis.

  17. Endocrine disruption and oxidative stress implications of artemether-lumefantrine combination therapy in the ovary and uterus of rats.

    PubMed

    Abolaji, A O; Adesanoye, O A; Awogbindin, I; Farombi, E O

    2016-01-25

    In the current study, we evaluated the endocrine disruption effect and oxidative stress implication of therapeutic dose of artemether-lumefantrine combination therapy on the ovary and uterus of rats. In this respect, female rats were divided into four groups: animals were per orally treated with tween 80 (control), artemether (4 mg kg(-1) body weight), lumefantrine (24 mg kg(-1) body weight) and artemether-lumefantrine (artemether, 4 mg kg(-1) body weight and lumefantrine, 24 mg kg(-1) body weight). We found that therapeutic doses of the drugs did not change the levels of ovarian hydrogen peroxide (H2O2) and malondialdehyde (MDA), but increased uterine levels of H2O2 and MDA and reduced ovarian and uterine levels of reduced glutathione. In addition, whilst ovarian glutathione peroxidase (GPx) activity reduced in the lumefantrine monotherapy group, uterine GPx increased in the artemether monotherapy as well as the artemether-lumefantrine groups. Furthermore, the drugs reduced ovarian and uterine glutathione-S-transferase and uterine superoxide dismutase activities. The drugs reduced oestrogen level, whereas follicle-stimulating hormone was reduced by lumefantrine and artemether-lumefantrine therapies. Additionally, artemether and lumefantrine monotherapies significantly increased prolactin and progesterone levels compared with the control (p < 0.05). The results suggest that in the absence of malarial parasite infection, the drugs induced oxidative stress in the ovary and uterus and disrupt hormonal balance in the rats.

  18. Noradrenaline modulates the presence of gonadotropin-releasing hormone in ovary. The importance of its interrelation on the ovarian steroidogenesis and apoptosis on dioestrus II in rat.

    PubMed

    Bronzi, Cynthia D; Orozco, Adriana S Vega; Rodriguez, Diego; Rastrilla, Ana María; Sosa, Zulema Y; Casais, Marilina

    2015-11-01

    The aim of this work was to investigate if noradrenaline (NA), added in the coeliac ganglion -superior ovarian nerve- ovary system (CG-SON-O) and in ovary incubation, modifies the release of ovarian progesterone (P4), gonadotropin-releasing hormone (GnRH) and oestradiol (E2), and the expression of 3β-HSD and 20α-HSD and proapoptotic bax and antiapoptotic bcl-2 on dioestrus II in the rat. The CG-SON-O system and the ovary were removed and placed in one cuvette containing Krebs-Ringer solution (control groups), and NA was added to the ganglion compartment in the ex vivo system and in the ovary compartment in the ovary incubation (experimental groups). P4, GnRH and E2 were measured by RIA, and gene expression was measured by RT-PCR. In the ex-vivo system, the release of ovarian P4 and GnRH and the expression of 3β-HSD and bax decreased; E2 and bcl-2 increased, and the bax/bcl-2 ratio decreased. However, in the ovary incubation, P4, GnRH, the expression of 3β-HSD and bax increased; E2, the expression of 20α-HSD and bcl-2 decreased while the bax/bcl-2 ratio increased, thus favoring apoptosis. The peripheral nervous system protected the ovary from the apoptotic mechanisms while in the ovary incubation the effect was reverted. Our results indicate that NA regulates ovarian steroidogenesis and apoptosis by modulating GnRH release from the coeliac ganglion and ovary, being NA a possible generator of a GnRH-gonadotropins axis in the ovary. This work is expected to contribute with new evidence of the clinical importance of catecholamines and GnRH in therapy and prevention of ovarian pathologies.

  19. Adrenomedullin2 (ADM2)/Intermedin (IMD) in Rat Ovary: Changes in Estrous Cycle and Pregnancy and Its Role in Ovulation and Steroidogenesis1

    PubMed Central

    Chauhan, Madhu; Balakrishnan, Meena; Blesson, Chellakkan S.; Yallampalli, Chandra

    2014-01-01

    ABSTRACT Adrenomedullin2 (ADM2) is reported to facilitate embryo implantation and placental development. Therefore, the current study was undertaken to identify if ADM2 has a functional role in ovary to facilitate its reproductive actions. This study shows that the expression of ADM2 is differentially regulated in rat estrous cycle and that ADM2 increases the synthesis and secretion of 17beta-estradiol accompanied with an increase in the expression of steroidogenic factor 1 (Sf1), estrogen receptor Esr1, and enzymes involved in steroidogenesis in equine chorionic gonadotropin (eCG)-treated rat ovaries. In addition, inhibition of endogenous ADM2 function in eCG-treated immature rats caused impaired ovulation. Furthermore, the mRNA expression of Adm2 and receptor activity modifying protein 3 is higher in the ovary on Day 18 compared to nonpregnant and pregnant rats on Day 22. ADM2-like immunoreactivity is localized in granulosa cells, blood vessels, oocytes, cumulous oophorus, and corpus luteum of pregnant ovaries, suggesting a potential role for ADM2 in the ovary. This is supported by the presence of ADM2-like immunoreactivity in the corpus luteum during pregnancy and a decline in aromatase immunoreactivity in corpus luteum on Day 9 of gestation in rats infused with ADM2 antagonist during implantation and decidualization phase. Taken together, this study suggests a potential involvement of ADM2 in the rat ovary in regulating synthesis of estradiol to support ovulation and facilitate efficient implantation and placental development for a successful pregnancy. PMID:25395681

  20. Stereological study on the effect of vitamin C in preventing the adverse effects of bisphenol A on rat ovary

    PubMed Central

    Soleimani Mehranjani, Malek; Mansoori, Tayebeh

    2016-01-01

    Background: Bisphenol A (BPA), an environmental pollutant, can generate free radicals which damages the reproductive system. Vitamin C is an antioxidant which may prevent the adverse effects of free radicals. Objective: The aim was to investigate the effect of vitamin C on the ovary tissue in rats treated with BPA. Materials and Methods: In this experimental study, 24 female Wistar rats (200±20 gr) were randomly divided into 4 groups (n=6): control, BPA (60 µg/Kg/day), vitamin C (150 mg/Kg/day) and BPA + vitamin C and orally treated for 20 days. The left ovaries were taken out, fixed for tissue processing and studied using stereological methods. Data were analyzed with SPSS using one-way ANOVA, and the means were considered significantly different at (p<0.05). Results: The total volume of ovary and cortex (p<0.01), medulla (p<0.05), the volume of corpus luteum (p<0.001) and the mean number of antral follicles (p<0.001) significantly reduced in BPA group compared with control, while the number of atretic follicles increased (p<0.05). The volume of oocyte (p<0.01) and its nucleus (p<0.001) in the antral follicles and the thickness of zona pellucida (ZP) in the secondary (p<0.05) and antral (p<0.001) follicles significantly decreased in BPA group compared with controls. The above parameters in the BPA + vitamin C group were compensated to control level. Conclusion: Vitamin C can be used as a potential antioxidant in the case of BPA toxication PMID:27525324

  1. Comparison of early morphological and molecular changes induced by 17-alpha-methyltestosterone and estradiol benzoate in the rat ovary.

    PubMed

    Ferre, Céline; Belluco, Sara; Tinwell, Helen; Bars, Rémi; Benahmed, Mohamed; Rouquie, David; Schorsch, Frédéric

    2013-05-01

    Repeated exposure to 17-α-methyltestosterone (17MT) and estradiol benzoate (EB) for 28 or 90 days in rats induce similar ovarian atrophy. The objective of the present work was to identify and compare the early effects induced by 17MT and EB on the ovary using molecular and histopathological tools. Female rats were evaluated after 1, 3 or 7 days following an oral exposure by gavage at a daily dose of 600 mg/kg/day for 17MT and 5 mg/kg/day for EB. All animals were found to be acyclic after 3 or 7 days of treatment with 17MT and EB. Histopathological changes were present in the ovary, uterus, vagina and mammary gland after both treatments. Ovarian atrophy known as the long term effect of 17MT and EB was not yet detected after 7 days of treatment. But non regressive corpora lutea and cystic follicles were identically observed in the ovary of 17MT and EB treated females. Both compounds induced a decrease of LH transcripts together with an increase of plasma progesterone and prolactin levels. Differences in the profile of regulation of the aromatase were noted after 1 and 3 days of treatment in 17MT treated animals (upregulated) when compared to EB treated animals (downregulated). In summary, we have shown that despite the different nature of hormonal activity, EB and 17MT induce very early endocrine perturbation which presents several similarities. Our work indicated that the detection of early key hormonal markers in short term studies can help to predict the adverse long term effects on target tissues.

  2. Vasoactive intestinal peptide enhanced aromatase activity in the neonatal rat ovary before development of primary follicles or responsiveness to follicle-stimulating hormone

    SciTech Connect

    George, F.W.; Ojeda, S.R.

    1987-08-01

    The authors have investigated the factors that regulate aromatase activity in fetal-neonatal rat ovaries. Ovarian aromatase activity (assessed by measuring the amount of /sup 3/H/sub 2/O formed from (1..beta..-/sup 3/H)testosterone) is low prior to birth and increases to values greater than 30 pmol/hr per mg of protein between days 8 and 12 after birth. The appearance of ovarian aromatase coincides with the development of primordial follicles. Fetal-neonatal ovaries maintained in serum-free organ culture do not develop aromatase activity at the expected time. Ovine follicle-stimulating hormone, ovine luteinizing hormone, or their combination failed to induce the enzyme activity in cultured fetal ovaries, whereas follicle-stimulating hormone is effective in preventing the decline in aromatase activity when postnatal day 8 ovaries are placed in culture. In contrast to follicle-stimulating hormone, dibutyryl-cAMP markedly enhances ovarian aromatase in cultured fetal ovaries. Likewise, enhancement of endogenouse cAMP formation with forskolin or cholera toxin caused an increase in enzyme activity within 24 hr. Vasoactive intestinal peptide, a peptide known to occur in ovarian nerves, caused a dose-dependent increase in aromatase activity in fetal ovaries prior to folliculogenesis. Of related peptides tested, only the peptide having N-terminal histidine and C-terminal isoleucine amide was capable of inducing aromatase activity in fetal ovaries. The fact that VIP can induce aromatase activity in fetal rat ovaries prior to follicle formation and prior to responsiveness to follicle-stimulating hormone suggests that this neuropeptide may play a critical role in ovarian differentiation.

  3. Vasoactive intestinal peptide enhances aromatase activity in the neonatal rat ovary before development of primary follicles or responsiveness to follicle-stimulating hormone.

    PubMed Central

    George, F W; Ojeda, S R

    1987-01-01

    We have investigated the factors that regulate aromatase activity in fetal-neonatal rat ovaries. Ovarian aromatase activity (assessed by measuring the amount of 3H2O) formed from [1 beta-3H]testosterone) is low prior to birth (less than 0.5 pmol/hr per mg of protein) and increases to values greater than 30 pmol/hr per mg of protein between days 8 and 12 after birth. The appearance of ovarian aromatase (postnatal days 2-4) coincides with the development of primordial follicles. Fetal-neonatal ovaries maintained in serum-free organ culture do not develop aromatase activity at the expected time. Ovine follicle-stimulating hormone (0.1-1 microgram/ml), ovine luteinizing hormone (0.1 microgram/ml), or their combination failed to induce the enzyme activity in cultured fetal ovaries, whereas follicle-stimulating hormone is effective in preventing the decline in aromatase activity when postnatal day 8 ovaries are placed in culture. In contrast to follicle-stimulating hormone, dibutyryl-cAMP markedly enhances ovarian aromatase in cultured fetal ovaries. Likewise, enhancement of endogenous cAMP formation with forskolin or cholera toxin caused an increase in enzyme activity within 24 hr. Vasoactive intestinal peptide, a peptide known to occur in ovarian nerves, caused a dose-dependent increase in aromatase activity in fetal ovaries prior to folliculogenesis. Of related peptides tested, only the peptide having N-terminal histidine and C-terminal isoleucine amide was capable of inducing aromatase activity in fetal ovaries. The fact that VIP can induce aromatase activity in fetal rat ovaries prior to follicle formation and prior to responsiveness to follicle-stimulating hormone suggests that this neuropeptide may play a critical role in ovarian differentiation. Images PMID:3039508

  4. Effects of nerve growth factor (NGF) on blood vessels area and expression of the angiogenic factors VEGF and TGFbeta1 in the rat ovary

    PubMed Central

    Julio-Pieper, Marcela; Lara, Hernán E; Bravo, Javier A; Romero, Carmen

    2006-01-01

    Background Angiogenesis is a crucial process in follicular development and luteogenesis. The nerve growth factor (NGF) promotes angiogenesis in various tissues. An impaired production of this neurotrophin has been associated with delayed wound healing. A variety of ovarian functions are regulated by NGF, but its effects on ovarian angiogenesis remain unknown. The aim of this study was to elucidate if NGF modulates 1) the amount of follicular blood vessels and 2) ovarian expression of two angiogenic factors: vascular endothelial growth factor (VEGF) and transforming growth factor beta 1 (TGFbeta1), in the rat ovary. Results In cultured neonatal rat ovaries, NGF increased VEGF mRNA and protein levels, whereas TGFbeta1 expression did not change. Sectioning of the superior ovarian nerve, which increases ovarian NGF protein content, augmented VEGF immunoreactivity and the area of capillary vessels in ovaries of prepubertal rats compared to control ovaries. Conclusion Results indicate that NGF may be important in the maintenance of the follicular and luteal vasculature in adult rodents, either indirectly, by increasing the expression of VEGF in the ovary, or directly via promoting the proliferation of vascular cells. This data suggests that a disruption on NGF regulation could be a component in ovarian disorders related with impaired angiogenesis. PMID:17096853

  5. Quercetin exerts preventive, ameliorative and prophylactic effects on cadmium chloride - induced oxidative stress in the uterus and ovaries of female Wistar rats.

    PubMed

    Nna, Victor Udo; Usman, Umar Zayyanu; Ofutet, Emmanuel Oleba; Owu, Daniel Udofia

    2017-04-01

    This study examined the possible protective effect of quercetin(QE) on cadmium chloride (CdCl2) - induced reproductive toxicity in female rats. Cadmium (Cd) accumulated in the uterus and ovaries of rats, decreased antioxidants [superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione (GSH)], and raised the concentrations of malondialdehyde (MDA) and hydrogen peroxide (H2O2) in the uterus and ovaries of rats. Serum concentrations of estradiol, progesterone, follicle stimulating hormone and luteinizing hormone decreased significantly after CdCl2 administration. Caspase-3 activity significantly increased in the ovaries, with an increase in Bax and a decrease in Bcl-2 protein expressions after CdCl2 treatment. Histopathology of the ovaries revealed significant decrease in follicle number, while the uterus showed cyst-like endometrial glands. All three models of QE treatment [pre-treatment (QE + CdCl2), post-treatment (CdCl2+QE), simultaneous treatment (CdCl2/QE)] decreased Cd accumulation, MDA, H2O2, and increased SOD, CAT and GPx activities in the uterus and ovaries, decreased apoptosis of follicular cells, and increased serum reproductive hormones. However, the QE pre-treated model offered better protection against CdCl2 relative to the other two models. These results suggest that, QE exerts multi-mechanistic protective effects against cadmium toxicity attributable to its antioxidant and anti-apoptotic actions. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Effects of chamomile extract on biochemical and clinical parameters in a rat model of polycystic ovary syndrome.

    PubMed

    Farideh, Zafari Zangeneh; Bagher, Minaee; Ashraf, Amirzargar; Akram, Ahangarpour; Kazem, Mousavizadeh

    2010-10-01

    Polycystic ovary syndrome (PCOS) is a complex endocrine and metabolic disorder associated with ovulatory dysfunction. Presently, little is known about the primary factors that initiate PCOS. Chamomile flowers are used in alternative medicine for its anti-spasmolytic and anti-inflammatory effects. Antispasmodic properties of chamomile ease menstrual cramps and lessen the possibility of premature labor. This medicinal herb also stimulates menstruation. In this study, we evaluated the effects of Chamomile alcoholic-extract on the biochemical and clinical parameters in a rat model of PCOS. Estrous cyclicity of 30 virgin adult cycling rats was monitored by vaginal smears obtained between 0800 and 1200 hours. After about 4 days, each rat received an i.m. injection of Estradiol Valerate (Aburaihan Co., Iran), 2 mg in 0.2 ml of corn oil, to induce PCO. Corn oil was injected to the rats in the control group. All the rats in the experimental group were evaluated for follicular cysts 60 days after the injection. Rats with PCOS were treated by multiple doses (25, 50, 75 mg/kg) of intraperitoneal injections of Chamomile alcoholic-extract for ten days. The data were statistically analyzed at a significance level of p<0.05 by ANOVA, followed by the Student Newman-Keuls post hoc test. The histological and hormonal results showed that Chamomile can decrease the signs of PCOS in the ovarian tissue and help LH secretion in rats (p<0.05). The alcoholic-extract of dried Matricaria chamomilla L. flowers can not only induce recovery from a PCO induced state in rats, but also increase dominant follicles. Additionally better endometrial tissue arrangements can be regarded as another therapeutic effect of Chamomile.

  7. Effects of Chamomile Extract on Biochemical and Clinical Parameters in a Rat Model of Polycystic Ovary Syndrome

    PubMed Central

    Zafari Zangeneh, Farideh; Minaee, Bagher; Amirzargar, Ashraf; Ahangarpour, Akram; Mousavizadeh, Kazem

    2010-01-01

    Introduction Polycystic ovary syndrome (PCOS) is a complex endocrine and metabolic disorder associated with ovulatory dysfunction. Presently, little is known about the primary factors that initiate PCOS. Chamomile flowers are used in alternative medicine for its anti-spasmolytic and anti-inflammatory effects. Antispasmodic properties of chamomile ease menstrual cramps and lessen the possibility of premature labor. This medicinal herb also stimulates menstruation. In this study, we evaluated the effects of Chamomile alcoholic-extract on the biochemical and clinical parameters in a rat model of PCOS. Materials and Methods Estrous cyclicity of 30 virgin adult cycling rats was monitored by vaginal smears obtained between 0800 and 1200 hours. After about 4 days, each rat received an i.m. injection of Estradiol Valerate (Aburaihan Co., Iran), 2 mg in 0.2 ml of corn oil, to induce PCO. Corn oil was injected to the rats in the control group. All the rats in the experimental group were evaluated for follicular cysts 60 days after the injection. Rats with PCOS were treated by multiple doses (25, 50, 75 mg/kg) of intraperitoneal injections of Chamomile alcoholic-extract for ten days. The data were statistically analyzed at a significance level of p<0.05 by ANOVA, followed by the Student Newman-Keuls post hoc test. Results The histological and hormonal results showed that Chamomile can decrease the signs of PCOS in the ovarian tissue and help LH secretion in rats (p<0.05). Conclusion The alcoholic-extract of dried Matricaria chamomilla L. flowers can not only induce recovery from a PCO induced state in rats, but also increase dominant follicles. Additionally better endometrial tissue arrangements can be regarded as another therapeutic effect of Chamomile. PMID:23926485

  8. Steroid-induced polycystic ovaries in rats: effect of electro-acupuncture on concentrations of endothelin-1 and nerve growth factor (NGF), and expression of NGF mRNA in the ovaries, the adrenal glands, and the central nervous system.

    PubMed

    Stener-Victorin, Elisabet; Lundeberg, Thomas; Cajander, Stefan; Aloe, Luigi; Manni, Luigi; Waldenström, Urban; Janson, Per Olof

    2003-04-08

    Previous studies on the effect of repeated electro-acupuncture (EA) treatments in rats with steriod-induced polycystic ovaries (PCO), EA has been shown to modulate nerve growth factor (NGF) concentration in the ovaries as well as corticotropin releasing factor (CRF) in the median eminence (ME). In the present study we tested the hypothesis that repeated EA treatments modulates sympathetic nerve activity in rats with PCO. This was done by analysing endothelin-1 (ET-1), a potent vasoconstrictor involved in ovarian functions, as well as NGF and NGF mRNA expression involved in the pathophysiological process underlying steroid-induced PCO. The main result in the present study was that concentrations of ET-1 in the ovaries were significantly lower in the PCO group receiving EA compared with the healthy control group (p < 0.05). In the hypothalamus, however, ET-1 concentrations were found to be significantly higher in the PCO group receiving EA than in the healthy control group (p < 0.05). Concentrations of ovarian NGF protein were significantly higher in the PCO control group compared with the healthy control group (p < 0.001), and these concentrations decreased significantly after repeated EA treatments compared with those in the PCO control group (p < 0.05) and were found to be the same as those in the healthy control group. In conclusion, these results indicate that EA modulates the neuroendocrinological state of the ovaries, most likely by modulating the sympathetic nerve activity in the ovaries, which may be a factor in the maintenance of steroid-induced PCO.

  9. Hypothalamic transcriptional expression of the kisspeptin system and sex steroid receptors differs among polycystic ovary syndrome rat models with different endocrine phenotypes

    PubMed Central

    Marcondes, Rodrigo Rodrigues; Carvalho, Kátia Cândido; Giannocco, Gisele; Duarte, Daniele Coelho; Garcia, Natália; Soares-Junior, José Maria; da Silva, Ismael Dale Cotrim Guerreiro; Maliqueo, Manuel; Baracat, Edmund Chada; Maciel, Gustavo Arantes Rosa

    2017-01-01

    OBJECTIVES: Polycystic ovary syndrome is a heterogeneous endocrine disorder that affects reproductive-age women. The mechanisms underlying the endocrine heterogeneity and neuroendocrinology of polycystic ovary syndrome are still unclear. In this study, we investigated the expression of the kisspeptin system and gonadotropin-releasing hormone pulse regulators in the hypothalamus as well as factors related to luteinizing hormone secretion in the pituitary of polycystic ovary syndrome rat models induced by testosterone or estradiol. METHODS: A single injection of testosterone propionate (1.25 mg) (n=10) or estradiol benzoate (0.5 mg) (n=10) was administered to female rats at 2 days of age to induce experimental polycystic ovary syndrome. Controls were injected with a vehicle (n=10). Animals were euthanized at 90-94 days of age, and the hypothalamus and pituitary gland were used for gene expression analysis. RESULTS: Rats exposed to testosterone exhibited increased transcriptional expression of the androgen receptor and estrogen receptor-β and reduced expression of kisspeptin in the hypothalamus. However, rats exposed to estradiol did not show any significant changes in hormone levels relative to controls but exhibited hypothalamic downregulation of kisspeptin, tachykinin 3 and estrogen receptor-α genes and upregulation of the gene that encodes the kisspeptin receptor. CONCLUSIONS: Testosterone- and estradiol-exposed rats with different endocrine phenotypes showed differential transcriptional expression of members of the kisspeptin system and sex steroid receptors in the hypothalamus. These differences might account for the different endocrine phenotypes found in testosterone- and estradiol-induced polycystic ovary syndrome rats.

  10. Proliferation of the Superficial Epithelium of Ovaries in Senile Female Rats Following Oral Administration of Conjugated Equine Estrogens

    PubMed Central

    Perniconi, Sergio Eduardo; de Jesus Simões, Manuel; dos Santos Simões, Ricardo; Haidar, Mauro Abi; Baracat, Edmund C; Soares, Jose Maria

    2008-01-01

    OBJECTIVE To evaluate the effect of different concentrations of estrogen on the ovarian superficial epithelium in senile female rats. Design: Fifty female rats at 15 months of age and with irregular estrous cycles were selected and randomly divided into five experimental groups containing equal numbers of animals in each: GPROP, control group receiving vehicle only; GE0.05mg, group receiving conjugated equine estrogens (CEE) at a dose of 50 μg/kg; GE0.5mg, group receiving CEE at 500 μg/kg; GE1mg, group receiving CEE at 1 mg/kg; and GE2mg, receiving CEE at 2 mg/kg. The length of treatment was 21 days. After this period, the animals were anesthetized and the ovaries were fixed in 10% formaldehyde and processed for routine histology. Histomorphology was analyzed by light microscopy, and histomorphometrics were evaluated using the Imagelab program. RESULTS In the GPROP and GE0.05mg groups, the superficial epithelium of the ovary had a simple cuboidal shape, and as the estrogen dose increased, the epithelium thickened, with pseudo-stratified or stratified epithelium appearing in the GE2mg group. The animals in the group given the highest estrogen dose (GE2mg) showed the thickest ovarian epithelium and the largest perimeter and surface area of the surface ovarian epithelium (P < 0.01). However, the difference in epithelium thickness between the GE0.5mg and GE1mg groups was only slight. CONCLUSION Our data suggest that CEE at a dose of 2 mg/kg may induce marked proliferation of rat ovarian epithelium. PMID:18568250

  11. Trace glucose and lipid metabolism in high androgen and high-fat diet induced polycystic ovary syndrome rats

    PubMed Central

    2012-01-01

    Background There is a high prevalence of diabetes mellitus (DM) and dyslipidemia in women with polycystic ovary syndrome (PCOS). The purpose of this study was to investigate the role of different metabolic pathways in the development of diabetes mellitus in high-androgen female mice fed with a high-fat diet. Methods Female Sprague-Dawley rats were divided into 3 groups: the control group(C), n = 10; the andronate-treated group (Andronate), n = 10 (treated with andronate, 1 mg/100 g body weight/day for 8 weeks); and the andronate-treated and high-fat diet group (Andronate+HFD), n = 10. The rate of glucose appearance (Ra of glucose), gluconeogenesis (GNG), and the rate of glycerol appearance (Ra of glycerol) were assessed with a stable isotope tracer. The serum sex hormone levels, insulin levels, glucose concentration, and the lipid profile were also measured. Results Compared with control group, both andronate-treated groups exhibited obesity with higher insulin concentrations (P < 0.05) but similar blood glucose concentrations. Of the two andronate-treated groups, the andronate+HFD group had the most serious insulin resistance (IR). Estrus cycles were completely acyclic, with polycystic ovaries and elevated serum lipid profiles in the andronate+HFD group (P < 0.05). Ra of glucose and GNG increased significantly in the andronate+HFD rats. However, the Ra of glycerol was similar in the three groups. Conclusions Andronate with HFD rat model showed ovarian and metabolic features of PCOS, significant increase in glucose Ra, GNG, and lipid profiles, as well as normal blood glucose levels. Therefore, aberrant IR, increased glucose Ra, GNG, and lipid metabolism may represent the early-stage of glucose and lipid kinetics disorder, thereby might be used as potential early-stage treatment targets for PCOS. PMID:22276997

  12. Oxidative stress in ventral prostate, ovary, and breast by 2,4-dichlorophenoxyacetic acid in pre- and postnatal exposed rats.

    PubMed

    Pochettino, Aristides A; Bongiovanni, Bettina; Duffard, Ricardo O; Evangelista de Duffard, Ana María

    2013-01-01

    The herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) has been widely used in agriculture and forestry since the 1940s. 2,4-D has been shown to produce a wide range of adverse effects-from embryotoxicity and teratogenicity to neurotoxicity-on animal and human health. The purpose of this study was to determine the possible effects of pre- and postnatal exposure to 2,4-D on oxidative stress in ventral prostate, ovary and breast. Pregnant rats were daily exposed to oral doses of 70 mg/kg/day of 2,4-D from 16 days of gestation up to 23 days after delivery. Then, the pups were sacrificed by decapitation at postnatal day (PND) 45, 60, or 90. Antioxidant enzyme activities and some parameters of the oxidative stress were assessed in ventral prostate, breast, and ovary. Results show that 2,4-D produced three different effects. First, it increased the concentration of some radical oxygen species and the rates of lipid peroxidation and protein oxidation in ventral prostate, thereby causing oxidative stress at all ages studied. Although an increase in the activity of some antioxidant enzymes was detected, this seemed to have been not enough to counteract the oxidative stress. Second, 2,4-D promoted the oxidative stress in the breasts, mainly during puberty and adulthood, probably because the developing gland is more sensitive to xenobiotics than the adult organ. Third, 2,4-D altered the activity of some antioxidant enzymes and increased lipid peroxide concentration in the ovary. This effect could reflect the variety of ovarian cell types and their different responses to endocrine changes during development. Copyright © 2011 Wiley Periodicals, Inc.

  13. Nitric oxide in prepubertal rat ovary contribution of the ganglionic nitric oxide synthase system via superior ovarian nerve.

    PubMed

    Casais, Marilina; Delgado, Silvia Marcela; Vallcaneras, Sandra; Sosa, Zulema; Rastrilla, Ana María

    2007-02-01

    Both peripheral innervation and nitric oxide (NO) participate in ovarian steroidogenesis. Considering the existence of the nitric oxide/ nitric oxide synthase system in the peripheral neural system and in the ovary, the aim of this work was to analyze if the liberation of NO in the ovarian compartment of prepubertal rats is of ovarian and/or ganglionic origin. The analysis is carried out from a physiological point of view using the experimental coeliac ganglion--Superior Ovarian Nerve--ovary model with and without ganglionic cholinergic stimulus Acetylcholine (Ach) 10(-6) M. Non selective and selective inhibitors of the synthase nitric oxide enzyme were added to the ovarian and ganglionic compartment, and the liberation of nitrites (soluble metabolite of the nitric oxide) in the ovarian incubation liquid was measured. We found that the non-selective inhibitor L-nitro-arginina methyl ester (L-NAME) in the ovarian compartment decreased the liberation of nitrites, and that Aminoguanidine (AG) in two concentrations in a non-dose dependent form provoked the same effect. The addition of Ach in ganglion magnified the effect of the inhibitors of the NOS enzyme. The most relevant results after the addition of inhibitors in ganglion were obtained with AG 400 and 800 microM. The inhibition was made evident with and without the joint action of Ach in ganglion. These data suggest that the greatest production of NO in the ovarian compartment comes from the ovary, mainly the iNOS isoform, though the coeliac ganglion also contributes through the superior ovarian nerve but with less quantity.

  14. Effects of hypophysectomy and administration of pituitary hormones on luteal function and uptake of high density lipoproteins by luteinized ovaries and adrenals of the rat

    SciTech Connect

    Murphy, B.D.; Rajkumar, K.; McKibbin, P.E.; Macdonald, G.J.; Buhr, M.M.; Grinwich, D.L.

    1985-04-01

    The role of plasma lipoproteins and hypophyseal hormones in the maintenance of progesterone secretion by the rat corpus luteum was investigated. In the first experiment, rats were treated daily from days 1-6 of pregnancy with 5 mg/kg 4-aminopyrozolopyramidine (4APP), a blocker of hepatic lipoprotein secretion, or with 5 mg/kg 4APP and 1 or 2 mg ovine PRL or 0.1 ml 0.5% phosphoric acid (4APP vehicle). The administration of 4APP reduced serum cholesterol and progesterone levels on days 2-6 of pregnancy and ovarian progesterone on day 6. The reduced progesterone secretion had no effect on embryo implantation. PRL, in the doses used, was incapable of abrogating the effects of 4APP on circulating or ovarian progesterone levels. Ovaries and adrenals, but not kidneys, of pseudopregnant rats exhibited specific and saturable uptake of porcine high density lipoprotein (HDL). Time-course studies indicated that the uptake of HDL was rapid in ovaries compared to that in adrenals. Ovaries from rats not only exhibited uptake of porcine HDL, but also were capable of using it for progesterone synthesis. Treatment with 4APP increased the adrenal uptake of HDL, but ovarian uptake was not different from that in the control group. Hypophysectomy reduced both adrenal and ovarian uptake of HDL. In adrenals only ACTH at the dose employed ameliorated reduction of HDL uptake induced by hypophysectomy, while in the ovaries, both PRL and LH reversed the effect of hypophysectomy. The effect of PRL on uptake was specific to (/sup 125/I)HDL and did not alter (/sup 125/I)albumin uptake. It is concluded that: 1) hypophysectomy reduces HDL uptake in the luteinized rat ovary; and 2) PRL and LH replacement therapy maintain ovarian uptake of HDL, suggesting a direct effect of these luteotropins on lipoprotein uptake.

  15. Hypothalamic Neuroendocrine Functions in Rats with Dihydrotestosterone-Induced Polycystic Ovary Syndrome: Effects of Low-Frequency Electro-Acupuncture

    PubMed Central

    Feng, Yi; Johansson, Julia; Shao, Ruijin; Mannerås, Louise; Fernandez-Rodriguez, Julia; Billig, Håkan; Stener-Victorin, Elisabet

    2009-01-01

    Adult female rats continuously exposed to androgens from prepuberty have reproductive and metabolic features of polycystic ovary syndrome (PCOS). We investigated whether such exposure adversely affects estrous cyclicity and the expression and distribution of gonadotropin-releasing hormone (GnRH), GnRH receptors, and corticotrophin-releasing hormone (CRH) in the hypothalamus and whether the effects are mediated by the androgen receptor (AR). We also assessed the effect of low-frequency electro-acupuncture (EA) on those variables. At 21 days of age, rats were randomly divided into three groups (control, PCOS, and PCOS EA; n = 12/group) and implanted subcutaneously with 90-day continuous-release pellets containing vehicle or 5α-dihydrostestosterone (DHT). From age 70 days, PCOS EA rats received 2-Hz EA (evoking muscle twitches) five times/week for 4–5 weeks. Hypothalamic protein expression was measured by immunohistochemistry and western blot. DHT-treated rats were acyclic, but controls had regular estrous cycles. In PCOS rats, hypothalamic medial preoptic AR protein expression and the number of AR- and GnRH-immunoreactive cells were increased, but CRH was not affected; however, GnRH receptor expression was decreased in both the pituitary and hypothalamus. Low-frequency EA restored estrous cyclicity within 1 week and reduced the elevated hypothalamic GnRH and AR expression levels. EA did not affect GnRH receptor or CRH expression. Interestingly, nuclear AR co-localized with GnRH in the hypothalamus. Thus, rats with DHT-induced PCOS have disrupted estrous cyclicity and an increased number of hypothalamic cells expressing GnRH, most likely mediated by AR activation. Repeated low-frequency EA normalized estrous cyclicity and restored GnRH and AR protein expression. These results may help explain the beneficial neuroendocrine effects of low-frequency EA in women with PCOS. PMID:19680559

  16. Developmental effects of imatinib mesylate on follicle assembly and early activation of primordial follicle pool in postnatal rat ovary.

    PubMed

    Asadi-Azarbaijani, Babak; Santos, Regiane R; Jahnukainen, Kirsi; Braber, Saskia; van Duursen, Majorie B M; Toppari, Jorma; Saugstad, Ola D; Nurmio, Mirja; Oskam, Irma C

    2017-03-01

    Imatinib mesylate is an anti-cancer agent that competitively inhibits several receptor tyrosine kinases (RTKs). RTKs play important roles in the regulation of primordial follicle formation, the recruitment of primordial follicles into the pool of growing follicles and maturation of the follicles. In the present study, we investigated the effects of the tyrosine kinase inhibitor imatinib on primordial follicle assembly and early folliculogenesis in postnatal rats. Female Sprague-Dawley rats were treated with either imatinib (150mg/kg) or placebo (water) on postnatal days 2-4. Bilateral ovariectomy was performed on postnatal day 2 and 5. Histology, immunohistochemistry, and mRNA analysis were performed. Imatinib treatment was associated with increased density of the multi-oocyte follicles (P<0.01), oogonia (p<0.01) and germline clusters (P<0.05), decreased activation of primordial follicles, increased expression of c-Kit and AMH, and decreased protein expression of Kit-ligand and GDF9 when compared to age-matched controls. In conclusion, imatinib affects folliculogenesis in postnatal rat ovaries by delaying the cluster breakdown, follicular assembly and early activation of the primordial follicle pool. Copyright © 2016 Society for Biology of Reproduction & the Institute of Animal Reproduction and Food Research of Polish Academy of Sciences in Olsztyn. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  17. 7,12-Dimethylbenz[a]anthracene exposure induces the DNA repair response in neonatal rat ovaries

    SciTech Connect

    Ganesan, Shanthi Bhattacharya, Poulomi Keating, Aileen F.

    2013-11-01

    7,12-Dimethylbenz[a]anthracene (DMBA) destroys ovarian follicles at all stages of development. This study investigated DMBA-induced DNA double strand break (DSB) formation with subsequent activation of the ovarian DNA repair response in models of pre-antral or pre-ovulatory follicle loss. Postnatal day (PND) 4 Fisher 344 (F344) rat ovaries were cultured for 4 days followed by single exposures of vehicle control (1% DMSO) or DMBA (12.5 nM or 75 nM) and maintained in culture for 4 or 8 days. Alternately, PND4 F344 rat ovaries were exposed to 1 μM DMBA at the start of culture for 2 days. Total RNA or protein was isolated, followed by qPCR or Western blotting to quantify mRNA or protein level, respectively. γH2AX and phosphorylated ATM were localized and quantified using immunofluorescence staining. DMBA exposure increased caspase 3 and γH2AX protein. Additionally, DMBA (12.5 nM and 1 μM) increased levels of mRNA encoding Atm, Xrcc6, Brca1 and Rad51. In contrast, Parp1 mRNA was decreased on d4 and increased on d8 of DMBA exposure, while PARP1 protein increased after 8 days of DMBA exposure. Total ATM increased in a concentration-dependent temporal pattern (75 nM d4; 12.5 nM d8), while pATM was localized in large primary and secondary follicles and increased after 8 days of 75 nM DMBA exposure compared to both control and 12.5 nM DMBA. These findings support that, despite some concentration effects, DMBA induces ovarian DNA damage and that DNA repair mechanisms are induced as a potential mechanism to prevent follicle loss. - Highlights: • DMBA exposure increases ovarian caspase-3 protein expression. • DMBA exposure increases the γH2AX protein in oocytes. • DMBA exposure activates a DNA repair response in the ovary.

  18. Local administration of platelet-derived growth factor B (PDGFB) improves follicular development and ovarian angiogenesis in a rat model of Polycystic Ovary Syndrome.

    PubMed

    Di Pietro, Mariana; Scotti, Leopoldina; Irusta, Griselda; Tesone, Marta; Parborell, Fernanda; Abramovich, Dalhia

    2016-09-15

    Alterations in ovarian angiogenesis are common features in Polycystic Ovary Syndrome (PCOS) patients; the most studied of these alterations is the increase in vascular endothelial growth factor (VEGF) production by ovarian cells. Platelet-derived growth factor B (PDGFB) and D (PDGFD) are decreased in follicular fluid of PCOS patients and in the ovaries of a rat model of PCOS. In the present study, we aimed to analyze the effects of local administration of PDGFB on ovarian angiogenesis, follicular development and ovulation in a DHEA-induced PCOS rat model. Ovarian PDGFB administration to PCOS rats partially restored follicular development, decreased the percentage of cysts, increased the percentage of corpora lutea, and decreased the production of anti-Müllerian hormone. In addition, PDGFB administration improved ovarian angiogenesis by reversing the increase in periendothelial cell area and restoring VEGF levels. Our results shed light into the mechanisms that lead to altered ovarian function in PCOS and provide new data for potential therapeutic strategies.

  19. Participation of vasoactive intestinal polypeptide in ovarian steroids production during the rat estrous cycle and in the development of estradiol valerate-induced polycystic ovary.

    PubMed

    Parra, Claudio; Fiedler, Jenny L; Luna, S Leticia; Greiner, Monika; Padmanabhan, Vasantha; Lara, Hernán E

    2007-01-01

    Vasoactive intestinal polypeptide (VIP) stimulates estradiol and progesterone release from ovarian granulosa cells in vitro. Very little information is available as to the role VIP plays in the control of steroid secretion during reproductive cyclicity and in ovarian pathologies involving altered steroid secretion. In this study, we determined the involvement of VIP in regulating ovarian androgen and estradiol release during estrous cyclicity and estradiol valerate (EV)-induced polycystic ovarian development in rats. Our findings show that androgen and estradiol release from ovaries obtained during different stages of rat estrous cycle mimic cyclic changes in steroid release observed in vivo with maximal release occurring during late proestrus. VIP increased androgen release from ovaries of all cycle stages except late proestrus and estradiol release from all cycle stages. Increases in VIP-induced androgen and estradiol release were maximal at early proestrus. Inclusion of saturating concentrations of androstenedione increased magnitude of VIP-induced estradiol release at diestrus and estrus but not proestrus. Magnitude of VIP-induced androgen and estradiol release tended to be greater in the ovaries from EV-treated rats with polycystic ovary compared with estrous controls. At the tissue level, ovarian VIP concentration was cycle stage dependent with highest level seen in diestrus. Maximum concentration of VIP was found in EV-treated rats. Changes in VIP were inversely related to changes in ovarian nerve growth factor, a neuropeptide involved in ovarian androgen secretion. These results strongly suggest that intraovarian VIP participates in the control of estradiol secretion during the rat estrous cycle and possibly in the maintenance of increased ovarian estradiol secretory activity of EV-treated rats.

  20. Edaravone Mitigates Hexavalent Chromium-Induced Oxidative Stress and Depletion of Antioxidant Enzymes while Estrogen Restores Antioxidant Enzymes in the Rat Ovary in F1 Offspring1

    PubMed Central

    Stanley, Jone A.; Sivakumar, Kirthiram K.; Arosh, Joe A.; Burghardt, Robert C.; Banu, Sakhila K.

    2014-01-01

    ABSTRACT Environmental contamination of drinking water with chromium (Cr) has been increasing in more than 30 cities in the United States. Previous studies from our group have shown that Cr affects reproductive functions in female Sprague Dawley rats. Although it is impossible to completely remove Cr from the drinking water, it is imperative to develop effective intervention strategies to inhibit Cr-induced deleterious health effects. Edaravone (EDA), a potential inhibitor of free radicals, has been clinically used to treat cancer and cardiac ischemia. This study evaluated the efficacy of EDA against Cr-induced ovarian toxicity. Results showed that maternal exposure to CrVI in rats increased follicular atresia, decreased steroidogenesis, and delayed puberty in F1 offspring. CrVI increased oxidative stress and decreased antioxidant (AOX) enzyme levels in the ovary. CrVI increased follicle atresia by increased expression of cleaved caspase 3, and decreased expression of Bcl2 and Bcl2l1 in the ovary. EDA mitigated or inhibited the effects of CrVI on follicle atresia, pubertal onset, steroid hormone levels, and AOX enzyme activity, as well as the expression of Bcl2 and Bcl2l1 in the ovary. In a second study, CrVI treatment was withdrawn, and F1 rats were injected with estradiol (E2) (10 μg in PBS/ethanol per 100 g body weight) for a period of 2 wk to evaluate whether E2 treatment will restore Cr-induced depletion of AOX enzymes. E2 restored CrVI-induced depletion of glutathione peroxidase 1, catalase, thioredoxin 2, and peroxiredoxin 3 in the ovary. This is the first study to demonstrate the protective effects of EDA against any toxicant in the ovary. PMID:24804965

  1. Edaravone mitigates hexavalent chromium-induced oxidative stress and depletion of antioxidant enzymes while estrogen restores antioxidant enzymes in the rat ovary in F1 offspring.

    PubMed

    Stanley, Jone A; Sivakumar, Kirthiram K; Arosh, Joe A; Burghardt, Robert C; Banu, Sakhila K

    2014-07-01

    Environmental contamination of drinking water with chromium (Cr) has been increasing in more than 30 cities in the United States. Previous studies from our group have shown that Cr affects reproductive functions in female Sprague Dawley rats. Although it is impossible to completely remove Cr from the drinking water, it is imperative to develop effective intervention strategies to inhibit Cr-induced deleterious health effects. Edaravone (EDA), a potential inhibitor of free radicals, has been clinically used to treat cancer and cardiac ischemia. This study evaluated the efficacy of EDA against Cr-induced ovarian toxicity. Results showed that maternal exposure to CrVI in rats increased follicular atresia, decreased steroidogenesis, and delayed puberty in F1 offspring. CrVI increased oxidative stress and decreased antioxidant (AOX) enzyme levels in the ovary. CrVI increased follicle atresia by increased expression of cleaved caspase 3, and decreased expression of Bcl2 and Bcl2l1 in the ovary. EDA mitigated or inhibited the effects of CrVI on follicle atresia, pubertal onset, steroid hormone levels, and AOX enzyme activity, as well as the expression of Bcl2 and Bcl2l1 in the ovary. In a second study, CrVI treatment was withdrawn, and F1 rats were injected with estradiol (E₂) (10 μg in PBS/ethanol per 100 g body weight) for a period of 2 wk to evaluate whether E₂ treatment will restore Cr-induced depletion of AOX enzymes. E₂ restored CrVI-induced depletion of glutathione peroxidase 1, catalase, thioredoxin 2, and peroxiredoxin 3 in the ovary. This is the first study to demonstrate the protective effects of EDA against any toxicant in the ovary.

  2. [The effect of soy isoflavones on ATP binding cassette A1 expression level in rats without ovaries with atherosclerotic plaque].

    PubMed

    Li, Xian-biao; Ji, Li-li; Li, Yong; Zhang, Yu-mei

    2009-10-01

    To study the effect of soy isoflavones (SI) on ATP binding cassette A1 (ABCA1) expression in rats without ovary with atherosclerosis. After they were raised for a week by given basic feed, the ovaries of 50 12-week old SPF rats were removed. The rats were randomly divided into groups by weight. Ten rats were selected as the basic control group (A) that basic feed was given all through the research. The other 40 rats were given high-fat diets and at the end of 4 weeks, these rats were randomly divided into four groups by blood lipid level: atherosclerotic model group (B) that was given high-fat diets through the research, low isoflavones group (C) that was given high-fat diets plus 30 mg/kg SI, middle isoflavones group (D) that was given high-fat diets plus 90 mg/kg SI, and high isoflavones group (E) that was given high-fat diets plus 270 mg/kg SI. After 22 weeks, all rats were executed to measure morphological change on the aorta wall, assessing the ABCA1 gene expression in aorta wall by real-time PCR and protein expression by Western blotting in aorta wall, small intestine and liver. Serum lipid level of A, B, C, D, E groups: TC levels were (6.82 +/- 0.22), (15.73 +/- 1.51), (10.77 +/- 1.12), (9.95 +/- 1.18), (9.11 +/- 1.12) mmol/L respectively (F = 72.882, P < 0.01); TG levels were: (2.49 +/- 0.24), (0.78 +/- 0.13), (0.39 +/- 0.08), (0.29 +/- 0.09), (0.24 +/- 0.09) mmol/L respectively (F = 378.515, P < 0.01); LDL-C levels were (1.29 +/- 0.08), (14.76 +/- 1.23), (8.18 +/- 0.80), (7.85 +/- 0.72), (7.16 +/- 0.64)mmol/L respectively (F = 320.936, P < 0.01); HDL-C levels were (1.94 +/- 0.18), (1.04 +/- 0.10), (1.55 +/- 0.14), (1.88 +/- 0.17), (2.11 +/- 0.22) mmol/L respectively (F = 49.450, P < 0.01). ABCA1 protein expression in intestine, liver and aorta: for A, B, C, E groups in intestine were 96.577 +/- 9.743, 5.218 +/- 2.048, 18.060 +/- 5.179, 54.725 +/- 8.960, respectively (F = 172.272, P < 0.01); ABCA1 protein expression in liver of groups of A, B, C, E were: 13

  3. Involvement of the ganglion cholinergic receptors in gonadotropin-releasing hormone, catecholamines, and progesterone release in the rat ovary.

    PubMed

    Daneri, Cristina; Orozco, Adriana Vega; Bronzi, Daniela; Mohn, Claudia; Rastrilla, Ana M; Sosa, Zulema Y

    2013-06-01

    To investigate whether cholinergic ganglionic stimulus modifies the release of gonadotropin-releasing hormone (GnRH), catecholamines, and progesterone at the ovarian level. Animal study. University animal laboratory. Six to eight virgin adult Holtzman rats. Superior mesenteric ganglion-ovarian nerve plexus-ovary system removed and placed in one cuvette with two compartments, with acetylcholine added to the ganglion in the experimental group. Measurement of ovarian liquid obtained from catecholamines by high-performance liquid chromatography; measurement of progesterone (P(4)), GnRH, and luteinizing hormone (LH) by radioimmunoassay; and measurement of gene expression of 3β-hydroxysteroid dehydrogenase (3β-HSD) and 20α-hydroxysteroid dehydrogenase (20α-HSD) by reverse-transcriptase polymerase chain reaction (RT-PCR). The study focused on the estrus and diestrus II (DII) stages. On the estrus days, the release of GnRH, NA, and 20α-HSD increased, while P(4) and 3β-HSD decreased. On the DII days, GnRH, P(4), and 3β-HSD increased, while 20α-HSD and NA decreased. The ovarian liquid with GnRH showed biologic activity, namely, an increase in LH release during the DII stage and a decrease during the estrus stage. Neural stimulus from the superior mesenteric ganglion influences the release of NA, adrenaline, and GnRH. We also have demonstrated that these neurotransmitters participate in the atretogenic processes of the ovary, thus providing evidence of the necessity of the sympathetic neural pathway. Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  4. Ovarian iodide uptake and triiodothyronine generation in follicular fluid. The enigma of the thyroid ovary interaction.

    PubMed

    Slebodziński, A B

    2005-07-01

    Since 1928, the iodine concentration in the ovary has been known to be higher than in every other organs except the thyroid. The ovarian iodide uptake varies with sexual activities, is enhanced by estrogens and a hypothyroid state and blocked by goitrogens. The recent discovery of a sodium iodide symporter (NIS) in ovaries has offered a possible mechanism for ovarian iodide uptake and other functional similarities to its thyroid counterpart. Nevertheless, the physiological significance of ovarian iodine uptake and accumulation remains unknown. The presence of thyroid hormones (TH) in follicular fluid (FF) has been established recently. Our preliminary studies on TH in FF (1996-1998) in rabbits, pigs, horses showed that the concentration of T4 is generally lower than that in serum and that for T3 is within the normal range or higher. A positive correlation exists between the T4 levels in FF and serum but not between the corresponding T3 levels. These studies revealed, for the first time, the presence of the ovarian 5'-monodeiodinase system in FF capable of generating T3 (ovary-born T3) by outer ring deiodination of T4. In mares, seasonal polyestrus, ovarian 5'-monodeiodinase (MD) activity and FF T3 levels have been found to be higher during the ovulatory period than in the anovulatory one. The exact physiological significance of this system generating T3 and coexisting with isoforms of TH receptors in granulosa cells has not been elucidated. A direct role of T3 for the early follicular development, differentiation and for the steroidogenic capability of granulosa cells, although strongly suggested by data obtained from in vitro studies, has to be elucidated.

  5. Biphasic action of iodine in excess at different doses on ovary in adult rats.

    PubMed

    Mahapatra, Dakshayani; Chandra, Amar K

    2017-01-01

    Iodine consumption in excess of its recommended levels over a prolonged period of time is well known to cause thyroid disorders. The thyroid hormones on the other hand are responsible in maintenance of the physiology of the reproductive system. Excess iodine intake affects male reproductive physiology. However, the effects of excess iodine on the ovarian structure and function is yet to be established. The present study has thus been undertaken to investigate the effect of excess iodine on the ovarian physiology. Excess iodine was administered through oral gavage in the form of potassium iodide (KI) for duration of 60days, at two different doses. The doses used were 100 EI, i.e., 100 times more than the recommended level but tolerable to the thyroid gland and 500 EI, i.e., 500 times more than the recommended level that altered thyroid physiology. The animals were divided into three groups, one control group, and the other two receiving two separate doses (100 EI and 500 EI) of excess KI. Estrous cyclical changes, ovarian morphological changes, ovarian iodine accumulation and ovarian steroidogenic enzyme activities were analysed. The thyroid functional status was studied from the serum thyroid hormones levels. The overall results revealed a biphasic action of excess iodine that depends on its dose. At 100 EI, excess iodine did not alter thyroid physiology but lead to the development of a hypoestrogenic state. There was an increased accumulation of iodine in the ovary with decreased activity of ovarian steroidogenic enzymes and lowered serum estradiol levels. However, at 500 EI, excess iodine developed a hyperthyroid condition, which further leads to a hyperestrogenic state. There was an increased activity of serum steroidogenic enzymes as well as elevated serum estradiol levels. Fertility index was zero in both the 100 EI and 500 EI treated groups of experimental animals. Thus excess iodine (100 EI) ingestion within tolerable range though maintained a euthyroid

  6. The effects of melatonin on oxidative stress and prevention of primordial follicle loss via activation of mTOR pathway in the rat ovary.

    PubMed

    Behram Kandemir, Y; Aydin, C; Gorgisen, G

    2017-02-28

    Mammalian Target of Rapamycin (mTOR) signaling pathway has important roles in the regulation of puberty onset, gonadotropin secretion, follicular development and ovulation. Melatonin (N-acetyl-5-methoxytryptamine) is a lipophilic hormone has multiple functions in regulating the fertility. Recent studies have shown that melatonin affected the number or maturation of follicles in the ovary. The aim of this study was to investigate the effects of melatonin on mTOR expression and quantity of follicle in rat ovary. In the present study, a total of 45 female rats were randomly divided into three groups. Group 1; Control (C), Group 2: Vehicle (V) and Group 3; Melatonin (M). Melatonin was administered intraperitoneally at a dose of 50 mg/kg/day for 30 days in Melatonin group. The effects of Melatonin on the expression of mTOR and downstream components  were determined by Western Blot and Reverse Transcriptase PCR analysis. Upon Western Blot and RT-PCR evaluations, we detected higher expression and activation of mTOR, P70S6K, PKCalpha, PCNA and higher numbers of primordial  follicles in melatonin group compared with V and C group. In addition to this results, melatonin decreased oxidative stress markers, such as MDA, on the contrary, levels of antioxidative markers, such as CAT and GPx, were increased by melatonin in rat ovary. This study indicated that melatonin may have a significant protective effect on primordial follicles and increase the expression of mTOR and downstream components in rat ovary. Melatonin treatment may have a beneficial effect on fertility.

  7. Central leptin resistance and hypothalamic inflammation are involved in letrozole-induced polycystic ovary syndrome rats.

    PubMed

    Lian, Yuling; Zhao, Fangui; Wang, Wenjun

    2016-08-05

    Accumulating evidence indicates that leptin acts as an important mediator in energy homeostasis and reproduction. Since dysfunction of reproduction and metabolism are major characteristics of polycystic ovarian syndrome (PCOS), the role of leptin in pathogenesis of PCOS needs further research. Many studies have shown that central leptin resistance existed in obesity rats through leptin intracerebroventricular (icv) injection; however, central leptin resistance in PCOS rats has not been reported. This study aimed to investigate whether there was a state of central leptin resistance in PCOS rats, as well as explore the possible association of hypothalamic inflammation with central leptin resistance. First, letrozole was used to induce the PCOS model, 24 h food intake, 24 h body weight changes and the expression of p-STAT3 were determined following leptin or artificial cerebrospinal fluid (aCSF) icv injection in rats. Second, we further evaluated the expressions of IL-1β, IL-6, TNF-α, p-IKKβ, NF-κB, p-NF-κB, IκBα, p-IκBα and SOCS3 in hypothalamus. The results showed that 24 h food intake and body weight were decreased, while the expression of p-STAT3 was increased in control group rats following leptin icv injection compared with aCSF icv injection; however, both of them showed no significant difference in PCOS rats. Furthermore, inflammatory markers were upregulated in the hypothalami of PCOS rats. Taken together, our data indicated that there was a state of chronic low-grade inflammation in hypothalamus which might be the possible mechanism for central leptin resistance in PCOS rats. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Expression of ODC1, SPD, SPM and AZIN1 in the hypothalamus, ovary and uterus during rat estrous cycle.

    PubMed

    Fernandes, Joseph R D; Jain, Sammit; Banerjee, Arnab

    2017-05-15

    The aim of the present study was to investigate variation in the expression pattern of ornithine decarboxylase (ODC1), spermine (SPM), spermidine (SPD) and antizyme inhibitor (AZIN1) in hypothalamus, ovary and uterus during the estrous cycle of rats. Further, to understand any correlation between polyamines and GnRH I expression in hypothalamus; effect of putrescine treatment on GnRH I expression in hypothalamus and progesterone and estradiol levels in serum were investigated. The study also aims in quantifying all the immunohistochemistry images obtained based on pixel counting algorithm to yield the relative pixel count. This algorithm uses a red green blue (RGB) colour thresholding approach to quantify the intensity of the chromogen present. The result of the present study demonstrates almost similar expression pattern of polyamine and polyamine related factors, ODC1, SPD, SPM and AZIN1, with that of hypothalamic GnRH I, all of which mainly localized in the medial preoptic area (MPA) of the hypothalamus, during the proestrus, estrus and diestrus. This suggest that hypothalamic GnRH I expression is under regulation of polyamines. The study showed significant increase in hypothalamic GnRH I expression for both the doses of putrescine treatment to adult female rats. Further, it was shown that in ovary expression pattern of ODC1, SPM, SPD and AZIN1 were similar with that of steroidogenic factor, StAR during the estrous cycle, and putrescine supplementation increased significantly estradiol and progesterone levels in serum, all suggesting ovarian polyamines are involved in regulation of ovarian steroidogenesis. Localization of these factors in the theca and granulosa cells suggest involvement of polyamines in the process of folliculogenesis and luteinization; and ODC1, SPD, SPM and AZIN1 in oocyte further suggests polyamine role in maintenance of oocyte physiology. Finally, in uterus SPM and AZIN1 were localized throughout the estrous cycle, being comparatively more

  9. Protective properties of 6-gingerol-rich fraction from Zingiber officinale (Ginger) on chlorpyrifos-induced oxidative damage and inflammation in the brain, ovary and uterus of rats.

    PubMed

    Abolaji, Amos O; Ojo, Mercy; Afolabi, Tosin T; Arowoogun, Mary D; Nwawolor, Darlinton; Farombi, Ebenezer O

    2017-03-31

    Chlorpyrifos (CPF) is an organophosphorus pesticide widely used in agricultural applications and household environments. 6-Gingerol-rich fraction from Zingiber officinale (Ginger, 6-GRF) has been reported to possess potent anti-oxidative, anti-inflammatory and anti-apoptotic properties. Here, we investigated the protective properties of 6-GRF on CPF-induced oxidative damage and inflammation in the brain, ovary and uterus of rats. Five groups of rats containing 14 rats/group received corn oil (control), CPF (5 mg/kg), 6-GRF (100 mg/kg), CPF (5 mg/kg) + 6-GRF (50 mg/kg) and CPF (5 mg/kg) + 6-GRF (100 mg/kg) through gavage once per day for 35 days respectively. The results showed that 6-GRF protected against CPF-induced increases in oxidative stress (hydrogen peroxide (H2O2) and malondialdehyde (MDA)), inflammatory (myeloperoxidase (MPO), nitric oxide (NO) and tumour necrosis factor-α (TNF- α), and apoptotic (caspase-3) markers. Also, 6-GRF improved the activities of antioxidant enzymes catalase, superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione S-transferase (GST) as well as glutathione (GSH) level in the brain, ovary and uterus of rats exposed to CPF (p < 0.05). Overall, the protective effects of 6-GRF on CPF-induced toxicity in the brain and reproductive organs of rats may be due to its potent antioxidative, anti-inflammatory and antiapoptotic properties.

  10. Metabolic, Behavioral and Reproductive Effects of Vertical Sleeve Gastrectomy in an Obese Rat Model of Polycystic Ovary Syndrome

    PubMed Central

    Ressler, Ilana B.; Grayson, Bernadette E.; Seeley, Randy J.

    2014-01-01

    Introduction Polycystic ovary syndrome (PCOS) is the most common endocrinopathy affecting women of reproductive age. Its clinical expression is diverse, including metabolic, behavioral and reproductive effects, with many affected by obesity and decreased quality of life. Women with PCOS who have undergone surgically-induced weight loss have reported tremendous benefit, not only with weight loss, but also improvement of hyperandrogenism and menstrual cyclicity. Methods In a rat model of PCOS achieved via chronic administration of dihydrotestosterone (DHT) exposure, we investigated the ability of bariatric surgery, specifically vertical sleeve gastrectomy (VSG), to ameliorate the metabolic, behavioral and reproductive abnormalities invoked by this PCOS model. Results We found that DHT-treatment combined with exposure to a high-fat diet resulted in increased body weight and body fat, impaired fasting glucose, hirsutism, anxiety and irregular cycles. VSG resulted in reduced food intake, body weight and adiposity with improved fasting glucose and triglycerides. VSG induced lower basal corticosterone levels and attenuated stress responsivity. Once the DHT levels decreased to normal, regular estrous cyclicity was also restored. Conclusion VSG, therefore, improved PCOS manifestations in a comprehensive manner and may represent a potential therapeutic approach for specific aspects of PCOS. PMID:24408363

  11. Identification of the enzymic control point in 'de-differentiation' of oestrogen synthesis in superovulated rat ovary.

    PubMed

    Stevenson, P M; Klinken, S P; Boyne, P; Delhaize, E

    1982-11-12

    The superovulated rat model was used to investigate the enzymic focus for the decrease in oestrogen synthesis which occurs in ovary at the time of ovulation. Radioimmunoassays of progesterone, 17 alpha-hydroxyprogesterone, androstenedione, testosterone and 17 beta-oestradiol were used to measure the steroid concentrations in plasma for 6 days after the initiation of follicular development with pregnant mare's gonadotropin, and the long-term and acute effects of choriogonadotropin on these circulatory concentrations. The results showed that the cross-over point following the mid-cycle administration of gonadotropin was between 17 alpha-hydroxyprogesterone and androstenedione, and suggested that choriogonadotropin affected the 17 alpha-hydroxyprogesterone 17:20 lyase. In vitro assay of this microsomal enzyme confirmed that choriogonadotropin given in vivo at intervals before death caused 50% reduction in 17:20 lyase activity in 4 h and 93% reduction in 6 h. It was concluded that the synthesis of oestrogens declined following ovulation because the substrate (testosterone) was not available in sufficient concentration for the aromatase enzymes to use it.

  12. Evidence for monomeric and oligomeric hormone-binding domains in affinity-purified gonadotropin receptor from rat ovary

    SciTech Connect

    Zhang, Q.Y.; Menon, K.M.J. )

    1989-11-01

    Rat ovarian lutropin/choriogonadotropin receptor was purified from a Triton X-100-solubilized membrane preparation by affinity chromatography with Affi-Gel 10 coupled to purified human choriogonadotropin. The affinity-purified receptor preparations contained a single class of high-affinity binding sites for {sup 125}I-labeled human choriogonadotropin, with an equilibrium dissociation constant (K{sub d}) of 2.5 {times} 10{sup {minus}9} M, which is comparable to the K{sub d} values for membrane-bound and solubilized receptors. The purified receptor appeared as two dominant bands with molecular weights of 135,000 and 92,000 after sodium dodecyl sulfate/polyacrylamide gel electrophoresis (SDS/PAGE) under nonreducing conditions. When the individual affinity-purified receptor bands were electroeluted from the gel and analyzed again by SDS/PAGE under nonreducing conditions, both the M{sub r} 92,000 and the 135,000 proteins retained their original molecular form even when 8 M urea was included in the gel. However, when the electrophoretically purified M{sub r} 92,000 and 135,000 bands were subjected to SDS/PAGE under reducing conditions, the M{sub r} 135,000 species was almost completely converted to a M{sub r} 92,000 band, but the M{sub r} 92,000 species did not undergo any alteration in molecular weight. The results suggest that the lutropin/choriogonadotropin receptor from rat ovary exists in two molecular forms, and the higher molecular weight form appears to be composed of disulfide-linked M{sup r} 92,000 subunit, which comprises the hormone-binding domain.

  13. Protective effect of vitamin E on cypermethrin-induced follicular atresia in rat ovary: Evidence for energy dependent mechanism

    PubMed Central

    Molavi, Morteza; Razi, Mazdak; Cheraghi, Hadi; Khorramjouy, Mona; Ostadi, Araz; Gholirad, Safa

    2016-01-01

    It has been shown that chronic exposure to cypermethrin (CPM), a pyrethroid pesticide, results in follicular atresia via pathologically affecting angiogenesis, disrupting endocrine potential and enhancing oxidative stress. This study was aimed to uncover the CPM-exposed energy dependent follicular cells apoptosis and to estimate protective effect of vitamin E (VitE) as a potent antioxidant. Thirty six Wistar rats were divided into six groups (n = 6 rats for each group) including; control-sham, CPM-received (CPM, 75 mg kg-1, intraperitoneally), and CPM and VitE-treated (VitE, 150 mg kg-1, orally) for 14 and 24 days. The protein biosynthesis of glucose transporter-1 (GLUT-1) and caspase-3 in follicles were estimated by using immuno-histochemical staining at preantral and antral stages. Moreover, the periodic acid Schiff (PAS) staining was performed in order to evaluate the intracytoplasmic carbohydrate ratio in follicular cells and oocyte. Percentages of follicles with GLUT-1, Caspase-3 and PAS-positive cells were compared between groups. Immunohistochemical analyses showed that, VitE significantly up-regulated the GLUT-1 expression and improved the intracytoplasmic carbohydrate supplementation especially at preantral follicles. The cross sections from the CPM-exposed ovaries represented remarkable elevation in percentage of atretic preantral and antral follicles with caspase-3 biosynthesis, which was remarkably (p < 0.05) diminished in VitE co-treated groups. In conclusion, our data showed that VitE by up-regulating of the GLUT-1 biosynthesis improved glucose uptake at follicular cells and oocyte levels that in turn inhibited pro-apoptotic protein caspase-3 biosynthesis. PMID:27482357

  14. [Peculiarities of the ovary structure in the rat offspring developing under conditions of the removed thyroid gland of female rat with the thyroxine replacement therapy and external radiation exposure in utero].

    PubMed

    Konoplia, E F; Pavlenko, V S; Banetskaia, N V; Krylova, I I

    2011-01-01

    The influence of a single external gamma-radiation at a dose of 1.0 Gy (dose rate 9.08 x 10(-4) Gy/sec) on the 15th day of gestation in case of the removed complex of thyroid and parathyroid glands (thyroidparathyroidectomy) on the first day of gestation, as well as introduction of thyroxin and CaC12 on the structure of offspring ovary in postnatal ontogenesis (30-day old animals) was studied. It has been shown that thyroidparathyroidectomy of a female mother rat with thyroxine replacement therapy and irradiation, as well as the combination of these factors disturb the structure of ovarian tissues of the offspring. A single external irradiation on the 15th day of embryogenesis causes death of a considerable part of primordial follicles in the offspring ovary and growth of follicular layers in the secondary follicles. Thyroidparathyroidectomy of female rat on the first day of gestation with thyroxine replacement therapy causes delay in the development of follicles in the ovary at the early stages of maturation of 30-day old animals. The radiosensitivity of the ovarian tissues of the offspring that has been developed under the combined effect of the factors studied increases and results in an almost full loss of pool cells in the ovary of infant rats.

