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Sample records for puberty rats induced

  1. Maturation of kisspeptinergic neurons coincides with puberty onset in male rats

    DEFF Research Database (Denmark)

    Bentsen, Agnete H; Ansel, Laura; Simonneaux, Valerie

    2010-01-01

    receptor is the primary component in the initiation of puberty and where in the hypothalamus regulation of the kisspeptin/Kiss1R system occurs is unresolved. Using immunohistochemistry and in situ hybridization, we analyzed the level of Kiss1 mRNA and kisspeptin-immunoreactivity in the anteroventral...... periventricular nucleus (AVPV) and the arcuate nucleus of male rats along pubertal development. Neurons expressing Kiss1 mRNA were first detected at PND15, but increased significantly around puberty, and declined again in the adult rat. While virtually no immunoreactive cell bodies were detectable in the AVPV...... that the regulation of kisspeptin synthesis and release are key events in puberty onset in the male rat....

  2. Effect of a postnatal high-fat diet exposure on puberty onset, estrous cycle regularity, and kisspeptin expression in female rats

    DEFF Research Database (Denmark)

    Lie, Maria Elena Klibo; Overgaard, Agnete; Mikkelsen, Jens D

    2013-01-01

    Kisspeptin, encoded by Kiss1, plays a key role in pubertal maturation and reproduction as a positive upstream regulator of the hypothalamic-pituitary-gonadal (HPG) axis. To examine the role of high-fat diet (HFD) on puberty onset, estrous cycle regularity, and kisspeptin expression, female rats...... were exposed to HFD in distinct postnatal periods. Three groups of rats were exposed to HFD containing 60% energy from fat during the pre-weaning period (postnatal day (PND) 1-16, HFD PND 1-16), post-weaning period (HFD PND 21-34), or during both periods (HFD PND 1-34). Puberty onset, evaluated...... that postnatal HFD exposure induced irregular estrous cycles, but had no effect on puberty onset or kisspeptin....

  3. Maturation of kisspeptinergic neurons coincides with puberty onset in male rats

    DEFF Research Database (Denmark)

    Bentsen, Agnete H; Ansel, Laura; Simonneaux, Valerie

    2010-01-01

    receptor is the primary component in the initiation of puberty and where in the hypothalamus regulation of the kisspeptin/Kiss1R system occurs is unresolved. Using immunohistochemistry and in situ hybridization, we analyzed the level of Kiss1 mRNA and kisspeptin-immunoreactivity in the anteroventral...... periventricular nucleus (AVPV) and the arcuate nucleus of male rats along pubertal development. Neurons expressing Kiss1 mRNA were first detected at PND15, but increased significantly around puberty, and declined again in the adult rat. While virtually no immunoreactive cell bodies were detectable in the AVPV...... at any age, numerous kisspeptin-positive neurons in the arcuate nucleus were detected in the adult rat. Increasing doses of kisspeptin-54 given peripherally to male rats at PND15, 30, 45, and 60 evoked roughly similar effects, as revealed by the induction of c-Fos in the pituitary and secretion of LH...

  4. Chronic leptin infusion advances, and immunoneutralization of leptin postpones puberty onset in normally fed and feed restricted female rats

    NARCIS (Netherlands)

    Zeinoaldini, S.; Swarts, J.J.M.; Heijning, van de B.J.M.

    2006-01-01

    Does leptin play a vital role in initiating puberty in female rats and can it overrule a nutrionally imposed (i.e. a 30% feed restriction, FR) delay in puberty onset? Prepubertal female rats were chronically infused for 14 days with leptin (icv or sc) or leptin-antiserum (icv) while puberty onset

  5. Prepubertal exposure to cow's milk reduces susceptibility to carcinogen-induced mammary tumorigenesis in rats

    DEFF Research Database (Denmark)

    Nielsen, Tina Skau; Khan, Galam; Davis, Jennifer

    2011-01-01

    Cow's milk contains high levels of estrogens, progesterone and insulin-like growth factor 1 (IGF-1), all of which are associated with breast cancer. We investigated whether prepubertal milk exposure affects mammary gland development and carcinogenesis in rats. Sprague-Dawley rats were given either...... whole milk or tap water to drink from postnatal day (PND) 14 to PND 35, and thereafter normal tap water. Mammary tumorigenesis was induced by administering 7,12-dimethylbenz[a]anthracene on PND 50. Milk exposure increased circulating E2 levels on PND 25 by 10-fold (p ... opening, which marks puberty onset, by 2.5 days (p milk before puberty exhibited reduced carcinogen-induced mammary carcinogenesis; that is, their tumor latency was longer (p

  6. Development of rat female genital cortex and control of female puberty by sexual touch.

    Directory of Open Access Journals (Sweden)

    Constanze Lenschow

    2017-09-01

    Full Text Available Rat somatosensory cortex contains a large sexually monomorphic genital representation. Genital cortex undergoes an unusual 2-fold expansion during puberty. Here, we investigate genital cortex development and female rat sexual maturation. Ovariectomies and estradiol injections suggested sex hormones cause the pubertal genital cortex expansion but not its maintenance at adult size. Genital cortex expanded by thalamic afferents invading surrounding dysgranular cortex. Genital touch was a dominant factor driving female sexual maturation. Raising female rats in contact with adult males promoted genital cortex expansion, whereas contact to adult females or nontactile (audio-visual-olfactory male cues did not. Genital touch imposed by human experimenters powerfully advanced female genital cortex development and sexual maturation. Long-term blocking of genital cortex by tetrodotoxin in pubescent females housed with males prevented genital cortex expansion and decelerated vaginal opening. Sex hormones, sexual experience, and neural activity shape genital cortex, which contributes to the puberty promoting effects of sexual touch.

  7. Development of rat female genital cortex and control of female puberty by sexual touch.

    Science.gov (United States)

    Lenschow, Constanze; Sigl-Glöckner, Johanna; Brecht, Michael

    2017-09-01

    Rat somatosensory cortex contains a large sexually monomorphic genital representation. Genital cortex undergoes an unusual 2-fold expansion during puberty. Here, we investigate genital cortex development and female rat sexual maturation. Ovariectomies and estradiol injections suggested sex hormones cause the pubertal genital cortex expansion but not its maintenance at adult size. Genital cortex expanded by thalamic afferents invading surrounding dysgranular cortex. Genital touch was a dominant factor driving female sexual maturation. Raising female rats in contact with adult males promoted genital cortex expansion, whereas contact to adult females or nontactile (audio-visual-olfactory) male cues did not. Genital touch imposed by human experimenters powerfully advanced female genital cortex development and sexual maturation. Long-term blocking of genital cortex by tetrodotoxin in pubescent females housed with males prevented genital cortex expansion and decelerated vaginal opening. Sex hormones, sexual experience, and neural activity shape genital cortex, which contributes to the puberty promoting effects of sexual touch.

  8. Pubertal administration of DEHP delays puberty, suppresses testosterone production and inhibits reproductive tract development in male Sprague-Dawley and Long-Evans Rats

    Science.gov (United States)

    While is clear that exposure to high dosage levels of some phthalates delays the onset of puberty in the male rat it has been hypothesized that low levels of DEHP accelerate puberty by enhancing testicular androgen synthesis. The current study was designed to determine if the do...

  9. Adolescent TBI-induced hypopituitarism causes sexual dysfunction in adult male rats.

    Science.gov (United States)

    Greco, Tiffany; Hovda, David A; Prins, Mayumi L

    2015-02-01

    Adolescents are at greatest risk for traumatic brain injury (TBI) and repeat TBI (RTBI). TBI-induced hypopituitarism has been documented in both adults and juveniles and despite the necessity of pituitary function for normal physical and brain development, it is still unrecognized and untreated in adolescents following TBI. TBI induced hormonal dysfunction during a critical developmental window has the potential to cause long-term cognitive and behavioral deficits and the topic currently remains unaddressed. The purpose of this study was to determine if four mild TBIs delivered to adolescent male rats disrupts testosterone production and adult behavioral outcomes. Plasma testosterone was quantified from 72 hrs preinjury to 3 months postinjury and pubertal onset, reproductive organ growth, erectile function and reproductive behaviors were assessed at 1 and 2 months postinjury. RTBI resulted in both acute and chronic decreases in testosterone production and delayed onset of puberty. Significant deficits were observed in reproductive organ growth, erectile function and reproductive behaviors in adult rats at both 1 and 2 months postinjury. These data suggest adolescent RTBI-induced hypopituitarism underlies abnormal behavioral changes observed during adulthood. The impact of undiagnosed hypopituitarism following RTBI in adolescence has significance not only for growth and puberty, but also for brain development and neurobehavioral function as adults. © 2014 Wiley Periodicals, Inc.

  10. Neurokinin B receptor antagonism decreases luteinising hormone pulse frequency and amplitude and delays puberty onset in the female rat.

    Science.gov (United States)

    Li, S Y; Li, X F; Hu, M H; Shao, B; Poston, L; Lightman, S L; O'Byrne, K T

    2014-08-01

    The neural mechanisms controlling puberty onset remain enigmatic. Humans with loss of function mutations in TAC3 or TACR3, the genes encoding neurokinin B (NKB) or its receptor, neurokinin-3 receptor (NK3R), respectively, present with severe congenital gonadotrophin deficiency and pubertal failure. Animal studies have shown ambiguous actions of NKB-NK3R signalling with respect to controlling puberty onset. The present study aimed to determine the role of endogenous NKB-NK3R signalling in the control of pulsatile luteinising hormone (LH) secretion and the timing of puberty onset, and also whether precocious pubertal onset as a result of an obesogenic diet is similarly regulated by this neuropeptide system. Prepubertal female rats, chronically implanted with i.c.v. cannulae, were administered SB222200, a NK3R antagonist, or artificial cerebrospinal fluid via an osmotic mini-pump for 14 days. SB222200 significantly delayed the onset of vaginal opening and first oestrus (as markers of puberty) compared to controls in both normal and high-fat diet fed animals. Additionally, serial blood sampling, via chronic indwelling cardiac catheters, revealed that the increase in LH pulse frequency was delayed and that the LH pulse amplitude was reduced in response to NK3R antagonism, regardless of dietary status. These data suggest that endogenous NKB-NK3R signalling plays a role in controlling the timing of puberty and the associated acceleration of gonadotrophin-releasing hormone pulse generator frequency in the female rat. © 2014 British Society for Neuroendocrinology.

  11. CHARACTERIZATION OF SPONTANEOUS AND INDUCED PUBERTY IN GIRLS WITH TURNER SYNDROME.

    Science.gov (United States)

    Folsom, Lisal J; Slaven, James E; Nabhan, Zeina M; Eugster, Erica A

    2017-07-01

    To characterize puberty in girls with Turner syndrome (TS) and determine whether specific patient characteristics are associated with the timing of menarche. We also sought to compare spontaneous versus induced puberty in these patients. Medical records of girls followed in our Pediatric Endocrine clinic for TS from 2007 to 2015 were reviewed. Fifty-three girls were included, of whom 10 (19%) achieved menarche spontaneously and 43 (81%) received hormone replacement therapy (HRT). Of girls receiving HRT, a younger age at estrogen initiation correlated with a longer time to menarche (P = .02), and a mosaic karyotype was associated with a shorter time to menarche (P = .02), whereas no relationship was seen for body mass index, estrogen regimen, or maternal age at menarche. Nineteen girls (44%) receiving HRT had bleeding on estrogen alone at a wide dose range and were more likely to be on transdermal than oral preparations (P = .01). Girls with spontaneous puberty achieved menarche at a younger age (PTurner syndrome.

  12. Defining a novel leptin–melanocortin–kisspeptin pathway involved in the metabolic control of puberty

    Directory of Open Access Journals (Sweden)

    Maria Manfredi-Lozano

    2016-10-01

    Full Text Available Objective: Puberty is a key developmental phenomenon highly sensitive to metabolic modulation. Worrying trends of changes in the timing of puberty have been reported in humans. These might be linked to the escalating prevalence of childhood obesity and could have deleterious impacts on later (cardio-metabolic health, but their underlying mechanisms remain unsolved. The neuropeptide α-MSH, made by POMC neurons, plays a key role in energy homeostasis by mediating the actions of leptin and likely participates in the control of reproduction. However, its role in the metabolic regulation of puberty and interplay with kisspeptin, an essential puberty-regulating neuropeptide encoded by Kiss1, remain largely unknown. We aim here to unveil the potential contribution of central α-MSH signaling in the metabolic control of puberty by addressing its role in mediating the pubertal effects of leptin and its potential interaction with kisspeptin. Methods: Using wild type and genetically modified rodent models, we implemented pharmacological studies, expression analyses, electrophysiological recordings, and virogenetic approaches involving DREADD technology to selectively inhibit Kiss1 neurons, in order to interrogate the physiological role of a putative leptin→α-MSH→kisspeptin pathway in the metabolic control of puberty. Results: Stimulation of central α-MSH signaling robustly activated the reproductive axis in pubertal rats, whereas chronic inhibition of melanocortin receptors MC3/4R, delayed puberty, and prevented the permissive effect of leptin on puberty onset. Central blockade of MC3/4R or genetic elimination of kisspeptin receptors from POMC neurons did not affect kisspeptin effects. Conversely, congenital ablation of kisspeptin receptors or inducible, DREADD-mediated inhibition of arcuate nucleus (ARC Kiss1 neurons resulted in markedly attenuated gonadotropic responses to MC3/4R activation. Furthermore, close appositions were observed between

  13. Excess androgen during puberty disrupts circadian organization in female rats.

    Science.gov (United States)

    Sellix, Michael T; Murphy, Zachary C; Menaker, Michael

    2013-04-01

    Circadian clocks have been described in each tissue of the hypothalamo-pituitary-ovarian axis. Although a role for the clock in the timing of ovulation is indicated, the impact of diseases that disrupt fertility on clock function or the clocks' role in the etiology of these pathologies has yet to be fully appreciated. Polycystic ovary syndrome (PCOS) is a particularly devastating endocrinopathy, affecting approximately 10% of women at childbearing age. Common features of PCOS are a polycystic ovary, amenorrhea, and excess serum androgen. Approximately 40% of these women have metabolic syndrome, including hyperinsulinemia, dyslipidemia, and hyperleptinemia. It has been suggested that excess androgen is a critical factor in the etiology of PCOS. We have examined the effects of androgen excess during puberty on the phase of circadian clocks in tissues of the metabolic and hypothalamo-pituitary-ovarian axes. Female period1-luciferase (per1-luc) rats were exposed to androgen (5α-dihydrotestosterone [DHT]) or placebo for 4-6 weeks (short term) or 9-15 weeks (long term). As expected, DHT-treated animals gained more weight than controls and had disrupted estrous cycles. At the end of treatment, tissues, including the liver, lung, kidney, white adipose, cornea, pituitary, oviduct, and ovarian follicles, were cultured, and per1-luc expression in each was recorded. Analysis of per1-luc expression revealed that DHT exposure increased phase distribution of multiple oscillators, including ovarian follicles, liver, and adipose, and altered phase synchrony between animals. These data suggest that excess androgen during puberty, a common feature of PCOS, negatively affects internal circadian organization in both the reproductive and metabolic axes.

  14. Early metabolic programming of puberty onset: impact of changes in postnatal feeding and rearing conditions on the timing of puberty and development of the hypothalamic kisspeptin system

    DEFF Research Database (Denmark)

    Castellano, Juan M; Bentsen, Agnete H; Sánchez-Garrido, Miguel A

    2011-01-01

    the timing of puberty; however, the potential underlying mechanisms remain poorly defined. Here we report how changes in the pattern of postnatal feeding affect the onset of puberty and evaluate key hormonal and neuropeptide [Kiss1/kisspeptin (Kp)] alterations linked to these early nutritional manipulations...... of puberty, together with higher levels of leptin and hypothalamic Kiss1 mRNA. Conversely, postnatal underfeeding caused a persistent reduction in body weight, lower ovarian and uterus weights, and delayed vaginal opening, changes that were paralleled by a decrease in leptin and Kiss1 mRNA levels. Kisspeptin...... at puberty were similar in all groups, except for enhanced responsiveness to low doses of Kp-10 in postnatally underfed rats. In conclusion, our data document that the timing of puberty is sensitive to both overfeeding and subnutrition during early (postnatal) periods and suggest that alterations...

  15. Puberty in girls

    Science.gov (United States)

    Well child - puberty in girls; Development - puberty in girls; Menstruation - puberty in girls; Breast development - puberty in girls ... a year. When you are done going through puberty, you will be almost as tall as you ...

  16. EXPOSURE TO DIETHYL HEXYL PHTHALATE (DEHP) DELAYS PUBERTY AND REDUCES ANDROGEN-DEPENDENT TISSUE WEIGHTS IN LONG EVANS HOODED AND SPRAGUE DAWLEY MALE RATS

    Science.gov (United States)

    DEHP is a plasticizer that alters sexual differentiation in the male rat by reducing fetal Leydig cell testosterone synthesis and insl3 mRNA levels. When exposure includes the pubertal stage of life, DEHP and other phthalates delay puberty and reduce androgen-dependent tissue wei...

  17. Two organizational effects of pubertal testosterone in male rats: transient social memory and a shift away from long-term potentiation following a tetanus in hippocampal CA1.

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    Hebbard, Pamela C; King, Rebecca R; Malsbury, Charles W; Harley, Carolyn W

    2003-08-01

    The organizational role of pubertal androgen receptor (AR) activation in synaptic plasticity in hippocampal CA1 and in social memory was assessed. Earlier data suggest pubertal testosterone reduces adult hippocampal synaptic plasticity. Four groups were created following gonadectomy at the onset of puberty: rats given testosterone; rats given testosterone but with the AR antagonist flutamide, present during puberty; rats given testosterone at the end of puberty; and rats given cholesterol at the end of puberty. A tetanus normally inducing long-term potentiation (LTP) was used to stimulate CA1 in the urethane-anesthetized adults during the dark phase of their cycle. Social memory was assessed prior to electrophysiology. Social memory for a juvenile rat at 120 min was seen only in rats not exposed to AR activation during puberty. Pubertal AR activation may induce the reduced social memory of male rats. Early CA1 LTP occurred following tetanus in rats with no pubertal testosterone. Short-term potentiation occurred in rats exposed to pubertal testosterone. Unexpectedly, rats with pubertal AR activation developed long-term depression (LTD). The same pattern was seen in normal male rats. Lack of LTP during the dark phase is consistent with other data on circadian modulation of CA1 LTP. No correlations were seen among social memory scores and CA1 plasticity measures. These data argue for two organizational effects of pubertal testosterone: (1) CA1 synaptic plasticity shifts away from potentiation toward depression; (2) social memory is reduced. Enduring effects of pubertal androgen on limbic circuits may contribute to reorganized behaviors in the postpubertal period.

  18. Delayed Puberty

    Science.gov (United States)

    ... DPeulbayeertdy What Parents Need to Know What is puberty? Puberty is the time of life when a child’s body matures into an adult’s. • For girls, puberty can start as early as age 7½ years ...

  19. Precocious Puberty in Children

    International Nuclear Information System (INIS)

    Atta, I.; Laghari, T. M.; Khan, N. Y.; Lone, W. S.; Ibrahim, M.; Raza, J.

    2015-01-01

    Objective: To determine the etiology of precocious puberty in children and to compare the clinical and laboratory parameters of central and peripheral precocious puberty. Study Design: Cross-sectional study. Place and Duration of Study: Endocrine Clinic at National Institute of Child Health, Karachi, from January 2009 to December 2011. Methodology: Children presenting with precocious puberty were included. The age of onset of puberty was documented. Clinical evaluation, Tanner staging, height, height SDS, weight, weight SDS, body mass index, bone age, pelvic USG, plasma estradiol level and GnRH stimulation were done. Ultrasound of adrenal glands, serum level of 17 hydroxyprogesterone, ACTH, Renin, aldosterone and testosterone were performed in children with peripheral precocious puberty. MRI of adrenal glands and gonads was done in patients with suspected tumor of that organ and MRI of brain was done in patients with central precocious puberty. Skeletal survey was done in patients with Mc Cune-Albright syndrome. Results: CAH (81.8%) indentified as a main cause in peripheral percocious puberty and idiopathic (67.74%) in central precocious puberty. Eighty five patients were registered during this period. The conditions causing precocious puberty were central precocious puberty (36.47%), peripheral precocious puberty (38.82%), premature pubarche (10.58%) and premature thelarche (14.11%). There was a difference in the age of onset of puberty in case of central precocious puberty (mean=3, 2-6 years) versus peripheral precocious puberty (mean=5.25; 3.62 - 7.0 years). Children with central precocious puberty showed higher height SDS, weight SDS, FSH, LH than those with peripheral precocious puberty. Conclusion: Etiology in majority of cases with peripheral precocious puberty was congenital adrenal hyperplasia and idiopathic in central precocious puberty. Central precocious puberty children showed higher height SDS, weight SDS, FSH, LH than peripheral precocious puberty

  20. Epigenetic regulation of puberty via Zinc finger protein-mediated transcriptional repression.

    Science.gov (United States)

    Lomniczi, Alejandro; Wright, Hollis; Castellano, Juan Manuel; Matagne, Valerie; Toro, Carlos A; Ramaswamy, Suresh; Plant, Tony M; Ojeda, Sergio R

    2015-12-16

    In primates, puberty is unleashed by increased GnRH release from the hypothalamus following an interval of juvenile quiescence. GWAS implicates Zinc finger (ZNF) genes in timing human puberty. Here we show that hypothalamic expression of several ZNFs decreased in agonadal male monkeys in association with the pubertal reactivation of gonadotropin secretion. Expression of two of these ZNFs, GATAD1 and ZNF573, also decreases in peripubertal female monkeys. However, only GATAD1 abundance increases when gonadotropin secretion is suppressed during late infancy. Targeted delivery of GATAD1 or ZNF573 to the rat hypothalamus delays puberty by impairing the transition of a transcriptional network from an immature repressive epigenetic configuration to one of activation. GATAD1 represses transcription of two key puberty-related genes, KISS1 and TAC3, directly, and reduces the activating histone mark H3K4me2 at each promoter via recruitment of histone demethylase KDM1A. We conclude that GATAD1 epitomizes a subset of ZNFs involved in epigenetic repression of primate puberty.

  1. Puberty

    Science.gov (United States)

    ... or a period) usually happens last. In boys: Puberty usually begins with the testicles and penis getting bigger. Then hair grows in the pubic area and armpits. Muscles grow, the voice deepens, and facial hair develops as puberty continues. Both boys and girls may get acne. ...

  2. Delayed Puberty (For Teens)

    Science.gov (United States)

    ... Safe Videos for Educators Search English Español Delayed Puberty KidsHealth / For Teens / Delayed Puberty What's in this ... wonder if there's anything wrong. What Is Delayed Puberty? Puberty is the time when your body grows ...

  3. Substance p regulates puberty onset and fertility in the female mouse.

    Science.gov (United States)

    Simavli, Serap; Thompson, Iain R; Maguire, Caroline A; Gill, John C; Carroll, Rona S; Wolfe, Andrew; Kaiser, Ursula B; Navarro, Víctor M

    2015-06-01

    Puberty is a tightly regulated process that leads to reproductive capacity. Kiss1 neurons are crucial in this process by stimulating GnRH, yet how Kiss1 neurons are regulated remains unknown. Substance P (SP), an important neuropeptide in pain perception, induces gonadotropin release in adult mice in a kisspeptin-dependent manner. Here, we assessed whether SP, through binding to its receptor NK1R (neurokinin 1 receptor), participates in the timing of puberty onset and fertility in the mouse. We observed that 1) selective NK1R agonists induce gonadotropin release in prepubertal females; 2) the expression of Tac1 (encoding SP) and Tacr1 (NK1R) in the arcuate nucleus is maximal before puberty, suggesting increased SP tone; 3) repeated exposure to NK1R agonists prepubertally advances puberty onset; and 4) female Tac1(-/-) mice display delayed puberty; moreover, 5) SP deficiency leads to subfertility in females, showing fewer corpora lutea and antral follicles and leading to decreased litter size. Thus, our findings support a role for SP in the stimulation of gonadotropins before puberty, acting via Kiss1 neurons to stimulate GnRH release, and its involvement in the attainment of full reproductive capabilities in female mice.

  4. Binge-pattern alcohol exposure during puberty induces long-term changes in HPA axis reactivity.

    Directory of Open Access Journals (Sweden)

    Magdalena M Przybycien-Szymanska

    2011-04-01

    Full Text Available Adolescence is a dynamic and important period of brain development however, little is known about the long-term neurobiological consequences of alcohol consumption during puberty. Our previous studies showed that binge-pattern ethanol (EtOH treatment during pubertal development negatively dysregulated the responsiveness of the hypothalamo-pituitary-adrenal (HPA axis, as manifested by alterations in corticotrophin-releasing hormone (CRH, arginine vasopressin (AVP, and corticosterone (CORT during this time period. Thus, the primary goal of this study was to determine whether these observed changes in important central regulators of the stress response were permanent or transient. In this study, juvenile male Wistar rats were treated with a binge-pattern EtOH treatment paradigm or saline alone for 8 days. The animals were left undisturbed until adulthood when they received a second round of treatments consisting of saline alone, a single dose of EtOH, or a second binge-pattern treatment paradigm. The results showed that pubertal binge-pattern EtOH exposure induced striking long-lasting alterations of many HPA axis parameters. Overall, our data provide strong evidence that binge-pattern EtOH exposure during pubertal maturation has long-term detrimental effects for the healthy development of the HPA axis.

  5. Insulin Resistance of Puberty.

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    Kelsey, Megan M; Zeitler, Philip S

    2016-07-01

    Puberty is a time of considerable metabolic and hormonal change. Notably, puberty is associated with a marked decrease in insulin sensitivity, on par with that seen during pregnancy. In otherwise healthy youth, there is a nadir in insulin sensitivity in mid-puberty, and then it recovers at puberty completion. However, there is evidence that insulin resistance (IR) does not resolve in youth who are obese going into puberty and may result in increased cardiometabolic risk. Little is known about the underlying pathophysiology of IR in puberty, and how it might contribute to increased disease risk (e.g., type 2 diabetes). In this review, we have outlined what is known about the IR in puberty in terms of pattern, potential underlying mechanisms and other mediating factors. We also outline other potentially related metabolic changes that occur during puberty, and effects of underlying insulin resistant states (e.g., obesity) on pubertal changes in insulin sensitivity.

  6. Lactational exposure to hexavalent chromium delays puberty by impairing ovarian development, steroidogenesis and pituitary hormone synthesis in developing Wistar rats

    International Nuclear Information System (INIS)

    Banu, Sakhila K.; Samuel, Jawahar B.; Arosh, Joe A.; Burghardt, Robert C.; Aruldhas, Michael M.

    2008-01-01

    Hexavalent chromium (Cr-VI) is used in a wide range of industries. Cr-VI from chromate industries and atmospheric emissions contribute to the Cr contamination in the environment. Cr is a reproductive metal toxicant that can traverse the placental barrier and cause a wide range of fetal effects including ovotoxicity. Therefore, the goal of this study was to investigate the basic mechanisms involved in Cr(VI)-induced ovotoxicity, and the protective role of vitamin C on ovarian follicular development and function in Cr(VI)-induced reproductive toxicity using both in vivo and in vitro approaches. Lactating rats received potassium dichromate (200 mg/L) with or without vitamin C (500 mg/L), through drinking water from postpartum days 1-21. During postnatal days (PND) 1-21 the pups received Cr(VI) via the mother's milk. Pups from both control and treatment groups were continued on regular diet and water from PND-21 onwards, and euthanized on PND-21, -45 and -65. Cr(VI) decreased steroidogenesis, GH and PRL, increased FSH and did not alter LH. Cr(VI) delayed puberty, decreased follicle number, and extended estrous cycle. Spontaneously immortalized rat granulosa cells were treated with 12.5 μM (IC 50 ) potassium dichromate for 12 and 24 h, with or without vitamin C pre-treatment. Cr(VI) decreased the mRNA expressions of StAR, SF-1, 17β-HSD-1, 17β-HSD-2, FSHR, LHR, ERα and ERβ. Vitamin C pre-treatment protected ovary and granulosa cells from the deleterious effects of Cr(VI) toxicity, both in vivo and in vitro. Therefore, Cr(VI) toxicity could be a potential risk to the reproductive system in developing females, and vitamin C plays a protective role against Cr(VI)-induced ovotoxicity

  7. Delayed Puberty

    DEFF Research Database (Denmark)

    Kolby, Nanna; Busch, Alexander Siegfried; Juul, Anders

    2017-01-01

    . The underlying reasons for the large variation in the age at pubertal onset are not fully established; however, nutritional status and socioeconomic and environmental factors are known to be influencing, and a significant amount of influencing genetic factors have also been identified. The challenges...... optimal in discriminating especially CDGP from HH. Management of the delayed puberty depends on the etiology. For boys with CDGP an observational period will often reveal imminent puberty. If puberty is not progressing spontaneously, sex steroid replacement is effective in stimulating the development...

  8. Delayed puberty in boys

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/007695.htm Delayed puberty in boys To use the sharing features on this page, please enable JavaScript. Delayed puberty in boys is when puberty does not begin ...

  9. Delayed puberty in girls

    Science.gov (United States)

    ... sexual development - girls; Pubertal delay - girls; Constitutional delayed puberty ... In most cases of delayed puberty, growth changes just begin later than usual, sometimes called a late bloomer. Once puberty begins, it progresses normally. This pattern runs ...

  10. Timing and Stages of Puberty

    Science.gov (United States)

    ... and stages of puberty Timing and stages of puberty Adolescence and puberty can be so confusing! Here’s some info on what to expect and when: Puberty in girls usually starts between the ages of ...

  11. Understanding Puberty (For Parents)

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    ... Safe Videos for Educators Search English Español Understanding Puberty KidsHealth / For Parents / Understanding Puberty What's in this ... your child through all the changes? Stages of Puberty Sure, most of us know the telltale signs ...

  12. Does salt have a permissive role in the induction of puberty?

    Science.gov (United States)

    Pitynski, Dori; Flynn, Francis W; Skinner, Donal C

    2015-10-01

    Puberty is starting earlier than ever before and there are serious physiological and sociological implications as a result of this development. Current research has focused on the potential role of high caloric, and commensurate high adiposity, contributions to early puberty. However, girls with normal BMI also appear to be initiating puberty earlier. Westernized diets, in addition to being high in fat and sugar, are also high in salt. To date, no research has investigated a link between elevated salt and the reproductive axis. We hypothesize that a high salt diet can result in an earlier onset of puberty through three mechanisms that are not mutually exclusive. (1) High salt activates neurokinin B, a hormone that is involved in both the reproductive axis and salt regulation, and this induces kisspeptin release and ultimate activation of the reproductive axis. (2) Vasopressin released in response to high salt acts on vasopressin receptors expressed on kisspeptin neurons in the anteroventral periventricular nucleus, thereby stimulating gonadotropin releasing hormone and subsequently luteinizing hormone secretion. (3) Salt induces metabolic changes that affect the reproductive axis. Specifically, salt acts indirectly to modulate adiposity, ties in with the obesity epidemic, and further compounds the pathologic effects of obesity. Our overall hypothesis offers an additional cause behind the induction of puberty and provides testable postulates to determine the mechanism of potential salt-mediated affects on puberty. Copyright © 2015. Published by Elsevier Ltd.

  13. [Soy isoflavones and human health: breast cancer and puberty timing].

    Science.gov (United States)

    Valladares, Luis; Garrido, Argelia; Sierralta, Walter

    2012-04-01

    Accumulated exposure to high levels of estrogen is associated with an increased incidence of breast cancer. Thus, factors such as early puberty, late menopause and hormone replacement therapy are considered to be risk factors, whereas early childbirth, breastfeeding and puberty at a later age are known to consistently decrease the lifetime breast cancer risk. Epidemiological studies suggest that consumption of isoflavones correlates with a lower incidence of breast cancer. Data from human intervention studies show that the effects of isoflavones on early breast cancer markers differ between pre- and post-menopausal women. The reports from experimental animals (rats and mice) on mammary tumors are variable. These results taken together with heterogeneous outcomes of human interventions, have led to a controversy surrounding the intake of isoflavones to reduce breast cancer risk. This review summarizes recent studies and analyzes factors that could explain the variability of results. In mammary tissue, from the cellular endocrine viewpoint, we analyze the effect of isoflavones on the estrogen receptor and their capacity to act as agonists or antagonists. On the issue of puberty timing, we analyze the mechanisms by which girls, but not boys, with higher prepuberal isoflavone intakes appear to enter puberty at a later age.

  14. Critical androgen-sensitive periods of rat penis and clitoris development.

    Science.gov (United States)

    Welsh, Michelle; MacLeod, David J; Walker, Marion; Smith, Lee B; Sharpe, Richard M

    2010-02-01

    Androgen control of penis development/growth is unclear. In rats, androgen action in a foetal 'masculinisation programming window' (MPW; e15.5-e18.5)' predetermines penile length and hypospadias occurrence. This has implications for humans (e.g. micropenis). Our studies aimed to establish in rats when androgen action/administration affects development/growth of the penis and if deficits in MPW androgen action were rescuable postnatally. Thus, pregnant rats were treated with flutamide during the MPW +/- postnatal testosterone propionate (TP) treatment. To assess penile growth responsiveness, rats were treated with TP in various time windows (late foetal, neonatal through early puberty, puberty onset, or combinations thereof). Phallus length, weight, and morphology, hypospadias and anogenital distance (AGD) were measured in mid-puberty (d25) or adulthood (d90) in males and females, plus serum testosterone in adult males. MPW flutamide exposure reduced adult penile length and induced hypospadias dose-dependently; this was not rescued by postnatal TP treatment. In normal rats, foetal (e14.5-e21.5) TP exposure did not affect male penis size but increased female clitoral size. In males, TP exposure from postnatal d1-24 or at puberty (d15-24), increased penile length at d25, but not ultimately in adulthood. Foetal + postnatal TP (e14-postnatal d24) increased penile size at d25 but reduced it at d90 (due to reduced endogenous testosterone). In females, this treatment caused the biggest increase in adult clitoral size but, unlike in males, phallus size was unaffected by TP during puberty (d15-24). Postnatal TP treatment advanced penile histology at d25 to more resemble adult histology. AGD strongly correlated with final penis length. It is concluded that adult penile size depends critically on androgen action during the MPW but subsequent growth depends on later androgen exposure. Foetal and/or postnatal TP exposure does not increase adult penile size above its

  15. Sex- and brain region-specific patterns of gene expression associated with socially-mediated puberty in a eusocial mammal.

    Directory of Open Access Journals (Sweden)

    Mariela Faykoo-Martinez

    Full Text Available The social environment can alter pubertal timing through neuroendocrine mechanisms that are not fully understood; it is thought that stress hormones (e.g., glucocorticoids or corticotropin-releasing hormone influence the hypothalamic-pituitary-gonadal axis to inhibit puberty. Here, we use the eusocial naked mole-rat, a unique species in which social interactions in a colony (i.e. dominance of a breeding female suppress puberty in subordinate animals. Removing subordinate naked mole-rats from this social context initiates puberty, allowing for experimental control of pubertal timing. The present study quantified gene expression for reproduction- and stress-relevant genes acting upstream of gonadotropin-releasing hormone in brain regions with reproductive and social functions in pre-pubertal, post-pubertal, and opposite sex-paired animals (which are in various stages of pubertal transition. Results indicate sex differences in patterns of neural gene expression. Known functions of genes in brain suggest stress as a key contributing factor in regulating male pubertal delay. Network analysis implicates neurokinin B (Tac3 in the arcuate nucleus of the hypothalamus as a key node in this pathway. Results also suggest an unappreciated role for the nucleus accumbens in regulating puberty.

  16. All about Puberty (For Kids)

    Science.gov (United States)

    ... Videos for Educators Search English Español All About Puberty KidsHealth / For Kids / All About Puberty What's in ... you get older. Putting the P.U. in Puberty P.U.! A lot of kids notice that ...

  17. Puberty menorrhagia Requiring Inpatient Admission

    Directory of Open Access Journals (Sweden)

    AH Khosla

    2010-06-01

    Full Text Available INTRODUCTION: Puberty menorrhagia is a significant health problem in adolescent age group and severe cases may require admission and blood transfusion. Aim of this study was to evaluate the causes, associated complications and management of puberty menorrhagia. METHODS: Hospital records of all patients of puberty menorrhagia requiring admission were analyzed for etiology, duration since menarche, duration of bleeding, investigation profile and management. RESULTS: There were 18 patients of puberty menorrhagia requiring hospital admission. Etiology was anovulatory bleeding in 11 patients, bleeding disorders in five which included idiopathic thrombocytopenia purpura in three and one each with Von-Willebrand disease and leukemia. Two patients had hypothyroidism as the cause. Fourteen patients presented with severe anaemia and required blood transfusion. All except one responded to oral hormonal therapy. CONCLUSIONS: Puberty menorrhagia can be associated with severe complications and requiring blood transfusion. Although most common cause is anovulation but bleeding disorder, other medical condition and other organic causes must be ruled out in any patient of Puberty menorrhagia. KEYWORDS: anovulation, bleeding disorder, puberty, menorrhagia, anaemia.

  18. Boys and Puberty (For Kids)

    Science.gov (United States)

    ... Videos for Educators Search English Español Boys and Puberty KidsHealth / For Kids / Boys and Puberty What's in this article? Why Are Girls Taller ... as you grow up, especially as you reach puberty (say: PYOO-bur-tee), the name for the ...

  19. Adolescent THC exposure does not sensitize conditioned place preferences to subthreshold d-amphetamine in male and female rats.

    Science.gov (United States)

    Keeley, Robin J; Bye, Cameron; Trow, Jan; McDonald, Robert J

    2018-01-01

    The acute effects of marijuana consumption on brain physiology and behaviour are well documented, but the long-term effects of its chronic use are less well known. Chronic marijuana use during adolescence is of increased interest, given that the majority of individuals first use marijuana during this developmental stage , and  adolescent marijuana use is thought to increase the susceptibility to abusing other drugs when exposed later in life. It is possible that marijuana use during critical periods in adolescence could lead to increased sensitivity to other drugs of abuse later on. To test this, we chronically administered ∆ 9 -tetrahydrocannabinol (THC) to male and female Long-Evans (LER) and Wistar (WR) rats directly after puberty onset. Rats matured to postnatal day 90 before being exposed to a conditioned place preference task (CPP). A subthreshold dose of d-amphetamine, found not to induce place preference in drug naïve rats, was used as the unconditioned stimulus. The effect of d-amphetamine on neural activity was inferred by quantifying cfos expression in the nucleus accumbens and dorsal hippocampus following CPP training. Chronic exposure to THC post-puberty had no potentiating effect on a subthreshold dose of d-amphetamine to induce CPP. No differences in cfos expression were observed. These results show that chronic exposure to THC during puberty did not increase sensitivity to d-amphetamine in adult LER and WR rats. This supports the concept that THC may not sensitize the response to all drugs of abuse.

  20. Puberty and adolescent sexuality.

    Science.gov (United States)

    Fortenberry, J Dennis

    2013-07-01

    This article is part of a Special Issue "Puberty and Adolescence". Sexuality emerges as a major developmental element of puberty and the adolescent years that follow. However, connecting the sexuality that emerges with puberty and elements of adult sexuality is difficult because much adolescent sexuality research addresses the transition to partnered sexual behaviors (primarily coitus) and consequences such as unplanned pregnancy and sexually transmitted infections. This review proposes a framework of an expanded understanding of puberty and adolescent sexuality from the perspective of four hallmarks of adult sexuality: sexual desire; sexual arousal; sexual behaviors; and, sexual function. This approach thus addresses important gaps in understanding of the ontogeny of sex and the continuum of sexuality development from adolescence through the adult lifespan. Copyright © 2013 Elsevier Inc. All rights reserved.

  1. Age-dependent change in biological characteristics of stem cells in radiation-induced mammary carcinogenesis

    International Nuclear Information System (INIS)

    Shimada, Yoshiya; Nishimura, Mayumi; Kakinuma, Shizuko; Imaoka, Tatsuhiko; Yasukawa-Barnes, Jane; Gould, Michael N.; Clifton, Kelly H.