  15. Impact of 7,12-dimethylbenz[a]anthracene exposure on connexin gap junction proteins in cultured rat ovaries

    SciTech Connect

    Ganesan, Shanthi Keating, Aileen F.

    2014-01-15

    7,12-Dimethylbenz[a]anthracene (DMBA) destroys ovarian follicles in a concentration-dependent manner. The impact of DMBA on connexin (CX) proteins that mediate communication between follicular cell types along with pro-apoptotic factors p53 and Bax were investigated. Postnatal day (PND) 4 Fisher 344 rat ovaries were cultured for 4 days in vehicle medium (1% DMSO) followed by a single exposure to vehicle control (1% DMSO) or DMBA (12.5 nM or 75 nM) and cultured for 4 or 8 days. RT-PCR was performed to quantify Cx37, Cx43, p53 and Bax mRNA level. Western blotting and immunofluorescence staining were performed to determine CX37 or CX43 level and/or localization. Cx37 mRNA and protein increased (P < 0.05) at 4 days of 12.5 nM DMBA exposure. Relative to vehicle control-treated ovaries, mRNA encoding Cx43 decreased (P < 0.05) but CX43 protein increased (P < 0.05) at 4 days by both DMBA exposures. mRNA expression of pro-apoptotic p53 was decreased (P < 0.05) but no changes in Bax expression were observed after 4 days of DMBA exposures. In contrast, after 8 days, DMBA decreased Cx37 and Cx43 mRNA and protein but increased both p53 and Bax mRNA levels. CX43 protein was located between granulosa cells, while CX37 was located at the oocyte cell surface of all follicle stages. These findings support that DMBA exposure impacts ovarian Cx37 and Cx43 mRNA and protein prior to both observed changes in pro-apoptotic p53 and Bax and follicle loss. It is possible that such interference in follicular cell communication is detrimental to follicle viability, and may play a role in DMBA-induced follicular atresia. - Highlights: • DMBA increases Cx37 and Cx43 expression prior to follicle loss. • During follicle loss both Cx37 and Cx43 expressions are reduced. • CX43 protein is absent in follicle remnants lacking an oocyte.

  16. Roles of thyroid hormones in follicular development in the ovary of neonatal and immature rats.

    PubMed

    Fedail, Jaafar Sulieman; Zheng, Kaizhi; Wei, Quanwei; Kong, Lingfa; Shi, Fangxiong

    2014-08-01

    Thyroid hormones (TH) play a critical role in ovarian follicular development, maturation and the maintenance of various endocrine functions. However, whether TH can affect ovarian follicular development in neonatal and immature rats remains unclear. Therefore, the aim of the present study was to elucidate the effect of TH on ovarian follicular development in neonatal and immature rats. Thirty female post-lactation mothers of Sprague-Dawley rat pups were randomly divided into three groups: control, hyperthyroid (hyper), and hypothyroid (hypo). On postnatal days (PND) 10 and 21, body weights, serum hormones, ovarian histologic changes, and immunohistochemistry of thyroid hormone receptor alpha 1 (TRα1) and nitric oxide synthase types (NOS), and NOS activities, were determined. The data showed that body weights significantly decreased in both hyper and hypo groups compared with the control group (P < 0.05). In addition, the hyper group had increased serum concentrations of T3, T4, and E2; whereas the hypo group manifested reduced serum concentrations of T3, T4, and E2 on PND 10 and 21. The hyper and hypo groups showed significantly reduced total number of primordial, primary and secondary follicles on PND 10 and 21 compared with the control group (P < 0.05). Similarly, antral follicle numbers in the hyper and hypo groups were significantly decreased on PND 21 compared with the control group (P < 0.05). Immunostaining indicated that TRα1 and NOS were expressed in ovarian surface epithelium and oocytes of growing and antral follicles, with strong staining of the granulosa and theca cells of follicles. NOS activities were significantly augmented in the hyper, but diminished in the hypo groups on PND 10 and 21. In summary, our findings suggest that TH play important roles in ovarian functions and in the regulation of NOS activity. Our results also indicate that a relationship exists between the TH and NO signaling pathways during the process of ovarian follicular

  17. Obstructive sleep apnoea and polycystic ovary syndrome: A comprehensive review of clinical interactions and underlying pathophysiology.

    PubMed

    Kahal, Hassan; Kyrou, Ioannis; Tahrani, Abd A; Randeva, Harpal S

    2017-10-01

    Polycystic ovary syndrome (PCOS) is the most prevalent endocrine disorder in women of reproductive age. PCOS is associated with multiple comorbidities including, obesity, insulin resistance and type 2 diabetes, as well as mood disorders and impaired quality of life (QoL). Obstructive sleep apnoea (OSA) is also a common medical condition that is often undiagnosed, particularly in women. OSA is associated with a similar spectrum of comorbidities to that observed in PCOS, including manifestations of the metabolic syndrome and impaired QoL, whilst obesity frequently constitutes a common denominator in the pathophysiology of both OSA and PCOS. Hence, it is not surprising that OSA and PCOS may coexist in women of reproductive age, and the current clinical guidelines on the management of PCOS recommend screening for OSA symptoms in overweight/obese women with PCOS. In this review, we examine the relationship between OSA and PCOS and explore the potential underlying mechanisms that link these two conditions. © 2017 John Wiley & Sons Ltd.

  18. Amitriptyline plays important roles in modifying the ovarian morphology and improving its functions in rats with estradiol valerate-induced polycystic ovary.

    PubMed

    Li, Xinqiang; Wang, Shufen; Zhang, Li; Zhang, Lei; Liu, Jiali; Luo, Haoshu; Gou, Kemian; Cui, Sheng

    2017-09-08

    Previous studies demonstrated that depression is more prevalent in women with polycystic ovary syndrome (PCOS). In this study, we aimed to determine whether amitriptyline (AMT), an antidepressant drug, plays a role in preventing PCOS. The results showed that AMT modified ovarian morphology improved the ovarian functions and estrus cycle in estradiol valerate (EV)-induced polycystic ovary (PCO). AMT restored the levels of estradiol (E2), testosterone (T) and progesterone (P4) to normal, and elevated the level of luteinizing hormone (LH) in EV-induced PCO. No significant changes in follicle stimulating hormone (FSH) levels were observed in rats with EV or AMT treatment. The restoration of norepinephrine (NE) level was detected in rats with EV-induced PCO. AMT also altered the expression levels of steroidogenesis genes and beta2-adrenoceptor (beta2-AR) in EV-induced PCO. Our data revealed that AMT improves the ovarian morphology and modifies ovarian expression of beta2-AR and steroidogenesis genes in rats with EV-induced rat PCO. Our data provide support for the hypothesis that AMT is considered as a candidate drug for preventing and treating PCOS along with depression.

  19. Induction of oxidative stress and human leukocyte/endothelial cell interactions in polycystic ovary syndrome patients with insulin resistance.

    PubMed

    Victor, Victor M; Rocha, Milagros; Bañuls, Celia; Alvarez, Angeles; de Pablo, Carmen; Sanchez-Serrano, Maria; Gomez, Marcelino; Hernandez-Mijares, Antonio

    2011-10-01

    Insulin resistance is a feature of polycystic ovary syndrome (PCOS) and is related to mitochondrial and endothelial function. We tested whether hyperandrogenic insulin-resistant women with PCOS, who have an increased risk of vascular disease, display impaired leukocyte-endothelium interactions, and mitochondrial dysfunction. This was a prospective controlled study conducted in an academic medical center. The study population consisted of 43 lean reproductive-age women with PCOS and 39 controls subjects. We evaluated anthropometric and metabolic parameters, adhesion molecules, and interactions between leukocytes and human umbilical vein endothelial cells. Mitochondrial function was studied by assessing mitochondrial oxygen consumption, membrane potential, reactive oxygen species production, glutathione levels (GSH), and the oxidized glutathione (GSSG)/GSH ratio in polymorphonuclear cells. Impairment of mitochondrial function was observed in the PCOS patients, evident in a decrease in oxygen consumption, an increase in reactive oxygen species production, a decrease in the GSH/GSSG ratio and GSH levels, and an undermining of the membrane potential. PCOS was related to a decrease in polymorphonuclear cell rolling velocity and an increase in rolling flux and adhesion. Increases in IL-6 and TNFα and adhesion molecules (vascular cell adhesion molecule-1 and E-selectin) were also observed. This study supports the hypothesis of an association between insulin resistance and an impaired endothelial and mitochondrial oxidative metabolism. The evidence obtained shows that the inflammatory state related to insulin resistance in PCOS induces a leukocyte-endothelium interaction. These findings may explain the increased risk of vascular disease in women with PCOS.

  20. Behavior modulation of rats to a robotic rat in multi-rat interaction.

    PubMed

    Shi, Qing; Ishii, Hiroyuki; Tanaka, Katsuaki; Sugahara, Yusuke; Takanishi, Atsuo; Okabayashi, Satoshi; Huang, Qiang; Fukuda, Toshio

    2015-09-28

    In this paper, we study the behavioral response of rats to a robotic rat during multi-rat interaction. Experiments are conducted in an open-field where a robotic rat called WR-5 is put together with three laboratory rats. WR-5 is following one rat (target), while avoiding the other two rats (outside observers) during interaction. The behavioral characteristics of each target rat is evaluated by scoring its locomotor activity and frequencies of performing rearing, body grooming and mounting actions. Additionally, the frequency of being mounted by other rats is also measured. Experimental results show that the target becomes more active after interaction. The rat species, with more active behavioral characteristics, is more susceptible to being adjusted by the robot. The increased time spent by the outside observers in the vicinity of the robot indicates that a biomimetic robot has the promise for modulating rat behavior even without direct interaction. Thus, this study provide a novel approach to shaping the sociality of animals living in groups.

  1. Neonatal exposure to estradiol-17β modulates tumour necrosis factor alpha and cyclooxygenase-2 expression in brain and also in ovaries of adult female rats.

    PubMed

    Shridharan, Radhika Nagamangalam; Krishnagiri, Harshini; Govindaraj, Vijayakumar; Sarangi, SitiKantha; Rao, Addicam Jagannadha

    2016-02-01

    The sexually dimorphic organization in perinatal rat brain is influenced by steroid hormones. Exposure to high levels of estrogen or endocrine-disrupting compounds during perinatal period may perturb this process, resulting in compromised reproductive physiology and behavior as observed in adult In our recent observation neonatal exposure of the female rats to estradiol-17β resulted in down-regulation of TNF-α, up-regulation of COX-2 and increase in SDN-POA size in pre-optic area in the adulthood. It is known that the control of reproductive performance in female involves a complex interplay of the hypothalamus, pituitary, and ovary. The present study was undertaken to understand the possible molecular mechanism involved in changes observed in the ovarian morphology and expression of selected genes in the ovary. Administration of estradiol-17β (100 μg) on day 2 and 3 after birth revealed up-regulation of ER-α, ER-β, COX-2 and down-regulation of TNF-α expression. Also the decrease in the ovarian weight, altered ovarian morphology and changes in the 2D protein profiles were also seen. This is apparently the first report documenting that neonatal estradiol exposure modulates TNF-α and COX-2 expression in the ovary as seen during adult stage. Our results permit us to suggest that cues originating from the modified brain structure due to neonatal exposure of estradiol-17β remodel the ovary at the molecular level in such a way that there is a disharmony in the reproductive function during adulthood and these changes are perennial and can lead to infertility and changes of reproductive behavior.

  2. Angiotensin II type 2 receptor stimulation improves fatty acid ovarian uptake and hyperandrogenemia in an obese rat model of polycystic ovary syndrome.

    PubMed

    Leblanc, Samuel; Battista, Marie-Claude; Noll, Christophe; Hallberg, Anders; Gallo-Payet, Nicole; Carpentier, André C; Vine, Donna F; Baillargeon, Jean-Patrice

    2014-09-01

    Polycystic ovary syndrome (PCOS) is mainly defined by hyperandrogenism but is also characterized by insulin resistance (IR). Studies showed that overexposure of nonadipose tissues to nonesterified fatty acids (NEFA) may explain both IR and hyperandrogenism. Recent studies indicate that treatment with an angiotensin II type 2 receptor (AT2R)-selective agonist improves diet-induced IR. We thus hypothesized that PCOS hyperandrogenism is triggered by ovarian NEFA overexposure and is improved after treatment with an AT2R agonist. Experiments were conducted in 12-week-old female JCR:LA-cp/cp rats, which are characterized by visceral obesity, IR, hyperandrogenism, and polycystic ovaries. Control JCR:LA +/? rats have a normal phenotype. Rats were treated for 8 days with saline or the selective AT2R agonist C21/M24 and then assessed for: 1) fasting testosterone, NEFA, and insulin levels; and 2) an iv 14(R,S)-[(18)F]fluoro-6-thia-heptadecanoic acid test to determine NEFA ovarian tissue uptake (Km). Compared with controls, saline-treated PCOS/cp rats displayed higher insulin (100 vs 5.6 μU/mL), testosterone (0.12 vs 0.04 nmol/L), NEFA (0.98 vs 0.48 mmol/L), and Km (20.7 vs 12.9 nmol/g·min) (all P < .0001). In PCOS/cp rats, C21/M24 did not significantly improve insulin or NEFA but normalized testosterone (P = .004) and Km (P = .009), which were strongly correlated together in all PCOS/cp rats (ρ = 0.74, P = .009). In conclusion, in an obese PCOS rat model, ovarian NEFA uptake and testosterone levels are strongly associated and are both significantly reduced after short-term C21/M24 therapy. These findings provide new information on the role of NEFA in PCOS hyperandrogenemia and suggest a potential role for AT2R agonists in the treatment of PCOS.

  3. Metabolic profiling of polycystic ovary syndrome reveals interactions with abdominal obesity.

    PubMed

    Couto Alves, A; Valcarcel, B; Mäkinen, V-P; Morin-Papunen, L; Sebert, S; Kangas, A J; Soininen, P; Das, S; De Iorio, M; Coin, L; Ala-Korpela, M; Järvelin, M-R; Franks, S

    2017-09-01

    Polycystic ovary syndrome (PCOS) is a common reproductive disorder associated with metabolic disturbances including obesity, insulin resistance and diabetes mellitus. Here we investigate whether changes in the metabolic profile of PCOS women are driven by increased tendency to obesity or are specific features of PCOS related to increased testosterone levels. We conducted an NMR metabolomics association study of PCOS cases (n=145) and controls (n=687) nested in a population-based birth cohort (n=3127). Subjects were 31 years old at examination. The main analyses were adjusted for waist circumference (WC) as a proxy measure of central obesity. Subsequently, metabolite concentrations were compared between cases and controls within pre-defined WC strata. In each stratum, additional metabolomics association analyses with testosterone levels were conducted separately among cases and controls. Overall, women with PCOS showed more adverse metabolite profiles than the controls. Four lipid fractions in different subclasses of very low density lipoprotein (VLDL) were associated with PCOS, after adjusting for WC and correction for multiple testing (P<0.002). In stratified analysis the PCOS women within large WC strata (⩾98 cm) had significantly lower high density lipoprotein (HDL) levels, Apo A1 and albumin values compared with the controls. Testosterone levels were significantly associated with VLDL and serum lipids in PCOS cases with large WC but not in the controls. The higher testosterone levels, adjusted for WC, associated adversely with insulin levels and HOMA IR in cases but not in the controls. Our findings show that both abdominal obesity and hyperandrogenism contribute to the dyslipidaemia and other metabolic traits of PCOS which all may negatively contribute to the long-term health of women with PCOS.

  4. Estrogen receptor α and β expressions in hypothalamus-pituitary-ovary axis in rats exposed lactationally to soy isoflavones and bisphenol A.

    PubMed

    Yu, Bo; Chen, Qing-Feng; Liu, Zhao-Ping; Xu, He-Fei; Zhang, Xiao-Peng; Xiang, Qain; Zhang, Wen-Zhong; Cui, Wen-Ming; Zhang, Xin; Li, Ning

    2010-10-01

    This paper aims to investigate the uterotrophic activities of lactational exposure to combination of soy isoflavones (SIF) and bisphenol A (BPA) and to examine estrogen receptor α (ERα) and estrogen receptor β (ERβ) expressions in hypothalamus-pituitary-ovary axis and uterus. Maternal rats that were breeding about 8 litters were randomly divided into four groups with seven dams in each group. Dams in different treatment groups received corn oil (control), 150 mg/kg BW of SIF, 150 mg/kg BW of BPA or combination of 150 mg/kg BW of SIF and 150 mg/kg BW of BPA, respectively, from postnatal day 5 to 11 (PND5-11) by gavage. On PND12 and PND70, 10 female litters were killed and hypothalamus, pituitary, ovary and uterus were collected. ERα and ERβ expressions in these organs were detected with Western blotting assay. And vaginal opening time and estrus cycle were examined in animals fed for PND70. On PND12, the relative uterine weight of rats treated with ISF or BPA or their combination was significantly higher than that of untreated rats (P<0.05). But the relative uterine weight of rats in the co-exposure group was slightly lower than that in the group only exposed to SIF or BPA. On PND 70, however, the relative uterine weight in each treatment group was not statistically different from that in the control group (P>0.05). Vaginal opening time and estrus cycle in groups treated with SIF or BPA or their combination were similar to those in the control group (P>0.05). Exposure to SIF or BPA or their combination could up-regulate or down-regulate ERα and ERβ expressions in hypothalamus, pituitary, ovary and uterus on PND12 and PND70. These regulation patterns for ERα and ERβ were different in different organs at different time points. Lactational exposure to ISF or BPA or their combination could induce uterotrophic responses in neonate rats, which disappeared in later life. But these data fail to suggest a possibility for synergic actions between SIF and BPA. It was

  5. Adrenomedullin in rat follicles and corpora lutea: expression, functions and interaction with endothelin-1

    PubMed Central

    2011-01-01

    Background Adrenomedullin (ADM), a novel vasorelaxant peptide, was found in human/rat ovaries. The present study investigated the interaction of ADM and endothelin-1 (ET-1) in follicles and newly formed corpora lutea (CL) and the actions of ADM on progesterone production in CL during pregnancy. Methods The peptide and gene expression level of adrenomedullin in small antral follicles, large antral follicles and CL was studied by real-time RT-PCR and EIA. The effect of ADM treatment on oestradiol production in 5-day follicular culture and on progesterone production from CL of different pregnant stages was measured by EIA. The interaction of ADM and ET-1 in follicles and CL at their gene expression level was studied by real-time RT-PCR. Results In the rat ovary, the gene expression of Adm increased during development from small antral follicles to large antral follicles and CL. In vitro treatment of preantral follicular culture for 5 days with ADM increased oestradiol production but did not affect follicular growth or ovulation rate. The regulation of progesterone production by ADM in CL in culture was pregnancy-stage dependent, inhibitory at early and late pregnancy but stimulatory at mid-pregnancy, which might contribute to the high progesterone production rate of the CL at mid-pregnancy. Moreover, the interaction between ADM and ET-1 at both the production and functional levels indicates that these two vasoactive peptides may form an important local, fine-tuning regulatory system together with LH and prolactin for progesterone production in rat CL. Conclusions As the CL is the major source of progesterone production even after the formation of placenta in rats, ADM may be an important regulator in progesterone production to meet the requirement of pregnancy. PMID:21824440

  6. HemoHIM improves ovarian morphology and decreases expression of nerve growth factor in rats with steroid-induced polycystic ovaries.

    PubMed

    Kim, Sung Ho; Lee, Hae June; Kim, Joong Sun; Moon, Changjong; Kim, Jong Choon; Bae, Chun Sik; Park, Hae Ran; Jung, Uhee; Jo, Sung Kee

    2009-12-01

    Estradiol valerate (EV)-induced polycystic ovaries (PCOs) in rats cause the anovulation and cystic ovarian morphology. We investigated whether treatment with HemoHIM influences the ovarian morphology and the expression of nerve growth factor (NGF) in an EV-induced PCO rat model. PCO was induced by a single intramuscular injection of EV (4 mg, dissolved in sesame oil) in adult cycling rats. HemoHIM was either administered orally (100 mg/kg of body weight/day) for 35 consecutive days or injected intraperitoneally (50 mg/kg of body weight) every other day after EV injection. Ovarian morphology was almost normalized, and NGF was normalized in the PCO + HemoHIM group. HemoHIM lowered the high numbers of antral follicles and increased the number of corpora lutea in PCOs. The results are consistent with a beneficial effect of HemoHIM in the prevention and treatment of PCO syndrome.

  7. Exposure of Female Rats to an Environmentally Relevant Mixture of Brominated Flame Retardants Targets the Ovary, Affecting Folliculogenesis and Steroidogenesis1

    PubMed Central

    Lefèvre, Pavine L.C.; Berger, Robert G.; Ernest, Sheila R.; Gaertner, Dean W.; Rawn, Dorothea F.K.; Wade, Michael G.; Robaire, Bernard; Hales, Barbara F.

    2015-01-01

    Brominated flame retardants (BFRs) are incorporated into various consumer products to prevent flame propagation. These compounds leach into the domestic environment, resulting in chronic exposure and contamination. Pregnancy failure is associated with high levels of BFRs in human follicular fluid, raising serious questions regarding their impact on female reproductive health. The goal of this study is to elucidate the effects of an environmentally relevant BFR mixture on female rat ovarian functions (i.e., folliculogenesis and steroidogenesis). A BFR dietary mixture formulated to mimic the relative BFR congener levels in North American house dust was administered to adult female Sprague-Dawley rats from 2 to 3 wk before mating until Gestational Day 20; these diets were designed to deliver nominal doses of 0, 0.06, 20, or 60 mg/kg/day of the BFR mixture. Exposure to BFRs triggered an approximately 50% increase in the numbers of preantral and antral follicles and an enlargement of the antral follicles in the ovaries of the dams. A significant reduction in the expression of catalase, an antioxidant enzyme, and downregulation of the expression of insulin-like factor 3 (Insl3) and 17alpha-hydroxylase (Cyp17a1) were observed in the ovary. In addition, BFR exposure affected steroidogenesis; we observed a significant decrease in circulating 17-hydroxypregnenolone and an increase in testosterone concentrations in BFR-exposed dams. Thus, BFRs target ovarian function in the rat, adversely affecting both folliculogenesis and steroidogenesis. PMID:26607716

  8. An imbalance between apoptosis and proliferation contributes to follicular persistence in polycystic ovaries in rats

    PubMed Central

    Salvetti, Natalia R; Panzani, Carolina G; Gimeno, Eduardo J; Neme, Leandro G; Alfaro, Natalia S; Ortega, Hugo H

    2009-01-01

    Background Cystic ovarian disease is an important cause of infertility that affects bovine, ovine, caprine and porcine species and even human beings. Alterations in the ovarian micro-environment of females with follicular cysts could alter the normal processes of proliferation and programmed cell death in ovarian cells. Thus, our objective was to evaluate apoptosis and proliferation in ovarian cystic follicles in rats in order to investigate the cause of cystic follicle formation and persistence. Methods We compared the number of in situ apoptotic cells by TUNEL assay, expression of active caspase-3 and members of Bcl-2 family by immunohistochemistry; and cell proliferation by the expression of the proliferation markers: PCNA and Ki-67. Results The proliferation index was low in granulosa of tertiary and cystic follicles of light exposed rats when compared with tertiary follicles of control animals, while in theca interna only cystic follicles presented low proliferation index when compared with tertiary follicles (p < 0.05). The granulosa of cysts exhibited a similar cell DNA fragmentation to early atretic follicles. In the granulosa and theca interna, active caspase-3 shown similar immunostaining levels in tertiary and cystic follicles (p < 0.05). The granulosa cells presented high expression of Bcl-2, Bcl-xL and Bcl-w in the tertiary and cystic follicles with diminishing intensity in the atretic follicles, except with Bcl-w where the intensity was maintained in the atretic follicles (p < 0.05). The expression of Bax was weak in the healthy and cystic follicles. In the theca interna, Bcl-2 expression was the same as the pattern found in the granulosa; no differences were found between tertiary and cystic follicles from both groups for Bcl-xL and Bcl-w. The expression of Bax in this layer was higher in the tertiary follicles of the treated animals (p < 0.05) while the values for cystic follicles were similar to those in the tertiary follicles of controls. The

  9. Identification of polycystic ovary syndrome potential drug targets based on pathobiological similarity in the protein-protein interaction network

    PubMed Central

    Li, Wan; Wei, Wenqing; Li, Yiran; Xie, Ruiqiang; Guo, Shanshan; Wang, Yahui; Jiang, Jing; Chen, Binbin; Lv, Junjie; Zhang, Nana; Chen, Lina; He, Weiming

    2016-01-01

    Polycystic ovary syndrome (PCOS) is one of the most common endocrinological disorders in reproductive aged women. PCOS and Type 2 Diabetes (T2D) are closely linked in multiple levels and possess high pathobiological similarity. Here, we put forward a new computational approach based on the pathobiological similarity to identify PCOS potential drug target modules (PPDT-Modules) and PCOS potential drug targets in the protein-protein interaction network (PPIN). From the systems level and biological background, 1 PPDT-Module and 22 PCOS potential drug targets were identified, 21 of which were verified by literatures to be associated with the pathogenesis of PCOS. 42 drugs targeting to 13 PCOS potential drug targets were investigated experimentally or clinically for PCOS. Evaluated by independent datasets, the whole PPDT-Module and 22 PCOS potential drug targets could not only reveal the drug response, but also distinguish the statuses between normal and disease. Our identified PPDT-Module and PCOS potential drug targets would shed light on the treatment of PCOS. And our approach would provide valuable insights to research on the pathogenesis and drug response of other diseases. PMID:27191267

  10. The effect of Non- ionizing electromagnetic field with a frequency of 50 Hz in Rat ovary: A transmission electron microscopy study

    PubMed Central

    Khaki, Amir Afshin; Khaki, Arash; Ahmadi, Seyed Shahin

    2016-01-01

    Background: Recently, there are increasing concerns and interests about the potential effects of Electromagnetic Field (EMF) on both human and animal health. Objective: The goal of this study was to evaluate the harmful effects of 50 Hz non-ionizing EMF on rat oocytes. Materials and Methods: In this experimental study 30 rats were randomly taken from laboratory animals and their ags and weights were determined. These 3 month's old rats were randomly divided into 3 groups. The control group consisted of 10 rats without receiving any treatment and kept under normal conditions. Experimental group 1 (10 rats) received EMF for 8 weeks (3 weeks intrauterine +5 weeks after births) and experimental group 2 (10 rats) received EMF for 13 weeks (3 weeks intrauterine +10 weeks after birth). After removing the ovaries and isolating follicles, granulosa cells were fixed in glutaraldehyde and osmium tetroxide. Electron microscopy was used to investigate the traumatic effects of EMF on follicles. Results: In control group nucleus membrane and mitochondria in follicle’s cytoplasm seemed normal in appearance. Theca layer of primary follicles in experimental group was separated clearly, zona layer demonstrated trot with irregular thickness and ovarian stroma seemed isolated with dilated vessels showing infiltration. Conclusion: According to the results of this study, it can be concluded that EMF has harmful effects on the ovarian follicles. PMID:27200427

  11. Alcohol-induced oxidative stress and reduction in oxidation by ascorbate/L-cys/ L-met in the testis, ovary, kidney, and lung of rat.

    PubMed

    Amanvermez, Ramazan; Demir, Serif; Tunçel, Ozgür K; Alvur, Muhlise; Agar, Erdal

    2005-01-01

    Chronic exposure to high doses of alcohol results in many pathophysiologic changes in cellular function caused by the alcohol itself and the effects of its metabolism (ie, generation of acetaldehyde, nicotinamide adenine dinucleotide [NADH], free radicals, and oxidative stress). However, the role of each of these effects on the testis, ovary, kidney, and lung in chronic alcoholism must be investigated. It is hypothesized that cysteine-methionine and vitamin C might neutralize harmful compounds and potentiate the antioxidant capacity of the cell or tissue. In this study, rats were fed regular diets and were maintained in the following groups for 90 days: control group; alcoholic group (2.5 g of 50% ethanol/kg body wt administered intragastrically every other day); and alcoholic with antioxidant supplement group (2.5 g of 50% ethanol plus a solution containing 200 mg vitamin C, 100 mg cysteine, and 100 mg methionine/kg body wt administered intragastrically every other day). After treatment had been completed, rat blood, testis, ovary, kidney, and lung were taken for biochemical analysis. Mean alcohol level in the alcoholic group was raised (by 40%) compared with that in the control group, but it was lower (by 30%) in the antioxidant-supplemented group than in the alcoholic group. In accordance with the levels of alcohol, oxidized protein and lipid content in the testis, ovary, kidney, and lung were low in the control group, higher in the antioxidant-supplemented group, and highest in the alcoholic group. It is interesting to note that levels of glutathione in the testis and lung of the alcoholic group were lower than those in both the control and antioxidant-supplemented groups. In conclusion, chronic alcohol administration led to a significant increase in the level of protein oxidation in the ovary and kidney of rats. Simultaneous intake of ascorbate/L-cys/L-met, along with ethanol, partly attenuated the amount of lipid and protein oxidation that occurred in tissues

  12. Electrical and manual acupuncture stimulation affect oestrous cyclicity and neuroendocrine function in an 5α-dihydrotestosterone-induced rat polycystic ovary syndrome model.

    PubMed

    Feng, Yi; Johansson, Julia; Shao, Ruijin; Mannerås-Holm, Louise; Billig, Håkan; Stener-Victorin, Elisabet

    2012-05-01

    Both low-frequency electro-acupuncture (EA) and manual acupuncture improve menstrual frequency and decrease circulating androgens in women with polycystic ovary syndrome (PCOS). We sought to determine whether low-frequency EA is more effective than manual stimulation in regulating disturbed oestrous cyclicity in rats with PCOS induced by 5α-dihydrotestosterone. To identify the central mechanisms of the effects of stimulation, we assessed hypothalamic mRNA expression of molecules that regulate reproductive and neuroendocrine function. From age 70 days, rats received 2 Hz EA or manual stimulation with the needles five times per week for 4-5 weeks; untreated rats served as control animals. Specific hypothalamic nuclei were obtained by laser microdissection, and mRNA expression was measured with TaqMan low-density arrays. Untreated rats were acyclic. During the last 2 weeks of treatment, seven of eight (88%) rats in the EA group had epithelial keratinocytes, demonstrating oestrous cycle change (P = 0.034 versus control rats). In the manual group, five of eight (62%) rats had oestrous cycle changes (n.s. versus control animals). The mRNA expression of the opioid receptors Oprk1 and Oprm1 in the hypothalamic arcuate nucleus was lower in the EA group than in untreated control rats. The mRNA expression of the steroid hormone receptors Esr2, Pgr and Kiss1r was lower in the manual group than in the control animals. In rats with 5α-dihydrotestosterone-induced PCOS, low-frequency EA restored disturbed oestrous cyclicity but did not differ from the manual stimulation group, although electrical stimulation lowered serum testosterone in responders, those with restored oestrus cyclicity, and differed from both control animals and the manual stimulation group. Thus, EA cannot in all aspects be considered superior to manual stimulation. The effects of low-frequency EA may be mediated by central opioid receptors, while manual stimulation may involve regulation of steroid hormone

  13. Effect of phosphatidylinositol-3 kinase inhibition on ovotoxicity caused by 4-vinylcyclohexene diepoxide and 7, 12-dimethylbenz[a]anthracene in neonatal rat ovaries

    SciTech Connect

    Keating, Aileen F.; Mark, Connie J.; Sen, Nivedita; Sipes, I. Glenn; Hoyer, Patricia B.

    2009-12-01

    4-vinylcyclohexene diepoxide (VCD) is an ovotoxicant that specifically destroys primordial and small primary follicles in the ovaries of mice and rats. In contrast, 7,12-dimethylbenz[a]anthracene (DMBA) is ovotoxic to all ovarian follicle classes. This study investigated phosphatidylinositol-3 kinase signaling involvement in VCD- and DMBA-induced ovotoxicity. Postnatal day (PND) 4 Fischer 344 (F344) rat whole ovaries were cultured for 2-12 days in vehicle control, VCD (30 muM), or DMBA (1 muM), +- PI3 kinase inhibitor LY294002 (20 muM) or its inactive analog LY303511 (20 muM). Following culture, ovaries were histologically evaluated, and healthy follicles were classified and counted. PI3 kinase inhibition had no effect on primordial follicle number, but reduced (P < 0.05) small primary and larger follicles beginning on day 4. VCD caused primordial and small primary follicle loss (P < 0.05) beginning on day 6. With PI3 kinase inhibition, VCD did not affect primordial follicles (P > 0.05) at any time, but did cause loss (P < 0.05) of small primary follicles. DMBA exposure caused primordial and small primary follicle loss (P < 0.05) on day 6. Further, DMBA-induced primordial and small primary follicle loss was greater with PI3 kinase inhibition (P < 0.05) than with DMBA alone. These results support that (1) PI3 kinase mediates primordial to small primary follicle recruitment, (2) VCD, but not DMBA, enhances ovotoxicity by increasing primordial to small primary follicle recruitment, and (3) in addition to xenobiotic-induced ovotoxicity, VCD is also a useful model chemical with which to elucidate signaling mechanisms involved in primordial follicle recruitment.

  14. The use of primary rat hepatocytes to achieve metabolic activation of promutagens in the Chinese hamster ovary/hypoxantine-guanine phosphoribosyl transferase mutational assay

    SciTech Connect

    Bermudez, E.; Couch, D.B.; Tillery, D.

    1982-01-01

    A method is described in which primary rat hepatocytes have been cocultured with chinese hamster ovary (CHO) cells to provide metabolic activation of promutgens in the Chinese hamster ovary/hypoxanthine-guanine phosphoribosyl transferase (CHO/HGPRT) mutational assay. Single cell hepatocyte suspensions were prepared from male Fisher-344 rats using the in situ collagenase perfusion technique. Hepatocytes were allowed to attach for 1.5 hours in tissue culture dishes containing an approximately equal number of CHO cells in log growth. The cocultures were exposed to promutagens for up to 20 hours in serum-free medium. The survival and 6-thioguanine-resistant fraction of treated CHO cells were then determined as in the standard CHO/HGPRT assay. Aflatoxin B/sub 1/ (AFB/sub 1/) 7,12-dimethylbenz(a)anthracene (DMBA) and benzo(a)pyrene (B(a)P) were found to produce increases in the mutant fractions of treated CHO cells as a function of concentration. The time required for optimum expression of the mutant phenotype following exposure to DMBA and AFB/sub 1/ was approximately 8 days. Primary cell-mediated mutagenesis may be useful in elucidating methobolic pathways important in the production and detoxification of genotoxic products in vivo.

  15. The expression of hyperpolarization activated cyclic nucleotide gated (HCN) channels in the rat ovary are dependent on the type of cell and the reproductive age of the animal: a laboratory investigation

    PubMed Central

    Yeh, John; Kim, Beom Su; Gaines, Larry; Peresie, Jennifer; Page, Carly; Arroyo, Armando

    2008-01-01

    Background Aim of this study was to test the hypothesis that levels of hyperpolarization activated cyclic nucleotide gated channels 1 to 4 (HCN1-4) are linked to the reproductive age of the ovary. Methods Young, adult, and reproductively aged ovaries were collected from Sprague-Dawley rats. RT-PCR and western blot analysis of ovaries was performed to investigate the presence of mRNA and total protein for HCN1-4. Immunohistochemistry with semiquantitative H score analysis was performed using whole ovarian histologic sections. Results RT-PCR analysis showed the presence of mRNA for HCN1-4. Western blot analysis revealed HCN1-3 proteins in all ages of ovarian tissues. Immunohistochemistry with H score analysis demonstrated distinct age-related changes in patterns of HCN1-3 in the oocytes, granulosa cells, theca cells, and corpora lutea. HCN4 was present only in the oocytes, with declining levels during the reproduction lifespan. Conclusion The evidence presented here demonstrates cell-type and developmental age patterns of HCN1-4 channel expression in rat ovaries. Based on this, we hypothesize that HCN channels have functional significance in rat ovaries and may have changing roles in reproductive aging. PMID:18710573

  16. Reduced estradiol-induced vasodilation and poly-(ADP-ribose) polymerase (PARP) activity in the aortas of rats with experimental polycystic ovary syndrome (PCOS).

    PubMed

    Masszi, Gabriella; Horvath, Eszter Maria; Tarszabo, Robert; Benko, Rita; Novak, Agnes; Buday, Anna; Tokes, Anna-Maria; Nadasy, Gyorgy L; Hamar, Peter; Benyó, Zoltán; Varbiro, Szabolcs

    2013-01-01

    Polycystic ovary syndrome (PCOS) is a complex endocrine disorder characterized by hyperandrogenism and insulin resistance, both of which have been connected to atherosclerosis. Indeed, an increased risk of clinical manifestations of arterial vascular diseases has been described in PCOS. On the other hand endothelial dysfunction can be detected early on, before atherosclerosis develops. Thus we assumed that vascular dysfunction is also related directly to the hormonal imbalance rather than to its metabolic consequences. To detect early functional changes, we applied a novel rodent model of PCOS: rats were either sham operated or hyperandrogenism was achieved by implanting subcutaneous pellets of dihydrotestosterone (DHT). After ten weeks, myograph measurements were performed on isolated aortic rings. Previously we described an increased contractility to norepinephrine (NE). Here we found a reduced immediate relaxation to estradiol treatment in pre-contracted aortic rings from hyperandrogenic rats. Although the administration of vitamin D3 along with DHT reduced responsiveness to NE, it did not restore relaxation to estradiol. Poly-(ADP-ribose) polymerase (PARP) activity was assessed by poly-ADP-ribose immunostaining. Increased PAR staining in ovaries and circulating leukocytes from DHT rats showed enhanced DNA damage, which was reduced by concomitant vitamin D3 treatment. Surprisingly, PAR staining was reduced in both the endothelium and vascular smooth muscle cells of the aorta rings from hyperandrogenic rats. Thus in the early phase of PCOS, vascular tone is already shifted towards vasoconstriction, characterized by reduced vasorelaxation and vascular dysfunction is concomitant with altered PARP activity. Based on our findings, PARP inhibitors might have a future perspective in restoring metabolic disorders in PCOS.

  17. Low-frequency electro-acupuncture and physical exercise improve metabolic disturbances and modulate gene expression in adipose tissue in rats with dihydrotestosterone-induced polycystic ovary syndrome.

    PubMed

    Mannerås, Louise; Jonsdottir, Ingibjörg H; Holmäng, Agneta; Lönn, Malin; Stener-Victorin, Elisabet

    2008-07-01

    Polycystic ovary syndrome (PCOS) is a complex endocrine and metabolic disorder associated with ovulatory dysfunction, hyperandrogenism, abdominal obesity, and insulin resistance. Pharmacotherapy is often unsatisfactory. This study evaluates the effects of low-frequency electro-acupuncture (EA) and physical exercise on metabolic disturbances and adipose tissue mRNA expression of selected genes in a rat PCOS model characterized by insulin resistance and adiposity. Dihydrotestosterone (inducing PCOS) or vehicle (control) was administrated continuously, beginning before puberty. At age 10 wk, PCOS rats were randomly divided into three groups; PCOS, PCOS EA, and PCOS exercise. PCOS EA rats received 2-Hz EA (evoking muscle twitches) three times/wk during 4-5 wk. PCOS exercise rats had free access to a running wheel for 4-5 wk. EA and exercise improved insulin sensitivity, measured by clamp, in PCOS rats. Exercise also reduced adiposity, visceral adipocyte size, and plasma leptin. EA increased plasma IGF-I. Real-time RT-PCR revealed increased expression of leptin and IL-6 and decreased expression of uncoupling protein 2 in visceral adipose tissue of PCOS rats compared with controls. EA restored the expression of leptin and uncoupling protein 2, whereas exercise normalized adipose tissue leptin and IL-6 expression in PCOS rats. Thus, EA and exercise ameliorate insulin resistance in rats with PCOS. This effect may involve regulation of adipose tissue metabolism and production because EA and exercise each partly restore divergent adipose tissue gene expression associated with insulin resistance, obesity, and inflammation. In contrast to exercise, EA improves insulin sensitivity and modulates adipose tissue gene expression without influencing adipose tissue mass and cellularity.

  18. Histopathologycal findings in the ovaries and uterus of albino female rats promoted by co-administration of synthetic steroids and nicotine.

    PubMed

    Camargo, Isabel Cristina Cherici; Leite, Gabriel Adan Araújo; Pinto, Tiago; Ribeiro-Paes, João Tadeu

    2014-07-01

    The use of anabolic androgenic steroids is often associated with the use of other substances, licit or not, such as nicotine present in the tobacco. The present study investigated for the first time the effects of co-administration of synthetic steroids and nicotine on the ovarian and uterine tissue and fertility of adult female rats. Animals were submitted to treatment groups (n=16/group): nandrolone decanoate (ND; 7.5mg/kg BW/week); testosterone mixture (T; 7.5mg/kg BW/week); nicotine (N; 2.0mg/kg BW/day), and co-administration of ND/N, T/N and ND/T/N. The control group received saline solution daily. The injections were administered subcutaneously for 30 consecutive days. Results demonstrated that all androgenized rats exhibited estral acyclicity and there was suppression of reproductive capacity due to notable ovarian and uterine histological changes. Treatments promoted decrease (p<0.05) in the ovarian weight. Uterine weight increased (p<0.05) in the T and T/N groups, in comparison to control group. ND or T co-administered or not to nicotine promoted intense follicular degeneration, with formation of cysts in the ovaries. High levels of circulating androgens in the ND/T/N group induced the presence of ovarian sex cord-stromal tumors of Sertoli cell pattern. Androgenized females presented endometrial changes characterized by papilliferous or pleated luminal epithelium, oedematous and hemorrhagic stroma and presence of gland cysts. In conclusion, the co-administration of three drugs promoted atypical morphological pattern on the ovaries and uterus of female rats.

  19. A Novel Potential Reproductive Effects Of Pterocarpus Marsupium Methanolic Extract On Testosterone Propionate Induced Polycystic Ovary Syndrome In Female Albino Rats.

    PubMed

    Hugar, Aruna Lingappa; Kanjikar, Amarvani P; Londonkar, Ramesh L

    2017-09-12

    Objective To investigate potential reproductive effects of Pterocarpus marsupium methanolic extract on testosterone propionate induced Polycystic Ovarian Syndrome (PCOS) in female albino rats. Methodology PCOS was induced in female albino rats by daily injecting testosterone propionate for 15 days intraperitoneally. Animals are divided into five groups with six rats per group. Group 1: Control group received olive oil, Group 2: Testosterone propionate+natural recovery, Group 3: Testosterone propionate + a dose of clomiphene citrate (standard), Group 4 and 5: Testosterone propionate + low dose (200mg/kg) and high dose (400mg/kg) b.w respectively for 15 days. Various biochemical and histopathological investigations were assessed. Results Methanol extract of Pterocarpus marsupium was able to exert its protective effect successfully by restoring all the parameters to normal and diminishing the cysts found in ovaries. Conclusion Pterocarpus marsupium found to have potential reproductive effects in testosterone propionate induced PCOS female albino rats and could be used as an alternative therapy in treatment of PCOS. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  20. Cadmium exposure in newborn rats ovary induces developmental disorders of primordial follicles and the differential expression of SCF/c-kit gene.

    PubMed

    Zhang, Wenchang; Wu, Tingting; Zhang, Chenyun; Luo, Lingfeng; Xie, Meimei; Huang, Huiling

    2017-10-05

    Since the 1990s, the rising problem that gonad reproductive toxicity on adult female after exposing to cadmium (Cd), an environmental endocrine disruptor, has attracted high attention at home and abroad,and was systematically studied. Our research focuses on a further problem is that early cadmium exposure (during birth to before puberty) impact on development and function of ovarian cells and its possible mechanism. Our research focuses on the changes of ovarian cells growth and development after the newborn rat ovaries with cadmium exposure in vitro, and different expression of ovarian cells development-related factors, SCF/c-kit and changes of their DNA methylation status. We obtained ovaries from 4-day-old SD rats and cultured them in DMEM/F12 mixed with α-MEM media in vitro. Different doses of cadmium were designed as control, 0.5, 5, 10 and 50μM, and then the constituent ratio of ovarian follicle and follicular oocytes diameter were observed with microscope after 4-h exposure. We found that the increased constituent ratio of original follicle and decreased diameter of all levels of follicular oocytes(compared with control, with statistically significant differences, P<0.01).After the measurement of expression of SCF/c-kit by qRT-PCR and Western Blotting, the mRNA and protein expression of SCF/c-kit in ovarian were both decreased. We further found that the increased constituent ratio of growth follicle and increased diameter of oocytes under the treatment of adding SCF in cell culture media. Finally, MALDI-TOF-MS method showed DNA-low methylation status of SCF/c-kit promoter region after Cd exposure. Overall, we concluded that the exposure of cadimium (5-50μM) on newborn rats ovaries could inhibit follicle development.SCF/c-kit system might mediate follicle development damage caused by cadmium, which is associated with DNA hypomethylation of SCF/c-kit promoter region may be worthy of further study. Copyright © 2017. Published by Elsevier B.V.

  1. Interactions between respiratory oscillators in adult rats

    PubMed Central

    Huckstepp, Robert TR; Henderson, Lauren E; Cardoza, Kathryn P; Feldman, Jack L

    2016-01-01

    Breathing in mammals is hypothesized to result from the interaction of two distinct oscillators: the preBötzinger Complex (preBötC) driving inspiration and the lateral parafacial region (pFL) driving active expiration. To understand the interactions between these oscillators, we independently altered their excitability in spontaneously breathing vagotomized urethane-anesthetized adult rats. Hyperpolarizing preBötC neurons decreased inspiratory activity and initiated active expiration, ultimately progressing to apnea, i.e., cessation of both inspiration and active expiration. Depolarizing pFL neurons produced active expiration at rest, but not when inspiratory activity was suppressed by hyperpolarizing preBötC neurons. We conclude that in anesthetized adult rats active expiration is driven by the pFL but requires an additional form of network excitation, i.e., ongoing rhythmic preBötC activity sufficient to drive inspiratory motor output or increased chemosensory drive. The organization of this coupled oscillator system, which is essential for life, may have implications for other neural networks that contain multiple rhythm/pattern generators. DOI: http://dx.doi.org/10.7554/eLife.14203.001 PMID:27300271

  2. Hyperandrogenism and Insulin Resistance, Not Changes in Body Weight, Mediate the Development of Endothelial Dysfunction in a Female Rat Model of Polycystic Ovary Syndrome (PCOS).

    PubMed

    Hurliman, Amanda; Keller Brown, Jennifer; Maille, Nicole; Mandala, Maurizio; Casson, Peter; Osol, George

    2015-11-01

    This study was designed to differentiate the contributions of hyperandrogenism, insulin resistance (IR), and body weight to the development of endothelial dysfunction in polycystic ovary syndrome and determine the effectiveness of insulin sensitization and antiandrogenic therapy after the establishment of vascular and metabolic dysfunction using a rat model of polycystic ovary syndrome. We hypothesized that the observed endothelial dysfunction was a direct steroidal effect, as opposed to changes in insulin sensitivity or body weight. Prepubertal female rats were randomized to the implantation of a pellet containing DHT or sham procedure. In phase 1, DHT-exposed animals were randomized to pair feeding to prevent weight gain or metformin, an insulin-sensitizing agent, from 5 to 14 weeks. In phase 2, DHT-exposed animals were randomized to treatment with metformin or flutamide, a nonsteroidal androgen receptor blocker from 12 to 16 weeks. Endothelial function was assessed by the vasodilatory response of preconstricted arteries to acetylcholine. Serum steroid levels were analyzed in phase 1 animals. Fasting blood glucose and plasma insulin were analyzed and homeostasis model assessment index calculated in all animals. Our data confirm the presence of endothelial dysfunction as well as increased body weight, hypertension, hyperinsulinemia, and greater IR among DHT-treated animals. Even when normal weight was maintained through pair feeding, endothelial dysfunction, hyperinsulinemia, and IR still developed. Furthermore, despite weight gain, treatment with metformin and flutamide improved insulin sensitivity and blood pressure and restored normal endothelial function. Therefore, the observed endothelial dysfunction is most likely a direct result of hyperandrogenism-induced reductions in insulin sensitivity, as opposed to weight gain.

  3. Pyrrolidon carboxypeptidase activities in the hypothalamus-pituitary-thyroid and hypothalamus-pituitary-ovary axes of rats with mammary gland cancer induced by N-methyl nitrosourea.

    PubMed

    Carrera, M P; Ramírez-Expósito, M J; Valenzuela, M T; García, M J; Mayas, M D; Arias de Saavedra, J M; Sánchez, R; Pérez, M C; Martínez-Martos, J M

    2005-02-01

    Pyrrolidon carboxypeptidase is an omega-peptidase that hydrolyses N-terminal pyroglutamyl residues from biologically active peptides such as gonadotropin-releasing and thyrotrophin-releasing hormones. We previously described a decrease in both rat and human pyrrolidon carboxypeptidase activity with breast cancer, suggesting that gonadotropin-releasing hormone may be an important local intracrine, autocrine and/or paracrine hormonal factor in the pathogenesis of breast cancer while playing a role in the tumoral process. However, the other susceptible substrate of pyrrolidon carboxypeptidase, thyrotrophin-releasing hormone, may also be modified with breast cancer, supporting an association between breast cancer and thyroid disorders. The present work analyses soluble and membrane-bound pyrrolidon carboxypeptidase activities in the hypothalamus-pituitary-thyroid and hypothalamus-pituitary-ovary axes in N-methyl nitrosourea-induced breast cancer in rats. Our aim was to determine the possible relationship between gonadotropin-releasing hormone and thyrotrophin-releasing hormone regulation through pyrrolidon carboxypeptidase activity. We propose that pyrrolidon carboxypeptidase activity dysregulation at various local and systemic levels may participate in the initiation, promotion and progression of breast cancer induced in rat by N-methyl nitrosourea through the increase in gonadotropin-releasing hormone. Since pyrrolidon carboxypeptidase activity also acts on thyrotrophin-releasing hormone, the dysregulation of this enzyme's activity could indirectly affect hypothalamus-pituitary-thyroid axis function, and thus potentially represent a link between the diseases of thyroid and breast cancer.

  4. The effect of metamizole on ischemia/reperfusion injury in the rat ovary: An analysis of biochemistry, molecular gene expression, and histopathology

    PubMed Central

    Kumbasar, Serkan; Salman, Suleyman; Al, Ragip Atakan; Ozturk, Cengiz; Yarali, Oguzhan; Alp, Hamit Hakan; Altuner, Durdu; Suleyman, Bahadir

    2016-01-01

    Objectives: In this study, we investigated the effect of metamizole on ischemia/reperfusion (I/R) injury an analysis of biochemistry, molecular gene expression, and histopathology in the rat ovary of female albino Wistar rats. Materials and Methods: Animals were divided into four groups; control group with induced ischemia-reperfusion (IRC), ischemia-reperfusion +100 mg/kg metamizole sodium (MS) (IRM-100), ischemia-reperfusion +200 mg/kg MS (IRM-200), and healthy group applied sham operation (SG). Results: Myeloperoxidase (MPO) activity and gene expression increased significantly in IRC and IRM-100 group rat ovarian tissue compared with the SG group (P < 0.0001). However, MPO activity and gene expression in IRM-200 group ovarian tissue decreased significantly compared with the IRC and IRM-100 groups (P < 0.0001). Histopathologically, pronounced congestion, dilated vessels, hemorrhage, edema, degenerative cells, and neutrophil migration and adhesion to the endothelium were observed in the IRC and IRM-100 group ovarian tissues. A small number of congested dilated vessels, mild congestion, and edema were observed in the IRM-200 group, but no neutrophil migration and adhesion to the endothelium or degenerative cells. Conclusions: At 200 mg/kg dose metamizole prevented ovarian injury induced with I/R. This data show that metamizole can be used in the ovarian I/R injury treatment. PMID:26997719

  5. Anti-Inflammatory Effects of Curcumin on Insulin Resistance Index, Levels of Interleukin-6, C-Reactive Protein, and Liver Histology in Polycystic Ovary Syndrome-Induced Rats.

    PubMed

    Mohammadi, Shima; Karimzadeh Bardei, Latifeh; Hojati, Vida; Ghorbani, Azita Ghorbani; Nabiuni, Mohammad

    2017-10-01

    Curcumin protects the liver against injury and fibrosis through suppressing hepatic inflammation, attenuating hepatic oxidative stress (OS), and inhibiting hepatic stellate cells (HSCs) activation. Non-alcoholic fatty liver disease (NAFLD) and polycystic ovary syndrome (PCOS) are considered as common metabolic disorders. Low-grade chronic inflammation with different markers, such as elevated C-reactive protein (CRP) and interleukin-6 (IL-6) levels, play a crucial role in PCOS. This study aimed to evaluate the therapeutic effects of curcumin on IL-6 and CRP levels as well as insulin resistance (IR) index on liver function in PCOS rats. In this experimental study, 90 adult Wistar rats were divided into control (n=18), sham (n=18), PCOS (n=18) and curcumin-treated PCOS groups (n=36). PCOS group was injected subcutaneously with 2 mg estradio-valerate (E2V). After 60 days, PCOS group was treated with curcumin [100 and 300 mg/kg body weight (BW)] for 14 days and anesthetized by chloroform. Blood and liver samples were collected for histological and serological analyses. Data were analyzed using In-Stat 3 via one-way analysis of variance (ANOVA). Histological and serological analyses showed a reduction in number of necrotic cells, IR index, as well as IL-6 and CRP levels in PCOS rats that were treated with various concentrations of curcumin. In this study, curcumin decreased liver inflammation by induction of insulin sensitivity and reduction of hepatic necrosis. Therefore, curcumin may be considered as protective factor against inflammatory state of PCOS.

  6. The effects of 6-Gingerol on reproductive improvement, liver functioning and Cyclooxygenase-2 gene expression in estradiol valerate - Induced polycystic ovary syndrome in Wistar rats.

    PubMed

    Pournaderi, Parisa Sadat; Yaghmaei, Parichehreh; Khodaei, Hamidreza; Noormohammadi, Zahra; Hejazi, Seyed Hossein

    2017-03-04

    6-Gingerol is the major pungent ingredient of ginger with anti-inflammatory and antioxidant properties. In this study, we evaluate the effects of 6-gingerol on the biochemical parameters and ovarian histological improvements in estradiol valerate (EV) induced PCOS rats. Thirty six female Wistar rats were divided into 4 groups: control, received normal diet, PCOS control, received 4 mg/kg EV injection for 28 days and two experimental groups, received an EV injection for 28 days and followed by 6-gingerol (200 μg/kg and 400 μg/kg) for 14 days. The administration of EV led to increase body and ovarian weights, abnormality in serum sex steroid profile, decrease in antioxidant activity and increase in COX-2 gene expression. 6-gingerol treatments, particularly the 400 μg/kg dose, markedly attenuated these alterations. 6-gingerol showed beneficial effects in the EV induced PCOS rats via decreased expression of COX-2, restored biochemical parameters to normal and decreased of cysts in the ovaries.

  7. How do red and infrared low-level lasers affect folliculogenesis cycle in rat's ovary tissue in comparison with clomiphene under in vivo condition.

    PubMed

    Naseri, Paria; Alihemmati, Alireza; Rasta, Seyed Hossein

    2017-08-11

    Folliculogenesis is a cycle that produces the majority of oocyte. Any disruption to this cycle leads to ovulation diseases, like polycystic ovarian syndrome (PCOS). Treatments include drugs and surgery; lasers have also been used complementarily. Meanwhile, still there is no definite treatment for PCOS. This study investigated the photo-bio stimulation effect of near-infrared and red low-level laser on producing follicles and compared the result with result of using common drug, clomiphene. Therefore, the aim of this study was to propose the use of lasers autonomously treatment. So, there was one question: how do lasers affect folliculogenesis cycle in rat's ovary tissue? In this study, 28 rats were assigned to four groups as follows: control (CT), clomiphene drug (D), red laser (RL), and near-infrared laser (NIRL). Afterwards, 14 rats of RL and NIRL groups received laser on the first 2 days of estrous cycle, each 6 days, for 48 days. During treatment period, each rat received energy density of 5 J/cm(2). Seven rats in D group received clomiphene. After the experiment, lasers' effects at two wavelengths of 630 and 810 nm groups have been investigated and compared with clomiphene and CT groups. Producing different follicles to complement folliculogenesis cycle increased in NIRL and RL groups, but this increase was significant only in the NIRL group. This indicates that NIRL increases ovarian activity to produce oocyte that certainly can be used in future studies for finding a cure to ovarian negligence to produce more oocyte and treat diseases caused by it like PCOS.

  8. The role of nicotinamide–adenine dinucleotide phosphate-dependent malate dehydrogenase and isocitrate dehydrogenase in the supply of reduced nicotinamide–adenine dinucleotide phosphate for steroidogenesis in the superovulated rat ovary

    PubMed Central

    Flint, A. P. F.; Denton, R. M.

    1970-01-01

    1. Superovulated rat ovary was found to contain high activities of NADP–malate dehydrogenase and NADP–isocitrate dehydrogenase. The activity of each enzyme was approximately four times that of glucose 6-phosphate dehydrogenase and equalled or exceeded the activities reported to be present in other mammalian tissues. Fractionation of a whole tissue homogenate of superovulated rat ovary indicated that both enzymes were exclusively cytoplasmic. The tissue was also found to contain pyruvate carboxylase (exclusively mitochondrial), NAD–malate dehydrogenase and aspartate aminotransferase (both mitochondrial and cytoplasmic) and ATP–citrate lyase (exclusively cytoplasmic). 2. The kinetic properties of glucose 6-phosphate dehydrogenase, NADP–malate dehydrogenase and NADP–isocitrate dehydrogenase were determined and compared with the whole-tissue concentrations of their substrates and NADPH; NADPH is a competitive inhibitor of all three enzymes. The concentrations of glucose 6-phosphate, malate and isocitrate in incubated tissue slices were raised at least tenfold by the addition of glucose to the incubation medium, from the values below to values above the respective Km values of the dehydrogenases. Glucose doubled the tissue concentration of NADPH. 3. Steroidogenesis from acetate is stimulated by glucose in slices of superovulated rat ovary incubated in vitro. It was found that this stimulatory effect of glucose can be mimicked by malate, isocitrate, lactate and pyruvate. 4. It is concluded that NADP–malate dehydrogenase or NADP–isocitrate dehydrogenase or both may play an important role in the formation of NADPH in the superovulated rat ovary. It is suggested that the stimulatory effect of glucose on steroidogenesis from acetate results from an increased rate of NADPH formation through one or both dehydrogenases, brought about by the increases in the concentrations of malate, isocitrate or both. Possible pathways involving the two enzymes are discussed

  9. Electrical vs manual acupuncture stimulation in a rat model of polycystic ovary syndrome: different effects on muscle and fat tissue insulin signaling.

    PubMed

    Johansson, Julia; Mannerås-Holm, Louise; Shao, Ruijin; Olsson, AnneLiese; Lönn, Malin; Billig, Håkan; Stener-Victorin, Elisabet

    2013-01-01

    In rats with dihydrotestosterone (DHT)-induced polycystic ovary syndrome (PCOS), repeated low-frequency electrical stimulation of acupuncture needles restores whole-body insulin sensitivity measured by euglycemic hyperinsulinemic clamp. We hypothesized that electrical stimulation causing muscle contractions and manual stimulation causing needle sensation have different effects on insulin sensitivity and related signaling pathways in skeletal muscle and adipose tissue, with electrical stimulation being more effective in DHT-induced PCOS rats. From age 70 days, rats received manual or low-frequency electrical stimulation of needles in abdominal and hind limb muscle five times/wk for 4-5 wks; controls were handled but untreated rats. Low-frequency electrical stimulation modified gene expression (decreased Tbc1d1 in soleus, increased Nr4a3 in mesenteric fat) and protein expression (increased pAS160/AS160, Nr4a3 and decreased GLUT4) by western blot and increased GLUT4 expression by immunohistochemistry in soleus muscle; glucose clearance during oral glucose tolerance tests was unaffected. Manual stimulation led to faster glucose clearance and modified mainly gene expression in mesenteric adipose tissue (increased Nr4a3, Mapk3/Erk, Adcy3, Gsk3b), but not protein expression to the same extent; however, Nr4a3 was reduced in soleus muscle. The novel finding is that electrical and manual muscle stimulation affect glucose homeostasis in DHT-induced PCOS rats through different mechanisms. Repeated electrical stimulation regulated key functional molecular pathways important for insulin sensitivity in soleus muscle and mesenteric adipose tissue to a larger extent than manual stimulation. Manual stimulation improved whole-body glucose tolerance, an effect not observed after electrical stimulation, but did not affect molecular signaling pathways to the same extent as electrical stimulation. Although more functional signaling pathways related to insulin sensitivity were affected by

  10. Electrical vs Manual Acupuncture Stimulation in a Rat Model of Polycystic Ovary Syndrome: Different Effects on Muscle and Fat Tissue Insulin Signaling

    PubMed Central

    Johansson, Julia; Mannerås-Holm, Louise; Shao, Ruijin; Olsson, AnneLiese; Lönn, Malin; Billig, Håkan; Stener-Victorin, Elisabet

    2013-01-01

    In rats with dihydrotestosterone (DHT)-induced polycystic ovary syndrome (PCOS), repeated low-frequency electrical stimulation of acupuncture needles restores whole-body insulin sensitivity measured by euglycemic hyperinsulinemic clamp. We hypothesized that electrical stimulation causing muscle contractions and manual stimulation causing needle sensation have different effects on insulin sensitivity and related signaling pathways in skeletal muscle and adipose tissue, with electrical stimulation being more effective in DHT-induced PCOS rats. From age 70 days, rats received manual or low-frequency electrical stimulation of needles in abdominal and hind limb muscle five times/wk for 4–5 wks; controls were handled but untreated rats. Low-frequency electrical stimulation modified gene expression (decreased Tbc1d1 in soleus, increased Nr4a3 in mesenteric fat) and protein expression (increased pAS160/AS160, Nr4a3 and decreased GLUT4) by western blot and increased GLUT4 expression by immunohistochemistry in soleus muscle; glucose clearance during oral glucose tolerance tests was unaffected. Manual stimulation led to faster glucose clearance and modified mainly gene expression in mesenteric adipose tissue (increased Nr4a3, Mapk3/Erk, Adcy3, Gsk3b), but not protein expression to the same extent; however, Nr4a3 was reduced in soleus muscle. The novel finding is that electrical and manual muscle stimulation affect glucose homeostasis in DHT-induced PCOS rats through different mechanisms. Repeated electrical stimulation regulated key functional molecular pathways important for insulin sensitivity in soleus muscle and mesenteric adipose tissue to a larger extent than manual stimulation. Manual stimulation improved whole-body glucose tolerance, an effect not observed after electrical stimulation, but did not affect molecular signaling pathways to the same extent as electrical stimulation. Although more functional signaling pathways related to insulin sensitivity were affected

  11. Ameliorative effect of vitamin C on hexavalent chromium-induced delay in sexual maturation and oxidative stress in developing Wistar rat ovary and uterus.

    PubMed

    Samuel, Jawahar B; Stanley, Jone A; Vengatesh, Ganapathy; Princess, Rajendran A; Muthusami, Sridhar; Roopha, Dailiah P; Suthagar, Esakky; Kumar, Kathiresh M; Sebastian, Maria S; Aruldhas, Michael M

    2012-09-01

    Hexavalent chromium (CrVI) is a highly toxic metal and major environmental pollutant and is extensively used in more than 50 industries. The major route of CrVI exposure for the general population is oral intake. Chromium is considered an important nutrient responsible for carbohydrate metabolism. However, excess CrVI exposure is associated with various pathological conditions including reproductive dysfunction. CrVI can traverse the placental barrier and cause wide range of abnormalities in fetal development. Cr is transported to offspring through mother's milk in lactating women exposed to CrVI. Therefore, the present study was carried out to determine the toxic effects of lactational CrVI exposure on ovary and uterus and the beneficial role of vitamin C in preventing/ameliorating the toxic effects of CrVI in developing female Wistar rats. Generation of oxidative stress is considered one of the plausible mechanisms behind Cr-induced cellular deteriorations. The present study evidenced a decrease in the specific activities of antioxidants, serum testosterone and progesterone and an increase in the levels of H₂O₂, lipid peroxidation (LPO) and follicle stimulating hormone in rats exposed to CrVI when compared to control. CrVI exposure also delayed the sexual maturation and extended the estrous cycle. Simultaneous administration of vitamin C significantly prevented the increase in LPO and enhanced the antioxidant status. These results suggest the protective effect of vitamin C against the CrVI exposure-induced toxicity and attest the significance of antioxidants in diet.

  12. Effects of chronic opioid exposure on guinea pig mu opioid receptor in Chinese hamster ovary cells: Comparison with human and rat receptor

    PubMed Central

    Wallisch, Michael; Nelson, Cole S.; Mulvaney, Julia M.; Hernandez, Heather S.; Smith, Sue Ann; Olsen, George D.

    2007-01-01

    Chronic opioid treatment leads to agonist-specific effects at the mu opioid receptor. The molecular mechanisms resulting from chronic opioid exposure include desensitization, internalization and down-regulation of membrane-bound mu opioid receptors (MOP). The purpose of this study was to compare the cellular regulation of guinea pig, human and rat MOP expressed in Chinese hamster ovary (CHO) cells, following exposure to two clinically important opioids, morphine and methadone. MOP expressing CHO cells were treated in culture with methadone or morphine for up to 48 hours. Radioligand diprenorphine and [D-AIa2,N-Me-Phe4,Gly5-ol]-enkephalin (DAMGO)-stimulated GTPγS binding assays were carried out using paired control and opioid-exposed CHO cells. Methadone induced downregulation of the mu opioid receptor, while morphine induced desensitization of the receptor for all three species. Furthermore, morphine predominantly decreased the potency of DAMGO to stimulate GTPγS binding, whereas methadone primarily reduced its efficacy. Changes in DAMGO potency and efficacy differed among species and depended on the opioid used to treat the cells. Our results showed similarities between guinea pig and human MOP for morphine-induced desensitization, but identified differences between the two for methadone-induced desensitization. In contrast, human and rat MOP differed in response to morphine treatment, but were not distinct in their response to methadone treatment. The guinea pig is an excellent and established animal model to study opioid effects, but its molecular opioid pharmacology has not been investigated thus far. These results can assist in understanding species differences in the effects of opioid ligands activating the mu opioid receptor. PMID:17343833

  13. Polycystic Ovary Syndrome

    MedlinePlus

    Polycystic ovary syndrome (PCOS) Overview Polycystic ovary syndrome (PCOS) is a hormonal disorder common among women of reproductive age. Women with PCOS may have infrequent or prolonged menstrual periods ...

  14. Arrhenoblastoma of ovary

    MedlinePlus

    ... medlineplus.gov/ency/article/001507.htm Arrhenoblastoma of ovary To use the sharing features on this page, please enable JavaScript. Arrhenoblastoma of the ovary is an ovarian tumor that releases the male ...

  15. Polycystic Ovary Syndrome

    MedlinePlus

    Polycystic ovary syndrome (PCOS) Overview By Mayo Clinic Staff Polycystic ovary syndrome (PCOS) is a hormonal disorder common among women of reproductive age. Women with PCOS may have infrequent or prolonged menstrual periods or ...

  16. Trophic Garnishes: Cat–Rat Interactions in an Urban Environment

    PubMed Central

    Glass, Gregory E.; Gardner-Santana, Lynne C.; Holt, Robert D.; Chen, Jessica; Shields, Timothy M.; Roy, Manojit; Schachterle, Stephen; Klein, Sabra L.

    2009-01-01

    Background Community interactions can produce complex dynamics with counterintuitive responses. Synanthropic community members are of increasing practical interest for their effects on biodiversity and public health. Most studies incorporating introduced species have been performed on islands where they may pose a risk to the native fauna. Few have examined their interactions in urban environments where they represent the majority of species. We characterized house cat (Felis catus) predation on wild Norway rats (Rattus norvegicus), and its population effects in an urban area as a model system. Three aspects of predation likely to influence population dynamics were examined; the stratum of the prey population killed by predators, the intensity of the predation, and the size of the predator population. Methodology/Principal Findings Predation pressure was estimated from the sizes of the rat and cat populations, and the characteristics of rats killed in 20 alleys. Short and long term responses of rat population to perturbations were examined by removal trapping. Perturbations removed an average of 56% of the rats/alley but had no negative long-term impact on the size of the rat population (49.6±12.5 rats/alley and 123.8±42.2 rats/alley over two years). The sizes of the cat population during two years (3.5 animals/alley and 2.7 animals/alley) also were unaffected by rat population perturbations. Predation by cats occurred in 9/20 alleys. Predated rats were predominantly juveniles and significantly smaller (144.6 g±17.8 g) than the trapped rats (385.0 g±135.6 g). Cats rarely preyed on the larger, older portion of the rat population. Conclusions/Significance The rat population appears resilient to perturbation from even substantial population reduction using targeted removal. In this area there is a relatively low population density of cats and they only occasionally prey on the rat population. This occasional predation primarily removes the juvenile proportion of

  17. Time-of-flight secondary ion mass spectrometry imaging demonstrates the specific localization of deca-bromo-diphenyl-ether residues in the ovaries and adrenal glands of exposed rats.

    PubMed

    Seyer, Alexandre; Riu, Anne; Debrauwer, Laurent; Bourgès-Abella, Nathalie; Brunelle, Alain; Laprévote, Olivier; Zalko, Daniel

    2010-11-01

    Deca-bromo-diphenyl ether (DBDE) is one of the most efficient brominated flame retardant (BFR) available on the market. We recently demonstrated that when administered to female rat by oral route, DBDE is efficiently absorbed, with the highest residual concentrations found in two endocrine glands, namely the adrenal glands and the ovaries. Time-of-flight secondary ion mass spectrometry (TOF-SIMS) imaging, a technique usually used for the study of endogenous compounds, was applied for the first time to a persistent organic pollutant, allowing to detect and to precisely localize DBDE residues in these two target tissues. The detection of the bromide ion ((81)Br isotope) by TOF-SIMS mass spectrometry imaging allowed us to demonstrate a marked cortical tropism of DBDE residues for the adrenal glands in female rats dosed per os 2 mg·kg(-1) DBDE, daily, over 96 h. In ovaries, DBDE residues were found to be concentrated in spots corresponding to part of the corpora lutea. Hepatic residues of DBDE were found to be homogeneously distributed. Due to the intrinsic toxicity of DBDE, its accumulation in the adrenal glands and the ovaries may be connected to the mechanisms of actions by which DBDE could trigger endocrine disruption in mammals. Copyright © 2010 American Society for Mass Spectrometry. Published by Elsevier Inc. All rights reserved.

  18. The Complex Interaction Between Polycystic Ovary Syndrome and Hereditary Angioedema: Case Reports and Review of the Literature.

    PubMed

    Iahn-Aun, Marina; Aun, Marcelo Vivolo; Motta, Antonio Abílio; Kalil, Jorge; Giavina-Bianchi, Pedro; Hayashida, Sylvia Asaka; Baracat, Edmund Chada; Maciel, Gustavo Arantes

    2017-07-01

    Hereditary angioedema (HAE) is a rare but severe disease, with high risk of death, and attacks have been associated to high estrogen levels. Polycystic ovary syndrome (PCOS) is a common hyperandrogenic condition, which is frequently treated with combined oral contraceptives. The aim of this study was to describe 2 clinical cases of young women diagnosed as having PCOS who developed HAE attacks after the introduction of combined estrogen-progestin pills to treat PCOS symptoms. Literature review of sex hormones' role in genesis of HAE attacks and possible mechanisms involved. In the cases reported, after initiation of combined contraceptives, patients presented with facial swelling with airway involvement (laryngeal edema) and abdominal pain. They had a familial history of angioedema and normal C1 inhibitor (C1-INH) levels, leading to the diagnosis of HAE with normal C1-INH (HAEnC1-INH) or HAE type III. After suspension of exogenous estrogen, patients remained asymptomatic from HAE. HAEnC1-INH is an estrogen-dependent form of HAE. It is well established that exogenous estrogen triggers attacks of all types of HAE. However, this is the first description of the association between PCOS and HAE, in which PCOS could be masking HAE symptoms. We propose that PCOS might have a protective role regarding HAE attacks, because of its particular hormonal features, that is, hyperandrogenism and relative stable levels of estradiol. The use of combined estrogen-progestin compounds in women with PCOS and HAE must be avoided, and treatment must be individualized.

  19. Morphometrical investigations on the reproductive activity of the ovaries in rats subjected to immobilization and to motion activity

    NASA Technical Reports Server (NTRS)

    Konstantinov, N.; Cheresharov, L.; Toshkova, S.

    1982-01-01

    Wistar-strain white female rats were divided into three groups, with the first group subjected to motion loading, the second used as control, and the third group was immobilized. A considerable reduction in numbers of corpora lutea was observed in the immobilized group, together with smaller numbers of embryos, high percent of embryo mortality, fetal growth retardation, and endometrium disorders. The control group showed no deviation from normal conditions, and there was slight improvement in reproductive activity of animals under motion loading.

  20. Gestational and postnatal protein deficiency affects postnatal development and histomorphometry of liver, kidneys, and ovaries of female rats' offspring.

    PubMed

    Almeida, Fernanda R C L; Silva, Gerluza A B; Fiúza, Aparecida T L; Chianca, Deoclécio A; Ferreira, Anderson J; Chiarini-Garcia, Hélio

    2012-04-01

    Pre- and postnatal protein deficiency may lead to decreased foetal intra-uterine development and postnatal growth, which is common in developing countries. The present study aimed to investigate the consequences of a low-protein intake during gestation and postnatally on adult female rats' offspring. Female rats were given either a control or a protein-deficient diet throughout the gestation and lactation periods. A subset of females was killed at day 20 of pregnancy for foetal and placental measurements. Another subset of females farrowed and the number, length, and weight of the offspring were measured. After weaning, the offspring received the same diet as their dams until 70 days of age. They were sacrificed, and some organs were weighed and collected for histomorphometrical analyses. Placental weight and size and foetal weight were lower in protein-deficient dams. The weight and length of pups at birth were also lower in the deficient group. The organs to body weight ratio were higher in the deficient animals at 70 days of age. The protein-deficient female offspring had a smaller ovarian area, greater numbers of primordial follicles and developing follicles per square millimetres of ovarian cortex, and no corpora lutea. The liver showed smaller nuclear diameter of the hepatocytes and height of the hepatocytes cords. The kidneys showed smaller cortical area with reduced glomerular number and diameter. These results provide the first evidence of the histomorphological changes of the association between gestational and postnatal protein deficiency in female rats' offspring.

  1. Polycystic Ovary Syndrome (PCOS) Fact Sheet

    MedlinePlus

    ... Health Topics > Polycystic ovary syndrome Polycystic ovary syndrome Polycystic ovary syndrome Polycystic ovary syndrome (PCOS) is a health problem ... of infertility. Expand all | Collapse all What is polycystic ovary syndrome (PCOS)? Polycystic (pah-lee-SIS-tik) ovary syndrome ( ...

  2. Oocyte-somatic cell interactions in the human ovary-novel role of bone morphogenetic proteins and growth differentiation factors.

    PubMed

    Chang, Hsun-Ming; Qiao, Jie; Leung, Peter C K

    2016-12-01

    Initially identified for their capability to induce heterotopic bone formation, bone morphogenetic proteins (BMPs) are multifunctional growth factors that belong to the transforming growth factor β superfamily. Using cellular and molecular genetic approaches, recent studies have implicated intra-ovarian BMPs as potent regulators of ovarian follicular function. The bi-directional communication of oocytes and the surrounding somatic cells is mandatory for normal follicle development and oocyte maturation. This review summarizes the current knowledge on the physiological role and molecular determinants of these ovarian regulatory factors within the human germline-somatic regulatory loop. The regulation of ovarian function remains poorly characterized in humans because, while the fundamental process of follicular development and oocyte maturation is highly similar across species, most information on the regulation of ovarian function is obtained from studies using rodent models. Thus, this review focuses on the studies that used human biological materials to gain knowledge about human ovarian biology and disorders and to develop strategies for preventing, diagnosing and treating these abnormalities. Relevant English-language publications describing the roles of BMPs or growth differentiation factors (GDFs) in human ovarian biology and phenotypes were comprehensively searched using PubMed and the Google Scholar database. The publications included those published since the initial identification of BMPs in the mammalian ovary in 1999 through July 2016. Studies using human biological materials have revealed the expression of BMPs, GDFs and their putative receptors as well as their molecular signaling in the fundamental cells (oocyte, cumulus/granulosa cells (GCs) and theca/stroma cells) of the ovarian follicles throughout follicle development. With the availability of recombinant human BMPs/GDFs and the development of immortalized human cell lines, functional studies

  3. Detection of DNA single-strand breaks induced by procarcinogens in Chinese hamster ovary cells cocultured with rat hepatocytes

    SciTech Connect

    Yang, K.H.; Shin, C.G.; Choe, S.Y.; Kim, D.H.

    1984-01-01

    DNA single-strand breaks induced by procarcinogens were detected in Chinese hamster overy (CHO) cell cocultured with adult rat hepatocytes. Freshly isolated adult rat hepatocytes were added to the CHO cell culture prelabeled with (/sup 3/H) thymidine. After allowing the hepatocytes to attach on or near the CHO cells, aflatoxin B/sub 1/ or benzo(a)pyrene was added to the culture and incubated for the desired time. DNA single-strand breaks in CHO cells were measured by the alkaline elution technique. Aflatoxin B/sub 1/ induced some DNA single-strand breaks in CHO cells cultured alone, but in coculture system with hepatocytes the number of DNA single-strand breaks increased greatly. The magnitude of the increase was related to the dose and the time of exposure to aflatoxin B/sub 1/. Addition of proteinase-K to the cell lysates increased the elution of DNA compared to that of samples without proteinase-K. Benzo(a)pyrene did not induce any DNA single-strand breaks in CHO cells in the absence of liver cells, but a significant number of single-strand breaks were detected in the coculture system.

  4. Optical forced oscillation for the study of lectin-glycoprotein interaction at the cellular membrane of a Chinese hamster ovary cell

    NASA Astrophysics Data System (ADS)

    Liu, Shang-Ling; Karmenyan, Artashes; Wei, Ming-Tzo; Huang, Chun-Chieh; Lin, Chi-Hung; Chiou, Arthur

    2007-03-01

    We report the application of a set of twin optical tweezers to trap and oscillate a ConA (lectin)- coated polystyrene particle and to measure its interaction with glycoprotein receptors at the cellular plasma membrane of a Chinese hamster ovary (CHO) cell. The particle was trapped between two quadratic potential wells defined by a set of twin optical tweezers and was forced to oscillate by chopping on and off one of the trapping beams. We tracked the oscillatory motion of the particle via a quadrant photodiode and measured with a lock-in amplifier the amplitude of the oscillation as a function of frequency at the fundamental component of the driving frequency over a frequency range from 10Hz to 600Hz. By analyzing the amplitude as a function of frequency for a free particle suspended in buffer solution without the presence of the CHO cell and compared with the corresponding data when the particle was interacting with the CHO cell, we deduced the transverse force constant associated with the optical trap and that associated with the interaction by treating both the optical trap and the interaction as linear springs. The force constants were determined to be approximately 2.15pN/μm for the trap and 2.53pN/μm for the lectin-glycoprotein interaction. When the CHO cell was treated with lantrunculin A, a drug that is known to destroy the cytoskeleton of the cell, the oscillation amplitude increased with time, indicating the softening of the cellular membrane, until a steady state with a smaller force constant was reached. The steady state value of the force constant depended on the drug concentration.

  5. Angiotensin II-noradrenergic interactions in renovascular hypertensive rats.

    PubMed Central

    Zimmerman, J B; Robertson, D; Jackson, E K

    1987-01-01

    This study tested the hypothesis that interactions of endogenous angiotensin II (AII) with the noradrenergic neuroeffector junction are important in renin-dependent hypertension. In the in situ blood-perfused rat mesentery, in normal rats exogenous AII potentiated mesenteric vascular responses to periarterial (sympathetic) nerve stimulation (PNS) more than vascular responses to exogenous norepinephrine (NE). In 2-kidney-1-clip (2K-1C) rats with renovascular hypertension mesenteric vascular responses to PNS and NE were greater than in sham-operated rats, and renovascular hypertension mimicked the effects of exogenous AII with respect to enhancing responses to PNS more than responses to NE. In 2K-1C rats, but not in sham-operated rats, 1-Sar-8-Ile-AII markedly suppressed vascular responses to PNS, without influencing responses to NE. Finally, 1-Sar-8-Ile-AII attenuated sympathetic nerve stimulation-induced neuronal spillover of NE in 2K-1C rats, but not in sham-operated rats. These data indicate that renovascular hypertension enhances noradrenergic neurotransmission, and that this enhancement is mediated in part by AII-induced facilitation of NE release. PMID:3301900

  6. Glutathione S-transferase class μ regulation of apoptosis signal-regulating kinase 1 protein during VCD-induced ovotoxicity in neonatal rat ovaries.

    PubMed

    Bhattacharya, Poulomi; Madden, Jill A; Sen, Nivedita; Hoyer, Patricia B; Keating, Aileen F

    2013-02-15

    4-Vinylcyclohexene diepoxide (VCD) destroys ovarian primordial and small primary follicles via apoptosis. In mice, VCD exposure induces ovarian mRNA expression of glutathione S-transferase (GST) family members, including isoform mu (Gstm). Extra-ovarian GSTM negatively regulates pro-apoptotic apoptosis signal-regulating kinase 1 (ASK1) through protein complex formation, which dissociates during stress, thereby initiating ASK1-induced apoptosis. The present study investigated the ovarian response of Gstm mRNA and protein to VCD. Induction of Ask1 mRNA at VCD-induced follicle loss onset was determined. Ovarian GSTM:ASK1 protein complex formation was investigated and VCD exposure effects thereon evaluated. Phosphatidylinositol-3 kinase (PI3K) regulation of GSTM protein was also studied. Postnatal day (PND) 4 rat ovaries were cultured in control media ± 1) VCD (30 μM) for 2-8 days; 2) VCD (30 μM) for 2 days, followed by incubation in control media for 4 days (acute VCD exposure); or 3) LY294002 (20 μM) for 6 days. VCD exposure did not alter Gstm mRNA expression, however, GSTM protein increased (P<0.05) after 6 days of both the acute and chronic treatments. Ask1 mRNA increased (0.33-fold; P<0.05) relative to control after 6 days of VCD exposure. Ovarian GSTM:ASK1 protein complex formation was confirmed and, relative to control, the amount of GSTM bound to ASK1 increased 33% (P<0.05) by chronic but with no effect of acute VCD exposure. PI3K inhibition increased (P<0.05) GSTM protein by 40% and 71% on d4 and d6, respectively. These findings support involvement of GSTM in the ovarian response to VCD exposure, through regulation of pro-apoptotic ASK1.

  7. Expression of progesterone receptor membrane component-2 within the immature rat ovary and its role in regulating mitosis and apoptosis of spontaneously immortalized granulosa cells.

    PubMed

    Griffin, Daniel; Liu, Xiufang; Pru, Cindy; Pru, James K; Peluso, John J

    2014-08-01

    Progesterone receptor membrane component 2 (Pgrmc2) mRNA was detected in the immature rat ovary. By 48 h after eCG, Pgrmc2 mRNA levels decreased by 40% and were maintained at 48 h post-hCG. Immunohistochemical studies detected PGRMC2 in oocytes and ovarian surface epithelial, interstitial, thecal, granulosa, and luteal cells. PGRMC2 was also present in spontaneously immortalized granulosa cells, localizing to the cytoplasm of interphase cells and apparently to the mitotic spindle of cells in metaphase. Interestingly, PGRMC2 levels appeared to decrease during the G1 stage of the cell cycle. Moreover, overexpression of PGRMC2 suppressed entry into the cell cycle, possibly by binding the p58 form of cyclin dependent kinase 11b. Conversely, Pgrmc2 small interfering RNA (siRNA) treatment increased the percentage of cells in G1 and M stage but did not increase the number of cells, which was likely due to an increase in apoptosis. Depleting PGRMC2 did not inhibit cellular (3)H-progesterone binding, but attenuated the ability of progesterone to suppress mitosis and apoptosis. Taken together these studies suggest that PGRMC2 affects granulosa cell mitosis by acting at two specific stages of the cell cycle. First, PGRMC2 regulates the progression from the G0 into the G1 stage of the cell cycle. Second, PGRMC2 appears to localize to the mitotic spindle, where it likely promotes the final stages of mitosis. Finally, siRNA knockdown studies indicate that PGRMC2 is required for progesterone to slow the rate of granulosa cell mitosis and apoptosis. These findings support a role for PGRMC2 in ovarian follicle development.

  8. Activation of protein kinase Czeta mediates luteinizing hormone- or forskolin-induced NGFI-B expression in preovulatory granulosa cells of rat ovary.

    PubMed

    Park, Jae-Il; Kim, Sun-Gyun; Chun, Jang-Soo; Seo, You-Mi; Jeon, Mi-Jin; Ohba, Motoi; Kim, Hyun-Jin; Chun, Sang-Young

    2007-05-30

    We have previously demonstrated that luteinizing hormone (LH) induces a rapid and transient expression of NGFI-B in the ovary. In this report, we investigated the signaling pathway for LH- and forskolin-induced NGFI-B expression in cultured rat granulosa cells of preovulatory follicles. LH- or forskolin-induced NGFI-B expression was suppressed by high dose of protein kinase C (PKC) inhibitor RO 31-8220 (10 microM), but not by low doses RO 31-8220 (0.1-1.0 microM) or adenylate cyclase inhibitor MDL-12,300A, implicating the involvement of atypical PKCs. Kinase assay revealed that LH treatment of granulosa cells resulted in a rapid stimulation of atypical PKCzeta activity. Interestingly, like LH, forskolin was also able to activate PKCzeta. Treatment with the cell-permeable PKCzeta-specific inhibitor pseudosubstrate peptide inhibited LH-or forskolin-induced NGFI-B expression, indicating the essential role of PKCzeta. Consistent with this promise, in granulosa cells depleted of diacylglycerol sensitive PKCs by prolonged treatment with tetradecanoylphobol-13-acetate, LH or forskolin could still induce NGFI-B expression, and RO 31-8220 or the PKCzeta pseudosubstrate peptide inhibited LH- or forskolin-induced NGFI-B expression. Furthermore, overexpression of dominant-negative PKCzeta in primary granulosa cells using a replication-defective adenovirus vector resulted in the suppression of LH- or forskolin-induced NGFI-B expression. Our findings demonstrate that PKCzeta, which is activated by LH or forskolin, contributes to the induction of NGFI-B in granulosa cells of preovulatory follicles.

  9. Acute 7,12-dimethylbenz[a]anthracene exposure causes differential concentration-dependent follicle depletion and gene expression in neonatal rat ovaries

    SciTech Connect

    Madden, Jill A.; Hoyer, Patricia B.; Devine, Patrick J.; Keating, Aileen F.

    2014-05-01

    Chronic exposure to the polycyclic aromatic hydrocarbon 7,12-dimethylbenz[a]anthracene (DMBA), generated during combustion of organic matter including cigarette smoke, depletes all ovarian follicle types in the mouse and rat, and in vitro models mimic this effect. To investigate the mechanisms involved in follicular depletion during acute DMBA exposure, two concentrations of DMBA at which follicle depletion has (75 nM) and has not (12.5 nM) been observed were investigated. Postnatal day four F344 rat ovaries were maintained in culture for four days before a single exposure to vehicle control (1% DMSO; CT) or DMBA (12 nM; low-concentration or 75 nM; high-concentration). After four or eight additional days of culture, DMBA-induced follicle depletion was evaluated via follicle enumeration. Relative to control, DMBA did not affect follicle numbers after 4 days of exposure, but induced large primary follicle loss at both concentrations after 8 days; while, the low-concentration DMBA also caused secondary follicle depletion. Neither concentration affected primordial or small primary follicle number. RNA was isolated and quantitative RT-PCR performed prior to follicle loss to measure mRNA levels of genes involved in xenobiotic metabolism (Cyp2e1, Gstmu, Gstpi, Ephx1), autophagy (Atg7, Becn1), oxidative stress response (Sod1, Sod2) and the phosphatidylinositol 3-kinase (PI3K) pathway (Kitlg, cKit, Akt1) 1, 2 and 4 days after exposure. With the exception of Atg7 and cKit, DMBA increased (P < 0.05) expression of all genes investigated. Also, BECN1 and pAKT{sup Thr308} protein levels were increased while cKIT was decreased by DMBA exposure. Taken together, these results suggest an increase in DMBA bioactivation, add to the mechanistic understanding of DMBA-induced ovotoxicity and raise concern regarding female low concentration DMBA exposures. - Highlights: • Acute DMBA exposures induce large primary and/or secondary follicle loss. • Acute DMBA exposure did not impact

  10. Polycystic Ovary Syndrome (For Teens)

    MedlinePlus

    ... Loss Surgery? A Week of Healthy Breakfasts Shyness Polycystic Ovary Syndrome KidsHealth > For Teens > Polycystic Ovary Syndrome A A ... condition called polycystic ovary sydrome (PCOS) . What Is Polycystic Ovary Syndrome? Polycystic (pronounced: pol-ee-SISS-tik) ovary syndrome ...

  11. Pharmacokinetic interaction between febuxostat and morin in rats.

    PubMed

    Sahu, Kapendra; Siddiqui, Anees A; Shaharyar, Mohammad; Malik, Sachin

    2014-03-01

    Due to wide consumption of flavonoids in the dietary supplement, and an imperative role of CYPs and P-glycoprotein inhibition in drug disposition. So there is increasing scientific interest in drug-flavonoid interactions. The present study aims to investigate the effect of morin, a flavonoid, on the pharmacokinetics of febuxostat in rats. A simple ultra-performance liquid chromatography method has been developed for the calculation of febuxostat in 100 µl rat plasma using febuxostat D7 as an internal standard (IS). The assay procedure involved a single-step, liquid-liquid extraction of febuxostat and IS from plasma with methanol. Pharmacokinetic parameters of febuxostat were determined in rats after an oral administration of febuxostat (5 mg/kg) to rats in the control, coadministered and pretreated groups of morin (10 mg/kg). Compared to the control rats given febuxostat alone, the Cmax and AUC of febuxostat increased by 18 - 20 and 47 - 50%, respectively, in rats pretreated with morin. The plasma half-life (t1/2) of the pretreated group is increased by 2.5-fold compared with the control group. Consequently, relative bioavailability values of febuxostat in the rats pretreated with morin were significantly higher (p < 0.05) than those from the control and coadministered groups. Increased bioavailability indicates that the presence of morin could be effective in inhibiting CYP1A1, CYP1A2 and CYP3A4-mediated metabolism and/or effective in inhibiting P-glycoprotein-mediated cellular efflux of febuxostat. The presence of morin significantly enhanced the oral exposure of febuxostat, suggesting that concurrent use of morin or morin-containing dietary supplements with febuxostat should be verified to avoid drug-flavonoid interactions.

  12. Glutathione S-transferase class mu regulation of apoptosis signal-regulating kinase 1 protein during VCD-induced ovotoxicity in neonatal rat ovaries

    SciTech Connect

    Bhattacharya, Poulomi; Madden, Jill A.; Sen, Nivedita; Hoyer, Patricia B.; Keating, Aileen F.

    2013-02-15

    4-Vinylcyclohexene diepoxide (VCD) destroys ovarian primordial and small primary follicles via apoptosis. In mice, VCD exposure induces ovarian mRNA expression of glutathione S-transferase (GST) family members, including isoform mu (Gstm). Extra-ovarian GSTM negatively regulates pro-apoptotic apoptosis signal-regulating kinase 1 (ASK1) through protein complex formation, which dissociates during stress, thereby initiating ASK1-induced apoptosis. The present study investigated the ovarian response of Gstm mRNA and protein to VCD. Induction of Ask1 mRNA at VCD-induced follicle loss onset was determined. Ovarian GSTM:ASK1 protein complex formation was investigated and VCD exposure effects thereon evaluated. Phosphatidylinositol-3 kinase (PI3K) regulation of GSTM protein was also studied. Postnatal day (PND) 4 rat ovaries were cultured in control media ± 1) VCD (30 μM) for 2–8 days; 2) VCD (30 μM) for 2 days, followed by incubation in control media for 4 days (acute VCD exposure); or 3) LY294002 (20 μM) for 6 days. VCD exposure did not alter Gstm mRNA expression, however, GSTM protein increased (P < 0.05) after 6 days of both the acute and chronic treatments. Ask1 mRNA increased (0.33-fold; P < 0.05) relative to control after 6 days of VCD exposure. Ovarian GSTM:ASK1 protein complex formation was confirmed and, relative to control, the amount of GSTM bound to ASK1 increased 33% (P < 0.05) by chronic but with no effect of acute VCD exposure. PI3K inhibition increased (P < 0.05) GSTM protein by 40% and 71% on d4 and d6, respectively. These findings support involvement of GSTM in the ovarian response to VCD exposure, through regulation of pro-apoptotic ASK1. - Highlights: ► GSTM protein increases in response to ovarian VCD exposure. ► VCD increases Ask1 mRNA at the onset of follicle loss. ► Ovarian GSTM binds more ASK1 protein during VCD-induced ovotoxicity. ► PI3K regulates ovarian GSTM protein.

  13. The Pharmacokinetic Interaction Study between Carvedilol and Bupropion in Rats.

    PubMed

    Abrudan, Maria Bianca; Muntean, Dana Maria; Gheldiu, Ana Maria; Neag, Maria Adriana; Vlase, Laurian

    2017-01-01

    The effects of multiple-dose bupropion on the pharmacokinetics of single-dose carvedilol were investigated in order to evaluate this possible drug-drug interaction. A preclinical study was conducted among white male Wistar rats. Each rat was cannulated on the femoral vein prior to being connected to BASi Culex ABC®. During the reference period, each rat received an intravenous and an oral dose of 3.57 mg/kg body weight (b.w.) carvedilol, at 2 days distance. After 5 days of pretreatment with 21.42 mg/kg b.w. bupropion (by oral route, twice a day - given in order to reach the steady state), during the sixth day, 3.57 mg/kg b.w. carvedilol and 21.42 mg/kg b.w. bupropion were orally co-administrated (test period). After each administration of carvedilol, several samples of 200 µL blood were collected. The pharmacokinetic parameters of carvedilol were analyzed by the noncompartmental method. The 5 days pretreatment with bupropion increased the exposure to carvedilol in rats by 180%, considering the modifications observed in the area under the curve of carvedilol. Carvedilol was shown to have higher plasma concentrations, delay in maximum concentration, and a prolonged half-life, after being pretreated with bupropion. The administration of multiple-dose bupropion influences the pharmacokinetics of carvedilol (single oral dose) in rats. © 2017 S. Karger AG, Basel.

  14. Pharmacokinetic Interaction of Chrysin with Caffeine in Rats

    PubMed Central

    Noh, Keumhan; Oh, Do Gyeong; Nepal, Mahesh Raj; Jeong, Ki Sun; Choi, Yongjoo; Kang, Mi Jeong; Kang, Wonku; Jeong, Hye Gwang; Jeong, Tae Cheon

    2016-01-01

    Pharmacokinetic interaction of chrysin, a flavone present in honey, propolis and herbs, with caffeine was investigated in male Sprague-Dawley rats. Because chrysin inhibited CYP1A-selective ethoxyresorufin O-deethylase and methoxyresorufin O-demethylase activities in enriched rat liver microsomes, the pharmacokinetics of caffeine, a CYP 1A substrate, was studied following an intragastric administration with 100 mg/kg chrysin. In addition to the oral bioavailability of chrysin, its phase 2 metabolites, chrysin sulfate and chrysin glucuronide, were determined in rat plasma. As results, the pharmacokinetic parameters for caffeine and its three metabolites (i.e., paraxanthine, theobromine and theophylline) were not changed following chrysin treatment in vivo, despite of its inhibitory effect on CYP 1A in vitro. The bioavailability of chrysin was found to be almost zero, because chrysin was rapidly metabolized to its sulfate and glucuronide conjugates in rats. Taken together, it was concluded that the little interaction of chrysin with caffeine might be resulted from the rapid metabolism of chrysin to its phase 2 metabolites which would not have inhibitory effects on CYP enzymes responsible for caffeine metabolism. PMID:27098862

  15. Sympathetic regulation of estradiol secretion from the ovary.

    PubMed

    Uchida, Sae

    2015-01-01

    It is well known that hormone secretion from endocrine glands is regulated by hierarchical feedback mechanisms. However, although Cannon revealed in the 1920s that sympathoadrenal medullary function increased during emergency situations, no studies on the autonomic nervous regulation of hormone secretion have been undertaken for many years. In the past 40 years, the autonomic nervous regulation of insulin secretion from the pancreas, gastrin secretion from the stomach, glucocorticoid secretion from the adrenal cortex, etc., has been demonstrated. Estradiol secretion from the ovary is strongly controlled by the hypothalamic-pituitary-ovarian axis, and its possible regulation by autonomic nerves has been largely unnoticed. Some histological studies have revealed rich adrenergic sympathetic innervation in the ovary. Recently, it has been demonstrated that the activation of the sympathetic nerves to the ovary directly reduces estradiol secretion from the ovary. This article reviews physiological and morphological studies, primarily in rats, on the sympathetic regulation of estradiol secretion from the ovary.

  16. Effects of Electromagnetic Radiation Use on Oxidant/Antioxidant Status and DNA Turn-over Enzyme Activities in Erythrocytes and Heart, Kidney, Liver, and Ovary Tissues From Rats: Possible Protective Role of Vitamin C.

    PubMed

    Devrim, Erdinç; Ergüder, Imge B; Kılıçoğlu, Bülent; Yaykaşlı, Emine; Cetin, Recep; Durak, Ilker

    2008-01-01

    ABSTRACT In this study, the aim was to investigate possible effects of Electromagnetic Radiation (EMR) use on oxidant and antioxidant status in erythrocytes and kidney, heart, liver, and ovary tissues from rats, and possible protective role of vitamin C. For this aim, 40 Wistar albino female rats were used throughout the study. The treatment group was exposed to EMR in a frequency of 900 MHz, the EMR plus vitamin C group was exposed to the same EMR frequency and given vitamin C (250 mg/kg/day) orally for 4 weeks. There were 10 animals in each group including control and vitamin C groups. At the end of the study period, blood samples were obtained from the animals to get erythrocyte sediments. Then the animals were sacrificed and heart, kidney, liver, and ovary tissues were removed. Malondialdehyde (MDA) levels and superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), xanthine oxidase (XO), and adenosine deaminase (ADA) enzyme activities were measured in the tissues and erythrocytes. It was observed that MDA level, XO, and GSH-Px activities significantly increased in the EMR group as compared with those of the control group in the erythrocytes. In the kidney tissues, it was found that MDA level and CAT activity significantly increased, whereas XO and ADA activities decreased in the cellular phone group as compared with those of the control group. However, in the heart tissues it was observed that MDA level, ADA, and XO activities significantly decreased in the cellular phone group as compared with those of the control group. The results suggest that EMR at the frequency generated by a cell phone causes oxidative stress and peroxidation in the erythrocytes and kidney tissues from rats. In the erythrocytes, vitamin C seems to make partial protection against the oxidant stress.

  17. [Polycystic ovary syndrome].

    PubMed

    Vrbíková, Jana

    2015-10-01

    For diagnosing of polycystic ovary syndrome (PCOS) it is currently recommended to follow the ESHRE criteria. For diagnosis according to them two of the following three symptoms are sufficient: 1. morphology of polycystic ovaria, 2. clinical manifestations of hyperandrogenism or laboratory proof of hyperandrogenemia, and 3. oligo-anovulation. PCOS is a complex disorder in whose pathogenesis genetic and environmental effects interact. It is not a gynecological disorder alone, the syndrome is accompanied by insulin resistance which leads to increased incidence of type 2 diabetes mellitus and impaired glucose tolerance (4 times and twice, independently of BMI). Also gestational DM occurs more frequently. Dyslipidemia, arterial hypertension, elevated CRP and homocysteine levels, endothelial dysfunction and greater intima-media thickness are also more frequent. It is not quite clear, however, whether women with PCOS suffer cardiovascular events more frequently as well. More often than is accidental PCOS is associated with depression, anxiety and eating disorders, further with nonalcoholic steatohepatitis and with the sleep apnoea syndrome - especially in obese women. Therapeutic measures include non-pharmacological methods - lifestyle adjustments focused on weight reduction in obese individuals, cosmetic measures for dermatologic manifestation of hyperandrogenism, in particular laser and pharmacotherapy (combined hormonal contraceptives and antiandrogens). Menstrual irregularities can be treated with contraceptives or cyclical administration of gestagens, also metformin can be used.

  18. Polycystic ovary disease

    MedlinePlus

    ... hormones. This may lead to changes in the menstrual cycle, cysts in the ovaries , trouble getting pregnant, and ... Symptoms Symptoms of PCOS include changes in the menstrual cycle, such as: Not getting a period after you ...

  19. Overproductive ovaries (image)

    MedlinePlus

    ... imbalance can be caused by tumors in the ovaries or adrenal glands, or by polycystic ovarian syndrome. Hyperandrogenism may include growth of excess body and facial hair, acne, amenorrhea (loss of menstrual periods), and changes in ...

  20. Interaction of tomato lycopene and ketosamine against rat prostate tumorigenesis.

    PubMed

    Mossine, Valeri V; Chopra, Pankaj; Mawhinney, Thomas P

    2008-06-01

    Prior investigations on the beneficial effect of dietary processed tomato products and lycopene on prostate cancer risk suggested that lycopene may require the presence of other constituents to exert its chemopreventive potential. We investigated whether ketosamines, a group of carbohydrate derivatives present in dehydrated tomato products, may interact with lycopene against prostate tumorigenesis. One ketosamine, FruHis, strongly synergized with lycopene against proliferation of the highly metastatic rat prostate adenocarcinoma MAT-LyLu cell line in vitro. The FruHis/lycopene combination significantly inhibited in vivo tumor formation by MAT-LyLu cells in syngeneic Copenhagen rats. Energy-balanced diets, supplemented with tomato paste, tomato powder, or tomato paste plus FruHis, were fed to Wistar-Unilever rats (n = 20 per group) treated with N-nitroso-N-methylurea and testosterone to induce prostate carcinogenesis. Survival from carcinogenesis was lowest in the control group (median survival time, 40 weeks) and highest in the group fed the tomato paste/FruHis diet (51 weeks; P = 0.004, versus control). The proportions of dying rats with macroscopic prostate tumors in the control, tomato paste, tomato powder, and tomato paste/FruHis groups were 63% (12 of 19), 39% (5 of 13), 43% (6 of 14), and 18% (2 of 11), respectively. FruHis completely blocked DNA oxidative degradation at >250 micromol/L in vitro, whereas neither ascorbate nor phenolic antioxidants from tomato were effective protectors in this assay. FruHis, therefore, may exert tumor-preventive effect through its antioxidant activity and interaction with lycopene.

  1. Pattern of human chorionic gonadotropin binding in the polycystic ovary

    SciTech Connect

    Brawer, J.; Richard, M.; Farookhi, R. )

    1989-08-01

    The histologic evolution of polycystic ovaries in the estradiol valerate-treated rat coincides with the development of a unique plasma pattern of luteinizing hormone. To assess the role of luteinizing hormone in polycystic ovaries, it is necessary to evaluate the luteinizing hormone sensitivity of the specific tissues in the polycystic ovary. Therefore, we examined the pattern of luteinizing hormone binding sites in polycystic ovaries. Rats at 4 or 8 weeks after estradiol valerate treatment each received an intrajugular injection of iodine 125-labeled human chorionic gonadotropin. Some rats also received a 1000-fold excess of unlabeled human chorionic gonadotropin in the same injection. Ovaries were prepared for autoradiography. Dense accumulations of grains occurred over the theca of normal and atretic secondary follicles in all ovaries and over clusters of secondary interstitial cells. The iodine label was variable over the typically hypertrophied theca of precystic follicles. The theca of definitive cysts showed little or no label. These results indicate that cyst formation coincides with the loss of luteinizing hormone/human chorionic gonadotropin binding to the affected follicles.

  2. A Dietary Medium-Chain Fatty Acid, Decanoic Acid, Inhibits Recruitment of Nur77 to the HSD3B2 Promoter In Vitro and Reverses Endocrine and Metabolic Abnormalities in a Rat Model of Polycystic Ovary Syndrome.

    PubMed

    Lee, Bao Hui; Indran, Inthrani Raja; Tan, Huey Min; Li, Yu; Zhang, Zhiwei; Li, Jun; Yong, Eu-Leong

    2016-01-01

    Hyperandrogenism is the central feature of polycystic ovary syndrome (PCOS). Due to the intricate relationship between hyperandrogenism and insulin resistance in PCOS, 50%-70% of these patients also present with hyperinsulinemia. Metformin, an insulin sensitizer, has been used to reduce insulin resistance and improve fertility in women with PCOS. In previous work, we have noted that a dietary medium-chain fatty acid, decanoic acid (DA), improves glucose tolerance and lipid profile in a mouse model of diabetes. Here, we report for the first time that DA, like metformin, inhibits androgen biosynthesis in NCI-H295R steroidogenic cells by regulating the enzyme 3β-hydroxysteroid dehydrogenase/Δ5-Δ4-isomerase type 2 (HSD3B2). The inhibitory effect on HSD3B2 and androgen production required cAMP stimulation, suggesting a mechanistic action via the cAMP-stimulated pathway. Specifically, both DA and metformin reduced cAMP-enhanced recruitment of the orphan nuclear receptor Nur77 to the HSD3B2 promoter, coupled with decreased transcription and protein expression of HSD3B2. In a letrozole-induced PCOS rat model, treatment with DA or metformin reduced serum-free testosterone, lowered fasting insulin, and restored estrous cyclicity. In addition, DA treatment lowered serum total testosterone and decreased HSD3B2 protein expression in the adrenals and ovaries. We conclude that DA inhibits androgen biosynthesis via mechanisms resulting in the suppression of HSD3B2 expression, an effect consistently observed both in vitro and in vivo. The efficacy of DA in reversing the endocrine and metabolic abnormalities of the letrozole-induced PCOS rat model are promising, raising the possibility that diets including DA could be beneficial for the management of both hyperandrogenism and insulin resistance in PCOS.

  3. Neonatal exposure to single doses of estradiol or testosterone programs ovarian follicular development-modified hypothalamic neurotransmitters and causes polycystic ovary during adulthood in the rat.

    PubMed

    Sotomayor-Zárate, Ramón; Tiszavari, Michelle; Cruz, Gonzalo; Lara, Hernán E

    2011-12-01

    To investigate the hormones participating in early follicular development and hypothalamic neurotransmitters in rats during adulthood. Experimental basic study. University animal laboratory. Twenty-three neonatal rats injected with single subcutaneous injection of estradiol valerate (EV), testosterone propionate (TP), or dihydrotestosterone (DHT) and killed by decapitation at 60 days of age. Measurements of neurotransmitter in ventromedial hypothalamus-arcuate nucleus (VMH-AN) and ovarian morphometry in the adult rat. Noradrenaline (NA), dopamine (DA), serotonin (5-HT), glutamic acid (Glu), and gamma-aminobutyric acid (GABA) content by high performance liquid chromatography medial basal hypothalamus and ovarian morphology. EV exposure increased 5-HT, DA, NA, and Glu and decreased GABA levels in the VMH-AN. Exposure to TP increased Glu and decreased 5-HT in the VMH-AN. Neonatal EV and TP decreased the number of primordial follicles but EV increased the atresia of antral follicles and TP decreased it. Neonatal exposure to DHT did not cause morphologic changes in the adult ovary. Neonatal exposure to EV activated the reproductive hypothalamus and permanently modified ovarian follicular development. TP exposure had some similar effects as EV at the hypothalamus, and it modified ovarian development mimicking the effects of EV. This last effect could be through TP conversion to estradiol because DHT, a nonaromatizable androgen, did not modify follicular development. Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  4. [Effects of intranasal insulin and serotonin on functional activity of the adenylyl cyclase system in the myocardium, ovaries, and uterus of rats with prolonged neonatal model of diabetes mellitus].

    PubMed

    Shpakov, A O; Derkach, K V; Chistiakova, O V; Moĭseiuk, I V; Sukhov, I B; Bondareva, V M

    2013-01-01

    Disturbances in hormonal signaling systems, in the adenylyl cyclase system (ACS) in particular, occur at early stages of diabetes mellitus (DM) and are one of the key causes of its complications. Since there is a correlation between the severity of DM and of disturbances in the ACS, the study of the ACS activity can be used to monitor DM and its complications and to evaluate effectiveness of their treatment. Comparatively recently, for treatment of the type 2 DM, there began to be used the intranasal insulin (I-I) and drugs increasing brain serotonin level, which effectively restore CNS functions. However, mechanisms of their action on peripheral tissues and organs with DM remain to be not understood. The goal of this work was to study effects. of I-I and intranasal serotonin (I-S) on the ACS functional activity in myocardium, ovary, and uterus of rats with a neonatal model of the type 2 DM. In tissues of diabetic rats there were revealed changes in regulation of adenylyl cyclase (AC) by guanine nucleotides and hormones that both stimulated and inhibited this enzyme, such changes being characterized by the receptor and tissue specificity. In diabetic rats, I-I restored the AC stimulating effects of isoproterenol in the myocardium, guanine nucleotides and gonadotropin in ovaries and relaxin in uterus, as well as the AC inhibitory effects of somatostatin in all tissues, and of noradrenaline in myocardium. Treatment with IS led to a partial restoration of the AC-inhibitory effect of noradrenalin in the diabetic myocardium, but did not affect regulation of AC by other hormones. These data indicate that I-I normalizes the ACS functional activity in myocardium and in tissues of the reproductive system of female rats with neonatal DM, whereas the effect of I-S on in the studied tissues is less pronounced. These results are necessary to be taken into account at development and optimization of strategy of use of I-I and I-S for treatment of DM and of its complications.

  5. Polycystic ovaries: MR imaging.

    PubMed

    Mitchell, D G; Gefter, W B; Spritzer, C E; Blasco, L; Nulson, J; Livolsi, V; Axel, L; Arger, P H; Kressel, H Y

    1986-08-01

    To determine the characteristic appearance of polycystic ovaries on magnetic resonance (MR) images, seven women with polycystic ovarian disease (PCOD) underwent MR examination of the pelvis. These MR images were compared with sonograms. Histologic material was available in two patients. Six of the seven women had characteristic, small peripheral cysts, best seen on T2-weighted MR images; these cysts were seen sonographically in only one case. The centers of nine of 14 ovaries were of low intensity with all MR pulse sequences; this low intensity corresponded with low echogenicity in six cases. Histologically, these areas correlated with hypertrophic cellular stroma. Coexisting central teratomas were seen in three ovaries. The ability of MR to display the findings of PCOD better than ultrasound and its ability to demonstrate coexisting pathologic conditions are valuable in imaging the female pelvis.

  6. Pharmacokinetic interaction between Kaempferia parviflora extract and sildenafil in rats.

    PubMed

    Mekjaruskul, Catheleeya; Sripanidkulchai, Bungorn

    2015-04-01

    Kaempferia parviflora (KP) is a plant widely used in Southeast Asia. Its major compounds are 3,5,7,3',4'-pentamethoxyflavone (PMF), 5,7,4'-trimethoxylflavone (TMF), and 5,7-dimethoxyflavone (DMF). This study investigated the effect of KP extract on the blood levels and pharmacokinetics of sildenafil co-administration in rats. Rats were randomly assigned to four groups. Groups 1, 2, and 3 were given sildenafil 20 mg/kg daily for 9 days. On days 4-9 of each treatment period, the treated rats received KP extract (250 mg/kg) and vehicle (groups 2 and 3, respectively). Group 4 received KP extract only (250 mg/kg daily for 9 days). Daily blood concentrations of sildenafil, PMF, TMF, and DMF were determined by HPLC to evaluate the daily blood level interactions. Additional blood samples were collected at various times on the last day of treatment to evaluate the pharmacokinetic interactions. The KP extract decreased blood levels of sildenafil on the first day of co-administration by 95 % but the percentage reduction was insignificant on subsequent days. When co-administered with KP extract, the area under the curve (AUC), maximum concentration (C max), and half-life (T 1/2) of sildenafil were decreased by 60-65, 40-52, and 32-54 %, respectively, with the elimination rate constant (K e) increased by 37-77 %. In addition, PMF, TMF, and DMF concentrations and their AUC, C max, T max, K e, and T 1/2 values were changed after co-administration of KP extract and sildenafil.

  7. Baclofen interactions with nicotine in rats: effects on memory.

    PubMed

    Levin, Edward D; Weber, Elyssa; Icenogle, Laura

    2004-10-01

    Nicotine has been shown in numerous previous studies to significantly improve memory on the radial-arm maze, yet the critical mechanisms underlying this effect are not fully characterized. Nicotine stimulates the release of a number of neurotransmitters important for memory function including (gamma-aminobutyric acid) GABA. The importance of nicotinic-GABA interactions regarding memory is currently unknown. The purpose of the current study was to determine the interactive effects of nicotine and the GABA agonist baclofen on working memory function as measured by choice accuracy in the radial-arm maze. Female Sprague-Dawley rats trained to asymptotic performance levels on a win-shift eight-arm radial maze task were used for assessment of nicotine-baclofen interactions. Low doses of baclofen improved memory performance while higher doses impaired it. Nicotine, as seen before, improved memory performance. Nicotine also significantly reversed the higher dose baclofen-induced deficit. These data show the importance of both nicotinic and GABA systems in working memory function and the interactions between these two transmitter receptor systems. This not only provides information concerning the neural bases of cognitive performance, it also lends insight into new combination treatments for memory impairment.

  8. Removal of Toxin (Tetrodotoxin) from Puffer Ovary by Traditional Fermentation

    PubMed Central

    Anraku, Kensaku; Nonaka, Kiku; Yamaga, Toshitaka; Yamamoto, Takatoshi; Shin, Min-Chul; Wakita, Masahito; Hamamoto, Ayaka; Akaike, Norio

    2013-01-01

    The amounts of puffer toxin (tetrodotoxin, TTX) extracted from the fresh and the traditional Japanese salted and fermented “Nukazuke” and “Kasuzuke” ovaries of Takifugu stictonotus (T. stictonotus) were quantitatively analyzed in the voltage-dependent sodium current (INa) recorded from mechanically dissociated single rat hippocampal CA1 neurons. The amount of TTX contained in “Nukazuke” and “Kasuzuke” ovaries decreased to 1/50–1/90 times of that of fresh ovary during a salted and successive fermented period over a few years. The final toxin concentration after fermentation was almost close to the TTX level extracted from T. Rubripes” fresh muscle that is normally eaten. It was concluded that the fermented “Nukazuke” and “Kasuzuke” ovaries of puffer fish T. Stictonotus are safe and harmless as food. PMID:23334671

  9. Removal of toxin (tetrodotoxin) from puffer ovary by traditional fermentation.

    PubMed

    Anraku, Kensaku; Nonaka, Kiku; Yamaga, Toshitaka; Yamamoto, Takatoshi; Shin, Min-Chul; Wakita, Masahito; Hamamoto, Ayaka; Akaike, Norio

    2013-01-18

    The amounts of puffer toxin (tetrodotoxin, TTX) extracted from the fresh and the traditional Japanese salted and fermented "Nukazuke" and "Kasuzuke" ovaries of Takifugu stictonotus (T. stictonotus) were quantitatively analyzed in the voltage-dependent sodium current (I(Na)) recorded from mechanically dissociated single rat hippocampal CA1 neurons. The amount of TTX contained in "Nukazuke" and "Kasuzuke" ovaries decreased to 1/50-1/90 times of that of fresh ovary during a salted and successive fermented period over a few years. The final toxin concentration after fermentation was almost close to the TTX level extracted from T. Rubripes" fresh muscle that is normally eaten. It was concluded that the fermented "Nukazuke" and "Kasuzuke" ovaries of puffer fish T. Stictonotus are safe and harmless as food.

  10. [Interaction of fluorine, calcium and iodine on weight of rats].

    PubMed

    Zou, Yan; Wang, Jian-Hua; Xiao, Jing; Ling, Xin; Dong, Guo-Bin

    2008-09-01

    To study the interaction of fluorine (F), calcium (Ca) and iodine (I) on body weight of rats. One-month-old Wistar rats were randomly divided into 8 groups: moderate concentrations of F, Ca, I (group 1); moderate concentrations of F, I and high concentration of Ca (group 2); moderate concentrations of Ca, I and high concentration of F (group 3); moderate concentration of I and high concentrations of F, Ca (group 4); moderate concentrations of F, Ca and low concentration of I (group 5); moderate concentration of F,high concentration of Ca and low concentration of I (group 6); moderate concentration of Ca, high concentration of F and low concentration of I (group 7); high concentrations of F, Ca and low concentration of I (group 8) based on 2 x 2 x 2 factorial design. The moderate concentration of F was 90 microg/d and the high concentration of F was 2700 microg/d. The moderate Ca concentration was 13 mg/d and the high Ca concentration was 260 mg/d. The moderate concentration of I was 3.5 microg/d and the low concentration of I was 0.23 microg/d. After twenty weeks, body weight was measured. According to the results of factorial ANOVA, significant interaction effects of F with Ca were found (F = 5.933, P = 0.017). The empty body weight was measured at the end of the fifth month. When both iodine and fluorine were at the optimal level, the weight of group 2 [(262.5 +/- 47.1) g] and group 1 [(307.9 +/- 55.0) g] showed significant difference (t = 4.24, P < 0.05). When both iodine and fluorine were at low level, the weight of group 6 [(248.8 +/- 30.0) g] and group 5 [(293.3 +/- 19.7) g] showed significant difference (t = 4.16, P < 0.05). Animals with optimal iodine and calcium [(269.3 +/- 27.3) g] showed significant difference compared to the weight of low level iodine and optimal fluorine [(307.9 +/- 55.0) g]. When the low level iodine and optimal calcium were applied, weight of group 7 [(261.9 +/- 31.3) g] and group 5 [(293.3 +/- 19.7) g] showed significant difference

  11. Pharmacokinetic interaction of garlic and atorvastatin in dyslipidemic rats

    PubMed Central

    Reddy, G. Dilip; Reddy, A. Gopala; Rao, G.S.; Kumar, M. Vijay

    2012-01-01

    Objective: To assess pharmacokinetic interaction of garlic with atorvastatin in dyslipidemic rats. Materials and Methods: Sprague Dawley rats with induced dyslipidemia were divided into five groups of eight rats each. Group 1 was given atorvastatin (10 mg/kg body weight (b.wt) orally), group 2 was given atorvastatin (10 mg/kg b.wt orally)+garlic (1% w/w in feed), group 3 was maintained on atorvastatin (5 mg/kg b.wt orally)+garlic (0.5% w/w in feed), group 4 was maintained on atorvastatin (7.5 mg/kg b.wt orally)+garlic (0.25% w/w in feed), and group 5 was maintained on atorvastatin (2.5 mg/kg b.wt orally)+garlic (0.75% w/w in feed) for 12 weeks. Blood samples were collected at predetermined time intervals for kinetic analysis after the first and last oral dosing of atorvastatin for single and multiple dose studies, respectively. Plasma samples were assayed for atorvastatin concentration by High-Performance Liquid Chromatography (HPLC) and then the concentration-time data were analyzed. Results: Maximum observed plasma concentration (Cmax), half-life, Area Under Plasma Concentration Time Curve (AUC), and Mean Resident Time (MRT) were significantly (P<0.05) increased during multiple dose kinetic study and elimination rate constant was significantly (P<0.05) decreased in comparison with their respective single-dose values, while there was no significant difference in time to achieve maximum concentration (tmax) in all groups during both phases of the study. The highest values for kinetic parameters were observed in group 2 with correspondingly low activity of Cytochrome P450 (CYP450). Conclusion: The study revealed higher values [Cmax, AUC, Area Under The Moment Curve (AUMC), MRT, and half-life] of atorvastatin in garlic-treated groups. PMID:22529485

  12. Chromium and manganese interactions in streptozocin-diabetic rats

    SciTech Connect

    Davis, M.L.; Jarrett, C.R.; Adeleye, B.O.; Stoecker, B.J. )

    1991-03-15

    Weanling male rats were fed casein-based diets low in chromium and manganese ({minus}Cr-MN) or supplemented with 1 ppm chromium as chromium chloride (+Cr) and/or 55 ppm manganese as manganous carbonate in a factorial design. After 7 weeks on the experimental diets, half of the rats in each group were injected on 2 consecutive days with 55 mg/kg streptozocin (STZ) in citrate buffer pH 4. Four weeks after injection, serum glucose in the diabetic group supplement with both Cr and Mn was not different from non-diabetic animals; however, diabetic animals in {minus}Cr groups or in the +Cr-Mn group had significantly elevated serum glucose. Serum insulin was reduced by STZ. A significant interaction between Mn and diabetes affected serum cortisol concentrations. More new tissue was formed on a polyvinyl sponge inserted under the skin in +Mn animals. In this study, the STZ animals were more sensitive than the control animals to dietary Cr and Mn concentrations.

  13. Interactions between two propagating waves in rat visual cortex

    PubMed Central

    Gao, Xin; Xu, Weifeng; Wang, Zhijie; Takagaki, Kentaroh; Li, Bing; Wu, Jian-young

    2012-01-01

    Sensory-evoked propagating waves are frequently observed in sensory cortex. However, it is largely unknown how an evoked propagating wave affects the activity evoked by subsequent sensory inputs, or how two propagating waves interact when evoked by simultaneous sensory inputs. Using voltage-sensitive dye imaging, we investigated the interactions between two evoked waves in rat visual cortex, and the spatiotemporal patterns of depolarization in the neuronal population due to wave-to-wave interactions. We have found that visually-evoked propagating waves have a refractory period of about 300 ms, within which the response to a subsequent visual stimulus is suppressed. Simultaneous presentation of two visual stimuli at different locations can evoke two waves propagating toward each other, and these two waves fuse. Fusion significantly shortens the latency and half-width of the response, leading to changes in the spatial profile of evoked population activity. The visually-evoked propagating wave may also be suppressed by a preceding spontaneous wave. The refractory period following a propagating wave and the fusion between two waves may contribute to visual sensory processing by modifying the spatiotemporal profile of population neuronal activity evoked by sensory events. PMID:22561730

  14. QUANTITATIVE STUDIES ON THE MIXED LYMPHOCYTE INTERACTION IN RATS

    PubMed Central

    Wilson, Darcy B.; Blyth, Janet L.; Nowell, Peter C.

    1968-01-01

    The proliferative interaction of cultured rat lymphocytes of immunogenetically disparate origin—the mixed lymphocyte interaction—was employed as an experimental model to examine the initial stages of the immune response mechanism. Using mixed cultures of cells derived from parental strain and F1 hybrid rats, in which only the parental lymphocytes respond, the following observations were made on the magnitude and kinetics of the reaction. After initiation of the cultures, there was a latent period of approximately 40 hours during which time no mitotic activity was detected. This inactive phase was followed by a period of proliferation in which previously nondividing cells entered the mitotic cycle for the first time. Activity in the cultures, as detected by incorporation of radioactive thymidine and measured by radioautography or scintillation spectrometry, increased exponentially with a doubling time (T2) of 9–10 hr. In this exponential proliferative phase, lasting approximately 100 hr, the dividing cells underwent a series of rapid sequential divisions with a generation time (Tc) of 8 hr, and few, if any, dropped out of the mitotic cycle. In addition to the cells which first entered mitosis at the beginning of the proliferative phase and then proceeded through multiple divisions, significant numbers of new, previously nondividing cells continued to enter the mitotic cycle during the entire exponential growth phase. The total number of these newly responsive, first division cells throughout the total culture period amounted to 1–3% of the original parental cell inoculum. This is a surprisingly large proportion of peripheral blood lymphocytes with demonstrable reactivity to a particular antigen system, if it is assumed that these first division cells in vitro are functionally related to the hypothetical antigen-sensitive cells which proliferate and differentiate into immunological effector cells. At present there is no entirely satisfactory explanation for

  15. Neuronal-glial interactions in rats fed a ketogenic diet.

    PubMed

    Melø, Torun Margareta; Nehlig, Astrid; Sonnewald, Ursula

    2006-01-01

    Glucose is the preferred energy substrate for the adult brain. However, during periods of fasting and consumption of a high fat, low carbohydrate (ketogenic) diet, ketone bodies become major brain fuels. The present study was conducted to investigate how the ketogenic diet influences neuronal-glial interactions in amino acid neurotransmitter metabolism. Rats were kept on a standard or ketogenic diet. After 21 days all animals received an injection of [1-(13)C]glucose plus [1,2-(13)C]acetate, the preferential substrates of neurons and astrocytes, respectively. Extracts from cerebral cortex and plasma were analyzed by (13)C and (1)H nuclear magnetic resonance spectroscopy and HPLC. Increased amounts of valine, leucine and isoleucine and a decreased amount of glutamate were found in the brains of rats receiving the ketogenic diet. Glycolysis was decreased in ketotic rats compared with controls, evidenced by the reduced amounts of [3-(13)C]alanine and [3-(13)C]lactate. Additionally, neuronal oxidative metabolism of [1-(13)C]glucose was decreased in ketotic rats compared with controls, since amounts of [4-(13)C]glutamate and [4-(13)C]glutamine were lower than those of controls. Although the amount of glutamate from [1-(13)C]glucose was decreased, this was not the case for GABA, indicating that relatively more [4-(13)C]glutamate is converted to GABA. Astrocytic metabolism was increased in response to ketosis, shown by increased amounts of [4,5-(13)C]glutamine, [4,5-(13)C]glutamate, [1,2-(13)C]GABA and [3,4-(13)C]-/[1,2-(13)C]aspartate derived from [1,2-(13)C]acetate. The pyruvate carboxylation over dehydrogenation ratio for glutamine was increased in the ketotic animals compared to controls, giving further indication of increased astrocytic metabolism. Interestingly, pyruvate recycling was higher in glutamine than in glutamate in both groups of animals. An increase in this pathway was detected in glutamate in response to ketosis. The decreased glycolysis and oxidative

  16. Combination of a GnRH agonist with an antagonist prevents flare-up effects and protects primordial ovarian follicles in the rat ovary from cisplatin-induced toxicity: a controlled experimental animal study

    PubMed Central

    2013-01-01

    Background With the continuous improvement of surgery and chemotherapeutic treatments, many tumour patients increasingly achieve long-term survival and can even be completely cured. However, platinum-containing drugs, which are widely used to treat a variety of types of cancer, cause menstrual disorders and ovarian failure, which in turn lead to infertility. Thus far, gonadotropin releasing hormone (GnRH) agonist (GnRHa) and antagonist (GnRHant) are reported to act as protective agents of the ovary in chemotherapy through the inhibition of the female gonadal axis. Nevertheless, they both have disadvantages that limit their use. GnRHa causes a flare-up effect during the first week after administration, and no long-acting GnRHant agent is available. GnRHa combined with GnRHant may prevent the flare-up effect of GnRHa and rapidly inhibit the female gonadal axis. Several clinical studies with small sample sizes have reported controversial conclusions. In this strictly controlled animal study, we investigated the advantages of combination treatment with GnRHa and GnRHant. Methods Rats aged 12 weeks were divided into six groups: Control, cisplatin (CDDP), GnRHa, GnRHant, Combination (sht, short-term) and Combination (lng, long-term) of GnRHa and GnRHant. The last four groups received Triptorelin (1 mg/kg·d, for 14 days), Cetrorelix (0.5 mg/kg·d, for 10 days), a combination of Triptorelin (1 mg/kg·d, for 10 days) and Cetrorelix (0.5 mg/kg·d, for 10 days) in the long-term group and for 3 days in the short-term group. The Control and CDDP groups received saline (1 ml/kg·d, for 10 day). Then, all groups apart from the Control group received cisplatin (1 mg/kg·d, for 10 days), and the Control group received another 10 days of saline as described above. Blood samples were collected to detect the serum levels of E2, LH and FSH. Observation of oestrous cyclicity was also performed after drug administration. Finally, bilateral ovaries were collected for

  17. Beaming into the Rat World: Enabling Real-Time Interaction between Rat and Human Each at Their Own Scale

    PubMed Central

    Normand, Jean-Marie; Sanchez-Vives, Maria V.; Waechter, Christian; Giannopoulos, Elias; Grosswindhager, Bernhard; Spanlang, Bernhard; Guger, Christoph; Klinker, Gudrun; Srinivasan, Mandayam A.; Slater, Mel

    2012-01-01

    Immersive virtual reality (IVR) typically generates the illusion in participants that they are in the displayed virtual scene where they can experience and interact in events as if they were really happening. Teleoperator (TO) systems place people at a remote physical destination embodied as a robotic device, and where typically participants have the sensation of being at the destination, with the ability to interact with entities there. In this paper, we show how to combine IVR and TO to allow a new class of application. The participant in the IVR is represented in the destination by a physical robot (TO) and simultaneously the remote place and entities within it are represented to the participant in the IVR. Hence, the IVR participant has a normal virtual reality experience, but where his or her actions and behaviour control the remote robot and can therefore have physical consequences. Here, we show how such a system can be deployed to allow a human and a rat to operate together, but the human interacting with the rat on a human scale, and the rat interacting with the human on the rat scale. The human is represented in a rat arena by a small robot that is slaved to the human’s movements, whereas the tracked rat is represented to the human in the virtual reality by a humanoid avatar. We describe the system and also a study that was designed to test whether humans can successfully play a game with the rat. The results show that the system functioned well and that the humans were able to interact with the rat to fulfil the tasks of the game. This system opens up the possibility of new applications in the life sciences involving participant observation of and interaction with animals but at human scale. PMID:23118987

  18. Development of mammalian ovary.

    PubMed

    Smith, Peter; Wilhelm, Dagmar; Rodgers, Raymond J

    2014-06-01

    Pre-natal and early post-natal ovarian development has become a field of increasing importance over recent years. The full effects of perturbations of ovarian development on adult fertility, through environmental changes or genetic anomalies, are only now being truly appreciated. Mitigation of these perturbations requires an understanding of the processes involved in the development of the ovary. Herein, we review some recent findings from mice, sheep, and cattle on the key events involved in ovarian development. We discuss the key process of germ cell migration, ovigerous cord formation, meiosis, and follicle formation and activation. We also review the key contributions of mesonephric cells to ovarian development and propose roles for these cells. Finally, we discuss polycystic ovary syndrome, premature ovarian failure, and pre-natal undernutrition; three key areas in which perturbations to ovarian development appear to have major effects on post-natal fertility.

  19. 4: Polycystic ovary syndrome.

    PubMed

    Norman, Robert J; Wu, Ruijin; Stankiewicz, Marcin T

    2004-02-02

    Polycystic ovary syndrome (PCOS) is a common condition characterised by menstrual abnormalities and clinical or biochemical features of hyperandrogenism. Features of PCOS may manifest at any age, ranging from childhood (premature puberty), teenage years (hirsutism, menstrual abnormalities), early adulthood and middle life (infertility, glucose intolerance) to later life (diabetes mellitus and cardiovascular disease). While pelvic ultrasound examination is useful, many women without PCOS have polycystic ovaries; ultrasound evidence is not necessary for the diagnosis. Testing for glucose intolerance and hyperlipidaemia is wise, especially in obese women, as diabetes mellitus is common in PCOS. Lifestyle changes as recommended in diabetes are fundamental for treatment; addition of insulin-sensitising agents (eg, metformin) may be valuable in circumstances such as anovulatory infertility. Infertility can be treated successfully in most women by diet and exercise, clomiphene citrate with or without metformin, ovarian drilling, or ovulation induction with gonadotrophins; in-vitro fertilisation should be avoided unless there are other indications.

  20. The Mammalian Ovary from Genesis to Revelation

    PubMed Central

    Edson, Mark A.; Nagaraja, Ankur K.; Matzuk, Martin M.