    2003-01-01

    If you ask what types of cells are the targets for carcinogenesis, a popular answer would be that cancer arises from stem cells. Stem cells are cells that are capable of both self-renewal and generation of differentiated progenies. If the hypothesis of 'cancer as stem cell disease' is correct, the risk of carcinogenesis should be a function of the number of stem cells and their responsiveness of carcinogen-induced damage. In the present study, we addressed the feasibility of this hypothesis using the rat mammary carcinogenesis model. One of the important conclusions emerging from studies on atomic bomb survivors concerns age-related changes in the susceptibility to breast cancer. The relative risk of breast cancer is very high among women exposed to ionizing radiation before or during puberty, and it decreases thereafter. Little information is available, however, on age-related changes in the radiobiological nature of mammary stem cells. We examined age-associated changes in the number of mammary stem-like cells (clonogens) and their susceptibility to radiation in terms of cell death and carcinogenic initiation frequency. The results were as follows. (1) During the prepubertal period, the total number of mammary clonogens per rat increased exponentially with a population doubling time of ∼4 days. After puberty, the doubling time lengthened to ∼30 days. The total number of clonogens in abdominal and inguinal mammary glands was ∼200 in 2-week-old rats, while it was ∼5600 in 8-week-old rats. (2) The survival curves of clonogenic cells after irradiation indicated that radiation sensitivity of the cells before and during puberty was much higher than after puberty. (3) The initiation frequency of the clonogens from prepubertal rats after 5 Gy irradiation was four times higher than that of the clonogens from post-pubertal rats. These results suggest that changes in the number of stem cells and their radiobiological characteristics underlie the age

  2. Age-dependent change in biological characteristics of stem cells in radiation-induced mammary carcinogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Shimada, Yoshiya; Nishimura, Mayumi; Kakinuma, Shizuko; Imaoka, Tatsuhiko [National Institute of Radiological Sciences, Anagawa, Chiba (Japan); Yasukawa-Barnes, Jane; Gould, Michael N.; Clifton, Kelly H. [Univ. of Wisconsin, Department of Human Oncology, Madison, WI (United States)

    2003-07-01

    If you ask what types of cells are the targets for carcinogenesis, a popular answer would be that cancer arises from stem cells. Stem cells are cells that are capable of both self-renewal and generation of differentiated progenies. If the hypothesis of 'cancer as stem cell disease' is correct, the risk of carcinogenesis should be a function of the number of stem cells and their responsiveness of carcinogen-induced damage. In the present study, we addressed the feasibility of this hypothesis using the rat mammary carcinogenesis model. One of the important conclusions emerging from studies on atomic bomb survivors concerns age-related changes in the susceptibility to breast cancer. The relative risk of breast cancer is very high among women exposed to ionizing radiation before or during puberty, and it decreases thereafter. Little information is available, however, on age-related changes in the radiobiological nature of mammary stem cells. We examined age-associated changes in the number of mammary stem-like cells (clonogens) and their susceptibility to radiation in terms of cell death and carcinogenic initiation frequency. The results were as follows. (1) During the prepubertal period, the total number of mammary clonogens per rat increased exponentially with a population doubling time of {approx}4 days. After puberty, the doubling time lengthened to {approx}30 days. The total number of clonogens in abdominal and inguinal mammary glands was {approx}200 in 2-week-old rats, while it was {approx}5600 in 8-week-old rats. (2) The survival curves of clonogenic cells after irradiation indicated that radiation sensitivity of the cells before and during puberty was much higher than after puberty. (3) The initiation frequency of the clonogens from prepubertal rats after 5 Gy irradiation was four times higher than that of the clonogens from post-pubertal rats. These results suggest that changes in the number of stem cells and their radiobiological characteristics

  3. Kisspeptin and Puberty in Mammals

    Science.gov (United States)

    Terasawa, Ei; Guerriero, Kathryn A.; Plant, Tony M.

    2014-01-01

    Since the discovery of the G-protein coupled receptor (kisspeptin receptor) and its ligand, kisspeptin, our understanding of the neurobiological mechanisms that govern the pituitary-gonadal axis has evolved dramatically. In this chapter, we have reviewed progress regarding the relationship between kisspeptin and puberty, and have proposed a novel hypothesis for the role of kisspeptin signaling in the onset of this crucial developmental event. According to this hypothesis, although kisspeptin neurons in the arcuate nucleus (ARC) are critical for puberty, this is simply because these cells are an integral component of the hypothalamic GnRH pulse generating mechanism that drives intermittent release of the decapeptide, as an increase in GnRH is obligatory for the onset of puberty. In our model, ARC kisspeptin neurons play no “regulatory” role in controlling the timing of puberty. Rather, as a component of the neural network responsible for GnRH pulse generation, they subserve upstream regulatory mechanisms that are responsible for the timing of puberty. PMID:23550010

  4. What Are Common Treatments for Problems of Puberty?

    Science.gov (United States)

    ... Print What are common treatments for problems of puberty? Precocious Puberty There are a number of reasons to treat ... hormone (LH) and follicle-stimulating hormone (FSH). Delayed Puberty With delayed puberty or hypogonadism, treatment varies with ...

  5. Concerns Boys Have about Puberty

    Science.gov (United States)

    ... Size Email Print Share Concerns Boys Have About Puberty Page Content Article Body Boys have pubertal concerns ... just part of growing up. Involuntary Erections During puberty, boys get erections spontaneously, without touching their penis ...

  6. Prenatal androgen excess enhances stimulation of the GNRH pulse in pubertal female rats.

    Science.gov (United States)

    Yan, Xiaonan; Yuan, Chun; Zhao, Nannan; Cui, Yugui; Liu, Jiayin

    2014-07-01

    In adolescent girls with polycystic ovary syndrome (PCOS), neuroendocrine derangements manifest after the onset of puberty, characterized by rapid LH pulse frequency. The early mechanism underlying the pubertal regulation of the GNRH/LH pulsatile release in adolescents with PCOS remains uncertain. To determine the effects of prenatal androgen exposure on the activation of GNRH neurons and generation of LH pulse at puberty, we administrated 5α-dihydrotestosterone to pregnant rats and observed serum LH levels and expression of hypothalamic genes in female offspring from postnatal 4 to 8 weeks. The 6-week-old prenatally androgenized (PNA) female rats exhibited an increase in LH pulse frequency. The hypothalamic expression of neurokinin B (Nkb (Tac2)) and Lepr mRNA levels in PNA rats increased remarkably before puberty and remained high during puberty, whereas elevated Kiss1 mRNA levels were detected only after the onset of puberty. Exogenous kisspeptin, NK3R agonist, and leptin triggered tonic stimulation of GNRH neurons and increased LH secretion in 6-week-old PNA rats. Leptin upregulated Kiss1 mRNA levels in the hypothalamus of pubertal PNA rats; however, pretreatment with a kisspeptin antagonist failed to suppress the elevated serum LH stimulated by leptin, indicating that the stimulatory effects of leptin may be conveyed indirectly to GNRH neurons via other neural components within the GNRH neuronal network, rather than through the kisspeptin-GPR54 pathway. These findings validate the hypotheses that NKB and leptin play an essential role in the activation of GNRH neurons and initiation of increased LH pulse frequency in PNA female rats at puberty and that kisspeptin may coordinate their stimulatory effects on LH release. © 2014 Society for Endocrinology.

  7. Puberty as an accelerator for diabetes complications.

    Science.gov (United States)

    Cho, Yoon Hi; Craig, Maria E; Donaghue, Kim C

    2014-02-01

    Much is written about how difficult it is to deal with diabetes during adolescence, and rightly so. Less is understood as to how puberty may be an accelerator of vascular complications. With the increase in childhood diabetes, complication risks need to be revisited in relation to puberty and the secular increase in adiposity. Recent data suggest greater risk for severe vascular complications in those with diabetes during puberty, compared with young people who develop diabetes after puberty. It is also widely recognized that higher hemoglobin A1c (HbA1c) results are often seen during the pubertal period. This article will review complication outcomes in relation to puberty and examine mechanisms by which puberty may modify risk above glycemic exposure, and possible gender disparities in the risk of complications in the adolescent period. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  8. Puberty and Its Measurement: A Decade in Review

    Science.gov (United States)

    Dorn, Lorah D.; Biro, Frank M.

    2011-01-01

    Since the early 1980s, the focus on the importance of puberty to adolescent development has continued with variability in the methodology selected to measure puberty. To capture the relevant and important issues regarding the measurement of puberty in the last decade, this paper will address (1) the neuroendocrine aspects of puberty and its…

  9. Protein- and tryptophan-restricted diets induce changes in rat gonadal hormone levels.

    Science.gov (United States)

    Del Angel-Meza, A R.; Feria-Velasco, A; Ontiveros-Martínez, L; Gallardo, L; Gonzalez-Burgos, I; Beas-Zárate, C

    2001-04-01

    The release of gonadotrophic hormones starts at puberty and, along with the subsequent estral cyclicity, is subject to hormonal feedback systems and to the action of diverse neuroactive substances such as gamma amino butyric acid and catecholamines. This study shows the effect of the administration during 40 days of protein-restricted and corn-based (tryptophan- and lysine-deficient) diets on the serotonin concentration in medial hypothalamic fragments as well as in follicle-stimulating luteinizing hormones, 17-beta-estradiol and progesterone serum levels, and estral cyclicity in 60- and 100-day-old rats (young, mature, and in gestation). In young rats, a delay in vaginal aperture development, and a lengthening of the estral cycle to a continuous anestral state was observed, mainly in the group fed corn. This group showed a 25% decrease in the serotonin concentration compared with the protein-restricted group, which exhibited an increase of 9% over the control group. Luteinizing hormone levels decreased in 16% and 13%, whereas follicle-stimulating hormone increased in 13% and 5% in the young animals of restricted groups, respectively, compared with the control group. Serum progesterone levels decreased only in young restricted versus control animals, and no differences were seen among adult and gestational rats. Serum levels of 17-beta-estradiol in restricted animals showed different concentration patterns, mainly in the corn group, which was higher at the 20th gestational day, falling drastically postpartum. The results obtained in this study show serotonin to be a very important factor in the release of gonadotrophic hormones and the start of puberty.

  10. Epigenetic regulation of female puberty.

    Science.gov (United States)

    Lomniczi, Alejandro; Wright, Hollis; Ojeda, Sergio R

    2015-01-01

    Substantial progress has been made in recent years toward deciphering the molecular and genetic underpinnings of the pubertal process. The availability of powerful new methods to interrogate the human genome has led to the identification of genes that are essential for puberty to occur. Evidence has also emerged suggesting that the initiation of puberty requires the coordinated activity of gene sets organized into functional networks. At a cellular level, it is currently thought that loss of transsynaptic inhibition, accompanied by an increase in excitatory inputs, results in the pubertal activation of GnRH release. This concept notwithstanding, a mechanism of epigenetic repression targeting genes required for the pubertal activation of GnRH neurons was recently identified as a core component of the molecular machinery underlying the central restraint of puberty. In this chapter we will discuss the potential contribution of various mechanisms of epigenetic regulation to the hypothalamic control of female puberty. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. Adolescent THC exposure does not sensitize conditioned place preferences to subthreshold d-amphetamine in male and female rats [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Robin J Keeley

    2018-03-01

    Full Text Available The acute effects of marijuana consumption on brain physiology and behaviour are well documented, but the long-term effects of its chronic use are less well known. Chronic marijuana use during adolescence is of increased interest, given that the majority of individuals first use marijuana during this developmental stage , and  adolescent marijuana use is thought to increase the susceptibility to abusing other drugs when exposed later in life. It is possible that marijuana use during critical periods in adolescence could lead to increased sensitivity to other drugs of abuse later on. To test this, we chronically administered ∆9-tetrahydrocannabinol (THC to male and female Long-Evans (LER and Wistar (WR rats directly after puberty onset. Rats matured to postnatal day 90 before being exposed to a conditioned place preference task (CPP. A subthreshold dose of d-amphetamine, found not to induce place preference in drug naïve rats, was used as the unconditioned stimulus. The effect of d-amphetamine on neural activity was inferred by quantifying cfos expression in the nucleus accumbens and dorsal hippocampus following CPP training. Chronic exposure to THC post-puberty had no potentiating effect on a subthreshold dose of d-amphetamine to induce CPP. No differences in cfos expression were observed. These results show that chronic exposure to THC during puberty did not increase sensitivity to d-amphetamine in adult LER and WR rats. This supports the concept that THC may not sensitize the response to all drugs of abuse.

  12. Genetics Home Reference: familial male-limited precocious puberty

    Science.gov (United States)

    ... male-limited precocious puberty Familial male-limited precocious puberty Printable PDF Open All Close All Enable Javascript ... expand/collapse boxes. Description Familial male-limited precocious puberty is a condition that causes early sexual development ...

  13. Charles River Sprague Dawley rats lack early age-dependent susceptibility to DMBA-induced mammary carcinogenesis.

    Science.gov (United States)

    Gear, R B; Yan, M; Schneider, J; Succop, P; Heffelfinger, S C; Clegg, D J

    2007-10-04

    Developmental stages of mammary glands influence their susceptibility to initiating events related to carcinogenesis. The "window of susceptibility" to mammary carcinogenesis is classically defined as the time in early puberty when the mammary gland morphology is most sensitive to initiation events. Administration of the polyaromatic hydrocarbon, 7,12-dimethylbenz(a)anthracene (DMBA), in a single oral dose yields maximal mammary tumor formation when administered in this "window". We examined the DMBA treated mammary glands, precursor lesions, and morphology of the uninvolved mammary epithelium for the first 100 days of life for Charles River Sprague Dawley CD(R) IGS. Our goal was to determine the DMBA dose at which 50% of the rats (IC50) developed carcinoma in situ (CIS) within three months of dosing. Here we demonstrate, rather than the classical U-shaped dose curve in which there is maximum sensitivity for DMBA at 50 days, there is an increasing degree of sensitivity with age in the CD(R) IGS rat. Additionally, we report that vehicle-treated animals developed mammary CIS without any known initiator, and 100 day virgin animals demonstrated lactational changes, independent of DMBA exposure or dose. Lastly, we demonstrate this strain of virgin female rats has elevated pituitary prolactin immunoreactivity independent of the level of mammary differentiation. We conclude this strain of Charles River Sprague Dawley rats has prolactin-induced pituitary stimulation, and therefore, the window of susceptibility for mammary tumorigenesis is absent.

  14. Evaluation of 451 Danish Boys With Delayed Puberty

    DEFF Research Database (Denmark)

    Lawaetz, Jacob Gerner; P. Hagen, Casper; Mieritz, Mikkel Grunnet

    2015-01-01

    Context: Few data exist on the diagnostic criteria, and on the effects of puberty induction, in boyswith constitutional delay in growth and puberty (CDGP). Objective: To develop puberty nomograms based on Danish boys with normal pubertal development.To evaluate the different diagnostic criteria...... and the effect of oral testosterone undecanoate(TU) in boys with CDGP. Design: A cross-sectional and longitudinal study of Danish boys with normal pubertal development(COPENHAGEN puberty study). A retrospective observational study of 451 boys evaluated fordelayed puberty between 1990 and 2013. Setting: Tertiary...... by the puberty nomogram(genital stage 2 SD for age) versus the classical criteria (genital stage 1 at 14 years). The effectof one year of oral TU treatment on pubertal progression, circulating hormones, height, andpredicted adult height (PAH). Results: Seventy-eight (27%) of the 287 boys had delayed pubertal...

  15. Hormonal regulation of puberty onset in female rats: is leptin a missing link?

    NARCIS (Netherlands)

    Zeinoaldini, S.

    2005-01-01

    Numerous factors in the hypothalamus-pituitary-gonadal axis (HPG) are involved in the timing of puberty onset.Leptin signals the nutritional status and the presence of an adequate amount of loaded adipose tissue, as a long-term

  16. Enhanced Striatal β1-Adrenergic Receptor Expression Following Hormone Loss in Adulthood Is Programmed by Both Early Sexual Differentiation and Puberty: A Study of Humans and Rats

    Science.gov (United States)

    Perry, Adam N.; Westenbroek, Christel; Hedges, Valerie L.; Becker, Jill B.; Mermelstein, Paul G.

    2013-01-01

    After reproductive senescence or gonadectomy, changes occur in neural gene expression, ultimately altering brain function. The endocrine mechanisms underlying these changes in gene expression beyond immediate hormone loss are poorly understood. To investigate this, we measured changes in gene expression the dorsal striatum, where 17β-estradiol modulates catecholamine signaling. In human caudate, quantitative PCR determined a significant elevation in β1-adrenergic receptor (β1AR) expression in menopausal females when compared with similarly aged males. No differences were detected in β2-adrenergic and D1- and D2-dopamine receptor expression. Consistent with humans, adult ovariectomized female rats exhibited a similar increase in β1AR expression when compared with gonadectomized males. No sex difference in β1AR expression was detected between intact adults, prepubertal juveniles, or adults gonadectomized before puberty, indicating the necessity of pubertal development and adult ovariectomy. Additionally, increased β1AR expression in adult ovariectomized females was not observed if animals were masculinized/defeminized with testosterone injections as neonates. To generate a model system for assessing functional impact, increased β1AR expression was induced in female-derived cultured striatal neurons via exposure to and then removal of hormone-containing serum. Increased β1AR action on cAMP formation, cAMP response element-binding protein phosphorylation and gene expression was observed. This up-regulation of β1AR action was eliminated with 17β-estradiol addition to the media, directly implicating this hormone as a regulator of β1AR expression. Beyond having implications for the known sex differences in striatal function and pathologies, these data collectively demonstrate that critical periods early in life and at puberty program adult gene responsiveness to hormone loss after gonadectomy and potentially reproductive senescence. PMID:23533220

  17. Neuroendocrine control of the onset of puberty.

    Science.gov (United States)

    Plant, Tony M

    2015-07-01

    This chapter is based on the Geoffrey Harris Memorial Lecture presented at the 8th International Congress of Neuroendocrinology, which was held in Sydney, August 2014. It provides the development of our understanding of the neuroendocrine control of puberty since Harris proposed in his 1955 monograph (Harris, 1955) that "a major factor responsible for puberty is an increased rate of release of pituitary gonadotrophin" and posited "that a neural (hypothalamic) stimulus, via the hypophysial portal vessels, may be involved." Emphasis is placed on the neurobiological mechanisms governing puberty in highly evolved primates, although an attempt is made to reverse translate a model for the timing of puberty in man and monkey to non-primate species. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Short-Term High-Fat Diet Increases Leptin Activation of CART Neurons and Advances Puberty in Female Mice.

    Science.gov (United States)

    Venancio, Jade Cabestre; Margatho, Lisandra Oliveira; Rorato, Rodrigo; Rosales, Roberta Ribeiro Costa; Debarba, Lucas Kniess; Coletti, Ricardo; Antunes-Rodrigues, Jose; Elias, Carol F; Elias, Lucila Leico K

    2017-11-01

    Leptin is a permissive factor for puberty initiation, participating as a metabolic cue in the activation of the kisspeptin (Kiss1)-gonadotropin-releasing hormone neuronal circuitry; however, it has no direct effect on Kiss1 neurons. Leptin acts on hypothalamic cocaine- and amphetamine-regulated transcript (CART) neurons, participating in the regulation of energy homeostasis. We investigated the influence of a short-term high-fat diet (HFD) on the effect of leptin on puberty timing. Kiss1-hrGFP female mice received a HFD or regular diet (RD) after weaning at postnatal day (PN)21 and were studied at PN28 and PN32. The HFD increased body weight and plasma leptin concentrations and decreased the age at vaginal opening (HFD, 32 ± 0.53 days; RD, 38 ± 0.67 days). Similar colocalization of neurokinin B and dynorphin in Kiss1-hrGFP neurons of the arcuate nucleus (ARC) was observed between the HFD and RD groups. The HFD increased CART expression in the ARC and Kiss1 messenger RNA expression in the anteroventral periventricular (AVPV)/anterior periventricular (Pe). The HFD also increased the number of ARC CART neurons expressing leptin-induced phosphorylated STAT3 (signal transducer and activator of transcription 3) at PN32. Close apposition of CART fibers to Kiss1-hrGFP neurons was observed in the ARC of both RD- and HFD-fed mice. In conclusion, these data reinforce the notion that a HFD increases kisspeptin expression in the AVPV/Pe and advances puberty initiation. Furthermore, we have demonstrated that the HFD-induced earlier puberty is associated with an increase in CART expression in the ARC. Therefore, these data indicate that CART neurons in the ARC can mediate the effect of leptin on Kiss1 neurons in early puberty induced by a HFD. Copyright © 2017 Endocrine Society.

  19. Metabolic control of female puberty: potential therapeutic targets.

    Science.gov (United States)

    Castellano, Juan M; Tena-Sempere, Manuel

    2016-10-01

    The onset of puberty in females is highly sensitive to the nutritional status and the amount of energy reserves of the organism. This metabolic information is sensed and transmitted to hypothalamic GnRH neurons, considered to be ultimately responsible for triggering puberty through the coordinated action of different peripheral hormones, central neurotransmitters, and molecular mediators. This article will review and discuss (i) the relevant actions of the adipose hormone leptin, as a stimulatory/permissive signal, and the gut hormone ghrelin, as an inhibitory factor, in the metabolic control of female puberty; (ii) the crucial role of the hypothalamic kisspeptin neurons, recently emerged as essential gatekeepers of puberty, in transmitting this metabolic information to GnRH neurons; and (iii) the potential involvement of key cellular energy sensors, such as mTOR, as molecular mediators in this setting. The thorough characterization of the physiological roles of the above elements in the metabolic control of female puberty, along with the discovery of novel factors, pathways, and mechanisms involved, will promote our understanding of the complex networks connecting metabolism and puberty and, ultimately, will aid in the design of target-specific treatments for female pubertal disorders linked to conditions of metabolic stress.

  20. Circulating MKRN3 Levels Decline During Puberty in Healthy Boys

    DEFF Research Database (Denmark)

    Busch, Alexander S.; Hagen, Casper P; Almstrup, Kristian

    2016-01-01

    CONTEXT: Initiation and progression of puberty requires concerted action of hypothalamic activating and inhibiting factors. Recently, cases of familial central precocious puberty have been linked to loss-of-function mutations of makorin RING-finger protein 3 (MKRN3) indicating a pivotal inhibitory.......8-11.8) years at baseline followed for 6.0 (0.5-7.6) years (2006-2014) with blood sampling every 6 months. INTERVENTION: None. MAIN OUTCOME MEASURES: Serum levels of MKRN3: 623 samples, median (range) 12 (2-14) per boy. RESULTS: MKRN3 levels declined before onset of puberty; the geometric mean (95% confidence...... interval) 5 years before onset of puberty vs last visit before onset of puberty was 216 (169-272) pg/mL vs 128 (118-139) pg/mL (P puberty progressed. MKRN3 levels were not associated with age at onset of puberty. CONCLUSION: Declining MKRN3...

  1. Leuprolide acetate-stimulated androgen response during female puberty.

    Science.gov (United States)

    Hernandez, María Isabel; Martinez-Aguayo, Alejandro; Cavada, Gabriel; Avila, Alejandra; Iñiguez, German; Mericq, Veronica

    2015-08-01

    A physiological increase in androgen levels occurs during adolescence. Measuring androgen concentrations is the best method to distinguish normal evolution processes from hyperandrogenic disorders. The increase in circulating androgens during puberty is inversely associated with insulin sensitivity in normal weight girls. To assess circulating levels of ovarian androgens and anti-Müllerian hormone (AMH) at baseline and after GnRH analogue (GnRH-a) stimulation in normal pubertal girls across different Tanner stages. We also studied the association between this response and insulin sensitivity. Prospective study of healthy girls (6-12 years) from the local community (n = 63). Tanner I (n = 23) subjects were assessed cross-sectionally, and Tanner II girls (n = 40) were evaluated every 6 months until they reached Tanner V. Early morning dehydroepiandrosterone sulphate (DHEA-S), AMH, sex hormone-binding globulin (SHBG), androstenedione, glucose and insulin levels were measured. A GnRH-a test (500 μg/m(2) ; sc) and oral glucose intolerance test (OGTT) were performed. Differences throughout puberty were evaluated. Basal and/or stimulated Testosterone DHEA-S and 17-hydroxyprogesterone (17OHP) were inversely associated with insulin sensitivity (WIBSI) from the beginning of puberty, whereas androstenedione was directly associated with gonadotrophins. AMH was inversely associated with basal and stimulated gonadotrophins and directly with insulin area under the curve (AUC) only in the early stages of puberty. 17OHP and testosterone responsiveness increased significantly during puberty in all subjects, whereas testosterone levels changed less consistently. This pattern of ovarian-steroidogenic response was most evident during mid- and late puberty. Moreover, during late puberty only, basal 17OHP, testosterone and DHEA-S were positively associated with gonadotrophins. In normal nonobese girls born appropriate for gestational age, androgen synthesis was associated with

  2. NEUROBEHAVIORAL RELATIONSHIPS AND PUBERTY - ANOTHER TRANSFORMATION

    NARCIS (Netherlands)

    SOORANILUNSING, RJ

    In a follow-up study of the Groningen Perinatal Project (GPP) on minor neurological dysfunction (MND) at 12 and 14 years the onset of puberty appeared to play a role. The children were selected on the presence (n = 185) and absence (n = 185) of MND at 9 years. Puberty was defined by the presence of

  3. Congenital hypogonadotropic hypogonadism: implications of absent mini-puberty.

    Science.gov (United States)

    Dwyer, Andrew A; Jayasena, Channa N; Quinton, Richard

    2016-06-01

    The phenomenon known as "mini-puberty" refers to activation of the neonatal hypothalamo-pituitary axis causing serum concentrations of gonadotrophins and testosterone (T) to approach adult male levels. This early neonatal period is a key proliferative window for testicular germ cells and immature Sertoli cells. Although failure to spontaneously initiate (adolescent) puberty is the most evident consequence of a defective gonadotropin-releasing hormone (GnRH) neurosecretory network, absent mini-puberty is also likely to have a major impact on the reproductive phenotype of men with congenital hypogonadotrophic hypogonadism (CHH). Furthermore, the phase of male mini-puberty represents a key window-of-opportunity to identify congenital GnRH deficiency (either isolated CHH, or as part of combined pituitary hormone deficiency) in childhood. Among male neonates exhibiting "red flag" indicators for CHH (i.e. maldescended testes with or without cryptorchidism) a single serum sample (between 4-8 weeks of life) can pinpoint congenital GnRH deficiency far more rapidly and with much greater accuracy than dynamic tests performed in later childhood or adolescence. Potential consequences for missing absent mini-puberty in a male neonate include the lack of monitoring of pubertal progression/lack of progression, and the missed opportunity for early therapeutic intervention. This article will review our current understanding of the mechanisms and clinical consequences of mini-puberty. Furthermore, evidence for the optimal clinical management of patients with absent mini-puberty will be discussed.

  4. The influence of puberty on subcortical brain development.

    Science.gov (United States)

    Goddings, Anne-Lise; Mills, Kathryn L; Clasen, Liv S; Giedd, Jay N; Viner, Russell M; Blakemore, Sarah-Jayne

    2014-03-01

    Puberty is characterized by hormonal, physical and psychological transformation. The human brain undergoes significant changes between childhood and adulthood, but little is known about how puberty influences its structural development. Using a longitudinal sample of 711 magnetic resonance imaging scans from 275 individuals aged 7-20years, we examined how subcortical brain regions change in relation to puberty. Our regions of interest included the amygdala, hippocampus and corpus striatum including the nucleus accumbens (NA), caudate, putamen and globus pallidus (GP). Pubertal development was significantly related to structural volume in all six regions in both sexes. Pubertal development and age had both independent and interactive influences on volume for the amygdala, hippocampus and putamen in both sexes, and the caudate in females. There was an interactive puberty-by-age effect on volume for the NA and GP in both sexes, and the caudate in males. These findings suggest a significant role for puberty in structural brain development. © 2013. Published by Elsevier Inc. All rights reserved.

  5. [Precocious puberty and von Recklinghausen's disease].

    Science.gov (United States)

    Barg, Ewa; Wikiera, Beata; Basiak, Aleksander; Głab, Ewa

    2006-01-01

    Von Recklinghausen's disease belongs to a group of neurocutaneous syndromes and is characterised by skin, nerve and bone abnormalities. We present a case of von Recklinghausen's disease and precocious puberty in 7-year-old boy. At the age of three café au lait spots on the skin and an incranial tumour situated near the optic chiasm--qualified as inoperable--were discovered. At the age of 7 first signs of precocious puberty appeared (pubic hair P3 and enlargement of the testes (15 ml) and penis). Laboratory measurements included: LH 7.5 mIU/ml, FSH 1.1 mIU/ml, testosterone 183 ng/ml, assessment of bone age: 9 years. The response to LHRH stimulation was characteristic for true precocious puberty (LH 15.9 mIU/ml and FSH 1.5 mIU/ml after 30 minutes). The MRI of the brain showed a tumour of the suprasellar region with compression of pituitary stalk. True precocious puberty was diagnosed. Treatment with Diphereline was introduced. At present the boy is 9 years old and has been treated with Diphereline for 16 months. The volume of the testicles has decreased to 7 ml and loss of pubic hair was noted. The MRI does not show any progression in tumour growth. The authors would like to underline the need of close observation of children with von Reclinghausen disease with regard to possibility of uncovering true precocious puberty which is critical for rapid diagnosis and introduction of correct treatment.

  6. Testicular growth and development in puberty.

    Science.gov (United States)

    Koskenniemi, Jaakko J; Virtanen, Helena E; Toppari, Jorma

    2017-06-01

    To describe pubertal testicular growth in humans, changes in testicular cell populations that result in testicular growth, and the role of testosterone and gonadotrophins follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in testicular growth. When human data were not available, studies in nonhuman primates and/or rodents were used as surrogates. Testicular growth in puberty follows a sigmoidal growth curve, with a large variation in timing of testicular growth and adult testicular volume. Testicular growth early in puberty is due to increase in Sertoli cell number and length of seminiferous tubules, whereas the largest and fastest growth results from the increase in the diameter of the seminiferous tubules first due to spermatogonial proliferation and then due to the expansion of meiotic and haploid germ cells. FSH stimulates Sertoli cell and spermatogonial proliferation, whereas LH/testosterone is mandatory to complete spermatogenesis. However, FSH and LH/testosterone work in synergy and are both needed for normal spermatogenesis. Testicular growth during puberty is rapid, and mostly due to germ cell expansion and growth in seminiferous tubule diameter triggered by androgens. Pre-treatment with FSH before the induction of puberty may improve the treatment of hypogonadotropic hypogonadism, but remains to be proven.

  7. Public health implications of altered puberty timing

    DEFF Research Database (Denmark)

    Golub, M.S.; Collman, G.W.; Foster, P.M.

    2008-01-01

    sexual debut, potential sexual abuse, and psychosocial difficulties. Altered puberty timing is also of concern for the development of reproductive tract cancers later in life. For example, an early age of menarche is a risk factor for breast cancer. A low age at male puberty is associated...

  8. The effect of puberty on diurnal sodium regulation.

    Science.gov (United States)

    Mahler, B; Kamperis, K; Ankarberg-Lindgren, C; Djurhuus, J C; Rittig, S

    2015-11-15

    The aim of this study was to investigate the impact of sex and puberty stage on circadian changes in sodium excretion, sodium-regulating hormones, and hemodynamics. Thirty-nine healthy volunteers (9 prepuberty boys, 10 prepuberty girls, 10 puberty boys, and 10 puberty girls) were included. They all underwent a 24-h circadian in-patient study under standardized conditions regarding activity, diet, and fluid intake. Blood samples were drawn every 4 h, and the urine was collected in fractions. Blood pressure and heart rate were noninvasively monitored. Atrial natriuretic peptide (ANP), angiotensin II, aldosterone, and renin were measured in blood. Children in puberty had lower plasma levels of renin (Ppuberty group. There is a circadian rhythm of sodium excretion and sodium regulation in 7- to 15-yr-old children. This rhythm is similar in boys and girls. As an important new finding, puberty changes the plasma levels of renin and angiotensin II without changing the amount of sodium excreted or the day to night sodium excretion ratio. Copyright © 2015 the American Physiological Society.

  9. Trends in puberty timing in humans and environmental modifiers

    DEFF Research Database (Denmark)

    Toppari, Jorma; Juul, Anders

    2010-01-01

    Secular trends in timing of puberty appear to continue although under-nutrition has not been any longer a limiting factor for pubertal development. Now obesity and other environmental reasons have been suspected to cause this trend, and endocrine disrupting chemicals have become into focus...... as possible contributors. Epidemiological studies on endocrine disrupters are still scarce and show only weak associations between exposures and timing of puberty. Since genetic background explains 50-80% of variability in the timing of puberty, it is not surprising that the observed environmental effects...... are rather modest when individual exposures are assessed. Despite that, some exposures have been reported to be associated to early (e.g., polybrominated biphenyls) or delayed (e.g., lead) puberty. Here we shortly review the available data on recent trends in timing of puberty and the possible role...

  10. Central precocious puberty: from physiopathological mechanisms to treatment.

    Science.gov (United States)

    Chirico, V; Lacquaniti, A; Salpietro, V; Buemi, M; Salpietro, C; Arrigo, T

    2014-01-01

    Puberty is a complex, coordinated biological process with multiple levels of regulations. The timing of puberty varies greatly in children and it is influenced by environmental, endocrine and genetic factors. Precocious puberty (PP) is an important issue, affecting between 1 in 5.000-10.000 children. The physiopathological mechanism is still unknown. From an etiological point of view, PP may be subdivided into gonadotropin-releasing hormone (GnRH) -dependent and independent causes. GnRH-dependent PP, often called central precocious puberty (CPP), is based on hypothalamic-pituitary-gonadal axis activation associated with progressive pubertal development, accelerated growth rate and advancement of skeletal age. Conversely, peripheral precocious puberty (PPP) is related to sex steroid exposure, independently of hypothalamic-–pituitary-–gonadal (HPG) axis activation. Kisspeptins play a central role in the modulation of GnRH secretion with peripheral factors that influence the timing of puberty, such as adipokines and endocrine disrupting chemicals. Moreover, PP could be related to genetic disorders, involving pivotal genes of the HPG axis. The standard test used to verify HPG activity is the gonadotropin response to administered GnRH analogs. We describe the physiopathological mechanisms of PP and its clinical implications, analysing diagnostic flow-chart and new potential biomarkers that could reveal PP. An update of the current literature was also carried out regarding the recent novelty for treatment.

  11. Timing of Puberty in Overweight Versus Obese Boys.

    Science.gov (United States)

    Lee, Joyce M; Wasserman, Richard; Kaciroti, Niko; Gebremariam, Achamyeleh; Steffes, Jennifer; Dowshen, Steven; Harris, Donna; Serwint, Janet; Abney, Dianna; Smitherman, Lynn; Reiter, Edward; Herman-Giddens, Marcia E

    2016-02-01

    Studies of the relationship of weight status with timing of puberty in boys have been mixed. This study examined whether overweight and obesity are associated with differences in the timing of puberty in US boys. We reanalyzed recent community-based pubertal data from the American Academy of Pediatrics' Pediatric Research in Office Settings study in which trained clinicians assessed boys 6 to 16 years for height, weight, Tanner stages, testicular volume (TV), and other pubertal variables. We classified children based on BMI as normal weight, overweight, or obese and compared median age at a given Tanner stage or greater by weight class using probit and ordinal probit models and a Bayesian approach. Half of boys (49.9%, n = 1931) were white, 25.8% (n = 1000) were African American, and 24.3% (n = 941) were Hispanic. For genital development in white and African American boys across a variety of Tanner stages, we found earlier puberty in overweight compared with normal weight boys, and later puberty in obese compared with overweight, but no significant differences for Hispanics. For TV (≥3 mL or ≥4 mL), our findings support earlier puberty for overweight compared with normal weight white boys. In a large, racially diverse, community-based sample of US boys, we found evidence of earlier puberty for overweight compared with normal or obese, and later puberty for obese boys compared with normal and overweight boys. Additional studies are needed to understand the possible relationships among race/ethnicity, gender, BMI, and the timing of pubertal development. Copyright © 2016 by the American Academy of Pediatrics.

  12. Pubertal development in children diagnosed with diabetes mellitus type 1 before puberty.

    Science.gov (United States)

    Pereira, K C X; Pugliese, B S; Guimarães, M M; Gama, M P

    2015-02-01

    To investigate an association between pubertal development and timing of menarche with glycemic control, disease duration, and body mass index (BMI) in patients diagnosed with diabetes mellitus type 1 (DM1) before puberty. Retrospective study. The study was performed at the diabetes outpatient clinic of Instituto de Puericultura e Pediatria Martagão Gesteira--IPPMG of the Federal University of Rio de Janeiro--UFRJ. A total of 131 children, 61 girls and 70 boys, diagnosed with DM1 before puberty participated in the study. The study investigated how age at puberty onset relates to mean glycated hemoglobin (HbA1c) before puberty, BMI percentile, and disease duration; how puberty duration relates to mean HbA1c before and during puberty and to disease duration; and how timing of menarche relates to mean HbA1c before puberty, BMI percentile, and disease duration. Age at puberty onset was positively correlated with mean HbA1c before puberty (r = 0.204, R(2) = 0.042; P = .019) and disease duration (r = 0.451, R(2) = 0.203; P puberty later than those diagnosed more recently. Girls in higher BMI percentiles reached menarche sooner.

  13. Ontogenic studies of the neural control of adenohypophyseal hormones in the rat. II. Prolactin.

    Science.gov (United States)

    Becú-Villalobos, D; Lacau-Mengido, I M; Díaz-Torga, G S; Libertun, C

    1992-02-01

    1. Serum prolactin levels are low during the first 20 days of life and gradually increase toward puberty, in both male and female rats. 2. There is an age-related increase in the cell population engaged in prolactin secretion, as well as an increase in the synthesis of prolactin and of the amount of prolactin secreted from individual lactotropes. 3. The gradual increase in prolactin levels in the third week of life is not related to a decrease in dopaminergic inhibition but to an increase in the efficiency of prolactin releasing factors such as estrogen, serotonin, opiates, and posterior pituitary extracts. 4. Prolactin release induced by physiological factors, such as stress, cervical stimulation, or the expression of spontaneous diurnal and nocturnal surges, requires maturational events within the hypothalamic-pituitary axis which are evident at the end of the third week of life. 5. In the female rat the steadily increasing levels of prolactin are involved in the timing of puberty eclosion acting at the ovary and at the brain. 6. In the prepubertal male rat increasing titers of prolactin may be involved in testicular and accessory organ development and may facilitate the actions of luteinizing hormone, follicle stimulating hormone, and testosterone on male sexual organs.

  14. Normal female puberty in a developmental perspective

    DEFF Research Database (Denmark)

    Bourguignon, Jean-Pierre; Juul, Anders

    2012-01-01

    Puberty is unique in the sense that its onset shows an extraordinary individual variability of about 5 years, the basis of which being still elusive despite research efforts to understand the reason why. Continuing changes in environmental influences and interaction with genetic determinants...... with less obvious changes in menarcheal age. Conceptually, puberty and subsequent reproduction appear now to be influenced by conditions not only at the time when they occur, but also during fetal and perinatal life. In addition, these influences can be apparently opposing since early maturation follows...... fetal malnourishment and postnatal overfeeding. In this review, the semiology and pathophysiology of puberty are discussed in a lifelong developmental perspective....

  15. Circulating MKRN3 Levels Decline During Puberty in Healthy Boys.

    Science.gov (United States)

    Busch, Alexander S; Hagen, Casper P; Almstrup, Kristian; Juul, Anders

    2016-06-01

    Initiation and progression of puberty requires concerted action of hypothalamic activating and inhibiting factors. Recently, cases of familial central precocious puberty have been linked to loss-of-function mutations of makorin RING-finger protein 3 (MKRN3) indicating a pivotal inhibitory role of the protein on GnRH secretion. To investigate peripubertal circulating MKRN3 levels in healthy boys. Population-based longitudinal study in healthy Danish boys. General community. Healthy boys (n = 60) aged (median [range]) 9.3 (5.8-11.8) years at baseline followed for 6.0 (0.5-7.6) years (2006-2014) with blood sampling every 6 months. None. Serum levels of MKRN3: 623 samples, median (range) 12 (2-14) per boy. MKRN3 levels declined before onset of puberty; the geometric mean (95% confidence interval) 5 years before onset of puberty vs last visit before onset of puberty was 216 (169-272) pg/mL vs 128 (118-139) pg/mL (P puberty progressed. MKRN3 levels were not associated with age at onset of puberty. Declining MKRN3 before pubertal onset support MKRN3 as an inhibitor of GnRH secretion during midchildhood.

  16. [Age of puberty and western young women sexuality].

    Science.gov (United States)

    Tresch, C; Ohl, J

    2015-02-01

    The onset of menarche and age of first sexual experience have both lowered over the past century. Does the age of puberty influence the sexuality of the girl/young occidental woman? If so, to what degree? Besides, is the acquisition of reproductive function, regardless of age, a sign of sufficient maturity to engage in sexual activity? Studies show that early puberty, early sex, unprotected sexual intercourse in adolescence and number of sexual partners in early adulthood are closely related. These early sexual experiences could be stimulated by early drug use as well as by depressive disorders. The age of puberty has a real influence on sexuality but this link will be modulated by a number of social behavioral factors and it is not sustainable. The age of puberty is not a good indicator of maturity for teenage sexuality; early maturation and early sexual activity are usually associated with risky behaviors. However, other studies on the subject are required, including a consideration of the issues associated with delayed puberty, a subject virtually absent from the literature. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  17. Relative importance of prenatal and postnatal androgen action in determining growth of the penis and anogenital distance in the rat before, during and after puberty.

    Science.gov (United States)

    van den Driesche, S; Scott, H M; MacLeod, D J; Fisken, M; Walker, M; Sharpe, R M

    2011-12-01

    Experimental animal studies show that measurement of anogenital distance (AGD) and/or penis length may provide lifelong 'read-outs' of foetal androgen exposure during the masculinization programming window (MPW). However, variation in postnatal androgen exposure may complicate interpretation of such measurements. This is important to clarify if such measurements are to be applied to humans. The present aim was to evaluate effects of prenatal and/or postnatal manipulation of androgen production/action on growth of AGD and the penis in rats. Pregnant rats were treated daily before (e13.5-e21.5) and after birth (postnatal days 1-15) with either vehicle, 500 mg/kg di(n-butyl) phthalate (DBP) or 100 mg/kg flutamide (postnatal only) in prenatal + postnatal treatment combinations (N = 6 treatment combinations); DBP impairs androgen production whereas flutamide impairs androgen action. Male offspring were killed on postnatal day 8 (prepuberty), 25 (early puberty) or 90 (adulthood) when AGD was measured, the penis dissected out and its weight and length measured; plasma testosterone and ventral prostate weight were measured at day 90 to assess endogenous androgen exposure. In controls, penis length, girth and AGD increased 2.2-, 5.3-and 5.9-fold respectively from day 8 to day 90. Significant inhibition of penis growth and final length and girth was induced by treatments that inhibited postnatal androgen action. Conversely, growth and ultimate (adult) AGD was inhibited by prenatal inhibition of androgen production whereas postnatal androgen inhibition had negligible effect. Nevertheless, AGD and penis length were highly correlated at every age (R(2) > 0.33; p penis size reflects both prenatal + postnatal androgen exposure. At the group treatment level, prepubertal measurement of either AGD or penis size accurately predicts their size in adulthood. © 2011 The Authors. International Journal of Andrology © 2011 European Academy of Andrology.