    2009-01-01

    Two major functions of the mammalian ovary are the production of germ cells (oocytes), which allow continuation of the species, and the generation of bioactive molecules, primarily steroids (mainly estrogens and progestins) and peptide growth factors, which are critical for ovarian function, regulation of the hypothalamic-pituitary-ovarian axis, and development of secondary sex characteristics. The female germline is created during embryogenesis when the precursors of primordial germ cells differentiate from somatic lineages of the embryo and take a unique route to reach the urogenital ridge. This undifferentiated gonad will differentiate along a female pathway, and the newly formed oocytes will proliferate and subsequently enter meiosis. At this point, the oocyte has two alternative fates: die, a common destiny of millions of oocytes, or be fertilized, a fate of at most approximately 100 oocytes, depending on the species. At every step from germline development and ovary formation to oogenesis and ovarian development and differentiation, there are coordinated interactions of hundreds of proteins and small RNAs. These studies have helped reproductive biologists to understand not only the normal functioning of the ovary but also the pathophysiology and genetics of diseases such as infertility and ovarian cancer. Over the last two decades, parallel progress has been made in the assisted reproductive technology clinic including better hormonal preparations, prenatal genetic testing, and optimal oocyte and embryo analysis and cryopreservation. Clearly, we have learned much about the mammalian ovary and manipulating its most important cargo, the oocyte, since the birth of Louise Brown over 30 yr ago. PMID:19776209

  1. Ovary of Fundulus heteroclitus

    SciTech Connect

    Brummett, A.R.; Dumont, J.N.; Larkin, J.R.

    1982-01-01

    Scanning and transmission electron microscopy, together with dissection and light microscopy, have produced heretofore unavailable structural detail of the ovary of Fundulus heteroclitus. Structural and functional interrelationships among developing follicles and other histological elements, particularly as they might relate to vascularization of follicles, oocyte development, and ovulation, are described and discussed. Mature eggs, ovulated into the ovarian lumen, accumulate in the posterior ovisac region of the ovary prior to oviposition. This ovisac region is thin-walled and apparently nongerminal. The temporary retention of ovulated eggs permits cyclical oviposition even though oogenesis and ovulation are asynchronous. The histological differences between the ovisac and the anterior ovigerous region of the ovary are described. The lumenal epithelium of the ovisac displays a localized population of unusual cells with long cytoplasmic extensions. The ultrastructure of these cells suggests that they might function in the transport of ovulated eggs into the oviduct and/or in secreting the substance (jelly) which forms the surface coat of extruded eggs.

  2. Polycystic ovary syndrome (PCOS).

    PubMed

    Dewailly, D; Hieronimus, S; Mirakian, P; Hugues, J-N

    2010-02-01

    1. The Rotterdam classification should be used to define PCOS in the event of: menstrual cycle anomalies; amenorrhoea, oligomenorrhoea or long cycles, clinical and/or biochemical hyperandrogenism and ultrasound appearance of polycystic ovaries. 2. The presence of two of these three criteria is sufficient once all other diagnoses have been ruled out. 3. Diagnosis of hirsutism should not be based on the Ferriman-Gallway score. 4. The ultrasound definition of PCOS contains precise criteria that must be included in the report: presence of at least 12 follicles in each ovary measuring 2-9 mm in diameter, and/or increase in ovary size>10 ml. 5. Screening for elevated plasma LH no longer necessary. Testing for GnRH serves no purpose. 6. Routine screening for metabolic abnormalities should be carried out systematically based on weight, height and BMI, waist circumference, blood pressure and laboratory parameters: plasma glucose, triglycerides, HDL cholesterol. 7. In the case of obesity (BMI>30 kg/m(2)), oral glucose tolerance testing (OGTT) is recommended where fasting serum glucose is normal. 8. Clomiphene citrate (CC) remains the first-line therapy for ovulation induction. In patients with BMI>30, it should be preceded by improvement of metabolic status through appropriate lifestyle modifications.

  3. Pharmacokinetic interactions between phenylpropanolamine, caffeine and chlorpheniramine in rats.

    PubMed

    Kaddoumi, Amal; Nakashima, Mihoko N; Wada, Mitsuhiro; Nakashima, Kenichiro

    2004-06-01

    As the mechanism involved in the serious adverse effects associated with phenylpropanolamine (PPA) has not yet been clarified, and as PPA in usual cases is not being ingested without other drugs combination, the aim of this study was to characterize the possibility of pharmacokinetic interactions between PPA and most often combined drugs existing in the same dosage. The pharmacokinetics of PPA in rat brain and blood were evaluated when administered alone (group I), combined with caffeine (group II), combined with chlorpheniramine (group III), combined with both caffeine and chlorpheniramine (group IV) and finally when existed in one of the available OTC products (group V). This product contains multiple ingredients of PPA, caffeine and chlorpheniramine. In brain the pharmacokinetic parameters of PPA were significantly affected with the combined administration of caffeine and/or chlorpheniramine. The single intraperitoneal administration of caffeine (5 mg/kg) with PPA (2.5 mg/kg) to rats caused 1.6-fold increase in the AUC of PPA in brain compared to the single administration of PPA, and was comparable to the 1.5-fold increase caused by chlorpheniramine (0.4 mg/kg). The multiple combinations caused an increase in the AUC by 1.9-fold, which is comparable to the increase in the AUC of PPA obtained from the OTC product (2.2-fold). On the other hand, there was no significant difference in the pharmacokinetics of PPA in blood between the groups except for the C(max) of PPA in groups I and IV. The observed adverse effects associated with PPA use could be related to the significant increase in its levels in the brain.

  4. Interaction of rat liver glucocorticoid receptor with sodium tungstate.

    PubMed

    Murakami, N; Healy, S P; Moudgil, V K

    1982-06-15

    Effects of sodium tungstate on various properties of rat liver glucocorticoid receptor were examined at pH7 and pH 8. At pH 7, [3H]triamcinolone acetonide binding in rat liver cytosol preparations was completely blocked in the presence of 10--20 mM-sodium tungstate at 4 degrees C, whereas at 37 degrees C a 30 min incubation of cytosol receptor preparation with 1 mM-sodium tungstate reduced the loss of unoccupied receptor by 50%. At pH 8.0, tungstate presence during the 37 degrees C incubation maintained the steroid-binding capacity of unoccupied glucocorticoid receptor at control (4 degrees C) levels. In addition, heat-activation of cytosolic glucocorticoid-receptor complex was blocked by 1 mM- and 10 mM-sodium tungstate at pH 7 and pH 8 respectively. The DNA-cellulose binding by activated receptor was also inhibited completely and irreversibly by 5 mM-tungstate at pH 7, whereas at pH 8 no significant effect was observed with up to 20 mM-tungstate. The entire DNA-cellulose-bound glucocorticoid-receptor complex from control samples could be extracted by incubation with 1 mM- and 20 mM-tungstate at pH 7 and pH 8 respectively, and appeared to sediment as a 4.3--4.6 S molecule, both in 0.01 M- and 0.3 M-KCl-containing sucrose gradients. Tungstate effects are, therefore, pH-dependent and appear to involve an interaction with both the non-activated and the activated forms of the glucocorticoid receptor.

  5. Concentration-time interactions in hydrogen sulphide toxicity in rats.

    PubMed Central

    Prior, M G; Sharma, A K; Yong, S; Lopez, A

    1988-01-01

    Concentration-time interactions were investigated in young male and female Sprague-Dawley, Long Evans and Fischer-344 rats exposed to hydrogen sulphide for two, four or six hours. Higher concentrations caused more deaths, with no significant difference for duration of exposure. A significant sex effect was noted with 30% mortality in males and 20% in females, with no significant difference among strains. Changes in weight were significant: increasing with concentration, higher in males than in females, different among strains (Fischer-344 less than Sprague Dawley less than Long Evans), and affected by duration of exposure. Lethal concentration values (LC50 and LC10) were estimated, for the pooled data set (n = 456); the probit equation was Y = -5.74749 + 3.8259X where X is log10 dose of hydrogen sulphide in parts per million. The LC50/LC10 values were 644/298 parts per million (902/417 mg m-3) respectively. Individual probit analyses were also performed for strain, hours of exposure and sex. The LC50 and LC10 values for male, female and strain were not different. Significant differences were observed among LC50/LC10 values for hours of exposure (2 h = 587/549 parts per million, 822/769 mg m-3; 4 h = 501/422 parts per million, 701/591 mg m-3; 6 h = 335/299 parts per million, 469/491 mg m-3). There was no effect of spatial position in the exposure chamber on the distribution of mortality. All rats of all strains dying had severe pulmonary edema. PMID:3167719

  6. Cytotoxicity and mutagenicity of vapor-phase pollutants in rat lung epithelial cells and Chinese hamster ovary cells grown on collagen gels

    SciTech Connect

    Zamora, P.O.; Benson, J.M.; Marshall, T.C.; Mokler, B.V.; Li, A.P.; Dahl, A.R.; Brooks, A.L.; McClellan, R.O.

    1983-01-01

    Lung epithelial cell (cell line designated LEC) and Chinese hamster ovary (CHO) cells were grown on hydrated collagen gels and exposed directly to toxic vapor-phase pollutants. The cells were exposed to graded concentrations of phenol, formaldehyde, a volatile fraction of process stream material from an experimental coal gasifier, and the nonparticulate, vapor phase of diesel engine exhaust. During exposures, the cells were maintained at an air/collagen interface by removing the medium overlying the hydrated collagen gel. Morphological changes indicative of cell retraction were found in LEC cell cultures exposed to phenol, formaldehyde, or diesel exhaust. Damage following exposure to the toxicants was quantitated in LEC and CHO cells by Trypan blue dye exclusion, a measure of plasma membrane integrity. Clone-forming ability was also used to measure cell survival in CHO cells. When measured by Trypan blue dye exclusion, phenol (EC50 = 2.1 mg/l) caused membrane damage to LEC cells but not CHO cells, while formaldehyde (EC50 = 31 and 42 ..mu..g/l for LEC and CHO, respectively) and diesel exhaust (EC50 = 11 and 29% of tailpipe exhaust in LEC and CHO cells, respectively) caused damage to both cell types. No cytotoxicity was observed in LEC or CHO cells exposed to the fraction from the coal gasifier. Essentially no mutagenic activity was associated with the exposure of CHO cells to formaldehyde or the vapor phase of diesel exhaust. Mutagenic activity was found in CHO cells exposed to ethylene oxide, the positive control.

  7. Female Reproductive Aging Is Master-Planned at the Level of Ovary

    PubMed Central

    Banerjee, Sayani; Banerjee, Sutapa; Saraswat, Ghungroo; Bandyopadhyay, Soma Aditya; Kabir, Syed N.

    2014-01-01

    The ovary receives a finite pool of follicles during fetal life. Atresia remains the major form of follicular expenditure at all stages since development of ovary. The follicular reserve, however, declines at an exponential rate leading to accelerated rate of decay during the years preceding menopause. We examined if diminished follicle reserve that characterizes ovarian aging impacts the attrition rate. Premature ovarian aging was induced in rats by intra-embryonic injection of galactosyltransferase-antibody on embryonic day 10. On post-natal day 35 of the female litters, either a wedge of fat (sham control) or a wild type ovary collected from 25-day old control rats, was transplanted under the ovarian bursa in both sides. Follicular growth and atresia, and ovarian microenvironment were evaluated in the follicle-deficient host ovary and transplanted ovary by real time RT-PCR analysis of growth differentiation factor-9, bone morphogenetic protein 15, and kit ligand, biochemical evaluation of ovarian lipid peroxidation, superoxide dismutase (SOD) and catalase activity, and western blot analysis of ovarian pro- and anti-apoptotic factors including p53, bax, bcl2, and caspase 3. Results demonstrated that the rate of follicular atresia, which was highly preponderant in the follicle-deficient ovary of the sham-operated group, was significantly prevented in the presence of the transplanted ovary. As against the follicle-deficient ovary of the sham-operated group, the follicle-deficient host ovary as well as the transplanted ovary in the ovary-transplanted group exhibited stimulated follicle growth with increased expression of anti-apoptotic factors and down regulation of pro-apoptotic factors. Both the host and transplanted ovaries also had significantly lower rate of lipid peroxidation with increased SOD and catalase activity. We conclude that the declining follicular reserve is perhaps the immediate thrust that increases the rate of follicle depletion during the final

  8. Female reproductive aging is master-planned at the level of ovary.

    PubMed

    Banerjee, Sayani; Banerjee, Sutapa; Saraswat, Ghungroo; Bandyopadhyay, Soma Aditya; Kabir, Syed N

    2014-01-01

    The ovary receives a finite pool of follicles during fetal life. Atresia remains the major form of follicular expenditure at all stages since development of ovary. The follicular reserve, however, declines at an exponential rate leading to accelerated rate of decay during the years preceding menopause. We examined if diminished follicle reserve that characterizes ovarian aging impacts the attrition rate. Premature ovarian aging was induced in rats by intra-embryonic injection of galactosyltransferase-antibody on embryonic day 10. On post-natal day 35 of the female litters, either a wedge of fat (sham control) or a wild type ovary collected from 25-day old control rats, was transplanted under the ovarian bursa in both sides. Follicular growth and atresia, and ovarian microenvironment were evaluated in the follicle-deficient host ovary and transplanted ovary by real time RT-PCR analysis of growth differentiation factor-9, bone morphogenetic protein 15, and kit ligand, biochemical evaluation of ovarian lipid peroxidation, superoxide dismutase (SOD) and catalase activity, and western blot analysis of ovarian pro- and anti-apoptotic factors including p53, bax, bcl2, and caspase 3. Results demonstrated that the rate of follicular atresia, which was highly preponderant in the follicle-deficient ovary of the sham-operated group, was significantly prevented in the presence of the transplanted ovary. As against the follicle-deficient ovary of the sham-operated group, the follicle-deficient host ovary as well as the transplanted ovary in the ovary-transplanted group exhibited stimulated follicle growth with increased expression of anti-apoptotic factors and down regulation of pro-apoptotic factors. Both the host and transplanted ovaries also had significantly lower rate of lipid peroxidation with increased SOD and catalase activity. We conclude that the declining follicular reserve is perhaps the immediate thrust that increases the rate of follicle depletion during the final

  9. Circulating gonadotropins and ovarian adiponectin system are modulated by acupuncture independently of sex steroid or β-adrenergic action in a female hyperandrogenic rat model of polycystic ovary syndrome.

    PubMed

    Maliqueo, Manuel; Benrick, Anna; Alvi, Asif; Johansson, Julia; Sun, Miao; Labrie, Fernand; Ohlsson, Claes; Stener-Victorin, Elisabet

    2015-09-05

    Acupuncture with combined manual and low-frequency electrical stimulation, or electroacupuncture (EA), reduces endocrine and reproductive dysfunction in women with polycystic ovary syndrome (PCOS), likely by modulating sympathetic nerve activity or sex steroid synthesis. To test this hypothesis, we induced PCOS in rats by prepubertal implantation of continuous-release letrozole pellets (200 µg/day) or vehicle. Six weeks later, rats were treated for 5-6 weeks with low-frequency EA 5 days/week, subcutaneous injection of 17β-estradiol (2.0 µg) every fourth day, or a β-adrenergic blocker (propranolol hydrochloride, 0.1 mg/kg) 5 days/week. Letrozole controls were handled without needle insertion or injected with sesame oil every fourth day. Estrous cyclicity, ovarian morphology, sex steroids, gonadotropins, insulin-like growth factor I, bone mineral density, and gene and protein expression in ovarian tissue were measured. Low-frequency EA induced estrous-cycle changes, decreased high levels of circulating luteinizing hormone (LH) and the LH/follicle-stimulating hormone (FSH) ratio, decreased high ovarian gene expression of adiponectin receptor 2, and increased expression of adiponectin receptor 2 protein and phosphorylation of ERK1/2. EA also increased cortical bone mineral density. Propranolol decreased ovarian expression of Foxo3, Srd5a1, and Hif1a. Estradiol decreased circulating LH, induced estrous cycle changes, and decreased ovarian expression of Adipor1, Foxo3, and Pik3r1. Further, total bone mineral density was higher in the letrozole-estradiol group. Thus, EA modulates the circulating gonadotropin levels independently of sex steroids or β-adrenergic action and affects the expression of ovarian adiponectin system. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  10. Differences in social interaction- vs. cocaine reward in mouse vs. rat.

    PubMed

    Kummer, Kai K; Hofhansel, Lena; Barwitz, Constanze M; Schardl, Aurelia; Prast, Janine M; Salti, Ahmad; El Rawas, Rana; Zernig, Gerald

    2014-01-01

    We previously developed rat experimental models based on the conditioned place preference (CPP) paradigm in which only four 15-min episodes of dyadic social interaction with a sex- and weight-matched male Sprague Dawley (SD) rat (1) reversed CPP from cocaine to social interaction despite continuing cocaine training, and (2) prevented the reacquisition/re-expression of cocaine CPP. In a concurrent conditioning schedule, pairing one compartment with social interaction and the other compartment with 15 mg/kg cocaine injections, rats spent the same amount of time in both compartments and the most rewarding sensory component of the composite stimulus social interaction was touch (taction). In the present study, we validated our experimental paradigm in C57BL/6 mice to investigate if our experimental paradigm may be useful for the considerable number of genetically modified mouse models. Only 71% of the tested mice developed place preference for social interaction, whereas 85% of the rats did. Accordingly, 29% of the mice developed conditioned place aversion (CPA) to social interaction, whereas this was true for only 15% of the rats. In support of the lesser likelihood of mice to develop a preference for social interaction, the average amount of time spent in direct contact was 17% for mice vs. 79% for rats. In animals that were concurrently conditioned for social interaction vs. cocaine, the relative reward strength for cocaine was 300-fold higher in mice than in rats. Considering that human addicts regularly prefer drugs of abuse to drug-free social interaction, the present findings suggest that our experimental paradigm of concurrent CPP for cocaine vs. social interaction is of even greater translational power if performed in C57BL/6 mice, the genetic background for most transgenic rodent models, than in rats.

  11. Placental lactogen secretion during prolonged-pregnancy in the rat: the ovary plays a pivotal role in the control of placental function.

    PubMed

    Shiota, K; Furuyama, N; Takahashi, M

    1991-10-01

    The serum of rats at mid-pregnancy contains at least 2 distinct placental lactogen (PL)-like substances tentatively termed placental lactogen-alpha (PL-alpha) and placental lactogen-beta (PL-beta) (Endocrinol Japon 38: 533-540, 1991). We have investigated the secretory patterns of three placental lactogens (PL-alpha, PL-beta and placental lactogen-II) during normal pregnancy and in two prolonged-pregnancy models. Pregnancy was prolonged by the introduction of new corpora lutea by inducing ovulation on day 15 of pregnancy by successive treatments with PMSG (30 IU/rat, sc on day 12) and hCG (10 IU/rat, iv on day 14), and in the second model by progesterone implants on day 15 of pregnancy. During normal pregnancy, each of the 3 PLs exhibited only one secretory peak in the serum; PL-alpha and PL-beta on day 12 and placental lactogen II (PL-II) on day 20. Interestingly, in the rats with new sets of corpora lutea, serum PL-alpha and PL-beta levels began to increase again on day 18 and showed peaks on day 20 for PL-alpha and on day 22 for PL-beta. In this model, the initiation of PL-II secretion was not affected, but high levels were maintained until day 26, when parturition occurred. In rats receiving either PMSG or hCG, the secretory patterns of the PLs were similar to as those during normal pregnancy.(ABSTRACT TRUNCATED AT 250 WORDS)

  12. Cadmium-2-acetylaminofluorene interaction in isolated rat hepatocytes.

    PubMed

    Moffatt, P; Marion, M; Denizeau, F

    1992-01-01

    Cadmium (Cd) is a non-essential, highly toxic heavy metal and a ubiquitous environmental contaminant. Evidence exists that Cd can affect parameters which are of great importance in the response towards xenobiotics. However, there is a lack of information about the mechanisms that take place at the cellular and molecular levels upon dual exposure to Cd and other toxins. The purpose of the present work was therefore to examine the biochemical interactions between Cd and a well-known genotoxic hepatocarcinogen, 2-acetylaminofluorene (AAF) in isolated rat hepatocytes. The cells were incubated for 10 hr with a sub-cytotoxic concentration (0.22 microM) of 109Cd. This was followed by a 10 hr exposure to 1 microM [3H]AAF. Cellular distribution of Cd and 3H was determined. Sephadex G-75 elution profiles of the cytosol showed that Cd was almost entirely associated with the intermediate molecular weight (IMW) fractions containing metallothionein (MT) ( > 80%), and with high molecular weight proteins. In parallel, the highest proportion of 3H was found in the low molecular weight components. Further analysis of IMW fractions by DEAE A-25 anion-exchange chromatography revealed that, in addition to Cd, there was some 3H which coeluted along with MT-I and MT-II isoforms, but preferentially with MT-I. Moreover, Cd pretreatment caused a 1.6-fold increase in MT level, as measured by the silver-saturation assay. Under these conditions, there was a 17% lower binding of 3H to the DNA. This reduced binding was neither accompanied by diminished AAF uptake nor by inhibition of cytochrome P-450 activity. Taken together, these results suggest that Cd exposure has a protective effect against the genotoxicity of AAF. MT, whose synthesis is induced, could play a role in the Cd-AAF interaction through scavenging of reactive metabolites.

  13. Interaction of human lactoferrin with the rat liver

    SciTech Connect

    Debanne, M.T.; Regoeczi, E.; Sweeney, G.D.; Krestynski, F.

    1985-04-01

    Binding of human lactoferrin (hLf) by purified rat liver plasma membranes was studied to clarify whether the liver possesses specific hLf receptors. The binding was rapid between 4 degrees and 37 degrees C, with a pH optimum close to 5.0. At 22 degrees C and in glycine-NaOH (5 mM, pH 7.4) containing 150 mM NaCl and 0.5% albumin, 1 microgram of membrane bound a maximum of 11.8 ng hLf. The dissociation constant of the interaction was 1.6 X 10(-7) M. Other proteins of high isoelectric points (lactoperoxidase, lysozyme, and particularly salmine sulfate) and a piperazine derivative inhibited hLf binding in a concentration- dependent manner. In contrast, monosaccharides (galactose, N- acetylgalactosamine, mannose, and fucose) were ineffective. By omitting NaCl from the incubation buffer, binding was increased 3.6-fold. Erythrocyte ghosts bound hLf less firmly and alveolar macrophages more firmly than hepatic plasma membranes. Liver cell fractionations performed after the intravenous injection of labeled hLf showed that approximately 88% of the hepatic radioligand was associated with parenchymal cells. When binding was expressed per unit of cell volume, however, more hLf was present in nonparenchymal than in parenchymal cells, implying that the above value was determined by the relative cell masses rather than affinities alone. It is concluded that the binding of hLf by hepatic plasma membranes is electrostatic, i.e., is mediated by the cationic nature of the ligand, and that it is explicable in terms of a ''specific nonreceptor interaction'' of the generalized type proposed by Cuatrecasas and Hollenberg.

  14. Polycystic Ovary Syndrome (For Teens)

    MedlinePlus

    ... I Cope With Polycystic Ovary Syndrome? en español Síndrome de ovario poliquístico What Is Polycystic Ovary Syndrome? ... PCOS. Medicines used to treat PCOS will slow down or stop excessive hair growth for many girls. ...

  15. Polycystic ovary syndrome and acne.

    PubMed

    Chuan, Sandy S; Chang, R Jeffrey

    2010-01-01

    Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in reproductive aged women. It is typically characterized by hyperandrogenism, chronic anovulation, and polycystic ovaries. Women with PCOS often experience dermatologic manifestations of hyperandrogenism, including hirsutism, acne vulgaris, and androgenic alopecia. This article will review the treatments for acne due to androgen excess in PCOS women.

  16. Ovary and uterus transplantation.

    PubMed

    Gosden, Roger G

    2008-12-01

    Ovarian and uterine transplantation are procedures gaining more attention again because of potential applications in respectively fertility preservation for cancer and other patients and, more tentatively, women with uterine agenesis or hysterectomy. Cryopreservation of tissue slices, and possibly whole organs, is providing opportunities for banking ovaries for indefinite periods before transplanting them back to restore fertility. The natural plasticity of this organ facilitates grafting to different sites where they can be revascularized and rapidly restore the normal physiology of secretion and ovulation. Ischemic damage is a chief limitation because many follicles are lost, at least in avascular grafts, and functional longevity is reduced. Nevertheless, grafts of young ovarian tissue, even after cryopreservation, can be highly fertile in laboratory rodents and, in humans, autografts have functioned for up to 3 years before needing replacement. Transplantation by vascular anastomosis provides potentially longer function but it is technically much more demanding and riskier for the recipient. It is the only practicable method with the uterus, and has enabled successful pregnancies in several species, but not yet in humans. Contrary to claims made many years ago, neither organ is privileged immunologically, and allografts become rapidly rejected except in hosts whose immune system is deficient or suppressed pharmacologically. All in all, transplantation of these organs, especially the ovary, provides a broad platform of opportunities for research and new applications in reproductive medicine and conservation biology.

  17. Central interaction between physostigmine and histamine during yawning in rats.

    PubMed

    Tamaddonfard, Esmaeal; Soraya, Hamid; Hamzeh-Gooshchi, Nasrin

    2008-01-01

    In this study, the effects of intraperitoneal (ip) injection of physostigmine, subcutaneous (sc) injection of atropine, and intracerebroventricular (icv) injections of histamine, chlorpheniramine (H(1)-receptor antagonist), and ranitidine (H(2)-receptor antagonist) in separate and combined treatments were investigated during yawning in rats. Physostigmine at a dose of 0.25 mg/kg produced the highest number of yawns. Atropine, used alone, was without effect, but physostigmine (0.25 mg/kg, ip)-induced yawning was blocked by pretreatment with atropine (1 mg/kg, sc). Histamine at the doses of 10, 20 and 40 microg produced yawning. Chlorpheniramine and ranitidine, used alone, had no effect, whereas pretreatments with chlorpheniramine and ranitidine at the same dose of 80 microg prevented histamine (40 microg, icv)-induced yawning. The suppressive effect of chlorpheniramine was more than that of ranitidine. Histamine (10 and 40 microg, icv) enhanced, whereas chlorpheniramine and ranitidine at the same dose of 80 microg suppressed, physostigmine (0.25 mg/kg, ip)-induced yawning. Atropine (1 mg/kg, sc) not only suppressed histamine-induced yawning, but also enhanced the inhibitory effect of chlorpheniramine, but not of ranitidine on yawning induced by histamine. These results indicate that muscarinic receptors mediate yawning induced by physostigmine. Histamine central H(1), and to a lesser extent H(2) receptors, may be involved in histamine-induced yawning. Cholinergic muscarinic receptors, as well as histaminergic H(1) and to a lesser extent H(2) receptors, may lso be involved in the interaction between brain acetylcholine and histamine.

  18. Thyroid Hormone-Carbohydrate Interaction in the Rat

    PubMed Central

    Forciea, Mary Ann; Schwartz, Harold L.; Towle, Howard C.; Mariash, Cary N.; Kaiser, F. E.; Oppenheimer, J. H.

    1981-01-01

    Previous studies from this laboratory have demonstrated an age-related decrease in hepatic malic enzyme (ME) levels and in the response of ME to triiodo-l-thyronine (T3). Moreover, we have recently shown a synergistic interaction of T3 and a high carbohydrate diet in the induction of this enzyme. Studies were therefore undertaken to assess the response of aging rats to a high carbohydrate diet and to test the effect of such dietary manipulations on the responsiveness of ME to T3. For this purpose, a new radio-immunoassay for ME was developed that, because of a 10-fold higher sensitivity, was particularly suited to the measurement of the low concentrations of hepatic enzyme in older animals. The level of ME per milligram of DNA fell ∼70% between 1 and 6 mo with only minor further changes demonstrated between 6 and 18 mo. In contrast, the level of ME per milligram DNA in brain was slightly increased in the older animals. Although the absolute increment of hepatic ME resulting from seven daily injections of T3 (15 μg/100 g body wt) fell with age, the ratio of the ME content per milligram DNA to that observed in control animals maintained on a regular chow diet remained relatively constant with an average value of 11.1. The responsivity of hepatic ME to a high carbohydrate, fat-free diet also decreased with age and could not be attributed exclusively to a reduction in food consumption. The age-related reduction in ME responsivity to dietary stimuli appeared to be due to a reduction in the formation of the specific messenger, (m)RNA for ME as determined in an in vitro translational assay. Our data are consistent with the following hypothesis. There is an age-related decreased hepatic responsivity to a high carbohydrate dietary stimulus. Thyroid hormone administration, as previously postulated by us, interacts with a product or an intermediate of carbohydrate metabolism in a multiplicative fashion. As a consequence, the absolute increment of ME induced by T3

  19. Regulatory effect of hypoxia-inducible factor-1α on hCG-stimulated endothelin-2 expression in granulosa cells from the PMSG-treated rat ovary.

    PubMed

    Zhang, Jisen; Zhang, Zhenghong; Wu, Yanqing; Chen, Liyun; Luo, Qianping; Chen, Jiajie; Huang, Xiaohong; Cheng, Yong; Wang, Zhengchao

    2012-01-01

    Endothelin (ET)-2 plays a crucial role in ovarian ovulation in mammals. The present study was designed to test the hypothesis that hypoxia-inducible factor (HIF)-1α-mediated transcriptional activation contributes to the increased expression of ET-2 gene in response to hCG in rat ovarian granulosa cells (GCs) during gonadotropin-induced superovulation. By real-time RT-PCR analysis, ET-2 mRNA expression was found to significantly increase in cultured ovarian GCs after treatment with hCG, or even N-carbobenzoxyl-L-leucinyl-L-leucinyl-L-norvalinal (MG-132), while this increased ET-2 mRNA expression could also be blocked by ferrous ammonium sulfate (FAS) under human chorionic gonadotropin (hCG) treatment. Further analysis also found that these changes of ET-2 mRNA were consistent with HIF-1α expression or HIF-1 activity, and HIF-1α inhibitor echinomycin inhibited ovulation in rats. Taken together, these results indicate that ET-2 is transcriptionally activated by hCG through HIF-1α-mediated mechanism in GCs. This HIF-1α-induced transcriptional activation may be one of the important mechanisms mediating the increase of ET-2 expression in GCs during the gonadotropin-induced mammalian ovulatory process in vivo.

  20. Conditioned place preference for social interaction in rats: contribution of sensory components.

    PubMed

    Kummer, Kai; Klement, Sabine; Eggart, Vincent; Mayr, Michael J; Saria, Alois; Zernig, Gerald

    2011-01-01

    A main challenge in the therapy of drug dependent individuals is to help them reactivate interest in non-drug-associated activities. We previously developed a rat experimental model based on the conditioned place preference (CPP) paradigm in which only four 15-min episodes of social interaction with a gender- and weight-matched male Sprague Dawley rat (1) reversed CPP from cocaine to social interaction despite continuing cocaine training and (2) prevented the reinstatement of cocaine CPP. In the present study, we investigated which of the sensory modalities of the composite stimulus "social interaction" contributes most to the rats' preference for it. If touch was limited by steel bars spaced at a distance of 2 cm and running across the whole length of a partitioning, CPP was still acquired, albeit to a lesser degree. If both rats were placed on the same side of a partitioning, rats did not develop CPP for social interaction. Thus, decreasing the available area for social interaction from 750 to 375 cm(2) prevented the acquisition of CPP to social interaction despite the fact that animals could touch each other more intensely than through the bars of the partitioning. When touch was fully restricted by a glass screen dividing the conditioning chambers, and the only sensory modalities left were visual and olfactory cues, place preference shifted to place aversion. Overall, our findings indicate that the major rewarding sensory component of the composite stimulus "social interaction" is touch (taction).

  1. Polycystic ovary syndrome.

    PubMed

    Homburg, Roy

    2008-04-01

    Polycystic ovary syndrome (PCOS) is the most common female endocrinopathy, affecting 5-10% of the female population. It involves overproduction of ovarian androgens leading to a heterogeneous range of symptoms including hirsutism, acne, anovulation and infertility. Hyperinsulinaemia, exacerbated by obesity, is often a key feature. Treatment depends on the presenting symptoms, which may often be ameliorated by weight loss where relevant. Anti-androgen preparations are used for hyperandrogenic symptoms, and clomiphene citrate (CC) is the first-line treatment for anovulation and infertility. Aromatase inhibitors are being investigated as an alternative to CC. Failure to conceive with CC can be treated in a number of ways, including the addition of insulin-lowering agents (mainly metformin), low-dose gonadotrophin therapy or surgically by laparoscopic ovarian drilling. Although the exact aetiology of PCOS is not known, the therapeutic alternatives provide reasonably successful symptomatic treatment.

  2. Soy but not Bisphenol A (BPA) Induces Hallmarks of Polycystic Ovary Syndrome (PCOS) and Related Metabolic co-Morbidities in Rats

    PubMed Central

    Patisaul, Heather B.; Mabrey, Natalie; Adewale, Heather B.; Sullivan, Alana W.

    2014-01-01

    Polycystic ovarian syndrome (PCOS) is the most common female endocrine disorder with a prevalence as high as 8–15% depending on ethnicity and the diagnostic criteria employed. The basic pathophysiology and mode of inheritance remain unclear, but environmental factors such as diet, stress and chemical exposures are thought to be contributory. Developmental exposure to endocrine disrupting compounds (EDCs) have been hypothesized to exacerbate risk, in part because PCOS hallmarks and associated metabolic co-morbidities can be reliably induced in animal models by perinatal androgen exposure. Here we show that lifetime exposure to a soy diet, containing endocrine active phytoestrogens, but not developmental exposure (gestational day 6 – lactational day 40) to the endocrine disrupting monomer Bisphenol A (BPA), can induce key features of PCOS in the rat; results which support the hypothesis that hormonally active diets may contribute to risk when consumed throughout gestation and post-natal life. PMID:25242113

  3. Brown adipose tissue transplantation ameliorates polycystic ovary syndrome

    PubMed Central

    Yuan, Xiaoxue; Hu, Tao; Zhao, Han; Huang, Yuanyuan; Ye, Rongcai; Lin, Jun; Zhang, Chuanhai; Zhang, Hanlin; Wei, Gang; Zhou, Huiqiao; Dong, Meng; Zhao, Jun; Wang, Haibin; Liu, Qingsong; Lee, Hyuek Jong; Jin, Wanzhu; Chen, Zi-Jiang

    2016-01-01

    Polycystic ovary syndrome (PCOS), which is characterized by anovulation, hyperandrogenism, and polycystic ovaries, is a complex endocrinopathy. Because the cause of PCOS at the molecular level is largely unknown, there is no cure or specific treatment for PCOS. Here, we show that transplantation of brown adipose tissue (BAT) reversed anovulation, hyperandrogenism, and polycystic ovaries in a dehydroepiandrosterone (DHEA)-induced PCOS rat. BAT transplantation into a PCOS rat significantly stabilized menstrual irregularity and improved systemic insulin sensitivity up to a normal level, which was not shown in a sham-operated or muscle-transplanted PCOS rat. Moreover, BAT transplantation, not sham operation or muscle transplantation, surprisingly improved fertility in PCOS rats. Interestingly, BAT transplantation activated endogenous BAT and thereby increased the circulating level of adiponectin, which plays a prominent role in whole-body energy metabolism and ovarian physiology. Consistent with BAT transplantation, administration of adiponectin protein dramatically rescued DHEA-induced PCOS phenotypes. These results highlight that endogenous BAT activity is closely related to the development of PCOS phenotypes and that BAT activation might be a promising therapeutic option for the treatment of PCOS. PMID:26903641

  4. Progesterone Regulation of Primordial Follicle Assembly In Bovine Fetal Ovaries

    PubMed Central

    Nilsson, Eric E.; Skinner, Michael K.

    2009-01-01

    Fertility in mammals is dependant on females having an adequate primordial follicle pool to supply oocytes for fertilization. The formation of primordial follicles is called ovarian follicular assembly. In rats and mice progesterone and estradiol have been shown to inhibit follicle assembly with assembly occurring after birth when the pups are removed from the high-steroid maternal environment. In contrast, primordial follicle assembly in other species, such as cattle and humans, occurs during fetal development before birth. The objective of the current study is to determine if progesterone levels regulate primordial follicle assembly in fetal bovine ovaries. Ovaries and blood were collected from bovine fetuses. Interestingly, ovarian progesterone and estradiol concentrations were found to decrease with increasing fetal age and correlated to increased primordial follicle assembly. Microarray analysis of fetal ovary RNA suggests that progesterone membrane receptor and estrogen nuclear receptor are expressed. Treatment of fetal bovine ovary cultures with a higher progesterone concentration significantly decreased primordial follicle assembly. Observations indicate that progesterone affects ovarian primordial follicle assembly in cattle, as it does in rats and mice. PMID:19747959

  5. Cannabidiol reverses the reduction in social interaction produced by low dose Delta(9)-tetrahydrocannabinol in rats.

    PubMed

    Malone, Daniel Thomas; Jongejan, Dennis; Taylor, David Alan

    2009-08-01

    While Delta(9)-tetrahydrocannabinol (THC) is the main psychoactive constituent of the cannabis plant, a non-psychoactive constituent is cannabidiol (CBD). CBD has been implicated as a potential treatment of a number of disorders including schizophrenia and epilepsy and has been included with THC in a 1:1 combination for the treatment of conditions such as neuropathic pain. This study investigated the effect of THC and CBD, alone or in combination, on some objective behaviours of rats in the open field. Pairs of rats were injected with CBD or vehicle followed by THC or vehicle and behaviour in the open field was assessed for 10 min. In vehicle pretreated rats THC (1 mg/kg) significantly reduced social interaction between rat pairs. Treatment with CBD had no significant effect alone, but pretreatment with CBD (20 mg/kg) reversed the THC-induced decreases in social interaction. A higher dose of THC (10 mg/kg) produced no significant effect on social interaction. However, the combination of high dose CBD and high dose THC significantly reduced social interaction between rat pairs, as well as producing a significant decrease in locomotor activity. This data suggests that CBD can reverse social withdrawal induced by low dose THC, but the combination of high dose THC and CBD impairs social interaction, possibly by decreasing locomotor activity.

  6. Age-related audiovisual interactions in the superior colliculus of the rat.

    PubMed

    Costa, M; Piché, M; Lepore, F; Guillemot, J-P

    2016-04-21

    It is well established that multisensory integration is a functional characteristic of the superior colliculus that disambiguates external stimuli and therefore reduces the reaction times toward simple audiovisual targets in space. However, in a condition where a complex audiovisual stimulus is used, such as the optical flow in the presence of modulated audio signals, little is known about the processing of the multisensory integration in the superior colliculus. Furthermore, since visual and auditory deficits constitute hallmark signs during aging, we sought to gain some insight on whether audiovisual processes in the superior colliculus are altered with age. Extracellular single-unit recordings were conducted in the superior colliculus of anesthetized Sprague-Dawley adult (10-12 months) and aged (21-22 months) rats. Looming circular concentric sinusoidal (CCS) gratings were presented alone and in the presence of sinusoidally amplitude modulated white noise. In both groups of rats, two different audiovisual response interactions were encountered in the spatial domain: superadditive, and suppressive. In contrast, additive audiovisual interactions were found only in adult rats. Hence, superior colliculus audiovisual interactions were more numerous in adult rats (38%) than in aged rats (8%). These results suggest that intersensory interactions in the superior colliculus play an essential role in space processing toward audiovisual moving objects during self-motion. Moreover, aging has a deleterious effect on complex audiovisual interactions. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  7. Social interaction reward decreases p38 activation in the nucleus accumbens shell of rats.

    PubMed

    Salti, Ahmad; Kummer, Kai K; Sadangi, Chinmaya; Dechant, Georg; Saria, Alois; El Rawas, Rana

    2015-12-01

    We have previously shown that animals acquired robust conditioned place preference (CPP) to either social interaction alone or cocaine alone. Recently it has been reported that drugs of abuse abnormally activated p38, a member of mitogen-activated protein kinase family, in the nucleus accumbens. In this study, we aimed to investigate the expression of the activated form of p38 (pp38) in the nucleus accumbens shell and core of rats expressing either cocaine CPP or social interaction CPP 1 h, 2 h and 24 h after the CPP test. We hypothesized that cocaine CPP will increase pp38 in the nucleus accumbens shell/core as compared to social interaction CPP. Surprisingly, we found that 24 h after social interaction CPP, pp38 neuronal levels were decreased in the nucleus accumbens shell to the level of naïve rats. Control saline rats that received saline in both compartments of the CPP apparatus and cocaine CPP rats showed similar enhanced p38 activation as compared to naïve and social interaction CPP rats. We also found that the percentage of neurons expressing dopaminergic receptor D2R and pp38 was also decreased in the shell of the nucleus accumbens of social interaction CPP rats as compared to controls. Given the emerging role of p38 in stress/anxiety behaviors, these results suggest that (1) social interaction reward has anti-stress effects; (2) cocaine conditioning per se does not affect p38 activation and that (3) marginal stress is sufficient to induce p38 activation in the shell of the nucleus accumbens.

  8. Social interaction reward decreases p38 activation in the nucleus accumbens shell of rats

    PubMed Central

    Salti, Ahmad; Kummer, Kai K.; Sadangi, Chinmaya; Dechant, Georg; Saria, Alois; El Rawas, Rana

    2016-01-01

    We have previously shown that animals acquired robust conditioned place preference (CPP) to either social interaction alone or cocaine alone. Recently it has been reported that drugs of abuse abnormally activated p38, a member of mitogen-activated protein kinase family, in the nucleus accumbens. In this study, we aimed to investigate the expression of the activated form of p38 (pp38) in the nucleus accumbens shell and core of rats expressing either cocaine CPP or social interaction CPP 1 h, 2 h and 24 h after the CPP test. We hypothesized that cocaine CPP will increase pp38 in the nucleus accumbens shell/core as compared to social interaction CPP. Surprisingly, we found that 24 h after social interaction CPP, pp38 neuronal levels were decreased in the nucleus accumbens shell to the level of naïve rats. Control saline rats that received saline in both compartments of the CPP apparatus and cocaine CPP rats showed similar enhanced p38 activation as compared to naïve and social interaction CPP rats. We also found that the percentage of neurons expressing dopaminergic receptor D2R and pp38 was also decreased in the shell of the nucleus accumbens of social interaction CPP rats as compared to controls. Given the emerging role of p38 in stress/anxiety behaviors, these results suggest that (1) social interaction reward has anti-stress effects; (2) cocaine conditioning per se does not affect p38 activation and that (3) marginal stress is sufficient to induce p38 activation in the shell of the nucleus accumbens. PMID:26300300

  9. Assessment of pharmacokinetic interaction of spirulina with glitazone in a type 2 diabetes rat model.

    PubMed

    Gupta, Annu; Nair, Anroop; Kumria, Rachna; Al-Dhubiab, Bandar-E; Chattopadhyaya, Ipshita; Gupta, Sumeet

    2013-12-01

    The objective of the current study was to assess the possible pharmacokinetic interactions of spirulina with glitazones in an insulin resistance rat model. Wistar male albino rats were equally divided into five groups: insulin resistant rats+spirulina (500 mg/kg)+pioglitazone (10 mg/kg), insulin resistant rats+pioglitazone (10 mg/kg), insulin resistant rats+spirulina (500 mg/kg)+rosiglitazone (10 mg/kg), insulin resistant rats+rosiglitazone (10 mg/kg), and insulin resistant rats+spirulina (500 mg/kg). Described doses of pioglitazone, rosiglitazone, or spirulina were per orally administered and the plasma drug concentrations were determined. The pharmacokinetic parameters such as Tmax, Cmax, AUC(0-α), t1/2, and Kel were determined by plotting the drug concentration as a function of time. The data observed in this acute study indicated that there was no statistically significant difference in any of the pharmacokinetic parameters (Tmax, Cmax, AUC(0-α), t1/2, and Kel) of glitazones (pioglitazone, rosiglitazone) or spirulina, when they were coadministered. Given the promising results, this study concludes that the coadministration of spirulina does not influence the pharmacokinetics of glitazones in a type 2 diabetes rat model. Further chronic in vivo studies are recommended to assess the real time effect.

  10. Interactions between deliberation and delay-discounting in rats

    PubMed Central

    Papale, Andrew E.; Stott, Jeffrey J.; Powell, Nathaniel J.; Regier, Paul S.

    2013-01-01

    When faced with decisions, rats sometimes pause and look back and forth between possible alternatives, a phenomenon termed vicarious trial and error (VTE). When it was first observed in the 1930s, VTE was theorized to be a mechanism for exploration. Later theories suggested that VTE aided the resolution of sensory or neuroeconomic conflict. In contrast, recent neurophysiological data suggest that VTE reflects a dynamic search and evaluation process. These theories make unique predictions about the timing of VTE on behavioral tasks. We tested these theories of VTE on a T-maze with return rails, where rats were given a choice between a smaller reward available after one delay or a larger reward available after an adjustable delay. Rats showed three clear phases of behavior on this task: investigation, characterized by discovery of task parameters; titration, characterized by iterative adjustment of the delay to a preferred interval; and exploitation, characterized by alternation to hold the delay at the preferred interval. We found that VTE events occurred during adjustment laps more often than during alternation laps. Results were incompatible with theories of VTE as an exploratory behavior, as reflecting sensory conflict, or as a simple neuroeconomic valuation process. Instead, our results were most consistent with VTE as reflecting a search process during deliberative decision making. This pattern of VTE that we observed is reminiscent of current navigational theories proposing a transition from a deliberative to a habitual decision-making mechanism. PMID:22588853

  11. Interaction of physical trainings and coffee intakes in fuel utilization during exercise in rats

    PubMed Central

    Choi, Eun-Young

    2013-01-01

    This study investigates the impact of exercises, coffee intakes, and physical trainings on fuel utilization in rats. Ninety-six rats were fed a control diet with either water (C) or coffee (CF; 0.12 g freeze-dried instant coffee/100 g body weight/d). Additionally, the animals go through physical training (TC and TCF) or no training (NTC and NTCF) for 4 weeks. For physical training, animals have to exercise on treadmills for 30 minutes (5 d per week, 15° incline, 0.5-0.8 km/h). At the end of week 4, the animals in each group were subdivided into three exercise groups: before exercise (BE), during exercise (DE), and after exercise (AE). The DE rats exercised on treadmills for 1 hour immediately before being sacrificed. Hemoglobin, hematocrit, glucose, glycogen, protein, triglyceride (TG), and free fatty acid (FFA) levels in the plasma, liver, and skeletal muscle of the rats were compared accordingly. Organ weights were also measured. Coffee-training interaction had a significant impact on heart weight, visceral fat, hemoglobin, hematocrit, liver glycogen in DE and AE, and liver triglyceride in DE and AE. Exercise (meaning exercised on a treadmill for 1 hour immediately before being sacrificed) training interaction was significant in liver glycogen, muscle glycogen in control diet and control diet with coffee, FFA and muscle TG levels at control diet with coffee group. Exercise-coffee interactions significantly influenced the FFA with no training groups. Exercise-coffee-training interaction significantly effects on FFA, Liver TG and Muscle TG. Coffee intakes can increase lipolysis during exercising but coffee consumptions delay the recovery of liver glycogen levels in trained rats after exercising. Coffee intakes can increase lipolysis during exercising but coffee consumptions delay the recovery of liver glycogen levels in trained rats after exercising. Coffee can be an effective ergogenic aid during exercise for physically trained rats. PMID:23766878

  12. Social isolation increases aggressive behaviour and alters the effects of diazepam in the rat social interaction test.

    PubMed

    Wongwitdecha, N; Marsden, C A

    1996-02-01

    Isolation rearing in the early stages of life has been shown to modify a variety of behaviours in many animals and the responsitivity to psychotropic drugs. The aims of the present study were to investigate the effects of isolation rearing on anxiety using the social interaction paradigm and to compare the effects of diazepam on social interaction behaviours in isolation and socially reared rats. Male Lister hooded rats were reared from weaning either alone (isolation reared) or in groups of four (socially reared) for 6 weeks and then were tested for social interaction. Both isolation and socially reared rats were exposed to the social interaction test either without drug treatment or following saline or diazepam (1 and 2.5 mg/kg, i.p., 30 min before testing). The results demonstrate that under high light in an unfamiliar arena, the isolation compared to the socially reared rats showed a significantly (P < 0.01) higher level of social interaction, manifested as increases in aggressive and avoidance behaviours, and that this interaction occur for a greater length of time during the test period (10 min). However, when the light level was decreased or when the arena was familiar, active social interaction of isolation reared rats decreased but increased in the socially reared rats. In both conditions the isolation reared rats displayed more aggressive behaviours, in particular biting and boxing the partners which did not occur with the socially reared rats. Pretreatment of diazepam (1 and 2.5 mg/kg., i.p.) caused a dose-related reduction in aggressive behaviours in rats reared under both conditions but increased passive interactions in the socially reared rats. In contrast diazepam (2.5 mg/kg) reduced active interaction in the isolation reared rats but had no effect on passive interaction. These results indicate that isolation rearing increases aggressive behaviours and alters the effects of diazepam.

  13. Interactions between Kisspeptin Neurons and Hypothalamic Tuberoinfundibular Dopaminergic Neurons in Aged Female Rats

    PubMed Central

    Iwata, Kinuyo; Ikehara, Masaaki; Kunimura, Yuyu; Ozawa, Hitoshi

    2016-01-01

    Kisspeptin neurons in the arcuate nucleus (ARC) regulate prolactin secretion, and are in physical contact with tuberoinfundibular dopaminergic (TIDA) neurons, which inhibit prolactin secretion. Prolactin levels in the blood are increased with advancing age in rats; therefore, we investigated the interactions with TIDA neurons and kisspeptin neurons in aged female rats (24 months of age), relative to those of young adult female rats (9–10 weeks of age). Plasma prolactin levels in the aged rats were significantly higher than those of young adult rats. Tyrosine hydroxylase (TH)-immunoreactive (ir) cell bodies and kisspeptin-ir nerve fibers were found in the dorsomedial ARC of both groups. The number of TH-ir cell bodies in the dorsomedial ARC did not differ significantly between groups. Additionally, no significant differences in the number of TH-ir cells in contact with kisspeptin-ir fibers was observed between groups. However, the number of kisspeptin-ir or Kiss1 mRNA-expressing cells in the ARC was significantly reduced in the aged rats compared with that of the young rats. These results suggest that the contacts between TIDA neurons and kisspeptin neurons are maintained after reproductive senescence, while production of kisspeptin in the ARC decreases significantly during aging. PMID:28127107

  14. Interaction between isolation rearing and social development on exploratory behavior in male rats.

    PubMed

    Arakawa, Hiroyuki

    2005-11-01

    The effect of isolation on exploratory behavior has been shown to differ depending on the developmental stages of male rats. However, there has been little systematic comparison of the frequencies and the patterns of exploratory behavior across the developmental stages. The present study assessed the frequencies of exploration using the emergence test and exploratory patterns in the open-field test in three developmental stages of male rats: juvenile, post-puberty, and adult. A lower propensity for exploration was observed in rats isolated during the juvenile stage, as assessed by increased latency and decreased duration of exploratory behaviors compared to pair-reared rats, and this tendency was maintained in adulthood. Altered patterns of exploratory behavior were demonstrated both in rats isolated in adulthood, who showed an increased active pattern, and those pair-reared following puberty, who shifted to a more passive pattern. However, rats isolated during the juvenile stage did not change their exploratory patterns following puberty. These results suggest that the changes in the exploratory pattern, which can be observed in adulthood, are associated with the emergence of adult-like dominance relationships. Juvenile-isolated rats did not show these changes following puberty, suggesting the importance of social interaction as juveniles for the ontogenetic emergence of behavioral flexibility implicated in the regulation of exploratory patterns.

  15. Sexual interactions with unfamiliar females reduce hippocampal neurogenesis among adult male rats.

    PubMed

    Spritzer, M D; Curtis, M G; DeLoach, J P; Maher, J; Shulman, L M

    2016-03-24

    Recent experiments have shown that sexual interactions prior to cell proliferation cause an increase in neurogenesis in adult male rats. Because adult neurogenesis is critical for some forms of memory, we hypothesized that sexually induced changes in neurogenesis may be involved in mate recognition. Sexually naive adult male rats were either exposed repeatedly to the same sexual partner (familiar group) or to a series of novel sexual partners (unfamiliar group), while control males never engaged in sexual interactions. Ovariectomized female rats were induced into estrus every four days. Males were given two injections of 5-bromo-2'-deoxyuridine (BrdU) (200mg/kg) to label proliferating cells, and the first sexual interactions occurred three days later. Males in the familiar and unfamiliar groups engaged in four, 30-min sexual interactions at four-day intervals, and brain tissue was collected the day after the last sexual interaction. Immunohistochemistry followed by microscopy was used to quantify BrdU-labeled cells. Sexual interactions with unfamiliar females caused a significant reduction in neurogenesis in the dentate gyrus compared to males that interacted with familiar females and compared to the control group. The familiar group showed no difference in neurogenesis compared to the control group. Males in the familiar group engaged in significantly more sexual behavior (ejaculations and intromissions) than did males in the unfamiliar group, suggesting that level of sexual activity may influence neurogenesis levels. In a second experiment, we tested whether this effect was unique to sexual interactions by replicating the entire procedure using anestrus females. We found that interactions with unfamiliar anestrus females reduced neurogenesis relative to the other groups, but this effect was not statistically significant. In combination, these results indicate that interactions with unfamiliar females reduce adult neurogenesis and the effect is stronger for sexual

  16. SEXUAL INTERACTIONS WITH UNFAMILIAR FEMALES REDUCE HIPPOCAMPAL NEUROGENESIS AMONG ADULT MALE RATS

    PubMed Central

    Spritzer, Mark D.; Curtis, Molly G.; DeLoach, Julia P.; Maher, Jack; Shulman, Leanne M.

    2016-01-01

    Recent experiments have shown that sexual interactions prior to cell proliferation cause an increase in neurogenesis in adult male rats. Because adult neurogenesis is critical for some forms of memory, we hypothesized that sexually induced changes in neurogenesis may be involved in mate recognition. Sexually naive adult male rats were either exposed repeatedly to the same sexual partner (familiar group) or to a series of novel sexual partners (unfamiliar group), while control males never engaged in sexual interactions. Ovariectomized female rats were induced into estrus every four days. Males were given two injections of BrdU (200 mg/kg) to label proliferating cells, and the first sexual interactions occurred three days later. Males in the familiar and unfamiliar groups engaged in four, 30 min sexual interactions at four-day intervals, and brain tissue was collected the day after the last sexual interaction. Immunohisotchemistry followed by microscopy was used to quantify BrdU-labeled cells. Sexual interactions with unfamiliar females caused a significant reduction in neurogenesis in the dentate gyrus compared to males that interacted with familiar females and compared to the control group. The familiar group showed no difference in neurogenesis compared to the control group. There were no differences in the amount of sexual behavior (mounts, intromissions, ejaculations, or contact time) that the familiar and unfamiliar groups engaged in, indicating that the differences in neurogenesis were not due to the relative amounts of sexual activity. In a second experiment, we tested whether this effect was unique to sexual interactions by replicating the entire procedure using anestrus females. We found that interactions with unfamiliar anestrus females reduced neurogenesis relative to the other groups, but this effect was not statistically significant. In combination, these results indicate that interactions with unfamiliar females reduce adult neurogenesis and the effect

  17. Ring-Oxidative Biotransformation and Drug Interactions of Propofol in the Livers of Rats

    PubMed Central

    Tai, Yu-Ting; Lin, Yi-Ling; Chang, Chia-Chen; Cherng, Yih-Giun; Don, Ming-Jaw; Chen, Ruei-Ming

    2015-01-01

    Propofol, an intravenous anesthetic agent, is widely used for inducing and maintaining anesthesia during surgical procedures and for sedating intensive care unit patients. In the clinic, rapid elimination is one of the major advantages of propofol. Meanwhile, the biotransformation and drug interactions of propofol in rat livers are still little known. In this study, we evaluated the ring-oxidative metabolism of propofol in phenobarbital-treated rat livers and possible drug interactions. Administration of phenobarbital to male Wistar rats significantly increased levels of hepatic cytochrome P450 (CYP) 2B1/2 and microsomal pentoxyresorufin O-dealkylase (PROD) activity. Analyses by high-performance liquid chromatography and liquid chromatography mass spectroscopy revealed that propofol was metabolized by phenobarbital-treated rat liver microsomes into 4-hydroxypropofol. In comparison, PROD activity and 4-hydroxy-propofol production from propofol metabolism were suppressed by orphenodrine, an inhibitor of CYP2B1/2, and a polyclonal antibody against rat CYP2B1/2 protein. Furthermore, exposure of rats to propofol did not affect the basal or phenobarbital-enhanced levels of hepatic CYP2B1/2 protein. Meanwhile, propofol decreased the dealkylation of pentoxyresorufin by phenobarbital-treated rat liver microsomes in a concentration-dependent manner. Taken together, this study shows that rat hepatic CYP2B1/2 plays a critical role in the ring-oxidative metabolism of propofol into 4-hydroxypropofol, and this anesthetic agent can inhibit CYP2B1/2 activity without affecting protein synthesis. PMID:25710017

  18. Positive interactions between desert granivores: localized facilitation of harvester ants by kangaroo rats.

    PubMed

    Edelman, Andrew J

    2012-01-01

    Facilitation, when one species enhances the environment or performance of another species, can be highly localized in space. While facilitation in plant communities has been intensely studied, the role of facilitation in shaping animal communities is less well understood. In the Chihuahuan Desert, both kangaroo rats and harvester ants depend on the abundant seeds of annual plants. Kangaroo rats, however, are hypothesized to facilitate harvester ants through soil disturbance and selective seed predation rather than competing with them. I used a spatially explicit approach to examine whether a positive or negative interaction exists between banner-tailed kangaroo rat (Dipodomys spectabilis) mounds and rough harvester ant (Pogonomyrmex rugosus) colonies. The presence of a scale-dependent interaction between mounds and colonies was tested by comparing fitted spatial point process models with and without interspecific effects. Also, the effect of proximity to a mound on colony mortality and spatial patterns of surviving colonies was examined. The spatial pattern of kangaroo rat mounds and harvester ant colonies was consistent with a positive interspecific interaction at small scales (<10 m). Mortality risk of vulnerable, recently founded harvester ant colonies was lower when located close to a kangaroo rat mound and proximity to a mound partly predicted the spatial pattern of surviving colonies. My findings support localized facilitation of harvester ants by kangaroo rats, likely mediated through ecosystem engineering and foraging effects on plant cover and composition. The scale-dependent effect of kangaroo rats on abiotic and biotic factors appears to result in greater founding and survivorship of young colonies near mounds. These results suggest that soil disturbance and foraging by rodents can have subtle impacts on the distribution and demography of other species.

  19. Neurofibromin interacts with CRMP-2 and CRMP-4 in rat brain

    SciTech Connect

    Lin, Y.-L.; Hsueh, Y.-P.

    2008-05-02

    Neurofibromin, encoded by the neurofibromatosis type 1 (NF1) gene, regulates the Ras and cAMP pathways and plays a role in proliferation and neuronal morphogenesis. The details of the molecular mechanism of neurofibromin action in these processes are still unclear. In this study, immunoprecipitation and proteomics were used to identify novel proteins from rat brain that interact with neurofibromin. Mass spectrometry analysis showed that two proteins, the collapsin response mediator protein-2 (CRMP-2) and propionyl-CoA carboxylase alpha chain (PCCA), associated with neurofibromin. Immunoprecipitation-immunoblotting analysis confirmed the interactions between neurofibromin and CRMP-2 and CRMP-4, but not CRMP-1, in rat brain. CDK5, a kinase that regulates CRMP-2 in axonal outgrowth, was required for the interaction between neurofibromin and CRMP-2. Since both neurofibromin and CRMP proteins are involved in proliferation and axonal morphogenesis, these results suggest that the interaction with CRMPs contributes to the function of neurofibromin in tumorigenesis and neuronal morphogenesis.

  20. Protein-DNA interactions at the major and minor promoters of the divergently transcribed dhfr and rep3 genes during the Chinese hamster ovary cell cycle.

    PubMed Central

    Wells, J; Held, P; Illenye, S; Heintz, N H

    1996-01-01

    In mammals, two TATA-less bidirectional promoters regulate expression of the divergently transcribed dihydrofolate reductase (dhfr) and rep3 genes. In CHOC 400 cells, dhfr mRNA levels increase about fourfold during the G1-to-S phase transition of the cell cycle, whereas the levels of rep3 transcripts vary less than twofold during this time. To assess the role of DNA-binding proteins in transcriptional regulation of the dhfr and rep3 genes, the major and minor dhfr-rep3 promoter regions were analyzed by high-resolution genomic footprinting during the cell cycle. At the major dhfr promoter, prominent DNase I footprints over four upstream Sp1 binding sites did not vary throughout G1 and entry into the S phase. Genomic footprinting revealed that a protein is constitutively bound to the overlapping E2F sites throughout the G1-to-S phase transition, an interaction that is most evident on the transcribed template strand. On the nontranscribed strand, multiple changes in the DNase I cleavage pattern are observed during transit through G1 and entry into the S phase. By using gel mobility shift assays and a series of sequence-specific probes, two different species of E2F were shown to interact with the dhfr promoter during the cell cycle. The DNA binding activity of one E2F species, which preferentially recognizes the sequence TTTGGCGC, did not vary significantly during the cell cycle. The DNA binding activity of the second E2F species, which preferentially recognizes the sequence TTTCGCGC, increased during the G1-to-S phase transition. Together, these results indicate that Sp1 and the species of E2F that binds TTTGGCGC participate in the formation of a basal transcription complex, while the species of E2F that binds TTTCGCGC regulates dhfr gene expression during the G1-to-S phase transition. At the minor promoter, DNase I footprints at a consensus c-Myc binding site and three Sp1 binding sites showed little variation during the G1-to-S phase transition. In addition to

  1. Isolation of monoclonal antibody from a Chinese hamster ovary supernatant. II: dynamics of the integrated separation on ion exchange and hydrophobic interaction chromatography media.

    PubMed

    Marek, Wojciech; Muca, Renata; Woś, Sylwia; Piątkowski, Wojciech; Antos, Dorota

    2013-08-30

    Dynamics of the purification process of a CHO derived monoclonal antibody by ion exchange chromatography (IEC), hydrophobic interaction chromatography (HIC) and their integration has been investigated. To quantify the adsorption behavior of the target protein (IgG1) and impurities contained in the supernatant, their elution course on IEC and HIC columns has been analyzed versus pH and/or the salt concentration in the mobile phase. A short-cut method has been proposed for mathematical modeling and determining underlying kinetic and thermodynamic parameters. The accuracy of the model predictions has been verified by comparing the simulated and experimental band profiles recorded in both chromatographic processes. After verification, the model was used to optimize operating conditions for the column loading and chromatographic elution in the integrated process IEC/HIC. Two alternative loading techniques based on the upstream and downstream feed dilution were taken into account in the optimization routine. In the first one the feed stream was diluted with the loading buffer prior to the column loading, while in the latter one the feed dilution was realized inside the column using the multiple-injection technique. It was shown that the downstream dilution allowed significant reduction of the contact time between the protein and the loading buffer.

  2. Association between Polycystic Ovary Syndrome and Gut Microbiota

    PubMed Central

    Guo, Yanjie; Qi, Yane; Yang, Xuefei; Zhao, Lihui; Wen, Shu; Liu, Yinhui; Tang, Li

    2016-01-01

    Polycystic ovary syndrome (PCOS) is the most frequent endocrinopathy in women of reproductive age. It is difficult to treat PCOS because of its complex etiology and pathogenesis. Here, we characterized the roles of gut microbiota on the pathogenesis and treatments in letrozole (a nonsteroidal aromatase inhibitor) induced PCOS rat model. Changes in estrous cycles, hormonal levels, ovarian morphology and gut microbiota by PCR-DGGE and real-time PCR were determined. The results showed that PCOS rats displayed abnormal estrous cycles with increasing androgen biosynthesis and exhibited multiple large cysts with diminished granulosa layers in ovarian tissues. Meanwhile, the composition of gut microbiota in letrozole-treated rats was different from that in the controls. Lactobacillus, Ruminococcus and Clostridium were lower while Prevotella was higher in PCOS rats when compared with control rats. After treating PCOS rats with Lactobacillus and fecal microbiota transplantation (FMT) from healthy rats, it was found that the estrous cycles were improved in all 8 rats in FMT group, and in 6 of the 8 rats in Lactobacillus transplantation group with decreasing androgen biosynthesis. Their ovarian morphologies normalized. The composition of gut microbiota restored in both FMT and Lactobacillus treated groups with increasing of Lactobacillus and Clostridium, and decreasing of Prevotella. These results indicated that dysbiosis of gut microbiota was associated with the pathogenesis of PCOS. Microbiota interventions through FMT and Lactobacillus transplantation were beneficial for the treatments of PCOS rats. PMID:27093642

  3. Cryopreservation of ovaries from neonatal marmoset monkeys

    PubMed Central

    Motohashi, Hideyuki H.; Ishibashi, Hidetoshi

    2016-01-01

    The ovary of neonatal nonhuman primates contains the highest number of immature oocytes, but its cryopreservation has not yet been sufficiently investigated in all life stages. In the current study, we investigated cryodamage after vitrification/warming of neonatal ovaries from a nonhuman primate, the common marmoset (Callithrix jacchus). A Cryotop was used for cryopreservation of whole ovaries. The morphology of the vitrified/warmed ovaries was found to be equivalent to that of fresh ovaries. No significant difference in the number of oocytes retaining normal morphology per unit area in histological sections was found between the two groups. In an analysis of dispersed cells from the ovaries, however, the cell viability of the vitrified/warmed group tended to be decreased. The results of a comet assay showed no significant differences in DNA damage. These results show that cryopreservation of neonatal marmoset ovaries using vitrification may be useful as a storage system for whole ovaries. PMID:26876597

  4. NATURE OF BINDING INTERACTION OF SELECTED CHEMICALS WITH RAT ESTROGEN RECEPTORS

    EPA Science Inventory

    The US EPA is currently validating a rat uterine estrogen receptor (ER) binding assay as part of the Tier 1 Screening Battery for the Endocrine Disruptor Program. An eventual goal is to use interactive data to create computerized structure-activity models. However, more informati...

  5. NATURE OF BINDING INTERACTION OF SELECTED CHEMICALS WITH RAT ESTROGEN RECEPTORS

    EPA Science Inventory

    The US EPA is currently validating a rat uterine estrogen receptor (ER) binding assay as part of the Tier 1 Screening Battery for the Endocrine Disruptor Program. An eventual goal is to use interactive data to create computerized structure-activity models. However, more informati...

  6. Pharmacokinetic Interaction between Nevirapine and Nortriptyline in Rats: Inhibition of Nevirapine Metabolism by Nortriptyline

    PubMed Central

    Usach, Iris; Melis, Virginia; Gandía, Patricia

    2014-01-01

    One of the most frequent comorbidities of HIV infection is depression, with a lifetime prevalence of 22 to 45%. Therefore, it was decided to study a potential pharmacokinetic interaction between the nonnucleoside reverse transcriptase inhibitor nevirapine (NVP) and the tricyclic antidepressant nortriptyline (NT). NVP and NT were administered to rats either orally, intraduodenally, or intravenously, and the changes in plasma levels and pharmacokinetic parameters were analyzed. Experiments with rat and human hepatic microsomes were carried out to evaluate the inhibitory effects of NT on NVP metabolism. NVP plasma concentrations were significantly higher when this drug was coadministered with NT. The maximum plasma concentrations of NVP were increased 2 to 5 times and the total plasma clearance was decreased 7-fold in the presence of NT. However, statistically significant differences in the pharmacokinetic parameters of NT in the absence and presence of NVP were not found. In vitro studies with rat and human hepatic microsomes confirmed the inhibition of NVP hepatic metabolism by NT in a concentration-dependent way, with the inhibition being more intense in the case of rat microsomes. In conclusion, a pharmacokinetic interaction between NVP and NT was detected. This interaction was a consequence of the inhibition of hepatic metabolism of NVP by NT. In vivo human studies are required to evaluate the effects of this interaction on the pharmacokinetics of NVP before it can be taken into account for patients receiving NVP. PMID:25224004

  7. Pharmacokinetic interaction between nevirapine and nortriptyline in rats: inhibition of nevirapine metabolism by nortriptyline.

    PubMed

    Usach, Iris; Melis, Virginia; Gandía, Patricia; Peris, José-Esteban

    2014-12-01

    One of the most frequent comorbidities of HIV infection is depression, with a lifetime prevalence of 22 to 45%. Therefore, it was decided to study a potential pharmacokinetic interaction between the nonnucleoside reverse transcriptase inhibitor nevirapine (NVP) and the tricyclic antidepressant nortriptyline (NT). NVP and NT were administered to rats either orally, intraduodenally, or intravenously, and the changes in plasma levels and pharmacokinetic parameters were analyzed. Experiments with rat and human hepatic microsomes were carried out to evaluate the inhibitory effects of NT on NVP metabolism. NVP plasma concentrations were significantly higher when this drug was coadministered with NT. The maximum plasma concentrations of NVP were increased 2 to 5 times and the total plasma clearance was decreased 7-fold in the presence of NT. However, statistically significant differences in the pharmacokinetic parameters of NT in the absence and presence of NVP were not found. In vitro studies with rat and human hepatic microsomes confirmed the inhibition of NVP hepatic metabolism by NT in a concentration-dependent way, with the inhibition being more intense in the case of rat microsomes. In conclusion, a pharmacokinetic interaction between NVP and NT was detected. This interaction was a consequence of the inhibition of hepatic metabolism of NVP by NT. In vivo human studies are required to evaluate the effects of this interaction on the pharmacokinetics of NVP before it can be taken into account for patients receiving NVP.

  8. Distribution and responsiveness of rat anti-Müllerian hormone during ovarian development and VCD-induced ovotoxicity.

    PubMed

    Mark-Kappeler, Connie J; Sen, Nivedita; Keating, Aileen F; Sipes, I Glenn; Hoyer, Patricia B

    2010-11-15

    Anti-Müllerian hormone (AMH) is produced by granulosa cells in primary to small antral follicles of the adult ovary and helps maintain primordial follicles in a dormant state. The industrial chemical, 4-vinylcyclohexene diepoxide (VCD) causes specific ovotoxicity in primordial and small primary follicles of mice and rats. Previous studies suggest that this ovotoxicity involves acceleration of primordial to primary follicle recruitment via interactions with the Kit/Kit ligand signaling pathway. Because of its accepted role in inhibiting primordial follicle recruitment, the present study was designed to investigate a possible interaction between AMH and VCD-induced ovotoxicity. Protein distribution of AMH was compared in neonatal and adult F344 rat ovaries. AMH protein was visualized by immunofluorescence microscopy in large primary and secondary follicles of the adult ovary, but in small primary follicles in neonatal rat ovaries. In cultured postnatal day (PND) 4 F344 rat ovaries, VCD exposure (30 μM, 2-8 days) decreased (P<0.05) AMH mRNA (d4-8) and protein (d6-8). Recombinant AMH (100-400 mg/ml) in PND4 ovaries cultured 8 days±VCD (30 μM) caused an increase (P<0.05) in primordial, and a decrease (P<0.05) in small primary follicles, supporting that AMH retarded primordial follicle recruitment. However, no concentration of AMH had an effect on VCD-induced ovotoxicity. Whereas, VCD caused a reduction in expression of AMH (d4-d8), it followed previously reported initial disruptions in Kit signaling induced by VCD (d2). Thus, collectively, these results do not support a mechanism whereby VCD causes ovotoxicity via generalized activation of primordial follicle recruitment, but instead provide further support for the specificity of other intracellular mechanisms involved in VCD-induced ovotoxicity.

  9. Distribution and responsiveness of rat anti-Muellerian hormone during ovarian development and VCD-induced ovotoxicity

    SciTech Connect

    Mark-Kappeler, Connie J.; Sen, Nivedita; Keating, Aileen F.; Sipes, I. Glenn; Hoyer, Patricia B.

    2010-11-15

    Anti-Muellerian hormone (AMH) is produced by granulosa cells in primary to small antral follicles of the adult ovary and helps maintain primordial follicles in a dormant state. The industrial chemical, 4-vinylcyclohexene diepoxide (VCD) causes specific ovotoxicity in primordial and small primary follicles of mice and rats. Previous studies suggest that this ovotoxicity involves acceleration of primordial to primary follicle recruitment via interactions with the Kit/Kit ligand signaling pathway. Because of its accepted role in inhibiting primordial follicle recruitment, the present study was designed to investigate a possible interaction between AMH and VCD-induced ovotoxicity. Protein distribution of AMH was compared in neonatal and adult F344 rat ovaries. AMH protein was visualized by immunofluorescence microscopy in large primary and secondary follicles of the adult ovary, but in small primary follicles in neonatal rat ovaries. In cultured postnatal day (PND) 4 F344 rat ovaries, VCD exposure (30 {mu}M, 2-8 days) decreased (P < 0.05) AMH mRNA (d4-8) and protein (d6-8). Recombinant AMH (100-400 mg/ml) in PND4 ovaries cultured 8 days {+-} VCD (30 {mu}M) caused an increase (P < 0.05) in primordial, and a decrease (P < 0.05) in small primary follicles, supporting that AMH retarded primordial follicle recruitment. However, no concentration of AMH had an effect on VCD-induced ovotoxicity. Whereas, VCD caused a reduction in expression of AMH (d4-d8), it followed previously reported initial disruptions in Kit signaling induced by VCD (d2). Thus, collectively, these results do not support a mechanism whereby VCD causes ovotoxicity via generalized activation of primordial follicle recruitment, but instead provide further support for the specificity of other intracellular mechanisms involved in VCD-induced ovotoxicity.

  10. Pharmacokinetics interaction between imatinib and genistein in rats.

    PubMed

    Wang, Zhe; Wang, Li; Xia, Meng-Ming; Sun, Wei; Huang, Cheng-Ke; Cui, Xiao; Hu, Guo-Xin; Lian, Qing-Quan; Wang, Zeng-Shou

    2015-01-01

    The objective of this work was to investigate the effect of orally administered genistein on the pharmacokinetics of imatinib and N-desmethyl imatinib in rats. Twenty-five healthy male SD (Sprague-Dawley) rats were randomly divided into five groups: A group (control group), B group (multiple dose of 100 mg/kg genistein for consecutive 15 days), C group (multiple dose of 50 mg/kg genistein for consecutive 15 days), D group (a single dose of 100 mg/kg genistein), and E group (a single dose of 50 mg/kg genistein). A single dose of imatinib is administered orally 30 min after administration of genistein (100 mg/kg or 50 mg/kg). The pharmacokinetic parameters of imatinib and N-desmethyl imatinib were calculated by DAS 3.0 software. The multiple dose of 100 mg/kg or 50 mg/kg genistein significantly (P < 0.05) decreased the AUC0-t and C max of imatinib. AUC0-t and the C max of N-desmethyl imatinib were also increased, but without any significant difference. However, the single dose of 100 mg/kg or 50 mg/kg genistein has no effect on the pharmacokinetics of imatinib and N-desmethyl imatinib. Those results indicated that multiple dose of genistein (100 mg/kg or 50 mg/kg) induces the metabolism of imatinib, while single dose of genistein has no effect.

  11. Sliding indirect hernia containing both ovaries.

    PubMed

    Fowler, Carol L

    2005-09-01

    Although sliding indirect inguinal hernias containing the ipsilateral ovary and fallopian tube are not uncommon in infant girls, sliding hernias containing both ovaries are rare. This report describes a large indirect inguinal hernia in a 1-year-old infant girl that contained the left uterine fundus, left bladder ear, as well as both ovaries and fallopian tubes.

  12. Prenatal Stress and Stress Coping Style Interact to Predict Metabolic Risk in Male Rats

    PubMed Central

    Moghadam, Alexander A.; Cordner, Zachary A.; Tamashiro, Kellie L.

    2014-01-01

    Both prenatal stress (PNS) exposure and a passive stress-coping style have been identified as risk factors for insulin resistance in rats. In the current study, we test the hypothesis that PNS and stress-coping style may interact in predicting susceptibility for metabolic disease. To test this hypothesis, adult male control and PNS offspring were behaviorally characterized using a defensive burying test to have either a passive or proactive stress-coping style. In adulthood, all rats were fed either a standard chow or a high-fat diet for 3 weeks. After 3 weeks of diet exposure, glucose and insulin levels were assessed during an oral glucose tolerance test. Under high-fat diet conditions, PNS rats display elevated glucose and insulin responses to the oral glucose tolerance test, indicative of glucose intolerance. Interestingly, these effects of PNS were far more pronounced in rats characterized by a passive stress-coping style. Additionally, the passively coping PNS rats also gained more weight on the high-fat diet than all other rats tested. This observation suggests that a stressful prenatal environment in combination with a passive stress-coping strategy may prime an individual to be sensitive to diet-induced obesity and type 2 diabetes. PMID:24467745

  13. Strong interactions between learned helplessness and risky decision-making in a rat gambling model

    PubMed Central

    Nobrega, José N.; Hedayatmofidi, Parisa S.; Lobo, Daniela S.

    2016-01-01

    Risky decision-making is characteristic of depression and of addictive disorders, including pathological gambling. However it is not clear whether a propensity to risky choices predisposes to depressive symptoms or whether the converse is the case. Here we tested the hypothesis that rats showing risky decision-making in a rat gambling task (rGT) would be more prone to depressive-like behaviour in the learned helplessness (LH) model. Results showed that baseline rGT choice behaviour did not predict escape deficits in the LH protocol. In contrast, exposure to the LH protocol resulted in a significant increase in risky rGT choices on retest. Unexpectedly, control rats subjected only to escapable stress in the LH protocol showed a subsequent decrease in riskier rGT choices. Further analyses indicated that the LH protocol affected primarily rats with high baseline levels of risky choices and that among these it had opposite effects in rats exposed to LH-inducing stress compared to rats exposed only to the escape trials. Together these findings suggest that while baseline risky decision making may not predict LH behaviour it interacts strongly with LH conditions in modulating subsequent decision-making behaviour. The suggested possibility that stress controllability may be a key factor should be further investigated. PMID:27857171

  14. Interaction of macrolide antibiotics with intestinally expressed human and rat organic anion-transporting polypeptides.

    PubMed

    Lan, Tian; Rao, Anuradha; Haywood, Jamie; Davis, Charles B; Han, Chao; Garver, Eric; Dawson, Paul A

    2009-12-01

    The macrolide antibiotics azithromycin and clarithromycin are large molecular weight compounds that exhibit moderate to excellent oral bioavailability in preclinical species and humans. Previous concomitant dosing studies in rats using rifamycin SV, a general organic anion-transporting polypeptide (OATP) inhibitor, suggested that the high oral absorption of azithromycin and clarithromycin may be caused by facilitative uptake by intestinal Oatps. In this study, we used OATP/Oatp-expressing cells to investigate the interaction of macrolides with rat Oatp1a5, human OATP1A2, and human/rat OATP2B1/Oatp2b1. These experiments showed that azithromycin and clarithromycin were potent inhibitors of rat Oatp1a5-mediated taurocholate uptake with apparent inhibitor constant (K(i)) values of 3.3 and 2.4 microM, respectively. The macrolides functioned as noncompetitive inhibitors but were not transport substrates for rat Oatp1a5, as assessed by direct uptake measurements of radiolabeled azithromycin and clarithromycin. cis-Inhibition and direct uptake studies further showed that azithromycin and clarithromycin were only very weak inhibitors and not substrates for human OATP1A2 and human/rat OATP2B1/Oatp2b1. In summary, these results indicate that the macrolides azithromycin and clarithromycin potently inhibit rat Oatp1a5 but do not significantly interact with OATP1A2 and OATP2B1/Oatp2b1. These intestinally expressed OATP/Oatp(s) are not responsible for the postulated facilitative uptake of azithromycin and clarithromycin, and alternative facilitative pathways must exist for their intestinal absorption.

  15. Food-drug interaction of tacrolimus with pomelo, ginger, and turmeric juice in rats.

    PubMed

    Egashira, Kanoko; Sasaki, Hitoshi; Higuchi, Shun; Ieiri, Ichiro

    2012-01-01

    Tacrolimus is a well-known potent immunosuppressant agent, which has various drug-drug or food-drug interactions. Previously, we found a renal transplant recipient who increased tacrolimus blood concentrations after ingestion of pomelo as a rare case. So, we investigated the effect of pomelo after its administration for one day or 3 consecutive days on the pharmacokinetics of tacrolimus in rats. We also confirmed the effects of grapefruit, turmeric, and ginger. The tacrolimus blood concentrations of the rats pre-treated with 100% pomelo juice were significantly higher than those pre-treated with water. On the other hand, the tacrolimus blood concentrations of the rats pre-treated with 50% pomelo juice were not significantly different from those pre-treated with water. The pomelo-tacrolimus interaction showed concentration dependency. Even low concentration of pomelo juice could enhance the blood concentrations of tacrolimus by repeated administration. The inhibitory effect of 100% pomelo juice disappeared 3 days after intake. The AUC values of tacrolimus in the rats pre-treated with grapefruit juice, ginger juice, and turmeric juice were significantly larger than those pre-treated with water. We could confirm the pomelo-tacrolimus interaction, which we discovered in a case study, quantitatively. We newly found the influence of turmeric and ginger on tacrolimus pharmacokinetics, comparable to pomelo.

  16. Interactions of stress and CRF in ethanol-withdrawal induced anxiety in adolescent and adult rats.

    PubMed

    Wills, Tiffany A; Knapp, Darin J; Overstreet, David H; Breese, George R

    2010-09-01

    Repeated stress or administration of corticotropin-releasing factor (CRF) prior to ethanol exposure sensitizes anxiety-like behavior in adult rats. Current experiments determined whether adolescent rats were more sensitive to these challenges in sensitizing ethanol withdrawal-induced anxiety and altering CRF levels in brain during withdrawal. Male adult and adolescent Sprague-Dawley rats were restraint stressed (1 hour) twice 1 week apart prior to a single 5-day cycle of ethanol diet (ED; stress/withdrawal paradigm). Other rats received control diet (CD) and three 1-hour restraint stress sessions. Rats were then tested 5, 24, or 48 hours after the final withdrawal for anxiety-like behavior in the social interaction (SI) test. In other experiments, adolescent rats were given two microinjections of CRF icv 1 week apart followed by 5 days of either CD or ED and tested in social interaction 5 hours into withdrawal. Finally, CRF immunoreactivity was measured in the central nucleus of the amygdala (CeA) and paraventricular nucleus (PVN) after rats experienced control diet, repeated ethanol withdrawals, or stress/withdrawal. Rats of both ages had reduced SI following the stress/withdrawal paradigm, and this effect recovered within 24 hours. Higher CRF doses were required to reduce SI in adolescents than previously reported in adults. CRF immunohistochemical levels were higher in the PVN and CeA of CD-exposed adolescents. In adolescent rats, repeated ethanol withdrawals decreased CRF in the CeA but was not associated with decreased CRF cell number. There was no change in CRF from adult treatments. In the production of anxiety-like behavior, adolescent rats have equal sensitivity with stress and lower sensitivity with CRF compared to adults. Further, adolescents had higher basal levels of CRF within the PVN and CeA and reduced CRF levels following repeated ethanol withdrawals. This reduced CRF within the CeA could indicate increased release of CRF, and future work will

  17. APOPTOSIS IN WHOLE MOUSE OVARIES

    EPA Science Inventory

    Apoptosis in Whole Mouse Ovaries
    Robert M. Zucker Susan C. Jeffay and Sally D. Perreault
    Reproductive Toxicology Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina, 27711.

  18. APOPTOSIS IN WHOLE MOUSE OVARIES

    EPA Science Inventory

    Apoptosis in Whole Mouse Ovaries
    Robert M. Zucker Susan C. Jeffay and Sally D. Perreault
    Reproductive Toxicology Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina, 27711.

  19. An autoradiographic map of (3H)diprenorphine binding in rat brain: effects of social interaction

    SciTech Connect

    Panksepp, J.; Bishop, P.

    1981-10-01

    (3H)Diprenorphine binding was analyzed autoradiographically in the brains of 33 day old rat pups. A photographic atlas of diprenorphine binding in the coronal plane is provided to highlight the dispersion of opioid receptor systems through the brain. To determine whether brain opioid release may be induced by social interactions, half the animals were sacrificed following a 30 min period of social interaction while the other half were sacrificed following 30 min of social isolation. Opioid binding was higher in isolate-tested animals than socially-tested ones, suggesting that social interaction may promote endogenous brain opioid release.

  20. Interactions of ozone and antineoplastic drugs on rat lung fibroblasts and Walker rat carcinoma cells

    SciTech Connect

    Wenzel, D.G.; Morgan, D.L.

    1983-05-01

    Cultured rat lung fibroblasts (F-cells) and Walker rat carcinoma cells (WRC-cells) labeled with /sup 51/Cr were exposed to the following antitumor drugs alone or with O/sub 3/: carmustine (BCNU), doxorubicin (Dox), cisplatin (CPt), mitomycin C (Mit C) or vitamin K/sub 3/ (Vit K). Release of /sup 51/Cr (cell injury) was greater for F-cells than WRC-cells with any single treatment. Pretreatment with any drug (400 microM), except for Vit K with WRC-cells, did not significantly increase O/sub 3/-induced loss of /sup 51/Cr. Co-exposure of F-cells to drugs and O/sub 3/ resulted in a marked potentiation of O/sub 3/-induced injury with Vit K, and an inhibition with Dox.

  1. Lack of pharmacokinetic interaction between dipyridamole and zalcitabine in rats.

    PubMed

    Abobo, C V; Xian, Y

    1997-11-01

    Resistance usually manifests following long-term dideoxynucleoside therapy of HIV-1 infection. This period appears to coincide with reduced dosage regimens. Resistance that is associated with long-term monotherapy may, in part, be due to decreased intracellular drug concentrations. It has been reported that intracellular uptake of the dideoxynucleosides is enhanced by dipyridamole. Hence, dipyridamole may potentially be used to optimize the effects of zalcitabine in HIV-1 antiretroviral "cocktail". The purpose of this study was to characterize the pharmacokinetics of zalcitabine when administered alone and concomitantly with dipyridamole. Also, we determined, indirectly, whether dipyridamole modulated the intracellular uptake of zalcitabine. Rats were intravenously administered either zalcitabine 100 mg/kg alone or with dipyridamole 15 mg/kg. Except renal clearance (CIR), there were no statistically significant differences in the pharmacokinetic parameters including the steady-state volume of distribution and distribution coefficient. Zalcitabine plasma concentrations declined rapidly in a bi-exponential fashion, with a terminal half-life of 1.03 +/- 0.18 hr. alone versus 1.08 +/- 0.22 hr. with dipyridamole. The area under the concentration-time curve was not significantly different with or without dipyridamole. ClR, was 1.42 +/- 0.37 l/hr./kg for zalcitabine alone versus 1.09 +/- 0.28 l/hr./kg with dipyridamole. Our single dose study show that zalcitabine disposition kinetics were not significantly modulated by dipyridamole.

  2. Features of Polycystic Ovary Syndrome in adolescence

    PubMed Central

    Tsikouras, P; Spyros, L; Manav, B; Zervoudis, S; Poiana, C; Nikolaos, T; Petros, P; Dimitraki, M; Koukouli, C; Galazios, G; von Tempelhoff, GF

    2015-01-01

    Rationale: To elucidate the prepubertal risk factors associated with the development of Polycystic Ovary Syndrome (PCOS) and determine the special clinical manifestations of the syndrome in this transitional time of a woman’s life. Objective: To propose therapeutic targets and regimens, not only to prevent the long-term complications of the syndrome, but also to improve the self-esteem of a young girl who matures into womanhood. Methods and Results: A systematic review of literature was performed through electronic database searches (Pubmed, Medline and Embase). Studies published in English-language, peer-reviewed journals from 1996 to 2013 were included. The selected studies focused on the risk factors, the unique features and treatment options of the PCOS in puberty. The pathogenesis of the PCOS was hypothesized to be based on interactions between genetic and certain environmental factors. The diagnosis was usually difficult in young girls. The syndrome was related to a greater risk of future infertility, type II diabetes mellitus, the metabolic syndrome and cardiovascular disease. Early treatment was crucial to prevent the long-term complications of the syndrome, especially infertility and cardiovascular disease. Discussion:The recognition of the early signs of PCOS during or even before adolescence is of great importance. It is essential to establish the correct diagnosis for PCOS and rule out other causes of androgen excess in young women with hyperandrogenism. The type of treatment applied should be considered on an individual basis. Abbreviations: PCOS = Polycystic Ovary Syndrome PMID:26351529

  3. Interaction of propionate and carnitine metabolism in isolated rat hepatocytes

    SciTech Connect

    Brass, E.P.; Beyerinck, R.A.

    1987-05-01

    Propionate (P) and its metabolic products P-CoA and methylmalonyl-CoA can disrupt normal hepatic metabolism. Carnitine (Cn) has been shown to partially restore cellular function in the presence of P. This effect of Cn may result from removal of propionyl groups as propionylcarnitine (P-Cn). The present study examined the kinetics of P-Cn formation in rat hepatocytes, and the consequence of P-Cn formation on P and Cn metabolism. /sup 14/C-P was converted to CO/sub 2/, glucose and P-Cn in the hepatocyte system. Increasing concentrations of Cn up to 10.0 mM increased P-Cn formation from P without affecting CO/sub 2/ or glucose formation. Thus, 10.0 mM Cn increased total P metabolism by 40%. Metabolism of P was associated with a decrease in Cn concentration and an increase in short chain acylcarnitines (SCCn). In the absence of added Cn, 60 min incubation with P decreased Cn from 6.8 to 2.5 ..mu..M with a corresponding increase in SCCn. This effect of P to deplete free Cn was not seen to the same degree with butyrate in place of P. Similar increases in the formation of SCCn in the presence of P at the expense of free Cn were seen when the incubation Cn concentration was increased to 50 ..mu..M or 150 ..mu..M. HPLC methodologies to study specific acylcarnitines demonstrated the accumulation of large amounts of P-Cn in the incubations containing P, accounting for the depletion of free Cn.

  4. Interaction of chelating agents with cadmium in mice and rats.

    PubMed Central

    Eybl, V; Sýkora, J; Koutenský, J; Caisová, D; Schwartz, A; Mertl, F

    1984-01-01

    The influence of several chelating agents (CaDTPA, ZnDTPA, CaEDTA, ZnEDTA, DMSA, D-penicillamine and DMPS, DMP and DDC) on the acute toxicity of CdCl2 and on the whole body retention and tissue distribution of cadmium after the IV application of 115mCdCl2 was compared in mice. The chelating agents were applied immediately after the application of cadmium. CaDTPA, ZnDTPA and DMSA appeared to be the most effective antidotes. However, DMSA increased the amount of cadmium retained in kidneys. The treatment of cadmium-poisoned mice with the combination of DMSA (IP) and ZnDTPA (SC) (all the compounds were injected in equimolar dose) decreased the toxicity of cadmium more than treatment with one chelating agents (given in a 2:1 dose). However, by studying the effect of these chelating agents and their combination of the retention and distribution of Cd in mice, it was demonstrated that the combined application of the antidotes showed little or no improvement over the results obtained with the most effective of the individual components. In the urine of rats injected with CdCl2 and treated with the chelating agents (CaDTPA, ZnDTPA, DMSA), the presence of cadmium complexes was demonstrated. The formation of mixed ligand chelates in vivo was not proved. Experiments in mice given a single injection of 115mCd-labeled Cd complexes of DMPS, DMSA and DTPA showed a high retention of cadmium in the organisms after the IV application of CdDMPS and CdDMSA complexes. PMID:6734561

  5. Interaction of chelating agents with cadmium in mice and rats

    SciTech Connect

    Eybl, V.; Sykora, J.; Koutensky, J.; Caisova, D.; Schwartz, A.; Mertl, F.

    1984-03-01

    The influence of several chelating agents (CaDTPA, ZnDTPA, CaEDTA, ZnEDTA, DMSA, D-penicillamine and DMPS, DMP and DDC) on the acute toxicity of CdCl/sub 2/ and on the whole body retention and tissue distribution of cadmium after the IV application of /sup 115mCdCl/sub 2/ was compared in mice. The chelating agents were applied immediately after the application of cadmium. CaDTPA, ZnDTPA and DMSA appeared to be the most effective antidotes. However, DMSA increased the amount of cadmium retained in kidneys. The treatement of cadmium-poisoned mice with the combination of DMSA (IP) and ZnDTPA (SC) (all the compounds were injected in equimolar dose) decreased the toxicity of cadmium more than treatment with one chelating agents (given in a 2:1 dose). However, by studying the effect of these chelating agents and their combination application of the antidotes showed little or no improvement over the results obtained with the most effective of the individual components. In the urine of rats injected with CdCl/sub 2/ and treated with the chelating agents (CaDTPA, ZnDTPA, DMSA), the presence of cadmium complexes was demonstrated. The formation of mixed ligand chelates in vivo was not proved. Experiments in mice given a single injection of /sup 115m/Cd-labeled Cd complexes of DMPS, DMSA and DTPA showed a high retention of cadmium in the organisms after the IV application of CdDMPS and CdDMSA complexes.

  6. Dihydroergotoxine decreases blood pressure in spontaneously hypertensive rats by interacting with peripheral dopamine receptors.

    PubMed

    Memo, M; Sagheddu, G; Carruba, M O; Spano, P

    1985-04-22

    Dihydroergotoxine (10 micrograms/kg s.c.) decreased mean carotid blood pressure in urethane-anaesthetized spontaneously hypertensive rats but failed to modify the same parameter in normotensive rats. The effect was statistically significant 20 min after the injection and relatively long lasting (up to 90 min). Pharmacological characterization of the phenomenon indicated that it is mediated by stimulation of dopamine receptors, since pretreatment with haloperidol, cis-flupentixol but not with trans-flupentixol, completely prevent the reduction in blood pressure induced by dihydroergotoxine. Moreover, a challenge dose of dihydroergotoxine did not reduce mean blood pressure values in spontaneously hypertensive rats pretreated with domperidone or (-)sulpiride, but not with (+)sulpiride. These results suggest that the ergot derivative modifies the cardiovascular system by interaction with peripheral dopamine receptors of the DA2 type.

  7. Ovulation requires the activation on proestrus of M₁ muscarinic receptors in the left ovary.

    PubMed

    Cruz, M E; Flores, A; Alvarado, B E; Hernández, C G; Zárate, A; Chavira, R; Cárdenas, M; Arrieta-Cruz, I; Gutiérrez-Juárez, R

    2015-08-01

    We analyzed the effects of chemically blocking type 1 muscarinic receptors (M1R) on either the left or right ovary on ovulation rate, number of ova shed and steroid hormones levels. M1R were unilaterally blocked in ovary with the M1R selective antagonist pirenzepine (PZP). PZP was delivered into the bursa ovarica of the left or right ovary of adult rats at 13:00 h on proestrus day. PZP treatment in the left but not in the right ovary blocked ovulation. PZP did not modify the number of ova shed, nor progesterone or 17β-estradiol serum levels. The surge of luteinizing hormone levels was diminished while that of follicle-stimulating hormone did not change in animals treated with PZP in the left ovary. Interestingly, treatment with either synthetic luteinizing hormone-releasing hormone or human chorionic gonadotropin 1 h after PZP administration in the left ovary restored ovulation in both ovaries. The presence of M1R protein in the theca cells of the ovarian follicles as well as in cells of the corpus luteum was detected on proestrus day. These results suggest that M1R activation in the left ovary is required for pre-ovulatory gonadotropin-releasing hormone (GnRH) secretion and ovulation. Furthermore, these results also suggest that M1R in the left ovary might be regulating ovulation asymmetrically through a stimulatory neural signal relayed to the hypothalamus via the vagus nerve to induce the GnRH secretion which then triggers ovulation.

  8. Striatal adenosine-cannabinoid receptor interactions in rats over-expressing adenosine A2A receptors.

    PubMed

    Chiodi, Valentina; Ferrante, Antonella; Ferraro, Luca; Potenza, Rosa Luisa; Armida, Monica; Beggiato, Sarah; Pèzzola, Antonella; Bader, Michael; Fuxe, Kjell; Popoli, Patrizia; Domenici, Maria Rosaria

    2016-03-01

    Adenosine A2A receptors (A2 A Rs) and cannabinoid CB1 receptors (CB1 Rs) are highly expressed in the striatum, where they functionally interact and form A2A /CB1 heteroreceptor complexes. We investigated the effects of CB1 R stimulation in a transgenic rat strain over-expressing A2 A Rs under the control of the neural-specific enolase promoter (NSEA2A rats) and in age-matched wild-type (WT) animals. The effects of the CB1 R agonist WIN 55,212-2 (WIN) were significantly lower in NSEA2A rats than in WT animals, as demonstrated by i) electrophysiological recordings of synaptic transmission in corticostriatal slices; ii) the measurement of glutamate outflow from striatal synaptosomes and iii) in vivo experiments on locomotor activity. Moreover, while the effects of WIN were modulated by both A2 A R agonist (CGS 21680) and antagonists (ZM 241385, KW-6002 and SCH-442416) in WT animals, the A2 A R antagonists failed to influence WIN-mediated effects in NSEA2A rats. The present results demonstrate that in rats with genetic neuronal over-expression of A2 A Rs, the effects mediated by CB1 R activation in the striatum are significantly reduced, suggesting a change in the stoichiometry of A2A and CB1 receptors and providing a strategy to dissect the involvement of A2 A R forming or not forming heteromers in the modulation of striatal functions. These findings add additional evidence for the existence of an interaction between striatal A2 A Rs and CB1 Rs, playing a fundamental role in the regulation of striatal functions. We studied A2A -CB1 receptor interaction in transgenic rats over-expressing adenosine A2A receptors under the control of the neuron-specific enolase promoter (NSEA2A ). In these rats, we demonstrated a reduced effect of the CB1 receptor agonist WIN 55,212-2 in the modulation of corticostriatal synaptic transmission and locomotor activity, while CB1 receptor expression level did not change with respect to WT rats. A reduction in the expression of A2A -CB1

  9. Erythromycin potentiates PR interval prolonging effect of verapamil in the rat: A pharmacodynamic drug interaction

    SciTech Connect

    Dakhel, Yaman; Jamali, Fakhreddin . E-mail: fjamali@ualberta.ca

    2006-07-01

    Calcium channel blockers and macrolide antibiotics account for many drug interactions. Anecdotal reports suggest interactions between the two resulting in severe side effects. We studied the interaction between verapamil and erythromycin in the rat to see whether it occurs at the pharmacokinetics or pharmacodynamic level. Adult male Sprague-Dawley rats received doses of 1 mg/kg verapamil or 100 mg/kg erythromycin alone or in combination (n = 6/group). Serial blood samples (0-6 h) were taken for determination of the drug concentrations using HPLC. Electrocardiograms were recorded (0-6 h) through subcutaneously inserted lead II. Binding of the drugs to plasma proteins was studied using spiked plasma. Verapamil prolonged PR but not QT interval. Erythromycin prolonged QT but not PR interval. The combination resulted in a significant increase in PR interval prolongation and AV node blocks but did not further prolong QT interval. Pharmacokinetics and protein binding of neither drug were altered by the other. Our rat data confirm the anecdotal human case reports that combination of erythromycin and verapamil can result in potentiation of the cardiovascular response. The interaction appears to be at the pharmacodynamic rather than pharmacokinetic level hence may be extrapolated to other calcium channel antagonists.

  10. Synergistic interaction between nicotine and social rewards in adolescent male rats

    PubMed Central

    Thiel, Kenneth J.; Sanabria, Federico; Neisewander, Janet L.

    2010-01-01

    Rationale Smoking typically begins during adolescence and is largely reinforced by social cues. During adolescence in rats, sensitivity to both social cues and drugs of abuse is enhanced. Objectives We have previously demonstrated in adolescent male rats that a low dose of cocaine interacts with social reward to produce an enhanced conditioned place preference (CPP) relative to either reward given alone. The present study further examined the nature of drug:social reward interactions using nicotine. Methods Dose-effect functions for nicotine-CPP were established using two different routes of administration (vehicle, 0.1, 0.3, and 0.6 mg/kg, SC and vehicle, 0.01, 0.03, and 0.06 mg/kg, IV). The effects of nicotine on social reward-CPP and social play behavior were next examined using parameters presumed to be sub-threshold for establishing social reward- and nicotine-CPP. Results Dose-dependent nicotine-CPP was observed using both routes of administration. Two pairings of the initially non-preferred side of the apparatus with either SC nicotine or another adolescent rat failed to produce CPP when examined alone, but together produced a robust CPP despite nicotine reducing social play. This interaction effect was not observed with the IV nicotine. A final experiment demonstrated that the enhancement of CPP with the combination of rewards was not due to additive effects of weak, sub-threshold conditioning. Conclusions These findings suggest that nicotine and social rewards interact synergistically in adolescent rats resulting in a greater, perhaps qualitatively different, reward than either reward given alone. Understanding drug:social reward interactions may provide new directions for development of preventions and interventions of adolescent smoking. PMID:19224200

  11. Drug-drug Interaction between Pravastatin and Gemfibrozil (Antihyperlipidemic) with Gliclazide (Antidiabetic) in Rats.

    PubMed

    Sultanpur, Cm; Satyanarayana, S; Reddy, Ns; Kumar, Ke; Kumar, S

    2010-04-01

    Diabetes mellitus is a condition of increased blood glucose level in the body. Antihyperlipidemic drugs like statins and fibrates are widely used for prophylactic treatment in dyslipideamia and atherosclerosis. Diabetic dislipidemia exists with increased triglycerides, low HDL and high LDL levels. Hence, with oral hypoglycemic drugs, the addition of a lipid-lowering drug is necessary for controlling dislipidemia. In such a situation, there may be chances of drug-drug interactions between antidiabetic and antihyperlipidemic drugs. The present study is planned to evaluate the safety of gliclazide (antidiabetic) in the presence of pravastatin and gemfibrozil (antihyperlpidemic) in rats. Studies in normal and alloxan-induced diabetic rats were conducted with oral doses of gliclazide and their combination with pravastatin and gemfibrozil, with an adequate washout period in between the treatments. Blood samples were collected in rats by retroorbital puncture at 0, 1, 2, 3, 4, 6, 8, 10 and 12 h. All the blood samples were analyzed for glucose by GOD -POD. Gliclazide (½ TD) produced hypoglycemic activity in normal and diabetic rats, with peak activity at 2 and 8 h. Pravastatin (TD) + gemfibrozil (TD) combination treatment increased the hypoglycemic effect of gliclazide in normal rats or diabetic rats when administered together. The interaction observed due to inhibition of both the enzymes (CYP 450 2C9 and CYP 450 3A4) responsible for the metabolism of gliclazide showed increased half-life, which was seen in the present study. Because concomitant administration of gliclazide with provastatin and gemfibrozil in diabetes is associated with atherosclerosis, it should be contraindicated or used with caution.

  12. Drug–drug Interaction between Pravastatin and Gemfibrozil (Antihyperlipidemic) with Gliclazide (Antidiabetic) in Rats

    PubMed Central

    Sultanpur, CM; Satyanarayana, S; Reddy, NS; Kumar, KE; Kumar, S

    2010-01-01

    Diabetes mellitus is a condition of increased blood glucose level in the body. Antihyperlipidemic drugs like statins and fibrates are widely used for prophylactic treatment in dyslipideamia and atherosclerosis. Diabetic dislipidemia exists with increased triglycerides, low HDL and high LDL levels. Hence, with oral hypoglycemic drugs, the addition of a lipid-lowering drug is necessary for controlling dislipidemia. In such a situation, there may be chances of drug–drug interactions between antidiabetic and antihyperlipidemic drugs. The present study is planned to evaluate the safety of gliclazide (antidiabetic) in the presence of pravastatin and gemfibrozil (antihyperlpidemic) in rats. Studies in normal and alloxan-induced diabetic rats were conducted with oral doses of gliclazide and their combination with pravastatin and gemfibrozil, with an adequate washout period in between the treatments. Blood samples were collected in rats by retroorbital puncture at 0, 1, 2, 3, 4, 6, 8, 10 and 12 h. All the blood samples were analyzed for glucose by GOD –POD. Gliclazide (½ TD) produced hypoglycemic activity in normal and diabetic rats, with peak activity at 2 and 8 h. Pravastatin (TD) + gemfibrozil (TD) combination treatment increased the hypoglycemic effect of gliclazide in normal rats or diabetic rats when administered together. The interaction observed due to inhibition of both the enzymes (CYP 450 2C9 and CYP 450 3A4) responsible for the metabolism of gliclazide showed increased half-life, which was seen in the present study. Because concomitant administration of gliclazide with provastatin and gemfibrozil in diabetes is associated with atherosclerosis, it should be contraindicated or used with caution. PMID:21264118

  13. Characterizing Olfactory Binary Mixture Interactions in Fischer 344 Rats Using Behavioral Reaction Times

    PubMed Central

    Yoder, Wendy M.; Gaynor, Leslie; Windham, Ethan; Lyman, Michelle; Munizza, Olivia; Setlow, Barry; Bizon, Jennifer L.

    2015-01-01

    Response times provide essential subthreshold perceptual data that extend beyond accuracy alone. Behavioral reaction times (RTs) were used to characterize rats’ ability to detect individual odorants in a series of complimentary binary odorant mixture ratios. We employed an automated, liquid-dilution olfactometer to train Fischer 344 rats (N = 8) on an odor identification task using nonreinforced probe trials. Binary mixture ratios composed of aliphatic odorants (citral and octanol) were arranged such that relative contributions of the 2 components varied systematically by a factor of 1% (v/v). Odorant concentrations for the target (S+), control (S−), and mixture (S+:S−) odorants were presented relative to threshold for each rat. Rats were initially trained to respond by licking at a spout to obtain liquid reward for either citral or octanol as the reinforced target (S+) odorant. After achieving 100% accuracy, rats were transferred to variable ratio (VR 2) reinforcement for correct responding. Nonreinforced probe trials (2 per block of 22 trials) were tested for each mixture ratio and recorded as either S+ (rats lick-responded in the presence of the mixture) or S− (rats refrained from licking), thereby indicating detection of the trained, S+ odorant. To determine the perceived salience for each ratio, RTs (latency from odorant onset to lick response) were recorded for each trial. Consistent with previous studies, RTs for both odorants were shortest (~150–200ms) when the probe trials consisted of a single, monomolecular component. Binary mixtures that contained as little as 1% of the S−, nontarget odorant, however, were sufficiently different perceptually to increase behavioral RTs (i.e., rats hesitated longer before responding); RTs changed systematically as a function of the binary ratio. Interestingly, the rate of RT change was dependent on which odorant served as the S+, suggesting an asymmetric interaction between the 2 odorants. The data demonstrate

  14. Interaction of human and rat organic anion transporter 2 with various cephalosporin antibiotics.

    PubMed

    Khamdang, Suparat; Takeda, Michio; Babu, Ellappan; Noshiro, Rie; Onozato, Maristela Lika; Tojo, Akihiro; Enomoto, Atsushi; Huang, Xiu-Lin; Narikawa, Shinichi; Anzai, Naohiko; Piyachaturawat, Pawinee; Endou, Hitoshi

    2003-03-28

    Cephalosporin antibiotics are thought to be excreted into the urine via organic anion transporters (OATs) and OAT can mediate nephrotoxicity by cephalosporins, particularly by cephaloridine. The purpose of this study was to elucidate the interaction of human-OAT2 and rat-OAT2 with cephalosporin antibiotics using proximal tubule cells stably expressing human-OAT2 and rat-OAT2. Human-OAT2 is localized to the basolateral side of the proximal tubule, whereas rat-OAT2 is localized to the apical side of the proximal tubule. Cephalosporins tested were cephalothin, cefoperazone, cefazolin, ceftriaxone, cephaloridine, cefotaxime, cefadroxil and cefamandole. These cephalosporins dose-dependently inhibited organic anion uptake mediated by human-OAT2 and rat-OAT2. There was no species difference observed for the effects of OAT2 with cephalosporins between human and rat transporters. Kinetic analysis revealed that the inhibitory effects for human-OAT2 were competitive. Cephaloridine significantly decreased the viability of cells stably expressing human-OAT2, human-OAT1, human-OAT3 and human-OAT4. The decreased viability of cells stably expressing human-OAT1, human-OAT3 and human-OAT4 but not human-OAT2 was reversed by probenecid. In conclusion, human-OAT2 interacts with cephalosporins, and thus, human-OAT2 may mediate the uptake of cephalosporins on the basolateral side of the proximal tubule. The interaction of human-OAT2 with cephalosporins was the weakest among the basolateral human-OATs tested. In addition, it is suggested that human-OATs mediate cephaloridine-induced nephrotoxicity.

  15. A 3D-Video-Based Computerized Analysis of Social and Sexual Interactions in Rats

    PubMed Central

    Matsumoto, Jumpei; Urakawa, Susumu; Takamura, Yusaku; Malcher-Lopes, Renato; Hori, Etsuro; Tomaz, Carlos; Ono, Taketoshi; Nishijo, Hisao

    2013-01-01

    A large number of studies have analyzed social and sexual interactions between rodents in relation to neural activity. Computerized video analysis has been successfully used to detect numerous behaviors quickly and objectively; however, to date only 2D video recording has been used, which cannot determine the 3D locations of animals and encounters difficulties in tracking animals when they are overlapping, e.g., when mounting. To overcome these limitations, we developed a novel 3D video analysis system for examining social and sexual interactions in rats. A 3D image was reconstructed by integrating images captured by multiple depth cameras at different viewpoints. The 3D positions of body parts of the rats were then estimated by fitting skeleton models of the rats to the 3D images using a physics-based fitting algorithm, and various behaviors were recognized based on the spatio-temporal patterns of the 3D movements of the body parts. Comparisons between the data collected by the 3D system and those by visual inspection indicated that this system could precisely estimate the 3D positions of body parts for 2 rats during social and sexual interactions with few manual interventions, and could compute the traces of the 2 animals even during mounting. We then analyzed the effects of AM-251 (a cannabinoid CB1 receptor antagonist) on male rat sexual behavior, and found that AM-251 decreased movements and trunk height before sexual behavior, but increased the duration of head-head contact during sexual behavior. These results demonstrate that the use of this 3D system in behavioral studies could open the door to new approaches for investigating the neuroscience of social and sexual behavior. PMID:24205238

  16. A 3D-video-based computerized analysis of social and sexual interactions in rats.

    PubMed

    Matsumoto, Jumpei; Urakawa, Susumu; Takamura, Yusaku; Malcher-Lopes, Renato; Hori, Etsuro; Tomaz, Carlos; Ono, Taketoshi; Nishijo, Hisao

    2013-01-01

    A large number of studies have analyzed social and sexual interactions between rodents in relation to neural activity. Computerized video analysis has been successfully used to detect numerous behaviors quickly and objectively; however, to date only 2D video recording has been used, which cannot determine the 3D locations of animals and encounters difficulties in tracking animals when they are overlapping, e.g., when mounting. To overcome these limitations, we developed a novel 3D video analysis system for examining social and sexual interactions in rats. A 3D image was reconstructed by integrating images captured by multiple depth cameras at different viewpoints. The 3D positions of body parts of the rats were then estimated by fitting skeleton models of the rats to the 3D images using a physics-based fitting algorithm, and various behaviors were recognized based on the spatio-temporal patterns of the 3D movements of the body parts. Comparisons between the data collected by the 3D system and those by visual inspection indicated that this system could precisely estimate the 3D positions of body parts for 2 rats during social and sexual interactions with few manual interventions, and could compute the traces of the 2 animals even during mounting. We then analyzed the effects of AM-251 (a cannabinoid CB1 receptor antagonist) on male rat sexual behavior, and found that AM-251 decreased movements and trunk height before sexual behavior, but increased the duration of head-head contact during sexual behavior. These results demonstrate that the use of this 3D system in behavioral studies could open the door to new approaches for investigating the neuroscience of social and sexual behavior.

  17. Interaction between nanoparticles generated by zinc chloride treatment and oxidative responses in rat liver

    PubMed Central

    Azzouz, Inès; Trabelsi, Hamdi; Hanini, Amel; Ferchichi, Soumaya; Tebourbi, Olfa; Sakly, Mohsen; Abdelmelek, Hafedh

    2014-01-01

    The aim of the present study was to investigate the interaction of zinc chloride (3 mg/kg, intraperitoneally [ip]) in rat liver in terms of the biosynthesis of nanoparticles. Zinc treatment increased zinc content in rat liver. Analysis of fluorescence revealed the presence of red fluorescence in the liver following zinc treatment. Interestingly, the co-exposure to zinc (3 mg/kg, ip) and selenium (0.20 mg/L, per os [by mouth]) led to a higher intensity of red fluorescence compared to zinc-treated rats. In addition, X-ray diffraction measurements carried out on liver fractions of zinc-treated rats point to the biosynthesis of zinc sulfide and/or selenide nanocomplexes at nearly 51.60 nm in size. Moreover, co-exposure led to nanocomplexes of about 72.60 nm in size. The interaction of zinc with other mineral elements (S, Se) generates several nanocomplexes, such as ZnS and/or ZnSe. The nanocomplex ZnX could interact directly with enzyme activity or indirectly by the disruption of mineral elements’ bioavailability in cells. Subacute zinc or selenium treatment decreased malondialdehyde levels, indicating a drop in lipid peroxidation. In addition, antioxidant enzyme assays showed that treatment with zinc or co-treatment with zinc and selenium increased the activities of glutathione peroxidase, catalase, and superoxide dismutase. Consequently, zinc complexation with sulfur and/or selenium at nanoscale level could enhance antioxidative responses, which is correlated to the ratio of number of ZnX nanoparticles (X=sulfur or X=selenium) to malondialdehyde level in rat liver. PMID:24403828

  18. Interaction between nanoparticles generated by zinc chloride treatment and oxidative responses in rat liver.

    PubMed

    Azzouz, Inès; Trabelsi, Hamdi; Hanini, Amel; Ferchichi, Soumaya; Tebourbi, Olfa; Sakly, Mohsen; Abdelmelek, Hafedh

    2014-01-01

    The aim of the present study was to investigate the interaction of zinc chloride (3 mg/kg, intraperitoneally [ip]) in rat liver in terms of the biosynthesis of nanoparticles. Zinc treatment increased zinc content in rat liver. Analysis of fluorescence revealed the presence of red fluorescence in the liver following zinc treatment. Interestingly, the co-exposure to zinc (3 mg/kg, ip) and selenium (0.20 mg/L, per os [by mouth]) led to a higher intensity of red fluorescence compared to zinc-treated rats. In addition, X-ray diffraction measurements carried out on liver fractions of zinc-treated rats point to the biosynthesis of zinc sulfide and/or selenide nanocomplexes at nearly 51.60 nm in size. Moreover, co-exposure led to nanocomplexes of about 72.60 nm in size. The interaction of zinc with other mineral elements (S, Se) generates several nanocomplexes, such as ZnS and/or ZnSe. The nanocomplex ZnX could interact directly with enzyme activity or indirectly by the disruption of mineral elements' bioavailability in cells. Subacute zinc or selenium treatment decreased malondialdehyde levels, indicating a drop in lipid peroxidation. In addition, antioxidant enzyme assays showed that treatment with zinc or co-treatment with zinc and selenium increased the activities of glutathione peroxidase, catalase, and superoxide dismutase. Consequently, zinc complexation with sulfur and/or selenium at nanoscale level could enhance antioxidative responses, which is correlated to the ratio of number of ZnX nanoparticles (X=sulfur or X=selenium) to malondialdehyde level in rat liver.

  19. The Interaction of Intramuscular Ketorolac (Toradol) and Concussion in a Rat Model.

    PubMed

    Esquivel, Amanda O; Sherman, Sarah S; Bir, Cynthia A; Lemos, Stephen E

    2017-02-13

    The purpose of this study was to examine the interaction of a single dose of Toradol and head impact in an in vivo rat model for sport-related concussion using a validated rat concussion model. Thirty-five Sprague-Dawley rats were placed into one of four groups: (1) Control, (2) Impact Only, (3) Toradol Only, (4) Impact and Toradol. Animals in the impact groups were subjected to a single head impact. Animals in the Toradol group received a single intramuscular injection of Toradol prior to impact. We examined magnetic resonance imaging, serum S100-B and cognitive function using a Morris Water Maze. In the control group, latency decreased significantly from day 0 (74.9 s) to 24 h (57.4 s) after anesthesia. There was no statistically significant difference between time zero and 24 h after impact in the Impact only or Impact and Toradol group. Our findings indicate that there were no differences between cognitive ability, MRI findings or S100B in rats that were administered a single dose of Toradol and subjected to a single impact and rats that were subjected to a single impact only. In both impact groups there were transient changes in cognitive ability as measured by the Morris Water Maze.

  20. Molecular cloning of the rat Tpx-1 responsible for the interaction between spermatogenic and Sertoli cells.

    PubMed

    Maeda, T; Sakashita, M; Ohba, Y; Nakanishi, Y

    1998-07-09

    We previously showed in a primary culture of rat testicular cells that spermatogenic cells specifically bind to somatic Sertoli cells and that this interaction is needed for spermatogenic cells to differentiate in vitro. Adopting an expression cloning procedure, we here isolated a cDNA coding for a spermatogenic cell protein whose expression gave a cultured cell line the ability to bind to Sertoli cells. The protein, 243 amino acids with a putative N-terminal signal peptide and a C-terminal Cys-rich region, turned out to be the rat homologue of a testicular protein called Tpx-1 whose function had yet to be determined. A polyclonal antibody raised against bacterially expressed Tpx-1 significantly inhibited the binding of spermatogenic cells to Sertoli cells. The above results indicated that Tpx-1 is a testicular cell adhesion molecule responsible for the specific interaction between spermatogenic and Sertoli cells.

  1. Defects in insulin signaling pathways in ovarian steroidogenesis and other tissues in polycystic ovary syndrome (PCOS).

    PubMed

    Diamanti-Kandarakis, Evanthia; Argyrakopoulou, Georgia; Economou, Frangiskos; Kandaraki, Eleni; Koutsilieris, Michael

    2008-04-01

    The polycystic ovary syndrome (PCOS) is the most common endocrinopathy in women of reproductive age today. Women with PCOS often demonstrate defective ovarian steroid biosynthesis and present with hyperandrogenemia. Moreover, 50-70% of PCOS women are insulin resistant and hyperinsulinemic. Insulin acts on the ovary via its own receptor and interacts with gonadotrophins, modulating steroidogenesis. The precise role of insulin and the molecular mechanisms that take place are not yet completely explicated. This review will be focused on insulin's action on the ovary and other target tissues, describing the intracellular signaling pathways implicated in steroidogenesis and their defects in women with PCOS.

  2. Social interaction with a rhythmic rat enhances the circadian pattern of the motor activity and temperature of LL-induced arrhythmic rats.

    PubMed

    Cambras, Trinitat; Castejón, Lucía; Díez-Noguera, Antoni

    2012-02-01

    Although light is the main factor that influences circadian rhythms, social interaction may also have a role on their regulation. Here, the influence of social interaction on rat circadian behavior was investigated, addressing the question of whether cohabitation would induce the appearance of a circadian rhythm in arrhythmic rats due to constant light. To this end, circadian rhythms of motor activity and body temperature of male and female LL-induced arrhythmic rats were studied before, during and after a 20-day period in which rats stayed in the same cage with a rat of the same sex but with stronger rhythm. Results showed that the manifestation of the circadian motor activity rhythm of LL-induced arrhythmic rats increased after cohabitation. In the case of the expression of the body temperature rhythm, there was a progressive daily increase in the power content of a daily 24 hour pattern throughout the cohabitation days, which remained when animals were again isolated. Thus, the presence of a rhythmic rat increases the strength of the circadian behavior of rats showing a weak circadian rhythm.

  3. Polycystic ovary syndrome - an update.

    PubMed

    Boyle, Jacqueline; Teede, Helena J

    2012-10-01

    Polycystic ovary syndrome (PCOS) is a common condition, present in 12-21% of women of reproductive age. Up to 70% of women with PCOS remain undiagnosed. This article summarises the 2011 national PCOS guideline, Evidence-based guideline for the assessment and management of polycystic ovary syndrome, for the general practice context, with particular reference to the needs of Indigenous Australian women. Women with PCOS may present with a wide range of symptoms. The Rotterdam criteria are the most widely accepted for diagnosis and the national guideline references these criteria. Women with PCOS have a higher risk of metabolic syndrome and its cardiovascular sequelae. This is particularly important for Indigenous women who are already at increased baseline risk. Management of PCOS involves attention to current symptoms, fertility and psychosocial issues, as well as prevention of related future health problems including diabetes. Resources are available to help guide management and patients may benefit most from a team approach to care.

  4. Polycystic ovary syndrome in adolescents.

    PubMed

    Rothenberg, Stephanie S; Beverley, Rachel; Barnard, Emily; Baradaran-Shoraka, Massoud; Sanfilippo, Joseph S

    2017-09-01

    Polycystic ovary syndrome (PCOS) typically manifests with a combination of menstrual dysfunction and evidence of hyperandrogenism in the adolescent population. No single cause has been identified; however, evidence suggests a complex interplay between genetic and environmental factors. Polycystic ovary syndrome presents a particular diagnostic challenge in adolescents as normal pubertal changes can present with a similar phenotype. Management of PCOS in the adolescent population should focus on a multi-modal approach with lifestyle modification and pharmacologic treatment to address bothersome symptoms. This chapter outlines the pathogenesis of PCOS, including the effects of obesity, insulin resistance, genetic, and environmental factors. The evolution of the diagnostic criteria of PCOS as well as specific challenges of diagnosis in the adolescent population are reviewed. Finally, evidence for lifestyle modification and pharmacologic treatments are discussed. Copyright © 2017. Published by Elsevier Ltd.

  5. Lactoferrin interacts with bile acids and increases fecal cholesterol excretion in rats.

    PubMed

    Nakamura, Kanae; Morishita, Satoru; Ono, Tomoji; Murakoshi, Michiaki; Sugiyama, Keikichi; Kato, Hisanori; Ikeda, Ikuo; Nishino, Hoyoku

    2017-02-01

    Lactoferrin (LF) is a multifunctional cationic protein (pI 8.2-8.9) in mammalian milk. We previously reported that enteric-LF prevented hypercholesterolemia and atherosclerosis in a diet-induced atherosclerosis model using Microminipig, although the underlying mechanisms remain unclear. Because LF is assumed to electrostatically interact with bile acids to inhibit intestinal cholesterol absorption, LF could promote cholesterol excretion. In this study, we assessed the interaction between LF and taurocholate in vitro, and the effect of LF on cholesterol excretion in rats. The binding rate of taurocholate to LF was significantly higher than that to transferrin (pI 5.2-6.3). When rats were administered a high-cholesterol diet (HCD) containing 5% LF, LF was detected using ELISA in the upper small intestine from 7.5 to 60 min after the administration. Rats were fed one of the following diets: control, HCD, or HCD + 5% LF for 21 days. Fecal neutral steroids and hepatic cholesterol levels in the HCD group were significantly higher than those in the control group. The addition of LF to a HCD significantly increased fecal neutral steroids levels (22% increase, p < 0.05) and reduced hepatic cholesterol levels (17% decrease, p < 0.05). These parameters were inversely correlated (R = -0.63, p < 0.05). These results suggest that LF promotes cholesterol excretion via interactions with bile acids.

  6. Pharmacokinetic drug interaction between fexofenadine and fluvastatin mediated by organic anion-transporting polypeptides in rats.

    PubMed

    Qiang, Fu; Lee, Beom-Jin; Lee, Wonjae; Han, Hyo-Kyung

    2009-06-28

    This study aimed to examine the transporter-mediated drug interaction between fexofenadine and fluvastatin in rats. Compared to the control group given fluvastatin alone, the concurrent use of fexofenadine (10 or 20mg/kg) prior to the oral administration of fluvastatin (5mg/kg) decreased the systemic exposure of fluvastatin by 17-51% in rats. Consequently, the bioavailability of oral fluvastatin was significantly lower (p<0.05) in the presence of fexofenadine compared to that from the control group. Furthermore, the intravenous pharmacokinetics of fluvastatin (2mg/kg) was significantly altered by the pretreatment with fexofenadine (20mg/kg, p.o.). The plasma clearance of fluvastatin was reduced by 44% in the presence of fexofenadine. The effect of fluvastatin on the pharmacokinetics of fexofenadine was also investigated in rats. The pretreatment with fluvastatin (5 or 10mg/kg) decreased AUC and C(max) of oral fexofenadine (10mg/kg) by 47-53% and 28-60%, respectively, while it did not affect the intravenous pharmacokinetics of fexofenadine. Given that both fluvastatin and fexofenadine can interact with organic anion-transporting polypeptides (OATPs) expressed in intestine and liver, the present results suggest the potential drug interaction between fluvastatin and fexofenadine via the competition for the OATP-mediated cellular transport pathway during intestinal absorption and/or hepatic uptake of drugs.

  7. [Natural history of ovary cancer].

    PubMed

    Novoa-Vargas, Arturo

    2014-09-01

    Ovary cancer is a disease charged of paradigms and a serious health problem. It's important to know its natural history, because has a multifactor origins, and understanding its behavior since risk factors until patient's death because metastatic disease is a challenger for oncology group. In this work we made a bibliographic, analytic review that brings up concepts related to its origin, evolution, risk factors, preclinical horizon, and clinical symptoms until the death of patient.

  8. Metabolic Syndrome: Polycystic Ovary Syndrome.

    PubMed

    Mortada, Rami; Williams, Tracy

    2015-08-01

    Polycystic ovary syndrome (PCOS) is a heterogeneous condition characterized by androgen excess, ovulatory dysfunction, and polycystic ovaries. It is the most common endocrinopathy among women of reproductive age, affecting between 6.5% and 8% of women, and is the most common cause of infertility. Insulin resistance is almost always present in women with PCOS, regardless of weight, and they often develop diabetes and metabolic syndrome. The Rotterdam criteria are widely used for diagnosis. These criteria require that patients have at least two of the following conditions: hyperandrogenism, ovulatory dysfunction, and polycystic ovaries. The diagnosis of PCOS also requires exclusion of other potential etiologies of hyperandrogenism and ovulatory dysfunction. The approach to PCOS management differs according to the presenting symptoms and treatment goals, particularly the patient's desire for pregnancy. Weight loss through dietary modifications and exercise is recommended for patients with PCOS who are overweight. Oral contraceptives are the first-line treatment for regulating menstrual cycles and reducing manifestations of hyperandrogenism, such as acne and hirsutism. Clomiphene is the first-line drug for management of anovulatory infertility. Metformin is recommended for metabolic abnormalities such as prediabetes, and a statin should be prescribed for cardioprotection if the patient meets standard criteria for statin therapy.

  9. [Diagnosis of polycystic ovary syndrome].

    PubMed

    Belosi, C; Giuliani, M; Suriano, R; Sagnella, F; Lanzone, A

    2004-02-01

    Polycystic ovary syndrome (PCOS) is the most common endocrine disorders among women in reproductive age, but diagnostic criteria used in clinical practice are still controversial. In 1990 the National Institute of HEALTH (NIH) conference on PCOS recommended that diagnostic criteria should include biochemical evidence of hyperandrogenism and ovarian dysfunction (in the absence of non-classical adrenal hyperplasia) without considering the morphological diagnosis of polycystic ovary by ultrasound as an essential part of the diagnosis. In the Rotterdam PCOS workshop of May 2003, however, PCOS is diagnosed when 2 of the following criteria are recognized: oligomenorrhea and/or anovulation, clinical or biochemical signs of hyperandrogenism, ultrasound findings of polycystic ovary. Further-more, it is underlined that the metabolic study is not necessary for PCOS diagnosis, while it is suggested for "at risk patients" (obesity, diabetes, familiar and obstetrical history) with an oral glucose tolerance test (OGTT). A recent study carried out by our group underlined the role of ultrasound parameter, in particular suggesting a ratio between ovarian stroma area and total area of the ovarian section (S/A), with a cut-off of 0.34, as "gold parameter" for PCOS diagnosis, because it shows high sensitivity and specificity (96.3%, 97.0% for the S/A).

  10. Social instability stress in adolescent male rats reduces social interaction and social recognition performance and increases oxytocin receptor binding.

    PubMed

    Hodges, Travis E; Baumbach, Jennet L; Marcolin, Marina L; Bredewold, Remco; Veenema, Alexa H; McCormick, Cheryl M

    2017-09-17

    Social experiences in adolescence are essential for displaying context-appropriate social behaviors in adulthood. We previously found that adult male rats that underwent social instability stress (SS) in adolescence had reduced social interactions with unfamiliar peers compared with non-stressed controls (CTL). Here we determined whether SS altered social recognition and social reward and brain oxytocin and vasopressin receptor density in adolescence. We confirmed that SS rats spent less time interacting with unfamiliar peers than did CTL rats (p=0.006). Furthermore, CTL rats showed a preference for novel over familiar conspecifics in a social recognition test whereas SS rats did not, which may reflect reduced recognition, impaired memory, or reduced preference for novelty in SS rats. The reward value of social interactions was not affected by SS based on conditioned place preference tests and based on the greater time SS rats spent investigating stimulus rats than did CTL rats when the stimulus rat was behind wire mesh (p=0.03). Finally, oxytocin receptor binding density was higher in the dorsal lateral septum and nucleus accumbens shell in SS rats compared with CTL rats (p=0.02, p=0.01, respectively). No effect of SS was found for vasopressin 1a receptor binding density in any of the brain regions analyzed. We discuss the extent to which the differences in social behavior exhibited after social instability in adolescence involve changes in social salience and social competency, and the possibility that changes in oxytocin signaling in the brain underlie the differences in social behavior. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  11. The interaction of glycolysis, gluconeogenesis and the tricarboxylic acid cycle in rat liver in vivo

    PubMed Central

    Heath, D. F.; Threlfall, C. J.

    1968-01-01

    oxaloacetate did not equilibrate with fumarate in either. From this and other findings it was deduced: (b) that malate or fumarate or both left the mitochondrion, and not oxaloacetate; (c) that there was a loss from the mitochondrion of a fraction of the malate or fumarate or both formed from succinate, and (d) the resulting deficiency of oxaloacetate for the perpetuation of the tricarboxylic acid cycle was made up from pyruvate in fed and post-absorptive rats, but (e) in the starved rat could only be made up by utilization of glutamate. (f) In the fed rat the tricarboxylic acid cycle ran mostly on pyruvate, but in the post-absorptive and starved rat mostly on fat. (g) In the injured rat the tricarboxylic acid cycle was slowed, label in oxaloacetate was completely symmetrized (cf. conclusion a), and the tricarboxylic acid cycle utilized glutamate. (h) The conclusions were not invalidated by isotopic exchange, i.e. flux of label without net flux of compound, nor by interaction with lipogenic processes. (i) In the kidneys interaction between the tricarboxylic acid cycle and gluconeogenesis was different from in the liver, and was much less. The effects on the theory were roughly assessed, and were small. 4. The experiments and optimum experimental conditions required to check the theory are listed, and several predictions, open to experimental confirmation, are made. PMID:5726212

  12. Interactive effects of growth hormone and exercise on muscle mass in suspended rats

    NASA Technical Reports Server (NTRS)

    Grindeland, Richard E.; Roy, Roland R.; Edgerton, V. Reggie; Grossman, Elena J.; Mukku, Venkat R.; Jiang, Bian; Pierotti, David J.; Rudolph, Ingrid

    1994-01-01

    Measures to attenuate muscle atrophy in rats in response to simulated microgravity (hindlimb suspension (HS)) have been only partially successful. In the present study, hypophysectomized rats were in HS for 7 days, and the effects of recombinant human growth hormone (GH), exercise (Ex), or GH+Ex on the weights, protein concentrations, and fiber cross-sectional areas (CSAs) of hindlimb muscles were determined. The weights of four extensor muscles, i.e., the soleus (Sol), medial (MG) and lateral (LG) gastrocnemius, and plantaris (Plt), and one adductor, i.e., the adductor longus (AL), were decreased by 10-22% after HS. Fiber CSAs were decreased by 34% in the Sol and by 1 17% in the MG after HS. In contrast, two flexors, i.e., the tibialis anterior (TA) and extensor digitorum longus (EDL), did not atrophy. In HS rats, GH treatment alone maintained the weights of the fast extensors (MG, LG, Plt) and flexors (TA, EDL) at or above those of control rats. This effect was not observed in the slow extensor (Sol) or AL. Exercise had no significant effect on the weight of any muscle in HS rats. A combination of GH and Ex treatments yielded a significant increase in the weights of the fast extensors and in the CSA of both fast and slow fibers of the MG and significantly increased Sol weight and CSA of the slow fibers of the Sol. The AL was not responsive to either GH or Ex treatments. Protein concentrations of the Sol and MG were higher only in the Sol of Ex and GH+Ex rats. These results suggest that while GH treatment or intermittent high intensity exercise alone have a minimal effect in maintaining the mass of unloaded muscle, there is a strong interactive effect of these two treatments.