  18. Copper Induces Vasorelaxation and Antagonizes Noradrenaline -Induced Vasoconstriction in Rat Mesenteric Artery

    Directory of Open Access Journals (Sweden)

    Yu-Chun Wang

    2013-11-01

    Full Text Available Background/Aims: Copper is an essential trace element for normal cellular function and contributes to critical physiological or pathological processes. The aim of the study was to investigate the effects of copper on vascular tone of rat mesenteric artery and compare the effects of copper on noradrenaline (NA and high K+ induced vasoconstriction. Methods: The rat mesenteric arteries were isolated and the vessel tone was measured by using multi wire myograph system in vitro. Blood pressure of carotid artery in rabbits was measured by using physiological data acquisition and analysis system in vivo. Results: Copper dose-dependently blunted NA-induced vasoconstriction of rat mesenteric artery. Copper-induced vasorelaxation was inhibited when the vessels were pretreated with NG-nitro-L-arginine methyl ester (L-NAME. Copper did not blunt high K+-induced vasoconstriction. Copper preincubation inhibited NA-evoked vasoconstriction and the inhibition was not affected by the presence of L-NAME. Copper preincubation showed no effect on high K+-evoked vasoconstriction. Copper chelator diethyldithiocarbamate trihydrate (DTC antagonized the vasoactivity induced by copper in rat mesenteric artery. In vivo experiments showed that copper injection (iv significantly decreased blood pressure of rabbits and NA or DTC injection (iv did not rescue the copper-induced hypotension and animal death. Conclusion: Copper blunted NA but not high K+-induced vasoconstriction of rat mesenteric artery. The acute effect of copper on NA-induced vasoconstriction was depended on nitric oxide (NO, but the effect of copper pretreatment on NA-induced vasoconstriction was independed on NO, suggesting that copper affected NA-induced vasoconstriction by two distinct mechanisms.

  19. The physiology and timing of male puberty

    DEFF Research Database (Denmark)

    Tinggaard, Jeanette; Mieritz, Mikkel Grunnet; Sørensen, Kaspar

    2012-01-01

    To describe available markers of male puberty, discuss associations between adiposity and pubertal timing and to review recent evidence of a possible secular trend in male pubertal timing.......To describe available markers of male puberty, discuss associations between adiposity and pubertal timing and to review recent evidence of a possible secular trend in male pubertal timing....

  20. Pubertal dependent effects of cadmium on episodic prolactin secretion in male rats

    Energy Technology Data Exchange (ETDEWEB)

    Lafuente, A.; Alvarez-Demanuel, E.; Marquez, N. [Fac. de Cienicas, Orense (Spain). Lab. de Toxicologia; Esquifino, A.I. [Dept. Bioquimica, Facultad de Medicina, Universidad Complutense, 28040-Madrid (Spain)

    1999-02-01

    This work was undertaken to assess if exposure to cadmium related to puberty may affect the episodic pattern of prolactin. Male rats were submitted to cadmium exposure, from day 30 to 60 or from day 60 to 90 of life respectively, at a dose of 50 ppm in the drinking water. Control age-matched rats received cadmium-free water. Prepubertal cadmium administration decreased mean serum prolactin levels and the absolute amplitude of the prolactin pulses. Subchronic exposure to cadmium of adult rats decreased mean serum prolactin levels, the absolute amplitude of the prolactin pulses and their duration, and the mean half-life of the hormone. These results suggest that subchronic cadmium exposure changes the secretory pattern of prolactin in adult male rats in a puberty-dependent way. (orig.) With 1 fig., 1 tab., 37 refs.

  1. Puberty in boys

    Science.gov (United States)

    Your body makes hormones to get puberty started. Here are some changes you will start seeing. You will: See your testicles and penis get bigger. Grow body hair. You may grow hair on your face around your upper lip, cheeks, and chin. You may see ...

  2. Premature pubarche before one year of age: distinguishing between mini-puberty variants and precocious puberty.

    Science.gov (United States)

    Bourayou, Rafik; Giabicani, Eloïse; Pouillot, Monique; Brailly-Tabard, Sylvie; Brauner, Raja

    2015-04-02

    The aim of this study was to facilitate the distinction between the benign "mini-puberty of early infancy" and precocious puberty (PP). We compared 59 patients (21 boys and 38 girls) seen for pubic hair development before one year of age diagnosed as mini-puberty to 13 patients (2 boys) in whom pubertal development before one year revealed a PP. The boys with mini-puberty presented with pubic hair development and prepubertal testicular volume, with low plasma testosterone concentrations. Their gonadotropin responses to gonadotropin releasing hormone (GnRH) test showed predominant luteinising hormone increase in 9/13. The girls presented with pubic hair development that was accompanied by breast development in 47% of cases, with low plasma estradiol concentrations. Their gonadotropin responses showed predominant follicle-stimulating hormone increase in the 17 evaluated. The patients with PP had organic central PP (5 hypothalamic hamartoma) or idiopathic central PP (n=6), or peripheral PP (one ovarian tumor and one congenital adrenal hyperplasia). The diagnosis was challenging only in 3 girls with idiopathic central PP presenting with prepubertal plasma estradiol concentrations and responses to GnRH test. The diagnosis of PP was easily determined based on the clinical presentation and the pubertal concentrations of testosterone in boys or of estradiol in girls, as was the diagnosis of central or peripheral origin of PP based on gonadotropin response to the GnRH test. Once PP is excluded, these patients need careful follow-up and physician consultation is needed if clinical pubertal signs progress.

  3. Lipopolysaccharide-induced acute renal failure in conscious rats

    DEFF Research Database (Denmark)

    Jonassen, Thomas E N; Graebe, Martin; Promeneur, Dominique

    2002-01-01

    In conscious, chronically instrumented rats we examined 1) renal tubular functional changes involved in lipopolysaccharide (LPS)-induced acute renal failure; 2) the effects of LPS on the expression of selected renal tubular water and sodium transporters; and 3) effects of milrinone......-alpha and lactate, inhibited the LPS-induced tachycardia, and exacerbated the acute LPS-induced fall in GFR. Furthermore, Ro-20-1724-treated rats were unable to maintain MAP. We conclude 1) PDE3 or PDE4 inhibition exacerbates LPS-induced renal failure in conscious rats; and 2) LPS treated rats develop an escape......, a phosphodiesterase type 3 (PDE3) inhibitor, and Ro-20-1724, a PDE4 inhibitor, on LPS-induced changes in renal function. Intravenous infusion of LPS (4 mg/kg b.wt. over 1 h) caused an immediate decrease in glomerular filtration rate (GFR) and proximal tubular outflow without changes in mean arterial pressure (MAP...

  4. Sertoli cell specific knockdown of RAR-related orphan receptor (ROR) alpha at puberty reduces sperm count in rats.

    Science.gov (United States)

    Mandal, Kamal; Sarkar, Rajesh K; Sen Sharma, Souvik; Jain, Ayushi; Majumdar, Subeer S

    2018-01-30

    Globally, there is an alarming decline in sperm count. Very often hormonal supplementation fails to restore normal sperm count. Sertoli cells (Sc) present within seminiferous tubules provide appropriate niche and factors required for the differentiation of germ cells (Gc) into mature sperm (spermatogenesis). Functionally compromised Sc may be one of the reasons for failure of hormones to facilitate normal spermatogenesis. Although role of secretory proteins and signaling molecules of Sc has been studied well, role of transcription factors regulating sperm count has not been addressed appropriately. Retinoic acid receptor-related orphan receptor (ROR)-alpha is one of such transcription factors reported in testis but its role in testicular function is not yet known. In a separate study, we found abundant ROR-alpha binding sites on promoter regions of several genes upregulated in pubertal rat Sc as compared to infant Sc. Immunostaining studies also revealed presence of ROR alpha in nucleus of pubertal Sc. We generated a transgenic knockdown rat model expressing shRNA targeted to ROR-alpha under Sc specific promoter, which is transcriptionally active only at and after puberty. ROR-alpha knockdown animals were found to have abnormal association of Sc and Gc, including Gc sloughing and restricted release of sperm. The knockdown animals displayed compromised spermatogenesis leading to significant reduction in sperm count. This is the first report describing the Sc specific role of ROR-alpha in maintaining quantitatively normal sperm output. Identification of various such molecules can generate avenues to limit or reverse an alarmingly declining sperm count witnessed globally in men. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Supplementation of fenugreek leaves lower lipid profile in streptozotocin-induced diabetic rats.

    Science.gov (United States)

    Annida, B; Stanely Mainzen Prince, P

    2004-01-01

    The present study was undertaken to evaluate the lipid-lowering effect of fenugreek leaves in diabetes mellitus. Albino Wistar rats were randomly divided into six groups: normal untreated rats; streptozotocin (STZ)-induced diabetic rats; STZ-induced rats + fenugreek leaves (0.5 g/kg of body weight); STZ-induced rats + fenugreek leaves (1 g/kg of body weight); STZ-induced rats + glibenclamide (600 microg/kg of body weight); and STZ-induced rats + insulin (6 units/kg of body weight). Rats were made diabetic by STZ (40 mg/kg) injected intraperitoneally. Fenugreek leaves were supplemented in the diet daily to diabetic rats for 45 days, and food intake was recorded daily. Blood glucose, total cholesterol, triglycerides, and free fatty acids were determined in serum, liver, heart, and kidney. Our results show that blood glucose and serum and tissue lipids were elevated in STZ-induced diabetic rats. Supplementation of fenugreek leaves lowered the lipid profile in STZ-induced diabetic rats.

  6. Air puff-induced 22-kHz calls in F344 rats.

    Science.gov (United States)

    Inagaki, Hideaki; Sato, Jun

    2016-03-01

    Air puff-induced ultrasonic vocalizations in adult rats, termed "22-kHz calls," have been applied as a useful animal model to develop psychoneurological and psychopharmacological studies focusing on human aversive affective disorders. To date, all previous studies on air puff-induced 22-kHz calls have used outbred rats. Furthermore, newly developed gene targeting technologies, which are essential for further advancement of biomedical experiments using air puff-induced 22-kHz calls, have enabled the production of genetically modified rats using inbred rat strains. Therefore, we considered it necessary to assess air puff-induced 22-kHz calls in inbred rats. In this study, we assessed differences in air puff-induced 22-kHz calls between inbred F344 rats and outbred Wistar rats. Male F344 rats displayed similar total (summed) duration of air puff-induced 22 kHz vocalizations to that of male Wistar rats, however, Wistar rats emitted fewer calls of longer duration, while F344 rats emitted higher number of vocalizations of shorter duration. Additionally, female F344 rats emitted fewer air puff-induced 22-kHz calls than did males, thus confirming the existence of a sex difference that was previously reported for outbred Wistar rats. The results of this study could confirm the reliability of air puff stimulus for induction of a similar amount of emissions of 22-kHz calls in different rat strains, enabling the use of air puff-induced 22-kHz calls in inbred F344 rats and derived genetically modified animals in future studies concerning human aversive affective disorders. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Impact of Puberty Health Education on Anxiety of Adolescents

    Directory of Open Access Journals (Sweden)

    Hoda Mokari

    2016-05-01

    Full Text Available Adolescents, as a large group in the world, face many physical changes and psychological evolutions in their puberty period. If enough attention is not paid to such changes, negative effects on their health and knowledge may be induced. Thus, it is very important to hold health education approperiate for their needs using new educational methods and confident sources. The main goal of this study is to explore the impact of puberty health education on the anxiety of girls. Itis a quasi-experimental study using clustered sampling which was done on 159 girls from two high schools in Tehran divided into two experimental (N=86 and control (N=73 groups. Then,using a systematic educational plan revised by the researcher and expert panel from Department of Midwifery, all the students and their parents in the experimental group were instructed. Data were gathered by demographic questionnaire and Spielberger Scale. Questionnaires were completed by students in three phases including before, after, and three months after the end of the educational program. Data analysis was performed by paired t-test, independent t-test, Chi square, and multivariate tests. Mean anxiety scores in the experimental and control groups were 90.45 and 85.36 before the education, 78.79 and 85.49 at the end of the education, and 78.46 as well as 87.33 3 months later, respectively.Anxiety scores were statistically different post-intervention (p<0.001 and three months later(p<0.001. Puberty health education programs could reduce anxiety in female adolescents.

  8. Pubertal neurocranium growth in thymectomized rats.

    Science.gov (United States)

    Rino, W; Teixeira, D

    1979-01-01

    Differences in neurocranium growth at puberty were studied in rats of both sexes thymectomized and sham-thymectomized at 2, 4, 6, 8, 10, 12 and 14 days of age and in controls of matched age and sex; skull length, width and height, and skull base length and face length were measured. The neurocranium of the thymectomized rats was significantly smaller than that of the sham-thymectomized and control rats of both sexes and in all age-groups.

  9. Effects of Sex Steroids on the Spinal Gastrin-Releasing Peptide System Controlling Male Sexual Function in Rats.

    Science.gov (United States)

    Oti, Takumi; Takanami, Keiko; Ito, Saya; Ueda, Takashi; Matsuda, Ken Ichi; Kawata, Mitsuhiro; Soh, Jintetsu; Ukimura, Osamu; Sakamoto, Tatsuya; Sakamoto, Hirotaka

    2018-04-01

    The gastrin-releasing peptide (GRP) system in the lumbosacral spinal cord controls male sexual function in rats. In contrast, in female rats, GRP neurons could scarcely be detected around puberty when circulating ovarian steroid hormones such as estradiol and progesterone levels are increasing. However, little information is available on feminizing or demasculinizing effects of ovarian steroids on the central nervous system in female puberty and adulthood. In this study, to visualize the spinal GRP neurons in vivo, we generated a GRP-promoter-Venus transgenic (Tg) rat line and studied the effects of the sex steroid hormones on GRP expression in the rat lumbar cord by examining the Venus fluorescence. In these Tg rats, the sexually dimorphic spinal GRP neurons controlling male sexual function were clearly labeled with Venus fluorescence. As expected, Venus fluorescence in the male lumbar cord was markedly decreased after castration and restored by chronic androgen replacement. Furthermore, androgen-induced Venus expression in the spinal cord of adult Tg males was significantly attenuated by chronic treatment with progesterone but not with estradiol. A luciferase assay using a human GRP-promoter construct showed that androgens enhance the spinal GRP system, and more strikingly, that progesterone acts to inhibit the GRP system via an androgen receptor-mediated mechanism. These results demonstrate that circulating androgens may play an important role in the spinal GRP system controlling male sexual function not only in rats but also in humans and that progesterone could be an important feminizing factor in the spinal GRP system in females during pubertal development.

  10. Role of basal and provocative serum prolactin in differentiating idiopathic hypogonadotropic hypogonadism and constitutional delayed puberty--a diagnostic dilemma.

    Science.gov (United States)

    Ali, Liaqat; Adeel, Afrose

    2012-01-01

    The prevalence of Idiopathic Hypogonadotropic Hypogonadism (IHH) is approximately 1 in 10,000 men. Objectives of this study were to evaluate the role of basal and stimulated serum prolactin in differentiating Constitutional Delayed Puberty (CDP) from IHH. This cross-sectional study was carried out at the Department of Diabetes and Endocrinology, Military Hospital, Rawalpindi. A total of 20 male patients presenting with provisional diagnosis of IHH/CDP were enrolled in the study. Patients with known diseases were excluded from the study. Baseline FSH, LH, testosterone, and prolactin were estimated and the patients were subjected to provocative prolactin stimulation by Thyrotropin releasing hormone stimulation (TRH) test and chlorpromazine challenge. At each 6 monthly follow-up visit for 4 years, the patients were evaluated for adrenarche, pubarche and other secondary sexual characters. Tanner scale was taken as standards for comparing stage of puberty at a particular age. No treatment was given to both groups for 2 years. At the end of 2 years IHH patients with failed puberty or progression of puberty and CDP who lagged behind by more than 2 years by Tanner scale or 4 years per bone age with compelling psychosocial or psychosexual reasons at school or at home were given short courses of 50 mg injection testosterone in an attempt to expedite the onset or progression of puberty. Patients from either group with failed puberty after low dose testosterone were managed with high dose testosterone therapy to induce secondary sexual characters. Twenty patients enrolled in the study were provisionally divided into 2 groups called IHH (n = 9), and CDP (n = 11) based on high basal and provocative serum prolactin levels in CDP group. Two patients from CDP group were lost in the follow-up leaving 9 patients in each group. A total of 10 (56%) patients, 3 (17%) from IHH group and 7 (39%) from CDP group achieved grade 4 puberty without any treatment. Remaining 8 (44%) patients, 6

  11. Strain and sex differences in puberty onset and the effects of THC administration on weight gain and brain volumes.

    Science.gov (United States)

    Keeley, R J; Trow, J; McDonald, R J

    2015-10-01

    The use of recreational marijuana is widespread and frequently begins and persists through adolescence. Some research has shown negative consequences of adolescent marijuana use, but this is not seen across studies, and certain factors, like genetic background and sex, may influence the results. It is critical to identify which characteristics predispose an individual to be susceptible to the negative consequences of chronic exposure to marijuana in adolescence on brain health and behavior. To this end, using males and females of two strains of rats, Long-Evans hooded (LER) and Wistar (WR) rats, we explored whether these anatomically and behaviorally dimorphic strains demonstrated differences in puberty onset and strain-specific effects of adolescent exposure to Δ9-tetrahydrocannabinol (THC), the main psychoactive component of marijuana. Daily 5 mg/kg treatment began on the day of puberty onset and continued for 14 days. Of particular interest were metrics of growth and volumetric estimates of brain areas involved in cognition that contain high densities of cannabinoid receptors, including the hippocampus and its subregions, the amygdala, and the frontal cortex. Brain volumetrics were analyzed immediately following the treatment period. LER and WR females started puberty at different ages, but no strain differences were observed in brain volumes. THC decreased weight gain throughout the treatment period for all groups. Only the hippocampus and some of its subregions were affected by THC, and increased volumes with THC administration was observed exclusively in females, regardless of strain. Long-term treatment of THC did not affect all individuals equally, and females displayed evidence of increased sensitivity to the effects of THC, and by extension, marijuana. Identifying differences in adolescent physiology of WR and LER rats could help determine the cause for strain and sex differences in brain and behavior of adults and help to refine the use of animal models

  12. Control of the onset of puberty.

    Science.gov (United States)

    Livadas, Sarantis; Chrousos, George P

    2016-08-01

    The mechanism of puberty initiation remains an enigma, despite extensive research in the field. Pulsatile pituitary gonadotropin secretion under the guidance of hypothalamic gonadotropin-releasing hormone (GnRH) constitutes a sine qua non for pubertal onset. In turn, the secretion of GnRH in the human hypothalamus is regulated by kisspeptin and its receptor as well as by permissive or opposing signals mediated by neurokinin B and dynorphin acting on their respective receptors. These three supra-GnRH regulators compose the Kisspeptin, Neurokinin B and Dynorhin neurons (KNDy) system, a key player in pubertal onset and progression. The recent discovery that makorin ring finger protein 3 is also involved in puberty initiation provided further insights into the regulation of the KNDy pathway. In fact, the inhibitory (γ-amino butyric acid, neuropeptide Y, and RFamide-related peptide-3) and stimulatory signals (glutamate) acting upstream of KNDy called into question the role of makorin ring finger protein 3 as the gatekeeper of puberty. Meanwhile, the findings that 'neuroestradiol' produced locally and endocrine disruptors from the environment may influence GnRH secretion is intriguing. Finally, epigenetic mechanisms have been implicated in pubertal onset through recently discovered mechanisms. The exact molecular machinery underlying puberty initiation in humans is under intensive investigation. In this review, we summarize research evidence in the field, while emphasizing the areas of uncertainty and underlining the impact of current information on the evolving theory regarding this fascinating phenomenon.

  13. Precocious Puberty (For Parents)

    Science.gov (United States)

    ... spurt" start of menstruation (her period) acne "mature" body odor In boys, the signs of precocious puberty before ... growth — a growth "spurt" voice deepening acne "mature" body odor Many kids who show some of the early ...

  14. Back pain reporting in young girls appears to be puberty-related

    Directory of Open Access Journals (Sweden)

    Froberg Karsten

    2005-11-01

    Full Text Available Abstract Background There is a large increase in back pain reporting in the early teens. In no previous study has the prevalence of low back pain been investigated in relation to the onset of puberty. The objective of this study was to establish whether the onset of puberty is associated with back pain reporting in young girls. Methods A subsample of 254 girls aged 8–10 years and 165 girls aged 14–16 years from a cross-sectional survey of 481 children aged 8–10 years and 325 adolescents aged 14–16 years of both sexes. Main outcome measures were back pain defined as low back pain, mid back pain, and/or neck pain in the past month. Other variables of interest were Puberty (five different stages, age, body mass index, and smoking. Independent information on onset of puberty was obtained through a physical examination and on back pain through an individual structured interview. The association was studied between onset of puberty and the outcome variable (the one month period prevalence of back pain, controlling for overweight, and smoking. Odds ratios with 95% confidence intervals were used to describe bivariate associations, logistic regression with robust standard errors was used for multivariate analyses. Results There is a highly significant trend for increased back pain reporting with increasing level of puberty until maturity is reached. The biggest leap appears between the second level (beginning of puberty and the third level (mid puberty and the findings remain after controlling for the covariates. These results emanate from the low back, whereas pain in the mid back and neck do not seem to be linked with pubertal stage. Conclusion In girls, the reporting of low back pain increases in frequency during puberty until maturity, regardless of age. Why some girls are susceptible to back pain in the early stage of puberty is unknown.

  15. Trends in puberty timing in humans and environmental modifiers

    DEFF Research Database (Denmark)

    Toppari, Jorma; Juul, Anders

    2010-01-01

    Secular trends in timing of puberty appear to continue although under-nutrition has not been any longer a limiting factor for pubertal development. Now obesity and other environmental reasons have been suspected to cause this trend, and endocrine disrupting chemicals have become into focus...... as possible contributors. Epidemiological studies on endocrine disrupters are still scarce and show only weak associations between exposures and timing of puberty. Since genetic background explains 50-80% of variability in the timing of puberty, it is not surprising that the observed environmental effects...

  16. Delayed puberty and hypogonadotropic hypogonadism. Differential diagnosis and treatment

    NARCIS (Netherlands)

    Snoep, Marinus Cornelis

    1978-01-01

    This thesis describes a method enabling a prospecrive differential diagnosis to be made berween delayed puberty (DP) and hypogonadotropic hypogonadism (HH). The influence of androgen administration on the gonadal feedback sysrem of patients with delayed puberty was also studied. ... Zie: Summary

  17. Early Female Puberty: A Review of Research on Etiology and Implications

    Science.gov (United States)

    Daniel, Eileen; Balog, Linda F.

    2009-01-01

    The age of female puberty appears to have decreased in the United States and western countries as child health and nutrition have improved and obesity has become more prevalent. Also, environmental contaminants, particularly endocrine disruptors, may also play a role in lowering the age of puberty. Puberty at an early age increases the risk of…

  18. [Neuroendocrine mechanisms of puberty onset].

    Science.gov (United States)

    Teinturier, C

    2002-10-01

    An increase in pulsatile release of GnRH is essential for the onset of puberty. However, the mechanism controlling the pubertal increase in GnRH release is still unclear. The GnRH neurosecretory system is already active during the neonatal period but subsequently enters a dormant state by central inhibition in the juvenile period. When this central inhibition is removed or diminished, an increase in GnRH release occurs with increase in synthesis and release of gonadotropins and gonadal steroids, followed by the appearance of secondary sexual characteristics. Recent studies suggest that disinhibition of GnRH neurons from GABA (gamma-aminobutyric acid) appears to be a critical factor in female rhesus monkey. After central inhibition is removed, increases in stimulatory input from glutamatergic neurons as well as new stimulatory input from norepinephrine and NPY neurons and inhibitory input from beta endorphin neurons appear to control pulsatile GnRH release as well as gonadal steroids. Nonetheless, the most important question still remains: what determines the timing to remove central inhibition? Because many genes are turned on or turned off to establish a complex series of events occurring during puberty, the timing of puberty must be regulated by a master gene or genes, as a part of developmental events.

  19. Etiology of precocious puberty, 10 years study in Endocrine Reserch Centre (Firouzgar, Tehran

    Directory of Open Access Journals (Sweden)

    Fatemeh Safari

    2012-01-01

    Full Text Available Background: Precocious puberty, as early physical development and low final height might lead to psychosocial problems.Objective: To evaluate etiology and clinical feature of precocious puberty in a cohort of Iranian children.Materials and Methods: In this case-series study, 44 girls and 8 boys with precocious puberty referred to Endocrine Reserch Centre (Firouzgar, Institute of Endocrinology and Metabolism (Hemmat Campus, were examined in a 10 years period of time. Results: Mean age of girls and boys was 7.43±1.4 years and 5.8±2.1 years respectively. Most of the patients fell within the age category of 7-7.9 years old (40.9% for girls and 50% for boys. Patients, concerning etiology of precocious puberty were classified in three categories: 42.6% of patients had central precocious puberty (CPP, including idiopathic CPP (87.5% and neurogenic CPP (12.5%. 23.3% of patients had peripheral precocious puberty (PPP, including congenital adrenal hyperplasia (CAH (42.8%, ovarian cysts (28.4%, McCune-Albright syndrome (14.2% and adrenal carcinoma (14.2%. 34.1% of girls and 25% of boys had normal variant puberty including premature thelarche (57%, premature adrenarche (38% as well as premature menarche (4.7%l. Conclusion: The most common etiology of precocious puberty in girls was idiopathic central precocious puberty and premature thelarche, while in boys they were neurogenic central precocious puberty and CAH. Therefore precocious puberty in girls is usually benign. In boys, CNS anomalies should first be considered in the differential diagnosis of CPP. Therefore brain Magnetic Resonance Imaging (MRI is mandatory in all cases.

  20. Chlorella vulgaris triggers apoptosis in hepatocarcinogenesis-induced rats*

    Science.gov (United States)

    Mohd Azamai, Emey Suhana; Sulaiman, Suhaniza; Mohd Habib, Shafina Hanim; Looi, Mee Lee; Das, Srijit; Abdul Hamid, Nor Aini; Wan Ngah, Wan Zurinah; Mohd Yusof, Yasmin Anum

    2009-01-01

    Chlorella vulgaris (CV) has been reported to have antioxidant and anticancer properties. We evaluated the effect of CV on apoptotic regulator protein expression in liver cancer-induced rats. Male Wistar rats (200~250 g) were divided into eight groups: control group (normal diet), CDE group (choline deficient diet supplemented with ethionine in drinking water to induce hepatocarcinogenesis), CV groups with three different doses of CV (50, 150, and 300 mg/kg body weight), and CDE groups treated with different doses of CV (50, 150, and 300 mg/kg body weight). Rats were sacrificed at various weeks and liver tissues were embedded in paraffin blocks for immunohistochemistry studies. CV, at increasing doses, decreased the expression of anti-apoptotic protein, Bcl-2, but increased the expression of pro-apoptotic protein, caspase 8, in CDE rats, which was correlated with decreased hepatoctyes proliferation and increased apoptosis as determined by bromodeoxy-uridine (BrdU) labeling and terminal deoxynucleotidyl transferase mediated dUTP nick-end labeling (TUNEL) assay, respectively. Our study shows that CV has definite chemopreventive effect by inducing apoptosis via decreasing the expression of Bcl-2 and increasing the expression of caspase 8 in hepatocarcinogenesis-induced rats. PMID:19198018

  1. Physalis minima Leaves Extract Induces Re-Endothelialization in Deoxycorticosterone Acetate-Salt-Induced Endothelial Dysfunction in Rats

    Directory of Open Access Journals (Sweden)

    Dian Nugrahenny

    2018-02-01

    Full Text Available The administration of deoxy-corticosterone acetate (DOCA-salt can induce oxidative stress leading to decrease the bioavailability of nitric oxide (NO, increase senescence of circulating endothelial progenitor cells (EPCs, thus contributing to endothelial dysfunction. This study was aimed to investigate the effects of Physalis minima L. leaves extract on serum NO levels, circulating EPCs number, and histopathology of tail artery endothelial cells in DOCA-salt-induced endothelial dysfunction in rats. Twenty-five male Wistar rats were randomly divided into five groups: rats without any treatment (normal, rats treated with DOCA (10 mg/kgBW s.c. twice weekly and given 0.9% NaCl to drink ad libitum for 6 weeks, and DOCA-salt-induced rats orally supplemented with P. minima leaves extract at doses of 500, 1500, or 2500 mg/kgBW for 4 weeks. Serum NO levels were measured by colorimetry. The number of circulating EPCs (CD34+/CD133+ cells was determined by flow cytometry. The tail artery sections were histologically processed with hematoxylin-eosin staining. DOCA-salt-induced rats showed significantly (p<0.05 decrease in serum NO levels and circulating EPCs number compared to the normal. There was also more detached tail artery endothelial cells in DOCA-salt-induced rats. P. minima leaves extract at a dose of 500 mg/kgBW significantly (p<0.05 increased serum NO level and circulating EPCs number, and also induced an optimal re-endothelialization in DOCA-salt-induced rats. P. minima leave extract dose-dependently increases NO bioavailability contributing to enhanced EPCs mobilization, thereby promoting re-endothelialization in DOCA-salt-induced endothelial dysfunction in rats.

  2. MRI study of pituitary in girls with central precocious puberty

    International Nuclear Information System (INIS)

    Ye Zhiqiu; Guo Qinglu; Feng Changzheng; Wei Beiyang; Liu Yongxi; Zhang Yan

    2008-01-01

    Objective: To study the shape, size and signal intensity of pituitary gland in girls aged 3-10 year old with central precocious puberty. Methods: MRI data of pituitary glands in 40 girls aged 3-10 years old with central precocious puberty were selected. The shape, height and the appearances of pituitary glands were measured and observed on sagittal T 1 WI. Results: Quantitative data about size, shape and single intensity changes of pituitary glands in central precocious puberty were obtained in two groups, including girls aged from 3-5 and 5-10. The convex pituitary gland were 85.0% in former group. The height of pituitary gland were 6.1±0.2mm (former group) and 6.4± 0.4mm (latter one) respectively. The width of pituitary stalk was 1.93±0.50mm. The posterior pituitary gland demonstrated high signal intensity in all cases. Conclusion: Obvious changes of the size and shape of pituitary glands were found in central precocious puberty of girls aged from 3-10. The pituitary glands manifested physiologic hypertrophy with more convex in central precocious puberty girls than in normal ones. The changes on MRI could reflect the function of hypothalamus-pituitary-gonadal axis. It is of important value and significance in the diagnosis of central precocious puberty. (authors)

  3. BMI change during puberty and the risk of heart failure.

    Science.gov (United States)

    Kindblom, J M; Bygdell, M; Sondén, A; Célind, J; Rosengren, A; Ohlsson, C

    2018-03-12

    Hospitalization for heart failure amongst younger men has increased. The reason for this is unknown but it coincides with the obesity epidemic. The aim of this study was to evaluate the association between childhood BMI (Body Mass Index) and BMI change during puberty for risk of adult heart failure in men. Using the BMI Epidemiology Study (BEST), a population-based study in Gothenburg, Sweden, we collected information on childhood BMI at age 8 years and BMI change during puberty (BMI at age 20 - BMI at 8) for men born 1945-1961, followed until December 2013 (n = 37 670). BMI was collected from paediatric growth charts and mandatory military conscription tests. Information on heart failure was retrieved from high-quality national registers (342 first hospitalizations for heart failure). BMI change during puberty was independently of childhood BMI associated with risk of heart failure in a nonlinear J-shaped manner. Subjects in the upper quartile of BMI change during puberty (Q4) had more than twofold increased risk of heart failure compared with subjects in Q1 [HR (Hazard Ratio) = 2.29, 95% CI (Confidence Interval) 1.68-3.12]. Childhood BMI was not independently associated with risk of heart failure. Boys developing overweight during puberty (HR 3.14; 95% CI 2.25-4.38) but not boys with childhood overweight that normalized during puberty (HR 1.12, 95% CI 0.63-2.00) had increased risk of heart failure compared with boys without childhood or young adult overweight. BMI change during puberty is a novel risk factor for adult heart failure in men. © 2018 The Association for the Publication of the Journal of Internal Medicine.

  4. Transition in endocrinology: induction of puberty.

    Science.gov (United States)

    Dunkel, Leo; Quinton, Richard

    2014-06-01

    Puberty is the period during which we attain adult secondary sexual characteristics and reproductive capability. Its onset depends upon reactivation of pulsative GNRH, secretion from its relative quiescence during childhood, on the background of intact potential for pituitary-gonadal function. This review is intended: to highlight those current practices in diagnosis and management that are evidence based and those that are not; to help clinicians deal with areas of uncertainty with reference to physiologic first principles; by sign-posting relevant data arising from other patient groups with shared issues; to illustrate how recent scientific advances are (or should be) altering clinician perceptions of pubertal delay; and finally, to emphasise that the management of men and women presenting in advanced adult life with absent puberty cannot simply be extrapolated from paediatric practice. There is a broad spectrum of pubertal timing that varies among different populations, separated in time and space. Delayed puberty usually represents an extreme of the normal, a developmental pattern referred to as constitutional delay of growth and puberty (CDGP), but organic defects of the hypothalamo-pituitary-gonadal axis predisposing to hypogonadism may not always be initially distinguishable from it. CDGP and organic, or congenital hypogonadotrophic hypogonadism are both significantly more common in boys than girls. Moreover, around 1/3 of adults with organic hypogonadotrophic hypogonadism had evidence of partial puberty at presentation and, confusingly, some 5-10% of these subsequently may exhibit recovery of endogenous gonadotrophin secretion, including men with Kallmann syndrome. However, the distinction is crucial as expectative ('watch-and-wait') management is inappropriate in the context of hypogonadism. The probability of pubertal delay being caused by organic hypogonadism rises exponentially both with increasing age at presentation and the presence of associated 'red

  5. Metabolic control of puberty: roles of leptin and kisspeptins.

    Science.gov (United States)

    Sanchez-Garrido, Miguel A; Tena-Sempere, Manuel

    2013-07-01

    This article is part of a Special Issue "Puberty and Adolescence". Reproduction is an energy-demanding function. Accordingly, puberty is metabolically gated, as a means to prevent fertility in conditions of energy insufficiency. In addition, obesity has been shown to impact the timing of puberty and may be among the causes for the earlier trends of pubertal age reported in various countries. The metabolic control of puberty in such a spectrum of situations, ranging from energy deficit to extreme overweight, is the result of the concerted action of different peripheral hormones and central transmitters that sense the metabolic state of the organism and transmit this information to the various elements of the reproductive axis, mainly the GnRH neurons. Among the peripheral signals involved, the adipose hormone, leptin, is known to play an essential role in the regulation of puberty, especially in females. Yet, although it is clear that the effects of leptin on puberty onset are predominantly permissive and mainly conducted at central (hypothalamic) levels, the primary sites and mechanisms of action of leptin within the reproductive brain remain unsolved. In this context, neurons expressing kisspeptins, the products of the Kiss1 gene that have emerged recently as essential upstream regulators of GnRH neurons, operate as key sensors of the metabolic state and funnel of the reproductive effects of leptin. Yet, much debate has arisen recently on whether the putative actions of leptin on the Kiss1 system are actually indirect and/or may primarily target Kiss1-independent pathways, such as those originating from the ventral premmamilary nucleus. Moreover, evidence has been presented for extra-hypothalamic or peripheral actions of leptin, including direct gonadal effects, which may contribute to the metabolic control of reproduction in extreme body weight conditions. In this work, we will critically review the experimental evidence supporting a role of leptin, kisspeptin

  6. Carbon tetrachloride treatment induces anorexia independently of hepatitis in rats.

    Science.gov (United States)

    Okamoto, T; Okabe, S

    2000-08-01

    Oxidative stress is involved in the development of anorexia. In the present study, we examined the possible involvement of anorexia in oxygen radical-induced hepatitis. A low dose of carbon tetrachloride (1 ml/kg of a 1:1 solution with olive oil) was orally administered to rats with and without food restriction. In rats with food restriction, carbon tetrachloride treatment induced hepatitis and reduced the body weight gain. In contrast, carbon tetrachloride treatment did not induce hepatitis in rats without food restriction, but the body weight was decreased. In these rats, the loss of body weight was accompanied by a decrease in food intake. The present results indicate that the administration of a low dose of carbon tetrachloride to rats without food restriction induced anorexia independently of hepatitis.

  7. Concerns Girls Have about Puberty

    Science.gov (United States)

    ... Stages Listen Español Text Size Email Print Share Concerns Girls Have About Puberty Page Content Article Body Girls have pubertal concerns and worries, too, including: Breast Development Some girls ...

  8. Puberty and structural brain development in humans.

    Science.gov (United States)

    Herting, Megan M; Sowell, Elizabeth R

    2017-01-01

    Adolescence is a transitional period of physical and behavioral development between childhood and adulthood. Puberty is a distinct period of sexual maturation that occurs during adolescence. Since the advent of magnetic resonance imaging (MRI), human studies have largely examined neurodevelopment in the context of age. A breadth of animal findings suggest that sex hormones continue to influence the brain beyond the prenatal period, with both organizational and activational effects occurring during puberty. Given the animal evidence, human MRI research has also set out to determine how puberty may influence otherwise known patterns of age-related neurodevelopment. Here we review structural-based MRI studies and show that pubertal maturation is a key variable to consider in elucidating sex- and individual- based differences in patterns of human brain development. We also highlight the continuing challenges faced, as well as future considerations, for this vital avenue of research. Copyright © 2016. Published by Elsevier Inc.

  9. Idiopathic precocious puberty in girls: Psychosexual development.

    Science.gov (United States)

    Meyer-Bahlburg, H F; Ehrhardt, A A; Bell, J J; Cohen, S F; Healey, J M; Feldman, J F; Morishima, A; Baker, S W; New, M I

    1985-08-01

    A promising model syndrome for the examination of the role of physical maturation in the development of female sexuality is idiopathic precocious puberty (IPP). In this first controlled study of psychosexual development in IPP females, 16 females between 13 and 20 years of age with a history of IPP were compared to 16 control subjects with a history of normal puberty pair-matched to the index subjects on the basis of sex, race, age, socioeconomic level, and menarcheal status. The psychosexual history and the current psychosexual status were assessed by a systematic half-structured interview. The IPP females on average passed the psychosexual milestones at an earlier age than their normal maturing peers, with a particularly early onset of masturbation. Those who were sociosexually active tended to report a higher total orgasmic outlet and a higher sex drive. There was no increase in homosexuality among IPP girls. The timing of puberty has a (modest) influence on psychosexual development in females.

  10. Is Puberty Education Evident in Australia's First National Curriculum?

    Science.gov (United States)

    Collier-Harris, Christine A.; Goldman, Juliette D. G.

    2017-01-01

    The processes of puberty, including reproductive fertility and social-role transitions, now begin earlier, last longer, and are experienced in very different contexts. Because of this, all children and adolescents need good-quality puberty education in school curricula, and this need is supported by positive cost-benefit analysis and international…

  11. Environmental pollutants and dysregulation of male puberty--a comparison among species.

    Science.gov (United States)

    Magnusson, Ulf; Ljungvall, Karl

    2014-04-01

    The scientific literature on altered onset of puberty predominantly involves studies on females. This paper reviews current knowledge on the role of environmental pollutants in dysregulation of male puberty in humans, laboratory rodents and farm animals. The methods used to determine the onset of puberty are well developed in humans and farm animals, and standardized across studies in humans. In laboratory rodents standardized external morphological endpoints are used. There is an increasing weight of evidence from epidemiological studies in humans, as well as from experiments in animals, indicating that environmental pollutants dysregulate puberty in males. Most data are from studies on "classical" persistent environmental pollutants. Assessing the effect of multichemical environmental pollution on dysregulation of puberty in humans is more challenging; further solid epidemiological data would likely contribute most to our understanding, especially if combined with systematically collected field-data from selected wildlife. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  12. Childhood family disruption and adult height: is there a mediating role of puberty?

    Science.gov (United States)

    Sheppard, Paula; Garcia, Justin R; Sear, Rebecca

    2015-11-24

    Childhood family background is known to be associated with child growth and development, including the onset of puberty, but less is known about the influence of childhood family disruption on outcomes in later life. Given the associations between early family disruption and childhood development, we predicted that there may be long-term health-relevant consequences of childhood disruption. Using data from a large US interview sample (n = 16 207), we test if death or divorce of parents, at different childhood periods, was associated with adult stature, and whether age at puberty mediated this relationship, for men and women. RESULTS MEN: : parental death and divorce during early childhood was associated with shorter adult height, and later puberty. Later puberty was associated with shorter adult height. Path analyses demonstrated that the relationship between parental divorce and height was completely mediated by age at puberty; although parental death was only partially mediated by age at puberty. WOMEN: the father's death during early childhood was associated with earlier puberty, which was in turn associated with shorter adult stature. The relationship between paternal death and height is entirely mediated by age at puberty; no evidence of a direct relationship between childhood family disruption and adult height. Early childhood familial disruption is associated with shorter height for men, and is partially mediated by later puberty. For women, the relationship between father's death, and height was completely mediated by earlier puberty. These findings indicate that disruption during childhood can have long-reaching health repercussions, particularly for boys. © The Author(s) 2015. Published by Oxford University Press on behalf of the Foundation for Evolution, Medicine, and Public Health.