  13. Dextromethorphan interactions with histaminergic and serotonergic treatments to reduce nicotine self-administration in rats.

    PubMed

    Briggs, Scott A; Hall, Brandon J; Wells, Corinne; Slade, Susan; Jaskowski, Paul; Morrison, Margaret; Rezvani, Amir H; Rose, Jed E; Levin, Edward D

    2016-03-01

    Combining effective treatments with diverse mechanisms of action for smoking cessation may provide better therapy by targeting multiple points of control in the neural circuits underlying addiction. Previous research in a rat model has shown that dextromethorphan, which has α3β4 nicotinic and NMDA glutamatergic antagonist actions, significantly decreases nicotine self-administration. We have found in the rat model that the H1 histamine antagonist pyrilamine and the serotonin 5HT2C agonist lorcaserin also significantly reduce nicotine self-administration. The current studies were conducted to determine the interactive effects of dextromethorphan with pyrilamine and lorcaserin on nicotine self-administration in rats. Young adult female rats were fitted with jugular IV catheters and trained to self-administer a nicotine infusion dose of 0.03-mg/kg/infusion. In an initial dose-effect function study of dextromethorphan, we found a monotonic decrease in nicotine self-administration over a dose range of 1 to 30-mg/kg with the lowest effective dose of 3-mg/kg. Then, with two separate cohorts of rats, dextromethorphan (0, 3.3, and 10-mg/kg) interactions with pyrilamine (0, 4.43, and 13.3-mg/kg) were investigated as well as interactions with lorcaserin (0, 0.3125 and 0.625-mg/kg). In the pyrilamine-dextromethorphan interaction study, an acute dose of pyrilamine (13.3-mg/kg) as well as an acute dose of dextromethorphan caused a significant decrease in nicotine self-administration. There were mutually augmenting effects of these two drugs. The combination of dextromethorphan (10-mg/kg) and pyrilamine (13.3-mg/kg) significantly lowered nicotine self-administration relative to either 10-mg/kg of dextromethorphan alone (p<0.05) or 13.3-mg/kg of pyrilamine alone (p<0.0005). In the lorcaserin-dextromethorphan study, an acute dose of lorcaserin (0.312-mg/kg) as well as an acute dose of dextromethorphan (10-mg/kg) caused a significant decrease in nicotine self

  14. Dextromethorphan Interactions with Histaminergic and Serotonergic Treatments to Reduce Nicotine Self-administration in Rats

    PubMed Central

    Briggs, Scott A.; Hall, Brandon J.; Wells, Corinne; Slade, Susan; Jaskowski, Paul; Morrison, Margaret; Rezvani, Amir H.; Rose, Jed E.; Levin, Edward D.

    2015-01-01

    Combining effective treatments with diverse mechanisms of action for smoking cessation may provide better therapy by targeting multiple points of control in the neural circuits underlying addiction. Previous research in a rat model has shown that dextromethorphan, which has α3β4 nicotinic and NMDA glutamatergic antagonist actions, significantly decreases nicotine self-administration. We have found in the rat model that the H1 histamine antagonist pyrilamine and the serotonin 5HT2c agonist lorcaserin also significantly reduce nicotine self-administration. The current studies were conducted to determine the interactive effects of dextromethorphan with pyrilamine and lorcaserin on nicotine self-administration in rats. Young adult female rats were fitted with jugular IV catheters and trained to self-administer a nicotine infusion dose of 0.03-mg/kg/infusion. In an initial dose-effect function study of dextromethorphan, we found a monotonic decrease in nicotine self-administration over a dose range of 1 to 30-mg/kg with a lowest effective dose of 3-mg/kg. Then, with two separate cohorts of rats, dextromethorphan (0, 3.3, and 10-mg/kg) interactions with pyrilamine (0, 4.43, and 13.3-mg/kg) were investigated as well as interactions with lorcaserin (0, 0.3125 and 0.625-mg/kg). In the pyrilamine-dextromethorphan interaction study, the acute dose of pyrilamine (13.3-mg/kg) as well as an acute dose of dextromethorphan caused a significant decrease in nicotine self-administration. There were mutually augmenting effects of these two drugs. The combination of dextromethorphan (10-mg/kg) and pyrilamine (13.3-mg/kg) significantly lowered nicotine self-administration relative to either 10-mg/kg of dextromethorphan alone (p<0.05) or 13.3-mg/kg of pyrilamine alone (p<0.0005). In the lorcaserin-dextromethorphan study, an acute dose of lorcaserin (0.312-mg/kg) as well as an acute dose of dextromethorphan (10-mg/kg) caused a significant decrease in nicotine self

  15. From visual affordances in monkey parietal cortex to hippocampo-parietal interactions underlying rat navigation.

    PubMed Central

    Arbib, M A

    1997-01-01

    This paper explores the hypothesis that various subregions (but by no means all) of the posterior parietal cortex are specialized to process visual information to extract a variety of affordances for behaviour. Two biologically based models of regions of the posterior parietal cortex of the monkey are introduced. The model of the lateral intraparietal area (LIP) emphasizes its roles in dynamic remapping of the representation of targets during a double saccade task, and in combining stored, updated input with current visual input. The model of the anterior intraparietal area (AIP) addresses parietal-premotor interactions involved in grasping, and analyses the interaction between the AIP and premotor area F5. The model represents the role of other intraparietal areas working in concert with the inferotemporal cortex as well as with corollary discharge from F5 to provide and augment the affordance information in the AIP, and suggests how various constraints may resolve the action opportunities provided by multiple affordances. Finally, a systems-level model of hippocampo parietal interactions underlying rat navigation is developed, motivated by the monkey data used in developing the above two models as well as by data on neurones in the posterior parietal cortex of the monkey that are sensitive to visual motion. The formal similarity between dynamic remapping (primate saccades) and path integration (rat navigation) is noted, and certain available data on rat posterior parietal cortex in terms of affordances for locomotion are explained. The utility of further modelling, linking the World Graph model of cognitive maps for motivated behaviour with hippocampal-parietal interactions involved in navigation, is also suggested. These models demonstrate that posterior parietal cortex is not only itself a network of interacting subsystems, but functions through cooperative computation with many other brain regions. PMID:9368931

  16. Changes in the sexual behavior and testosterone levels of male rats in response to daily interactions with estrus females

    PubMed Central

    Shulman, Leanne M.; Spritzer, Mark D.

    2014-01-01

    Male rat sexual behavior has been intensively studied over the past 100 years, but few studies have examined how sexual behavior changes over the course of several days of interactions. In this experiment, adult male rats (n = 12) were given daily access to estrus females for 30 min per day for 15 consecutive days and control males did not interact with females. Ovariectomized females were induced into estrus with hormonal injections, and males interacted with a different female each day. The amount of sexual activity (mounts, intromissions, and ejaculations) was found to cycle with a period of approximately 4 days in most male rats. Additionally, blood was collected every other day following sexual interactions to assess serum testosterone levels. Testosterone was found to peak on the first day of interaction and then fell back to near the level of control rats that did not interact with females. Following the initial peak, testosterone concentrations fluctuated less in males exposed to females than in controls. Sexual activity was not found to predict testosterone concentration. We conclude that when male rats have daily sexual interactions, sexual behavior tends to show cyclic changes and testosterone is significantly elevated only on the first day of interactions. PMID:24813700

  17. Synergistic Interaction Between Dexmedetomidine and Ulinastatin Against Vincristine-Induced Neuropathic Pain in Rats.

    PubMed

    Nie, Bilin; Zhang, Subo; Huang, Zhuxi; Huang, Jingxiu; Chen, Xiaodi; Zheng, Yaochao; Bai, Xiaohui; Zeng, Weian; Ouyang, Handong

    2017-07-08

    Antimicrotubulin chemotherapeutic agents such as vincristine (VCR), often induce peripheral neuropathic pain. It is usually permanent and seriously harmful to cancer patients' quality of life and can result in the hampering of clinical treatments. Currently, there is no definitive therapy, and many of the drugs approved for the treatment of other neuropathic pain have shown little or no analgesic effect. It is therefore vital to find new and novel therapeutic strategies for patients suffering from chemotherapeutic agent-induced neuropathic pain to improve patients' quality of life. This study shows that intrathecal injections of dexmedetomidine (DEX), or intraperitoneally administered ulinastatin (UTI) significantly reduces Sprague Dawley rats' mechanical allodynia induced by VCR via upregulation of interleukin-10 expression and activating the α2-adrenergic receptor in dorsal root ganglion (DRG). Moreover, when combined there is a synergistic interaction between DEX and UTI, which acts against VCR-induced neuropathic pain. This synergistic interaction between DEX and UTI may be partly attributed to a common analgesic pathway in which the upregulation of interleukin -10 plays an important role via activating α2-adrenergic receptor in rat dorsal root ganglion. The combined use of DEX and UTI does not affect the rat's blood pressure, heart rate, sedation, motor score, spatial learning, or memory function. All of these show that the combined use of DEX and UTI is an effective method in relieving VCR-induced neuropathic pain in rats. This article documents the synergistic interaction between 2 widely used drugs, DEX and UTI, against VCR-induced neuropathic pain. The results provide a potential target and novel drug administrated method for the clinical treatment of chemotherapy-induced peripheral neuropathic pain. Copyright © 2017 American Pain Society. Published by Elsevier Inc. All rights reserved.

  18. Effect of alcohol and kolanut interaction on brain sodium pump activity in Wistar albino rats.

    PubMed

    Obochi, G O; Abara, A E; Malu, S P; Obi-Abang, M; Edu, F E; Eteng, M U; Umoh, I B

    2007-01-01

    Effect of alcohol-kolanut interaction on sodium pump activity in wistar albino rats was studied. Thirty wistar albino rats were divided into six groups of five (5) rats per group and used for the study. The control group (1) received via oral route a placebo (4 ml of distilled water). Groups 2 to 6 were treated for a period of 21 days, with (10% v/v) of alcohol (group 2), 50mg/kg body weight of kolanut (group 3), 50 mg/kg body weight of caffeine (group 4), 4 ml of 10% v/v of alcohol and 50 mg/kg body weight kolanut (group 5), 4 ml of 10% v/v of alcohol and 50 mg/kg body weight of caffeine in 4.0 ml of the vehicle via gastric intubation respectively. A day after the final exposure, the brain of each rat was harvested and processed to examine several biochemical parameters, i.e., total ATpase, ouabain-insensitive ATpase, ouabain sensitive ATpase (Na(+)-K(+)ATPase), non-enzymatic breakdown of ATP and inorganic phosphate (Pi) released. The results showed that the essential enzyme of the brain responsible for neuronal function, Na(+)-K(+)ATPase, was inhibited by alcohol-kolanut co-administration relative to control, resulting in a decrease in Na(+)-K(+)ATPase activity, ATP production, ion transport and action potential, leading to loss of neuronal activities.

  19. Honeybee product therapeutic as stem cells homing for ovary failure.

    PubMed

    Safitri, Erma; Widiyatno, Thomas V; Prasetyo, R Heru

    2016-11-01

    Complexity of the method of isolation, cultivation in vitro and the expensive cost of transplantation process of stem cells, it would require an innovation to homing and differentiation of stem cells and increase folliculogenesis. The stem cells homing was achieved through the provision of food or beverages derived from natural materials like honeybee product. Through honeybee product, there will be homing of stem cells and accompany with the sources from the body itself will take place in regeneration of the ovary. Female rats model of degenerative ovary was obtained through food fasting but still have drinking water for 5 days. It caused malnutrition and damage of the ovarian tissue. The administration of 50% honeybee product (T1) was performed for 10 consecutive days, while the positive control group (T0+) was fasted and not given honeybee product and the negative control (T0-) not fasted and without honeybee product. Observations were taken for homing of stem cells, raised of folliculogenesis, differentiation of stem cells, and regeneration of the ovarian tissue using routine H&E staining. Homing of stem cells shown the vascular endothelial growth factor and granulocyte colony-stimulating factor expression; enhancement of folliculogenesis was indicated by an increase of follicle dee Graaf count; enhancement of differentiation of stem cells was indicated by growth differentiation factor-9 expression; and regeneration of ovarian tissue indicated by intact ovarian tissue with growing follicles. Honeybee product can be induced endogenous stem cells in regeneration of ovary failure due to malnutrition.

  20. Characterizing olfactory binary mixture interactions in Fischer 344 rats using behavioral reaction times.

    PubMed

    Yoder, Wendy M; Gaynor, Leslie; Windham, Ethan; Lyman, Michelle; Munizza, Olivia; Setlow, Barry; Bizon, Jennifer L; Smith, David W

    2015-06-01

    Response times provide essential subthreshold perceptual data that extend beyond accuracy alone. Behavioral reaction times (RTs) were used to characterize rats' ability to detect individual odorants in a series of complimentary binary odorant mixture ratios. We employed an automated, liquid-dilution olfactometer to train Fischer 344 rats (N = 8) on an odor identification task using nonreinforced probe trials. Binary mixture ratios composed of aliphatic odorants (citral and octanol) were arranged such that relative contributions of the 2 components varied systematically by a factor of 1% (v/v). Odorant concentrations for the target (S+), control (S-), and mixture (S+:S-) odorants were presented relative to threshold for each rat. Rats were initially trained to respond by licking at a spout to obtain liquid reward for either citral or octanol as the reinforced target (S+) odorant. After achieving 100% accuracy, rats were transferred to variable ratio (VR 2) reinforcement for correct responding. Nonreinforced probe trials (2 per block of 22 trials) were tested for each mixture ratio and recorded as either S+ (rats lick-responded in the presence of the mixture) or S- (rats refrained from licking), thereby indicating detection of the trained, S+ odorant. To determine the perceived salience for each ratio, RTs (latency from odorant onset to lick response) were recorded for each trial. Consistent with previous studies, RTs for both odorants were shortest (~150-200ms) when the probe trials consisted of a single, monomolecular component. Binary mixtures that contained as little as 1% of the S-, nontarget odorant, however, were sufficiently different perceptually to increase behavioral RTs (i.e., rats hesitated longer before responding); RTs changed systematically as a function of the binary ratio. Interestingly, the rate of RT change was dependent on which odorant served as the S+, suggesting an asymmetric interaction between the 2 odorants. The data demonstrate the value

  1. Pharmacokinetic evaluation of the interaction between oral kaempferol and ethanol in rats.

    PubMed

    Zhou, Zhaoxiang; Wang, Meng; Guo, Zengjun; Zhang, Xiaoying

    2016-12-01

    This study was aimed at investigating the effect of ethanol on oral bioavailability of kaempferol in rats, namely, at disclosing their possible interaction. Kaempferol (100 or 250 mg kg-1 bm) was administered to the rats by oral gavage with or without ethanol (600 mg kg-1 bm) co-administration. Intravenous administration (10 and 25 mg kg-1 bm) of kaempferol was used to determine the bioavailability. The concentration of kaempferol in plasma was estimated by ultra high performance liquid chromatography. During coadministration, a significant increase of the area under the plasma concentration-time curve as well as the peak concentration were observed, along with a dramatic decrease in total body clearance. Consequently, the bioavailability of kaempferol in oral control groups was 3.1 % (100 mg kg-1 bm) and 2.1 % (250 mg kg-1 bm). The first was increased by 4.3 % and the other by 2.8 % during ethanol co-administration. Increased permeability of cell membrane and ethanolkaempferol interactions on CYP450 enzymes may enhance the oral bioavailability of kaempferol in rats.

  2. Developmental morphology of the neonatal alligator (Alligator mississippiensis) ovary.

    PubMed

    Moore, Brandon C; Uribe-Aranzábal, Mari Carmen; Boggs, Ashley S P; Guillette, Louis J

    2008-03-01

    American alligator (Alligator mississippiensis) ovary development is incomplete at hatching. During the months following hatching, the cortical processes of oogenesis started in ovo continues and folliculogenesis is initiated. Additionally, the medullary region of the gonad undergoes dramatic restructuring. We describe alligator ovarian histology at hatching, 1 week, 1 month, and 3 months of age in order to characterize the timing of morphological development and compare these findings to chicken ovary development. At hatching, the ovarian cortex presents a germinal epithelium containing oogonia and a few primary oocytes irregularly scattered between somatic epithelial cells. The hatchling medulla shows fragmentation indicative of the formation of lacunae. By 1 week of age, oocytes form growing nests and show increased interactions with somatic cells, indicative of the initiation of folliculogenesis. Medullary lacunae increase in diameter and contain secretory material in their lumen. At 1 month, nest sizes and lacunar diameters continue to enlarge. Pachytene oocytes surrounded by somatic cells are more frequent. Trabeculae composed of dense irregular connective tissue divide cortical nests. Three months after hatching oocytes in meiotic stages of prophase I up to diplotene are present. The ovary displays many enlarged follicles with oocytes in diplotene arrest, thecal layers, lampbrush chromosomes, and complete layers of follicular cells. The medulla is an elaborated complex of vascularized lacunae underlying the cortex and often containing discrete lymphoid aggregates. While the general morphology of the alligator ovary is similar to that of the chicken ovary, the progression of oogenesis and folliculogenesis around hatching is notably slower in alligators. Diplotene oocytes are observed at hatching in chickens, but not until 3 months in alligators. Folliculogenesis is completed at 3 weeks in chickens whereas it is still progressing at 3 months in alligators.

  3. Behavioral and Endocrine Consequences of Simultaneous Exposure to Two Different Stressors in Rats: Interaction or Independence?

    PubMed Central

    Muñoz-Abellán, Cristina; Rabasa, Cristina; Daviu, Nuria; Nadal, Roser; Armario, Antonio

    2011-01-01

    Although behavioral and endocrine consequences of acute exposure to stressors have been extensively studied, little is known about how simultaneous exposure to two different stressors interacts to induce short- and long-term effects. In the present experiment we studied this interaction in adult male rats exposed to cat fur odor (impregnated cloth) or immobilization on boards either separately or simultaneously. We reasoned that exposure to the odor of a potential predator while immobilized, may potentiate its negative consequences as compared to exposure to only one of the stressors. Exposure to cat odor elicited the expected reduction of activity and avoidance of the area where the impregnated cloth was located. The endocrine response (plasma levels of ACTH and corticosterone, as a measure of the hypothalamic-pituitary-adrenal axis, HPA) was markedly greater after immobilization than after cat fur odor and no additive effects were found by simultaneous exposure to both stressors. Cat odor, but not immobilization, increased anxiety-like behavior as evaluated in the elevated plus-maze 7 days after the stressors, with no evidence of enhanced HPA activation. In addition, cat odor exposure resulted in long-lasting (8 days later) fear conditioning to the box containing a clean cloth, which was reflected by hypoactivity, avoidance of the cloth area and enhanced HPA activation. All these effects were similarly observed in rats exposed simultaneously to cat odor and immobilization. In rats only exposed to immobilization, only some weak behavioral signs of fear conditioning were found, but HPA activation in response to the context paired to immobilization was enhanced to the same extent as in cat odor-exposed animals, supporting a certain degree of endocrine conditioning. The present results did not reveal important behavioral interactions between the two stressors when animals experienced both simultaneously, whereas some interactions were found regarding HPA activation

  4. Interaction of a rat lung lectin with the exopolysaccharides of Pseudomonas aeruginosa.

    PubMed Central

    McArthur, H A; Ceri, H

    1983-01-01

    The specific interaction between the exopolysaccharide purified from a number of Pseudomonas aeruginosa isolates from cystic fibrosis patients and a rat lung heparin-lectin was assayed. The polysaccharide prepared from Homma serotypes M, B, I, and G did not act as hapten inhibitors of lectin activity, whereas the polymers prepared from ca. 80% of strains that did not type with Homma serum did act as hapten inhibitors. Inhibition was shown not to be due to lipopolysaccharide. The infrared spectrums of both inhibitory and noninhibitory polymers appeared very similar, although small amounts of glucose and an unidentified amino sugar were found only in the nontypable strains. This evidence suggests that rat lung lectin recognizes and distinguishes a specific type of alginate-like polymer prevalent on the Homma nontypable P. aeruginosa. PMID:6417018

  5. [Identification of rat and human hemoglobin acetilation sites after its interaction with acetylsalicylic acid].

    PubMed

    Shreĭner, E V; Murashko, E A; Dubrovskiĭ, Ia D; Krasnov, N V; Podol'skaia, E P; Babakov, V N

    2012-01-01

    The possibility of interaction of 0.1 mg/mL acetylsalicylic acid with purified human and rat globin in vitro during 24 h at 37 degrees C was investigated. The rat globin can be modified with acetylsalicylic acid on aminoacid residues K-17, K-57, K-91, K-140 in alpha subunit as well as on K-18, K-77 in beta subunit. The human globin can be modified with acetylsalicylic acid on aminoacid residues K-17, K-41, K-57 and K-91 in alpha subunit as well as on K-18, K-96 and K- 133 in beta subunit. We identified of acetetylated lysines K-17 and K-57 in alpha subunit of human hemoglobin after incubation whole blood with 0.1 mg/mL acetylsalicylic acid during 3 h.

  6. Interactions between tactile and noxious visceral inputs in rat nucleus gracilus.

    PubMed

    Rong, Pei-Jing; Zhang, Jian-Liang; Zhang, Hong-Qi

    2004-05-20

    Recent studies have revealed that noxious visceral inputs travel in the dorsal column pathway, and interactions between colorectal noxious and tactile inputs occur in the ventrobasal thalamus. This investigation was to test whether the somatovisceral interactions also take place at a lower level in the dorsal column nuclei. Extracellular single neuron recordings were carried out in nucleus gracilus of anesthetized rats. Forty-three neurons responsive to colorectal distension (CRD) all had excitatory responses to tactile stimuli, and their tactile responses were predominantly (31/43 units) enhanced by preceding CRD. In contrast, the neuronal responses to CRD were reduced in 22/43 units when preceded by tactile stimulation but in two units there was an enhancement. The similarity and differences in the gracile response features in comparison with the thalamic recordings suggest that somatovisceral interactions take place at multiple levels in the dorsal column-medial lemniscus system.

  7. Interaction of exposure concentration and duration in determining acute toxic effects of sarin vapor in rats.

    PubMed

    Mioduszewski, R; Manthei, J; Way, R; Burnett, D; Gaviola, B; Muse, W; Thomson, S; Sommerville, D; Crosier, R

    2002-04-01

    Sarin (GB) vapor exposure is associated with both systemic and local toxic effects occurring primarily via the inhalation and ocular routes. The objective of these studies was to develop models for predicting dose-response effects of GB vapor concentrations as a function of exposure duration. Thus, the probability of GB vapor-induced lethality was estimated in rats exposed to various combinations of exposure concentration and duration. Groups of male and female Sprague-Dawley rats were exposed to one of a series of GB vapor concentrations for a single duration (5-360 min) in a whole-body dynamic chamber. The onset of clinical signs and changes in blood cholinesterase activity were measured with each exposure. Separate effective concentrations for lethality in 50% of the exposed population (LC50) and corresponding dose-response slopes were determined for each exposure duration by the Bliss probit method. Contrary to that predicted by Haber's rule, the interaction of LC50 x time (LCT50) values increased with exposure duration (i.e., the CT for 50% lethality in the exposed population and corresponding dose-response slope was not constant over time). A plot of log (LCT50) versus log (exposure time) showed significant curvature. Predictive models derived from multifactor probit analysis of results describing the relationship between exposure conditions and probability of lethality in the rat are discussed. Overall, female rats were more sensitive to GB vapor toxicity than male rats over the range of exposure concentration and duration studied. Miosis was the initial clinical sign noted after the start of GB vapor exposure. Although blood cholinesterase activity was significantly inhibited by GB vapor exposure, poor correlation between cholinesterase inhibition and exposure conditions or cholinesterase inhibition and severity of clinical signs was noted.

  8. Drug-drug interaction between voriconazole and oral hypoglycemic agents in diabetic rats

    PubMed Central

    Kumar, Boyina Hemanth; Joshi, Bheemachari; Singh, Jayasingh Chellammal Hanish; Diwan, Prakash V.

    2013-01-01

    Objective: The objective was to study the of drug-drug interaction between voriconazole and oral hypoglycemic agents in normal and alloxan induced diabetic rats. Materials and Methods: The study was designed in two phases. In the first phase, influence of glibenclamide (0.45 mg/kg, p.o.) and pioglitazone (2.7 mg/kg, p.o. once daily) on blood glucose levels in normoglycemic rats was studied and then influence of voriconazole (18 mg/kg, p.o. twice daily.) pre-treatment on the hypoglycemic activity studied. Simultaneously the influence of voriconazole treatment for seven consecutive days (per se effect) on blood glucose levels was also studied in normoglycemic rats. In the second phase of the study alloxan-induced diabetic rats were used to find out the influence of voriconazole pre-treatment on glibenclamide and pioglitazone induced hypoglycemic effect in pathophysiological condition. Blood samples were collected from retro orbital plexus at regular intervals of 0.0, 0.5, 1.0, 2.0, 4.0, 8.0, 12.0, 18.0 and 24.0 h after drug treatment. All the blood samples were analyzed for plasma glucose by glucose oxidase peroxidase method (GOD/POD). Results: The therapeutic dose of voriconazole potentiates the hypoglycemic activity of glibenclamide and pioglitazone both in normoglycemic and diabetic rats respectively. Conclusion: The results indicate that the dose of oral hypoglycemic agents needs to be adjusted if co-administered with voriconazole. PMID:23716892

  9. Negligible Pharmacokinetic Interaction of Red Ginseng and Losartan, an Antihypertensive Agent, in Sprague-Dawley Rats.

    PubMed

    Ryu, Sung Ha; Kim, Yong Soon; Jang, Hyun-Jun; Kim, Kyu-Bong

    2015-01-01

    Red ginseng (RG) is one of the top selling herbal medicines in Korea, but is not recommended in hypertensive patients. In this study, the pharmacokinetic (PK) interaction between RG and losartan, an antihypertensive drug, was examined. RG was orally administered for 2 wk to male Sprague-Dawley (S-D) rats at either control (0), 0.5, 1, or 2 g/kg/d for 2 wk. After the last administration of RG and 30 min later, all animals were treated with 10 mg/kg losartan by oral route. In addition, some S-D rats were administered RG orally for 21 d at 2 g/kg followed by losartan intravenously (iv) at 10 mg/kg/d. Post losartan administration, plasma samples were collected at 5, 15, and 30 min and 1, 1.5, 2, 3, 6, 12, and 24 h. Plasma concentrations of losartan and E-3174, the active metabolite of losartan, were analyzed by a high-pressure liquid chromatography-tandem mass spectrometer system (LC-MS/MS). Oral losartan administration showed dose-dependent pharmacokinetics (PK) increase with time to maximum plasma, but this was not significant between different groups. There was no significant change in tmax with E-3174 PK. With iv losartan, pharmacokinetics showed elevation of area under the plasma concentration-time curve from time zero extrapolated to infinitity. There was not a significant change in AUCinf with E-3174 PK. Therefore, RG appeared to interfere with biotransformation of losartan, as RG exerted no marked effect on E-3174 PK in S-D rats. Data demonstrated that oral or iv treatment with losartan in rats pretreated with RG for 2 wk showed that losartan PK was affected but E-3174 PK remained unchanged among different dose groups. These results suggested that RG induces negligible influence on losartan and E-3174 PK in rats.

  10. Propensity for social interaction predicts nicotine reinforced behaviors in outbred rats

    PubMed Central

    Wang, Tengfei; Han, Wenyan; Wang, Bin; Jiang, Qin; Solberg-Woods, Leah C.; Palmer, Abraham A.; Chen, Hao

    2014-01-01

    Social and genetic factors can influence smoking behavior. Using olfactogustatory stimuli as the sensory cue for intravenous nicotine self-administration (SA), we previously showed that social learning of nicotine contingent odor cue prevented rats from developing conditioned taste aversion and allowed them to instead establish stable nicotine self-administration. We hypothesized that genetic factors influenced socially acquired nicotine SA. A heterogenous stock (HS; N/NIH) of outbred rats was trained to self-administer nicotine using the social learning protocol. Both male and female HS rats acquired nicotine self-administration, but females self-administered more nicotine than males. After extinction, the context previously paired with nicotine self-administration, in conjunction with socially-transmitted drug cues, were sufficient to cause reinstatement of drug-seeking behavior. Wide variation in both nicotine intake and reinstatement were observed. Using multiple regression analysis, we found measures of social interaction were significant predictors of nicotine intake and reinstatement of drug-seeking in both males and females. Furthermore, measures of depression were predictors of nicotine intake in both males and females while anxiety was a predictor only in males and response to novelty was a predictor only in females. In males, measures of both depression and anxiety predicted nicotine reinstatement. Together, these data supported the ideas that genetically determined propensities for emotional and social phenotypes are significant determinants for nicotine reinforced behavior, and that the heterogeneous stock rat is a suitable tool for dissecting genetic mechanisms that may underlie the interaction between social behavior, anxiety, depression and smoking. PMID:24289793

  11. The interaction between working and reference spatial memories in rats on a radial maze.

    PubMed

    Guitar, Nicole A; Roberts, William A

    2015-03-01

    The interaction of reference and working memory was studied in rats on an eight-arm radial maze. Each trial involved a two-phase procedure in which a rat was forced to enter four arms on the maze in a study phase and then was allowed to choose among all eight arms in a test phase given 5-s later, with choice of only the previously unvisited arms rewarded. For each rat, two arms on the maze were designated as reference memory arms because they were never entered in the study phase and were always rewarded in the test phase. The other two arms never entered in the study phase and rewarded in the test phase were working memory arms and varied randomly from trial to trial. In Experiment 1, rats showed acquisition of equivalent preference for entering the reference and working memory arms in their first four choices of the test phase. Subsequent tests carried out in Experiment 2 compared performance at 5-s, 1-h, and 24-h retention intervals when reference memory and working memory were congruent and incongruent. Higher accuracy for choice of reference memory arms than working memory arms appeared at the 1-h and 24-h retention intervals on congruent tests but not on incongruent tests. A process dissociation procedure analysis indicated that working memory but not reference memory declined over the 24-h retention interval. The interaction of working and reference memory was shown by superior choice of reference memory arms on congruent tests than on incongruent tests at 1-h and 24-h retention intervals but not at the 5-s retention interval. These findings suggest that working and reference memory are independent systems that can facilitate and compete with one another. This article is part of a Special Issue entitled: Tribute to Tom Zentall.

  12. Herb-drug pharmacokinetic interaction between carica papaya extract and amiodarone in rats.

    PubMed

    Rodrigues, Márcio; Alves, Gilberto; Francisco, Joana; Fortuna, Ana; Falcão, Amílcar

    2014-01-01

    Carica papaya has been traditionally used worldwide in folk medicine to treat a wide range of ailments in humans, including the management of obesity and digestive disorders. However, scientific information about its potential to interact with conventional drugs is lacking. Thus, this work aimed to investigate the interference of a standardized C. papaya extract (GMP certificate) on the systemic exposure to amiodarone (a narrow therapeutic index drug) in rats. In the first pharmacokinetic study, rats were simultaneously co-administered with a single-dose of C. papaya (1230 mg/kg, p.o.) and amiodarone (50 mg/kg, p.o.); in the second study, rats were pre-treated for 14 days with C. papaya (1230 mg/kg/day, p.o.) and received amiodarone (50 mg/kg, p.o.) on the 15th day. Rats of the control groups received the herbal extract vehicle. Blood samples were collected before dosing and at 0.25, 0.5, 1, 2, 4, 6, 8 and 12 h following amiodarone administration; in addition, at 24 h post-dose, blood and tissues (heart, liver, kidneys and lungs) were also harvested. Thereafter, the concentrations of amiodarone and its major metabolite (mono-N-desethylamiodarone) were determined in plasma and tissue samples employing a high-performance liquid chromatography-diode array detection method previously developed and validated. In both studies was observed a delay in attaining the maximum plasma concentrations of amiodarone (tmax) in the rats treated with the extract. Nevertheless, it must be highlighted the marked increase (60-70%) of the extent of amiodarone systemic exposure (as assessed by AUC0-t and AUC0-∞) in the rats pre-treated with C. papaya comparatively with the control (vehicle) group. The results herein found suggest an herb-drug interaction between C. papaya extract and amiodarone, which clearly increase the drug bioavailability. To reliably assess the clinical impact of these findings appropriate human studies should be conducted.

  13. Bilateral Inguinal Hernias Containing Ovaries

    PubMed Central

    Basrur, Gurudutt Bhaskar

    2015-01-01

    Inguinal hernias are rare in females. The authors report a case of bilateral inguinal hernias in a 10-year-old female. On exploration, the patient was found to be having a sliding hernia containing incarcerated ovary as contents on both sides. Peroperatively the contents were reduced, the sac was transfixed at its base and the redundant sac was excised. The repair of this form of hernias is more difficult because of adhesions between the contents and the wall of the sac and risk of damage during dissection. A description of this clinical presentation in the pre operative assessment and operative management are discussed in this report. PMID:25918632

  14. A subtoxic interactive toxicity study of ethanol and chromium in male Wistar rats.

    PubMed

    Acharya, S; Mehta, K; Krishnan, S; Rao, C V

    2001-02-01

    The purpose of this study was to evaluate the interactive toxicity of ethanol with potassium dichromate (K2Cr2O7-chromium). Young, male Wistar rats (100-120 g) were divided into four groups of five or six animals each and were dosed, through water, with 10% ethanol (vol./vol.) or 25 ppm chromium or were dosed with a combination of ethanol+chromium at the same concentrations for a period of 22 weeks ad libitum and were maintained on normal diet. Control animals were maintained on a normal diet and water for the same period. The serum succinate dehydrogenase and liver total triglyceride levels were significantly reduced in the three treated groups. The serum alkaline phosphatase levels were significantly reduced in ethanol-treated rats, and there was no significant change in the acid phosphatase activity. Serum aspartate and alanine aminotransferase levels in the three treated groups were significantly increased. The liver glycogen significantly decreased in both the ethanol-treated and the chromium-treated rats. There was a significant increase in liver total cholesterol levels in chromium-treated rats. Total glutathione levels were significantly decreased in the livers of ethanol-treated and ethanol+chromium-treated rats. To further substantiate these findings, a histological examination of the liver and kidneys was undertaken. The livers of alcohol-treated animals showed altered hepatic architecture in the centrilobular and periportal areas, with increased sinusoidal space (space of Disse), vacuolation, and necrosis of hepatocytes. Similar changes were observed in a histological examination of the livers of chromium-treated rats, except that the damage to the hepatocytes was more confined to the periportal area. Moreover, histological examination of the livers of ethanol+chromium-treated rats revealed uniform damage in the centrilobular and periportal areas, as was observed in the groups treated either with ethanol or chromium. The histological examination of the

  15. Neural activity in the prelimbic and infralimbic cortices of freely moving rats during social interaction: Effect of isolation rearing

    PubMed Central

    Minami, Chihiro; Shimizu, Tomoko

    2017-01-01

    Sociability promotes a sound daily life for individuals. Reduced sociability is a central symptom of various neuropsychiatric disorders, and yet the neural mechanisms underlying reduced sociability remain unclear. The prelimbic cortex (PL) and infralimbic cortex (IL) have been suggested to play an important role in the neural mechanisms underlying sociability because isolation rearing in rats results in impairment of social behavior and structural changes in the PL and IL. One possible mechanism underlying reduced sociability involves dysfunction of the PL and IL. We made a wireless telemetry system to record multiunit activity in the PL and IL of pairs of freely moving rats during social interaction and examined the influence of isolation rearing on this activity. In group-reared rats, PL neurons increased firing when the rat showed approaching behavior and also contact behavior, especially when the rat attacked the partner. Conversely, IL neurons increased firing when the rat exhibited leaving behavior, especially when the partner left on its own accord. In social interaction, the PL may be involved in active actions toward others, whereas the IL may be involved in passive relief from cautionary subjects. Isolation rearing altered social behavior and neural activity. Isolation-reared rats showed an increased frequency and decreased duration of contact behavior. The increased firing of PL neurons during approaching and contact behavior, observed in group-reared rats, was preserved in isolation-reared rats, whereas the increased firing of IL neurons during leaving behavior, observed in group-reared rats, was suppressed in isolation-reared rats. This result indicates that isolation rearing differentially alters neural activity in the PL and IL during social behavior. The differential influence of isolation rearing on neural activity in the PL and IL may be one of the neural bases of isolation rearing-induced behavior. PMID:28459875

  16. Caffeine/nutrition interaction in the rat brain: Influence on latent inhibition and cortical spreading depression.

    PubMed

    de Aguiar, Márlison José Lima; de Aguiar, Cilene Rejane Ramos Alves; Guedes, Rubem Carlos Araújo

    2011-01-10

    Caffeine, like malnutrition, can produce behavioral and electrophysiological alterations. However, the interaction of both factors remains unclear. Here this interaction has been studied in male Wistar rats previously malnourished during the lactation period by feeding their dams the "regional basic diet" of Northeast Brazil, containing about 8% protein, predominantly from vegetable sources (RBD(8)). At 70-75days of life, a subset of the pups was treated intraperitoneally with 30mg/kg caffeine for 4days while being tested according to the behavioral model of latent inhibition. Another group was subjected to an electrophysiological recording of the phenomenon known as cortical spreading depression, and the effects of caffeine injected during the recording session were evaluated. Caffeine did not affect cortical spreading depression, but antagonized latent inhibition in both the RBD(8)-malnourished rats and in the well-nourished control group fed a chow diet with 22% protein. This effect of caffeine was not seen in malnourished rats fed a protein-supplemented RBD (protein increased to 22% by increasing the proportion of foodstuffs from vegetable origin; RBD(22) group), suggesting that the amino acid imbalance of this diet may modulate the caffeine effects on latent inhibition. The results indicate a differential effect of caffeine in the latent inhibition behavioral model, as compared to the cortical spreading depression phenomenon, and this effect is influenced by the early nutritional status of the animal. We suggest that caffeine may modulate dopaminergic subcortical receptors participating in attention processes, but does not interact at the cortical level, in a way that would affect cortical spreading depression. Copyright © 2010 Elsevier B.V. All rights reserved.

  17. Interaction effects of lead on bioavailability and pharmacokinetics of arsenic in the rat.

    PubMed

    Diacomanolis, Violet; Noller, Barry N; Ng, Jack C

    2013-12-01

    Arsenic (As) and lead (Pb) are common contaminants found in mine waste materials. For an evidence-based risk assessment, it is important to better understand the potential interaction of mixed contaminants; and this interaction study was investigated in an in vivo rat model. Following co-administration of a fixed dose of As(V) as in sodium arsenate and different doses of Pb as lead acetate to Sprague-Dawley rats, blood arsenic concentration and bioavailability decreased. A decrease in As blood concentration when lead was co-administered was observed with increasing lead doses. Pharmacokinetic parameters for As in the blood showed faster absorption and elimination of this metalloid in the presence of Pb. The elimination half-life of As decreased from 67 days in As solo group to 27-30 with doses of Pb. Bioavailability of As was also decreased by 30-43 % in the presence of Pb. Decreased urinary excretion of Pb and tissue accumulation were also observed. It indicates lower absorption of As when co-administered with Pb. A probable explanation for these findings is that As co-administration with Pb could have resulted in the formation of less soluble lead arsenate. However, such an interaction between As and Pb could only explain about one-third of the variation when real mine waste materials containing both of these elements were administered to rats. This suggests that other effects from physical and chemical parameters could contribute to the bioavailability of arsenic in complex real environmental samples.

  18. Immunological Interactive Effects between Pollen Grains and Their Cytoplasmic Granules on Brown Norway Rats.

    PubMed

    Abou Chakra, Oussama R; Sutra, Jean-Pierre; Rogerieux, Françoise; Peltre, Gabriel; Sénéchal, Hélène; Lacroix, Ghislaine

    2009-09-01

    : Grass pollen is one of the most important aeroallergen vectors in Europe. Under some meteorological factors, pollen grains can release pollen cytoplasmic granules (PCGs). PCGs induce allergic responses. Several studies have shown that during a period of thunderstorms the number of patients with asthma increases because of higher airborne concentrations of PCGs. : The aims of the study were to assess the allergenicity of interactive effects between pollen and PCGs and to compare it with allergenicity of Timothy grass pollen and PCGs in Brown Norway rats. : Rats were sensitized (day 0) and challenged (day 21) with pollen grains and/or PCGs. Four groups were studied: pollen-pollen (PP), PCGs-PCGs (GG), pollen-PCGs (PG), and PCGs-pollen (GP). Blood samples, bronchoalveolar lavage fluid, and bronchial lymph node were collected at day 25. IgE and IgG1 levels in sera were assessed by enzyme-linked immunosorbent assay. Alveolar cells, protein, and cytokine concentrations were quantified in bronchoalveolar lavage fluid. T-cell proliferation, in response to pollen or granules, was performed by lymph node assay. : Interactive effects between pollen and PCGs increased IgE and IgG1 levels when compared with those of the negative control. These increases were lower than those of the PP group but similar to the levels obtained by the GG group. Whatever was used in the sensitization and/or challenge phase, PCGs increased lymphocyte and Rantes levels compared with those of the pollen group. The interactive effects increased IL-1α and IL-1β compared with those of the PP and GG groups. : Immunologic interactive effects have been shown between pollen and PCGs. For humoral and cellular allergic responses, interactive effects between the 2 aeroallergenic sources used in this study seem to be influenced mainly by PCGs.

  19. Immunological Interactive Effects between Pollen Grains and Their Cytoplasmic Granules on Brown Norway Rats

    PubMed Central

    2009-01-01

    Background Grass pollen is one of the most important aeroallergen vectors in Europe. Under some meteorological factors, pollen grains can release pollen cytoplasmic granules (PCGs). PCGs induce allergic responses. Several studies have shown that during a period of thunderstorms the number of patients with asthma increases because of higher airborne concentrations of PCGs. Objective The aims of the study were to assess the allergenicity of interactive effects between pollen and PCGs and to compare it with allergenicity of Timothy grass pollen and PCGs in Brown Norway rats. Methods Rats were sensitized (day 0) and challenged (day 21) with pollen grains and/or PCGs. Four groups were studied: pollen-pollen (PP), PCGs-PCGs (GG), pollen-PCGs (PG), and PCGs-pollen (GP). Blood samples, bronchoalveolar lavage fluid, and bronchial lymph node were collected at day 25. IgE and IgG1 levels in sera were assessed by enzyme-linked immunosorbent assay. Alveolar cells, protein, and cytokine concentrations were quantified in bronchoalveolar lavage fluid. T-cell proliferation, in response to pollen or granules, was performed by lymph node assay. Results Interactive effects between pollen and PCGs increased IgE and IgG1 levels when compared with those of the negative control. These increases were lower than those of the PP group but similar to the levels obtained by the GG group. Whatever was used in the sensitization and/or challenge phase, PCGs increased lymphocyte and Rantes levels compared with those of the pollen group. The interactive effects increased IL-1α and IL-1β compared with those of the PP and GG groups. Conclusions Immunologic interactive effects have been shown between pollen and PCGs. For humoral and cellular allergic responses, interactive effects between the 2 aeroallergenic sources used in this study seem to be influenced mainly by PCGs. PMID:23283149

  20. Isobolographic Analyses of Proglumide-Celecoxib Interaction in Rats with Painful Diabetic Neuropathy.

    PubMed

    Suarez-Mendez, Samuel; Tovilla-Zarate, Carlos A; Ortega-Varela, Luis F; Bermudez-Ocaña, Deysi Y; Blé-Castillo, Jorge L; González-Castro, Thelma B; Zetina-Esquivel, Alma M; Diaz-Zagoya, Juan C; Esther Juárez-Rojop, Isela

    2017-03-01

    Preclinical Research The aim of the present study was to analyze the antihyperalgesic and antiallodynic interaction between the non-selective cholecystokinin (CCK) antagonist receptor, proglumide, and the selective cyclooxygenase-2 inhibitor, celecoxib in streptozotocin (STZ)-induced diabetic rats. Hyperalgesia was evaluated in the formalin test and tactile allodynia using von Frey filaments. Isobolographic analyses were employed to define the nature of the compound interactions, using a fixed dose ratio (0.5:0.5). Proglumide (20-160 mg/kg) and celecoxib (0.3-30 mg/kg) in these fixed dose ratio combinations induced dose-dependent antihyperalgesia and an antiallodynic effect in diabetic rats. ED40 values were calculated for the treatments and an isobologram was constructed. Theoretical ED40 values for combination proglumide-celecoxib estimated from the isobolograms for antihyperalgesic and antiallodynic activity (30.50 ± 1.90 mg/kg and 45.81 ± 4.55 mg/kg, respectively) were obtained, while experimental ED40 values for this antihyperalgesic and antiallodynic combined effect (13.83 ± 0.65 mg/kg and 17.74 ± 3.57 mg/kg; respectively) were significantly different. Coadministration of proglumide-celecoxib showed an interaction index value of 0.45 ± 0.03 for the antihyperalgesic effect and 0.39 ± 0.08 for the antiallodynic activity, indicating a synergistic interaction. These data suggest that proglumide and celecoxib can interact synergistically to reduce hyperalgesic and allodynic behaviors in diabetic neuropathy. This combination could be useful to treat neuropathic pain in diabetic patients. Drug Dev Res 78 : 116-123, 2017. ©2017 Wiley Periodicals, Inc.

  1. Surgical transposition of the ovary: Radiologic appearance

    SciTech Connect

    Bashist, B.; Friedman, W.N.; Killackey, M.A. )

    1989-12-01

    Therapeutic irradiation of the pelvis of a young female patient will result in loss of ovarian function. In a surgical technique termed ovarian transposition, the ovary is repositioned to the iliac fossa or paracolic gutter outside the radiation field. The computed tomographic (CT) scans and sonograms of five patients with cervical carcinoma who underwent this procedure were reviewed. The normal transposed ovary was of soft-tissue attenuation, often with one or more small cysts. Large cysts developed in the ovaries of three patients. One cyst was functional, another was due to a mesothelial inclusion cyst, and the third was most probably related to the transposition itself. Since the transposed ovary is difficult to palpate, CT or sonography can be used to demonstrate and follow up a cystic mass. Recognition of the appearance and location of the transposed ovary is important to avoid misinterpretation of a solid or cystic mass in patients who are at risk for tumor recurrence.

  2. Effects of cannabinoid and vanilloid receptor agonists and their interaction on learning and memory in rats.

    PubMed

    Shiri, Mariam; Komaki, Alireza; Oryan, Shahrbanoo; Taheri, Masoumeh; Komaki, Hamidreza; Etaee, Farshid

    2017-04-01

    Despite previous findings on the effects of cannabinoid and vanilloid systems on learning and memory, the effects of the combined stimulation of these 2 systems on learning and memory have not been studied. Therefore, in this study, we tested the interactive effects of cannabinoid and vanilloid systems on learning and memory in rats by using passive avoidance learning (PAL) tests. Forty male Wistar rats were divided into the following 4 groups: (1) control (DMSO+saline), (2) WIN55,212-2, (3) capsaicin, and (4) WIN55,212-2 + capsaicin. On test day, capsaicin, a vanilloid receptor type 1 (TRPV1) agonist, or WIN55,212-2, a cannabinoid receptor (CB1/CB2) agonist, or both substances were injected intraperitoneally. Compared to the control group, the group treated with capsaicin (TRPV1 agonist) had better scores in the PAL acquisition and retention test, whereas treatment with WIN55,212-2 (CB1/CB2 agonist) decreased the test scores. Capsaicin partly reduced the effects of WIN55,212-2 on PAL and memory. We conclude that the acute administration of a TRPV1 agonist improves the rats' cognitive performance in PAL tasks and that a vanilloid-related mechanism may underlie the agonistic effect of WIN55,212-2 on learning and memory.

  3. Food-drug interactions: effect of capsaicin on the pharmacokinetics of galantamine in rats.

    PubMed

    Zhai, Xue-jia; Lu, Yong-ning

    2012-11-01

    Capsaicin (trans-8-methyl-N-vanillyl-6-nonenamide, CAP) is a naturally occurring alkaloid extracted from the fruit of Capsicum plant family. It represents an important ingredient in spicy foods consumed throughout the world. However, little is known about the metabolic interactions between CAP and clinically used drugs. This study attempted to investigate the effect of CAP on the pharmacokinetics of galantamine, a competitive and reversible cholinesterase inhibitor. CAP, dexamethasone or sodium salt of carboxymethyl cellulose (CMC-Na) was given to rats for seven consecutive days and on the seventh day galantamine (10 mg/kg) was administered orally. Dexamethasone was used as a CYP inducer and CMC-Na was used as a vehicle. The results showed that the pretreatment of rats with CAP resulted in a decrease in the AUC(0-∞) of galantamine of about 49.70% (p < 0.01) compared with the control group. After oral administration of galantamine (10 mg/kg), the apparent oral clearance of galantamine was raised by 2.05-fold by pretreatment with CAP (p < 0.05). These results demonstrate that the chronic ingestion of high doses of CAP will decrease the bioavailability of galantamine to a significant extent in rats.

  4. Interactive effects of nutrition, environment, and rat-strain on cortical and vertebral bone geometry and biomechanics

    NASA Technical Reports Server (NTRS)

    Zernicke, R. F.; Li, K.-C.; Salem, G. J.; Vailas, A. C.; Grindeland, R. E.

    1990-01-01

    An investigation was conducted to generate comparative data on the sensitivity of cortical- and vertebral-bone adaptations in two different rat strains maintained at conditions typical for spaceborne experiments conducted by U.S.A. and USSR. The effects of cage environment, diet, and rat-strain on the cortical (humerus) and vertebral (T7) bones of male Taconic-Sprague-Dawley and Czechoslovakian-Wistar rats were investigated using different flight-simulation cages (one rat/cage for U.S.A.; ten rats/cage for USSR conditions) and fed either U.S.A. or USSR diet. The results showed significant effects of these factors on the humeral and vertebral geometry and mechanical properties, as well as significant interactive effects on the mechanical properties of the humerus.

  5. A SEX DIFFERENCE IN THE TEMPERATURE RESPONSE OF RATS TO EXERCISE,

    DTIC Science & Technology

    EXERCISE (PHYSIOLOGY), BODY TEMPERATURE), (*HEAT TOLERANCE, EXERCISE (PHYSIOLOGY)), (*BODY TEMPERATURE, RATS), SEX , SEX GLANDS, OVARIES, PROGESTERONE, TESTOSTERONE, EXCISION, TOLERANCES(PHYSIOLOGY), BLOOD VESSELS, MALES, FEMALES

  6. Cytosolic glucocorticoid receptor interaction with nuclear factor-kappa B proteins in rat liver cells.

    PubMed

    Widén, Christina; Gustafsson, Jan-Ake; Wikström, Ann-Charlotte

    2003-07-01

    The glucocorticoid receptor (GR) acts as an anti-inflammatory factor. To a large extent, this activity is exerted by the interference of pro-inflammatory nuclear factor kappa B (NF-kappa B) activity. In their respective inactive forms, both GR and NF-kappa B reside in the cytoplasm and translocate to the nucleus on relevant stimulation. Previously, p65, a component of the NF-kappa B complex, and GR have been shown to interact physically in vitro, and the interaction is assumed to take place in the nucleus of cells [McKay and Cidlowski (1999) Endocrine Rev. 20, 435-459]. We have studied the interaction between GR and NF-kappa B using in vivo -like conditions. Using immunoaffinity chromatography or immunoprecipitation, combined with Western blotting, we observed that, with endogenous protein levels in cytosolic extracts of rat liver and of H4-II-E-C3 hepatoma cells and in contrast with the current belief, p65, p50 and inhibitory kappa B alpha complex interact with GR, even in the absence of glucocorticoid or an inflammatory signal. The interaction between non-liganded/non-activated GR and p65/p50 has also been verified by both p65 and p50 co-immunoprecipitations. Intracellular localization studies, using Western blotting, revealed that glucocorticoids can decrease tumour necrosis factor alpha (TNFalpha)-induced nuclear entry of p65, whereas glucocorticoid-induced GR translocation was much less affected by TNFalpha. We were also able to demonstrate a nuclear interaction of GR and p65 and p50 using in vivo -like protein concentrations. Furthermore, nuclear GR interaction with heat-shock protein 90 was enhanced distinctly by TNFalpha treatment. In conclusion, our studies suggest a strong interconnectivity between the NF-kappa B and GR-signalling pathways where also, somewhat unexpectedly, a physical interaction in the cytosol constitutes an integral part of GR-NF-kappa B cross-talk.

  7. The Polycystic Ovary Morphology-Polycystic Ovary Syndrome Spectrum.

    PubMed

    Rosenfield, Robert L

    2015-12-01

    Polycystic ovary syndrome (PCOS) is the most common cause of chronic hyperandrogenic anovulation. Two-thirds of PCOS patients have functionally typical PCOS, with typical functional ovarian hyperandrogenism manifest as 17-hydroxyprogesterone hyper-responsiveness to gonadotropin stimulation. Most, but not all, of the remainder have atypical functional ovarian hyperandrogenism. Many asymptomatic volunteers with polycystic ovary morphology (PCOM) have similar abnormalities. The objective of this paper is to review the relationship of biochemical ovarian function to the clinical spectrum observed in PCOS and in normal volunteers with PCOM. Adolescents and adults with PCOS are similar clinically and biochemically. Ninety-five percent of functionally typical PCOS have classic PCOS, ie, hyperandrogenic anovulation with PCOM. In addition to having more severe hyperandrogenism and a greater prevalence of PCOM than other PCOS, they have a significantly greater prevalence of glucose intolerance although insulin resistance is similarly reduced. Half of normal-variant PCOM have PCOS-related steroidogenic dysfunction, which suggests a PCOS carrier state. There is a spectrum of ovarian androgenic dysfunction that ranges from subclinical hyperandrogenemia in some normal-variant PCOM to severe ovarian hyperandrogenism in most classic PCOS. A minority of mild PCOS cases do not fall on this spectrum of ovarian androgenic dysfunction, but rather seem to have obesity as the basis of their hyperandrogenism, or, less often, isolated adrenal androgenic dysfunction. Half of normal-variant PCOM also do not fall on the PCOS spectrum, and some of these seem to have excessive folliculogenesis as a variant that may confer mild prolongation of the reproductive lifespan. Improved understanding of PCOM in young women is needed. Copyright © 2015 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

  8. Social interaction and sex differences influence rat temperature circadian rhythm under LD cycles and constant light.

    PubMed

    Cambras, T; Castejón, L; Díez-Noguera, A

    2011-06-01

    Circadian rhythms produce an efficient organization of animal behaviour over the 24h day. In some species, social cues have been found to have a role as synchronizers of these rhythms. Here, the influence of social interaction on rat circadian behaviour was investigated, addressing the question of whether cohabitation would produce a delay in the appearance of arrhythmicity under constant light conditions. To this end, the circadian rhythms of male and female rat body temperature were studied for 10days under light-dark conditions, followed by 33days under constant bright light. Half of the animals were maintained in individual cages, whilst the others were maintained in larger cages in groups of three rats of the same sex. Results showed that individual circadian rhythms under 24hour light-dark (LD) cycles were more stable and with higher amplitude in grouped than in isolated animals, and higher in males than in females. During the first days under constant light (LL), the stability of the rhythm was also higher in males than in females, but there were no differences according to the group. Moreover, we did not find significant differences in the time of circadian rhythm loss under LL, since high individual variability was found for this variable. On the other hand, female rats living in isolation showed a delayed acrophase in the circadian rhythm under LD conditions compared with those living in groups. These results suggest that cohabitation increases the internal coherence of circadian behaviour, and could be interpreted as indicating that living in isolation may induce a level of stress that disturbs manifestation of the circadian rhythm, especially in females, which are also more reactive than males to external signals.

  9. Cocaine Treatment and Prenatal Environment Interact to Disrupt Intergenerational Maternal Behavior in Rats

    PubMed Central

    Johns, Josephine M.; Elliott, Deborah L.; Hofler, Vivian E.; Joyner, Paul W.; McMurray, Matthew S.; Jarrett, Thomas M.; Haslup, Amber M.; Middleton, Christopher L.; Elliott, Jay C.; Walker, Cheryl H.

    2011-01-01

    The link between impaired maternal behavior (MB) and cocaine treatment could result from drug-induced decreases in maternal reactivity to offspring, prenatal drug exposure (PDE) in offspring that could alter their ability to elicit MB, or the interaction of both, which could subsequently impair MB of the 1st-generation dams. Following chronic or intermittent cocaine or saline treatment during gestation, rat dams rearing natural or cross-fostered litters were compared along with untreated dams for MB. Untreated 1st-generation females with differentially treated rearing dams and PDE were tested for MB with their natural litters. The authors report disruptions in MB in dams and their 1st-generation offspring, attributable to main and interaction effects of maternal treatment, litter PDE, and rearing experience. PMID:16420163

  10. Night temperature and source–sink effects on overall growth, cell number and cell size in bell pepper ovaries

    PubMed Central

    Darnell, Rebecca L.; Cruz-Huerta, Nicacio; Williamson, Jeffrey G.

    2012-01-01

    Background and Aims Ovary swelling, and resultant fruit malformation, in bell pepper flowers is favoured by low night temperature or a high source–sink ratio. However, the interaction between night temperature and source–sink ratio on ovary swelling and the contribution of cell size and cell number to ovary swelling are unknown. The present research examined the interactive effects of night temperature and source–sink ratio on ovary size, cell number and cell size at anthesis in bell pepper flowers. Methods Bell pepper plants were grown in growth chambers at night temperatures of either 20 °C (HNT) or 12 °C (LNT). Within each temperature treatment, plants bore either 0 (non-fruiting) or two developing fruits per plant. Ovary fresh weight, cell size and cell number were measured. Key Results Ovary fresh weights in non-fruiting plants grown at LNT were the largest, while fresh weights were smallest in plants grown at HNT with fruits. In general, mesocarp cell size in ovaries was largest in non-fruiting plants grown at either LNT or HNT and smallest in fruiting plants at HNT. Mesocarp cell number was greater in non-fruiting plants under LNT than in the rest of the night temperature/fruiting treatments. These responses were more marked in ovaries sampled after 18 d of treatment compared with those sampled after 40 d of treatment. Conclusions Ovary fresh weight of flowers at anthesis increased 65 % in non-fruiting plants grown under LNT compared with fruiting plants grown under HNT. This increase was due primarily to increases in mesocarp cell number and size. These results indicate that the combined effects of LNT and high source–sink ratio on ovary swelling are additive. Furthermore, the combined effects of LNT and low source–sink ratio or HNT and high source–sink ratio can partially overcome the detrimental effects of LNT and high source–sink ratio. PMID:22933415

  11. Night temperature and source-sink effects on overall growth, cell number and cell size in bell pepper ovaries.

    PubMed

    Darnell, Rebecca L; Cruz-Huerta, Nicacio; Williamson, Jeffrey G

    2012-10-01

    Ovary swelling, and resultant fruit malformation, in bell pepper flowers is favoured by low night temperature or a high source-sink ratio. However, the interaction between night temperature and source-sink ratio on ovary swelling and the contribution of cell size and cell number to ovary swelling are unknown. The present research examined the interactive effects of night temperature and source-sink ratio on ovary size, cell number and cell size at anthesis in bell pepper flowers. Bell pepper plants were grown in growth chambers at night temperatures of either 20 °C (HNT) or 12 °C (LNT). Within each temperature treatment, plants bore either 0 (non-fruiting) or two developing fruits per plant. Ovary fresh weight, cell size and cell number were measured. Ovary fresh weights in non-fruiting plants grown at LNT were the largest, while fresh weights were smallest in plants grown at HNT with fruits. In general, mesocarp cell size in ovaries was largest in non-fruiting plants grown at either LNT or HNT and smallest in fruiting plants at HNT. Mesocarp cell number was greater in non-fruiting plants under LNT than in the rest of the night temperature/fruiting treatments. These responses were more marked in ovaries sampled after 18 d of treatment compared with those sampled after 40 d of treatment. Ovary fresh weight of flowers at anthesis increased 65 % in non-fruiting plants grown under LNT compared with fruiting plants grown under HNT. This increase was due primarily to increases in mesocarp cell number and size. These results indicate that the combined effects of LNT and high source-sink ratio on ovary swelling are additive. Furthermore, the combined effects of LNT and low source-sink ratio or HNT and high source-sink ratio can partially overcome the detrimental effects of LNT and high source-sink ratio.

  12. Identification of β-Catenin-Interacting Proteins in Nuclear Fractions of Native Rat Collecting Duct Cells.

    PubMed

    Hwang, Jacqueline R; Chou, Chung-Lin; Medvar, Barbara; Knepper, Mark A; Jung, Hyun Jun

    2017-03-15

    The gene encoding the aquaporin-2 water channel is regulated transcriptionally in response to vasopressin. In the renal collecting duct, vasopressin stimulates the nuclear translocation and phosphorylation (at Ser552) of β-catenin, a multifunctional protein that acts as a transcriptional co-regulator in the nucleus. The purpose of this study was to identify β-catenin interacting proteins that may be involved in transcriptional regulation in rat inner medullary collecting duct (IMCD) cells using both experimental and computational approaches. We used a standard chromatin immunoprecipitation procedure coupled to mass spectrometry (ChIP-MS) in a nuclear fraction isolated from rat IMCD suspensions. Over four biological replicates, we reproducibly identified 43 β-catenin binding proteins, including several known β-catenin binding partners as well as novel interacting proteins. Multiple proteins involved in transcriptional regulation were identified (Taf1, Jup, Tdrd3, Cdh1, Cenpj and several histones). Many of the identified β-catenin binding partners were found in prior studies to translocate to the nucleus in response to vasopressin. There was only one DNA-binding transcription factor (TF), specifically Taf1, part of the RNA-polymerase II pre-initiation complex. To identify sequence-specific TFs that may interact with β-catenin, Bayes' Theorem was used to integrate data from several information sources. The analysis identified several TFs with potential binding sites in the Aqp2 gene promoter that could interact with β-catenin in the regulation of Aqp2 gene transcription, specifically Jun, Junb, Jund, Atf1, Atf2, Mef2d, Usf1, Max, Pou2f1 and Rxra. The findings provide information necessary for modeling the transcriptional response to vasopressin.

  13. Synergistic effect of the interaction between curcumin and diclofenac on the formalin test in rats.

    PubMed

    De Paz-Campos, Marco A; Ortiz, Mario I; Chávez Piña, Aracely E; Zazueta-Beltrán, Liliana; Castañeda-Hernández, Gilberto

    2014-10-15

    The association of non-steroidal anti-inflammatory drugs with certain plant extracts can increase antinociceptive activity, permitting the use of lower doses and thus limiting side effects. Therefore, the aim objective of the current study was to examine the effects of curcumin on the nociception and pharmacokinetics of diclofenac in rats. Antinociception was assessed using the formalin test. Diluted formalin was injected subcutaneously into the dorsal surface of the right hind paw. Nociceptive behavior was quantified as the number of flinches of the injected paw during 60 min after injection, and a reduction in formalin-induced flinching was interpreted as an antinociceptive response. Rats were treated with oral diclofenac (1-31 mg/kg), curcumin (3.1-100 mg/kg) or the diclofenac-curcumin combination (2.4-38.4 mg/kg). To determine the possibility of a pharmacokinetic interaction, the oral bioavailability of diclofenac (10 mg/kg) was studied in presence and the absence of curcumin (31 mg/kg). Diclofenac, curcumin, or diclofenac-curcumin combination produced an antinociceptive effect on the formalin test. ED30 values were estimated for the individual drugs, and an isobologram was constructed. The derived theoretical ED30 for the antinociceptive effect (19.2 mg/kg) was significantly different from the observed experimental ED30 value (9.8 mg/kg); hence, the interaction between diclofenac and curcumin that mediates the antinociceptive effect was synergistic. Notwithstanding, the interaction does not appear to involve pharmacokinetic mechanisms, as oral curcumin failed to produce any significant alteration in oral diclofenac bioavailability. Data suggest that the diclofenac-curcumin combination can interact at the systemic level and may have therapeutic advantages for the clinical treatment of inflammatory pain. Copyright © 2014 Elsevier GmbH. All rights reserved.

  14. Muscarinic and PACAP receptor interactions at pontine level in the rat: significance for REM sleep regulation.

    PubMed

    Ahnaou, A; Laporte, A M; Ballet, S; Escourrou, P; Hamon, M; Adrien, J; Bourgin, P

    2000-12-01

    Cholinergic and PACAPergic systems within the oral pontine reticular nucleus (PnO) play a critical role in REM sleep generation in rats. In this present work, we have investigated whether REM sleep enhancement induced by carbachol (a cholinergic agonist) or PACAP, depends on an interaction between muscarinic and PACAP receptors. This hypothesis was tested by recording sleep-wake cycles in freely moving rats injected into the PnO with PACAP in combination with the muscarinic receptor antagonist atropine, or with carbachol in combination with the PACAP receptor antagonist PACAP6-27. When administered alone, PACAP (3 pmol) or carbachol (110 pmol) induced an enhancement of REM sleep during 8 h (+61%, n = 8; +70%, n = 5), which was totally prevented by infusion of atropine (290 pmol) for PACAP, or of PACAP6-27 (3 pmol) for carbachol. Quantitative autoradiographic studies indicated that (i) PACAP (10-9-10-7 M) induced in the PnO an increase (+35%) of the specific binding of the muscarinic antagonist [3H]quinuclidinyl benzylate, which could be completely prevented by PACAP6-27 (IC50 = 8 x 10-8 M) and (ii) both carbachol and PACAP enhanced [35S]GTP-gamma-S binding in a concentration-dependent manner in the PnO. The maximal increase due to carbachol was significantly higher in the presence (+126%) than in the absence (+102%) of PACAP (0.1 microM). These data showed that interactions between muscarinic and PACAP receptors do exist within the PnO and play a role in the local mechanisms of REM sleep control in the rat.

  15. Lack of interaction between orexinergic and alpha2-adrenergic neuronal systems in rat cerebrocortical slices.

    PubMed

    Hirota, Kazuyoshi; Kudo, Mihoko; Tose, Ryuji; Yoshida, Hitoshi; Kudo, Tsuyoshi; Kushikata, Tetsuya

    2005-10-14

    Orexinergic and norepinephrinergic alpha2-adrenoceptor expressing neurons contribute to the regulation of the sleep-wakefulness cycle. In the present study, we have examined a possible interaction between orexinergic and alpha2-adrenergic systems in orexin-A (100 nM)- and K+ (25 mM)-evoked norepinephrine release from slices of rat cerebrocortex. In this tissue norepinephrinergic neurons are predominantly innervated via the locus coeruleus. Clonidine concentration-dependently inhibited K+-evoked norepinephrine release with pIC50 (Imax) of 6.44+/-0.38 (48.8+/-6.9%). A selective orexin-1 receptor antagonist, SB-334867 was ineffective. SB-334867 concentration-dependently inhibited orexin A-evoked norepinephrine release with pIC50 (Imax) of 6.05+/-0.14 (86.4+/-5.4%); clonidine (alpha2-agonist) was ineffective. In contrast, yohimbine reversed the inhibitory effects of clonidine (1 microM) on K+-evoked norepinephrine release with pIC50 (Imax) of 6.50+/-0.34 (77.6+/-10.9%); orexin A was ineffective. The present data suggest a lack of interaction between orexinergic and alpha2-adrenergic neurons in rat cerebral cortex.

  16. Lack of interaction between dietary fructose and zinc (Zn) nutriture in rats

    SciTech Connect

    Smith, J.C.; Failla, M.L.; Fields, M.; Revett, K.R.; Rose, A.

    1986-03-05

    Dietary fructose, when compared to cornstarch, exacerbates copper deficiency. The purpose of this study was to determine whether Zn deficiency is similarly enhanced by high fructose intake. Seventy-five male SD rats were randomly assigned to one of the following diets containing 62% of the indicated carbohydrate: Zn deficient (0.6 ppm) X fructose; Zn deficient X starch; Zn supplemented (32 ppm) X fructose; Zn supplemented X starch. Animals were pair-fed to the Zn deficient X fructose group for 4 weeks. Survival, weight gain and tissue weight were also affected by dietary Zn, but not dietary carbohydrate. Dietary carbohydrate also failed to alter food intake of rats consuming Zn deficient diets. Unlike copper deficiency, the severity of Zn deficiency is not increased by feeding diets high in fructose compared to starch. The lack of a carbohydrate effect on zinc status indicates that the fructose-copper interaction is selective. This knowledge will facilitate the design of studies aimed at defining the mechanism(s) underlying fructose-trace element interaction.

  17. Synergistic antiallodynic interaction between gabapentin or carbamazepine and either benfotiamine or cyanocobalamin in neuropathic rats.

    PubMed

    Mixcoatl-Zecuatl, Teresa; Quinonez-Bastidas, Geovanna N; Caram-Salas, Nadia L; Ambriz-Tututi, Monica; Araiza-Saldana, Claudia I; Rocha-Gonzalez, Hector I; Medina-Santillan, Roberto; Reyes-Garcia, Gerardo; Granados-Soto, Vinicio

    2008-01-01

    Anticonvulsants, including gabapentin and carbamazepine, have shown activity against several types of neuropathic pain; however, they have limiting side effects that may minimize their use. In this study the possible synergistic interaction between anticonvulsants and benfotiamine or cyanocobalamin on spinal nerve ligation-induced tactile allodynia was assessed. Oral administration of gabapentin (15-300 mg/kg), carbamazepine (10-300 mg/kg), benfotiamine (30-600 mg/kg) or cyanocobalamin (0.3-6.0 mg/kg) significantly reduced tactile allodynia in rats. Maximal antiallodynic effects were reached with gabapentin 300 mg/kg (approximately 70%), carbamazepine 300 mg/kg (approximately 66%), benfotiamine 600 mg/kg (approximately 51%) and cyanocobalamin 6 mg/kg (approximately 59%). At the highest tested doses, gabapentin, but not carbamazepine, benfotiamine or cyanocobalamin, significantly reduced motor coordination. Coadministration of gabapentin or carbamazepine with benfotiamine or cyanocobalamin in a fixed ratio markedly reduced spinal nerve ligation-induced tactile allodynia, showing a synergistic interaction between anticonvulsants and B vitamins. Data indicate that combinations of anticonvulsants with benfotiamine or cyanocobalamin are able to reduce tactile allodynia without affecting motor coordination in rats, and suggest the possible clinical use of these combinations in the treatment of neuropathic pain in humans.

  18. Interactions between ingested kaolinite and the intestinal mucosa in rat: proteomic and cellular evidences.

    PubMed

    Reichardt, François; Habold, Caroline; Chaumande, Bertrand; Ackermann, Alain; Ehret-Sabatier, Laurence; Le Maho, Yvon; Angel, Fabielle; Liewig, Nicole; Lignot, Jean-Hervé

    2009-02-01

    Although some of the effects of clay ingestion by humans and animals, such as gastrointestinal wellness and the increase in food efficiency are well known, the underlying mechanisms are not yet fully understood. Therefore, the interactions between the intestinal mucosa and kaolinite particles and their effects on mucosal morphology were observed using light microscopy (LM), transmission electron microscopy (TEM), conventional (CSEM) and environmental (ESEM) scanning electron microscopy combined with an EDX micro-analysis system. Kaolinite consumption, given with free access to rats, varied considerably from one animal to the other but was regular through time for each individual. Some kaolinite particles appeared chemically dissociated in the lumen and within the mucus barrier. Aluminium (Al) originating from ingested clay and present in the mucus layer could directly cross the intestinal mucosa. A significant increase in the thickness of the villi with large vacuoles at the base of the mucosal cells and a decrease in the length of enterocyte microvilli characterized complemented animals. The proteomic analyses of the intestinal mucosa of complemented rats also revealed several modifications in the expression level of cytoskeleton proteins. In summary, kaolinite particles ingested as food complement interact with the intestinal mucosa and modify nutrient absorption. However, these data, together with the potential neurotoxicity of Al, need further investigation.

  19. Obesity and polycystic ovary syndrome.

    PubMed

    Naderpoor, N; Shorakae, S; Joham, A; Boyle, J; De Courten, B; Teede, H J

    2015-03-01

    Obesity is now a major international health concern. It is increasingly common in young women with reproductive, metabolic and psychological health impacts. Reproductive health impacts are often poorly appreciated and include polycystic ovary syndrome (PCOS), infertility and pregnancy complications. PCOS is the most common endocrine condition in women and is underpinned by hormonal disturbances including insulin resistance and hyperandrogenism. Obesity exacerbates hormonal and clinical features of PCOS and women with PCOS appear at higher risk of obesity, with multiple underlying mechanisms linking the conditions. Lifestyle intervention is first line in management of PCOS to both prevent weight gain and induce weight loss; however improved engagement and sustainability remain challenges with the need for more research. Medications like metformin, orlistat, GLP1 agonists and bariatric surgery have been used with the need for large scale randomised clinical trials to define their roles.

  20. Polycystic ovary syndrome: an overview.

    PubMed

    Whitaker, Kristin Nadine

    2011-02-01

    Polycystic ovary syndrome is the most common endocrine disorder in women of reproductive age. It affects 6% to 7% of the population and is characterized by hyperandrogenism and ovarian dysfunction. Women with the disorder often present with insulin resistance and obesity, making it importance for health care providers to monitor closely for signs and symptoms of metabolic syndrome and type 2 diabetes. Treatments are targeted toward improving insulin tolerance, reducing signs and symptoms of hyperandrogenism (hirsutism, anovulation, etc), restoring normal menstrual cycle function, and restoring fertility. Major treatment should include weight management through diet and exercise, regardless of body mass index and might include concurrent drug therapy. It is important that pharmacists understand the underlying pathophysiology of the disease and the available treatments, in addition to the importance of reducing risk of metabolic syndrome/type 2 diabetes, and cardiovascular disease in these patients.

  1. Polycystic ovary syndrome (PCOS): metformin

    PubMed Central

    2015-01-01

    Introduction Polycystic ovary syndrome (PCOS) is classically characterised by an accumulation of incompletely developed follicles in the ovaries due to anovulation. However, since the publication of the Rotterdam criteria, there is acceptance that menstrual cycle and endocrine dysfunction with hyperandrogenism is more important in reaching the diagnosis than ultrasound findings. It is diagnosed in up to 10% of women attending gynaecology clinics, but the prevalence in the population as a whole varies from 10% to 20%, depending on which diagnostic criteria are used. PCOS has been associated with hirsutism, infertility, acne, weight gain, type 2 diabetes, cardiovascular disease (CVD), and endometrial hyperplasia. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical question: What are the effects of metformin on hirsutism and menstrual frequency in women with PCOS? We searched: Medline, Embase, The Cochrane Library, and other important databases up to May 2014 (BMJ Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found 14 studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. Conclusions In this systematic review we present information relating to the effectiveness and safety of the following interventions: metformin compared with placebo/no treatment, metformin compared with weight loss intervention, or metformin compared with cyproterone acetate-ethinylestradiol. PMID:25814168

  2. Weight Loss and Medication in Polycystic Ovary Syndrome Therapy.

    PubMed

    Tolstoi, Linda G.; Josimovich, John B.

    2002-01-01

    Polycystic ovary syndrome, which is a complex syndrome, affects approximately 6% of reproductive-age women. Many abnormalities are associated with polycystic ovary syndrome, but confusion still exists about their causation. Diagnosis of polycystic ovary syndrome is by exclusion. Management of the metabolic aspects of polycystic ovary syndrome focuses on minimizing insulin resistance and hyperinsulinemia with diet therapy or insulin-lowering drugs.

  3. Metal-metal interactions among dietary toxic and essential trace metals in the rat

    SciTech Connect

    Elsenhans, B.; Schmolke, G.; Kolb, K.; Stokes, J.; Forth, W.

    1987-12-01

    Exposure to toxic and essential metals is thought to be reflected by corresponding metal concentrations in tissues. However, toxic and essential metals may influence each other in regard to their retention in the body. Therefore, a basic diet containing four toxic metals (As 7, Cd 9, Ni 13, and Pb 20 ppm) and adequate amounts of essential metals was fed to rats for 2 weeks. Test groups received the basic diet with increasing concentrations of one of the toxic metals (up to 90 ppm As, 180 ppm Cd, 365 ppm Ni, and 394 ppm Pb). As, Cd, Ni, Pb, Cu, Fe, Mn, and Zn were determined by atomic emission spectroscopy in liver, kidney, intestine, brain, muscle, bone, skin, hair, and blood. A linear relationship between diet and tissue concentration is observed for As and Ni in the kidney, for Cd in the liver, and for Pb in the bone. In other tissues saturation was observed. While Cd-Fe interactions were common to most of the tissues, other interactions were detected only in specific tissues, e.g., As-Cu in the kidney, Cd-Zn in the liver, and As-Mn, Cd-Mn, or Ni-Cu in the intestine. Increases of renal Pb and intestinal Cd by dietary Ni, and a decrease in bone As by dietary Pb were the most pronounced interactions between the toxic metals. The results demonstrate that potential target organs for the evaluation of metal exposure need to be carefully analyzed for interfering metal-metal interactions.

  4. Altered mechanical interaction between rat plantar flexors due to changes in intermuscular connectivity.

    PubMed

    Bernabei, M; van Dieën, J H; Maas, H

    2017-02-01

    Connective tissue formation following muscle injury and remedial surgery may involve changes in the stiffness and configuration of the connective tissues linking adjacent muscles. We investigated changes in mechanical interaction of muscles by implanting either a tissue-integrating mesh (n = 8) or an adhesion barrier (n = 8) to respectively increase or decrease the intermuscular connectivity between soleus muscle (SO) and the lateral gastrocnemius and plantaris complex (LG+PL) of the rat. As a measure of mechanical interaction, changes in SO tendon forces and proximal-distal LG+PL force differences in response to lengthening LG+PL proximally were assessed 1 and 2 weeks post-surgery. The extent of mechanical interaction was doubled 1 week post-implantation of the tissue-integrating mesh compared to an unaffected compartment (n = 8), and was more than four times higher 2 weeks post-surgery. This was found only for maximally activated muscles, but not when passive. Implanting the adhesion barrier did not result in a reduction of the mechanical interaction between these muscles. Our findings indicate that the ratio of force transmitted via myofascial, rather than myotendinous pathways, can increase substantially when the connectivity between muscles is enhanced. This improves our understanding of the consequences of connective tissue formation at the muscle boundary on skeletal muscle function.

  5. Laparoscopic management of tumor in supernumerary ovary

    PubMed Central

    Prakash, Ved; Kant, Anita; Parashar, Abha; Rani, Uma

    2016-01-01

    Laparoscopic management of most of the adnexal masses has become feasible in the present era of advancing endoscopic techniques. A postmenopausal lady presented with lump in the abdomen, appeared to be a solid ovarian mass on ultrasound, and magnetic resonance imaging. On laparoscopy, both the ovaries were normal and the mass was not connected to uterus or adnexa. The mass was removed and histopathology confirmed it to be ovarian tissue thus confirming it to be a tumor in a supernumerary ovary. Examples of supernumerary ovary are among the rarest of gynecological abnormalities. PMID:27134478

  6. Follicle dynamics and global organization in the intact mouse ovary

    PubMed Central

    Faire, Mehlika; Skillern, Amanda; Arora, Ripla; Nguyen, Daniel H.; Wong, Jason; Chamberlain, Chester; German, Michael S.; Fung, Jennifer C.; Laird, Diana J.

    2015-01-01

    Quantitative analysis of tissues and organs can reveal large-scale patterning as well as the impact of perturbations and aging on biological architecture. Here we develop tools for imaging of single cells in intact organs and computational approaches to assess spatial relationships in 3D. In the mouse ovary, we use nuclear volume of the oocyte to read out quiescence or growth of oocyte-somatic cell units known as follicles. This in-ovary quantification of non-growing follicle dynamics from neonate to adult fits a mathematical function, which corroborates the model of fixed oocyte reserve. Mapping approaches show that radial organization of folliculogenesis established in the newborn ovary is preserved through adulthood. By contrast, inter-follicle clustering increases during aging with different dynamics depending on size. These broadly applicable tools can reveal high dimensional phenotypes and age-related architectural changes in other organs. In the adult mouse pancreas, we find stochastic radial organization of the islets of Langerhans but evidence for localized interactions among the smallest islets. PMID:25889274

  7. Does genetic BDNF deficiency in rats interact with neurotransmitter control of prepulse inhibition? Implications for schizophrenia.

    PubMed

    van den Buuse, Maarten; Biel, Davina; Radscheit, Kathrin

    2017-04-03

    Several studies have suggested a role of BDNF in the development of schizophrenia. For example, post-mortem studies have shown significantly reduced levels of BDNF protein expression in the brain of schizophrenia patients. We investigated the relationship between reduced levels of BDNF in the brain and the regulation of prepulse inhibition (PPI), a behavioral endophenotype of schizophrenia. We used BDNF heterozygous mutant rats which display a 50% decrease of mature BDNF protein levels. Previously, we observed normal baseline PPI and responses to the dopamine D1/D2 receptor agonist, apomorphine, in these rats. Here, we focused on the effects of the NMDA receptor antagonist, MK-801, its interaction with mGluR2/3 and mGluR5 receptors, and the PPI response to serotonergic drugs. MK-801 administration caused a dose-dependent reduction of PPI and increase of startle amplitudes. Baseline PPI and the effect of 0.02-0.1mg/kg of MK-801 were not significantly altered in male or female BDNF heterozygous rats, although the MK-801-induced increase in startle levels was reduced. Co-treatment with the mGluR2/3 agonist, LY379,268, or the mGluR5 antagonist, MPEP, did not alter the effect of MK-801 on PPI in controls or BDNF mutant rats. Treatment with the serotonin-1A receptor agonist, 8-OH-DPAT, the serotonin-2A receptor agonist, DOI, or the serotonin releaser, fenfluramine, induced differential effects on PPI and startle but these effects were not different between the genotypes. These results show that a significant decrease of BDNF protein expression does not lead to reduced PPI at baseline or changes in the regulation of PPI via NMDA receptors or serotonergic mechanisms. These findings in a genetic rat model of BDNF deficiency do not support a role for similar reductions of BDNF levels in schizophrenia in the disruption of PPI, widely reported as an endophenotype of the illness. The potential implications of these results for our understanding of changes in PPI and BDNF

  8. Pharmacokinetic interactions between rebamipide and selected nonsteroidal anti-inflammatory drugs in rats.

    PubMed

    Cooper, Dustin L; Wood, Robert C; Wyatt, Jarrett E; Harirforoosh, Sam

    2014-03-12

    Nonsteroidal anti-inflammatory drugs (NSAIDs) cause gastrointestinal and renal side effects. Rebamipide is a mucoprotective agent that reduces gastrointenstinal side effects when administered concomitantly with NSAIDs. In this study, we investigated the pharmacokinetic drug interactions of rebamipide with two selected NSAIDs, celecoxib or diclofenac. Rats were randomly divided into five groups. Two groups received placebo and three groups were administered rebamipide (30 mg/kg) orally twice daily for two days. On day 3, the animals treated with placebo received celecoxib (40 mg/kg) or diclofenac (10mg/kg) and rats receiving rebamipide were administerd rebamipide followed by a single dose of placebo, celecoxib, or diclofenac. To investigate drug protein interactions, blank rat plasma was spiked with known concentrations of rebamipide, diclofenac plus rebamipide, or celecoxib plus rebamipide then dialyzed through a Rapid Equilibrium Dialysis device. AUC (139.70±24.97 μg h/mL), Cmax (42.99±2.98 μg/mL), and CLoral (0.08±0.02 L/h/kg) values of diclofenac in diclofenac plus rebamipide group altered when compared to those of diclofenac treated groups. Treatment with rebamipide showed no significant change in pharmacokinetic parameters of celecoxib treated rats. Cmax (7.80±1.22 μg/mL), AUC (56.46±7.30 μg h/mL), Vd/F (7.55±1.37 L/kg), and CLoral (0.58±0.09 L/h/kg) of rebamipide were significantly altered when diclofenac was co-administered with rebamipide. Pharmacokinetic parameters of rebamipide plus celecoxib group were not significantly different from those of rebamipide group. Plasma protein binding was not affected by concomitant administration of another drug. These results indicate alteration of pharmacokinetic parameters of both rebamipide and diclofenac when co-administered and cannot be explained by a variation in plasma protein binding. Copyright © 2013 Elsevier B.V. All rights reserved.

  9. Synergistic interaction between ketamine and magnesium in lowering body temperature in rats.

    PubMed

    Vučković, Sonja M; Savić Vujović, Katarina R; Srebro, Dragana P; Medić, Branislava M; Vučetić, Cedomir S; Prostran, Milan Š; Prostran, Milica Š

    2014-03-29

    A large body of evidence supports the existence of an endogenous glutamate system that tonically modulates body temperature via N-methyl-d-aspartate (NMDA) receptors. Ketamine and magnesium, both NMDA receptor antagonists, are known for their anesthetic, analgesic and anti-shivering properties. This study is aimed at evaluating the effects of ketamine and magnesium sulfate on body temperature in rats, and to determine the type of interaction between them. The body temperature was measured by insertion of a thermometer probe 5cm into the colon of unrestrained male Wistar rats (200-250g). Magnesium sulfate (5 and 60mg/kg, sc) showed influence neither on baseline, nor on morphine-evoked hyperthermic response. Subanesthetic doses of ketamine (5-30mg/kg, ip) given alone, produced significant dose-dependent reduction in both baseline colonic temperature and morphine-induced hyperthermia. Analysis of the log dose-response curves for the effects of ketamine and ketamine-magnesium sulfate combination on the baseline body temperature revealed synergistic interaction, and about 5.3 fold reduction in dosage of ketamine when the drugs were applied in fixed ratio (1:1) combinations. In addition, fixed low dose of magnesium sulfate (5mg/kg, sc) enhanced the temperature lowering effect of ketamine (1.25-10mg/kg, ip) on baseline body temperature and morphine-induced hyperthermia by factors of about 2.5 and 5.3, respectively. This study is the first to demonstrate the synergistic interaction between magnesium sulfate and ketamine in a whole animal study and its statistical confirmation. It is possible that the synergy between ketamine and magnesium may have clinical relevance. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. Posthatching development of Alligator mississippiensis ovary and testis.

    PubMed

    Moore, Brandon C; Hamlin, Heather J; Botteri, Nicole L; Lawler, Ashley N; Mathavan, Ketan K; Guillette, Louis J

    2010-05-01

    We investigated ovary and testis development of Alligator mississippiensis during the first 5 months posthatch. To better describe follicle assembly and seminiferous cord development, we used histochemical techniques to detect carbohydrate-rich extracellular matrix components in 1-week, 1-month, 3-month, and 5-month-old gonads. We found profound morphological changes in both ovary and testis. During this time, oogenesis progressed up to diplotene arrest and meiotic germ cells increasingly interacted with follicular cells. Concomitant with follicles becoming invested with full complements of granulosa cells, a periodic acid Schiff's (PAS)-positive basement membrane formed. As follicles enlarged and thecal layers were observed, basement membranes and thecal compartments gained periodic acid-methionine silver (PAMS)-reactive fibers. The ovarian medulla increased first PAS- and then PAMS reactivity as it fragmented into wide lacunae lined with low cuboidal to squamous epithelia. During this same period, testicular germ cells found along the tubule margins were observed progressing from spermatogonia to round spermatids located within the center of tubules. Accompanying this meiotic development, interstitial Leydig cell clusters become more visible and testicular capsules thickened. During the observed testis development, the thickening tunica albuginea and widening interstitial tissues showed increasing PAS- and PAMS reactivity. We observed putative intersex structures in both ovary and testis. On the coelomic aspect of testes were cell clusters with germ cell morphology and at the posterior end of ovaries, we observed "medullary rests" resembling immature testis cords. We hypothesize laboratory conditions accelerated gonad maturation due to optimum conditions, including nutrients and temperature. Laboratory alligators grew more rapidly and with increased body conditions compared with previous measured, field-caught animals. Additionally, we predict the morphological

  11. Post-hatching development of Alligator mississippiensis ovary and testis

    PubMed Central

    Moore, Brandon C.; Hamlin, Heather J.; Botteri, Nicole L.; Lawler, Ashley N.; Mathavan, Ketan K.; Guillette, Louis J.

    2009-01-01

    We investigated ovary and testis development of Alligator mississippiensis during the first five months post-hatch. To better describe follicle assembly and seminiferous cord development, we employed histochemical techniques to detect carbohydrate-rich extracellular matrix components in one-week, one-month, three-month, and five-month-old gonads. We found profound morphological changes in both ovary and testis. During this time, oogenesis progressed up to diplotene arrest and meiotic germ cells increasingly interacted with follicular cells. Concomitant with follicles becoming invested with full complements of granulosa cells, a periodic acid Schiff’s (PAS)-positive basement membrane formed. As follicles enlarged and thecal layers were observed, basement membranes and thecal compartments gained periodic acid-methionine silver (PAMS)-reactive fibers. The ovarian medulla increased first PAS- and then PAMS-reactivity as it fragmented into wide lacunae lined with low cuboidal to squamous epithelia. During this same period, testicular germ cells found along the tubule margins were observed progressing from spermatogonia to round spermatids located within the center of tubules. Accompanying this meiotic development, interstitial Leydig cell clusters become more visible and testicular capsules thickened. During the observed testis development, the thickening tunica albuginea and widening interstitial tissues showed increasing PAS- and PAMS-reactivity. We observed putative inter-sex structures in both ovary and testis. On the coelomic aspect of testes were cell clusters with germ cell morphology and at the posterior end of ovaries, we observed “medullary rests” resembling immature testis cords. We hypothesize laboratory conditions accelerated gonad maturation due to optimum conditions, including nutrients and temperature. Laboratory alligators grew more rapidly and with increased body conditions compared to previous measured, field-caught animals. Additionally, we

  12. Interactions between adenosine and metabotropic glutamate receptors in the rat hippocampal slice

    PubMed Central

    Shahraki, Ali; Stone, Trevor W

    2003-01-01

    We have examined excitatory postsynaptic potentials and paired-pulse interactions in rat hippocampal slices to obtain more information about the site and mechanism of interactions between metabotropic glutamate receptors and adenosine receptors. The results show that the suppression of adenosine sensitivity is explained by a selectively reduced responsiveness to A1 receptor stimulation, and does not involve any facilitation of A2A adenosine receptors, since it can be obtained in the absence of endogenous adenosine and is not prevented by the A2A receptor blocker ZM241385. The glutamate receptors involved are of the group I class since the suppression of adenosine sensitivity is produced by ACPD and the group I selective compound DHPG. Furthermore, the effects of DHPG could be prevented by LY367385, a selective antagonist at the mGlu1a subtype of group I receptors. The selective antagonist at mGlu5 receptors, SIB1893, did not prevent the suppression of adenosine sensitivity by DHPG. Blockade of the DHPG/adenosine interaction was also obtained by superfusion with the protein kinasae C inhibitor chelerythrine. Since the suppression of adenosine responses by metabotropic receptor agonists was seen in the paired-pulse paradigm, we conclude that the observed interactions occur at the level of the presynaptic terminals. The interaction with adenosine receptors is not specific, but applies also to a suppression of responses mediated by the GABAB receptor agonist baclofen. We conclude that activation of the mGlu1a subtype of receptor can suppress responses mediated via adenosine A1 receptors, probably by activating protein kinase C. Since the changes induced by metabotropic glutamate receptor agonists last for at least 60 min, the data also imply that these interactions could play an important role in changes of synaptic function long after even transient increases of glutamate release in the CNS. PMID:12684261

  13. Herb-Drug Interaction of Paullinia cupana (Guarana) Seed Extract on the Pharmacokinetics of Amiodarone in Rats.

    PubMed

    Rodrigues, Márcio; Alves, Gilberto; Lourenço, Nulita; Falcão, Amílcar

    2012-01-01

    Paullinia cupana is used in weight-loss programs as a constituent of medicinal/dietary supplements. This study aimed to assess a potential herb-drug interaction among a standardized (certified) Paullinia cupana extract and amiodarone (narrow therapeutic index drug) in rats. In a first pharmacokinetic study rats were simultaneously coadministered with a single dose of Paullinia cupana (821 mg/kg, p.o.) and amiodarone (50 mg/kg, p.o.), and in a second study rats were pretreated during 14 days with Paullinia cupana (821 mg/kg/day, p.o.) receiving amiodarone (50 mg/kg, p.o.) on the 15th day. Rats of the control groups received the corresponding volume of vehicle. Blood samples were collected at several time points after amiodarone dosing, and several tissues were harvested at the end of the experiments (24 h after dose). Plasma and tissue concentrations of amiodarone and its major metabolite (mono-N-desethylamiodarone) were measured and analysed. A significant reduction in the peak plasma concentration (73.2%) and in the extent of systemic exposure (57.8%) to amiodarone was found in rats simultaneously treated with Paullinia cupana and amiodarone; a decrease in tissue concentrations was also observed. This paper reports for the first time an herb-drug interaction between Paullinia cupana extract and amiodarone, which determined a great decrease on amiodarone bioavailability in rats.

  14. Herb-Drug Interaction of Paullinia cupana (Guarana) Seed Extract on the Pharmacokinetics of Amiodarone in Rats

    PubMed Central

    Rodrigues, Márcio; Alves, Gilberto; Lourenço, Nulita; Falcão, Amílcar

    2012-01-01

    Paullinia cupana is used in weight-loss programs as a constituent of medicinal/dietary supplements. This study aimed to assess a potential herb-drug interaction among a standardized (certified) Paullinia cupana extract and amiodarone (narrow therapeutic index drug) in rats. In a first pharmacokinetic study rats were simultaneously coadministered with a single dose of Paullinia cupana (821 mg/kg, p.o.) and amiodarone (50 mg/kg, p.o.), and in a second study rats were pretreated during 14 days with Paullinia cupana (821 mg/kg/day, p.o.) receiving amiodarone (50 mg/kg, p.o.) on the 15th day. Rats of the control groups received the corresponding volume of vehicle. Blood samples were collected at several time points after amiodarone dosing, and several tissues were harvested at the end of the experiments (24 h after dose). Plasma and tissue concentrations of amiodarone and its major metabolite (mono-N-desethylamiodarone) were measured and analysed. A significant reduction in the peak plasma concentration (73.2%) and in the extent of systemic exposure (57.8%) to amiodarone was found in rats simultaneously treated with Paullinia cupana and amiodarone; a decrease in tissue concentrations was also observed. This paper reports for the first time an herb-drug interaction between Paullinia cupana extract and amiodarone, which determined a great decrease on amiodarone bioavailability in rats. PMID:23304200

  15. Polycystic ovary syndrome and metabolic syndrome.

    PubMed

    Ali, Aus Tariq

    2015-08-01

    Polycystic ovary syndrome (PCOS) is a heterogeneous disorder, where the main clinical features include menstrual irregularities, sub-fertility, hyperandrogenism, and hirsutism. The prevalence of PCOS depends on ethnicity, environmental and genetic factors, as well as the criteria used to define it. On the other hand, metabolic syndrome is a constellation of metabolic disorders which include mainly abdominal obesity, insulin resistance, impaired glucose metabolism, hypertension and dyslipidaemia. These associated disorders directly increase the risk of Type 2 diabetes mellitus (DMT2), coronary heart disease (CHD), cardiovascular diseases (CVD) and endometrial cancer. Many patients with PCOS have features of metabolic syndrome such as visceral obesity, hyperinsulinaemia and insulin resistance. These place patients with PCOS under high risk of developing cardiovascular disease (CVD), Type 2 diabetes (DMT2) and gynecological cancer, in particular, endometrial cancer. Metabolic syndrome is also increased in infertile women with PCOS. The aim of this review is to provide clear and up to date information about PCOS and its relationship with metabolic syndrome, and the possible interaction between different metabolic disorders.

  16. Aging of oocyte, ovary, and human reproduction.

    PubMed

    Ottolenghi, Chris; Uda, Manuela; Hamatani, Toshio; Crisponi, Laura; Garcia, Jose-Elias; Ko, Minoru; Pilia, Giuseppe; Sforza, Chiarella; Schlessinger, David; Forabosco, Antonino

    2004-12-01

    We review age-related changes in the ovary and their effect on female fertility, with particular emphasis on follicle formation, follicle dynamics, and oocyte quality. The evidence indicates that the developmental processes leading to follicle formation set the rules determining follicle quiescence and growth. This regulatory system is maintained until menopause and is directly affected in at least some models of premature ovarian failure (POF), most strikingly in the Foxl2 mouse knockout, a model of human POF with monogenic etiology (blepharophimosis/ptosis/epicanthus inversus syndrome). Several lines of evidence indicate that if the ovarian germ cell lineage maintains regenerative potential, as recently suggested in the mouse, a role in follicle dynamics for germ stem cells, if any, is likely indirect or secondary. In addition, age-related variations in oocyte quality in animal models suggest that reproductive competence is acquired progressively and might depend on parallel growth and differentiation of follicle cells and stroma. Genomewide analyses of the mouse oocyte transcriptome have begun to be used to systematically investigate the mechanisms of reproductive competence that are altered with aging. Investigative and therapeutic strategies can benefit from considering the role of continuous interactions between follicle cells and oocytes from the beginning of histogenesis to full maturation.

  17. Schwann cell-neuronal interactions in the rat involve nerve growth factor.

    PubMed

    Urschel, B A; Hulsebosch, C E

    1990-06-01

    To gain some insight into possible functions of nerve growth factor (NGF), we suppressed the endogenous levels of NGF in newborn rats by subcutaneous injections (3 microliters/g body weight) of rabbit antibodies to purified mouse beta-NGF (ANTI-NGF). Fiber and axonal areas and perimeters were measured for unmyelinated and myelinated sensory fibers in T9 dorsal roots (DR) in three groups of animals: 1) ANTI-NGF treated littermates, 2) preimmune sera treated littermates (PREIMM), and 3) untreated littermates (UNTR). In some rats, fibers in ventral roots (VR) were measured and, in other rats, sensory processes in peripheral nerves (PN) were measured following radical ventral rhizotomy. The only outer area and perimeter measurements that were statistically different were those in the ventral root (P less than 0.013 and P less than 0.043, respectively). However, myelin thickness was significantly thinner in the dorsal roots of the ANTI-NGF group than in the dorsal roots of the UNTR and PREIMM groups (P less than 0.000009 and P less than 10(-6), respectively). Myelin thickness in the ventral roots of the ANTI-NGF group was also statistically thinner than that in the UNTR group (P less than 0.001). There were no statistically significant differences when comparing the UNTR group to the PREIMM group. In the peripheral nerves studied, there was no significant change in the myelin thickness between the ANTI-NGF and UNTR groups of animals. These results indicate that Schwann cell-neuronal interactions are altered by the inactivation of NGF, and that 1) the central processes of sensory fibers are affected and not the peripheral processes and 2) motor fiber myelination is altered.(ABSTRACT TRUNCATED AT 250 WORDS)

  18. Interaction of epicatechins derived from green tea with rat hepatic cytochrome P-450.

    PubMed

    Wang, Z Y; Das, M; Bickers, D R; Mukhtar, H

    1988-01-01

    Green tea has been used for generations in China and Asia as an antipyretic and diuretic. Prior studies have shown that extracts of green tea inhibit the mutagenicity of polycyclic aromatic hydrocarbons and aflatoxin B1. In this study, we investigated the interaction of certain flavonoid components of green tea epicatechin derivatives including (-)-epicatechin (EC), (-)-epigallocatechin (EGC), (-)-epicatechin-3-gallate (ECG), and (-)-epigallocatechin-3-gallate (EGCG) with rat hepatic microsomal cytochrome P-450 (P-450). The addition of EC, EGC, ECG, and EGCG to hepatic microsomes prepared from phenobarbital (PB)-treated rats resulted in spectral changes characterized by absorbance maxima at 420 nm and minima at 380 nm, typical of modified Type II (reverse Type I) binding. Of the epicatechin derivatives, EGCG and ECG showed greater spectral change with oxidized P-450 and time- and concentration-dependent inhibition of the binding of carbon monoxide to dithionite-reduced cytochrome P-450. The addition of EC, EGC, ECG, and EGCG to microsomes prepared from control, PB- or 3-methylcholanthrene-treated rats resulted in a dose-dependent inhibition of cytochrome P-450-dependent aryl hydrocarbon hydroxylase, 7-ethoxycoumarin O-deethylase, and 7-ethoxyresorufin O-deethylase activities. EGCG was the most potent in this regard. Green tea polyphenols and epicatechin derivatives also significantly inhibited NADPH-cytochrome c reductase activity. An examination of the structure activity relationship of epicatechin derivatives suggests that the inhibitory effect on the microsomal enzyme system may be due to the galloyl groups or hydroxyl groups on the molecule. Our data indicate that these extracts of green tea may have potential as anticarcinogens.

  19. Interaction of sanguinarine alkaloid, isolated from argemone oil, with hepatic cytochrome p450 in rats.

    PubMed

    Reddy, Naveen P; Das, Mukul

    2008-01-01

    ABSTRACT Prior studies have shown that argemone oil (AO), responsible for 'Epidemic dropsy', causes inhibition of catalytic activities of Cytochrome P450 (P450). In this study interaction of sanguinarine (SAN) alkaloid, isolated from AO, with rat hepatic P450 was investigated. Hepatic microsomes prepared from 3-methylcholantherene (3MC) treated rats when incubated with SAN (1-3 muM) resulted in a spectral peak at 385 nm and a trough at 415 nm, indicative of Type I binding. Incubation of SAN (50-200 muM) with hepatic microsomes prepared from phenobarbitone (PB) treated rats also showed a Type I spectra with a peak at 395 nm and a trough at 420 nm. Relative binding efficiency (DeltaA(max)/K(s)(app) factor) of SAN with P450 was found to be 1540 and 1030 absorbance units/nmol CYP/M for 3MC and PB induced microsomes, respectively. In a P450 spectral inhibition study SAN showed higher affinity towards 3MC eliciting inhibition at much lesser concentrations (0.25-5 muM) as compared to PB (100-300 muM). The IC50s of SAN with different catalytic markers of P450 isoforms, i.e. ethoxyresorufin-O-deethylase (EROD) for CYP1A1, was 2.8 muM and for methoxyresorufin-O-deethylase (MROD) for CYP1A2 was 2.2 muM in 3MC induced microsomes, while benzoyloxyresorufin-O-deethylase (BROD) for CYP 2B1/1A1 showed an IC50 of 50 muM but pentoxyresorufin-O-deethylase (PROD) for CYP2B1 showed no inhibition even at higher concentrations of SAN (> 60 muM) in PB-induced microsomes. These results indicate that higher affinity of SAN binding towards the CYP1A family may have a role in SAN toxicity.

  20. Rat gastroduodenal motility in vivo: interaction of GABA and VIP in control of spontaneous relaxations.

    PubMed

    Krantis, A; Mattar, K; Glasgow, I

    1998-11-01

    Spontaneous relaxations occurring within motor activity in the rat gastroduodenum in vivo can be distinguished by their dependence on either nitric oxide (NO) or ATP. We examined the interaction of gamma-aminobutyric acid (GABA) and vasoactive intestinal peptide (VIP) within pathways controlling this activity in the antrum (S) and duodenum (D) of anesthetized Sprague-Dawley rats, using miniaturized extraluminal foil strain gauges oriented perpendicular to (S1, D1) or in the axis of (S2) the circular smooth muscle. The NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME; 10 mg/kg iv) attenuated (P < 0.05) antral relaxations and, in the duodenum, nonpropagating "intergroup" relaxations. The GABAA receptor antagonist bicuculline (350 micrograms/kg sc) had similar effects. The GABAA agonist 3-amino-1-propanesulfonic acid stimulated L-NAME-sensitive relaxations at S1 and D1. Propagating "grouped" responses were unchanged. VIP (6 micrograms/kg iv) always induced a relaxation of the duodenum, which was attenuated by bicuculline and L-NAME. VIP caused simultaneous responses at S1 and S2; however, the antrum displayed either contraction or relaxation in response to VIP. All antral relaxations in response to VIP were attenuated (P < 0. 05) by L-NAME; however, only VIP-induced relaxations at S1 were sensitive to bicuculline. VIP-induced contractions were also unaffected. GABAA receptors mediate the pathway(s) controlling NO-related spontaneous relaxations of the antrum and duodenal circular muscle. All VIP-induced relaxations are mediated by NO. Spontaneous relaxations of the rat gastroduodenum include responses that involve a GABAAergic NO-related pathway, which is targeted by VIP. In addition, VIP can target NO relaxations of the antrum via other pathways.

  1. Treatment for Stromal Tumors of the Ovary

    MedlinePlus

    ... Epithelial Tumors of Low Malignant Potential Treatment for Germ Cell Tumors of the Ovary Treatment for Stromal Tumors ... used is what’s used in the treatment of germ cell tumors (PEB: cisplatin, etoposide, and bleomycin). The combination ...

  2. Herbal formula menoprogen alters insulin-like growth factor-1 and insulin-like growth factor binding protein-1 levels in the serum and ovaries of an aged female rat model of menopause.

    PubMed

    Wei, Min; Zheng, Sheng Z; Lu, Ye; Liu, Daniel; Ma, Hong; Mahady, Gail B

    2015-10-01

    Menoprogen (MPG), a traditional Chinese medicine formula for menopause, improves menopausal symptoms; however, its mechanism remains unknown. Previous studies have shown that MPG is not directly estrogenic; thus, the goal of this study was to investigate the effects of MPG on insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-1 (IGFBP-1) levels in an aged female rat model of menopause. In a six-arm study, 14-month-old female Sprague-Dawley rats (n = 8 per arm) were randomly divided into the following groups: untreated aged, 17β-estradiol-treated aged (estradiol [E2]), and three arms with increasing doses of MPG (162, 324, or 648 mg/kg/d). The sixth arm contained 4-month-old female Sprague-Dawley rats as a normal comparison group. Four weeks after MPG or E2 administration, animals were killed after blood draws, and ovarian tissues were excised. Levels of E2 and progesterone (P4) were determined by radioimmunoassay. Serum and ovarian tissue levels of IGF-1, IGFBP-1, and IGF-1 receptor were determined by enzyme-linked immunosorbent assay. Compared with the normal group, aged rats had significantly reduced serum levels of E2, P4, and IGF-1, and increased serum and ovarian tissue levels of IGFBP-1. MPG restored serum IGF-1 and IGFBP-1 levels and down-regulated ovarian levels of IGFBP-1, which were closely related to increases in E2 and P4 levels in aged rats. No significant differences in either IGF-1 or IGFBP-1 were observed between the three doses of MPG. MPG exerts a direct in vivo effect on aged female rats by positively regulating serum and ovarian IGF-1 and IGFBP-1 levels.

  3. THC-methadone and THC-naltrexone interactions on discrimination, antinociception, and locomotion in rats.

    PubMed

    Wakley, Alexa A; Craft, Rebecca M

    2011-09-01

    This study examined cannabinoid-opioid interactions within the same subjects on measures of discrimination, antinociception, horizontal locomotion, and catalepsy. Male Sprague-Dawley rats were trained to discriminate Δ(9)-tetrahydrocannabinol (THC, 3 mg/kg) from vehicle. THC alone (0.32-10 mg/kg) dose-dependently increased THC-appropriate lever responding and decreased response rate. THC alone also produced paw pressure antinociception and decreased locomotor activity, but did not produce catalepsy. Methadone (0.32-5.6 mg/kg) and naltrexone (0.32-3.2 mg/kg) alone produced low THC-appropriate lever responding up to doses that decreased response rate. When combined with THC, methadone (1.0 mg/kg) flattened the THC discrimination curve, but did not affect antinociceptive or motoric effects of THC. Naltrexone did not alter any effects of THC. In rats that were not trained to discriminate THC from vehicle, 1.0 mg/kg methadone did enhance THC antinociception. These results suggest that μ-opioid receptor agonists can disrupt the discriminative stimulus effects of cannabinoids while not significantly altering their antinociceptive or motoric effects, in chronically drug-exposed subjects. Further research is required to determine whether opioid enhancement of cannabinoid antinociception is limited to acute exposure, or simply requires higher doses in chronically drug-exposed subjects.

  4. Antinociceptive synergistic interaction between Achillea millefolium and Origanum vulgare L. extract encapsulated in liposome in rat.

    PubMed

    Hassanzadeh-Kiabi, Farshad; Negahdari, Babak

    2017-07-18

    This study aims to evaluate the antinociceptive effect of combined Achillea millefolium and Origanum extract encapsulated in liposome. The effect of Achillea millefolium and Origanum vulgare L. extract, and their liposome-incorporated form was assessed using 3% formalin test in rat. 12 male Wistar rats, 4 in each group, were used in this study, and increasing doses of Achillea millefolium (31.6, 100, 178, and 316 mg/kg) and Origanum vulgare L. extract (5.6, 10, 17.8, and 31.6 mg/kg), and co-administered extract were i.p. administered 10 min before 3% formalin. The mechanisms of action were evaluated for the liposomal encapsulated co-administered extract using N(G)-nitro-l-arginine methyl ester (L-NAME) (3 mg/kg) and naloxone (1 mg/kg). The interaction index and isobolographic analysis revealed a synergistic effect of the extracts. We observed a lower experimental ED30 as compared to the theoretical ED30. Naloxone also reduced the antinociceptive effect of the liposome encapsulated co-administered extract. These data suggest that the Achillea millefolium and Origanum vulgare L. extract encapsulated in liposome gave a synergistic effect.

  5. Interactions between iron(III)-hydroxide polymaltose complex and commonly used medications / laboratory studies in rats.

    PubMed

    Funk, Felix; Canclini, Camillo; Geisser, Peter

    2007-01-01

    Simple iron salts, such as iron sulphate, often interact with food and other medications reducing bioavailability and tolerability. Iron(III)-hydroxide polymaltose complex (IPC, Maltofer) provides a soluble form of non-ionic iron, making it an ideal form of oral iron supplementation. The physicochemical properties of IPC predict a low potential for interactions. The effects of co-administration with aluminium hydroxide (CAS 21645-51-2), acetylsalicylic acid (CAS 50-78-2), bromazepam (CAS 1812-30-2), calcium acetate (CAS 62-54-4), calcium carbonate (CAS 471-34-1), auranofin (CAS 34031-32-8), magnesium-L-aspartate hydrochloride (CAS 28184-71-6), methyldopa sesquihydrate (CAS 41372-08-1), paracetamol (CAS 103-90-2), penicillamine (CAS 52-67-5), sulfasalazine (CAS 599-79-1), tetracycline hydrochloride (CAS 64-75-5), calcium phosphate (CAS 7757-93-9) in combination with vitamin D3 (CAS 67-97-0), and a multi-vitamin preparation were tested in rats fed an iron-deficient diet. Uptake of iron from radiolabelled IPC with and without concomitant medications was compared. None of the medicines tested had a significant effect on iron uptake. Iron-59 retrieval from blood and major storage organs was 64-76% for IPC alone compared with 59-85% following co-administration with other medications. It is concluded that, under normal clinical conditions, IPC does not interact with these medications.

  6. Social interaction with a cagemate in pain facilitates subsequent spinal nociception via activation of the medial prefrontal cortex in rats.

    PubMed

    Li, Zhen; Lu, Yun-Fei; Li, Chun-Li; Wang, Yan; Sun, Wei; He, Ting; Chen, Xue-Feng; Wang, Xiao-Liang; Chen, Jun

    2014-07-01

    Empathy for the pain experience of others can lead to the activation of pain-related brain areas and can even induce aberrant responses to pain in human observers. Recent evidence shows this high-level emotional and cognitive process also exists in lower animals; however, the mechanisms underlying this phenomenon remain unknown. In the present study we found that, after social interaction with a rat that had received subcutaneous injection of bee venom (BV), only the cagemate observer (CO) but not the noncagemate observer (NCO) showed bilateral mechanical hypersensitivity and an enhanced paw flinch reflex following BV injection. Moreover, neuronal activities labeled by c-Fos immunoreactivity in the spinal dorsal horn of CO rats were also significantly increased relative to the control 1 hour after BV injection. A stress-related response can be excluded because serum corticosterone concentration following social interaction with demonstrator rats in pain was not changed in CO rats relative to NCO and isolated control rats. Anxiety can also be excluded because anxiety-like behaviors could be seen in both the CO and NCO rats tested in the open-field test. Finally, bilateral lesions of the medial prefrontal cortex eliminated the enhancement of the BV-induced paw flinch reflex in CO rats, but bilateral lesions of either the amygdala or the entorhinal cortex failed. Together, we have provided another line of evidence for the existence of familiarity-dependent empathy for pain in rats and have demonstrated that the medial prefrontal cortex plays a critical role in processing the empathy-related enhancement of spinal nociception.

  7. Honeybee product therapeutic as stem cells homing for ovary failure

    PubMed Central

    Safitri, Erma; Widiyatno, Thomas V.; Prasetyo, R. Heru

    2016-01-01

    Aim: Complexity of the method of isolation, cultivation in vitro and the expensive cost of transplantation process of stem cells, it would require an innovation to homing and differentiation of stem cells and increase folliculogenesis. The stem cells homing was achieved through the provision of food or beverages derived from natural materials like honeybee product. Through honeybee product, there will be homing of stem cells and accompany with the sources from the body itself will take place in regeneration of the ovary. Materials and Methods: Female rats model of degenerative ovary was obtained through food fasting but still have drinking water for 5 days. It caused malnutrition and damage of the ovarian tissue. The administration of 50% honeybee product (T1) was performed for 10 consecutive days, while the positive control group (T0+) was fasted and not given honeybee product and the negative control (T0−) not fasted and without honeybee product. Observations were taken for homing of stem cells, raised of folliculogenesis, differentiation of stem cells, and regeneration of the ovarian tissue using routine H&E staining. Results: Homing of stem cells shown the vascular endothelial growth factor and granulocyte colony-stimulating factor expression; enhancement of folliculogenesis was indicated by an increase of follicle dee Graaf count; enhancement of differentiation of stem cells was indicated by growth differentiation factor-9 expression; and regeneration of ovarian tissue indicated by intact ovarian tissue with growing follicles. Conclusion: Honeybee product can be induced endogenous stem cells in regeneration of ovary failure due to malnutrition. PMID:27956789

  8. The importance of neuronal growth factors in the ovary.

    PubMed

    Streiter, S; Fisch, B; Sabbah, B; Ao, A; Abir, R

    2016-01-01

    The neurotrophin family consists of nerve growth factor (NGF), neurotrophin 3 (NT3) and neurotrophin 4/5 (NT4/5), in addition to brain-derived neurotrophic factor (BDNF) and the neuronal growth factors, glial cell line-derived neurotrophic factor (GDNF) and vasointestinal peptide (VIP). Although there are a few literature reviews, mainly of animal studies, on the importance of neurotrophins in the ovary, we aimed to provide a complete review of neurotrophins as well as neuronal growth factors and their important roles in normal and pathological processes in the ovary. Follicular assembly is probably stimulated by complementary effects of NGF, NT4/5 and BDNF and their receptors. The neurotrophins, GDNF and VIP and their receptors have all been identified in preantral and antral follicles of mammalian species, including humans. Transgenic mice with mutations in the genes encoding for Ngf, Nt4/5 and Bdnf and their tropomyosin-related kinase β receptor showed a reduction in preantral follicles and an abnormal ovarian morphology, whereas NGF, NT3, GDNF and VIP increased the in vitro activation of primordial follicles in rats and goats. Additionally, NGF, NT3 and GDNF promoted follicular cell proliferation; NGF, BDNF and VIP were shown to be involved in ovulation; VIP inhibited follicular apoptosis; NT4/5, BDNF and GDNF promoted oocyte maturation and NGF, NT3 and VIP stimulated steroidogenesis. NGF may also exert a stimulatory effect in ovarian cancer and polycystic ovarian syndrome (PCOS). Low levels of NGF and BDNF in follicular fluid may be associated with diminished ovarian reserve and high levels with endometriosis. More knowledge of the roles of neuronal growth factors in the ovary has important implications for the development of new therapeutic drugs (such as anti-NGF agents) for ovarian cancer and PCOS as well as various infertility problems, warranting further research.

  9. A rat brain Sec1 homologue related to Rop and UNC18 interacts with syntaxin.

    PubMed Central

    Garcia, E P; Gatti, E; Butler, M; Burton, J; De Camilli, P

    1994-01-01

    Sec1 is a hydrophilic protein that plays an essential role in exocytosis from the yeast Saccharomyces cerevisiae. Two high copy suppressors of mutations in the Sec1 gene, SSO1 and SSO2, were recently identified that encode proteins of the syntaxin family. Syntaxin (a T-SNARE), together with SNAP-25 and synaptobrevin/VAMP (a T- and a V-SNARE, respectively), is thought to form the core of the docking-fusion complex in synaptic vesicle exocytosis. Proteins that exhibit similarity to Sec1 were identified in the nervous system of Drosophila melanogaster (Rop) and Caenorhabditis elegans (UNC18). Based on the amino acid sequence alignment of Sec1, Rop, and UNC18, we have used a PCR-based approach to isolate a rat brain cDNA encoding a Sec1 homologue. The cDNA hybridizes to a 3.5-kb brain-specific mRNA by Northern blot analysis and encodes a protein of 593 amino acids (rbSec1). Antibodies raised against a central portion of rbSec1 recognize a 67.5-kDa protein in total homogenates of rat brain but not of nonneuronal tissues. When incubated with a Triton X-100 brain extract, rbSec1-glutathione S-transferase (GST) fusion protein, but not GST protein alone, specifically interacts with syntaxin but not with SNAP-25 or synaptobrevin/VAMP. We conclude that the function of proteins of the Sec1 family in membrane fusion involves an interaction with a T-SNARE. Images PMID:8134339

  10. Pharmacodynamic and Pharmacokinetic Interactions of Propranolol with Garlic (Allium sativum) in Rats

    PubMed Central

    Asdaq, Syed Mohammed Basheeruddin; Inamdar, Mohammed Naseeruddin

    2011-01-01

    Garlic preparations and propranolol (PRO) are agents recognized as cardioprotective and potent antihypertensive agents when they are used individually. However, there is no report available to explain the role of combined therapy during simultaneous hypertension and myocardial damage in rats. We aimed to determine the pharmacokinetic and pharmacodynamic interaction of PRO with garlic homogenate (GH), in rats. The influence of garlic on pharmacokinetics of PRO was determined by HPLC method; while pharmacodynamic interaction was studied in animals with hypertension (10% fructose) and myocardial damage (isoproterenol, 175 mg kg−1, s.c. 2 days). PRO was given orally at 10 mg kg−1 for 1 week, whereas, GH was administered at three different doses of 125, 250 and 500 mg kg−1, p.o. in their respective groups during fourth to sixth week of high fructose (HF) period, once daily. Systolic blood pressure (SBP), heart rate, cholesterol, triglycerides, glucose, creatine phosphokinase-MB, lactate dehydrogenase, superoxide dismutase and catalase were measured and histopathological studies were carried out. The bioavailability and half life of PRO were significantly enhanced by 2- and 3-fold, respectively, in animals pretreated with garlic (250 mg kg−1). Administration of PRO and low to moderate doses of GH (125, 250 mg kg−1), either alone or together showed fall in fluid intake and body weight. The combined therapy of GH 250 mg kg−1 and PRO was found to be most effective in reducing SBP, cholesterol, triglycerides and glucose. These observations suggest that careful addition of garlic in moderate doses in PRO regimen might result in beneficial effect during treatment of hypertensive animals with myocardial damage. PMID:21792365

  11. Pharmacokinetic-pharmacodynamic modelling of the convulsant interaction between norfloxacin and biphenyl acetic acid in rats

    PubMed Central

    Marchand, Sandrine; Pariat, Claudine; Bouquet, Serge; Courtois, Philippe; Couet, William

    2000-01-01

    Fluoroquinolones (FQs) are associated with a low incidence of central nervous system (CNS) side effects, possibly leading to convulsions, especially when co-administered with nonsteroidal anti-inflammatory drugs (NSAIDS). Although the in vivo pro-convulsant activity of NSAIDS is essentially unknown, the convulsant potential of FQs is traditionally evaluated by in vitro γ-aminobutyric acid (GABA) binding experiments in the presence of 4-biphenyl acetic acid (BPAA), the active metabolite of fenbufen.The aim of this study was therefore to investigate the BPAA-norfloxacin convulsant interaction in vivo.Male Sprague-Dawley rats (n=27) were given BPAA orally, at various doses 1 h before norfloxacin infusion, which was maintained until the onset of maximal seizures, when cerebrospinal fluid (CSF) and plasma samples were collected for analysis.An inhibitory Emax effect model with a baseline effect parameter was fitted to the norfloxacin versus BPAA concentrations in the CSF, previously shown to be part of the biophase. This model includes three parameters: the concentrations of norfloxacin in the absence of BPAA (CCSF0, Nor), and when BPAA concentration tends toward infinity (CCSFbase, Nor), and the BPAA concentration for which half of the maximal effect is observed (CCSF50, BPAA). The maximal proconvulsant effect of BPAA is given by the CCSF0, Nor / CCSFbase, Nor ratio, estimated to approximately 6 in this study.Derived models were developed in plasma to account for the non-linear CSF diffusion of norfloxacin and protein binding of BPAA.In conclusion this study has shown that the convulsant interaction between norfloxacin and BPAA in rats, can be adequately characterized by modelling of the CSF concentrations of the two drugs at the onset of activity, following their administration in various proportions. PMID:10780965

  12. A Novel Bidirectional Interaction between endothelin-3 and Retinoic Acid in Rat Enteric Nervous System Precursors

    PubMed Central

    Gisser, Jonathan M.; Cohen, Ariella R.; Yin, Han; Gariepy, Cheryl E.

    2013-01-01

    Background Signaling through the endothelin receptor B (EDNRB) is critical for the development of the enteric nervous system (ENS) and mutations in endothelin system genes cause Hirschsprung’s aganglionosis in humans. Penetrance of the disease is modulated by other genetic factors. Mutations affecting retinoic acid (RA) signaling also produce aganglionosis in mice. Thus, we hypothesized that RA and endothelin signaling pathways may interact in controlling development of the ENS. Methods Rat immunoselected ENS precursor cells were cultured with the EDNRB ligand endothelin-3, an EDNRB-selective antagonist (BQ-788), and/or RA for 3 or 14 days. mRNA levels of genes related to ENS development, RA- and EDNRB-signaling were measured at 3 days. Proliferating cells and cells expressing neuronal, glial, and myofibroblast markers were quantified. Results Culture of isolated ENS precursors for 3 days with RA decreases expression of the endothelin-3 gene and that of its activation enzyme. These changes are associated with glial proliferation, a higher percentage of glia, and a lower percentage of neurons compared to cultures without RA. These changes are independent of EDNRB signaling. Conversely, EDNRB activation in these cultures decreases expression of RA receptors β and γ mRNA and affects the expression of the RA synthetic and degradative enzymes. These gene expression changes are associated with reduced glial proliferation and a lower percentage of glia in the culture. Over 14 days in the absence of EDNRB signaling, RA induces the formation of a heterocellular plexus replete with ganglia, glia and myofibroblasts. Conclusions A complex endothelin-RA interaction exists that coordinately regulates the development of rat ENS precursors in vitro. These results suggest that environmental RA may modulate the expression of aganglionosis in individuals with endothelin mutations. PMID:24040226

  13. Molecular characterization of cancer reveals interactions between ionizing radiation and chemicals on rat mammary carcinogenesis.

    PubMed

    Imaoka, Tatsuhiko; Nishimura, Mayumi; Doi, Kazutaka; Tani, Shusuke; Ishikawa, Ken-ichi; Yamashita, Satoshi; Ushijima, Toshikazu; Imai, Takashi; Shimada, Yoshiya

    2014-04-01

    Although various mechanisms have been inferred for combinatorial actions of multiple carcinogens, these mechanisms have not been well demonstrated in experimental carcinogenesis models. We evaluated mammary carcinogenesis initiated by combined exposure to various doses of radiation and chemical carcinogens. Female rats at 7 weeks of age were γ-irradiated (0.2-2 Gy) and/or exposed to 1-methyl-1-nitrosourea (MNU) (20 or 40 mg/kg, single intraperitoneal injection) or 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) (40 mg/kg/day by gavage for 10 days) and were observed until 50 weeks of age. The incidence of mammary carcinoma increased steadily as a function of radiation dose in the absence of chemicals; mathematical analysis supported an additive increase when radiation was combined with a chemical carcinogen, irrespective of the chemical species and its dose. Hras mutations were characteristic of carcinomas that developed after chemical carcinogen treatments and were overrepresented in carcinomas induced by the combination of radiation and MNU (but not PhIP), indicating an interaction of radiation and MNU at the level of initiation. The expression profiles of seven classifier genes, previously shown to distinguish two classes of rat mammary carcinomas, categorized almost all examined carcinomas that developed after individual or combined treatments with radiation (1 Gy) and chemicals as belonging to a single class; more comprehensive screening using microarrays and a separate test sample set failed to identify differences in gene expression profiles among these carcinomas. These results suggest that a complex, multilevel interaction underlies the combinatorial action of radiation and chemical carcinogens in the experimental model.

  14. Does Prenatal Valproate Interact with a Genetic Reduction in the Serotonin Transporter? A Rat Study on Anxiety and Cognition

    PubMed Central

    Ellenbroek, Bart A.; August, Caren; Youn, Jiun

    2016-01-01

    There is ample evidence that prenatal exposure to valproate (or valproic acid, VPA) enhances the risk of developing Autism Spectrum Disorders (ASD). In line with this, a single injection of VPA induces a multitude of ASD-like symptoms in animals, such as rats and mice. However, there is equally strong evidence that genetic factors contribute significantly to the risk of ASD and indeed, like most other psychiatric disorders, ASD is now generally thought to results from an interaction between genetic and environmental factors. Given that VPA significantly impacts on the serotonergic system, and serotonin has strong biochemical and genetic links to ASD, we aimed to investigate the interaction between genetic reduction in the serotonin transporter and prenatal valproate administration. More specifically, we exposed both wildtype (SERT+/+) rats and rats heterozygous for the serotonin transporter deletion (SERT+/−) to a single injection of 400 mg/kg VPA at gestational day (GD) 12. The offspring, in adulthood, was assessed in four different tests: Elevated Plus Maze and Novelty Suppressed Feeding as measures for anxiety and prepulse inhibition (PPI) and latent inhibition as measures for cognition and information processing. The results show that prenatal VPA significantly increased anxiety in both paradigm, reduced PPI and reduced conditioning in the latent inhibition paradigm. However, we failed to find a significant gene–environment interaction. We propose that this may be related to the timing of the VPA injection and suggest that whereas GD12 might be optimal for affecting normal rat, rats with a genetically compromised serotonergic system may be more sensitive to VPA at earlier time points during gestation. Overall our data are the first to investigate gene * environmental interactions in a genetic rat model for ASD and suggest that timing may be of crucial importance to the long-term outcome. PMID:27708559

  15. ETA receptor mediates altered leukocyte-endothelial cell interaction and adhesion molecules expression in DOCA-salt rats.

    PubMed

    Callera, Glaucia E; Montezano, Augusto C; Touyz, Rhian M; Zorn, Telma M T; Carvalho, Maria Helena C; Fortes, Zuleica B; Nigro, Dorothy; Schiffrin, Ernesto L; Tostes, Rita C

    2004-04-01

    Leukocyte adhesion to endothelial cells plays a key role in inflammatory processes associated with end-organ injury. Endothelin-1 (ET-1), which stimulates inflammatory processes, contributes to cardiovascular damage in deoxycorticosterone (DOCA)-salt hypertension. We investigated whether ETA receptor blockade modulates in vivo leukocyte-endothelial cell interactions and expression of cell adhesion molecules (CAM) involved in these processes. DOCA-salt and control uninephrectomized rats were treated with the ETA antagonist BMS182874 (40 mg/kg per day) or vehicle. Analysis of CAMs expression by reverse transcription-polymerase chain reaction and immunohistochemistry showed increased cardiac platelet selectin (P-selectin), detected mainly in endothelial cells, and vascular cell adhesion molecule-1 (VCAM-1), but not intercellular adhesion molecule-1 (ICAM-1), in DOCA-salt rats. Cardiac expression of endothelial selectin (E-selectin) was decreased, whereas immunoreactivity to ED-1 and myeloperoxidase (MPO) activity, markers of macrophage and leukocyte infiltration, respectively, were increased in DOCA-salt. Leukocyte-endothelial cell interaction, functionally assessed in venules of internal spermatic fascia by intravital microscopy, was significantly altered in DOCA-salt rats as evidenced by increased leukocyte adhesion and decreased rolling. BMS182874 treatment normalized leukocyte-endothelium interactions, decreased cardiac VCAM-1 expression in DOCA and control groups, and had no effects on ICAM-1 expression. BMS182874 also increased E-selectin and abolished P-selectin expression in DOCA-salt, but not in control rats. The ETA antagonist reduced cardiac ED-1 content and MPO activity and prevented cardiac damage in DOCA-salt rats. These data indicate that ET-1 participates, via activation of ETA receptors, in altered leukocyte-endothelial cell interactions in DOCA-salt rats, possibly by modulating expression of CAMs, and that the inflammatory status is associated with

  16. Social Interaction and Conditional Self-Discrimination under a Paradigm of Avoidance and Positive Reinforcement in Wistar Rats

    ERIC Educational Resources Information Center

    Penagos-Corzo, Julio C.; Pérez-Acosta, Andrés M.; Hernández, Ingrid

    2015-01-01

    The experiment reported here uses a conditional self-discrimination task to examine the influence of social interaction on the facilitation of self-discrimination in rats. The study is based on a previous report (Penagos- Corzo et al., 2011) showing positive evidence of such facilitation, but extending the exposition to social interaction…

  17. Effects of phorbol 12-myristate 13-acetate and cortisol interaction on steroid-binding capacity in the rat.

    PubMed Central

    Janssens, J P; de Loecker, W

    1979-01-01

    The specificity of the cortisol-receptor protein is examined in plasma and liver cytosol of rats. Phorbol 12-myristate 13-acetate does not inhibit the binding of cortisol to transcortin, nor does it affect the binding capacity of dexamethasone to the intracellular glucocorticoid receptor, but, by interacting with the cortisol molecule, it interferes with hormone-mediated processes in the cell. PMID:534535

  18. Synergistic Co-activation Increases the Extent of Mechanical Interaction between Rat Ankle Plantar-Flexors

    PubMed Central

    Tijs, Chris; van Dieën, Jaap H.; Baan, Guus C.; Maas, Huub

    2016-01-01

    Force transmission between rat ankle plantar-flexors has been found for physiological muscle lengths and relative positions, but only with all muscles maximally activated. The aims of this study were to assess intermuscular mechanical interactions between ankle plantar-flexors during (i) fully passive conditions, (ii) excitation of soleus (SO), (iii) excitation of lateral gastrocnemius (LG), and (iv) during co-activation of SO, and LG (SO&LG). We assessed effects of proximal lengthening of LG and plantaris (PL) muscles (i.e., simulating knee extension) on forces exerted at the distal SO tendon (FSO) and on the force difference between the proximal and distal LG+PL tendons (ΔFLG+PL) of the rat. LG+PL lengthening increased FSO to a larger extent (p = 0.017) during LG excitation (0.0026 N/mm) than during fully passive conditions (0.0009 N/mm). Changes in FSO in response to LG+PL lengthening were lower (p = 0.002) during SO only excitation (0.0056 N/mm) than during SO&LG excitation (0.0101 N/mm). LG+PL lengthening changed ΔFLG+PL to a larger extent (p = 0.007) during SO excitation (0.0211 N/mm) than during fully passive conditions (0.0157 N/mm). In contrast, changes in ΔFLG+PL in response to LG+PL lengthening during LG excitation (0.0331 N/mm) were similar (p = 0.161) to that during SO&LG excitation (0.0370 N/mm). In all conditions, changes of FSO were lower than those of ΔFLG+PL. This indicates that muscle forces were transmitted not only between LG+PL and SO, but also between LG+PL and other surrounding structures. In addition, epimuscular myofascial force transmission between rat ankle plantar-flexors was enhanced by muscle activation. However, the magnitude of this interaction was limited. PMID:27708589

  19. PHARMACOKINETIC AND PHARMACODYNAMIC INTERACTION FOR A BINARY MIXTURE OF CHLORPYRIFOS AND DIAZINON IN THE RAT

    SciTech Connect

    Timchalk, Chuck; Poet, Torka S.; Hinman, Melissa N.; Busby, Andrea L.; Kousba, Ahmed A.