  13. Age at puberty and the emerging obesity epidemic

    DEFF Research Database (Denmark)

    Aksglaede, Lise; Juul, Anders; Olsen, Lina W

    2009-01-01

    BACKGROUND: Recent studies have shown that puberty starts at younger ages than previously. It has been hypothesized that the increasing prevalence of childhood obesity is contributing to this trend. The purpose of this study was to analyze the association between prepubertal body mass index (BMI...... was significantly inversely associated with age at OGS and PHV. Dividing the children into five levels of prepubertal BMI, we found a similar secular trend toward earlier maturation in all BMI groups. CONCLUSION/SIGNIFICANCE: The heavier both boys and girls were at age seven, the earlier they entered puberty....... Irrespective of level of BMI at age seven, there was a downward trend in the age at attaining puberty in both boys and girls, which suggests that the obesity epidemic is not solely responsible for the trend....

  14. Tamoxifen induces regression of estradiol-induced mammary cancer in ACI.COP-Ept2 rat model

    OpenAIRE

    Ruhlen, Rachel L.; Willbrand, Dana M.; Besch-Williford, Cynthia L.; Ma, Lixin; Shull, James D.; Sauter, Edward R.

    2008-01-01

    The ACI rat is a unique model of human breast cancer in that mammary cancers are induced by estrogen without carcinogens, irradiation, xenografts or transgenic manipulations. We sought to characterize mammary cancers in a congenic variant of the ACI rat, the ACI.COP-Ept2. All rats with estradiol implants developed mammary cancers in 5–7 months. Rats bearing estradiol-induced mammary cancers were treated with tamoxifen for three weeks. Tamoxifen reduced tumor mass, measured by magnetic resonan...

  15. alpha-difluoromethylornithine modifies gonadotropin-releasing hormone release and follicle-stimulating hormone secretion in the immature female rat.

    Science.gov (United States)

    Thyssen, S M; Becú-Villalobos, D; Lacau-Mengido, I M; Libertun, C

    1997-06-01

    Polyamines play an essential role in tissue growth and differentiation, in body weight increment, in brain organization, and in the molecular mechanisms of hormonal action, intracellular signaling, and cell-to-cell communication. In a previous study, inhibition of their synthesis by alpha-difluoromethylornithine (DFMO), a specific and irreversible inhibitor of ornithine decarboxylase, during development in female rats, was followed by prolonged high follicle-stimulating hormone (FSH) serum level and a delayed puberty onset. Those changes were relatively independent of body mass and did not impair posterior fertility. The present work studies the mechanisms and site of action of polyamine participation in FSH secretion during development. DFMO was injected in female rats between Days 1 and 9 on alternate days. At 10 days of age, hypothalami from control and DFMO rats were perifused in vitro, and basal and potassium-induced gonadotropin-releasing hormone (GnRH) release were measured. The response to membrane depolarization was altered in DFMO hypothalami. Increased GnRH release in response to a low K+ concentration was evidenced. Adenohypophyses of the same treated prepubertal rats were perifused in vitro and the response to GnRH pulses was checked. In DFMO-treated rats, higher FSH release was observed, with no changes in LH or PRL secretion. Finally, pituitary GnRH receptor number in adenohypophyseal membranes from treated and control groups was quantified. A significant reduction in specific binding was evident in hypophyses from DFMO-treated rats when compared with binding in the control group. In summary, DFMO treatment in a critical developmental period in the female rat impacts the immature GnRH neuronal network and immature gonadotropes. A delay in maturation is evidenced by a higher sensitivity to secretagogs in both pituitary glands and hypothalamic explants. These events could explain the prolonged high FSH serum levels and delayed puberty onset seen in

  16. Analgesic exposure in pregnant rats affects fetal germ cell development with inter-generational reproductive consequences

    DEFF Research Database (Denmark)

    Dean, Afshan; van den Driesche, Sander; Wang, Yili

    2016-01-01

    Analgesics which affect prostaglandin (PG) pathways are used by most pregnant women. As germ cells (GC) undergo developmental and epigenetic changes in fetal life and are PG targets, we investigated if exposure of pregnant rats to analgesics (indomethacin or acetaminophen) affected GC development...... smaller ovaries and reduced follicle numbers during puberty/adulthood; as similar changes were found for F2 offspring of analgesic-exposed F1 fathers or mothers, we interpret this as potentially indicating an analgesic-induced change to GC in F1. Assuming our results are translatable to humans, they raise...

  17. Susceptibility to radiation-induced mammary carcinoma in genetically resistant Copenhagen rats

    International Nuclear Information System (INIS)

    Kamiya, Kenji; Nitta, Yumiko; Gould, M.N.

    2000-01-01

    The objective of this experiment was to compare the cellular basis of mammary cancer induction by a chemical carcinogen with induction by ionizing radiation in three strains of rats (inbred that have different genetic susceptibilities: COP rats, F344 rats, and WF rats). Rats were given a single intraperitoneal injection of 50 mg MNU/kg body weight as a mammary-tumor-inducing chemical carcinogen and were irradiated with a 3.0 Gy dose of 60 Co gamma rays at a dose rate of 26.58±1.19 cGy/min. The rats were inspected weekly, and they were killed and necropsied whenever palpable tumors were detected or they became moribund. The histopathological and immunohistochemical characteristics of the mammary tumors were investigated. A transplantation experiment using selected primary mammary tumors that developed in COP rats exposed to gamma rays was also performed to investigate the transplantability of mammary tumors induced by ionizing radiation. The sensitivity of the WF and F344 rats and the resistance of the COP rats to mammary carcinoma induction by the chemical carcinogen MNU was confirmed. In contrast to the chemical carcinogens, no difference in susceptibility to radiation induction of mammary carcinomas was detected among the three strains of rats, and immunohistochemical examination indicated that the radiation-induced carcinomas consisted of more highly differentiated cells than the MNU-induced cancers. The results of the experiment appear to support the hypothesis that differentiated mammary gland tissue is more resistant to chemical carcinogens than to cancer induction by radiation. The authors conclude that radiation-induced cancers in rats may develop via different pathways or from different cell populations than chemically induced cancers. (K.H.)

  18. Susceptibility to radiation-induced mammary carcinoma in genetically resistant Copenhagen rats

    Energy Technology Data Exchange (ETDEWEB)

    Kamiya, Kenji; Nitta, Yumiko [Hiroshima Univ. (Japan). Research Inst. for Radiation Biology and Medicine; Gould, M.N.

    2000-07-01

    The objective of this experiment was to compare the cellular basis of mammary cancer induction by a chemical carcinogen with induction by ionizing radiation in three strains of rats (inbred that have different genetic susceptibilities: COP rats, F344 rats, and WF rats). Rats were given a single intraperitoneal injection of 50 mg MNU/kg body weight as a mammary-tumor-inducing chemical carcinogen and were irradiated with a 3.0 Gy dose of {sup 60} Co gamma rays at a dose rate of 26.58{+-}1.19 cGy/min. The rats were inspected weekly, and they were killed and necropsied whenever palpable tumors were detected or they became moribund. The histopathological and immunohistochemical characteristics of the mammary tumors were investigated. A transplantation experiment using selected primary mammary tumors that developed in COP rats exposed to gamma rays was also performed to investigate the transplantability of mammary tumors induced by ionizing radiation. The sensitivity of the WF and F344 rats and the resistance of the COP rats to mammary carcinoma induction by the chemical carcinogen MNU was confirmed. In contrast to the chemical carcinogens, no difference in susceptibility to radiation induction of mammary carcinomas was detected among the three strains of rats, and immunohistochemical examination indicated that the radiation-induced carcinomas consisted of more highly differentiated cells than the MNU-induced cancers. The results of the experiment appear to support the hypothesis that differentiated mammary gland tissue is more resistant to chemical carcinogens than to cancer induction by radiation. The authors conclude that radiation-induced cancers in rats may develop via different pathways or from different cell populations than chemically induced cancers. (K.H.)

  19. A missense mutation in MKRN3 in a Danish girl with central precocious puberty and her brother with early puberty

    DEFF Research Database (Denmark)

    Känsäkoski, Johanna; Raivio, Taneli; Juul, Anders

    2015-01-01

    BACKGROUND: Idiopathic central precocious puberty (ICPP) results from the premature reactivation of the hypothalamic-pituitary-gonadal axis leading to development of secondary sexual characteristics prior to 8 y in girls or 9 y in boys. Since the initial discovery of mutations in the maternally...... hypothalamic complementary DNA (cDNA) was investigated by PCR. RESULTS: One paternally inherited rare variant, c.1034G>A (p.Arg345His), was identified in one girl with ICPP and in her brother with early puberty. The variant is predicted to be deleterious by three different in silico prediction programs....... Expression of MKRN3 was confirmed in adult human hypothalamus. CONCLUSION: Our results are in line with previous studies in which paternally inherited MKRN3 mutations have been found both in males and in females with ICPP or early puberty. Our report further expands the set of MKRN3 mutations identified...

  20. Significant adverse reactions to long-acting gonadotropin-releasing hormone agonists for the treatment of central precocious puberty and early onset puberty

    Directory of Open Access Journals (Sweden)

    Ji Woo Lee

    2014-09-01

    Full Text Available PurposeLong-acting gonadotropin-releasing hormone agonists (GnRHa are commonly used to treat central precocious puberty (CPP in Korea. Although rare, there have been reports on the characteristic of adverse reactions of GnRHa in CPP among the Korean population. This study was intended to report on our clinical experience regarding significant adverse reactions to long-acting GnRHa in CPP and early onset puberty and to evaluate the prevalence rate of serious side effects.MethodsThis retrospective study included children with CPP and early onset puberty, who were administered monthly with long-acting GnRHa (leuprolide acetate, triptorelin acetate at the outpatient clinic of Department of Pediatrics, at Inha University Hospital, between January 2011 and December 2013. We analyzed the clinical characteristics of patients who experienced significant adverse reactions and evaluated the prevalence rate.ResultsSix serious side effects (0.9% were observed among total of 621 CPP and early onset puberty children with GnRHa therapy. The number of sterile abscess formation was four in three patients (4 events of 621. Anaphylaxis occurred in only one patient, and unilateral slipped capital femoral epiphysis (SCFE in another one patient. Anaphylaxis occurred after the 6th administration of the monthly depot triptorelin acetate. Unilateral SCFE developed in GnRHa therapy.ConclusionSterile abscess formation occurred in 0.6% of CPP and early onset puberty patients from the administration of a monthly depot GnRHa therapy. The occurrences of anaphylaxis and SCFE are extremely rare, but can have serious implications on patients. Clinicians should be aware of these potential adverse effects related to GnRHa therapy in CPP.

  1. Abnormal morphology of the penis in male rats exposed neonatally to diethylstilbestrol is associated with altered profile of estrogen receptor-alpha protein, but not of androgen receptor protein: a developmental and immunocytochemical study.

    Science.gov (United States)

    Goyal, H O; Braden, T D; Williams, C S; Dalvi, P; Mansour, M M; Mansour, M; Williams, J W; Bartol, F F; Wiley, A A; Birch, L; Prins, G S

    2004-05-01

    Objectives of the study were to determine developmental changes in morphology and expression of androgen receptor (AR) and estrogen receptor (ER)alpha in the body of the rat penis exposed neonatally to diethylstilbestrol (DES). Male pups received DES at a dose of 10 microg per rat on alternate days from Postnatal Day 2 to Postnatal Day 12. Controls received olive oil vehicle only. Tissue samples were collected on Days 18 (prepuberty), 41 (puberty), and 120 (adult) of age. DES-induced abnormalities were evident at 18 days of age and included smaller, lighter, and thinner penis, loss of cavernous spaces and associated smooth muscle cells, and increased deposition of fat cells in the corpora cavernosa penis. Fat cells virtually filled the entire area of the corpora cavernosa at puberty and adulthood. Plasma testosterone (T) was reduced to an undetectable level, while LH was unaltered in all treated groups. AR-positive cells were ubiquitous and their profile (incidence and staining intensity) did not differ between control and treated rats of the respective age groups. Conversely, ERalpha-positive cells were limited to the stroma of corpus spongiosus in all age groups of both control and treated rats, but the expression in treated rats at 18 days was up-regulated in stromal cells of corpora cavernosa, coincident with the presence of morphological abnormalities. Hence, this study reports for the first time DES-induced developmental, morphological abnormalities in the body of the penis and suggests that these abnormalities may have resulted from decreased T and/or overexpression of ERalpha.

  2. The effects of puberty on white matter development in boys.

    Science.gov (United States)

    Menzies, Lara; Goddings, Anne-Lise; Whitaker, Kirstie J; Blakemore, Sarah-Jayne; Viner, Russell M

    2015-02-01

    Neuroimaging studies demonstrate considerable changes in white matter volume and microstructure during adolescence. Most studies have focused on age-related effects, whilst puberty-related changes are not well understood. Using diffusion tensor imaging and tract-based spatial statistics, we investigated the effects of pubertal status on white matter mean diffusivity (MD) and fractional anisotropy (FA) in 61 males aged 12.7-16.0 years. Participants were grouped into early-mid puberty (≤Tanner Stage 3 in pubic hair and gonadal development; n=22) and late-post puberty (≥Tanner Stage 4 in pubic hair or gonadal development; n=39). Salivary levels of pubertal hormones (testosterone, DHEA and oestradiol) were also measured. Pubertal stage was significantly related to MD in diverse white matter regions. No relationship was observed between pubertal status and FA. Regression modelling of MD in the significant regions demonstrated that an interaction model incorporating puberty, age and puberty×age best explained our findings. In addition, testosterone was correlated with MD in these pubertally significant regions. No relationship was observed between oestradiol or DHEA and MD. In conclusion, pubertal status was significantly related to MD, but not FA, and this relationship cannot be explained by changes in chronological age alone. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  3. Effects of puberty on cystic fibrosis related pulmonary exacerbations in women versus men.

    Science.gov (United States)

    Sutton, Shelby; Rosenbluth, Daniel; Raghavan, Deepa; Zheng, Jie; Jain, Raksha

    2014-01-01

    Epidemiologic data from studies of airway diseases, such as asthma, chronic obstructive pulmonary disease, and cystic fibrosis indicate a gender disparity where women have worse outcomes. The explanation for this is largely unknown. We hypothesize that female sex hormones play a role in this gender disparity, predisposing women to more exacerbations and decreased lung function post-puberty. In Cystic Fibrosis, to determine if puberty marks a point of increasing exacerbations and decreasing lung function in women relative to men. Using the United States Cystic Fibrosis Foundation Patient Registry, we used linear regression to compare lung function and rate of pulmonary exacerbations in men versus women before and after puberty. Of 5,137 subjects who met inclusion criteria, 2,689 were male and 2,448 were female. Average age of puberty was found to be 13.2 ± 2.2 years in men and 11.2 ± 2.0 years of age in women. Percent predicted FEV1 pre- and post-puberty were no different between males versus females (P = 0.44 pre-puberty and P = 0.16 post-puberty). In contrast, women had a significantly higher rate of pulmonary exacerbations post-puberty than men (1.17 ± 1.35 exacerbations per year in women versus 0.95 ± 1.27 in men; P puberty, the rate of pulmonary exacerbations increased in adolescent women relative to men with cystic fibrosis, supporting a role for sex hormones in the disease process. Further understanding of the mechanisms that modulate sex hormone receptors in airway disease may serve as future targets for therapy. © 2013 Wiley Periodicals, Inc.

  4. Central precocious puberty: evaluation by neuroimaging

    International Nuclear Information System (INIS)

    Kornreich, L.; Horev, G.; Blaser, S.; Daneman, D.; Kauli, R.; Grunebaum, M.

    1995-01-01

    To evaluate the incidence of abnormal intracranial findings in children with central precocious puberty, 62 children (51 girls, 11 boys) were examined by computerized tomography and/or magnetic resonance imaging (MRI) of the brain. Forty-four had normal examinations; 18 (11 girls, 7 boys) showed intracranial pathologies, including hamartoma of the tuber cinereum (8 cases), parenchymal loss (3 cases), hypothalamicchiasmatic lesions (2 cases), lesions of the corpus callosum (2 cases), suprasellar cyst (1 case), and pineal cyst and mesiotemporal sclerosis (1 case each). Based on the correlation between the clinical and the imaging results of this series, the authors recommend MRI as the imaging method of choice in the investigation of precocious puberty. (orig.)

  5. Central precocious puberty: evaluation by neuroimaging

    Energy Technology Data Exchange (ETDEWEB)

    Kornreich, L. [Dept. of Pediatric Imaging, Children`s Medical Center of Israel, Petah Tiqva (Israel)]|[Sackler Faculty of Medicine, Tel Aviv Univ. (Israel); Horev, G. [Dept. of Pediatric Imaging, Children`s Medical Center of Israel, Petah Tiqva (Israel)]|[Sackler Faculty of Medicine, Tel Aviv Univ. (Israel); Blaser, S. [Dept. of Radiology, Hospital for Sick Children, Toronto, ON (Canada); Daneman, D. [Div. of Endocrinology, Dept. of Pediatrics, Hospital for Sick Children, Toronto, ON (Canada); Kauli, R. [Sackler Faculty of Medicine, Tel Aviv Univ. (Israel)]|[Inst. of Pediatric and Adolescent Endocrinology, Children`s Medical Center of Israel, Petah Tiqva (Israel); Grunebaum, M. [Dept. of Pediatric Imaging, Children`s Medical Center of Israel, Petah Tiqva (Israel)]|[Sackler Faculty of Medicine, Tel Aviv Univ. (Israel)

    1995-02-01

    To evaluate the incidence of abnormal intracranial findings in children with central precocious puberty, 62 children (51 girls, 11 boys) were examined by computerized tomography and/or magnetic resonance imaging (MRI) of the brain. Forty-four had normal examinations; 18 (11 girls, 7 boys) showed intracranial pathologies, including hamartoma of the tuber cinereum (8 cases), parenchymal loss (3 cases), hypothalamicchiasmatic lesions (2 cases), lesions of the corpus callosum (2 cases), suprasellar cyst (1 case), and pineal cyst and mesiotemporal sclerosis (1 case each). Based on the correlation between the clinical and the imaging results of this series, the authors recommend MRI as the imaging method of choice in the investigation of precocious puberty. (orig.)

  6. Influence of ovarian hormones on development of ingestive responding to alterations in fatty acid oxidation in female rats

    Science.gov (United States)

    Swithers, Susan E.; McCurley, Melissa; Hamilton, Erica; Doerflinger, Alicia

    2008-01-01

    Adult male rats have been demonstrated to increase food intake in response to administration of drugs that interfere with oxidation of fatty acids (e.g. methyl palmoxirate and mercaptoacetate [MA]), effects that are larger in animals maintained on a high-fat diet. In contrast, while administration of MA has been reported to stimulate food intake in pre-pubertal female rats, food intake is not stimulated by MA in adult female rats. Instead, administration of MA to adult females results in changes in reproductive behavior and physiology. The present experiments were designed to examine the effects of administration of MA on food intake in adult female rats. The results demonstrated that, as previously reported, food intake was stimulated by MA in adult male rats on low-fat and high-fat diets, but food intake in was not stimulated by MA in gonadally-intact adult female rats on either low-fat or high-fat diet. Further, MA did not stimulate food intake in female rats ovariectomized as adults. However, when females were ovariectomized prior to the onset of puberty (postnatal day 25 – 28), food intake was stimulated by administration of MA in adulthood. Finally, cyclic injections of 17-β-estradiol benzoate given to females ovariectomized prior to the onset of puberty abolished the stimulatory effects of MA on food intake in adult females. Taken together, the data suggest that exposure to estrogens during the time of puberty in female rats can persistently alter adult ingestive responding to signals related to changes in energy utilization. PMID:18586247

  7. [Relevant factors of early puberty timing in urban primary schools in Chongqing].

    Science.gov (United States)

    Luo, Yan; Liu, Qin; Wen, Yi; Liu, Shudan; Lei, Xun; Wang, Hong

    2016-05-01

    To investigate the status of puberty timing and relevant factors of early puberty timing in children from grade one to four in urban primary schools of Chongqing. According to the purposive sample method, four urban primary schools in Chongqing were selected and of which 1471 children from grade one to four who have obtained informed consent were recruited. Questionnaire survey on social-demographic characteristics and family environment (e.g., age, parents' relationship, diet and lifestyle, etc), and Pubertal Development Scale (PDS) survey and physical examination (measurements of height, weight, pubertal development status, etc) were conducted. P25, P50, P75 ages of each important pubertal event were calculated by probit regression. Univariate and multivariate analysis were used to analyze relevant factors. The detection rate of early puberty timing was 17.7%, and the median ages of the onset of breast and testicular development were 10.77 and 11.48 years old, respectively. Multivariate logistic regression showed that early puberty timing occurred more likely in girls than in boys (OR = 0.561, 95% CI 0.406-0.774), and bad relationship between parents (OR = 1.320, 95% CI 1.007-1.729) and hair-products-use (OR = 1.685, 95%, CI 1.028-2.762) were risk factors of early puberty timing. Early onset of puberty in urban Chongqing is still exist. Gender, parents' relationship, and hair-products-use have an essential impact on early puberty timing.

  8. Sex Difference in Oxytocin-Induced Anti-Hyperalgesia at the Spinal Level in Rats with Intraplantar Carrageenan-Induced Inflammation.

    Science.gov (United States)

    Chow, Lok-Hi; Chen, Yuan-Hao; Wu, Wan-Chuan; Chang, En-Pei; Huang, Eagle Yi-Kung

    2016-01-01

    Previously, we demonstrated intrathecal administration of oxytocin strongly induced anti-hyperalgesia in male rats. By using an oxytocin-receptor antagonist (atosiban), the descending oxytocinergic pathway was found to regulate inflammatory hyperalgesia in our previous study using male rats. The activity of this neural pathway is elevated during hyperalgesia, but whether this effect differs in a sex-dependent manner remains unknown. We conducted plantar tests on adult male and female virgin rats in which paw inflammation was induced using carrageenan. Exogenous (i.t.) application of oxytocin exerted no anti-hyperalgesic effect in female rats, except at an extremely high dose. Female rats exhibited similar extent of hyperalgesia to male rats did when the animals received the same dose of carrageenan. When atosiban was administered alone, the severity of hyperalgesia was not increased in female rats. Moreover, insulin-regulated aminopeptidase (IRAP) was expressed at higher levels in the spinal cords of female rats compared with those of male rats. Oxytocin-induced anti-hyperalgesia exhibits a sex-dependent difference in rats. This difference can partially result from the higher expression of IRAP in the spinal cords of female rats, because IRAP functions as an enzyme that degrades oxytocin. Our study confirms the existence of a sex difference in oxytocin-induced anti-hyperalgesia at the spinal level in rats.

  9. Effects by periodontitis on pristane-induced arthritis in rats.

    Science.gov (United States)

    Eriksson, Kaja; Lönnblom, Erik; Tour, Gregory; Kats, Anna; Mydel, Piotr; Georgsson, Pierre; Hultgren, Catharina; Kharlamova, Nastya; Norin, Ulrika; Jönsson, Jörgen; Lundmark, Anna; Hellvard, Annelie; Lundberg, Karin; Jansson, Leif; Holmdahl, Rikard; Yucel-Lindberg, Tülay

    2016-11-03

    An infection-immune association of periodontal disease with rheumatoid arthritis has been suggested. This study aimed to investigate the effect of pre-existing periodontitis on the development and the immune/inflammatory response of pristane-induced arthritis. We investigated the effect of periodontitis induced by ligature placement and Porphyromonas gingivalis (P. gingivalis) infection, in combination with Fusobacterium nucleatum to promote its colonization, on the development of pristane-induced arthritis (PIA) in rats (Dark Agouti). Disease progression and severity of periodontitis and arthritis was monitored using clinical assessment, micro-computed tomography (micro-CT)/intraoral radiographs, antibody response, the inflammatory markers such as α-1-acid glycoprotein (α-1-AGP) and c-reactive protein (CRP) as well as cytokine multiplex profiling at different time intervals after induction. Experimentally induced periodontitis manifested clinically (P periodontitis-induction led to severe arthritis in all rats demonstrating that the severity of arthritis was not affected by the pre-existence of periodontitis. Endpoint analysis showed that 89% of the periodontitis-affected animals were positive for antibodies against arginine gingipain B and furthermore, the plasma antibody levels to a citrullinated P. gingivalis peptidylarginine deiminase (PPAD) peptide (denoted CPP3) were significantly (P periodontitis rats with PIA. Additionally, there was a trend towards increased pro-inflammatory and anti-inflammatory cytokine levels, and increased α-1-AGP levels in plasma from periodontitis-challenged PIA rats. Pre-existence of periodontitis induced antibodies against citrullinated peptide derived from PPAD in rats with PIA. However, there were no differences in the development or severity of PIA between periodontitis challenged and periodontitis free rats.

  10. Shared genetic aetiology of puberty timing between sexes and with health-related outcomes.

    Science.gov (United States)

    Day, Felix R; Bulik-Sullivan, Brendan; Hinds, David A; Finucane, Hilary K; Murabito, Joanne M; Tung, Joyce Y; Ong, Ken K; Perry, John R B

    2015-11-09

    Understanding of the genetic regulation of puberty timing has come largely from studies of rare disorders and population-based studies in women. Here, we report the largest genomic analysis for puberty timing in 55,871 men, based on recalled age at voice breaking. Analysis across all genomic variants reveals strong genetic correlation (0.74, P=2.7 × 10(-70)) between male and female puberty timing. However, some loci show sex-divergent effects, including directionally opposite effects between sexes at the SIM1/MCHR2 locus (Pheterogeneity=1.6 × 10(-12)). We find five novel loci for puberty timing (Ppuberty, LEPR and KAL1. Finally, we identify genetic correlations that indicate shared aetiologies in both sexes between puberty timing and body mass index, fasting insulin levels, lipid levels, type 2 diabetes and cardiovascular disease.

  11. Circulating MKRN3 levels decline prior to pubertal onset and through puberty

    DEFF Research Database (Denmark)

    Hagen, Casper P; Sørensen, Kaspar; Mieritz, Mikkel G

    2015-01-01

    CONTEXT: Puberty is initiated by a complex interaction of suppressing and stimulating factors. Genetic studies of familial central precocious puberty have suggested makorin ring finger protein 3 (MKRN3) as a major inhibitor of GnRH secretion during childhood. Furthermore, genetic variation near...... of hypothalamic GnRH secretion during childhood. Undetectable or low MKRN3 levels were observed in a subgroup of patients with early onset of puberty....

  12. Improving the assessment of endocrine disrupting chemical (EDC) effects on puberty

    Science.gov (United States)

    During puberty, key developmental events occur that are critical for normal adult male and female reproductive maturation. Recent studies raised concern that exposure to environmental chemicals alter the normal progression through puberty and lead to impaired reproductive functio...

  13. Quinine-induced tinnitus in rats.

    Science.gov (United States)

    Jastreboff, P J; Brennan, J F; Sasaki, C T

    1991-10-01

    Quinine ingestion reportedly induces tinnitus in humans. To expand our salicylate-based animal model of tinnitus, a series of conditioned suppression experiments was performed on 54 male-pigmented rats using quinine injections to induce tinnitus. Quinine induced changes in both the extent of suppression and recovery of licking, which followed a pattern that paralleled those produced after salicylate injections, and which may be interpreted as the result of tinnitus perception in animals. These changes depended on the dose and time schedule of quinine administration. Additionally, the calcium channel blocker, nimodipine, abolished the quinine-induced effect in a dose-dependent manner.

  14. Evaluation and Referral of Children With Signs of Early Puberty.

    Science.gov (United States)

    Kaplowitz, Paul; Bloch, Clifford

    2016-01-01

    Concerns about possible early pubertal development are a common cause for referral to pediatric medical subspecialists. Several recent studies have suggested that onset of breast and/or pubic hair development may be occurring earlier than in the past. Although there is a chance of finding pathology in girls with signs of puberty before 8 years of age and in boys before 9 years of age, the vast majority of these children with signs of apparent puberty have variations of normal growth and physical development and do not require laboratory testing, bone age radiographs, or intervention. The most common of these signs of early puberty are premature adrenarche (early onset of pubic hair and/or body odor), premature thelarche (nonprogressive breast development, usually occurring before 2 years of age), and lipomastia, in which girls have apparent breast development which, on careful palpation, is determined to be adipose tissue. Indicators that the signs of sexual maturation may represent true, central precocious puberty include progressive breast development over a 4- to 6-month period of observation or progressive penis and testicular enlargement, especially if accompanied by rapid linear growth. Children exhibiting these true indicators of early puberty need prompt evaluation by the appropriate pediatric medical subspecialist. Therapy with a gonadotropin-releasing hormone agonist may be indicated, as discussed in this report. Copyright © 2016 by the American Academy of Pediatrics.

  15. Effects of postnatal administration of diethylstilbestrol on puberty and thyroid function in male rats.

    Science.gov (United States)

    Shin, Jae-Ho; Kim, Tae Sung; Kang, Il Hyun; Kang, Tae Seok; Moon, Hyun Ju; Han, Soon-Young

    2009-10-01

    To examine the effects of diethylstilbestrol (DES) on male pubertal development and thyroid function, juvenile male Sprague-Dawley rats were given DES daily by oral intubation at doses of 10, 20 and 40 microg/kg/day from postnatal day 33 for 20 days. Prepuce separation was significantly delayed at the dose of 20 microg/kg/day and above in the DES-treated rats. DES treatment induced a significant reduction in the weights of testes, epididymides, the ventral prostate, seminal vesicles plus coagulating glands and fluid, levator ani bulbocavernosus muscles, Cowper's glands and the glans penis. The weights of the liver and adrenals increased in the DES-treated animals. DES caused a dose-dependent reduction in germ cells; in particular the spermatids were mainly affected. The serum levels of testosterone and luteinizing hormone were significantly reduced in the DES-treated groups, but that of estradiol decreased. No differences were observed in the serum thyroxine levels of the control and DES-treated groups. In microscopic observation of the DES-treated animals, degeneration of germ cells and tubular atrophy in the testis were noted, but there were no microscopic changes in the thyroid. These results indicate that DES affected the pubertal development of juvenile male rats and that its mode of action may be related to alterations in hormone levels.

  16. Environmental factors and puberty timing: expert panel research needs

    DEFF Research Database (Denmark)

    Louis, G.M. Buck; Jr, L.E. Gray; Marcus, M.

    2008-01-01

    Serono Symposia International convened an expert panel to review the impact of environmental influences on the regulation of pubertal onset and progression while identifying critical data gaps and future research priorities. An expert panel reviewed the literature on endocrine-disrupting chemicals......, body size, and puberty. The panel concluded that available experimental animal and human data support a possible role of endocrine-disrupting chemicals and body size in relation to alterations in pubertal onset and progression in boys and girls. Critical data gaps prioritized for future research......, and (3) basic research to identify the primary signal(s) for the onset of gonadotropin-releasing hormone-dependent/central puberty and gonadotropin-releasing hormone-independent/peripheral puberty. Prospective studies of couples who are planning pregnancies or pregnant women are needed to capture...

  17. Role of environmental factors in the timing of puberty

    DEFF Research Database (Denmark)

    Euling, S.Y.; Selevan, S.G.; Pescovitz, O.H.

    2008-01-01

    Puberty-timing measures have historically been used as indicators of adequate nutrition and growth. More recently, these measures have been examined in relation to exposure to estrogenic or antiandrogenic agents, as well as other environmental factors. The scientific community has debated whether...... puberty timing is occurring earlier today than in the mid-1900s in the United States and, if so, whether environmental factors play a role; however, no one has asked a multidisciplinary panel to resolve this question. Thus, a multidisciplinary expert panel jointly sponsored by the US Environmental...... Protection Agency, the National Institute of Environmental Health Sciences, and Serono Symposia International was convened to examine the evidence of a secular trend, identify potential environmental factors of concern, and identify research needs regarding environmental factors and puberty timing at "The...

  18. Changes in vascular reactivity induced by acute hyperthyroidism in isolated rat aortae.

    Science.gov (United States)

    Honda, H; Iwata, T; Mochizuki, T; Kogo, H

    2000-06-01

    Hyperthyroidism was induced by subcutaneous injections of L-thyroxine (T(4)) (500 mg/kg/day) for 3 days in order to study whether adrenergic and muscarinic receptor-mediated vascular responses alter at an early stage of the disease. T(4) treatment was sufficient to induce a significant degree of thyroid weight loss, tachycardia, cardiac hypertrophy, and an elevation in serum T(4) levels. The tension of aortic ring preparations isolated from rats was measured isometrically to investigate the influence of acute hyperthyroidism. The contractions induced by norepinephrine (NE) were significantly suppressed in aortic rings from rats treated with T(4) compared with control rats. N(G)-nitro-L-arginine (L-NOARG), an inhibitor of nitric oxide synthase (NOS), significantly enhanced NE-induced contraction in aortic rings from both control and T(4)-treated rats, and the enhancement was greater in rats treated with T(4) than control rats. The relaxations induced by either acetylcholine (ACh) or sodium nitroprusside (SNP) were also significantly enhanced by T(4) treatment. L-NOARG abolished the relaxation induced by ACh in aortic rings from both control and T(4)-treated rats. L-NOARG shifted SNP-induced relaxation curves of aortic rings from those of control rats to the left, but not with rats treated with T(4). T(4) treatment showed no influence on the amount of endothelial NOS (eNOS) protein. These results suggest that vascular responses alter at an early stage of hyperthyroidism and that it may be due to a modification in the NO system which is independent from the amount of eNOS protein.

  19. Vinclozolin exposure in utero induces postpubertal prostatitis and reduces sperm production via a reversible hormone-regulated mechanism.

    Science.gov (United States)

    Cowin, Prue A; Gold, Elspeth; Aleksova, Jasna; O'Bryan, Moira K; Foster, Paul M D; Scott, Hamish S; Risbridger, Gail P

    2010-02-01

    Vinclozolin is an endocrine-disrupting chemical (EDC) that binds with high affinity to the androgen receptor (AR) and blocks the action of gonadal hormones on male reproductive organs. An alternative mechanism of action of Vinclozolin involves transgenerational effects on the male reproductive tract. We previously reported in utero Vinclozolin exposure-induced prostatitis (prostate inflammation) in postpubertal rats concurrent with down-regulation of AR and increased nuclear factor-kappaB activation. We postulated the male reproductive abnormalities induced by in utero Vinclozolin exposure could be reversed by testosterone supplementation, in contrast to the permanent modifications involving DNA methyltransferases (Dnmts) described by others. To test this hypothesis, we administered high-dose testosterone at puberty to Vinclozolin-treated rats and determined the effect on anogenital distance (AGD); testicular germ cell apoptosis, concentration of elongated spermatids, and the onset of prostatitis. Concurrently we examined Dnmt1, -3A, -3B, and -3L mRNA expression. Consistent with previous reports, in utero exposure to Vinclozolin significantly reduced AGD, increased testicular germ cell apoptosis 3-fold, reduced elongated spermatid number by 40%, and induced postpubertal prostatitis in 100% of exposed males. Administration of high-dose testosterone (25 mg/kg) at puberty normalized AGD, reduced germ cell apoptosis, and restored elongated spermatid number. Testosterone restored AR and nuclear factor-kappaB expression in the prostate and abolished Vinclozolin-induced prostatitis. Altered Dnmt expression was evident with in utero Vinclozolin exposure and was not normalized after testosterone treatment. These data demonstrate in utero Vinclozolin-induced male reproductive tract abnormalities are AR mediated and reversible and involve a mechanism independent of Dnmt expression.

  20. Timing of puberty and physical growth in obese children: a longitudinal study in boys and girls.

    Science.gov (United States)

    De Leonibus, C; Marcovecchio, M L; Chiavaroli, V; de Giorgis, T; Chiarelli, F; Mohn, A

    2014-08-01

    To assess whether puberty and physical growth vary in obese when compared to normal-weight children. One hundred obese pre-pubertal children (44 boys; mean age (±SD): 9.01 ± 0.62 years; 56 girls; 8.70 ± 0.57 years) were compared to 55 normal-weight controls (27 boys; 9.17 ± 0.26 years; 28 girls; 8.71 ± 0.62 years). All study participants were followed prospectively with 6-monthly follow-up visits. At each study visit, height, weight, body mass index (BMI) and pubertal stage were assessed. Obese children entered puberty and achieved later stages of puberty earlier than controls (onset of puberty: boys: 11.66 ± 1.00 vs. 12.12 ± 0.91 years, P = 0.049; girls: 9.90 ± 0.78 vs. 10.32 ± 1.70, P = 0.016; late puberty: boys: 13.33 ± 0.71 vs. 14.47 ± 1.00 years, P puberty (β = -0.506, P puberty (β = -0.514, P puberty and completion of puberty and an impaired height gain during puberty. © 2013 The Authors. Pediatric Obesity © 2013 International Association for the Study of Obesity.

  1. Effects of ebselen on radiocontrast media-induced hepatotoxicity in rats.

    Science.gov (United States)

    Basarslan, Fatmagul; Yilmaz, Nigar; Davarci, Isil; Akin, Mustafa; Ozgur, Mustafa; Yilmaz, Cahide; Ulutas, Kemal Turker

    2013-09-01

    Oxidative stress is accepted as a potential responsible mechanism in the pathogenesis of radiocontrast media (RCM)-induced hepatotoxicity. Therefore, we aimed to investigate the protective effects of ebselen against RCM-induced hepatotoxicity by measuring tissue oxidant/antioxidant parameters and histological changes in rats. Wistar albino rats were randomly separated into four groups consisting of eight rats per group. Normal saline was given to the rats in control group (group 1). RCM was given to the rats in group 2, and both RCM and ebselen were given to the rats in group 3. Only ebselen was given to the rats in group 4. Liver sections of the killed animals were analyzed to measure the levels of malondialdehyde (MDA) and activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px), as well as histopathological changes. In RCM group, SOD and CAT levels were found increased. In RCM-ebselen group, MDA, SOD and CAT levels were found decreased. In RCM-ebselen group, however, GSH-Px activities of liver tissue increased. All these results indicated that ebselen produced a protective mechanism against RCM-induced hepatotoxicity and took part in oxidative stress.

  2. Lung volume and expiratory flow rates from pre- to post-puberty.

    Science.gov (United States)

    Smith, Joshua R; Emerson, Sam R; Kurti, Stephanie P; Gandhi, Kirti; Harms, Craig A

    2015-08-01

    The purpose was to determine if the airways and lungs grow disproportionately from pre- to post-puberty in boys and girls. We hypothesized that the airways grow at a slower rate than lung volume (i.e. dysanapsis growth) during puberty and boys would exhibit more dysanaptic growth compared to girls. Twenty-one pre-pubescent children [11 boys (pre 10.1 ± 0.5 years, post 15.3 ± 0.5 years); 10 girls (pre 9.4 ± 1.0 years, post 14.1 ± 1.0 years)] performed pulmonary function tests (PFTs) ~5 years ago from an original cohort of 40 children. These 21 children performed PFTs, which included forced vital capacity (FVC) and forced expiratory flow at 50 % FVC (FEF50). Static pressure at 50 % of FVC [Pst(L)50 %] was estimated based on age. Dysanapsis ratio (DR) was calculated [FEF50 × FVC(-1) × Pst(L) 50 % (-1) ]. Maturation status was determined via Tanner stages. Stage of maturation was not different (p > 0.05) between boys and girls (4.2 ± 0.6 stage vs. 3.7 ± 0.7 stage, respectively). FVC and FEF50 increased (p 0.05) from pre- to post-puberty. FEF50 and FVC significantly increased and DR decreased (p puberty for both sexes. Post-puberty, boys had a significantly larger FVC, but FEF50, DR, and FEF50/FVC were not different (p > 0.05) compared to girls. These data suggest that dysanaptic growth occurs during puberty and that it is not different between boys and girls.

  3. Aqueous Root Extract in Loperamide- Induced Constipated Rats

    African Journals Online (AJOL)

    central nervous system (CNS) depressant action of the plant has ... administration was done using metal oropharyngeal ... weight of constipated rats before treatment. .... constipation, abdominal bloating and refractory ... found in the plasma membrane and endoplasmic .... induced production of prostaglandins in rat isolated.

  4. Neonatal Handling Produces Sex Hormone-Dependent Resilience to Stress-Induced Muscle Hyperalgesia in Rats.

    Science.gov (United States)

    Alvarez, Pedro; Green, Paul G; Levine, Jon D

    2018-06-01

    Neonatal handling (NH) of male rat pups strongly attenuates stress response and stress-induced persistent muscle hyperalgesia in adults. Because female sex is a well established risk factor for stress-induced chronic muscle pain, we explored whether NH provides resilience to stress-induced hyperalgesia in adult female rats. Rat pups underwent NH, or standard (control) care. Muscle mechanical nociceptive threshold was assessed before and after water avoidance (WA) stress, when they were adults. In contrast to male rats, NH produced only a modest protection against WA stress-induced muscle hyperalgesia in female rats. Gonadectomy completely abolished NH-induced resilience in male rats but produced only a small increase in this protective effect in female rats. The administration of the antiestrogen drug fulvestrant, in addition to gonadectomy, did not enhance the protective effect of NH in female rats. Finally, knockdown of the androgen receptor by intrathecal antisense treatment attenuated the protective effect of NH in intact male rats. Together, these data indicate that androgens play a key role in NH-induced resilience to WA stress-induced muscle hyperalgesia. NH induces androgen-dependent resilience to stress-induced muscle pain. Therefore, androgens may contribute to sex differences observed in chronic musculoskeletal pain and its enhancement by stress. Copyright © 2018 The American Pain Society. Published by Elsevier Inc. All rights reserved.

  5. Genetics Home Reference: central precocious puberty

    Science.gov (United States)

    ... odor. Girls also develop breasts and begin their menstrual periods. Boys have growth of the penis and ... puberty earlier than normal. For most genes, both copies of the gene (one copy inherited from each ...

  6. Cardiometabolic risk factors and insulin resistance in obese children and adolescents: relation to puberty.

    Science.gov (United States)

    Tobisch, B; Blatniczky, L; Barkai, L

    2015-02-01

    The prevalence of obesity with concomitant increasing risk for having cardiometabolic diseases is rising in the childhood population. Insulin resistance has a key role in metabolic changes in these children. Insulin levels elevate as puberty commences in every individual. Children with increased risk for cardiometabolic diseases show significant differences in insulin levels even before the onset of puberty compared with those without risks. The pattern of appearance of dyslipidaemia also varies in children with risk factors even in the pre-pubertal group from those without risk. Children with metabolic syndrome display considerably pronounced changes in their metabolic parameters before the onset of puberty, which become more pronounced as puberty passes. Insulin resistance (IR) has a key role in the metabolic changes in obese children. In commencing puberty, the insulin levels elevate. It is not clear, however, how insulin levels develop if the metabolic syndrome appears. Metabolic changes were assessed in obese children before, during and after puberty to analyse the relationship between IR and puberty in subjects with and without metabolic syndrome. Three hundred thirty-four obese children (5-19 years) attended the study. The criteria of the International Diabetes Federation were used to assess the presence of cardiometabolic risks (CMRs). Subjects with increased CMR were compared with those without risk (nCMR). Pubertal staging, lipid levels, plasma glucose and insulin levels during oral glucose tolerance test were determined in each participant. IR was expressed by homeostasis model assessment (HOMA-IR) and the ratio of glucose and insulin areas under the curve (AUC-IR). Significantly higher AUC-IR were found in pre-pubertal CMR children compared with nCMR subjects (11.84 ± 1.03 vs. 8.00 ± 0.69; P puberty. HOMA-IR differs between CMR and nCMR only in post-puberty (6.03 ± 1.26 vs. 2.54 ± 0.23; P puberty. CMR is associated with increased

  7. Effect of aging on UVC-induced apoptosis of rat splenocytes

    International Nuclear Information System (INIS)

    Radziszewska, E.; Piwocka, K.; Bielak-Zmijewska, A.; Sikora, E.; Skierski, J.

    2000-01-01

    UVC-induced apoptotic symptoms such as morphological changes, DNA fragmentation, Bcl-2 and Bax protein expression were examined in primary splenocyte cultures from young (3 months) and old (24 months) rats. The activities of AP-1 and CRE transcription factors in UVC-irradiated splenocytes were also assessed. At 24 h after UVC irradiation 40% of cells derived from young rats were found to be apoptotic, which was twice as much as in splenocytes from old rats. Apoptosis in cells from old rats did not give typical symptoms like a ''DNA ladder'' and Bcl-2 protein downregulation, in contrast to splenocytes from young rats. No AP-1 transcription factor activity was found in UVC-irradiated splenocytes from old animals and only a trace activity in splenocytes from young animals. This indicates that, UVC-induced apoptosis in rat splenocytes is practically AP-1 independent and that cells from old rats are less sensitive to UVC irradiation than splenocytes from young rats. (author)

  8. Prostatic relaxation induced by agmatine is decreased in spontaneously hypertensive rats.

    Science.gov (United States)

    Lee, Liang-Ming; Tsai, Tsung-Chin; Chung, Hsien-Hui; Tong, Yat-Ching; Cheng, Juei-Tang

    2012-09-01

    What's known on the subject? and What does the study add? Neurotransmitters are known to control prostate contractility. Agmatine is one of them and induces relaxation through imidazoline receptors. The paper shows that the action of agmatine is reduced in hypertensive rats, and that this change is related to the decrease of ATP-sensitive potassium channels in the prostate. The findings can increase our understanding of the possible underlying mechanism for the development of clinical benign prostatic hyperplasia. To compare agmatine-induced prostatic relaxation in hypertensive and control rats. To investigate the responsible mechanism(s) and the role of the ATP-sensitive potassium channel. Prostate strips were isolated from male spontaneously hypertensive (SH) rats and normal Wistar-Kyoto (WKY) rats for measurement of isometric tension. The strips were precontracted with 1 µmol/L phenylephrine or 50 mmol/L KCl. Dose-dependent relaxation of the prostatic strips was studied by cumulative administration of agmatine, 1 to 100 µmol/L, into the organ bath. Effects of specific antagonists on agmatine-induced relaxation were studied. Western blotting analysis was used to measure the gene expression of the ATP-sensitive potassium channel in the rat prostate. Prostatic relaxation induced by agmatine was markedly reduced in SH rats compared with WKY rats. The relaxation caused by agmatine was abolished by BU224, a selective imidazoline I(2)-receptor antagonist, but was not modified by efaroxan at a dose sufficient to block imidazoline I(1)-receptors. The relaxation induced by diazoxide at a concentration sufficient to activate ATP-sensitive potassium channels was markedly reduced in the SH rat prostate. Expressions of ATP-sensitive potassium channel sulphonylurea receptor and inwardly rectifying potassium channel (Kir) 6.2 subunits were both decreased in the prostate of SH rats. The decrease of agmatine-induced prostatic relaxation in SH rats is related to the change in

  9. The timing of normal puberty and the age limits of sexual precocity

    DEFF Research Database (Denmark)

    Parent, Anne-Simone; Teilmann, Grete; Juul, Anders

    2003-01-01

    During the past decade, possible advancement in timing of puberty has been reported in the United States. In addition, early pubertal development and an increased incidence of sexual precocity have been noticed in children, primarily girls, migrating for foreign adoption in several Western European...... countries. These observations are raising the issues of current differences and secular trends in timing of puberty in relation to ethnic, geographical, and socioeconomic background. None of these factors provide an unequivocal explanation for the earlier onset of puberty seen in the United States....... In the formerly deprived migrating children, refeeding and catch-up growth may prime maturation. However, precocious puberty is seen also in some nondeprived migrating children. Attention has been paid to the changing milieu after migration, and recently, the possible role of endocrine- disrupting chemicals from...

  10. Diagnosis and constitutional and laboratory features of Korean girls referred for precocious puberty

    Directory of Open Access Journals (Sweden)

    Doosoo Kim

    2012-12-01

    Full Text Available &lt;B&gt;Purpose:&lt;/B&gt; Precocious puberty is defined as breast development before the age of 8 years in girls. The present study aimed to reveal the diagnosis of Korean girls referred for precocious puberty and to compare the constitutional and endocrinological features among diagnosis groups. &lt;B&gt;Methods:&lt;/B&gt; The present study used a retrospective chart review of 988 Korean girls who had visited a pediatric endocrinology clinic from 2006 to 2010 for the evaluation of precocious puberty. Study groups comprised fast puberty, true precocious puberty (PP, pseudo PP, premature thelarche, and control. We determined the height standard deviation score (HSDS, weight standard deviation score (WSDS, and body mass index standard deviation score (BMISDS of each group using the published 2007 Korean growth charts. Hormone tests were performed at our outpatient clinic. &lt;B&gt;Results:&lt;/B&gt; The PP groups comprised fast puberty (67%, premature thelarche (17%, true PP (15%, and pseudo PP (1%. Advanced bone age and levels of estradiol, basal luteinizing hormone (LH, and peak LH after gonadotropin-releasing hormone stimulation testing were significantly high in the fast puberty and true PP groups compared with the control group. HSDS, WSDS, and BMISDS were significantly higher in the true PP group than in the control group (P&lt;0.05. &lt;B&gt;Conclusion:&lt;/B&gt; The frequent causes of PP were found to be fast puberty, true PP, and premature thelarche. Furthermore, BMISDS were significantly elevated in the true PP group. Therefore, we emphasize the need for regular follow-up of girls who are heavier or taller than others in the same age group.

  11. Descriptive review: hormonal influences on risk for eating disorder symptoms during puberty and adolescence.

    Science.gov (United States)

    Harden, K Paige; Kretsch, Natalie; Moore, Sarah R; Mendle, Jane

    2014-11-01

    Puberty is an important period of risk for the onset of eating pathology in adolescent females. This review focuses on changes in reproductive hormones during puberty as one specific psychopathogenic mechanism. Studies of puberty and eating disorder-related phenotypes were identified using search databases and the reference sections of previous literature. Correlational studies of adult women and experimental studies of animals provide evidence for the effects of reproductive hormones on eating disorder symptoms. Very few studies of puberty, however, have directly measured or tested the effects of hormonal change in samples of human adolescents. Commonly used measures of pubertal development, such as menarche or self-reported pubertal status, are relatively poor indicators of individual differences in hormones. The extent to which puberty-related hormonal change accounts for elevated risk for disordered eating remains unclear. Future research is necessary to elucidate the specific relations between hormonal change during puberty and risk for disordered eating. In particular, there is a need for longitudinal studies with multivariate measurement of pubertal development, including direct measures of change in reproductive hormones. © 2014 Wiley Periodicals, Inc.

  12. Feeding prepubescent gilts a high-fat diet induces molecular changes in the hypothalamus-pituitary-gonadal axis and predicts early timing of puberty.

    Science.gov (United States)

    Zhuo, Yong; Zhou, Dongsheng; Che, Lianqiang; Fang, Zhengfeng; Lin, Yan; Wu, De

    2014-01-01

    The onset of puberty in females has been occurring earlier over the past decades, presumably as a result of improved nutrition in developed countries. However, the underlying molecular mechanisms responsible for the early attainment of puberty as a result of nutrition fortification remain largely unknown. The aim of this study was to evaluate the hormone and gene expression changes in prepubescent gilts fed a high-fat diet to investigate whether these changes could predict the early timing of puberty. Forty gilts were fed a daily basal diet (LE) or a basal diet with an additional 270 g/d or 340 g/d of fat (HE) during the prepubescent phase. Blood samples were collected during the prepubescent phase to detect hormone secretion changes in insulin-like growth factor-1, kisspeptin, estradiol, progesterone, and leptin. The gene expressions at the hypothalamus-pituitary-gonadal axis were examined on day 73 of the experiment (average age on day 177) during the prepubescent phase. An HE diet resulted in accelerated body weight gain and back-fat thickness at the P2 point compared with LE gilts during the prepubescent phase. Gilts that were fed HE diets attained puberty 12 d earlier than LE gilts, and a larger proportion of HE gilts reached puberty at day 180 or 190 of age. A postmortem analysis revealed a promoted development of the uterus and ovary tissue that was characterized by a 53.7% and 29.5% increase in the uterine and ovary weight, respectively, and an increased length of the uterine horn and oviduct tissue in HE gilts. Real-time quantitative polymerase chain reaction revealed that HE gilts had higher Kiss-1, G protein-coupled receptor 54, gonadotropin-releasing hormone and estrogen receptor α mRNA expression levels in the hypothalamic anteroventral periventricular nucleus; the leptin receptor mRNA expression level was higher in the hypothalamic arcuate nucleus and ovary tissue; the insulin-like growth factor-1 receptor expression was higher in the pituitary and

  13. Male patients presenting with rapidly progressive puberty associated with malignant tumors

    Directory of Open Access Journals (Sweden)

    Soo Jung Kim

    2016-03-01

    Full Text Available In males, precocious puberty (PP is defined as the development of secondary sexual characteristics before age 9 years. PP is usually idiopathic; though, organic abnormalities including tumors are more frequently found in male patients with PP. However, advanced puberty in male also can be an important clinical manifestation in tumors. We report 2 cases of rapidly progressive puberty in males, each associated with a germ-cell tumor. First, an 11-year-old boy presented with mild fever and weight loss for 1 month. Physical examination revealed a pubertal stage of G3P3 with 10-mL testes. Investigations revealed advanced bone age (16 years with elevated basal luteinizing hormone and testosterone levels. An anterior mediastinal tumor was identified by chest radiography and computed tomography, and elevated α-fetoprotein (AFP and β-human chorionic gonadotropin (β-hCG levels were noted. Histopathologic analysis confirmed a yolk-sac tumor. Second, a 12-year-old boy presented with diplopia, polydipsia, and polyuria for 4 months. Physical examination revealed a pubertal stage of G3P3 with 8-mL testes. Bone age was advanced (16 years and laboratory tests indicated panhypopituitarism with elevated testosterone level. A mixed germ-cell tumor was diagnosed with elevated AFP and β-hCG levels. Of course, these patients also have other symptoms of suspecting tumors, however, rapidly progressive puberty can be the more earlier screening sign of tumors. Therefore, in male patients with accelerated or advanced puberty, malignancy should be considered, with evaluation of tumor markers. In addition, advanced puberty in male should be recognized more widely as a unique sign of neoplasm.

  14. Classic congenital adrenal hyperplasia and puberty.

    Science.gov (United States)

    Charmandari, Evangelia; Brook, Charles G D; Hindmarsh, Peter C

    2004-11-01

    Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders resulting from deficiency of one of the five enzymes required for synthesis of cortisol in the adrenal cortex. The most common form of the disease is classic 21-hydroxylase deficiency, which is characterized by decreased synthesis of glucocorticoids and often mineralocorticoids, adrenal hyperandrogenism and impaired development and function of the adrenal medulla. The clinical management of classic 21-hydroxylase deficiency is often suboptimal, and patients are at risk of developing in tandem iatrogenic hypercortisolism and/or hyperandogenism. Limitations of current medical therapy include the inability to control hyperandrogenism without employing supraphysiologic doses of glucocorticoid, hyperresponsiveness of the hypertrophied adrenal glands to adrenocorticotropic hormone (ACTH) and difficulty in suppressing ACTH secretion from the anterior pituitary. Puberty imposes increased difficulty in attaining adrenocortical suppression despite optimal substitution therapy and adherence to medical treatment. Alterations in the endocrine milieu at puberty may influence cortisol pharmacokinetics and, consequently, the handling of hydrocortisone used as replacement therapy. Recent studies have demonstrated a significant increase in cortisol clearance at puberty and a shorter half-life of free cortisol in pubertal females compared with males. Furthermore, children with classic CAH have elevated fasting serum insulin concentrations and insulin resistance. The latter may further enhance adrenal and/or ovarian androgen secretion, decrease the therapeutic efficacy of glucocorticoids and contribute to later development of the metabolic syndrome and its complications.

  15. The Emerging Role of Epigenetics in the Regulation of Female Puberty.

    Science.gov (United States)

    Lomniczi, Alejandro; Ojeda, Sergio R

    2016-01-01

    In recent years the pace of discovering the molecular and genetic underpinnings of the pubertal process has accelerated considerably. Genes required for human puberty to occur have been identified and evidence has been provided suggesting that the initiation of puberty requires coordinated changes in the output of a multiplicity of genes organized into functional networks. Recent evidence suggests that a dual mechanism of epigenetic regulation affecting the transcriptional activity of neurons involved in stimulating gonadotropin-releasing hormone release plays a fundamental role in the timing of puberty. The Polycomb group (PcG) of transcriptional silencers appears to be a major component of the repressive arm of this mechanism. PcG proteins prevent the premature initiation of female puberty by silencing the Kiss1 gene in kisspeptin neurons of the arcuate nucleus (ARC) of the hypothalamus. Because the abundance of histone marks either catalyzed by--or associated with--the Trithorax group (TrxG) of transcriptional activators increases at the time when PcG control subsides, it appears that the TrxG complex is the counteracting partner of PcG-mediated gene silencing. In this chapter, we discuss the concept that a switch from epigenetic repression to activation within ARC kisspeptin neurons is a core mechanism underlying the initiation of female puberty. © 2016 S. Karger AG, Basel.

  16. Androgen-dependent and independent process of bone formation in the distal segment of Os penis in the rat.

    Science.gov (United States)

    Murakami, R; Izumi, K; Yamaoka, I

    1995-11-01

    The distal segment of the os penis of the rat develops as a fibrocartilage which is replaced with non-lamellar bone by endochondral ossification after puberty. Development of the fibrocartilage and its calcification have been shown to be induced by androgens, but androgen-dependency of the endochondral ossification has not been studied in detail. In the present study, immature male rats of various ages were castrated and the ossification of the fibrocartilage of os penis was examined. In rats castrated at 6 weeks, when the fibrocartilage was scarcely calcified, ossification did not occur even at 24 weeks. When the castrated rats were treated with testosterone, ossification started before 12 weeks of age. In rats castrated at 8 weeks, when the fibrocartilage was heavily calcified, endochondral ossification was observed in some of the animals (5/7) at 24 weeks of age. The results of this study indicate that once the fibrocartilage is calcified, the endochondral ossification can take place without androgen, although the androgen can promote the process of ossification.

  17. Hypoglycemic of Cajanus scarabaeoides in glucose overloaded and streptozotocin-induced diabetic rats

    Directory of Open Access Journals (Sweden)

    Suman Pattanayak, Siva Shankar Nayak, Durgaprasad Panda and Vikas Shende

    2009-12-01

    Full Text Available In light of traditional claim of Cajanus scarabaeoides (L in the treatment of diabetes, we studied the effects of different solvent extracts in normal, glucose over loaded normal rats and streptozotocin-induced diabetic rats. The methanolic extract (500 mg/kg orally was produce significantly reduce blood glucose level at normal, glucose over loaded normal rats, and streptozotocin-induced diabetic rats after 15 days treatment; whereas petroleum ether and chloroform extract (500 mg/kg orally did not exhibit any significant effect on three groups of rats. Histopathology studies on pancreas of streptozotocin-induced diabetic rats shows inflammatory changes in pancreatic islets, results from selective destroy of insulin producing β-cells. These changes are inhibited by C. scarabaeoides methanolic extract and gliclazide. The antidiabetic activity of methanolic extract may be due to the presence of flavonoids.

  18. Influences on the onset and tempo of puberty in human beings and implications for adolescent psychological development.

    Science.gov (United States)

    Lee, Yvonne; Styne, Dennis

    2013-07-01

    This article is part of a Special Issue "Puberty and Adolescence". Historical records reveal a secular trend toward earlier onset of puberty in both males and females, often attributed to improvements in nutrition and health status. The trend stabilized during the mid 20th century in many countries, but recent studies describe a recurrence of a decrease in age of pubertal onset. There appears to be an associated change in pubertal tempo in girls, such that girls who enter puberty earlier have a longer duration of puberty. Puberty is influenced by genetic factors but since these effects cannot change dramatically over the past century, environmental effects, including endocrine disrupting chemicals (EDCs), and perinatal conditions offer alternative etiologies. Observations that the secular trends in puberty in girls parallel the obesity epidemic provide another plausible explanation. Early puberty has implications for poor behavioral and psychosocial outcomes as well as health later in life. Irrespective of the underlying cause of the ongoing trend toward early puberty, experts in the field have debated whether these trends should lead clinicians to reconsider a lower age of normal puberty, or whether such a new definition will mask a pathologic etiology. Copyright © 2013 Elsevier Inc. All rights reserved.

  19. True precocious puberty following treatment of a Leydig cell tumour: two case reports and literature review

    Directory of Open Access Journals (Sweden)

    Alberto eVerrotti

    2015-11-01

    Full Text Available Leydig cell testicular tumours are a rare cause of precocious pseudopuberty in boys. Surgery is the main therapy and shows good overall prognosis. The physical signs of precocious puberty are expected to disappear shortly after surgical removal of the mass. We report two children, 7.5 and 7.7 year-old boys, who underwent testis-sparing surgery for a Leydig cell testicular tumour causing precocious pseudopuberty. During follow-up, after an immediate clinical and laboratory regression, both boys presented signs of precocious puberty and ultimately developed central precocious puberty. They were successfully treated with gonadotropin releasing hormone analogues. Only 6 other cases have been described regarding the development of central precocious puberty after successful treatment of a Leydig cell tumour causing precocious pseudo puberty. Gonadotropin-dependent precocious puberty should be considered in children treated for a Leydig cell tumour presenting persistent or recurrent physical signs of puberty activation. In such cases, therapy with gonadotropin releasing hormone analogues appears to be the most effective medical treatment.

  20. Muscarinic receptors mediate cold stress-induced detrusor overactivity in type 2 diabetes mellitus rats.

    Science.gov (United States)

    Imamura, Tetsuya; Ishizuka, Osamu; Ogawa, Teruyuki; Yamagishi, Takahiro; Yokoyama, Hitoshi; Minagawa, Tomonori; Nakazawa, Masaki; Gautam, Sudha Silwal; Nishizawa, Osamu

    2014-10-01

    This study determined if muscarinic receptors could mediate the cold stress-induced detrusor overactivity induced in type 2 diabetes mellitus rats. Ten-week-old female Goto-Kakizaki diabetic rats (n = 12) and Wister Kyoto non-diabetic rats (n = 12) were maintained on a high-fat diet for 4 weeks. Cystometric investigations of the unanesthetized rats were carried out at room temperature (27 ± 2°C) for 20 min. They were intravenously administered imidafenacin (0.3 mg/kg, n = 6) or vehicle (n = 6). After 5 min, the rats were transferred to a low temperature (4 ± 2°C) for 40 min where the cystometry was continued. The rats were then returned to room temperature for the final cystometric measurements. Afterwards, expressions of bladder muscarinic receptor M3 and M2 messenger ribonucleic acids and proteins were assessed by reverse transcription polymerase chain reaction and immunohistochemistry. In non-diabetic Wister Kyoto rats, imidafenacin did not reduce cold stress-induced detrusor overactivity. In diabetic Goto-Kakizaki rats, just after transfer to a low temperature, the cold stress-induced detrusor overactivity in imidafenacin-treated rats was reduced compared with vehicle-treated rats. Within the urinary bladders, the ratio of M3 to M2 receptor messenger ribonucleic acid in the diabetic Goto-Kakizaki rats was significantly higher than that of the non-diabetic Wister Kyoto rats. The proportion of muscarinic M3 receptor-positive area within the detrusor in diabetic Goto-Kakizaki rats was also significantly higher than that in non-diabetic Wister Kyoto rats. Imidafenacin partially inhibits cold stress-induced detrusor overactivity in diabetic Goto-Kakizaki rats. In this animal model, muscarinic M3 receptors partially mediate cold stress-induced detrusor overactivity. © 2014 The Japanese Urological Association.

  1. Sex hormone-binding globulin levels predict insulin sensitivity, disposition index, and cardiovascular risk during puberty

    DEFF Research Database (Denmark)

    Sørensen, Kaspar; Aksglaede, Lise; Munch-Andersen, Thor

    2009-01-01

    Early puberty is associated with increased risk of subsequent cardiovascular disease. Low sex hormone-binding globulin (SHBG) levels are a feature of early puberty and of conditions associated with increased cardiovascular risk. The aim of the present study was to evaluate SHBG as a predictor...... of glucose metabolism and metabolic risk during puberty....

  2. Environmental factors and puberty timing: expert panel research needs

    DEFF Research Database (Denmark)

    Louis, G.M. Buck; Jr, L.E. Gray; Marcus, M.

    2008-01-01

    initiatives include (1) etiologic research that focus on environmentally relevant levels of endocrine-disrupting chemicals and body size in relation to normal puberty as well as its variants, (2) exposure assessment of relevant endocrine-disrupting chemicals during critical windows of human development......, body size, and puberty. The panel concluded that available experimental animal and human data support a possible role of endocrine-disrupting chemicals and body size in relation to alterations in pubertal onset and progression in boys and girls. Critical data gaps prioritized for future research...

  3. The Effect of Bisphenol A on Puberty: A Critical Review of the Medical Literature.

    Science.gov (United States)

    Leonardi, Alberto; Cofini, Marta; Rigante, Donato; Lucchetti, Laura; Cipolla, Clelia; Penta, Laura; Esposito, Susanna

    2017-09-10

    Many scientific studies have revealed a trend towards an earlier onset of puberty and have disclosed an increasing number of children that display precocious puberty. As an explanation, some authors have considered the global socio-economic improvement across different populations, and other authors have considered the action of endocrine disrupting chemicals (EDCs). Among these, bisphenol A (BPA), an aromatic compound largely used worldwide as a precursor of some plastics and chemical additives, is well known for its molecular oestrogen-like and obesogenic actions. We reviewed the medical literature of the previous 20 years that examined associations between BPA exposure and the age of puberty in humans, considering only those referring to clinical or epidemiological data. Of 19 studies, only 7 showed a correlation between BPA and puberty. In particular, the possible disruptive role of BPA on puberty may be seen in those with central precocious puberty or isolated premature breast development aged 2 months to 4 years old, even if the mechanism is undefined. Some studies also found a close relationship between urinary BPA, body weight, and early puberty, which can be explained by the obesogenic effect of BPA itself. The currently available data do not allow establishment of a clear role for BPA in pubertal development because of the conflicting results among all clinical and epidemiological studies examined. Further research is needed to fully understand the potential role of exposure to EDCs and their adverse endocrine health outcomes.

  4. Excessive apoptosis and defective autophagy contribute to developmental testicular toxicity induced by fluoride

    International Nuclear Information System (INIS)

    Zhang, Shun; Niu, Qiang; Gao, Hui; Ma, Rulin; Lei, Rongrong; Zhang, Cheng; Xia, Tao; Li, Pei; Xu, Chunyan; Wang, Chao; Chen, Jingwen; Dong, Lixing; Zhao, Qian; Wang, Aiguo

    2016-01-01

    Fluoride, a ubiquitous environmental contaminant, is known to impair testicular functions and fertility; however the underlying mechanisms remain obscure. In this study, we used a rat model to mimic human exposure and sought to investigate the roles of apoptosis and autophagy in testicular toxicity of fluoride. Sprague–Dawley rats were developmentally exposed to 25, 50, or 100 mg/L sodium fluoride (NaF) via drinking water from pre-pregnancy to post-puberty, and then the testes of offspring were excised on postnatal day 56. Our results demonstrated that developmental NaF exposure induced an enhanced testicular apoptosis, as manifested by a series of hallmarks such as caspase-3 activation, chromatin condensation and DNA fragmentation. Further study revealed that fluoride exposure elicited significant elevations in the levels of cell surface death receptor Fas with a parallel increase in cytoplasmic cytochrome c, indicating the involvement of both extrinsic and intrinsic apoptotic pathways. Intriguingly, fluoride treatment also simultaneously increased the number of autophagosomes and the levels of autophagy marker LC3-II but not Beclin1. Unexpectedly, the expression of p62, a substrate that is degraded by autophagy, was also significantly elevated, suggesting that the accumulated autophagosomes resulted from impaired autophagy degradation rather than increased formation. Importantly, these were associated with marked histopathological lesions including spermatogenic failure and germ cell loss, along with severe ultrastructural abnormalities in testes. Taken together, our findings provide deeper insights into roles of excessive apoptosis and defective autophagy in the aggravation of testicular damage, which could contribute to a better understanding of fluoride-induced male reproductive toxicity. - Highlights: • Rats were developmentally exposed to fluoride from pre-pregnancy to post-puberty. • Both excessive apoptosis and defective autophagy are involved in

  5. Sevoflurane Induces Coherent Slow-Delta Oscillations in Rats

    Directory of Open Access Journals (Sweden)

    Jennifer A. Guidera

    2017-07-01

    Full Text Available Although general anesthetics are routinely administered to surgical patients to induce loss of consciousness, the mechanisms underlying anesthetic-induced unconsciousness are not fully understood. In rats, we characterized changes in the extradural EEG and intracranial local field potentials (LFPs within the prefrontal cortex (PFC, parietal cortex (PC, and central thalamus (CT in response to progressively higher doses of the inhaled anesthetic sevoflurane. During induction with a low dose of sevoflurane, beta/low gamma (12–40 Hz power increased in the frontal EEG and PFC, PC and CT LFPs, and PFC–CT and PFC–PFC LFP beta/low gamma coherence increased. Loss of movement (LOM coincided with an abrupt decrease in beta/low gamma PFC–CT LFP coherence. Following LOM, cortically coherent slow-delta (0.1–4 Hz oscillations were observed in the frontal EEG and PFC, PC and CT LFPs. At higher doses of sevoflurane sufficient to induce loss of the righting reflex, coherent slow-delta oscillations were dominant in the frontal EEG and PFC, PC and CT LFPs. Dynamics similar to those observed during induction were observed as animals emerged from sevoflurane anesthesia. We conclude that the rat is a useful animal model for sevoflurane-induced EEG oscillations in humans, and that coherent slow-delta oscillations are a correlate of sevoflurane-induced behavioral arrest and loss of righting in rats.

  6. Decrease in plasma high-density lipoprotein cholesterol levels at puberty in boys with delayed adolescence: correlation with plasma testosterone levels

    International Nuclear Information System (INIS)

    Kirkland, R.T.; Keenan, B.S.; Probstfield, J.L.; Patsch, W.; Lin, T.L.; Clayton, G.W.; Insull, W. Jr.

    1987-01-01

    A three-phase study tested the hypothesis that the decrease in the high-density lipoprotein cholesterol (HDL-C) level observed in boys at puberty is related to an increase in the plasma testosterone concentration. In phase I, 57 boys aged 10 to 17 years were categorized into four pubertal stages based on clinical parameters and plasma testosterone levels. These four groups showed increasing plasma testosterone values and decreasing HDL-C levels. In phase II, 14 boys with delayed adolescence were treated with testosterone enanthate. Plasma testosterone levels during therapy were in the adult male range. Levels of HDL-C decreased by a mean of 7.4 mg/dL (0.20 mmol/L) and 13.7 mg/dL (0.35 mmol/L), respectively, after the first two doses. In phase III, 13 boys with delayed adolescence demonstrated increasing plasma testosterone levels and decreasing HDL-C levels during spontaneous puberty. Levels of HDL-C and apolipoprotein A-1 were correlated during induced and spontaneous puberty. Testosterone should be considered a significant determinant of plasma HDL-C levels during pubertal development

  7. Efficient generation of rat induced pluripotent stem cells using a non-viral inducible vector.

    Directory of Open Access Journals (Sweden)

    Claudia Merkl

    Full Text Available Current methods of generating rat induced pluripotent stem cells are based on viral transduction of pluripotency inducing genes (Oct4, Sox2, c-myc and Klf4 into somatic cells. These activate endogenous pluripotency genes and reprogram the identity of the cell to an undifferentiated state. Epigenetic silencing of exogenous genes has to occur to allow normal iPS cell differentiation. To gain more control over the expression of exogenous reprogramming factors, we used a novel doxycycline-inducible plasmid vector encoding Oct4, Sox2, c-Myc and Klf4. To ensure efficient and controlled generation of iPS cells by plasmid transfection we equipped the reprogramming vector with a bacteriophage φC31 attB site and used a φC31 integrase expression vector to enhance vector integration. A series of doxycycline-independent rat iPS cell lines were established. These were characterized by immunocytochemical detection of Oct4, SSEA1 and SSEA4, alkaline phosphatase staining, methylation analysis of the endogenous Oct4 promoter and RT-PCR analysis of endogenous rat pluripotency genes. We also determined the number of vector integrations and the extent to which reprogramming factor gene expression was controlled. Protocols were developed to generate embryoid bodies and rat iPS cells demonstrated as pluripotent by generating derivatives of all three embryonic germ layers in vitro, and teratoma formation in vivo. All data suggest that our rat iPS cells, generated by plasmid based reprogramming, are similar to rat ES cells. Methods of DNA transfection, protein transduction and feeder-free monolayer culture of rat iPS cells were established to enable future applications.

  8. Sildenafil reduces polyuria in rats with lithium-induced NDI.

    Science.gov (United States)

    Sanches, Talita Rojas; Volpini, Rildo Aparecido; Massola Shimizu, Maria H; Bragança, Ana Carolina de; Oshiro-Monreal, Fabíola; Seguro, Antonio Carlos; Andrade, Lúcia

    2012-01-01

    Lithium (Li)-treated patients often develop urinary concentrating defect and polyuria, a condition known as nephrogenic diabetes insipidus (NDI). In a rat model of Li-induced NDI, we studied the effect that sildenafil (Sil), a phosphodiesterase 5 (PDE5) inhibitor, has on renal expression of aquaporin-2 (AQP2), urea transporter UT-A1, Na(+)/H(+) exchanger 3 (NHE3), Na(+)-K(+)-2Cl(-) cotransporter (NKCC2), epithelial Na channel (ENaC; α-, β-, and γ-subunits), endothelial nitric oxide synthase (eNOS), and inducible nitric oxide synthase. We also evaluated cGMP levels in medullary collecting duct cells in suspension. For 4 wk, Wistar rats received Li (40 mmol/kg food) or no treatment (control), some receiving, in weeks 2-4, Sil (200 mg/kg food) or Li and Sil (Li+Sil). In Li+Sil rats, urine output and free water clearance were markedly lower, whereas urinary osmolality was higher, than in Li rats. The cGMP levels in the suspensions of medullary collecting duct cells were markedly higher in the Li+Sil and Sil groups than in the control and Li groups. Semiquantitative immunoblotting revealed the following: in Li+Sil rats, AQP2 expression was partially normalized, whereas that of UT-A1, γ-ENaC, and eNOS was completely normalized; and expression of NKCC2 and NHE3 was significantly higher in Li rats than in controls. Inulin clearance was normal in all groups. Mean arterial pressure and plasma arginine vasopressin did not differ among the groups. Sil completely reversed the Li-induced increase in renal vascular resistance. We conclude that, in experimental Li-induced NDI, Sil reduces polyuria, increases urinary osmolality, and decreases free water clearance via upregulation of renal AQP2 and UT-A1.

  9. Hypothesis: exposure to endocrine-disrupting chemicals may interfere with timing of puberty

    DEFF Research Database (Denmark)

    Mouritsen, A; Aksglaede, L; Sørensen, K

    2010-01-01

    A recent decline in onset of puberty - especially among girls - has been observed, first in the US in the mid-1990s and now also in Europe. The development of breast tissue in girls occurs at a much younger age and the incidence of precocious puberty (PP) is increasing. Genetic factors...... of normal puberty are poorly understood. This hampers investigation of the possible role of environmental influences. There are many types of EDCs. One chemical may have more than one mode of action and the effects may depend on dose and duration of the exposure, as well as the developmental stage...... in life. Most known EDCs have oestrogenic and/or anti-androgenic actions and only few have androgenic or anti-oestrogenic effects. Thus, it appears plausible that they interfere with normal onset of puberty. The age at menarche has only declined by a few months whereas the age at breast development has...

  10. Hypothalamic hamartoma associated with precocious puberty: Case report

    International Nuclear Information System (INIS)

    Bae, Won Kyong; Kim, Pyo Nuyn; Kim, Il Young; Lee, Byoung Ho; Lee, Kyeong Seok; Bae, Hack Gun; Yun, Il Gyu

    1989-01-01

    Hamartoma of the hypothalamic area is a well recognized cause of central precocious puberty. We report a case of histologically proven hypothalamic hamartoma in a 8 year old girl with precocious puberty. The CT showed an isodense, nonenhancing mass in suprasellar area, measuring 4.2 X 3.1 cm, which, to our knowledge, seems to be the largest one of the published cases. On MR imaging, the signal intensity of the mass was homogeneous and isointense relative to gray matter on T1-, and hyperintense on T2-weighted images. The clinical and radiologic findings of the published cases of hypothalamic hamartoma are reviewed

  11. Hypothalamic hamartoma associated with precocious puberty: Case report

    Energy Technology Data Exchange (ETDEWEB)

    Bae, Won Kyong; Kim, Pyo Nuyn; Kim, Il Young; Lee, Byoung Ho; Lee, Kyeong Seok; Bae, Hack Gun; Yun, Il Gyu [Soonchunhyang University, Chonan Hospital, Chonan (Korea, Republic of)

    1989-12-15

    Hamartoma of the hypothalamic area is a well recognized cause of central precocious puberty. We report a case of histologically proven hypothalamic hamartoma in a 8 year old girl with precocious puberty. The CT showed an isodense, nonenhancing mass in suprasellar area, measuring 4.2 X 3.1 cm, which, to our knowledge, seems to be the largest one of the published cases. On MR imaging, the signal intensity of the mass was homogeneous and isointense relative to gray matter on T1-, and hyperintense on T2-weighted images. The clinical and radiologic findings of the published cases of hypothalamic hamartoma are reviewed.

  12. [Rapidly progressive puberty in a patient with mosaic Turner syndrome: a case report and literature review].

    Science.gov (United States)

    Liang, Y; Wei, H; Yu, X; Huang, W; Luo, X P

    2017-02-02

    Objective: To explore the clinical characteristics of diagnosis and treatment in patients with Turner syndrome and rapidly progressive puberty. Method: A rare case of rapidly progressive puberty in Turner syndrome with a mosaic karyotype of 45, X/46, X, del(X)(p21)(80%/20%)was diagnosed at Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology in January. 2015. Clinical characteristics and the related literature were reviewed. Original papers on precocious puberty or rapidly progressive puberty in Turner syndrome, published until Apr. 2016 were retrieved at PubMed and CNKI databases by the use of the key words "Turner syndrome" , "precocious puberty" and "rapidly progressive puberty" . Result: The patient was born at term with birth weight of 2 450 g and was diagnosed with SGA at 3 years of age for the first evaluating of growth and development. Then recombined human growth hormone (rhGH )was given at 4 years of age due to short stature (heightTurner syndrome is reported. Although short stature and ovarian dysgenesis are common in TS, precocious puberty may occur in TS, which is liable to cause delayed diagnosis and misdiagnosis. Careful examination is recommended for patients with unusual growth pattern, even though girls have normal height in accord with standard growth curve or spontaneous puberty. Evaluation for TS and subsequent investigation should be prompted.

  13. Role of Kisspeptin and Neurokinin B in Puberty in Female Non-Human Primates

    OpenAIRE

    Ei Terasawa; Ei Terasawa; James P. Garcia; Stephanie B. Seminara; Kim L. Keen

    2018-01-01

    In human patients, loss-of-function mutations in the genes encoding kisspeptin (KISS1) and neurokinin B (NKB) and their receptors (KISS1R and NK3R, respectively) result in an abnormal timing of puberty or the absence of puberty. To understand the neuroendocrine mechanism of puberty, we investigated the contribution of kisspeptin and NKB signaling to the pubertal increase in GnRH release using rhesus monkeys as a model. Direct measurements of GnRH and kisspeptin in the median eminence of the h...

  14. Evaluation of lipid profile and oxidative stress in STZ-induced rats treated with antioxidant vitamin

    Directory of Open Access Journals (Sweden)

    Danielle Ayr Tavares de Almeida

    2012-08-01

    Full Text Available The present study investigated the effect of supplementation of vitamin E on streptozotocin (STZ-induced diabetic rats by measuring blood glucose, changes in body weight, food and water intake, lipid profile, serum urea and creatinine level, and antioxidant enzyme activity. Male Wistar rats were divided into four groups: control rats (GI; rats receiving vitamin E (GII; STZ-induced diabetic rats (GIII and STZ-induced diabetic rats treated with vitamin E (GIV. Vitamin E reduced (p<0.05 blood glucose and urea, improved the lipid profile (decreased the serum levels of total cholesterol, LDL cholesterol, VLDL cholesterol and triacylglycerols, and increased HDL cholesterol and increased total protein in STZ-induced diabetic rats (GIV. Vitamin prevented changes in the activity of SOD and GSH-Px and in the concentration of lipid hydroperoxide. These results suggested that vitamin E improved hyperglycaemia and dyslipidaemia while inhibiting the progression of oxidative stress in STZ-induced diabetic rats.

  15. Talking to Your Child about Puberty

    Science.gov (United States)

    ... should know about puberty ahead of time. Many kids receive some sex education at school. Often, though, the lessons are ... January 2015 More on this topic for: Parents Kids Teens Sexual Development Questions and Answers About Sex A Parent's Guide to Surviving the Teen Years ...

  16. Activity/inactivity circadian rhythm shows high similarities between young obesity-induced rats and old rats.

    Science.gov (United States)

    Bravo Santos, R; Delgado, J; Cubero, J; Franco, L; Ruiz-Moyano, S; Mesa, M; Rodríguez, A B; Uguz, C; Barriga, C

    2016-03-01

    The objective of the present study was to compare differences between elderly rats and young obesity-induced rats in their activity/inactivity circadian rhythm. The investigation was motivated by the differences reported previously for the circadian rhythms of both obese and elderly humans (and other animals), and those of healthy, young or mature individuals. Three groups of rats were formed: a young control group which was fed a standard chow for rodents; a young obesity-induced group which was fed a high-fat diet for four months; and an elderly control group with rats aged 2.5 years that was fed a standard chow for rodents. Activity/inactivity data were registered through actimetry using infrared actimeter systems in each cage to detect activity. Data were logged on a computer and chronobiological analysis were performed. The results showed diurnal activity (sleep time), nocturnal activity (awake time), amplitude, acrophase, and interdaily stability to be similar between the young obesity-induced group and the elderly control group, but different in the young control group. We have concluded that obesity leads to a chronodisruption status in the body similar to the circadian rhythm degradation observed in the elderly.

  17. Serum inhibin B levels during male childhood and puberty

    DEFF Research Database (Denmark)

    Andersson, A M; Skakkebaek, N E

    2001-01-01

    Inhibin B is a testicular peptide hormone that regulates FSH secretion in a negative feedback loop. In males serum levels of inhibin B are detectable throughout life with prominent changes in the first year of life and during puberty. Serum inhibin B is normally detectable throughout childhood...... normal or near-normal levels are seen in cryptorchidism and disorders with preserved Sertoli cell function in spite of absence of germ cells or impaired androgen biosynthesis or action. During puberty a developmental change in the regulation of serum inhibin B occurs. In contrast to childhood inhibin B...

  18. Developmental changes in FSH secretion induced by 5-hydroxytryptophan, naloxone and haloperidol in male and female rats.

    Science.gov (United States)

    Becú-Villalobos, D; Lacau-Mengido, I M; Libertun, C

    1989-06-01

    Follicle-stimulating hormone (FSH) secretion is increased in the immature female rat from day 5 to days 17-18 of life, and decreases steadily thereafter until puberty. It has been reported that estradiol negative feedback and inhibin-like peptides are low during this period, while luteinizing hormone (LH) and FSH sensitivity to LH-releasing hormone (LHRH) are maximal. It was therefore of interest to study the effects of some neurotropic drugs on FSH release at 12 days of age, and to compare their effects at 1 and 20 days. Besides, as developmental patterns and regulation of FSH are different in male and female rats, the experiments were carried out using male and female littermates. The drugs chosen were haloperidol, 5-hydroxytryptophan and naloxone. These drugs release LH in the infantile female rat, the effect decreasing or disappearing as the animal matures; no effects of these drugs have been reported on FSH release in infantile rats to the present time. It was found that haloperidol (0.25 mg/kg), naloxone (2 mg/kg) and 5-hydroxytryptophan (50 mg/kg) markedly increased the already high titers of FSH in the 12-day-old female rat. This effect could not be discerned in newborn rats, and had disappeared at 20 days of age. Male littermates failed to respond at any age. When adult male and female rats in diestrus were tested, all drugs at the chosen doses were ineffective in altering FSH release. These data suggest that the infantile female rat represents an interesting physiological model to evaluate the neural regulation of FSH in a situation in which inhibitory signals provided by inhibin and estrogen in later life are diminished.