    2005-05-15

    Chlorpyrifos (CPF) and diazinon (DZN) are two commonly used organophosphorus (OP) insecticides and potential exists for concurrent exposures. The primary neurotoxic effects from OP pesticide exposures result from the inhibition of acetylcholinesterase (AChE) by their oxon metabolites. The pharmacokinetic and pharmacodynamic impact of acute binary exposures to CPF and DZN in rats were evaluated in this study. Rats were orally administered CPF, DZN or a CPF/DZN mixture (0, 15, 30 or 60 mg/kg) and blood (plasma and RBC), and brain were collected at 0, 3, 6, 12 and 24 h post-dosing, urine was also collected at 24 h. Chlorpyrifos, DZN and their respective metabolites 3,5,6-trichloro-2-pyridinol (TCP) and 2-isopropyl-4-methyl-6-hydroxypyrimidine (IMHP) were quantified in blood and/or urine and cholinesterase (ChE) inhibition was measured in brain, RBCs and plasma. Co-exposure to CPF/DZN at 15/15 mg/kg, did not appreciably alter the pharmacokinetics of CPF, DZN or their metabolites in blood; whereas, a 60/60 mg/kg dose resulted in a transient increase in Cmax, AUC, and decreased clearance of both compounds, likely due to competition between CPF and DZN for CYP450 metabolism. At lower doses, most likely to be encountered in occupational or environmental exposures, the pharmacokinetics were linear. A dose-dependent inhibition of ChE was noted in tissues for both the single and co-exposures. The overall potency for ChE inhibition was greater for CPF than DZN and the binary mixture response appeared to be strongly influenced by CPF. A comparison of the ChE binary response at the low dose (15 mg/kg), where there were no apparent pharmacokinetic interactions, suggested that the overall ChE response was additive. These are the first reported experiments we are aware of that characterize both the pharmacokinetic and pharmacodynamic interactions between CPF and DZN in the rat, and will be used to further develop a binary physiologically based pharmacokinetic and pharmacodynamic

  20. Metformin and Polycystic Ovary Syndrome

    PubMed Central

    Omran, Maha Yousef Soliman

    2007-01-01

    The polycystic ovary syndrome (PCOS), one of the most common causes of infertility due to anovulation, affects 4–7% of women). Etiology of PCOS remains largely unknown, familial aggregation of cases suggests genetic susceptibility to the disorder. Though genes involved remain unknown, recent evidence points to a gene of the insulin receptor. Genes implicated in ovarian follicular development may also play a role. A fundamental aspect of the syndrome seems to be a defect in insulin metabolism. There is consistent evidence that increase of body weight may favour a more severe hyperandrogenism. Treatment of PCOS has been mostly symptomatic. Only recently has the use of insulinomimetic or insulin sensitizing agents provided an option to treat the presumed underlying cause of this disorder, which is insulin resistance. Metformin appears to improve risk factors for cardiovascular disease in diabetic and non-diabetic patients, indicating that its use could be associated with a reduction in coronary heart disease in patients with PCOS. The use of metformin in hyperinsulinemic women with PCOS improved the lipid profile, including decreases in total cholesterol, low density lipoprotein cholesterol, and triglyceride concentration. PMID:21475454

  1. Polycystic ovary syndrome in adolescence.

    PubMed

    Driscoll, Deborah A

    2003-08-01

    Polycystic ovary syndrome (PCOS) is a relatively common disorder among adolescent women. The typical clinical features including menstrual irregularities and hirsutism are usually not apparent until middle to late adolescence. Yet studies suggest that PCOS may begin in early puberty. Young women with premature pubarche, a family history of PCOS, Caribbean Hispanic and African American ancestry, and/or obesity are more likely to develop PCOS. Adolescents with PCOS may have elevated total or free testosterone, androstenedione, and luteinizing hormone levels; insulin resistance; and hyperinsulinemia. The laboratory evaluation and management of the adolescent with suspected PCOS should be individualized on the basis of the clinical features and symptoms. The cornerstone of most treatment strategies includes either a combination oral contraceptive or progestin to decrease testosterone levels and regulate the menstrual cycle. Consideration of insulin-sensitizing agents, antiandrogens, topical treatments for acne and excess facial hair, and hair removal is dependent on the patient's symptoms and concerns. A healthy approach to eating, in some cases weight loss, and exercise is encouraged to reduce the risk of cardiovascular disease and type 2 diabetes mellitus. Management of the adolescent with PCOS is challenging and often requires a supportive, multidisciplinary team approach for optimal results.

  2. Androgen and FSH synergistically stimulate lipoprotein degradation and utilization by ovary granulosa cells

    SciTech Connect

    Schreiber, J.R.; Nakamura, K.; Schmit, V.; Weinstein, D.B.

    1984-01-01

    Androgen can directly modulate the induction of steroidogenic enzymes by FSH (follicle stimulating hormone) in ovary granulosa cells. In studies of its mechanism of action, the authors examined the androgen effect on granulosa cell interaction with lipoproteins, the physiologic source of cholesterol. After granulosa cells were cultured for 48 hours with and without androgen and/or FSH, the cells were incubated for 24 hours with /sup 125/I-lipoproteins (human high density lipoprotein (HDL), rat HDL, or human low density lipoprotein (LDL)). The media were then analyzed for lipoprotein protein coat degradation products (mainly /sup 125/I-monoiodotyrosine) and progestin (mainly 20 alpha-dihydroprogesterone (20 alpha-DHP)). In the absence of FSH and androgen, 2 X 10(5) granulosa cells degraded basal levels of all three lipoproteins, but produced no measurable 20 alpha-DHP. The addition of 10(-7) M androstenedione (A), testosterone (T), or 5 alpha-dihydrotestosterone (DHT) had no effect on lipoprotein protein degradation or 20 alpha-DHP production. FSH alone stimulated lipoprotein protein degradation by 50 to 300% while the addition of androgen synergistically augmented the FSH-stimulated 20 alpha-DHP production as well as protein coat degradation of all three lipoproteins. DHT and T were both effective, indicating that androgens themselves, and not estrogen products, were responsible for the effect on lipoprotein protein degradation and 20 alpha-DHP production.

  3. Insulin Resistance Influences Central Opioid Activity in Polycystic Ovary Syndrome

    PubMed Central

    Berent-Spillson, Alison; Love, Tiffany; Pop-Busui, Rodica; Sowers, MaryFran; Persad, Carol C.; Pennington, Kathryn P.; Eyvazaddeh, Aimee D.; Padmanabhan, Vasantha; Zubieta, Jon-Kar; Smith, Yolanda R.

    2011-01-01

    This pilot study describes a relationship between insulin resistance and µ-opioid neurotransmission in limbic appetite and mood-regulating regions in women with polycystic ovary syndrome, suggesting that insulin-opioid interactions may contribute to behavioral and reproductive pathologies of PCOS. We found that 1) insulin resistant PCOS patients (n=7) had greater limbic µ-opioid receptor availability (non-displaceable binding potential) than controls (n=5), 2) receptor availability was correlated with severity of insulin resistance, and 3) receptor availability normalized after insulin-regulating treatment. PMID:21486668

  4. Insulin resistance influences central opioid activity in polycystic ovary syndrome.

    PubMed

    Berent-Spillson, Alison; Love, Tiffany; Pop-Busui, Rodica; Sowers, MaryFran; Persad, Carol C; Pennington, Kathryn P; Eyvazaddeh, Aimee D; Padmanabhan, Vasantha; Zubieta, Jon-Kar; Smith, Yolanda R

    2011-06-30

    This pilot study describes a relationship between insulin resistance and μ-opioid neurotransmission in limbic appetite and mood-regulating regions in women with polycystic ovary syndrome (PCOS), suggesting that insulin-opioid interactions may contribute to behavioral and reproductive pathologies of PCOS. We found that [1] patients with PCOS who are insulin-resistant (n = 7) had greater limbic μ-opioid receptor availability (nondisplaceable binding potential) than controls (n = 5); [2] receptor availability was correlated with severity of insulin resistance; and [3] receptor availability normalized after insulin-regulating treatment.

  5. Stromal-epithelial paracrine interactions in the neoplastic rat and human prostate.

    PubMed

    Djakiew, D; Pflug, B; Onoda, M

    1993-01-01

    Homotypic paracrine interactions in the rat and human prostate have been investigated using prostatic stromal cells and neoplastic epithelial cells (PA-III, rat; TSU-pr1, human). Secretory proteins prepared from each cell type were used to determine the dose dependent regulation of growth (DNA synthesis) of the corresponding homotypic responder cell, as determined by 3H-thymidine incorporation. PA-III secretory protein stimulated rat stromal cell proliferation by 1.8-fold. This stimulatory activity of PA-III protein on stromal cell proliferation was partially reduced (approximately 35%) by treatment with nerve growth factor (NGF) antibody, whereas neither acidic fibroblast growth factor (aFGF) antibody nor basic fibroblast growth factor (bFGF) antibody immunoneutralized the stimulatory activity of PA-III cell protein. In the corresponding opposite interaction, rat stromal cell protein modulated PA-III growth in a biphasic manner. At lower concentrations of stromal cell protein (1.25 micrograms/ml) PA-III cell growth was stimulated by 1.6-fold, whereas at higher concentrations of protein (100 micrograms/ml) PA-III cell growth was inhibited to 60%. Treatment of the stromal cell protein (1.25 micrograms/ml and 100 micrograms/ml) with NGF antibody reduced PA-III cell relative growth to approximately 30% and 5%, respectively. bFGF antibody treatment of stromal cell protein at 1.25 micrograms/ml did not influence relative growth, whereas bFGF antibody treatment of 100 micrograms/ml stromal cell protein reduced relative growth by an additional 40%. Treatment of the stromal cell protein (1.25 micrograms/ml and 100 micrograms/ml) with aFGF antibodies reduced relative growth from that observed at these two protein concentrations by approximately 50% in both cases. Human epithelial TSU-pr1 protein stimulated human stromal cell proliferation approximately 1.7-fold. Treatment of TSU-pr1 protein with NGF antibody resulted in stimulation of human stromal cell proliferation (4

  6. Levetiracetam interacts synergistically with nonsteroidal analgesics and caffeine to produce antihyperalgesia in rats.

    PubMed

    Tomić, Maja A; Micov, Ana M; Stepanović-Petrović, Radica M

    2013-11-01

    Levetiracetam is a novel anticonvulsant with antihyperalgesic efficacy in inflammatory pain. Nonsteroidal analgesics and caffeine, as analgesic adjuvant, are widely used against inflammatory pain. This study characterized the manner in which levetiracetam interacts with analgesics (ibuprofen, celecoxib, and paracetamol) and caffeine to suppress hyperalgesia in a model of localized inflammation. Rat paw inflammation was induced by intraplantar carrageenan (.1 mL, 1%). Hyperalgesia and antihyperalgesic effects of levetiracetam (orally), analgesics (orally), and caffeine (intraperitoneally) alone and 2-drug combinations of levetiracetam with analgesics or caffeine were examined by a modified paw pressure test. The type of interaction between components was determined by isobolographic analysis or by analysis of the log dose-response curves for drug combination and drugs alone. Levetiracetam (10-200 mg/kg), ibuprofen (12.5-100 mg/kg), celecoxib (3.75-30 mg/kg), paracetamol (50-200 mg/kg), caffeine (15-100 mg/kg), and 2-drug combinations of levetiracetam with analgesics/caffeine produced a significant, dose-dependent reduction of inflammatory hyperalgesia. Isobolographic analysis revealed that levetiracetam exerts a synergistic interaction with analgesics, with approximately 7-, 9-, and 11-fold reduction of doses of both drugs in combination of levetiracetam with paracetamol, celecoxib, and ibuprofen, respectively. Analysis of the log dose-response curves for levetiracetam (1-50 mg/kg) in the presence of caffeine (10 mg/kg) and levetiracetam applied alone also revealed a synergistic interaction. Levetiracetam's ED50 in the presence of caffeine was reduced approximately 11-fold. The presented data suggest that 2-drug combinations of levetiracetam and nonsteroidal analgesics or caffeine could be useful in treatment of inflammatory pain. The efficacy and the adverse effects of those mixtures should be explored further in clinical settings. Copyright © 2013

  7. Investigating herb-drug interactions: the effect of Citrus aurantium fruit extract on the pharmacokinetics of amiodarone in rats.

    PubMed

    Rodrigues, Márcio; Alves, Gilberto; Falcão, Amílcar

    2013-10-01

    Citrus aurantium extract has been largely used in weight loss and sports performance dietary supplements. However, the safety of C. aurantium-containing products has been questioned mainly due to the association of its use with adverse events in the cardiovascular system. Therefore, this work aimed to assess the potential for herb-drug interactions among a standardized C. aurantium extract (GMP certificate) and amiodarone (narrow therapeutic index drug) in rats. In a first pharmacokinetic study, rats were simultaneously co-administered with a single-dose of C. aurantium (164 mg/kg, p.o.) and amiodarone (50 mg/kg, p.o.); in a second study, rats were pre-treated during 14 days with C. aurantium (164 mg/kg/day, p.o.) and received amiodarone (50 mg/kg, p.o.) on the 15th day. Rats of the control groups received the corresponding volume of vehicle. Overall, after analysis of the pharmacokinetic data, it deserves to be highlighted the significant increase of the peak plasma concentration of amiodarone in rats pre-treated with C. aurantium extract, while the extent of systemic exposure was comparable between both groups. This paper reports, for the first time, data on the potential of herb-drug interaction between C. aurantium extract and amiodarone. However, specific clinical trials should be performed to confirm these results in humans.

  8. Interaction between the antioxidant activity of curcumin and cholinergic system on memory retention in adult male Wistar rats

    PubMed Central

    Sarlak, Zeynab; Oryan, Shahrbanoo; Moghaddasi, Mehrnoush

    2015-01-01

    Objective(s): The cholinergic system plays an important role in learning and memory. This study investigated the effects of curcumin (turmeric extract) and the cholinergic system and their interaction on memory retention of passive avoidance learning in adult male Wistar rats. Materials and Methods: At first, an injection cannula was implanted in right ventricles of the animals. One week after the surgery, the animals were trained with a shuttle box set up. Post-training, injections were performed in all experiments. Administration of curcumin increased memory retention. Also administrations of nicotine and pilocarpine, the cholinergic receptor agonists, increased memory retention, while it is decreased by succinylcholine and scopolamine, the cholinergic receptor antagonists. Then co-administration of curcumin and cholinergic drugs were performed. Intraperitoneal and intracerebroventricular injections were applied for the curcumin and cholinergic drugs, respectively. Results: Co-administration of curcumin (45 mg/kg) with a low dose of nicotine (0.1 µg/rat) or pilocarpine (0.5 µg/rat) increased memory retention significantly. Effects of succinylcholine (0.01, 0.1 and 0.5 µg/rat) or scopolamine (0.1, 1 and 5 µg/rat) were attenuated by curcumin markedly (45 mg/kg). Conclusion: The results suggest that curcumin has a close interaction with cholinergic system in memory retention process. PMID:26019804

  9. Effects of juvenile isolation and morphine treatment on social interactions and opioid receptors in adult rats: behavioural and autoradiographic studies.

    PubMed

    Van den Berg, C L; Van Ree, J M; Spruijt, B M; Kitchen, I

    1999-09-01

    The consequences of juvenile isolation and morphine treatment during the isolation period on (social) behaviour and mu-, delta- and kappa-opioid receptors in adulthood were investigated by using a social interaction test and in vitro autoradiography in rats. Juvenile isolation reduced social exploration in adults. Morphine treatment counteracted this reduction in isolated rats, but decreased social exploration in nonisolated rats. Self-grooming and nonsocial exploration were enhanced after juvenile isolation. Morphine treatment had no effect on self-grooming, but suppressed nonsocial exploration in isolated rats. With respect to the opioid receptors, juvenile isolation resulted in regiospecific increases in mu-binding sites with a 58% increase in the basolateral amygdala and a 33% increase in the bed nucleus of stria terminalis. Morphine treatment in isolated rats reversed this upregulation in both areas. The number of delta-binding sites did not differ between the experimental groups. A general upregulation of kappa-binding sites was observed after juvenile isolation, predominantly in the cortical regions, the hippocampus and the substantia nigra. Morphine treatment did not affect the upregulation of kappa-receptors. The results show that juvenile isolation during the play period causes long-term effects on social and nonsocial behaviours and on the number of mu- and kappa- but not delta-opioid receptors in distinct brain areas. The number of mu-receptors in the basolateral amygdala appears to be negatively correlated with the amount of social exploration in adult rats.

  10. Interaction between prostanoids and nitric oxide in the control of tubular function in rats with chronic bile duct ligation.

    PubMed

    Criado, M; Flores, O; Hidalgo, F; López-Novoa, J M; Sánchez-Rodríguez, A

    1999-02-01

    Recent work indicates that both nitric oxide and cyclooxygenase products play an important role in the renal alterations of liver cirrhosis, although the interactions between them have not been completely established. The purpose of this study was to assess the effect of simultaneous blockade of nitric oxide synthase and cyclooxygenase in rats with chronic bile duct ligation and in control, sham-operated rats. Compared with control rats, chronic bile duct ligation rats, 23-25 days after surgery, showed a decreased mean arterial pressure, natriuresis, and kaliuresis, without differences in glomerular filtration rate, and an increased urinary nitrite excretion. Nitric oxide synthesis inhibition by administration of N(G)-nitro-L-arginine methyl ester induced, in control rats, an increase in mean arterial pressure, without significant changes in natriuresis or glomerular filtration rate. In chronic bile duct ligation rats, N(G)-nitro-L-arginine methyl ester induced an increase in mean arterial pressure, natriuresis, and kaliuresis, together with a reduction in urinary nitrite excretion and an increase in prostaglandin E2 excretion. Cyclooxygenase inhibition with indomethacin induced in both experimental groups a marked inhibition in urinary prostaglandin E2 excretion without significant changes in Na+ or K+ excretion, and a significant increase in urinary nitrite excretion in control rats. N(G)-Nitro-L-arginine methyl ester in addition to indomethacin prevented the indomethacin-induced increase in nitrite excretion and dramatically reduced sodium excretion in both experimental groups. Thus, the present study suggests that both nitric oxide and cyclooxygenase products interact in the control of urinary sodium excretion and that each system is activated in the absence of the other one.

  11. Involvement of the SLIT/ROBO pathway in follicle development in the fetal ovary.

    PubMed

    Dickinson, Rachel E; Hryhorskyj, Lynn; Tremewan, Hannah; Hogg, Kirsten; Thomson, Axel A; McNeilly, Alan S; Duncan, W Colin

    2010-02-01

    In humans and domestic mammals, pivotal processes in ovary development, including primordial follicle assembly, occur prenatally. These events are essential for determining fertility in adult life; however, they remain poorly understood at the mechanistic level. In mammals, the SLITs (SLIT1, SLIT2 and SLIT3) and their ROBO (ROBO1, ROBO2, ROBO3/RIG-1 and ROBO4/MAGIC ROBO) receptors regulate neural, leukocyte, vascular smooth muscle cell and endothelial cell migration. In addition, the SLIT/ROBO pathway has functional roles in embryonic development and in the adult ovary by inhibiting cell migration and promoting apoptosis. We therefore characterised follicle formation and investigated the expression and localisation of the ROBO/SLIT pathway in the ovine fetal ovary. Using RT-PCR, we identified SLIT2, SLIT3, ROBO1, ROBO2 and ROBO4 in sheep ovaries harvested across gestation. The real-time quantitative PCR results implied that ROBO2 expression and ROBO4 expression were elevated during the early stages of follicle formation and stayed abundant during primordial follicle maturation (P<0.05). Immunohistochemistry examination demonstrated that ROBO1 was localised to the pre-granulosa cells, while ROBO2, ROBO4 and SLIT2 were expressed in the oocytes of the developing primordial follicle. This indicates that in the fetal ovary, SLIT-ROBO signalling may require an autocrine and paracrine interaction. Furthermore, at the time of increased SLIT-ROBO expression, there was a significant reduction in the number of proliferating oocytes in the developing ovary (P<0.0001). Overall, these results suggest, for the first time, that the SLIT-ROBO pathway is expressed at the time of follicle formation during fetal ovary development.

  12. Reproductive toxicity of the industrial solvent 2-ethoxyethanol in rats and interactive effects of ethanol.

    PubMed

    Nelson, B K; Brightwell, W S; Setzer, J V; O'Donohue, T L

    1984-08-01

    The solvent, 2-ethoxyethanol, induced complete embryomortality in pregnant rats exposed to three times the current Federal permissible exposure limit (PEL). Following exposure to ethoxyethanol at a concentration only one-half the current PEL, the offspring evidenced behavioral and neurochemical deviations from controls. Subsequent studies found that ingestion of ethanol with concomitant inhalation of ethoxyethanol vapors early in pregnancy appeared to reduce the number of both behavioral and neurochemical deviations found for ethoxyethanol. In contrast, the concomitant exposure to ethanol and ethoxyethanol later in gestation potentiated the behavioral and neurochemical effects of ethoxyethanol. This research indicates that the industrial solvent 2-ethoxyethanol presents an occupational reproductive hazard and raises the issue of the importance of an interaction of social habits with occupational exposure to such hazards. The results would suggest that occupational physicians should advise pregnant workers in the chemical industry of the adverse effects of ethanol during pregnancy and of the possible interactions with other chemicals and should encourage them to be especially cautious with ethanol consumption since they may be at greater risk.

  13. Synergistic antinociceptive interaction of Syzygium aromaticum or Rosmarinus officinalis coadministered with ketorolac in rats.

    PubMed

    Beltrán-Villalobos, Karla Lyzet; Déciga-Campos, Myrna; Aguilar-Mariscal, Hidemi; González-Trujano, María Eva; Martínez-Salazar, María Fernanda; Ramírez-Cisneros, María de Los Ángeles; Rios, María Yolanda; López-Muñoz, Francisco Javier

    2017-10-01

    Syzygium aromaticum (L.) Merr. & L.M. Perry (Mirtaceae) and Rosmarinus officinalis L. (Lamiaceae) are both medicinal plants used for centuries to alleviate pain. The aim of the study was to demonstrate the therapeutic potential utility of herb-drug association of S. aromaticum essential oil or R. officinalis ethanolic extract coadministered with ketorolac. Antinociceptive pharmacological interaction was investigated by an isbolographic study using the formalin test in rats. Both alone and in combination with ketorolac; S. aromaticum and R. officinalis produced a dose-dependent antinociceptive response. To plot the isobologram, we used the effective dose 50 of each one component in a fixed 1:1 ratio. The isobolographic analysis showed that, in both combinations, ketorolac plus essential oil S. aromaticum and ketorolac plus ethanolic extract R. officinalis, the experimental value (Zexp) was lower than the theoretical value (Zadd). In addition, this study shows that eugenol, a metabolite present in S. aromaticum, and ursolic acid, a metabolite present in R. officinalis, also synergized the antinociceptive effect of ketorolac. While, the oleanolic acid present in both medicinal species did not show a synergistic antinociceptive effect in combination with ketorolac. No adverse effects were observed with these herb-drug interactions. These findings suggest that essential oil S. aromaticum and ethanolic extract R. officinalis could be useful in combination with ketorolac for the treatment of inflammatory pain. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  14. In vitro study of lovastatin interactions with amiodarone and with carbon tetrachloride in isolated rat hepatocytes

    PubMed Central

    Krasteva, AZ; Mitcheva, MK; Kondeva-Burdina, MS; Descatoire, VA

    2007-01-01

    AIM: To investigate the interactions at a metabolic level between lovastatin, amiodarone and carbon tetrachloride in isolated rat hepatocytes. METHODS: For cell isolation two-step collagenase liver perfusion was performed. Lovastatin was administered alone in increasing concentrations (1 μmol/L, 3 μmol/L, 5 μmol/L and 10 μmol/L) and in combination with CCl4 (86 μmol/L). The cells were also pretreated with 14 μmol/L amiodarone and then the other two compounds were added. RESULTS: Lovastatin promoted concentration-dependent significant toxicity estimated by decrease in cell viability and GSH level by 45% and 84%, respectively. LDH-activity increased by 114% and TBARS content by 90%. CCl4 induced the expected severe damage on the examined parameters. CCl4 induced toxicity was attenuated after lovastatin pretreatment, which was expressed in less increased values of LDH activity and TBARS levels, as well as in less decreased cell viability and GSH concentrations. However, the pretreatment of hepatocytes with amiodarone abolished the protective effect of lovastatin. CONCLUSION: We suggest that the observed cytopro-tective effect was due to interactions between lovastatin, CCl4 and amiodarone at a metabolic level. PMID:17465501

  15. Synergistic interaction between diclofenac and pyrilamine on nociception, inflammation, and gastric damage in rats.

    PubMed

    Ortiz, Mario I

    2017-01-01

    Experiments using nonsteroidal anti-inflammatory drugs (NSAIDs) alone have produced limited antinociceptive effects in animal models. For this reason, the number of studies involving the administration of NSAIDs along with an adjuvant drug harboring different mechanisms of action has increased enormously. Here, combinations of diclofenac and pyrilamine were used to determine their influence on nociception (formalin test), inflammation (paw inflammation produced by carrageenan), and gastric damage in rodents. Diclofenac, pyrilamine, or combinations of diclofenac and pyrilamine produced antinociceptive and anti-inflammatory effects in the rat. The systemic administration of diclofenac alone and in combination with pyrilamine produced significant gastric damage. Effective dose (ED) values were determined for each individual drug, and isobolograms were prepared. The theoretical ED values for the antinociceptive (systemic, 35.4 mg/kg; local, 343.4 μg/paw) and the anti-inflammatory (37.9 mg/kg) effects differed significantly from the experimental ED values (systemic antinociception, 18.1 mg/kg; local antinociception, 183.3 μg/paw; anti-inflammation, 10.6 mg/kg). Therefore, it was concluded that the interactions between diclofenac and pyrilamine are synergistic. The data suggest that the diclofenac-pyrilamine combinations can interact at the systemic and local peripheral levels, thereby offering a therapeutic alternative for the clinical management of inflammatory pain.

  16. Treadmill exercise alleviates stress-induced impairment of social interaction through 5-hydroxytryptamine 1A receptor activation in rats.

    PubMed

    Kim, Tae-Woon; Lim, Baek-Vin; Kim, Kijeong; Seo, Jin-Hee; Kim, Chang-Ju

    2015-08-01

    Brain-derived neurotrophic factor (BDNF) and its receptors tyrosine kinase B (trkB), and cyclic adenosine monophosphate response element binding protein (CREB) have been suggested as the neurobiological risk factors causing depressive disorder. Serotonin (5-hydroxytryptamine, 5-HT) plays an important role in the pathogenesis of depression. We in-vestigated the effect of treadmill exercise on social interaction in relation with BDNF and 5-HT expressions following stress in rats. Stress was induced by applying inescapable 0.2 mA electric foot shock to the rats for 7 days. The rats in the exercise groups were forced to run on a motorized treadmill for 30 min once a day for 4 weeks. Social interaction test and western blot for BDNF, TrkB, pCREB, and 5-HT1A in the hippocampus were performed. The results indicate that the spend time with unfamiliar partner was decreased by stress, in contrast, treadmill exercise increased the spending time in the stress-induced rats. Expressions of BDNF, TrkB, and pCREB were decreased by stress, in contrast, treadmill exercise enhanced expressions of BDNF, TrkB, and pCREB in the stress-induced rats. In addition, 5-HT1A receptor expression was de-creased by stress, in contrast, treadmill exercise enhanced 5-HT1A expression in the stress-induced rats. In the present study, treadmill exercise alleviated stress-induced social interaction impairment through enhancing hippocampal plasticity and serotonergic function in the hippocampus. These effects of treadmill exercise are achieved through 5-HT1A receptor activation.

  17. Treadmill exercise alleviates stress-induced impairment of social interaction through 5-hydroxytryptamine 1A receptor activation in rats

    PubMed Central

    Kim, Tae-Woon; Lim, Baek-Vin; Kim, Kijeong; Seo, Jin-Hee; Kim, Chang-Ju

    2015-01-01

    Brain-derived neurotrophic factor (BDNF) and its receptors tyrosine kinase B (trkB), and cyclic adenosine monophosphate response element binding protein (CREB) have been suggested as the neurobiological risk factors causing depressive disorder. Serotonin (5-hydroxytryptamine, 5-HT) plays an important role in the pathogenesis of depression. We in-vestigated the effect of treadmill exercise on social interaction in relation with BDNF and 5-HT expressions following stress in rats. Stress was induced by applying inescapable 0.2 mA electric foot shock to the rats for 7 days. The rats in the exercise groups were forced to run on a motorized treadmill for 30 min once a day for 4 weeks. Social interaction test and western blot for BDNF, TrkB, pCREB, and 5-HT1A in the hippocampus were performed. The results indicate that the spend time with unfamiliar partner was decreased by stress, in contrast, treadmill exercise increased the spending time in the stress-induced rats. Expressions of BDNF, TrkB, and pCREB were decreased by stress, in contrast, treadmill exercise enhanced expressions of BDNF, TrkB, and pCREB in the stress-induced rats. In addition, 5-HT1A receptor expression was de-creased by stress, in contrast, treadmill exercise enhanced 5-HT1A expression in the stress-induced rats. In the present study, treadmill exercise alleviated stress-induced social interaction impairment through enhancing hippocampal plasticity and serotonergic function in the hippocampus. These effects of treadmill exercise are achieved through 5-HT1A receptor activation. PMID:26331133

  18. Effect of the combination of metformin hydrochloride and melatonin on oxidative stress before and during pregnancy, and biochemical and histopathological analysis of the livers of rats after treatment for polycystic ovary syndrome

    SciTech Connect

    Lemos, Ana Janaina Jeanine M.; Peixoto, Christina A.; Teixeira, Álvaro Aguiar C.; Luna, Rayana Leal A.; Rocha, Sura Wanessa S.; Santos, Hilda Michelly P.; Silva, Amanda Karolina S.; Nunes, Ana Karolina S.; Wanderley-Teixeira, Valéria

    2014-10-01

    The aim of the present study was to analyze the effect of a combination of metformin hydrochloride and melatonin on oxidative stress together with a biochemical and histopathological analysis of the livers of Wistar rats induced with PCOS. The results indicated that a combination of the drugs was more effective in the reduction of plasmatic levels of liver enzyme alanine aminotransferase, nitric oxide and total glutathione, and decreased the inflammatory response and histopathological damage, producing results that were significantly similar to animals from the control group. A mixture of the drugs produced more effective results against liver toxicity caused by PCOS, encouraging the normalization of biochemical parameters. During pregnancy, there was reduced oxidative stress compared to monotherapeutic use of these drugs. Interestingly, the combination of the drugs caused a physiological reaction similar to responses identified in healthy rats without induction of the PCOS control group. However, the clinical and physiological effectiveness of the combination should be further explored, especially with respect to the possible side effects on offspring. - Highlights: • Studies have documented increased oxidative stress in patients with PCOS. • It has been noted that women with PCOS have a high prevalence of liver alterations. • Liver disease in pregnancy may be pre-existing increasing the newborn mortality. • Metformin/melatonin associated reduced oxidative stress in liver in pregnant rats. • Association of metformin/melatonin normalizes hepatic biochemical parameters.

  19. Effects of interactions between drugs on the renal excretion of trientine in rats--acetazolamide and furosemide increase trientine excretion.

    PubMed

    Kobayashi, M; Fujisaki, H; Sugawara, M; Iseki, K; Miyazaki, K

    1999-12-01

    To elucidate the effects of drug interactions on the urinary excretion of trientine in rats. Trientine and various other drugs were intravenously administered to rats and the urinary excretion of trientine was investigated. To clarify the mechanisms of drug-drug interactions, we also investigated the effects of various drugs on spermine uptake by rat renal brushborder membrane vesicles. Cimetidine, a substrate of the H+/organic cation antiporter, and aminoglycoside antibiotics did not affect trientine excretion, while acetazolamide and furosemide, which increase the concentration of sodium ions in renal proximal tubules, increased the excretion of trientine. However, trichlormethiazide, which acts in renal distal tubules, did not affect trientine excretion. Acetazolamide and furosemide did not directly affect the Na+/spermine transporter because these diuretics had no effect on the uptake of spermine into the rat renal brush-border membrane vesicles. There is no interaction between trientine and the substrate of the H+/organic cation antiporter or aminoglycoside antibiotics. However, drugs that change the concentration of sodium ions in renal proximal tubules, such as diuretics, can increase the trientine excretion since the increase in the luminal concentration of sodium ion accelerates the Na+/spermine antiporter.

  20. Differential neuronal expression of receptor interacting protein 3 in rat retina: involvement in ischemic stress response

    PubMed Central

    2013-01-01

    Background Receptor-interacting protein 3 (RIP3), a member of RIP family proteins, has been shown to participate in programmed necrosis or necroptosis in cell biology studies. Evidence suggests that necroptosis may be a mode of neuronal death in the retina. Results In the present study we determined the expression of RIP3 in normal rat retina and its changes following acute high intraocular pressure (aHIOP). RIP3 immunoreactivity (IR) was largely present in the inner retinal layers, localized to subsets of cells expressing neuron-specific nuclear antigen (NeuN), parvalbumin and calbindin in the ganglion cell layer (GCL) and inner nuclear layer (INL). No double labeling was detected for RIP3 with PKC-α or rhodopsin. RIP3 immunoreactivity was increased in the GCL at 6 hr and 12 hr, but reduced at 24 hr in the retina, without apparent alteration in laminar or cellular distribution pattern. Western blot analysis confirmed the above time-dependent alteration in RIP3 protein expression. RIP3 expressing cells frequently co-localized with propidium iodide (PI). A few co-localized cells were observed between RIP3 and Bax or cleaved caspase-3 in the GCL in 12 hr following aHIOP. Conclusions The results indicate that RIP3 is expressed differentially in retinal neurons in adult rats, including subsets of ganglion cells, amacrine and horizontal cells. RIP3 protein levels are elevated rapidly following aHIOP. RIP3 labeling co-localized with PI, Bax or cleaved caspase-3 among cells in the ganglion cell layer following aHIOP, which suggest its involvement of RIP3 in neuronal responses to acute ischemic insults. PMID:23374330

  1. Bupropion-varenicline interactions and nicotine self-administration behavior in rats.

    PubMed

    Hall, Brandon J; Slade, Susan; Wells, Corinne; Rose, Jed E; Levin, Edward D

    2015-03-01

    Varenicline and bupropion each have been shown to significantly improve cessation of tobacco addiction in humans. They act through different mechanisms and the question about the potential added efficacy with their combined used has arisen. Preclinical animal models of nicotine addiction can help with the evaluation of this combined approach and what dose combinations of varenicline and bupropion may be useful for enhancing tobacco cessation. In this study, we investigated the interacting dose-effect functions of varenicline and bupropion in a rat model of nicotine self-administration. Young adult female Sprague-Dawley rats were allowed to self-administer nicotine in 1-h sessions under an FR1 reinforcement schedule. Varenicline (0.3, 1. 3 mg/kg) and bupropion (8.33, 25, 75 mg/kg) were administered alone or together 15 min before each session. The vehicle saline was the control. Higher doses of each drug alone reduced nicotine self-administration compared to control with reductions of 62% and 75% with 3 mg/kg varenicline and 75 mg/kg bupropion respectively. Lower dose varenicline which does not by itself reduce nicotine self-administration, significantly augmented bupropion effects. The 0.3 mg/kg varenicline dose combined with the 25 and 75 mg/kg bupropion doses caused greater reductions of nicotine self-administration than either dose of bupropion given alone. However, higher dose varenicline did not have this effect. Lower dose bupropion did not augment varenicline effects. Only the high bupropion dose significantly enhanced the varenicline effect. Likewise, combining 1 mg/kg varenicline with 75 mg/kg bupropion reduced self-administration to a greater extent than either dose alone. These results demonstrate that combination therapy with varenicline and bupropion may be more beneficial than monotherapy with either drug alone. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Bupropion-Varenicline Interactions and Nicotine Self-Administration Behavior in Rats

    PubMed Central

    Hall, Brandon J; Slade, Susan; Wells, Corinne; Rose, Jed E.; Levin, Edward D.

    2015-01-01

    Varenicline and bupropion each have been shown to significantly improve cessation of tobacco addiction in humans. They act through different mechanisms and the question about the potential added efficacy with their combined used has arisen. Preclinical animal models of nicotine addiction can help with the evaluation of this combined approach and what dose combinations of varenicline and bupropion may be useful for enhancing tobacco cessation. In this study, we investigated the interacting dose-effect functions of varenicline and bupropion in a rat model of nicotine self-administration. Young adult female Sprague-Dawley rats were allowed to self-administer nicotine in one-hr sessions under an FR1 reinforcement schedule. Varenicline (0.3, 1. 3 mg/kg) and bupropion (8.33, 25, 75 mg/kg) were administered alone or together 15 min before each session. The vehicle saline was the control. Higher doses of each drug alone reduced nicotine self-administration compared to control with reductions of 62% and 75% with 3 mg/kg varenicline and 75 mg/kg bupropion respectively. Lower dose varenicline which does not by itself reduce nicotine self-administration, significantly augmented bupropion effects. The 0.3 mg/kg varenicline dose combined with the 25 and 75 mg/kg bupropion doses caused greater reductions of nicotine self-administration than either dose of bupropion given alone. However, higher dose varenicline did not have this effect. Lower dose bupropion did not augment varenicline effects. Only the high bupropion dose significantly enhanced the varenicline effect. Likewise, combinding 1 mg/kg varenicline with 75 mg/kg bupropion reduced self-administration to a greater extent than either dose alone. These results demonstrate that combination therapy with varenicline and bupropion may be more beneficial than monotherapy with either drug alone. PMID:25616031

  3. Interactive effects of acupuncture on pain and distress in major burns: An experiment with rats.

    PubMed

    Abali, Ayse Ebru; Cabioglu, Tugrul; Ozdemir, Handan; Haberal, Mehmet

    2015-06-01

    This study sought to investigate the interactive effects of acupuncture on pain and distress and the local progress in the burn wound in an experimental major burn model. Forty-eight male Sprague-Dawley rats were divided into six groups: S group (sham/observation during 7 days after injury); SA group (sham/acupuncture/observation during 7 days after injury); B1 group (burns/observation during 1h after injury); BA1 group (burns/acupuncture/observation during 1 h after injury); B7 group (burns/observation during 7 days after injury); and BA7 group (burns/acupuncture/observation during 7 days after injury). Pain and distress scores were evaluated throughout the study. The amounts of neutrophils and mononuclear cells were evaluated semiquantitatively, and the number of microvessels was evaluated quantitatively. Our data indicated that the average pain score of BA7 group was significantly lower than the other study groups. Histopathologic investigations indicate that the amounts of neutrophil and mononuclear cell and numbers of microvessels in the unburned skin were higher in acupuncture-applied groups. The number of microvessels in burn wounds of BA7 group was significantly higher than that of the other groups. Our data suggest that acupuncture provides low pain and distress scores in experimental rat model, and it contributes to wound healing with an enhanced angiogenesis during the acute phase of burns. Future clinical and experimental studies should be conducted to discern the benefits from acupuncture in pain management of burn patients. Copyright © 2014 Elsevier Ltd and ISBI. All rights reserved.

  4. Synergistic interaction between caloric restriction and amphetamine in food-unrelated approach behavior of rats

    PubMed Central

    Keller, Kristine L.; Vollrath-Smith, Fiori R.; Jafari, Mehrnoosh; Ikemoto, Satoshi

    2013-01-01

    Rationale Approach behavior is regulated by the brain integrating information about environment and body state. Psychoactive drugs interact with this process. Objectives We examined the extent to which caloric (i.e., food) restriction, amphetamine and lithium interact in potentiating locomotor activity and responding reinforced by visual stimulus (VS), a reward unrelated to energy homeostasis. Methods Rats either had ad-libitum access to food or received daily rations that maintained 85-90% of their original body weights. Leverpressing turned on a cue light for 1 sec and turned off house light for 5 sec. Amphetamine and lithium were administered through intraperitoneal injections and diet, respectively. Results Food-restriction or amphetamine (1 mg/kg) alone had little effect on VS-reinforced responding; however, the combination of the two conditions markedly potentiated VS-reinforced responding (4-fold). Food restriction lasting 7 days or longer was needed to augment amphetamine’s effect on VS-reinforced responding. Amphetamine (0.3 – 3 mg/kg) potentiated locomotor activity similarly between food-restricted and ad-libitum groups. Repeated injections of amphetamine sensitized locomotor activity, but not VS-reinforced responding. In addition, while chronic lithium treatments (0.2% lithium carbonate chow) reduced VS-reinforced responding, chronic lithium further augmented amphetamine-potentiated VS-reinforced responding. Conclusions Food-restriction interacts with psychoactive drugs to potentiate goal-directed responding unrelated to food-seeking in a much more powerful manner than previously thought. The novel finding that lithium can augment a psychostimulant effect of amphetamine suggests caution when combining lithium and psychostimulant drugs in clinical settings. PMID:24101157

  5. Interaction between propranolol and amino acids in the single-pass isolated, perfused rat liver.

    PubMed

    Semple, H A; Xia, F

    1995-08-01

    Propranolol (PL) bioavailability has been shown to increase substantially when it is administered with a protein-rich meal. A change in metabolic capacity or tissue uptake, induced by amino acids (AAs) released as a result of digestion of dietary protein, is a possible contributing mechanism to the food effect. This hypothesis was tested in isolated, perfused rat livers in the single-pass mode. Rac-PL (20 micrograms/ml) was infused to steady-state at 3 ml/min/g liver for 150 min. A balanced mixture of I-AA was coinfused from 70 to 110 min. The AA reversibly increased the steady-state concentration of PL by 18% and reduced steady-state concentrations of 4-hydroxypropranolol, N-deisopropylpranolol, PL glycol, naphthoxylactic acid, and naphthoxyacetic acid by an average of 41% and propanolol conjugates by almost 100%, indicating metabolic inhibition. In a second experiment, PL was coinfused with AAs from the beginning of the experiment, and tissue binding was compared with control livers. There was no significant effect of AAs on PL tissue binding. In a third study, the effect of four different concentrations of AAs coinfused from 70 to 110 min was assessed. The percentage change in PL and phase I metabolite levels was linearly correlated to the influent AA concentration. The large magnitude, reversibility, lack of pathway specificity, and concentration dependence of the AA interaction in the perfused liver are also features of food interaction in humans. These similarities constitute evidence that metabolic inhibition by AAs originating from dietary protein could contribute to the PL-food interaction.

  6. Antinociceptive Effect of Intrathecal Nefopam and Interaction with Morphine in Formalin-Induced Pain of Rats

    PubMed Central

    Cho, Soo Young; Park, A Reum; Yoon, Myung Ha; Lee, Hyung Gon; Kim, Woong Mo

    2013-01-01

    Background Nefopam, a non-opiate analgesic, has been regarded as a substance that reduces the requirement for morphine, but conflicting results have also been reported. The inhibition of monoamine reuptake is a mechanism of action for the analgesia of nefopam. The spinal cord is an important site for the action of monoamines however, the antinociceptive effect of intrathecal nefopam was not clear. This study was performed to examine the antinociceptive effect of intrathecal (i.t.) nefopam and the pattern of pharmacologic interaction with i.t. morphine in the formalin test. Methods Male Sprague-Dawley rats were implanted with an i.t. catheter, and were randomly treated with a vehicle, nefopam, or morphine. Formalin was injected into the hind-paw 10 min. after an i.t. injection of the above experiment drugs. After obtaining antinociceptive ED50 of nefopam and morphine, the mixture of nefopam and morphine was tested for the antinociceptive effect in the formalin test at a dose of 1/8, 1/4, 1/2 of ED50, or ED50 of each drug followed by an isobolographic analysis. Results Intrathecal nefopam significantly reduced the flinching responses in both phases of the formalin test in a dose-dependent manner. Its effect, however, peaked at a dose of 30 µg in phase 1 (39.8% of control) and 10 µg during phase 2 (37.6% of control). The isobolograhic analysis indicated an additive interaction of nefopam and morphine during phase 2, and a synergy effect in antinociception during phase 1. Conclusions This study demonstrated that i.t. nefopam produces an antinociceptive effect in formalin induced pain behavior during both phases of the formalin test, while interacting differently with i.t. morphine, synergistically during phase 1, and additively during phase 2. PMID:23342202

  7. Interactions between VTA orexin and glutamate in cue-induced reinstatement of cocaine seeking in rats

    PubMed Central

    Mahler, Stephen V.; Smith, Rachel J.

    2013-01-01

    Rationale Glutamate and orexin/hypocretin systems are involved in Pavlovian cue-triggered drug seeking. Objectives Here, we asked whether orexin and glutamate interact within ventral tegmental area (VTA) to promote reinstatement of extinguished cocaine seeking in a rat self-administration paradigm. Methods/results We first found that bilateral VTA micro-injections of the orexin 1 receptor (OX1R) antagonist SB-334867 (SB) or a cocktail of the AMPA and NMDA glutamate receptor antagonists CNQX/AP-5 reduced reinstatement of cocaine seeking elicited by cues. In contrast, neither of these microinjections nor systemic SB reduced cocaine-primed reinstatement. Additionally, unilateral VTA OX1R blockade combined with contralateral VTA glutamate blockade attenuated cue-induced reinstatement, indicating that VTA orexin and glutamate are simultaneously necessary for cue-induced reinstatement. We further probed the receptor specificity of glutamate actions in VTA, finding that CNQX, but not AP-5, dose-dependently attenuated cue-induced reinstatement, indicating that AMPA but not NMDA receptor transmission is required for this type of cocaine seeking. Given the necessary roles of both OX1 and AMPA receptors in VTA for cue-induced cocaine seeking, we hypothesized that these signaling pathways interact during this behavior. We found that PEPA, a positive allosteric modulator of AMPA receptors, completely reversed the SB-induced attenuation of reinstatement behavior. Intra-VTA PEPA alone did not alter cue-induced reinstatement, indicating that potentiating AMPA activity with this drug specifically compensates for OX1R blockade, rather than simply inducing or enhancing reinstatement itself. Conclusions These findings show that cue-induced, but not cocaine-primed, reinstatement of cocaine seeking is dependent upon orexin and AMPA receptor interactions in VTA. PMID:22411428

  8. Interactions between VTA orexin and glutamate in cue-induced reinstatement of cocaine seeking in rats.

    PubMed

    Mahler, Stephen V; Smith, Rachel J; Aston-Jones, Gary

    2013-04-01

    Glutamate and orexin/hypocretin systems are involved in Pavlovian cue-triggered drug seeking. Here, we asked whether orexin and glutamate interact within ventral tegmental area (VTA) to promote reinstatement of extinguished cocaine seeking in a rat self-administration paradigm. We first found that bilateral VTA microinjections of the orexin 1 receptor (OX1R) antagonist SB-334867 (SB) or a cocktail of the AMPA and NMDA glutamate receptor antagonists CNQX/AP-5 reduced reinstatement of cocaine seeking elicited by cues. In contrast, neither of these microinjections nor systemic SB reduced cocaine-primed reinstatement. Additionally, unilateral VTA OX1R blockade combined with contralateral VTA glutamate blockade attenuated cue-induced reinstatement, indicating that VTA orexin and glutamate are simultaneously necessary for cue-induced reinstatement. We further probed the receptor specificity of glutamate actions in VTA, finding that CNQX, but not AP-5, dose-dependently attenuated cue-induced reinstatement, indicating that AMPA but not NMDA receptor transmission is required for this type of cocaine seeking. Given the necessary roles of both OX1 and AMPA receptors in VTA for cue-induced cocaine seeking, we hypothesized that these signaling pathways interact during this behavior. We found that PEPA, a positive allosteric modulator of AMPA receptors, completely reversed the SB-induced attenuation of reinstatement behavior. Intra-VTA PEPA alone did not alter cue-induced reinstatement, indicating that potentiating AMPA activity with this drug specifically compensates for OX1R blockade, rather than simply inducing or enhancing reinstatement itself. These findings show that cue-induced, but not cocaine-primed, reinstatement of cocaine seeking is dependent upon orexin and AMPA receptor interactions in VTA.

  9. Ovary cryopreservation and transplantation for fertility preservation.

    PubMed

    Silber, S J

    2012-02-01

    The aim of this review is to summarize the state-of-the-art of ovarian transplantation and cryopreservation. This field has progressed over the last half century from simple animal experiments to sophisticated application in humans. The initial poor results in humans began to improve when a series of nine monozygotic (MZ) twin pairs discordant for premature ovarian failure (POF) underwent ovary transplantation at one center. All of these fresh ovary transplants were successful, resulting in 11 healthy babies in 7 of the 9 recipients. The same surgical techniques were then applied to 3 frozen ovary tissue transplants, up to 14 years after the ovary had been frozen, resulting in 3 more healthy babies. Around the world, the number of healthy babies has now risen to 28. Even ovary allotransplantation is being attempted in the not so uncommon situation where a previous bone marrow donor is now willing to donate ovarian tissue to the same recipient. Recipients routinely reinitiated ovulatory menstrual cycles and normal Day 3 serum FSH levels by 4.5 months. Most conceived naturally (three of them twice or three times from the same graft). The duration of function of fresh ovarian grafts, contrary to initial expectations, indicated minimal oocyte loss from ischemia time. Grafts of just modest portions of ovarian tissue have lasted >7 years. In vitro studies suggest that vitrification of ovarian tissue may be an improvement over the 70% oocyte viability loss from slow freeze.

  10. Interactions between cadmium and decabrominated diphenyl ether on blood cells count in rats-Multiple factorial regression analysis.

    PubMed

    Curcic, Marijana; Buha, Aleksandra; Stankovic, Sanja; Milovanovic, Vesna; Bulat, Zorica; Đukić-Ćosić, Danijela; Antonijević, Evica; Vučinić, Slavica; Matović, Vesna; Antonijevic, Biljana

    2017-02-01

    The objective of this study was to assess toxicity of Cd and BDE-209 mixture on haematological parameters in subacutely exposed rats and to determine the presence and type of interactions between these two chemicals using multiple factorial regression analysis. Furthermore, for the assessment of interaction type, an isobologram based methodology was applied and compared with multiple factorial regression analysis. Chemicals were given by oral gavage to the male Wistar rats weighing 200-240g for 28days. Animals were divided in 16 groups (8/group): control vehiculum group, three groups of rats were treated with 2.5, 7.5 or 15mg Cd/kg/day. These doses were chosen on the bases of literature data and reflect relatively high Cd environmental exposure, three groups of rats were treated with 1000, 2000 or 4000mg BDE-209/kg/bw/day, doses proved to induce toxic effects in rats. Furthermore, nine groups of animals were treated with different mixtures of Cd and BDE-209 containing doses of Cd and BDE-209 stated above. Blood samples were taken at the end of experiment and red blood cells, white blood cells and platelets counts were determined. For interaction assessment multiple factorial regression analysis and fitted isobologram approach were used. In this study, we focused on multiple factorial regression analysis as a method for interaction assessment. We also investigated the interactions between Cd and BDE-209 by the derived model for the description of the obtained fitted isobologram curves. Current study indicated that co-exposure to Cd and BDE-209 can result in significant decrease in RBC count, increase in WBC count and decrease in PLT count, when compared with controls. Multiple factorial regression analysis used for the assessment of interactions type between Cd and BDE-209 indicated synergism for the effect on RBC count and no interactions i.e. additivity for the effects on WBC and PLT counts. On the other hand, isobologram based approach showed slight antagonism

  11. Social interactions in adolescent and adult Sprague-Dawley rats: impact of social deprivation and test context familiarity.

    PubMed

    Varlinskaya, Elena I; Spear, Linda P

    2008-04-09

    Interactions with peers become particularly important during adolescence, and age differences in social interactions have been successfully modeled in rats. To determine the impact of social deprivation on social interactions under anxiogenic (unfamiliar) or non-anxiogenic (familiar) test circumstances during ontogeny, the present study used a modified social interaction test to assess the effects of 5 days of social isolation or group housing on different components of social behavior in early [postnatal day (P) 28], mid (P35), or late (P42) adolescent and adult (P70) male and female Sprague-Dawley rats. As expected, testing in an unfamiliar environment suppressed social interactions regardless of age, housing, and sex. Social deprivation drastically enhanced all forms of social behavior in P28 animals regardless of test situation, whereas depriving older animals of social interactions had more modest effects and was restricted predominantly to play fighting -- an adolescent-characteristic form of social interactions. Social investigation -- more adult-typical form of social behavior was relatively resistant to isolation-induced enhancement and was elevated in early adolescent isolates only. These findings confirm that different forms of social behavior are differentially sensitive to social deprivation across ontogeny.

  12. Prefrontocortical dopamine loss in rats delays long-term extinction of contextual conditioned fear, and reduces social interaction without affecting short-term social interaction memory.

    PubMed

    Fernandez Espejo, Emilio

    2003-03-01

    Prefrontal dopamine loss delays extinction of cued fear conditioning responses, but its role in contextual fear conditioning has not been explored. Medial prefrontal lesions also enhance social interaction in rats, but the role of prefrontal dopamine loss on social interaction memory is not known. Besides, a role for subcortical accumbal dopamine on mnesic changes after prefrontal dopamine manipulation has been proposed but not explored. The objective was to study the involvement of dopaminergic neurotransmission in the medial prefrontal cortex (mPFC) and nucleus accumbens in two mnesic tasks: contextual fear conditioning and social interaction memory. For contextual fear conditioning, short- and long-term freezing responses after an electric shock were studied, as well as extinction retention. Regarding social interaction memory, the recognition of a juvenile, a very sensitive short-term memory test, was used. Dopamine loss was carried out by injection of 6-hydroxydopamine, and postmortem catecholamine levels were analyzed by high-performance liquid chromatography. Prefrontocortical dopamine loss (>76%) led to a reactive enhancement of accumbal dopamine content (p<0.01), supporting the hypothesis that a hyperdopaminergic tone emerges in the nucleus accumbens after prefrontocortical dopamine loss. In lesioned rats, long-term extinction of contextual fear conditioning was significantly delayed and extinction retention was impaired without changes in acquisition and short-term contextual fear conditioning and, on the other hand, acquisition and short-term social interaction memory were not affected, although time spent on social interaction was significantly reduced. Added dopamine loss in the nucleus accumbens (>76%) did not alter these behavioral changes. In summary, the results of the present study indicate that the dopaminergic network in the mPFC (but not in the nucleus accumbens) coordinates the normal long-term extinction of contextual fear conditioning

  13. Effects of Different Peep Levels on Mesenteric Leukocyte-Endothelial Interactions in Rats During Mechanical Ventilation

    PubMed Central

    Aikawa, Priscila; Farsky, Sandra Helena Poliselli; de Oliveira, Maria Aparecida; Pazetti, Rogério; Mauad, Thaís; Sannomiya, Paulina; Nakagawa, Naomi Kondo

    2009-01-01

    INTRODUCTION: Mechanical ventilation with positive end expiratory pressure (PEEP) improves oxygenation and treats acute pulmonary failure. However, increased intrathoracic pressure may cause regional blood flow alterations that may contribute to mesenteric ischemia and gastrointestinal failure. We investigated the effects of different PEEP levels on mesenteric leukocyte-endothelial interactions. METHODS: Forty-four male Wistar rats were initially anesthetized (Pentobarbital I.P. 50mg/kg) and randomly assigned to one of the following groups: 1) NAIVE (only anesthesia; n=9), 2) PEEP 0 (PEEP of 0 cmH2O, n=13), 3) PEEP 5 (PEEP of 5 cmH2O, n=12), and 4) PEEP 10 (PEEP of 10 cmH2O, n=13). Positive end expiratory pressure groups were tracheostomized and mechanically ventilated with a tidal volume of 10 mL/kg, respiratory rate of 70 rpm, and inspired oxygen fraction of 1. Animals were maintained under isoflurane anesthesia. After two hours, laparotomy was performed, and leukocyte-endothelial interactions were evaluated by intravital microscopy. RESULTS: No significant changes were observed in mean arterial blood pressure among groups during the study. Tracheal peak pressure was smaller in PEEP 5 compared with PEEP 0 and PEEP 10 groups (11, 15, and 16 cmH2O, respectively; p<0.05). After two hours of MV, there were no differences among NAIVE, PEEP 0 and PEEP 5 groups in the number of rollers (118±9,127±14 and 147±26 cells/10minutes, respectively), adherent leukocytes (3±1,3±1 and 4±2 cells/100μm venule length, respectively), and migrated leukocytes (2±1,2±1 and 2±1 cells/5,000μm2, respectively) at the mesentery. However, the PEEP 10 group exhibited an increase in the number of rolling, adherent and migrated leukocytes (188±15 cells / 10 min, 8±1 cells / 100 μm and 12±1 cells / 5,000 μm2, respectively; p<0.05). CONCLUSIONS: High intrathoracic pressure was harmful to mesenteric microcirculation in the experimental model of rats with normal lungs and stable

  14. Role of the neural pathway from hindbrain to hypothalamus in interaction of GLP1 and leptin in rats.

    PubMed

    Akieda-Asai, Sayaka; Poleni, Paul-Emile; Hasegawa, Kazuya; Date, Yukari

    2014-02-01

    Glucagon-like peptide-1 (GLP1) and leptin are anorectic hormones. Previously, we have shown that i.p. coadministration of subthreshold GLP1 with leptin dramatically reduced food intake in rats. In this study, by using midbrain-transected rats, we investigated the role of the neural pathway from the hindbrain to the hypothalamus in the interaction of GLP1 and leptin in reducing food intake. Food intake reduction induced by coinjection of GLP1 and leptin was blocked in midbrain-transected rats. These findings indicate that the ascending neural pathway from the hindbrain plays an important role in transmitting the anorectic signals provided by coinjection of GLP1 and leptin.

  15. Targeting angiogenesis in the pathological ovary.

    PubMed

    Duncan, W Colin; Nio-Kobayashi, Junko

    2013-01-01

    The ovary is a key tissue in the study of physiological neo-vascularisation in the adult and its study has highlighted important molecules involved in the regulation of angiogenesis in vivo. These include vascular endothelial growth factor, delta-like ligand 4, thrombospondin-1, prokineticin-1 and prostaglandin E2. Targeting these molecular pathways has therapeutic potential and their manipulation has an increasing preclinical and clinical role in the management of the pathological ovary. Targeting angiogenic pathways has utility in the promotion of ovarian angiogenesis to improve tissue and follicle survival and function as well as the prevention and management of ovarian hyperstimulation syndrome. There is a theoretical possibility that targeting angiogenesis may improve the function of the polycystic ovary and a real role for targeting angiogenesis in ovarian cancer.

  16. Pharmacokinetic and Pharmacodynamic Interaction of Andrographolide and Standardized Extract of Andrographis paniculata (Nees) with Nabumetone in Wistar Rats.

    PubMed

    Balap, Aishwarya; Lohidasan, Sathiyanarayanan; Sinnathambi, Arulmozhi; Mahadik, Kakasaheb

    2017-01-01

    The aim of the study was to investigate the herb-drug interaction of Andrographis paniculata Nees (Acanthaceae) and Andrographolide (AN) with nabumetone (NAB) in wistar rats. Pharmacokinetic and pharmacodynamic interactions were studied after co-administration of APE and AN with NAB in Wistar rats. In pharmacokinetic studies, significant decrease in Cmax, AUC0-t and AUC0-∞ of 6-MNA after co-administration with pure AN and APE has been observed. Tmax of 6-MNA has been increased to 2 h from 1.5 h in AN + NAB treated group. Changes in mean residential time, clearance and volume of distribution of 6-MNA in APE + NAB treated group and AN + NAB treated group indicated interference of other components of APE other than AN. In pharmacodynamic study, significant decrease in antiarthritic activity of NAB on concomitant administration with APE and AN has been observed. The study concludes that NAB exhibits pharmacokinetic and pharmacodynamic interactions with APE and AN in rats thus alarms the concomitant use of herbal preparations containing APE and AN with NAB. Further study is needed to understand the mechanism and predict the herb-drug interaction in humans. Copyright © 2016 John Wiley & Sons, Ltd.

  17. Drug Improves Birth Rates for Women with Ovary Disorder

    MedlinePlus

    ... therapy in increasing live births for women with polycystic ovary syndrome. Letrozole could provide a less expensive, more effective treatment for women with this syndrome. Polycystic ovary syndrome (PCOS) is a leading cause of female infertility. ...

  18. Diagnosis and Treatment of Polycystic Ovary Syndrome.

    PubMed

    Williams, Tracy; Mortada, Rami; Porter, Samuel

    2016-07-15

    Polycystic ovary syndrome is the most common endocrinopathy among reproductive-aged women in the United States, affecting approximately 7% of female patients. Although the pathophysiology of the syndrome is complex and there is no single defect from which it is known to result, it is hypothesized that insulin resistance is a key factor. Metabolic syndrome is twice as common in patients with polycystic ovary syndrome compared with the general population, and patients with polycystic ovary syndrome are four times more likely than the general population to develop type 2 diabetes mellitus. Patient presentation is variable, ranging from asymptomatic to having multiple gynecologic, dermatologic, or metabolic manifestations. Guidelines from the Endocrine Society recommend using the Rotterdam criteria for diagnosis, which mandate the presence of two of the following three findings- hyperandrogenism, ovulatory dysfunction, and polycystic ovaries-plus the exclusion of other diagnoses that could result in hyperandrogenism or ovulatory dysfunction. It is reasonable to delay evaluation for polycystic ovary syndrome in adolescent patients until two years after menarche. For this age group, it is also recommended that all three Rotterdam criteria be met before the diagnosis is made. Patients who have marked virilization or rapid onset of symptoms require immediate evaluation for a potential androgen-secreting tumor. Treatment of polycystic ovary syndrome is individualized based on the patient's presentation and desire for pregnancy. For patients who are overweight, weight loss is recommended. Clomiphene and letrozole are first-line medications for infertility. Metformin is the first-line medication for metabolic manifestations, such as hyperglycemia. Hormonal contraceptives are first-line therapy for irregular menses and dermatologic manifestations.

  19. Pharmacokinetic drug interactions between ondansetron and tamoxifen in female Sprague-Dawley rats with DMBA-induced mammary tumor.

    PubMed

    Yang, Si Hyung; Suh, Jung Hwa; Lee, Myung Gull; Kim, So Hee

    2013-02-01

    Tamoxifen, which is used to treat breast cancer, and ondansetron, used for the treatment of chemotherapy-induced nausea, are commonly metabolized via cytochrome P450 (CYP) 2D subfamily and 3A1/2 in rats, as in humans. This study was conducted to investigate the pharmacokinetic interactions between ondansetron and tamoxifen after intravenous and oral administration of ondansetron (both 8 mg/kg) and/or tamoxifen (2 and 10 mg/kg for intravenous and oral administration, respectively), in rats bearing 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammarian tumors (DMBA rats), used as an animal model of human breast cancer. The total area under the plasma concentration-time curve, from time zero to infinity (AUC) of tamoxifen was significantly greater after both intravenous and oral administration with ondansetron, compared to that after administration of tamoxifen-alone. The hepatic and intestinal metabolism of tamoxifen in DMBA rats was inhibited by ondansetron. Taken together, the significant increase in tamoxifen AUC in DMBA rats after intravenous or oral administration with ondansetron may be attributed to non-competitive hepatic (intravenous) and competitive intestinal (oral) inhibition of CYP2D subfamily- and 3A1/2-mediated tamoxifen metabolism by ondansetron.

  20. Interaction of sertraline and nimodipine on some behavioural tests in rats.

    PubMed

    Kaygisiz, Bilgin; Ozatik, Fikriye Yasemin; Erol, Kevser

    2014-01-01

    Intracellular calcium contributes to the development of affective disorders. Also, calcium channel inhibitors influence the activity of many neurotransmitters and exert antidepressant and anxiolytic properties. The aim of this study was to examine the effects of sertraline on anxiety and depressive behaviors and the role of nimodipine, a calcium channel antagonist, on these effects. Forced swimming and elevated plus maze tests were used to assess depression and anxiety respectively in rats. Sertraline (10 mg/kg) was administered repeatedly for 7 days both alone and in combination with single (0.5 mg/kg) and repeated (0.5 mg/kg/7 days) nimodipine administrations. Both repeated sertraline (S) and its combination with single nimodipine administration (S + N) significantly decreased the immobility time compared to control. The combination of (S) with repeated doses of nimodipine (N/7d), significantly increased the immobility time compared to (S) and (S + N). Single dose of nimodipine (N) significantly increased the immobility time compared to (S) and (S + N), and decreased the number of divings compared to control. There was no significant difference between groups in terms of struggle and the time spent in closed arms of the elevated plus maze. There was no interaction between a single dose of sertraline and nimodipine when administered in combination, while repeated nimodipine administration reversed the antidepressant-like effect of sertraline. We suggest that L-type calcium channels are involved in the antidepressant-like effect of sertraline. Neither single nor repeated nimodipine administration had a significant effect on both depressive behaviour and anxiety. We also propose that there is no interaction between the effects of sertraline and nimodipine on anxitey behavior.

  1. Interactions of histamine and bradykinin on polymodal C-fibres in isolated rat skin.

    PubMed

    Koppert, W; Martus, P; Reeh, P W

    2001-01-01

    Patients suffering from pruritus due to atopic dermatitis show, in asymptomatic skin, reduced itch and flare responses to histamine, the major pruritogenic mediator. We hypothesized that this apparent loss in histamine sensitivity may be overcompensated in inflamed skin and investigated the interactions between histamine and bradykinin, the major inflammatory mediator. The studies were performed using the isolated rat skin-nerve preparation. Forty-two fibres were tested following four different experimental protocols. After characterization of the sensory properties, six fibres were treated repetitively with histamine (HIS1, HIS2) to exclude the possibility that the responses (spikes/min) increase simply by repetition. In 12 other units, histamine (HIS1) was followed by a wash-out period prior to bradykinin (BK) stimulation; in another 12 units, BK followed immediately after HIS1. A further 12 fibres were examined without preceding heat stimulation in order to avoid possible sensitization. If BK was administered after a wash-out period following HIS1, the BK responses were significantly higher than the HIS1 response. The BK response showed a peak discharge which was absent if BK followed directly upon HIS1. If HIS2 was applied directly following BK, the induced discharge was significantly larger than the first histamine response and not different from the BK response, whereas a washout period before HIS2 abolished the sensitizing effect of previous BK.A unidirectional sensitization by previous bradykinin or heat stimulation on the histamine responsiveness of polymodal nociceptors has been demonstrated. If 'itch fibres' in humans were subject to similar interactions of histamine with inflammatory mediators, this may compensate for a down-regulation of histamine receptors in eczematic skin and possibly account for the pruritus.

  2. Morphine decreases social interaction of adult male rats, while THC does not affect it.