  19. Effects of Thyroid Dysfunction on Reproductive Hormones in Female Rats.

    Science.gov (United States)

    Liu, Juan; Guo, Meng; Hu, Xusong; Weng, Xuechun; Tian, Ye; Xu, Kaili; Heng, Dai; Liu, Wenbo; Ding, Yu; Yang, Yanzhou; Zhang, Cheng

    2018-05-10

    Thyroid hormones (THs) play a critical role in the development of ovarian cells. Although the effects of THs on female reproduction are of great interest, the mechanism remains unclear. We investigated the effects of TH dysregulation on reproductive hormones in rats. Propylthiouracil (PTU) and L-thyroxine were administered to rats to induce hypo- and hyper-thyroidism, respectively, and the reproductive hormone profiles were analyzed by radioimmunoassay. Ovarian histology was evaluated with H&E staining, and gene protein level or mRNA content was analyzed by western blotting or RT-PCR. The serum levels of gonadotropin releasing hormone (GnRH) and follicle stimulating hormone (FSH) in both rat models were significantly decreased on day 21, although there were no significant changes at earlier time points. There were no significant differences in luteinizing hormone (LH) or progesterone levels between the treatment and the control groups. Both PTU and L-thyroxine treatments downregulated estradiol concentrations; however, the serum testosterone level was increased only in hypothyroid rats at day 21. In addition, the expression levels of FSH receptor, cholesterol side-chain cleavage enzyme (P450scc), and steroidogenic acute regulatory protein were decreased in both rat models. Moreover, the onset of puberty was significantly delayed in the hypothyroid group. These results provide evidence that TH dysregulation alters reproductive hormone profiles, and that the initiation of the estrous cycle is postponed in hypothyroidism.

  20. Tamoxifen induces regression of estradiol-induced mammary cancer in the ACI.COP-Ept2 rat model.

    Science.gov (United States)

    Ruhlen, Rachel L; Willbrand, Dana M; Besch-Williford, Cynthia L; Ma, Lixin; Shull, James D; Sauter, Edward R

    2009-10-01

    The ACI rat is a unique model of human breast cancer in that mammary cancers are induced by estrogen without carcinogens, irradiation, xenografts or transgenic manipulations. We sought to characterize mammary cancers in a congenic variant of the ACI rat, the ACI.COP-Ept2. All rats with estradiol implants developed mammary cancers in 5-7 months. Rats bearing estradiol-induced mammary cancers were treated with tamoxifen for three weeks. Tamoxifen reduced tumor mass, measured by magnetic resonance imaging, by 89%. Tumors expressed estrogen receptors (ER), progesterone receptor (PR), and Erbb2. ERalpha and PR were overexpressed in tumor compared to adjacent non-tumor mammary gland. Thus, this model is highly relevant to hormone responsive human breast cancers.

  1. Puberty suppression in adolescents with gender identity disorder: a prospective follow-up study.

    Science.gov (United States)

    de Vries, Annelou L C; Steensma, Thomas D; Doreleijers, Theo A H; Cohen-Kettenis, Peggy T

    2011-08-01

    Puberty suppression by means of gonadotropin-releasing hormone analogues (GnRHa) is used for young transsexuals between 12 and 16 years of age. The purpose of this intervention is to relieve the suffering caused by the development of secondary sex characteristics and to provide time to make a balanced decision regarding actual gender reassignment. To compare psychological functioning and gender dysphoria before and after puberty suppression in gender dysphoric adolescents. Of the first 70 eligible candidates who received puberty suppression between 2000 and 2008, psychological functioning and gender dysphoria were assessed twice: at T0, when attending the gender identity clinic, before the start of GnRHa; and at T1, shortly before the start of cross-sex hormone treatment. Behavioral and emotional problems (Child Behavior Checklist and the Youth-Self Report), depressive symptoms (Beck Depression Inventory), anxiety and anger (the Spielberger Trait Anxiety and Anger Scales), general functioning (the clinician's rated Children's Global Assessment Scale), gender dysphoria (the Utrecht Gender Dysphoria Scale), and body satisfaction (the Body Image Scale) were assessed. Behavioral and emotional problems and depressive symptoms decreased, while general functioning improved significantly during puberty suppression. Feelings of anxiety and anger did not change between T0 and T1. While changes over time were equal for both sexes, compared with natal males, natal females were older when they started puberty suppression and showed more problem behavior at both T0 and T1. Gender dysphoria and body satisfaction did not change between T0 and T1. No adolescent withdrew from puberty suppression, and all started cross-sex hormone treatment, the first step of actual gender reassignment. Puberty suppression may be considered a valuable contribution in the clinical management of gender dysphoria in adolescents. © 2010 International Society for Sexual Medicine.

  2. Ussefulnes of imaging techniques in the diagnostics of precocious puberty in boys

    International Nuclear Information System (INIS)

    Jakubowska, Anna; Grajewska-Ferens, Magdalena; Brzewski, Michał; Sopyło, Barbara

    2011-01-01

    Precocious puberty (PP) is defined as the appearance of symptoms of puberty in girls before 8 years of age and in boys under 9. Statistically, it occurs much more frequently in girls, while it is a rare pathology in boys. Over the period of 10 years, between 1999 and 2009, 39 girls and 17 boys aged 18 months – 9 years were diagnosed with precocious puberty,, and treated at the Endocrinology Clinic. The following tests were performed in all children: physical and anthropometric examinations, abdominal ultrasound scan (US) with evaluation of adrenal glands, examination of testes in boys or breasts and pelvic organs in girls, evaluation of skeletal age and, in selected cases, CT scans of the abdomen, MRI of the CNS, and hormonal laboratory tests. In the group of 17 boys the findings included: gonadotropin –dependent central puberty in 6 boys: idiopathic in 5 cases, and 1 case of a brain tumor – astrocytoma. Gonadotropin-independent precocious pseudopuberty was diagnosed in 11 boys: congenital adrenal hyperplasia in 5; in 1case – hyperandrogenism caused by overactivity of 5-α reductase; in 2 subjects – adrenal adenoma; in 2 boys adrenocortical carcinoma was diagnosed and Leydig cell tumor of testis in 1. 1. Precocious puberty occurs less often in boys, but in our population it was found in 17 boys of 56 treated children, which constituted as much as 30%. 2. Precocious pseudopuberty was found in 64% of the boys with PP. 3. Adrenal and testicular tumors were the causes of precocious puberty in the youngest group of boys aged 18 months – 6 years

  3. A missense mutation in MKRN3 in a Danish girl with central precocious puberty and her brother with early puberty.

    Science.gov (United States)

    Känsäkoski, Johanna; Raivio, Taneli; Juul, Anders; Tommiska, Johanna

    2015-12-01

    Idiopathic central precocious puberty (ICPP) results from the premature reactivation of the hypothalamic-pituitary-gonadal axis leading to development of secondary sexual characteristics prior to 8 y in girls or 9 y in boys. Since the initial discovery of mutations in the maternally imprinted MKRN3 gene in 2013, several case reports have described mutations in this gene in ICPP patients from different populations, highlighting the importance of MKRN3 as a regulator of pubertal onset. We screened 29 Danish girls with ICPP for mutations in MKRN3. Expression of MKRN3 in human hypothalamic complementary DNA (cDNA) was investigated by PCR. One paternally inherited rare variant, c.1034G>A (p.Arg345His), was identified in one girl with ICPP and in her brother with early puberty. The variant is predicted to be deleterious by three different in silico prediction programs. Expression of MKRN3 was confirmed in adult human hypothalamus. Our results are in line with previous studies in which paternally inherited MKRN3 mutations have been found both in males and in females with ICPP or early puberty. Our report further expands the set of MKRN3 mutations identified in ICPP patients across diverse populations, thus supporting the major regulatory function of MKRN3 in pubertal onset.

  4. Examination of US puberty-timing data from 1940 to 1994 for secular trends

    DEFF Research Database (Denmark)

    Euling, Susan Y; Herman-Giddens, Marcia E; Lee, Peter A

    2008-01-01

    or girls. A majority of the panelists agreed that data are sufficient to suggest a trend toward an earlier breast development onset and menarche in girls but not for other female pubertal markers. A minority of panelists concluded that the current data on girls' puberty timing for any marker...... are insufficient. Almost all panelists concluded, on the basis of few studies and reliability issues of some male puberty markers, that current data for boys are insufficient to evaluate secular trends in male pubertal development. The panel agreed that altered puberty timing should be considered an adverse effect......Whether children, especially girls, are entering and progressing through puberty earlier today than in the mid-1900s has been debated. Secular trend analysis, based on available data, is limited by data comparability among studies in different populations, in different periods of time, and using...

  5. Progression of nephropathy after islet of langerhans transplantation in alloxan-induced diabetic rats

    Directory of Open Access Journals (Sweden)

    César Tadeu Spadella

    1997-03-01

    Full Text Available We studied the effects of islet of Langerhans transplantation (IT on the kidney lesions of rats with alloxan-induced diabetes. Forty-five inbred male Lewis rats were randomly assigned to 3 experimental groups: group Gl included 15 non-diabetic control rats (NC, group GIT included 15 alloxan-induced diabetic rats (DC, and group III included 15 alloxan-induced diabetic rats that received pancreatic islet transplantation prepared by nonenzymatic method from normal donor Lewis rats and injected into the portal vein (IT. Each group was further divided into 3 subgroups of 5 rats which were sacrificed at 1, 3, and 6 months of follow-up, respectively. Clinical and laboratorial parameters were recorded in the mentioned periods in the 3 experimental groups. For histology, the kidneys of all rats of each subgroup were studied and 50 glomeruli and 50 tubules of each kidney were analyzed using light microscopy by two different investigators in a double blind study. The results showed progressive glomerular basement membrane thickening (GBMT, mesangial enlargement (ME, and Bowman's capsule thickening (BCT in the 3 experimental groups throughout the follow-up. These alterations were significantly more severe in DC rats at 6 months when compared to NC rats (p < 0.01. However, the degree of GBMT, ME, and BCT observed in DC rats was not statistically different from IT rats at 1, 3, and 6 months. In addition, Armanni-Ebstein lesions of the tubules (AE and tubular lumen protein (PRO observed in DC rats were also observed in IT rats all over the study. These lesions were never present in NC rats. We conclude that IT did not prevent progression of kidney lesions in alloxan-induced diabetic rats within 6 months after transplantation.

  6. Diuron-induced rat bladder epithelial cytotoxicity.

    Science.gov (United States)

    Da Rocha, Mitscheli S; Arnold, Lora L; Pennington, Karen L; Muirhead, David; Dodmane, Puttappa R; Anwar, Muhammad M; Battalora, Michael; De Camargo, João Lauro V; Cohen, Samuel M

    2012-12-01

    Diuron, a substituted urea herbicide, is carcinogenic to the rat urinary bladder at high dietary levels (2500 ppm). To further elucidate the mode of action, this study aimed to determine the time course and sequence of bladder cytotoxic and proliferative changes induced by diuron treatment of male Wistar rats. Rats were randomized into two groups (control and 2500 ppm diuron) and treated for 28 days. Ten rats from each group were terminated on each of study days 1, 3, 7, or 28. Scanning electron micro scopy (SEM) showed urothelial cell swelling beginning on day 1, and by day 28, showed extensive necrosis, exfoliation and piling up of cells suggestive of hyperplasia. No difference in the bromo deoxyuridine labeling index was detected. In a second experiment, rats were randomized into control and diuron-treated groups and treated for 7 days or 8 weeks. After 7 days, transmission electron microscopy showed cell degenerative changes and distention of the cytoplasm, organelles, and nuclei characteristic of cytolysis. This resulted in protrusion of the superficial cells into the lumen, corresponding to the cell swelling observed previously by SEM. After 8 weeks, bladders in the diuron-treated group showed an increased incidence of simple hyperplasia by light microscopy (6/10, p diuron exposure in rats.

  7. Effects of fetal hypothyroidism on uterine smooth muscle contraction and structure of offspring rats.

    Science.gov (United States)

    Bagheripuor, Fatemeh; Ghanbari, Mahboubeh; Piryaei, Abbas; Ghasemi, Asghar

    2018-05-01

    What is the central question of this study? Does fetal hypothyroidism in rats alter uterine contractions and structure in the adult offspring? What is the main finding and its importance? Our study indicated that maternal hypothyroidism during pregnancy increased gestational length and decreased litter size. In addition, maternal hypothyroidism caused delayed puberty onset, irregular uterine contractions and histological changes in the uterus in the female offspring. This model might contribute to a better understanding of the cellular and molecular mechanisms involved in uterine contractions in fetal hypothyroidism, studies which are not possible in humans, and might help to establish therapeutic methods for these disorders observed in uterine contractions. Thyroid hormones play an essential role in fetal growth. Hypothyroidism impairs reproductive function in both humans and animals. The aim of this study was to assess the effects of fetal hypothyroidism on uterine smooth muscle contraction and structure in the adult offspring. The control group of female Wistar rats consumed tap water, whereas the hypothyroid group received water containing 0.025% of 6-propyl-2-thiouracial throughout gestation from mating until delivery. Isometric contractility and histological changes in uterine tissue were evaluated in the adult female offspring. We tested the effects of carbachol (10 -10 -10 -3  m) and oxytocin (10 -13 -10 -8  m) on uterine smooth muscle contraction in the fetal hypothyroid (FH) and control groups. Compared with control uteri, carbachol induced contractions with lower amplitude in the FH group (area under the curve: 1820.0 ± 250.0 versus 1370.0 ± 125.0 a.u., control versus FH group, respectively, P muscle layer and the cross-sectional area of the uterus were also significantly lower in the FH group. Gestational length was longer and litter size smaller in FH rats compared with control animals; FH offspring also had delayed puberty. In conclusion

  8. Nocturnal Urinary Excretion of FSH and LH in Children and Adolescents With Normal and Early Puberty

    DEFF Research Database (Denmark)

    Kolby, Nanna; Busch, Alexander S; Aksglaede, Lise

    2017-01-01

    aimed to evaluate urinary and serum gonadotropin levels according to age, sex, and pubertal stage in healthy children and to assess the clinical use of FMV urinary gonadotropins in children with disordered puberty. Design: Cross-sectional part of the COPENHAGEN Puberty Study and longitudinal study...... of patients. Setting: Population-based and outpatient clinic. Patients or Other Participants: Eight hundred forty-three healthy children from the COPENHAGEN Puberty Study and 25 girls evaluated for central precocious puberty (CPP). Main Outcome Measures: Clinical pubertal staging, including serum and urinary...... gonadotropin levels. Results: Urinary gonadotropins increased with advancing age and pubertal development and were detectable in FMV urine before physical signs of puberty. FMV urinary LH correlated strongly with basal (r = 0.871, P

  9. Minocycline attenuates cognitive impairment induced by isoflurane anesthesia in aged rats.

    Directory of Open Access Journals (Sweden)

    Feijuan Kong

    Full Text Available Postoperative cognitive dysfunction (POCD is a clinical phenomenon characterized by cognitive deficits in patients after anesthesia and surgery, especially in geriatric surgical patients. Although it has been documented that isoflurane exposure impaired cognitive function in several aged animal models, there are few clinical interventions and treatments available to prevent this disorder. Minocycline has been well established to exert neuroprotective effects in various experimental animal models and neurodegenerative diseases. Therefore, we hypothesized that pretreatment with minocycline attenuates isoflurane-induced cognitive decline in aged rats. In the present study, twenty-month-old rats were administered minocycline or an equal volume of saline by intraperitoneal injection 12 h before exposure to isoflurane. Then the rats were exposed to 1.3% isoflurane for 4 h. Two weeks later, spatial learning and memory of the rats were examined using the Morris Water Maze. We found that pretreatment with minocycline mitigated isoflurane-induced cognitive deficits and suppressed the isoflurane-induced excessive release of IL-1β and caspase-3 in the hippocampal CA1 region at 4 h after isoflurane exposure, as well as the number of TUNEL-positive nuclei. In addition, minocycline treatment also prevented the changes of synaptic ultrastructure in the hippocampal CA1 region induced by isoflurane. In conclusion, pretreatment with minocycline attenuated isoflurane-induced cognitive impairment in aged rats.

  10. Epilepsy-induced electrocardiographic alterations following cardiac ischemia and reperfusion in rats

    Energy Technology Data Exchange (ETDEWEB)

    Tavares, J.G.P. [Departamento de Farmacologia, Universidade Federal de São Paulo, São Paulo, SP (Brazil); Universidade Iguaçu, Campos V, Itaperuna, RJ (Brazil); Faculdade de Minas, Muriaé, MG (Brazil); Vasques, E.R. [Departamento de Gastroenterologia, LIM 37, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Arida, R.M. [Departamento de Fisiologia, Universidade Federal de São Paulo, São Paulo, SP (Brazil); Cavalheiro, E.A. [Departamento de Neurologia e Neurocirurgia, Universidade Federal de São Paulo, São Paulo, SP (Brazil); Cabral, F.R.; Torres, L.B. [Hospital Israelita Albert Einstein, Instituto do Cérebro, São Paulo, SP (Brazil); Menezes-Rodrigues, F.S.; Jurkiewicz, A.; Caricati-Neto, A. [Departamento de Farmacologia, Universidade Federal de São Paulo, São Paulo, SP (Brazil); Godoy, C.M.G. [Departamento de Ciência e Tecnologia, Universidade Federal de São Paulo, São José dos Campos, SP (Brazil); Gomes da Silva, S. [Hospital Israelita Albert Einstein, Instituto do Cérebro, São Paulo, SP (Brazil); Núcleo de Pesquisas Tecnológicas, Programa Integrado em Engenharia Biomédica, Universidade de Mogi das Cruzes, Mogi das Cruzes, SP (Brazil)

    2015-01-13

    The present study evaluated electrocardiographic alterations in rats with epilepsy submitted to an acute myocardial infarction (AMI) model induced by cardiac ischemia and reperfusion. Rats were randomly divided into two groups: control (n=12) and epilepsy (n=14). It was found that rats with epilepsy presented a significant reduction in atrioventricular block incidence following the ischemia and reperfusion procedure. In addition, significant alterations were observed in electrocardiogram intervals during the stabilization, ischemia, and reperfusion periods of rats with epilepsy compared to control rats. It was noted that rats with epilepsy presented a significant increase in the QRS interval during the stabilization period in relation to control rats (P<0.01). During the ischemia period, there was an increase in the QRS interval (P<0.05) and a reduction in the P wave and QT intervals (P<0.05 for both) in rats with epilepsy compared to control rats. During the reperfusion period, a significant reduction in the QT interval (P<0.01) was verified in the epilepsy group in relation to the control group. Our results indicate that rats submitted to an epilepsy model induced by pilocarpine presented electrical conductivity alterations of cardiac tissue, mainly during an AMI episode.

  11. Epilepsy-induced electrocardiographic alterations following cardiac ischemia and reperfusion in rats

    International Nuclear Information System (INIS)

    Tavares, J.G.P.; Vasques, E.R.; Arida, R.M.; Cavalheiro, E.A.; Cabral, F.R.; Torres, L.B.; Menezes-Rodrigues, F.S.; Jurkiewicz, A.; Caricati-Neto, A.; Godoy, C.M.G.; Gomes da Silva, S.

    2015-01-01

    The present study evaluated electrocardiographic alterations in rats with epilepsy submitted to an acute myocardial infarction (AMI) model induced by cardiac ischemia and reperfusion. Rats were randomly divided into two groups: control (n=12) and epilepsy (n=14). It was found that rats with epilepsy presented a significant reduction in atrioventricular block incidence following the ischemia and reperfusion procedure. In addition, significant alterations were observed in electrocardiogram intervals during the stabilization, ischemia, and reperfusion periods of rats with epilepsy compared to control rats. It was noted that rats with epilepsy presented a significant increase in the QRS interval during the stabilization period in relation to control rats (P<0.01). During the ischemia period, there was an increase in the QRS interval (P<0.05) and a reduction in the P wave and QT intervals (P<0.05 for both) in rats with epilepsy compared to control rats. During the reperfusion period, a significant reduction in the QT interval (P<0.01) was verified in the epilepsy group in relation to the control group. Our results indicate that rats submitted to an epilepsy model induced by pilocarpine presented electrical conductivity alterations of cardiac tissue, mainly during an AMI episode

  12. Early Puberty, Negative Peer Influence, and Problem Behaviors in Adolescent Girls

    Science.gov (United States)

    Elliott, Marc N.; Davies, Susan; Tortolero, Susan R.; Cuccaro, Paula; Schuster, Mark A.

    2014-01-01

    OBJECTIVE: To determine how early puberty and peer deviance relate to trajectories of aggressive and delinquent behavior in early adolescence and whether these relationships differ by race/ethnicity. METHODS: In this longitudinal study, 2607 girls from 3 metropolitan areas and their parents were interviewed at ages 11, 13, and 16 years. Girls reported on their age of onset of menarche, best friend’s deviant behavior, delinquency, and physical, relational, and nonphysical aggression. Parents provided information on family sociodemographic characteristics and girls’ race/ethnicity. RESULTS: Sixteen percent of girls were classified as early maturers (defined by onset of menarche before age 11 years). Overall, relational and nonphysical aggression increased from age 11 to age 16, whereas delinquency and physical aggression remained stable. Early puberty was associated with elevated delinquency and physical aggression at age 11. The relationship with early puberty diminished over time for physical aggression but not for delinquency. Best friend’s deviant behavior was linked with higher levels of all problem behaviors, but the effect lessened over time for most outcomes. Early puberty was associated with a stronger link between best friend’s deviance and delinquency, suggesting increased vulnerability to negative peer influences among early-maturing girls. A similar vulnerability was observed for relational and nonphysical aggression among girls in the “other” racial/ethnic minority group only. CONCLUSIONS: Early puberty and friends’ deviance may increase the risk of problem behavior in young adolescent girls. Although many of these associations dissipate over time, early-maturing girls are at risk of persistently higher delinquency and stronger negative peer influences. PMID:24324002

  13. Early puberty, negative peer influence, and problem behaviors in adolescent girls.

    Science.gov (United States)

    Mrug, Sylvie; Elliott, Marc N; Davies, Susan; Tortolero, Susan R; Cuccaro, Paula; Schuster, Mark A

    2014-01-01

    To determine how early puberty and peer deviance relate to trajectories of aggressive and delinquent behavior in early adolescence and whether these relationships differ by race/ethnicity. In this longitudinal study, 2607 girls from 3 metropolitan areas and their parents were interviewed at ages 11, 13, and 16 years. Girls reported on their age of onset of menarche, best friend's deviant behavior, delinquency, and physical, relational, and nonphysical aggression. Parents provided information on family sociodemographic characteristics and girls' race/ethnicity. Sixteen percent of girls were classified as early maturers (defined by onset of menarche before age 11 years). Overall, relational and nonphysical aggression increased from age 11 to age 16, whereas delinquency and physical aggression remained stable. Early puberty was associated with elevated delinquency and physical aggression at age 11. The relationship with early puberty diminished over time for physical aggression but not for delinquency. Best friend's deviant behavior was linked with higher levels of all problem behaviors, but the effect lessened over time for most outcomes. Early puberty was associated with a stronger link between best friend's deviance and delinquency, suggesting increased vulnerability to negative peer influences among early-maturing girls. A similar vulnerability was observed for relational and nonphysical aggression among girls in the "other" racial/ethnic minority group only. Early puberty and friends' deviance may increase the risk of problem behavior in young adolescent girls. Although many of these associations dissipate over time, early-maturing girls are at risk of persistently higher delinquency and stronger negative peer influences.

  14. Puberty Health Status among Adolescent Girls: A Model- based Educational Program

    Directory of Open Access Journals (Sweden)

    Fatemeh Kheirollahi

    2017-07-01

    Full Text Available Background Adolescence is the period of transition from childhood to adulthood and is one of the fastest stages of human development which is simultaneous to start of puberty. This study aimed to investigate the puberty health status among adolescent girls through a model- based educational program. Materials and Methods The current study was an interventional quasi-experimental research. It was conducted on 152 girls aged 13 to 15 years old on the city of Qom- Iran. To select the subjects, first an education zone was randomly selected. In that zone, two schools were randomly selected as the intervention and control groups (76 for interventional group and 76 for control group.After confirming the reliability and validity of a researcher-made questionnaire, it was used to collect the required data via self-reports. Data were analyzed using SPSS version 20.0 software. Results The mean age and menarche of the students were 13.59 ± 0.87 and 12.38 ± 0.99 years, respectively. There was a statistically significant difference between the mean scores of knowledge and behavior in intervention and control groups after educational intervention, so that the mean scores of knowledge and behavior about puberty health in the intervention group were higher than the control group (P 0.05. Conclusion As the results showed, before the intervention the status of knowledge, attitude toward puberty health, and behavior about puberty health of the studied students was not favorable. Therefore, it is necessary to highlight the need for educational interventions and the role of health professionals in this field.

  15. Puberty as a critical risk period for eating disorders: a review of human and animal studies.

    Science.gov (United States)

    Klump, Kelly L

    2013-07-01

    This article is part of a Special Issue "Puberty and Adolescence". Puberty is one of the most frequently discussed risk periods for the development of eating disorders. Prevailing theories propose environmentally mediated sources of risk arising from the psychosocial effects (e.g., increased body dissatisfaction, decreased self-esteem) of pubertal development in girls. However, recent research highlights the potential role of ovarian hormones in phenotypic and genetic risk for eating disorders during puberty. The goal of this paper is to review data from human and animal studies in support of puberty as a critical risk period for eating disorders and evaluate the evidence for hormonal contributions. Data are consistent in suggesting that both pubertal status and pubertal timing significantly impact risk for most eating disorders in girls, such that advanced pubertal development and early pubertal timing are associated with increased rates of eating disorders and their symptoms in both cross-sectional and longitudinal research. Findings in boys have been much less consistent and suggest a smaller role for puberty in risk for eating disorders in boys. Twin and animal studies indicate that at least part of the female-specific risk is due to genetic factors associated with estrogen activation at puberty. In conclusion, data thus far support a role for puberty in risk for eating disorders and highlight the need for additional human and animal studies of hormonal and genetic risk for eating disorders during puberty. Copyright © 2013 Elsevier Inc. All rights reserved.

  16. Effects of environmental enrichment during abstinence in morphine dependent parents on anxiety, depressive-like behaviors and voluntary morphine consumption in rat offspring.

    Science.gov (United States)

    Pooriamehr, Alireza; Sabahi, Parviz; Miladi-Gorji, Hossein

    2017-08-24

    Chronic morphine exposure during puberty increased morphine-induced rewarding effects and sensitization in the next generation. Given the well-known beneficial effects of environmental enrichment on the severity of physical and psychological dependence on morphine, we examined effects of enriched environment during morphine abstinence in morphine dependent parental rats before mating on the anxiety and depressive-like behaviors, and voluntary morphine consumption in their offspring. Paternal and/or maternal rats were injected with bi-daily doses (10mg/kg, 12h intervals) of morphine for 14days followed by rearing in a standard environment (SE) or enriched environment (EE) during 30days of morphine abstinence before mating. The pubertal male and female rat offspring were tested for anxiety (the elevated plus maze- EPM) and depression (sucrose preference test-SPT), and voluntary morphine consumption using a two-bottle choice (TBC) paradigm. The results showed that EE experience in morphine-dependent both parents result in an increase in the percentage of time spent into open arms/time spent on both arms using EPM in male offspring, higher levels of sucrose preference in female offspring and lower levels of voluntary morphine consumption in male and female offspring. Thus, EE experience in morphine-dependent both parents reduced anxiety, depressive-like behavior and also the voluntary morphine consumption in their offspring during puberty which may prevent the vulnerability of the next generation to drug abuse. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Trithorax dependent changes in chromatin landscape at enhancer and promoter regions drive female puberty.

    Science.gov (United States)

    Toro, Carlos A; Wright, Hollis; Aylwin, Carlos F; Ojeda, Sergio R; Lomniczi, Alejandro

    2018-01-04

    Polycomb group (PcG) proteins control the timing of puberty by repressing the Kiss1 gene in hypothalamic arcuate nucleus (ARC) neurons. Here we identify two members of the Trithorax group (TrxG) of modifiers, mixed-lineage leukemia 1 (MLL1), and 3 (MLL3), as central components of an activating epigenetic machinery that dynamically counteracts PcG repression. Preceding puberty, MLL1 changes the chromatin configuration at the promoters of Kiss1 and Tac3, two genes required for puberty to occur, from repressive to permissive. Concomitantly, MLL3 institutes a chromatin structure that changes the functional status of a Kiss1 enhancer from poised to active. RNAi-mediated, ARC-specific Mll1 knockdown reduced Kiss1 and Tac3 expression, whereas CRISPR-Cas9-directed epigenome silencing of the Kiss1 enhancer selectively reduced Kiss1 activity. Both interventions delay puberty and disrupt reproductive cyclicity. Our results demonstrate that an epigenetic switch from transcriptional repression to activation is crucial to the regulatory mechanism controlling the timing of mammalian puberty.

  18. Serum levels of growth hormone binding protein in children with normal and precocious puberty

    DEFF Research Database (Denmark)

    Juul, A; Fisker, Sidse; Scheike, Thomas Harder

    2000-01-01

    To study the regulation of GHBP serum levels by gonadal steroids in normal and precocious puberty.......To study the regulation of GHBP serum levels by gonadal steroids in normal and precocious puberty....

  19. Nocturnal Urinary Excretion of FSH and LH in Children and Adolescents With Normal and Early Puberty.

    Science.gov (United States)

    Kolby, Nanna; Busch, Alexander S; Aksglaede, Lise; Sørensen, Kaspar; Petersen, Jorgen Holm; Andersson, Anna-Maria; Juul, Anders

    2017-10-01

    Clinical use of single serum gonadotropin measurements in children is limited by the pulsatile secretion of follicle-stimulating hormone (FSH) and luteinizing hormone (LH). However, first morning voided (FMV) urine may integrate the fluctuating gonadotropin serum levels. We aimed to evaluate urinary and serum gonadotropin levels according to age, sex, and pubertal stage in healthy children and to assess the clinical use of FMV urinary gonadotropins in children with disordered puberty. Cross-sectional part of the COPENHAGEN Puberty Study and longitudinal study of patients. Population-based and outpatient clinic. Eight hundred forty-three healthy children from the COPENHAGEN Puberty Study and 25 girls evaluated for central precocious puberty (CPP). Clinical pubertal staging, including serum and urinary gonadotropin levels. Urinary gonadotropins increased with advancing age and pubertal development and were detectable in FMV urine before physical signs of puberty. FMV urinary LH correlated strongly with basal (r = 0.871, P 5 IU/L). Urinary concentrations of LH decreased after 3 months of GnRH treatment to levels below +2 SDs. Urinary gonadotropin levels increased before the onset of puberty and were elevated in girls with CPP. We suggest urinary LH as an alternative noninvasive method to improve diagnosing and therapeutic management of children with disordered puberty. Copyright © 2017 Endocrine Society

  20. Moderate High Fat Diet Increases Sucrose Self-Administration In Young Rats

    OpenAIRE

    Figlewicz, Dianne P.; Jay, Jennifer L.; Acheson, Molly A.; Magrisso, Irwin J.; West, Constance H.; Zavosh, Aryana; Benoit, Stephen C.; Davis, Jon F.

    2012-01-01

    We have previously reported that a moderately high fat diet increases motivation for sucrose in adult rats. In this study, we tested the motivational, neurochemical, and metabolic effects of the high fat diet in male rats transitioning through puberty, during 5-8 weeks of age. We observed that the high fat diet increased motivated responding for sucrose, which was independent of either metabolic changes or changes in catecholamine neurotransmitter metabolites in the nucleus accumbens. However...

  1. Ovarian reaction and estrus manifestation in delayed puberty gilts after treatment with equine chorionic gonadotropin

    Directory of Open Access Journals (Sweden)

    Stančić Ivan B

    2012-08-01

    Full Text Available Abstract Background Prolonged pre-insemination anestrus (i.e. delayed puberty is a major contributing factor for culling up to 30% of the replacement gilts at large breeding farm units in Vojvodina. It is imperative to determine if these gilts are acyclic (prepubertal or cyclic, but just fail to exhibit behavioural estrus. Recent investigations demonstrate that treatment with equine chorionic gonadotropin (eCG can increase the diestrous phase duration in sexually mature gilts. Based on these finding, the aim of the present studies was to determine the reproductive status of delayed puberty gilts following injection with eCG. Methods Two experiments were conducted on a swine breeding farm in Vojvodina. In Exp. 1, 20 prepubertal (acyclic gilts, and 120 sexually mature (cyclic gilts were injected with a single injection of 400 IU eCG + 200 IU human chorionic gonadotropin (hCG or with 1000 IU eCG (cyclic gilts, at d5, d11 or d17 after spontaneous estrus detection, to determine their ovarian reaction and induced estrus manifestation. In Exp. 2, sixty delayed puberty gilts (estrus not detected until 8 month of age, av. 258 days were culled from breeding herd and slaughtered to determine their reproductive status based on ovarian anatomical features. The second group of gilts (n = 60 was treated with a single 1000 IU eCG injection to determine their reproductive status, based on the interval between eCG injection to estrus detection and duration. The data were analyzed by descriptive statistics, t-test, analysis of variance and Duncan’s test in the software package Statistics 10th. Results Ovulations were induced in 90% of acyclic (sexually immature and, on average, 93.3% of cyclic (sexually mature gilts after the eCG injection. On average, 4 days after the eCG injection, estrus was detected in 85% of the treated acyclic (sexually immature gilts and in 95% (19/20 of the cyclic (sexually mature gilts, treated with eCG on day 17

  2. Vaginal thread formation in the healthy offspring of untreated Long-Evans rats

    Science.gov (United States)

    Vaginal threads are characterized as cords of mesenchymal tissue that cross the vaginal opening. They are sometimes apparent in rats after weaning, and typically disappear within 1-2 days as the female reaches puberty. If persistent, they can increase uncertainty in assessing rep...

  3. Diet-Induced Ketosis Improves Cognitive Performance in Aged Rats

    Science.gov (United States)

    Xu, Kui; Sun, Xiaoyan; Eroku, Bernadette O.; Tsipis, Constantinos P.; Puchowicz, Michelle A.; LaManna, Joseph C.

    2010-01-01

    Aging is associated with increased susceptibility to hypoxic/ischemic insult and declines in behavioral function which may be due to attenuated adaptive/defense responses. We investigated if diet-induced ketosis would improve behavioral performance in the aged rats. Fischer 344 rats (3- and 22-month-old) were fed standard (STD) or ketogenic (KG) diet for 3 weeks and then exposed to hypobaric hypoxia. Cognitive function was measured using the T-maze and object recognition tests. Motor function was measured using the inclined-screen test. Results showed that KG diet significantly increased blood ketone levels in both young and old rats. In the aged rats, the KG diet improved cognitive performance under normoxic and hypoxic conditions; while motor performance remained unchanged. Capillary density and HIF-1α levels were elevated in the aged ketotic group independent of hypoxic challenge. These data suggest that diet-induced ketosis may be beneficial in the treatment of neurodegenerative conditions. PMID:20204773

  4. Exenatide Induces Impairment of Autophagy Flux to Damage Rat Pancreas.

    Science.gov (United States)

    Li, Zhiqiang; Huang, Lihua; Yu, Xiao; Yu, Can; Zhu, Hongwei; Li, Xia; Han, Duo; Huang, Hui

    2017-01-01

    The study aimed to explore the alteration of autophagy in rat pancreas treated with exenatide. Normal Sprague-Dawley rats and diabetes-model rats induced by 2-month high-sugar and high-fat diet and streptozotocin injection were subcutaneously injected with exenatide, respectively, for 10 weeks, with homologous rats treated with saline as control. Meanwhile, AR42J cells, pancreatic acinar cell line, were cultured with exenatide at doses of 5 pM for 3 days. The pancreas was disposed, and several sections were stained with hematoxylin-eosin. Immunohistochemistry was used to measure the expressions of glucagon-like peptide 1 receptor (GLP-1R) and cysteine-aspartic acid protease-3 in rat pancreas, and Western blot was used to test the expressions of GLP-1R, light chain 3B-I and -II, and p62 in rat pancreas and AR42J cells. The data were expressed as mean (standard deviation) and analyzed by unpaired Student's t-test. Exenatide can induce pathological changes in rat pancreas. The GLP-1R, p62, light chain 3B-II, and cysteine-aspartic acid protease-3 in rat pancreas and AR42J cells treated with exenatide were significantly overexpressed. Exenatide can activate and upregulate its receptor, GLP-1R, then impair autophagy flux and activate apoptosis in the pancreatic acinar cell, thus damaging rat pancreas.

  5. Nociceptive Response to L-DOPA-Induced Dyskinesia in Hemiparkinsonian Rats.

    Science.gov (United States)

    Nascimento, G C; Bariotto-Dos-Santos, K; Leite-Panissi, C R A; Del-Bel, E A; Bortolanza, M

    2018-04-02

    Non-motor symptoms are increasingly identified to present clinical and diagnostic importance for Parkinson's disease (PD). The multifactorial origin of pain in PD makes this symptom of great complexity. The dopamine precursor, L-DOPA (L-3,4-dihydroxyphenylalanine), the classic therapy for PD, seems to be effective in pain threshold; however, there are no studies correlating L-DOPA-induced dyskinesia (LID) and nociception development in experimental Parkinsonism. Here, we first investigated nociceptive responses in a 6-hydroxydopamine (6-OHDA)-lesioned rat model of Parkinson's disease to a hind paw-induced persistent inflammation. Further, the effect of L-DOPA on nociception behavior at different times of treatment was investigated. Pain threshold was determined using von Frey and Hot Plate/Tail Flick tests. Dyskinesia was measured by abnormal involuntary movements (AIMs) induced by L-DOPA administration. This data is consistent to show that 6-OHDA-lesioned rats had reduced nociceptive thresholds compared to non-lesioned rats. Additionally, when these rats were exposed to a persistent inflammatory challenge, we observed increased hypernociceptive responses, namely hyperalgesia. L-DOPA treatment alleviated pain responses on days 1 and 7 of treatment, but not on day 15. During that period, we observed an inverse relationship between LID and nociception threshold in these rats, with a high LID rate corresponding to a reduced nociception threshold. Interestingly, pain responses resulting from CFA-induced inflammation were significantly enhanced during established dyskinesia. These data suggest a pro-algesic effect of L-DOPA-induced dyskinesia, which is confirmed by the correlation founded here between AIMs and nociceptive indexes. In conclusion, our results are consistent with the notion that central dopaminergic mechanism is directly involved in nociceptive responses in Parkinsonism condition.

  6. Telmisartan attenuates diabetes induced depression in rats.

    Science.gov (United States)

    Aswar, Urmila; Chepurwar, Shilpa; Shintre, Sumit; Aswar, Manoj

    2017-04-01

    Role of brain renin angiotensin system (RAS) is well understood and various clinical studies have proposed neuroprotective effects of ARB's. It is also assumed that diabetic depression is associated with activation of brain RAS, HPA axis dysregulation and brain inflammatory events. Therefore, the present study was designed to investigate the antidepressant effect of low dose telmisartan (TMS) in diabetes induced depression (DID) in rats. Diabetes was induced by injecting streptozotocin. After 21days of treatment the rats were subjected to forced swim test (FST). The rats, with increased immobility time, were considered depressed and were treated with vehicle or TMS (0.05mg/kg, po) or metformin (200mg/kg, po) or fluoxetine (20mg/kg, po). A separate group was also maintained to study the combination of metformin and TMS. At the end of 21days of treatments, FST, open field test (OFT) and elevated plus maze (EPM) paradigm were performed. Blood was drawn to estimate serum cortisol, nitric oxide (NO), interleukin-6 (IL-6) and interleukin-1β (IL-1β). Persistent hyperglycemia resulted in depression and anxiety in rats as observed by increased immobility, reduced latency for immobility, reduced open arm entries and time spent. The depressed rats showed a significant rise in serum cortisol, NO, IL-6 and IL-1β (pdepression and anxiety. It also significantly attenuated serum cortisol, NO, IL-6 and IL-1β (pdepressive mood, reduces pro-inflammatory mediators and ameliorates the HPA axis function; thereby providing beneficial effects in DID. Copyright © 2016. Published by Elsevier Urban & Partner Sp. z o.o.

  7. Rebaudioside A inhibits pentylenetetrazol-induced convulsions in rats

    Directory of Open Access Journals (Sweden)

    Yigit Uyanikgil

    2016-09-01

    Full Text Available The safety of patients with epilepsy consuming sweetening agents, which is becoming increasingly prevalent for various reasons, is a topic that should be emphasized as sensitively as it is for other diseases. Patients with epilepsy consume sweetening agents for different reasons such being diabetic or overweight. They can occasionally be exposed to sweetening agents unrestrainedly through consuming convenience food, primarily beverages. This study aimed to investigate the effects of rebaudioside A (Reb-A, which is a steviol glycoside produced from the herb Stevia rebaudiana (Bertoni, on epileptic seizures and convulsions induced by pentylenetetrazole (PTZ. Forty-eight male rats were used. Twenty-four rats were administered 35 mg/kg PTZ to trigger epileptiform activity; the remaining 24 rats were administered 70 mg/kg PTZ to trigger the convulsion model. The epileptiform activity was evaluated by spike percentage, whereas convulsion was evaluated by Racine's Convulsion Scale and the onset time of the first myoclonic jerk. Statistical analysis revealed a statistically significant decrease in the Racine's Convulsion Scale score and increase in the latency of first myoclonic jerk in a dose-dependent manner for the rat groups in which PTZ epilepsy had been induced and Reb-A had been administered. For the groups that were administered Reb-A, the spike decrease was apparent in a dose-dependent manner, based on the spike percentage calculation. These results indicated that Reb-A has positive effects on PTZ-induced convulsions.

  8. The relationship between obesity and body compositions with respect to the timing of puberty in Chongqing adolescents: a cross-sectional study.

    Science.gov (United States)

    He, Fang; Guan, Peiyu; Liu, Qin; Crabtree, Donna; Peng, Linli; Wang, Hong

    2017-08-18

    It is well known that excess adiposity during childhood may influence pubertal development. However, the extent to which body compositions vary in throughout puberty in boys and girls is currently unknown. The aim of this study was to investigate whether obesity and body compositions correlate with the timing of puberty in boys and girls. By random cluster sampling, our study analyzed data from 1472 students (690 girls, 782 boys) aged 6-17 years from two schools in the Chongqing area. Data were collected by physical examination of weight, height, and skinfold thicknesses. Testicular volume was measured in boys and breast development in girls. By which we got the indicators of obesity, timing of puberty and body compositions. Probit regression analysis was used to group subjects into early puberty (>P 25 ), on-time puberty (P 25  ~ P 75 ), and delayed puberty (puberty groups by sex. Multivariate analysis of covariance was used to examine the association between timing of puberty and body composition indicators. There were significant differences in the distribution of fat levels (normal weigh, overweight, obesity) among different pubertal groups in different sex (boys:χ2 = 10.639, P = 0.031; girls:χ2 = 63.232, P = 0.000). Multivariate analysis of covariance showed that percentage of body fat, fat mass and fat-free mass in the delayed puberty girls were significantly lower than the girls in the on-time puberty and early puberty, while body density had the opposite result (all P puberty groups (all P > 0.05). In girls, delayed puberty was negatively correlated with Obesity, percentage of body fat, fat mass and fat-free mass, and positively correlated with body density. But in boys, delayed puberty was only negatively correlated with Obesity, the relation between puberty and body compositions was not found.

  9. Radiation-induced mesotheliomas in rats

    International Nuclear Information System (INIS)

    Hahn, F.F.; Haley, P.J.; Hubbs, A.F.; Hoover, M.D.; Lundgren, D.L.

    1990-01-01

    Mesotheliomas have been reported in rats that inhaled plutonium, but these tumors have not been extensively studied. To investigate a possible role for inhaled radionuclides in the induction of mesotheliomas, four life-span studies conducted at the Inhalation Toxicology Research Institute are reviewed. A total of 3076 F344 rats were exposed by inhalation to aerosols of 239 PuO 2 , mixed uranium-plutonium oxide, or 144 CeO 2 . Results showed that a low incidence of pleural mesotheliomas was induced by either alpha- or beta-emitting radionuclides deposited and retained in the lung. Chronic alpha irradiation was more effective per unit dose in producing mesotheliomas than chronic beta irradiation of the lung by a factor of 15. 7 refs., 1 tab., 7 figs

  10. [Age of onset of puberty in Chilean boys according to testicular volume and Tanner stage].

    Science.gov (United States)

    Gaete, Ximena; García, Roberto; Riquelme, Joel; Codner, Ethel

    2015-03-01

    A secular trend towards a younger age of puberty onset has been reported in Chilean girls. To evaluate the age of onset of puberty and prevalence of early puberty in Chilean boys. A pediatric endocrinologist examined 319 children attending schools in central Santiago. Pubertal development was assessed by testicular volume (TV) and genital inspection (GI) using Tanner graduation. Precocious and early puberty development was diagnosed if TV ≥ 4 ml or GI > stage 2 occurred in boys younger than 9 years and at 9-10 years of age, respectively. Pubertal onset occurred at 10.2 ± 1.5 years according to TV and at 11.1 ± 1.6 years according to GI (p puberty was observed in 23.8% of children according to TV and 9.5% according to GI. However, no child of less than 11 years old had a TV ≥ 4 ml, genital changes and pubic hair simultaneously. Late pubertal stages occurred at the same age according to both criteria used. Body mass index z score was not associated with the age of pubertal onset. Testicular enlargement occurs one year earlier than changes in genitalia according to inspection. Testicular growth, but not late stages of puberty, are occurring one year earlier than previously reported in Chile 10 years ago.

  11. Kefir treatment ameliorates dextran sulfate sodium-induced colitis in rats.

    Science.gov (United States)

    Senol, Altug; Isler, Mehmet; Sutcu, Recep; Akin, Mete; Cakir, Ebru; Ceyhan, Betul M; Kockar, M Cem

    2015-12-14

    To investigate the preventive effect of kefir on colitis induced with dextran sulfate sodium (DSS) in rats. Twenty-four male Wistar-albino rats were randomized into four groups: normal control, kefir-control, colitis, and kefir-colitis groups. Rats in the normal and kefir-control groups were administered tap water as drinking water for 14 d. Rats in the colitis and kefir-colitis groups were administered a 3% DSS solution as drinking water for 8-14 d to induce colitis. Rats in the kefir-control and kefir-colitis groups were administered 5 mL kefir once a day for 14 d while rats in the normal control and colitis group were administered an identical volume of the placebo (skim milk) using an orogastric feeding tube. Clinical colitis was evaluated with reference to the disease activity index (DAI), based on daily weight loss, stool consistency, and presence of bleeding in feces. Rats were sacrificed on the 15(th) day, blood specimens were collected, and colon tissues were rapidly removed. Levels of myeloperoxidase (MPO), tumor necrosis factor (TNF)-α, interleukin (IL)-10, malondialdehyde, and inducible nitric oxide synthase (iNOS) were measured in colon tissue. The DAI was lower in the kefir-colitis group than in the colitis group (on the 3(rd) and 5(th) days of colitis induction; P < 0.01). The DAI was also significantly higher in the colitis group between days 2 and 6 of colitis induction when compared to the normal control and kefir-control groups. The DAI was statistically higher only on the 6(th) day in the kefir-colitis group when compared to that in the normal control groups. Increased colon weight and decreased colon length were observed in colitis-induced rats. Mean colon length in the colitis group was significantly shorter than that of the kefir-control group. Kefir treatment significantly decreased histologic colitis scores (P < 0.05). MPO activity in the colitis group was significantly higher than in the kefir-control group (P < 0.05). Kefir treatment

  12. The Role of Mother in Informing Girls About Puberty: A Meta-Analysis Study

    Science.gov (United States)

    Sooki, Zahra; Shariati, Mohammad; Chaman, Reza; Khosravi, Ahmad; Effatpanah, Mohammad; Keramat, Afsaneh

    2016-01-01

    Context Family, especially the mother, has the most important role in the education, transformation of information, and health behaviors of girls in order for them to have a healthy transition from the critical stage of puberty, but there are different views in this regard. Objectives Considering the various findings about the source of information about puberty, a meta-analysis study was conducted to investigate the extent of the mother’s role in informing girls about puberty. Data Sources This meta-analysis study was based on English articles published from 2000 to February 2015 in the Scopus, PubMed, and Science direct databases and on Persian articles in the SID, Magiran, and Iran Medex databases with determined key words and their MeSH equivalent. Study Selection Quantitative cross-sectional articles were extracted by two independent researchers and finally 46 articles were selected based on inclusion criteria. STROBE list were used for evaluation of studies. Data Extraction The percent of mothers as the current and preferred source of gaining information about the process of puberty, menarche, and menstruation from the perspective of adolescent girls was extracted from the articles. The results of studies were analyzed using meta-analysis (random effects model) and the studies’ heterogeneity was analyzed using the I2 calculation index. Variance between studies was analyzed using tau squared (Tau2) and review manager 5 software. Results The results showed that, from the perspective of teenage girls in Iran and other countries, in 56% of cases, the mother was the current source of information about the process of puberty, menarche, and menstruation. The preferred source of information about the process of puberty, menarche, and menstruation was the mother in all studies at 60% (Iran 57%, and other countries 66%). Conclusions According to the findings of this study, it is essential that health professionals and officials of the ministry of health train

  13. Public health implications of altered puberty timing

    DEFF Research Database (Denmark)

    Golub, M.S.; Collman, G.W.; Foster, P.M.

    2008-01-01

    for chemicals. Recent US legislation has mandated improved chemical testing approaches for protecting children's health and screening for endocrine-disrupting agents, which has led to changes in the US Environmental Protection Agency's risk assessment and toxicity testing guidelines to include puberty...

  14. Puberty as a Critical Risk Period for Eating Disorders: A Review of Human and Animal Studies

    Science.gov (United States)

    Klump, Kelly L.

    2013-01-01

    Puberty is one of the most frequently discussed risk periods for the development of eating disorders. Prevailing theories propose environmentally mediated sources of risk arising from the psychosocial effects (e.g., increased body dissatisfaction, decreased self-esteem) of pubertal development in girls. However, recent research highlights the potential role of ovarian hormones in phenotypic and genetic risk for eating disorders during puberty. The goal of this paper is to review data from human and animal studies in support of puberty as a critical risk period for eating disorders and evaluate the evidence for hormonal contributions. Data are consistent in suggesting that both pubertal status and pubertal timing significantly impact risk for most eating disorders in girls, such that advanced pubertal development and early pubertal timing are associated with increased rates of eating disorders and their symptoms in both cross-sectional and longitudinal research. Findings in boys have been much less consistent and suggest a smaller role for puberty in risk for eating disorders in boys. Twin and animal studies indicate that at least part of the female-specific risk is due to genetic factors associated with estrogen activation at puberty. In conclusion, data thus far support a role for puberty in risk for eating disorders and highlight the need for additional human and animal studies of hormonal and genetic risk for eating disorders during puberty. PMID:23998681

  15. Increased risk of precocious puberty in internationally adopted children in Denmark

    DEFF Research Database (Denmark)

    Teilmann, G.; Pedersen, Carsten Bøcker; Skakkebæk, N.E.

    2006-01-01

    settings from birth to adoption, whereas most other countries are reported to take care of the children in orphanages before adoption. It can only be speculated whether a relation between preadoption living conditions and later risk of precocious puberty exists. Genetic factors play a key role...... identified through the unique Danish Civil Registration System and subsequently categorized as being Danish (N = 1,062,333), adopted (N = 10,997), immigrating with their family (N = 72,181), or being descendants of immigrants (N = 128,152). The incidence rate ratio of precocious puberty was estimated by log......-linear Poisson regression. All rate ratios were adjusted for age and its interaction with gender and calendar year. P values were based on likelihood ratio tests, and 95% confidence intervals were calculated by Wald's test. RESULTS: In the study period, 655 children developed precocious puberty during 5...

  16. Piracetam and vinpocetine ameliorate rotenone-induced Parkinsonism in rats.

    Science.gov (United States)

    Zaitone, Sawsan A; Abo-Elmatty, Dina M; Elshazly, Shimaa M

    2012-01-01

    To evaluate the neuroprotective effect of the nootropic drugs, piracetam (PIR) and vinpocetine (VIN), in rotenone-induced Parkinsonism in rats. Sixty male rats were divided into 6 groups of 10 rats each. The groups were administered vehicle, control (rotenone, 1.5 mg/kg/48 h/6 doses, s.c.), PIR (100 and 200 mg/kg/day, p.o.) and VIN (3 and 6 mg/kg/day, p.o.). The motor performance of the rats was evaluated by the open field and pole test. Striatal dopamine level, malondialdehyde (MDA), reduced glutathione (GSH) and tumor necrosis factor-α (TNF-α) were assayed. Histopathological study of the substantia nigra was also done. Results showed that rotenone-treated rats exhibited bradykinesia and motor impairment in the open-field test. In addition, GSH level was decreased whereas MDA and TNF-α increased in striata of rotenone-treated rats as compared to vehicle-treated rats. Marked degeneration of the substantia nigra pars compacta (SNpc) neurons and depletion of striatal dopamine was also observed in the rotenone-treated rats. Treatment with PIR or VIN significantly reversed the locomotor deficits and increased striatal dopamine level. Treatment with VIN significantly (P<0.05) reduced the striatal level of MDA and GSH in comparison to rotenone group whereas TNF-α production was found to be significantly decreased in PIR group (P<0.05). VIN and PIR exhibit neuroprotective activity in rotenone-induced Parkinsonism. Hence, these nootropic agents may be considered as possible candidates in the treatment of Parkinson's disease.

  17. Protective Effect of Bauhinia purpurea on Gentamicin-induced Nephrotoxicity in Rats

    Science.gov (United States)

    Lakshmi, B. V. S.; Neelima, N.; Kasthuri, N.; Umarani, V.; Sudhakar, M.

    2009-01-01

    The present study was undertaken to evaluate the ethanol extract of leaves of Bauhinia purpurea and unripe pods of Bauhinia purpurea for its protective effects on gentamicin-induced nephrotoxicity in rats. Nephrotoxicity was induced in Wistar rats by intraperitoneal administration of gentamicin 100 mg/kg/d for eight days. Effect of concurrent administration of ethanol extract of leaves of Bauhinia purpurea and unripe pods of Bauhinia purpurea at a dose of 300 mg/kg/d given by oral route was determined using serum creatinine, serum uric acid, blood urea nitrogen and serum urea as indicators of kidney damage. The study groups contained six rats in each group. It was observed that the ethanol extract of leaves of Bauhinia purpurea and unripe pods of Bauhinia purpurea significantly protect rat kidneys from gentamicin-induced histopathological changes. Gentamicin-induced glomerular congestion, blood vessel congestion, epithelial desquamation, accumulation of inflammatory cells and necrosis of the kidney cells were found to be reduced in the groups receiving the leaf and unripe pods extract of Bauhinia purpurea along with gentamicin. The extracts also normalized the gentamicin-induced increase in serum creatinine, serum uric acid and blood urea nitrogen levels. This is also evidenced by the histopathological studies. PMID:20502576

  18. Zinc Is Indispensable in Exercise-Induced Cardioprotection against Intermittent Hypoxia-Induced Left Ventricular Function Impairment in Rats.

    Directory of Open Access Journals (Sweden)

    Tsung-I Chen

    Full Text Available In obstructive sleep apnea (OSA, recurrent obstruction of the upper airway leads to intermittent hypoxia (IH during sleep, which can result in impairment of cardiac function. Although exercise can have beneficial effects against IH-induced cardiac dysfunction, the mechanism remains unclear. This study aimed to investigate the interactions of zinc and exercise on IH-triggered left ventricular dysfunction in a rat model that mimics IH in OSA patients. Nine-week-old male Sprague-Dawley rats were randomly assigned to either a control group (CON or to a group receiving 10 weeks of exercise training (EXE. During weeks 9 and 10, half the rats in each group were subjected to IH for 8 h per day for 14 days (IHCON, IHEXE, whereas the remainder continued to breathe room air. Rats within each of the CON, IHCON, EXE, and IHEXE groups were further randomly assigned to receive intraperitoneal injections of either zinc chloride, the zinc chelator N,N,N',N'-tetrakis(2-pyridylmethyl ethylenediamine (TPEN, or injection vehicle only. IH induced a lower left ventricular fractional shortening, reduced ejection fraction, higher myocardial levels of inflammatory factors, increased levels oxidative stress, and lower levels of antioxidative capacity, all of which were abolished by zinc treatment. IHEXE rats exhibited higher levels of cardiac function and antioxidant capacity and lower levels of inflammatory factors and oxidative stress than IHCON rats; however, IHEXE rats receiving TPEN did not exhibit these better outcomes. In conclusion, zinc is required for protecting against IH-induced LV functional impairment and likely plays a critical role in exercise-induced cardioprotection by exerting a dual antioxidant and anti-inflammatory effect.

  19. Zinc Is Indispensable in Exercise-Induced Cardioprotection against Intermittent Hypoxia-Induced Left Ventricular Function Impairment in Rats

    Science.gov (United States)

    Chen, Michael Yu-Chih

    2016-01-01

    In obstructive sleep apnea (OSA), recurrent obstruction of the upper airway leads to intermittent hypoxia (IH) during sleep, which can result in impairment of cardiac function. Although exercise can have beneficial effects against IH-induced cardiac dysfunction, the mechanism remains unclear. This study aimed to investigate the interactions of zinc and exercise on IH-triggered left ventricular dysfunction in a rat model that mimics IH in OSA patients. Nine-week-old male Sprague-Dawley rats were randomly assigned to either a control group (CON) or to a group receiving 10 weeks of exercise training (EXE). During weeks 9 and 10, half the rats in each group were subjected to IH for 8 h per day for 14 days (IHCON, IHEXE), whereas the remainder continued to breathe room air. Rats within each of the CON, IHCON, EXE, and IHEXE groups were further randomly assigned to receive intraperitoneal injections of either zinc chloride, the zinc chelator N,N,N',N'-tetrakis(2-pyridylmethyl) ethylenediamine (TPEN), or injection vehicle only. IH induced a lower left ventricular fractional shortening, reduced ejection fraction, higher myocardial levels of inflammatory factors, increased levels oxidative stress, and lower levels of antioxidative capacity, all of which were abolished by zinc treatment. IHEXE rats exhibited higher levels of cardiac function and antioxidant capacity and lower levels of inflammatory factors and oxidative stress than IHCON rats; however, IHEXE rats receiving TPEN did not exhibit these better outcomes. In conclusion, zinc is required for protecting against IH-induced LV functional impairment and likely plays a critical role in exercise-induced cardioprotection by exerting a dual antioxidant and anti-inflammatory effect. PMID:27977796

  20. Subfoveal Choroidal Thickness in 1323 Children Aged 11 to 12 Years and Association With Puberty

    DEFF Research Database (Denmark)

    Li, Xiao Qiang; Jeppesen, Pia; Larsen, Michael

    2014-01-01

    .0001). There was no effect of height or puberty in boys, who were less sexually mature than girls. CONCLUSIONS: Choroidal thickness in girls increased with body height and sexual maturation. The results suggest that puberty promotes choroidal thickening in girls, an effect that may be mediated by the pubertal growth spurt....... The lack of pubertal effect in boys may be related to a smaller proportion of boys in this study having entered puberty....

  1. LIN28B polymorphisms are associated with central precocious puberty and early puberty in girls

    Directory of Open Access Journals (Sweden)

    Sung Won Park

    2012-10-01

    Full Text Available &lt;B&gt;Purpose:&lt;/B&gt; Single-nucleotide polymorphism (SNP markers within &lt;i&gt;LIN28B&lt;/i&gt; have been reported to be related to the timing of pubertal growth. However, no study has investigated the frequency of genetic markers in girls with precocious puberty (PP or early puberty (EP. This study aimed to determine the frequency of putative genetic markers in girls with PP or EP. &lt;B&gt;Methods:&lt;/B&gt; Genomic DNAs were obtained from 77 and 109 girls that fulfilled the criteria for PP and EP, respectively. The controls in this study were 144 healthy volunteers between 20 and 30 years of age. The haplotypes were reconstructed using 11 SNPs of &lt;i&gt;LIN28B&lt;/i&gt;, and haplotype association analysis was performed. The haplotype frequencies were compared. Differences in the clinical and laboratory parameters were analyzed according to the haplotype dosage. &lt;B&gt;Results:&lt;/B&gt; Eleven SNPs in &lt;i&gt;LIN28B&lt;/i&gt; were all located in a block that was in linkage disequilibrium. The haplotype could be reconstructed using 2 representative SNPs, rs4946651 and rs369065. The AC haplotype was less frequently observed in the PP group than in the controls (0.069 vs. 0.144, &lt;I&gt;P&lt;/I&gt;=0.010. The trend that girls with non-AC haplotypes tended to have earlier puberty onset (&lt;I&gt;P&lt;/I&gt;=0.037 was illustrated even in the EP+PP patient group by Kaplan-Meier analysis. &lt;B&gt;Conclusion:&lt;/B&gt; The results of the present study showed that non-AC haplotypes of &lt;i&gt;LIN28B&lt;/i&gt;had a significant association with PP in girls.

  2. Protective effects of ebselen on sodium-selenite-induced experimental cataract in rats.

    Science.gov (United States)

    Aydemir, Orhan; Güler, Mete; Kaya, Mehmet Kaan; Deniz, Nurettin; Üstündağ, Bilal

    2012-12-01

    To determine whether ebselen has a protective effect or antioxidative potential in a sodium-selenite-induced experimental cataract model. Fırat University, Elazığ, Turkey. Experimental study. Twenty-one Sprague-Dawley rat pups were randomly divided into a control group, a sodium-selenite-induced-cataract group, and an ebselen-treated group; each group contained 7 rat pups. Rats in the control group received dimethyl sulfoxide (DMSO) intraperitoneally only and rats in the sodium-selenite-induced-cataract group received 30 nmol/g body weight sodium selenite subcutaneously and DMSO intraperitoneally 10 days postpartum. Rats in the ebselen group received 30 nmol/g body weight sodium selenite subcutaneously 10 days postpartum and were treated with 5 mg/kg body weight ebselen once a day for 4 consecutive days. Cataract development was assessed weekly for 3 weeks by slitlamp examination and graded using a scale. Reduced glutathione (GSH), total nitrite, and malondialdehyde (MDA) levels in lens supernatants were measured at the end of 3 weeks. In the control group, all lenses were clear. In the ebselen-treated group, the mean cataract stage was significantly lower than in the sodium-selenite-induced-cataract group (P = .022). The GSH levels were significantly lower in the sodium-selenite-induced-cataract group than in the control and ebselen groups (P ebselen group than in the sodium-selenite-induced-cataract group (P ebselen group (P = .001). Ebselen had a protective effect on cataract development in a sodium-selenite-induced experimental model. The protective effect of ebselen appears to be due to inhibition of oxidative stress. No author has a financial or proprietary interest in any material or method mentioned. Copyright © 2012 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.

  3. Serum IGF1 and insulin levels in girls with normal and precocious puberty

    DEFF Research Database (Denmark)

    Sørensen, Kaspar; Aksglaede, Lise; Petersen, Jørgen Holm

    2012-01-01

    IGF1 plays an important role in growth and metabolism during puberty. IGF1 levels are increased in girls with central precocious puberty (CPP). However, the relationship with insulin before and during gonadal suppression is unknown. In addition, the influence of the exon 3-deleted GH receptor gene...

  4. Acetylcholine-induced vasodilation in the uterine vascular bed of pregnant rats with adriamycin-induced nephrosis.

    Science.gov (United States)

    Yousif, Mariam H; Adeagbo, Ayotunde S; Kadavil, Elizabeth A; Chandrasekhar, Bindu; Oriowo, Mabayoje A

    2002-01-01

    This project was designed to study endothelium-dependent vasodilation in the uterine vascular bed during experimentally induced preeclampsia in rats. Uterine vascular beds were isolated from non-pregnant and pregnant rats with or without treatment with adriamycin (ADR) and perfused with physiological solution. Thereafter, vasodilator responses to acetylcholine were recorded. RECORDS: Pregnant ADR-treated rats displayed symptoms of preeclampsia including hypertension and proteinuria. Blood pressure was 110.0 +/- 4.7 mm Hg (n = 5) in control pregnant rats and 136.0 +/- 5.3 mm Hg (n = 5) in ADR-treated pregnant rats, and urinary protein concentrations were 0.35 mg/ml (n = 5) and 13.2 +/- 3.6 mg/ml (n = 9), respectively. Both blood pressure and proteinuria values were significantly (p acetylcholine-induced dose-dependent vasodilator responses in the vascular beds were not significantly different between the pregnant and nonpregnant rats. Although acetylcholine-induced vasodilation was significantly reduced by N omega-nitro-L-arginine methyl ester hydrochloride (L-NAME) in both groups, the residual response to acetylcholine was not affected by indomethacin, suggesting that prostanoids were not involved in this response. The L-NAME-resistant component, endothelium-derived hyperpolarizing factor (EDHF), was greater in ADR-treated uterine beds than in those of the controls, indicating a significant contribution from EDHF in these vessels. In the presence of an elevated external potassium ion concentration, acetylcholine produced similar vasodilator responses, indicating that the release of nitric oxide was not impaired. These results indicate that endothelium-dependent vasodilation was not impaired in this model of preeclampsia.

  5. The importance of puberty for adolescent development: conceptualization and measurement.

    Science.gov (United States)

    Berenbaum, Sheri A; Beltz, Adriene M; Corley, Robin

    2015-01-01

    How and why are teenagers different from children and adults? A key question concerns the ways in which pubertal development shapes psychological changes in adolescence directly through changes to the brain and indirectly through the social environment. Empirical work linking pubertal development to adolescent psychological function draws from several different perspectives, often with varying approaches and a focus on different outcomes and mechanisms. The main themes concern effects of atypical pubertal timing on behavior problems during adolescence, effects of pubertal status (and associated hormones) on normative changes in behaviors that can facilitate or hinder development (especially risk-taking, social reorientation, and stress responsivity), and the role of puberty in triggering psychopathology in vulnerable individuals. There is also interest in understanding the ways in which changes in the brain reflect pubertal processes and underlie psychological development in adolescence. In this chapter, we consider the ways that puberty might affect adolescent psychological development, and why this is of importance to developmentalists. We describe the processes of pubertal development; summarize what is known about pubertal influences on adolescent development; consider the assumptions that underlie most work and the methodological issues that affect the interpretation of results; and propose research directions to help understand paths from puberty to behavior. Throughout, we emphasize the importance of pubertal change in all aspects of psychological development, and the ways in which puberty represents an opportunity to study the interplay of biological and social influences. © 2015 Elsevier Inc. All rights reserved.

  6. Potential candidate genomic biomarkers of drug induced vascular injury in the rat

    International Nuclear Information System (INIS)

    Dalmas, Deidre A.; Scicchitano, Marshall S.; Mullins, David; Hughes-Earle, Angela; Tatsuoka, Kay; Magid-Slav, Michal; Frazier, Kendall S.; Thomas, Heath C.

    2011-01-01

    Drug-induced vascular injury is frequently observed in rats but the relevance and translation to humans present a hurdle for drug development. Numerous structurally diverse pharmacologic agents have been shown to induce mesenteric arterial medial necrosis in rats, but no consistent biomarkers have been identified. To address this need, a novel strategy was developed in rats to identify genes associated with the development of drug-induced mesenteric arterial medial necrosis. Separate groups (n = 6/group) of male rats were given 28 different toxicants (30 different treatments) for 1 or 4 days with each toxicant given at 3 different doses (low, mid and high) plus corresponding vehicle (912 total rats). Mesentery was collected, frozen and endothelial and vascular smooth muscle cells were microdissected from each artery. RNA was isolated, amplified and Affymetrix GeneChip® analysis was performed on selectively enriched samples and a novel panel of genes representing those which showed a dose responsive pattern for all treatments in which mesenteric arterial medial necrosis was histologically observed, was developed and verified in individual endothelial cell- and vascular smooth muscle cell-enriched samples. Data were confirmed in samples containing mesentery using quantitative real-time RT-PCR (TaqMan™) gene expression profiling. In addition, the performance of the panel was also confirmed using similarly collected samples obtained from a timecourse study in rats given a well established vascular toxicant (Fenoldopam). Although further validation is still required, a novel gene panel has been developed that represents a strategic opportunity that can potentially be used to help predict the occurrence of drug-induced mesenteric arterial medial necrosis in rats at an early stage in drug development. -- Highlights: ► A gene panel was developed to help predict rat drug-induced mesenteric MAN. ► A gene panel was identified following treatment of rats with 28

  7. Agmatine ameliorates adjuvant induced arthritis and inflammatory cachexia in rats.

    Science.gov (United States)

    Taksande, Brijesh G; Gawande, Dinesh Y; Chopde, Chandrabhan T; Umekar, Milind J; Kotagale, Nandkishor R

    2017-02-01

    The present study investigated the pharmacological effect of agmatine in Complete Freud Adjuvant (CFA) induced arthritis and cachexia in rats. The rats were injected with CFA (0.1ml/rat) to induced symptoms of arthritis. Day 8 onwards of CFA administration, rats were injected daily with agmatine for next 7days, and arthritis score, body weights and food intake were monitored daily (g). Since cachexia is known to produce severe inflammation, malnutrition and inhibition of albumin gene expression, we have also monitored the total proteins, albumin, TNF-α and IL-6 levels in arthritic rats and its modulation by agmatine. In the present study, CFA treated rats showed a progressive reduction in both food intake and body weight. In addition analysis of blood serum of arthritis animals showed a significant reduction in proteins and albumin and significant elevation in tumor necrosis factor (TNF)-α and Interleukins (IL)-6. Chronic agmatine (20-40mg/kg, ip) treatment not only attenuated the signs of arthritis but also reverses anorexia and body weight loss in CFA treated rats. In addition, agmatine restored total protein and albumin and reduces TNF-α and IL-6 levels in arthritis rats. These results suggest that agmatine administration can prevent the body weights loss and symptoms of arthritis via inhibition of inflammatory cytokines. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  8. Testicular Growth During Puberty in Boys With and Without a History of Congenital Cryptorchidism

    DEFF Research Database (Denmark)

    Sadov, Sergey; Koskenniemi, Jaakko J; Virtanen, Helena E

    2016-01-01

    CONTEXT: The pattern of testicular growth during puberty may provide important information about early testicular damage and reproductive potential in adulthood. OBJECTIVE: To evaluate pubertal testicular growth in boys with congenital cryptorchidism and controls. DESIGN: Longitudinal case...... mL by orchidometer and 25 mm by ruler as cut-offs in definition of the onset of puberty. An orchidometer size of 3 mL and ruler length of 25 mm corresponded to 1.6 and 1.7 mL by ultrasound (with Lambert's formula), respectively. CONCLUSIONS: Testicular growth in puberty was impaired in congenitally...

  9. Sex differences in MDMA-induced toxicity in Sprague-Dawley rats

    Science.gov (United States)

    Asl, Sara Soleimani; Mehdizadeh, Mehdi; Shahraki, Soudabeh Hamedi; Artimani, Tayebeh; Joghataei, Mohammad Taghi

    2015-01-01

    Summary Recent evidence demonstrates that female subjects show exaggerated responses to 3,4-methylenedioxymethamphetamine (MDMA) compared with males. The aim of our study was to evaluate sex differences and the role of endogenous gonadal hormones on the effects of MDMA. Fifty-six intact and gonadectomized male and female Sprague-Dawley rats were randomly assigned to either MDMA (5 mg/kg) or saline treatment. Learning and memory were assessed using the Morris water maze (MWM). The expression of Bax and Bcl-2 in the hippocampus was detected by Western blotting. Behavioral analysis showed that MDMA led to memory impairment in both male and female rats. The female rats showed more sensitivity to impairment than the males, as assessed using all the memory parameters in the MWM. Ovariectomy attenuated the MDMA-induced memory impairment. By contrast, orchiectomized rats showed more impairment than MDMA-treated intact male rats. Bcl-2 and Bax were down-regulated and up-regulated in MDMA-treated male and female rats, respectively. MDMA treatment in the orchiectomized rats led to up-regulation of Bax and down-regulation of Bcl-2. Ovariectomy attenuated the MDMA-induced up-regulation of Bax and caused more expression of Bcl-2 compared with what was observed in the MDMA-treated intact female rats. In summary, female rats showed exaggerated responses to the effects of MDMA and this may be explained by endogenous gonadal hormones. PMID:26415786

  10. Xanthine Oxidase Inhibitor, Allopurinol, Prevented Oxidative Stress, Fibrosis, and Myocardial Damage in Isoproterenol Induced Aged Rats.

    Science.gov (United States)

    Sagor, Md Abu Taher; Tabassum, Nabila; Potol, Md Abdullah; Alam, Md Ashraful

    2015-01-01

    We evaluated the preventive effect of allopurinol on isoproterenol (ISO) induced myocardial infarction in aged rats. Twelve- to fourteen-month-old male Long Evans rats were divided into three groups: control, ISO, and ISO + allopurinol. At the end of the study, all rats were sacrificed for blood and organ sample collection to evaluate biochemical parameters and oxidative stress markers analyses. Histopathological examinations were also conducted to assess inflammatory cell infiltration and fibrosis in heart and kidneys. Our investigation revealed that the levels of oxidative stress markers were significantly increased while the level of cellular antioxidants, catalase activity, and glutathione concentration in ISO induced rats decreased. Treatment with allopurinol to ISO induced rats prevented the elevated activities of AST, ALT, and ALP enzymes, and the levels of lipid peroxidation products and increased reduced glutathione concentration. ISO induced rats also showed massive inflammatory cells infiltration and fibrosis in heart and kidneys. Furthermore, allopurinol treatment prevented the inflammatory cells infiltration and fibrosis in ISO induced rats. In conclusion, the results of our study suggest that allopurinol treatment is capable of protecting heart of ISO induced myocardial infarction in rats probably by preventing oxidative stress, inflammation, and fibrosis.

  11. Jiangtang Xiaozhi Recipe () prevents diabetic retinopathy in streptozotocin-induced diabetic rats.

    Science.gov (United States)

    Li, Lin; Li, Yan-Lin; Zhou, Yun-Feng; Ge, Zheng-Yan; Wang, Li-Li; Li, Zhi-Qiang; Guo, Yu-Jie; Jin, Long; Ren, Ye; Liu, Jian-Xun; Xu, Yang

    2017-06-01

    To evaluate the prevention effect of diabetic retinopathy of Jiangtang Xiaozhi Recipe (, JXR) in streptozotocin (STZ)-induced diabetic rats. Sprague-Dawley rats were randomly divided into normal control group and diabetic group. Rats in the diabetic group were induced by intraperitoneal administration of STZ (50 mg/kg), and subdivided into 5 groups. Rats in the diabetic control group were given saline; four treatment groups were given metformin (300 mg/kg), JXR (2, 4 and 8 g/kg) respectively for 8 weeks, while rats in the normal control group were injected with citrate buffer and given the same volume of vehicle. Body weight and food intake were measured every week. The hypoglycaemic effects were determined by testing fasting blood glucose (FBG) every other week, and hemoglobin A1c (HbA1c), insulin, and glucagon at the end of the treatment. The preventive effects of JXR on STZ-induced diabetic rats were determined by histopathological examination with hematoxylin and eosin staining, and periodic acid-schiff staining. The effects were further evaluated by serum superoxide dismutase (SOD) activity and malondialdehyde (MDA). High-dose JXR significantly reduced FBG and HbA1c level at the 8th week of administration (Pdiabetic rats. Histopathological studies revealed that there were no basement membrane thickening and mild destruction in the treated groups. Morphometric measurements of retina microvascular showed that acellular capillary and capillary density decreased in treated rats while pericyte and endothelial cell increasing after the treatment. JXR have protective effect of diabetic retinopathy and its mechanism may be associated with the obvious hypoglycemic and antioxidant effect.

  12. Strain difference of cadmium-induced testicular toxicity in inbred Wistar-Imamichi and Fischer 344 rats

    Energy Technology Data Exchange (ETDEWEB)

    Shimada, Hideaki; Narumi, Rika [Kumamoto University, Faculty of Education, Kumamoto (Japan); Nagano, Masaaki; Yasutake, Akira [National Institute for Minamata Disease, Biochemistry Section, Kumamoto (Japan); Waalkes, Michael P. [National Cancer Institute at the National Institute of Environmental Health Sciences, Inorganic Carcinogenesis Section, Laboratory of Comparative Carcinogenesis, Research Triangle Park, NC (United States); Imamura, Yorishige [Kumamoto University, Graduate School of Pharmaceutical Sciences, Kumamoto (Japan)

    2009-07-15

    Previously, we reported that Wistar-Imamichi (WI) rats are highly resistant to cadmium (Cd)-induced lethality and hepatotoxicity compared to Fischer 344 (F344) rats. Since the testes are one of the most sensitive organs to acute Cd toxicity, we examined possible strain-related differences in Cd-induced testicular toxicity between inbred WI and F344 rats. Rats were treated with a single dose of 0.5, 1.0 or 2.0 mg Cd/kg, as CdCl{sub 2}, sc and killed 24 h later. Cd at doses of 1.0 and 2.0 mg/kg induced severe testicular hemorrhage, as assessed by pathological and testis hemoglobin content, in F344 rats, but not WI rats. After Cd treatment (2.0 mg/kg), the testicular Cd content was significantly lower in WI rats than in the F344 rats, indicating a toxiokinetic mechanism for the observed strain difference. Thus, the remarkable resistance to Cd-induced testicular toxicity in WI rats is associated, at least in part, with lower testicular accumulation of Cd. When zinc (Zn; 10 mg/kg, sc) was administered in combination with Cd (2.0 mg/kg) to F344 rats, the Cd-induced increase in testicular hemoglobin content, indicative of hemorrhage, was significantly reduced. Similarly, the testicular Cd content was significantly decreased with Zn co-treatment compared to Cd treatment alone. Thus, it can be concluded that the testicular Cd accumulation partly competes with Zn transport systems and that these systems may play an important role in the strain-related differences in Cd-induced testicular toxicity between WI and F344 rats. (orig.)

  13. Acute Alcohol Intoxication Exacerbates Rhabdomyolysis-Induced Acute Renal Failure in Rats.

    Science.gov (United States)

    Tsai, Jen-Pi; Lee, Chung-Jen; Subeq, Yi-Maun; Lee, Ru-Ping; Hsu, Bang-Gee

    2017-01-01

    Traumatic and nontraumatic rhabdomyolysis can lead to acute renal failure (ARF), and acute alcohol intoxication can lead to multiple abnormalities of the renal tubules. We examined the effect of acute alcohol intoxication in a rat model of rhabdomyolysis and ARF. Intravenous injections of 5 g/kg ethanol were given to rats over 3 h, followed by glycerol-induced rhabdomyolysis. Biochemical parameters, including blood urea nitrogen (BUN), creatinine (Cre), glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), and creatine phosphokinase (CPK), were measured before and after induction of rhabdomyolysis. Renal tissue injury score, renal tubular cell expression of E-cadherin, nuclear factor-κB (NF-κB), and inducible nitric oxide synthase (iNOS) were determined. Relative to rats in the vehicle group, rats in the glycerol-induced rhabdomyolysis group had significantly increased serum levels of BUN, Cre, GOT, GPT, and CPK, elevated renal tissue injury scores, increased expression of NF-κB and iNOS, and decreased expression of E-cadherin. Ethanol exacerbated all of these pathological responses. Our results suggest that acute alcohol intoxication exacerbates rhabdomyolysis-induced ARF through its pro-oxidant and inflammatory effects.

  14. Cyclin D expression in plutonium-induced lung tumors in F344 rats

    Energy Technology Data Exchange (ETDEWEB)

    Hahn, F.F.; Kelly, G. [SouthWest Scientific Resources, Inc., Albuquerque, NM (United States)

    1995-12-01

    The genetic mechanisms responsible for {alpha}-radiation-induced lung cancer in rats following inhalation of {sup 239}Pu is an ongoing area of research in our laboratory. Previous studies have examined the status of the p53 gene by immunohistochemistry. Only two tumors (2/26 squamous cell carcinomas) exhibited detectable levels of p53 products. Both were the result of mutations in codons 280 and 283. More recent studies of X-ray-induced lung tumors in rats showed a similar lack of involvement of p53. In conclusion, we found that {alpha}-radiation-induced rat lung tumors have a high incidence (31 of 39) of cyclin D{sub 1} overexpression.

  15. Hormone-induced rat model of polycystic ovary syndrome: A systematic review.

    Science.gov (United States)

    Noroozzadeh, Mahsa; Behboudi-Gandevani, Samira; Zadeh-Vakili, Azita; Ramezani Tehrani, Fahimeh

    2017-12-15

    Despite polycystic ovary syndrome (PCOS) being one of the most common endocrine disorders affecting reproductive-aged women, the etiopathogenesis and mechanisms of this syndrome remain unclear. Considering the ethical limitations in human studies, animal models that reflect many features of PCOS are crucial resources to investigate this syndrome. We aimed to introduce the most suitable rat model of PCOS that closely mimics the endocrine, ovarian and metabolic disturbances of human PCOS phenotype, while maintaining normal reproductive system morphology in adulthood, in order to further more detailed investigations about PCOS. We searched Pubmed, Science direct, and Web of science between 1990 and 2016, for relevant English manuscripts, using keywords including the "Polycystic Ovary Syndrome AND Rat Model" to generate a subset of citations relevant to our research. Included were those articles that compared at least both ovarian histology or estrous cycle and reproductive hormonal profiles in hormone-induced rat model of PCOS and controls. Differences in the findings between hormone-induced PCOS rats appear to be a result of the degree of transplacental transfer of the steroid administered into the fetus, dose and type of hormone, route of administration and timing and duration of exposure. We conclude that prenatal hormone-induced rat model with a lower dose and shorter time of exposure during the critical period of fetal development that exhibits endocrine, ovarian and metabolic disturbances similar to PCOS in women, while maintaining normal reproductive system morphology in adulthood is more suitable than postnatal hormone-induced rat model to facilitate studies regarding PCOS. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Protective effects of piperine on lead acetate induced-nephrotoxicity in rats

    Directory of Open Access Journals (Sweden)

    Sri Agus Sudjarwo

    2017-11-01

    Full Text Available Objective(s: In this study, we investigated the protective effects of piperine on lead acetate-induced renal damage in rat kidney tissue. Materials and Methods: Forty male rats were divided into 5 groups: negative control (rats were given aquadest daily, positive control (rats were given lead acetate 30 mg/kg BW orally once a day for 60 days, and the treatment group (rats were given piperine 50 mg; 100 mg and 200 mg/kg BW orally once a day for 65 days, and on 5th day, were given lead acetate 30 mg/kg BW one hr after piperine administration for 60 days. On day 65 levels of blood urea nitrogen (BUN, creatinine, malondialdehyde (MDA, Superoxide Dismutase (SOD, and Glutathione Peroxidase (GPx were measured. Also, kidney samples were collected for histopathological studies. Results: The results revealed that lead acetate toxicity induced a significant increase in the levels of BUN, creatinine, and MDA; moreover, a significant decrease in SOD and GPx. Lead acetate also altered kidney histopathology (kidney damage, necrosis of tubules compared to the negative control. However, administration of piperine significantly improved the kidney histopathology, decreased the levels of BUN, creatinine, and MDA, and also significantly increased the SOD and GPx in the kidney of lead acetate-treated rats. Conclusion: From the results of this study it was concluded that piperine could be a potent natural herbal product exhibiting nephroprotective effect against lead acetate induced nephrotoxicity in rats.

  17. Psychological Support, Puberty Suppression, and Psychosocial Functioning in Adolescents with Gender Dysphoria.

    Science.gov (United States)

    Costa, Rosalia; Dunsford, Michael; Skagerberg, Elin; Holt, Victoria; Carmichael, Polly; Colizzi, Marco

    2015-11-01

    Puberty suppression by gonadotropin-releasing hormone analogs (GnRHa) is prescribed to relieve the distress associated with pubertal development in adolescents with gender dysphoria (GD) and thereby to provide space for further exploration. However, there are limited longitudinal studies on puberty suppression outcome in GD. Also, studies on the effects of psychological support on its own on GD adolescents' well-being have not been reported. This study aimed to assess GD adolescents' global functioning after psychological support and puberty suppression. Two hundred one GD adolescents were included in this study. In a longitudinal design we evaluated adolescents' global functioning every 6 months from the first visit. All adolescents completed the Utrecht Gender Dysphoria Scale (UGDS), a self-report measure of GD-related discomfort. We used the Children's Global Assessment Scale (CGAS) to assess the psychosocial functioning of adolescents. At baseline, GD adolescents showed poor functioning with a CGAS mean score of 57.7 ± 12.3. GD adolescents' global functioning improved significantly after 6 months of psychological support (CGAS mean score: 60.7 ± 12.5; P puberty suppression had significantly better psychosocial functioning after 12 months of GnRHa (67.4 ± 13.9) compared with when they had received only psychological support (60.9 ± 12.2, P = 0.001). Psychological support and puberty suppression were both associated with an improved global psychosocial functioning in GD adolescents. Both these interventions may be considered effective in the clinical management of psychosocial functioning difficulties in GD adolescents. © 2015 International Society for Sexual Medicine.

  18. Memantine reverses social withdrawal induced by ketamine in rats.

    Science.gov (United States)

    Uribe, Ezequiel; Landaeta, José; Wix, Richard; Eblen, Antonio

    2013-03-01

    The objective of this study was to determine the effect of memantine on schizophrenia-like symptoms in a ketamine-induced social withdrawal model in rats. We examined therapeutic effects of memantine, an NMDA antagonist, and haloperidol, a classic antipsychotic drug, on this behavioral model. Administration of memantine (10 or 15 mg·kg(-1)) significantly reduced ketamine-induced social withdrawal, and this effect was more effective than that of haloperidol (0.25 mg·kg(-1)) by restoring the social interaction between rats with no modification in general motor activity. These results suggest that memantine could have a therapeutic potential for schizophrenia.

  19. Radiation-induced mesotheliomas in rats

    Energy Technology Data Exchange (ETDEWEB)

    Hahn, F.F.; Haley, P.J.; Hubbs, A.F.; Hoover, M.D.; Lundgren, D.L.

    1990-01-01

    Mesotheliomas have been reported in rats that inhaled plutonium, but these tumors have not been extensively studied. To investigate a possible role for inhaled radionuclides in the induction of mesotheliomas, four life-span studies conducted at the Inhalation Toxicology Research Institute are reviewed. A total of 3076 F344 rats were exposed by inhalation to aerosols of {sup 239}PuO{sub 2}, mixed uranium-plutonium oxide, or {sup 144}CeO{sub 2}. Results showed that a low incidence of pleural mesotheliomas was induced by either alpha- or beta-emitting radionuclides deposited and retained in the lung. Chronic alpha irradiation was more effective per unit dose in producing mesotheliomas than chronic beta irradiation of the lung by a factor of 15. 7 refs., 1 tab., 7 figs. (MHB)

  20. Puberty in the Girl Who is Retarded.

    Science.gov (United States)

    Pattullo, Ann

    Designed to help mothers of mentally retarded girls deal with the problems and concerns of puberty, the booklet provides information on physical and emotional changes, menstruation, masturbation, heterosexual behavior, contraception, protection against sexual aggression, the possibilities of marriage, and additional sources of information.…

  1. Food Color Induced Hepatotoxicity in Swiss Albino Rats, Rattus norvegicus

    OpenAIRE

    Saxena, Beenam; Sharma, Shiv

    2015-01-01

    Objective: Certain dietary constituents can induce toxicity and play a critical role in the development of several hepatic disorders. Tartrazine, metanil yellow and sunset yellow are widely used azo dyes in food products, so the present study is aimed to investigate the food color induced hepatotoxicity in Swiss albino rats. Materials and Methods: Swiss albino rats were divided into four groups, each group having six animals. Group I served as control, Group II, Group III and Group IV were ad...

  2. Multi-tissue omics analyses reveal molecular regulatory networks for puberty in composite beef cattle

    Science.gov (United States)

    Puberty is a complex physiological event by which animals mature into an adult capable of sexual reproduction. In order to enhance our understanding of the genes and regulatory pathways and networks involved in puberty, we characterized the transcriptome of five reproductive tissues (i.e., hypothal...

  3. Pharmacokinetic-pharmacodynamic modeling of diclofenac in normal and Freund's complete adjuvant-induced arthritic rats

    Science.gov (United States)

    Zhang, Jing; Li, Pei; Guo, Hai-fang; Liu, Li; Liu, Xiao-dong

    2012-01-01

    Aim: To characterize pharmacokinetic-pharmacodynamic modeling of diclofenac in Freund's complete adjuvant (FCA)-induced arthritic rats using prostaglandin E2 (PGE2) as a biomarker. Methods: The pharmacokinetics of diclofenac was investigated using 20-day-old arthritic rats. PGE2 level in the rats was measured using an enzyme immunoassay. A pharmacokinetic-pharmacodynamic (PK-PD) model was developed to illustrate the relationship between the plasma concentration of diclofenac and the inhibition of PGE2 production. The inhibition of diclofenac on lipopolysaccharide (LPS)-induced PGE2 production in blood cells was investigated in vitro. Results: Similar pharmacokinetic behavior of diclofenac was found both in normal and FCA-induced arthritic rats. Diclofenac significantly decreased the plasma levels of PGE2 in both normal and arthritic rats. The inhibitory effect on PGE2 levels in the plasma was in proportion to the plasma concentration of diclofenac. No delay in the onset of inhibition was observed, suggesting that the effect compartment was located in the central compartment. An inhibitory effect sigmoid Imax model was selected to characterize the relationship between the plasma concentration of diclofenac and the inhibition of PGE2 production in vivo. The Imax model was also used to illustrate the inhibition of diclofenac on LPS-induced PGE2 production in blood cells in vitro. Conclusion: Arthritis induced by FCA does not alter the pharmacokinetic behaviors of diclofenac in rats, but the pharmacodynamics of diclofenac is slightly affected. A PK-PD model characterizing an inhibitory effect sigmoid Imax can be used to fit the relationship between the plasma PGE2 and diclofenac levels in both normal rats and FCA-induced arthritic rats. PMID:22842736

  4. Repeated administration of amitriptyline reduces oxaliplatin-induced mechanical allodynia in rats.

    Science.gov (United States)

    Sada, Hikaru; Egashira, Nobuaki; Ushio, Soichiro; Kawashiri, Takehiro; Shirahama, Masafumi; Oishi, Ryozo

    2012-01-01

    Oxaliplatin is a key drug in the treatment of colorectal cancer, but it causes acute and chronic neuropathies in patients. Amitriptyline has widely been used in patients with painful neuropathy. In this study, we investigated the effect of amitriptyline on the oxaliplatin-induced neuropathy in rats. Repeated administration of amitriptyline (5 and 10 mg/kg, p.o., once a day) reduced the oxaliplatin-induced mechanical allodynia but not cold hyperalgesia and reversed the oxaliplatin-induced increase in the expression of NR2B protein and mRNA in rat spinal cord. These results suggest that amitriptyline is useful for the treatment of oxaliplatin-induced neuropathy clinically.

  5. Therapeutic Effects of Procainamide on Endotoxin-Induced Rhabdomyolysis in Rats.

    Directory of Open Access Journals (Sweden)

    Chih-Chin Shih

    Full Text Available Overt systemic inflammatory response is a predisposing mechanism for infection-induced skeletal muscle damage and rhabdomyolysis. Aberrant DNA methylation plays a crucial role in the pathophysiology of excessive inflammatory response. The antiarrhythmic drug procainamide is a non-nucleoside inhibitor of DNA methyltransferase 1 (DNMT1 used to alleviate DNA hypermethylation. Therefore, we evaluated the effects of procainamide on the syndromes and complications of rhabdomyolysis rats induced by lipopolysaccharide (LPS. Rhabdomyolysis animal model was established by intravenous infusion of LPS (5 mg/kg accompanied by procainamide therapy (50 mg/kg. During the experimental period, the changes of hemodynamics, muscle injury index, kidney function, blood gas, blood electrolytes, blood glucose, and plasma interleukin-6 (IL-6 levels were examined. Kidneys and lungs were exercised to analyze superoxide production, neutrophil infiltration, and DNMTs expression. The rats in this model showed similar clinical syndromes and complications of rhabdomyolysis including high levels of plasma creatine kinase, acute kidney injury, hyperkalemia, hypocalcemia, metabolic acidosis, hypotension, tachycardia, and hypoglycemia. The increases of lung DNMT1 expression and plasma IL-6 concentration were also observed in rhabdomyolysis animals induced by LPS. Treatment with procainamide not only inhibited the overexpression of DNMT1 but also diminished the overproduction of IL-6 in rhabdomyolysis rats. In addition, procainamide improved muscle damage, renal dysfunction, electrolytes disturbance, metabolic acidosis, hypotension, and hypoglycemia in the rats with rhabdomyolysis. Moreover, another DNMT inhibitor hydralazine mitigated hypoglycemia, muscle damage, and renal dysfunction in rhabdomyolysis rats. These findings reveal that therapeutic effects of procainamide could be based on the suppression of DNMT1 and pro-inflammatory cytokine in endotoxin-induced rhabdomyolysis.

  6. Therapeutic Effects of Procainamide on Endotoxin-Induced Rhabdomyolysis in Rats.

    Science.gov (United States)

    Shih, Chih-Chin; Hii, Hiong-Ping; Tsao, Cheng-Ming; Chen, Shiu-Jen; Ka, Shuk-Man; Liao, Mei-Hui; Wu, Chin-Chen

    2016-01-01

    Overt systemic inflammatory response is a predisposing mechanism for infection-induced skeletal muscle damage and rhabdomyolysis. Aberrant DNA methylation plays a crucial role in the pathophysiology of excessive inflammatory response. The antiarrhythmic drug procainamide is a non-nucleoside inhibitor of DNA methyltransferase 1 (DNMT1) used to alleviate DNA hypermethylation. Therefore, we evaluated the effects of procainamide on the syndromes and complications of rhabdomyolysis rats induced by lipopolysaccharide (LPS). Rhabdomyolysis animal model was established by intravenous infusion of LPS (5 mg/kg) accompanied by procainamide therapy (50 mg/kg). During the experimental period, the changes of hemodynamics, muscle injury index, kidney function, blood gas, blood electrolytes, blood glucose, and plasma interleukin-6 (IL-6) levels were examined. Kidneys and lungs were exercised to analyze superoxide production, neutrophil infiltration, and DNMTs expression. The rats in this model showed similar clinical syndromes and complications of rhabdomyolysis including high levels of plasma creatine kinase, acute kidney injury, hyperkalemia, hypocalcemia, metabolic acidosis, hypotension, tachycardia, and hypoglycemia. The increases of lung DNMT1 expression and plasma IL-6 concentration were also observed in rhabdomyolysis animals induced by LPS. Treatment with procainamide not only inhibited the overexpression of DNMT1 but also diminished the overproduction of IL-6 in rhabdomyolysis rats. In addition, procainamide improved muscle damage, renal dysfunction, electrolytes disturbance, metabolic acidosis, hypotension, and hypoglycemia in the rats with rhabdomyolysis. Moreover, another DNMT inhibitor hydralazine mitigated hypoglycemia, muscle damage, and renal dysfunction in rhabdomyolysis rats. These findings reveal that therapeutic effects of procainamide could be based on the suppression of DNMT1 and pro-inflammatory cytokine in endotoxin-induced rhabdomyolysis.

  7. An approach to constitutional delay of growth and puberty

    Directory of Open Access Journals (Sweden)

    Ashraf T Soliman

    2012-01-01

    Full Text Available Constitutional delay of growth and puberty is a transient state of hypogonadotropic hypogonadism associated with prolongation of childhood phase of growth, delayed skeletal maturation, delayed and attenuated pubertal growth spurt, and relatively low insulin-like growth factor-1 secretion. In a considerable number of cases, the final adult height (Ht does not reach the mid-parental or the predicted adult Ht for the individual, with some degree of disproportionately short trunk. In the pre-pubertal male, testosterone (T replacement therapy can be used to induce pubertal development, accelerate growth and relieve the psychosocial complaints of the adolescents. However, some issues in the management are still unresolved. These include type, optimal timing, dose and duration of sex steroid treatment and the possible use of adjunctive or alternate therapy including: oxandrolone, aromatase inhibitors and human growth hormone.

  8. Safety Extension Study Of Leuprolide Acetate (Lupron Depot) In The Treatment Of Central Precocious Puberty

    Science.gov (United States)

    2014-01-08

    Precocious; Leuprolide Acetate; Luteinizing Hormone (LH); Gonadotrophin-releasing Hormone Agonist (GnRHa); Tanner Staging; Depot Formulation; Suppression of LH; Central Precocious Puberty (CPP); Gonadotrophin-releasing Hormone (GnRH); Lupron; GnRH Analog; Pediatrics Central Precocious Puberty

  9. Histopathologic Evaluation of Nonalcoholic Fatty Liver Disease in Hypothyroidism-Induced Rats

    Directory of Open Access Journals (Sweden)

    Şule Demir

    2016-01-01

    Full Text Available It is speculated that thyroid hormones may be involved in nonalcoholic fatty liver disease (NAFLD pathogenesis. A literature scan, however, demonstrated conflicting results from studies investigating the relationship between hypothyroidism and NAFLD. Therefore, our study aims to evaluate NAFLD, from the histopathologic perspective, in hypothyroidism-induced rats. Wistar rats were divided into 2 groups: the experimental group consumed water containing methimazole 0.025% (MMI, Sigma, USA for 12 weeks and the control group consumed tap water. At the end of week 12, serum glucose, ALT, AST, triglyceride, HDL, LDL, TSH, fT4, fT3, visfatin, and insulin assays were performed. Sections were stained with hematoxylin-eosin and “Oil Red-O” for histopathologic examination of the livers. In our study, we detected mild hepatosteatosis in all hypothyroidism-induced rats. There was statistically significant difference with respect to obesity between the two groups (p0.05. In conclusion, we found that hypothyroidism-induced rats had mild hepatosteatosis as opposed to the control group histopathologically. Our study indicates that hypothyroidism can cause NAFLD.

  10. Modulatory role of chelating agents in diet-induced hypercholesterolemia in rats

    Directory of Open Access Journals (Sweden)

    Heba M. Mahmoud

    2014-06-01

    Conclusion: Pretreatment of hypercholesterolemic rats with simvastatin, CaNa2EDTA or DMSA attenuated most of the changes induced by feeding rats with cholesterol-rich diet owing to their observed anti-hyperlipidemic and antioxidant properties.

  11. Sucrose and IQ induced mutations in rat colon by independent

    DEFF Research Database (Denmark)

    Hansen, Max; Hald, M. T.; Autrup, H.

    2004-01-01

    Sucrose-rich diets have repeatedly been observed to have co-carcinogenic actions in colon and liver of rats and to increase the number of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) induced aberrant crypt foci in rat colon. To investigate a possible interaction between sucrose and IQ...... on the genotoxicity in rat liver and colon, we gave Big Blue rats(TM) a diet containing sucrose (0%, 3.45% or 13.4% w/w) and/or IQ (70 ppm) for a period of 3 weeks. Sucrose and IQ increased the mutation frequency in the colon. The effect of combined treatments with IQ and sucrose on the mutation frequencies...... was additive indicating that sucrose and IQ act independently. This was supported by the mutation spectra where sucrose expands the background mutations in the colon, whereas IQ, in other studies, more specifically has induced G:C --> T:A transversions. In the liver IQ increased the mutation frequency, whereas...

  12. Inhibition of cyclooxygenase-2 reduces hypothalamic excitation in rats with adriamycin-induced heart failure.

    Directory of Open Access Journals (Sweden)

    Min Zheng

    Full Text Available BACKGROUND: The paraventricular nucleus (PVN of the hypothalamus plays an important role in the progression of heart failure (HF. We investigated whether cyclooxygenase-2 (COX-2 inhibition in the PVN attenuates the activities of sympathetic nervous system (SNS and renin-angiotensin system (RAS in rats with adriamycin-induced heart failure. METHODOLOGY/PRINCIPAL FINDING: Heart failure was induced by intraperitoneal injection of adriamycin over a period of 2 weeks (cumulative dose of 15 mg/kg. On day 19, rats received intragastric administration daily with either COX-2 inhibitor celecoxib (CLB or normal saline. Treatment with CLB reduced mortality and attenuated both myocardial atrophy and pulmonary congestion in HF rats. Compared with the HF rats, ventricle to body weight (VW/BW and lung to body weight (LW/BW ratios, heart rate (HR, left ventricular end-diastolic pressure (LVEDP, left ventricular peak systolic pressure (LVPSP and maximum rate of change in left ventricular pressure (LV±dp/dtmax were improved in HF+CLB rats. Angiotensin II (ANG II, norepinephrine (NE, COX-2 and glutamate (Glu in the PVN were increased in HF rats. HF rats had higher levels of ANG II and NE in plasma, higher level of ANG II in myocardium, and lower levels of ANP in plasma and myocardium. Treatment with CLB attenuated these HF-induced changes. HF rats had more COX-2-positive neurons and more corticotropin releasing hormone (CRH positive neurons in the PVN than did control rats. Treatment with CLB decreased COX-2-positive neurons and CRH positive neurons in the PVN of HF rats. CONCLUSIONS: These results suggest that PVN COX-2 may be an intermediary step for PVN neuronal activation and excitatory neurotransmitter release, which further contributes to sympathoexcitation and RAS activation in adriamycin-induced heart failure. Treatment with COX-2 inhibitor attenuates sympathoexcitation and RAS activation in adriamycin-induced heart failure.

  13. Prenatal testosterone exposure worsen the reproductive performance of male rat at adulthood.

    Science.gov (United States)

    Ramezani Tehrani, Fahimeh; Noroozzadeh, Mahsa; Zahediasl, Saleh; Ghasemi, Asghar; Piryaei, Abbas; Azizi, Fereidoun

    2013-01-01

    The reproductive system is extremely susceptible to environmental insults, for example exogenous steroids during gestational development and differentiation. Experimental induction of androgen excess during prenatal life in female animal models reprograms their reproductive physiology, however the fetal programming of the male reproductive system by androgen excess has not been well studied. We aimed to determine the effect of prenatal exposure of two different doses of testosterone on different gestational days, on the male reproductive system using a rat model. Sixteen pregnant rats were randomly divided into two experimental groups and two control groups. Experimental group І were subcutaneously injected with 3 mg free testosterone on gestational days 16-19 and its controls received solvent for that time; experimental group П were subcutaneously injected with 20 mg free testosterone on day 20 of gestational period and its controls received solvent at the same time. The reproductive system morphology and function of 32 male offspring of these study groups were compared at days 6-30-60 of age and after puberty. The anogenital distance of the male offspring of both experimental groups had no significant differences on the different days of measurement, compared with controls. In the offspring of experimental group І, the testes weight, number of Sertoli, Spermatocyte and Spermatid cells, sperm count and motility and the serum concentration of testosterone after puberty were significantly decreased; except for reduction of sperm motility (pmale rat fetuses to excess testosterone disrupted reproductive function, an effect highly dependent on the time, duration and level of exposure. It seems that the reproductive system in individuals exposed to high levels of androgens during fetal life should be evaluated at puberty and likely to be treated.

  14. Pre-existing differences and diet-induced alterations in striatal dopamine systems of obesity-prone rats.

    Science.gov (United States)

    Vollbrecht, Peter J; Mabrouk, Omar S; Nelson, Andrew D; Kennedy, Robert T; Ferrario, Carrie R

    2016-03-01

    Interactions between pre-existing differences in mesolimbic function and neuroadaptations induced by consumption of fatty, sugary foods are thought to contribute to human obesity. This study examined basal and cocaine-induced changes in striatal neurotransmitter levels without diet manipulation and D2 /D3 dopamine receptor-mediated transmission prior to and after consumption of "junk-foods" in obesity-prone and obesity-resistant rats. Microdialysis and liquid chromatography-mass spectrometry were used to determine basal and cocaine-induced changes in neurotransmitter levels in real time with cocaine-induced locomotor activity. Sensitivity to the D2 /D3 dopamine receptor agonist quinpirole was examined before and after restricted junk-food exposure. Selectively bred obesity-prone and obesity-resistant rats were used. Cocaine-induced locomotion was greater in obesity-prone rats versus obesity-resistant rats prior to diet manipulation. Basal and cocaine-induced increases in dopamine and serotonin levels did not differ. Obesity-prone rats were more sensitive to the D2 receptor-mediated effects of quinpirole, and junk-food produced modest alterations in quinpirole sensitivity in obesity-resistant rats. These data show that mesolimbic systems differ prior to diet manipulation in susceptible versus resistant rats, and that consumption of fatty, sugary foods produce different neuroadaptations in these populations. These differences may contribute to enhanced food craving and an inability to limit food intake in susceptible individuals. © 2016 The Obesity Society.

  15. Can overeating induce conditioned taste avoidance in previously food restricted rats?

    Science.gov (United States)

    Hertel, Amanda; Eikelboom, Roelof

    2010-03-30

    While feeding is rewarding, the feeling of satiation has been theorized to have a mixed affect. Using a food restriction model of overeating we examined whether bingeing was capable of supporting conditioned taste avoidance (CTA). Adult male Sprague-Dawley rats were maintained on either an ad lib (n=8) or restricted (50% of regular consumption; n=24) food access for 20 days. On Days 9, 14, and 19 all rats were given access to a novel saccharin solution in place of water, and two groups of food restricted rats were given access to either 100% of regular food consumption or ad lib food. Ad lib access in the restricted rats induced significant overeating on all three exposures. After all rats were returned to ad lib feeding, a 24h two-bottle saccharin/water choice test displayed significantly reduced saccharin consumption in the overeating rats, compared to those in the other 3 groups. To determine whether this avoidance was due to a learned association, a second experiment used a latent inhibition paradigm, familiarizing half the rats with the saccharin for 8 days prior to pairing it with overeating. Using the design of Experiment 1, with only the continuously ad lib and the restricted to ad lib feeding groups, it was found that the overeating-induced saccharin avoidance was attenuated by the pre-exposure. These results suggest that self-induced overeating is capable of supporting a learned avoidance of a novel solution suggestive of a conditioned satiety or taste avoidance. (c) 2009 Elsevier Inc. All rights reserved.

  16. Thymoquinone ameliorates lead-induced brain damage in Sprague Dawley rats.

    Science.gov (United States)

    Radad, Khaled; Hassanein, Khaled; Al-Shraim, Mubarak; Moldzio, Rudolf; Rausch, Wolf-Dieter

    2014-01-01

    The present study aims to investigate the protective effects of thymoquinone, the major active ingredient of Nigella sativa seeds, against lead-induced brain damage in Sprague-Dawley rats. In which, 40 rats were divided into four groups (10 rats each). The first group served as control. The second, third and fourth groups received lead acetate, lead acetate and thymoquinone, and thymoquinone only, respectively, for one month. Lead acetate was given in drinking water at a concentration of 0.5 g/l (500 ppm). Thymoquinone was given daily at a dose of 20mg/kg b.w. in corn oil by gastric tube. Control and thymoquinone-treated rats showed normal brain histology. Treatment of rats with lead acetate was shown to produce degeneration of endothelial lining of brain blood vessels with peri-vascular cuffing of mononuclear cells consistent to lymphocytes, congestion of choroid plexus blood vessels, ischemic brain infarction, chromatolysis and neuronal degeneration, microglial reaction and neuronophagia, degeneration of hippocampal and cerebellar neurons, and axonal demyelination. On the other hand, co-administration of thymoquinone with lead acetate markedly decreased the incidence of lead acetate-induced pathological lesions. Thus the current study shed some light on the beneficial effects of thymoquinone against neurotoxic effects of lead in rats. Copyright © 2013 Elsevier GmbH. All rights reserved.

  17. Puberty and the manifestations of loss of control eating in children and adolescents.

    Science.gov (United States)

    Vannucci, Anna; Tanofsky-Kraff, Marian; Ranzenhofer, Lisa M; Kelly, Nichole R; Hannallah, Louise M; Pickworth, C Katie; Grygorenko, Mariya V; Brady, Sheila M; Condarco, Tania A; Kozlosky, Merel; Demidowich, Andrew P; Yanovski, Susan Z; Shomaker, Lauren B; Yanovski, Jack A

    2014-11-01

    We investigated the manifestations of pediatric loss of control (LOC) eating at different stages of pubertal development. Participants were a nonclinical sample of 468 youth (8-17 years). Physical examination determined pubertal stage. LOC eating and disordered eating attitudes were assessed with the Eating Disorder Examination. In a randomized crossover design, a subset (n = 244) ate ad libitum from two test meals designed to capture normal and LOC eating. There were no differences in the prevalence rates or frequency of reported LOC eating episodes across pubertal stages (ps ≥ 0.50). There were, however, puberty by LOC eating interactions in disordered eating attitudes and palatable food consumption (ps ≤ .05), even after adjusting for age and body composition. LOC eating was associated with elevated global disordered eating attitudes, weight concern, and shape concern in post-pubertal youth (ps ≤ .001), but not pre-pubertal youth (ps ≥ .49). In late-puberty, youth with LOC eating consumed less energy from protein (p puberty was not associated with differences in eating behavior (ps ≥ 0.20). Findings suggest that puberty may be a critical risk period, when LOC eating behaviors in boys and girls may become accompanied by greater weight and shape concerns and more obesogenic food consumption patterns. Interventions for LOC eating during pre-puberty should be evaluated to determine if they are particularly beneficial for the prevention of exacerbated eating disorder psychopathology and adverse weight outcomes. © 2014 Wiley Periodicals, Inc.

  18. Basolateral amygdala GABA-A receptors mediate stress-induced memory retrieval impairment in rats.

    Science.gov (United States)

    Sardari, Maryam; Rezayof, Ameneh; Khodagholi, Fariba; Zarrindast, Mohammad-Reza

    2014-04-01

    The present study was designed to investigate the involvement of GABA-A receptors of the basolateral amygdala (BLA) in the impairing effect of acute stress on memory retrieval. The BLAs of adult male Wistar rats were bilaterally cannulated and memory retrieval was measured in a step-through type passive avoidance apparatus. Acute stress was evoked by placing the animals on an elevated platform for 10, 20 and 30 min. The results indicated that exposure to 20 and 30 min stress, but not 10 min, before memory retrieval testing (pre-test exposure to stress) decreased the step-through latency, indicating stress-induced memory retrieval impairment. Intra-BLA microinjection of a GABA-A receptor agonist, muscimol (0.005-0.02 μg/rat), 5 min before exposure to an ineffective stress (10 min exposure to stress) induced memory retrieval impairment. It is important to note that pre-test intra-BLA microinjection of the same doses of muscimol had no effect on memory retrieval in the rats unexposed to 10 min stress. The blockade of GABA-A receptors of the BLA by injecting an antagonist, bicuculline (0.4-0.5 μg/rat), 5 min before 20 min exposure to stress, prevented stress-induced memory retrieval. Pre-test intra-BLA microinjection of the same doses of bicuculline (0.4-0.5 μg/rat) in rats unexposed to 20 min stress had no effect on memory retrieval. In addition, pre-treatment with bicuculline (0.1-0.4 μg/rat, intra-BLA) reversed muscimol (0.02 μg/rat, intra-BLA)-induced potentiation on the effect of stress in passive avoidance learning. It can be concluded that pre-test exposure to stress can induce memory retrieval impairment and the BLA GABA-A receptors may be involved in stress-induced memory retrieval impairment.

  19. The Effects of Acute Stress-Induced Sleep Disturbance on Acoustic Trauma-Induced Tinnitus in Rats

    Directory of Open Access Journals (Sweden)

    Yiwen Zheng

    2014-01-01

    Full Text Available Chronic tinnitus is a debilitating condition and often accompanied by anxiety, depression, and sleep disturbance. It has been suggested that sleep disturbance, such as insomnia, may be a risk factor/predictor for tinnitus-related distress and the two conditions may share common neurobiological mechanisms. This study investigated whether acute stress-induced sleep disturbance could increase the susceptibility to acoustic trauma-induced tinnitus in rats. The animals were exposed to unilateral acoustic trauma 24 h before sleep disturbance being induced using the cage exchange method. Tinnitus perception was assessed behaviourally using a conditioned lick suppression paradigm 3 weeks after the acoustic trauma. Changes in the orexin system in the hypothalamus, which plays an important role in maintaining long-lasting arousal, were also examined using immunohistochemistry. Cage exchange resulted in a significant reduction in the number of sleep episodes and acoustic trauma-induced tinnitus with acoustic features similar to a 32 kHz tone at 100 dB. However, sleep disturbance did not exacerbate the perception of tinnitus in rats. Neither tinnitus alone nor tinnitus plus sleep disturbance altered the number of orexin-expressing neurons. The results suggest that acute sleep disturbance does not cause long-term changes in the number of orexin neurons and does not change the perception of tinnitus induced by acoustic trauma in rats.

  20. Qualitative assessment of precocious puberty-related user-created contents on YouTube

    Directory of Open Access Journals (Sweden)

    Hyo-Kyoung Nam

    2015-09-01

    Full Text Available PurposeUser-created content (UCC has provided a considerable amount of medical information and become an important source. We aimed to evaluate the quality and scientific accuracy of precocious puberty-related UCC on YouTube.MethodsThe keywords "precocious puberty", "early puberty", "sexual precocity", and "precocity" were searched for on YouTube during June and July 2014. More than 1,500 UCC matched the keywords. According to the information provider, UCC was classified as medical, oriental, or commercial & others. We evaluated the quality and scientific accuracy of the information provided in UCC using the DISCERN instrument and information scores, respectively.ResultsWe selected 51 UCC, which were categorized into three types: medical (n=17, oriental (n=17, or commercial & others (n=17. The overall quality score for medical UCC (3.4 was significantly higher relative to those of oriental and commercial & others UCC (2.8 and 2.3, respectively (P<0.001. In the assessment of scientific accuracy, the mean information score for medical UCC (30.7 was significantly higher than those of oriental and commercial & others UCC (15.9 and 5.1, respectively (P<0.001. The mean duration of oriental UCC was the longest (P<0.001, however, it was viewed less frequently among them (P=0.086.ConclusionThe quality and accuracy of precocious puberty-related health information in UCC were variable and often unreliable. The overall quality of UCC regarding precocious puberty was moderate. Only medical UCC provided scientifically accurate information. As UCC becomes a popular source of health information, it is important to provide reliable, scientifically accurate information.

  1. Ascorbic acid deficiency aggravates stress-induced gastric mucosal lesions in genetically scorbutic ODS rats.

    Science.gov (United States)

    Ohta, Y; Chiba, S; Imai, Y; Kamiya, Y; Arisawa, T; Kitagawa, A

    2006-12-01

    We examined whether ascorbic acid (AA) deficiency aggravates water immersion restraint stress (WIRS)-induced gastric mucosal lesions in genetically scorbutic ODS rats. ODS rats received scorbutic diet with either distilled water containing AA (1 g/l) or distilled water for 2 weeks. AA-deficient rats had 12% of gastric mucosal AA content in AA-sufficient rats. AA-deficient rats showed more severe gastric mucosal lesions than AA-sufficient rats at 1, 3 or 6 h after the onset of WIRS, although AA-deficient rats had a slight decrease in gastric mucosal AA content, while AA-sufficient rats had a large decrease in that content. AA-deficient rats had more decreased gastric mucosal nonprotein SH and vitamin E contents and increased gastric mucosal lipid peroxide content than AA-sufficient rats at 1, 3 or 6 h of WIRS. These results indicate that AA deficiency aggravates WIRS-induced gastric mucosal lesions in ODS rats by enhancing oxidative damage in the gastric mucosa.

  2. Association between Obesity and Puberty Timing: A Systematic Review and Meta-Analysis.

    Science.gov (United States)

    Li, Wenyan; Liu, Qin; Deng, Xu; Chen, Yiwen; Liu, Shudan; Story, Mary

    2017-10-24

    This systematic review and meta-analysis examined the associations between obesity and puberty timing based on scientific evidence. Eight electronic databases were searched up to February 2017 for eligible studies, and two reviewers screened the articles and extracted the data independently. A total of 11 cohort studies with 4841 subjects met the inclusion criteria. Compared with the group of normal-weight girls, the obese group had more girls with menarche (RR: 1.87, 95% CI: 1.59-2.19, 2 studies). The number of girls with early puberty was significantly higher in the obese group than the normal weight group (RR: 2.44, 95% CI: 1.32-4.52, 5 studies). However, no differences were detected between girls who were obese or normal weight at age of menarche (WMD: -0.53 years, 95% CI: -1.24-0.19, 2 studies). There is no consistent result in the relationship between obesity and timing of pubertal onset in boys. Obesity may contribute to early onset of puberty in girls, while in boys, there is insufficient data. Given the limited number of cohort studies included in this meta-analysis, high-quality studies with strong markers of puberty onset, as well as standardized criteria for defining obesity are needed.

  3. Bone Density and Timing of Puberty in a Longitudinal Study of Girls.

    Science.gov (United States)

    Cattran, Ashley M; Kalkwarf, Heidi J; Pinney, Susan M; Huang, Bin; Biro, Frank M

    2015-06-01

    Primary: To examine the relationship between relative timing of puberty with bone mineral density (BMD) in a group of adolescent girls; Secondary: To determine if family history of breast cancer was associated with bone mineral density. Longitudinal study of girls recruited between 6 and 7 years of age seen every 6 months for 5 years, and subsequently seen annually. BMD of the lumbar spine was measured by dual-energy X-ray absorptiometry (DXA) at mean age of 12.5 years; age- and race-specific Z-scores (BMDz) were calculated. Age of pubertal onset was determined by the first occurrence of breast stage 2, and participants were categorized into race-specific early, on-time and late puberty onset groups. BMDz by timing of pubertal onset, and by family history of breast cancer. DXA scans were performed on 227 study participants, and a second scan was performed on 114 participants 2 years later. Age of onset of puberty was inversely correlated with BMDz, r = -0.31 (P puberty was associated with higher BMD. The high shared variance of BMD and timing of pubertal onset implies an underlying biologic basis. Copyright © 2015 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

  4. Association between Obesity and Puberty Timing: A Systematic Review and Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Wenyan Li

    2017-10-01

    Full Text Available This systematic review and meta-analysis examined the associations between obesity and puberty timing based on scientific evidence. Eight electronic databases were searched up to February 2017 for eligible studies, and two reviewers screened the articles and extracted the data independently. A total of 11 cohort studies with 4841 subjects met the inclusion criteria. Compared with the group of normal-weight girls, the obese group had more girls with menarche (RR: 1.87, 95% CI: 1.59–2.19, 2 studies. The number of girls with early puberty was significantly higher in the obese group than the normal weight group (RR: 2.44, 95% CI: 1.32–4.52, 5 studies. However, no differences were detected between girls who were obese or normal weight at age of menarche (WMD: −0.53 years, 95% CI: −1.24–0.19, 2 studies. There is no consistent result in the relationship between obesity and timing of pubertal onset in boys. Obesity may contribute to early onset of puberty in girls, while in boys, there is insufficient data. Given the limited number of cohort studies included in this meta-analysis, high-quality studies with strong markers of puberty onset, as well as standardized criteria for defining obesity are needed.

  5. Ontogeny of sensorimotor gating and short-term memory processing throughout the adolescent period in rats

    Directory of Open Access Journals (Sweden)

    Anja A. Goepfrich

    2017-06-01

    Full Text Available Adolescence and puberty are highly susceptible developmental periods during which the neuronal organization and maturation of the brain is completed. The endocannabinoid (eCB system, which is well known to modulate cognitive processing, undergoes profound and transient developmental changes during adolescence. With the present study we were aiming to examine the ontogeny of cognitive skills throughout adolescence in male rats and clarify the potential modulatory role of CB1 receptor signalling. Cognitive skills were assessed repeatedly every 10th day in rats throughout adolescence. All animals were tested for object recognition memory and prepulse inhibition of the acoustic startle reflex. Although cognitive performance in short-term memory as well as sensorimotor gating abilities were decreased during puberty compared to adulthood, both tasks were found to show different developmental trajectories throughout adolescence. A low dose of the CB1 receptor antagonist/inverse agonist SR141716 was found to improve recognition memory specifically in pubertal animals while not affecting behavioral performance at other ages tested. The present findings demonstrate that the developmental trajectory of cognitive abilities does not occur linearly for all cognitive processes and is strongly influenced by pubertal maturation. Developmental alterations within the eCB system at puberty onset may be involved in these changes in cognitive processing.

  6. Alcohol-induced retrograde memory impairment in rats: prevention by caffeine.

    Science.gov (United States)

    Spinetta, Michael J; Woodlee, Martin T; Feinberg, Leila M; Stroud, Chris; Schallert, Kellan; Cormack, Lawrence K; Schallert, Timothy

    2008-12-01

    Ethanol and caffeine are two of the most widely consumed drugs in the world, often used in the same setting. Animal models may help to understand the conditions under which incidental memories formed just before ethanol intoxication might be lost or become difficult to retrieve. Ethanol-induced retrograde amnesia was investigated using a new odor-recognition test. Rats thoroughly explored a wood bead taken from the cage of another rat, and habituated to this novel odor (N1) over three trials. Immediately following habituation, rats received saline, 25 mg/kg pentylenetetrazol (a seizure-producing agent known to cause retrograde amnesia) to validate the test, 1.0 g/kg ethanol, or 3.0 g/kg ethanol. The next day, they were presented again with N1 and also a bead from a new rat's cage (N2). Rats receiving saline or the lower dose of ethanol showed overnight memory for N1, indicated by preferential exploration of N2 over N1. Rats receiving pentylenetetrazol or the higher dose of ethanol appeared not to remember N1, in that they showed equal exploration of N1 and N2. Caffeine (5 mg/kg), delivered either 1 h after the higher dose of ethanol or 20 min prior to habituation to N1, negated ethanol-induced impairment of memory for N1. A combination of a phosphodiesterase-5 inhibitor and an adenosine A(2A) antagonist, mimicking two major mechanisms of action of caffeine, likewise prevented the memory impairment, though either drug alone had no such effect. Binge alcohol can induce retrograde, caffeine-reversible disruption of social odor memory storage or recall.

  7. Gender differences in asthma development and remission during transition through puberty : The TRacking Adolescents' Individual Lives Survey (TRAILS) study

    NARCIS (Netherlands)

    Vink, Nienke M; Postma, Dirkje S; Schouten, Jan P; Rosmalen, Judith G M; Boezen, Hendrika

    BACKGROUND: During puberty, a gender shift in asthma prevalence occurs, with a preponderance of boys before puberty. The mechanisms underlying this gender shift are unclear. OBJECTIVES: We assessed associations of pubertal stages and transition through puberty with (1) the prevalence, incidence, and

  8. Reduced ghrelin secretion in the hypothalamus of rats due to cisplatin-induced anorexia.

    Science.gov (United States)

    Yakabi, Koji; Sadakane, Chiharu; Noguchi, Masamichi; Ohno, Shino; Ro, Shoki; Chinen, Katsuya; Aoyama, Toru; Sakurada, Tomoya; Takabayashi, Hideaki; Hattori, Tomohisa

    2010-08-01

    Although chemotherapy with cisplatin is a widely used and effective cancer treatment, the undesirable gastrointestinal side effects associated with it, such as nausea, vomiting, and anorexia, markedly decrease patients' quality of life. To elucidate the mechanism underlying chemotherapy-induced anorexia, focusing on the hypothalamic ghrelin secretion-anorexia association, we measured hypothalamic ghrelin secretion in fasted and cisplatin-treated rats. Hypothalamic ghrelin secretion changes after vagotomy or administration of cisplatin. Cisplatin + rikkunshito, a serotonin 2C receptor antagonist or serotonin 3 receptor antagonist, was investigated. The effects of intracerebroventricular (icv) administration of ghrelin or the serotonin 2C receptor antagonist SB242084 on food intake were also evaluated in cisplatin-treated rats. Hypothalamic ghrelin secretion significantly increased in 24-h-fasted rats compared to freely fed rats and was markedly reduced 24 and 48 h after cisplatin treatment in cisplatin-treated rats compared to saline-treated rats, although their plasma ghrelin levels were comparable. In cisplatin-treated rats, icv ghrelin administration reversed the decrease in food intake, vagotomy partially restored hypothalamic ghrelin secretion, and hypothalamic serotonin 2C receptor mRNA expression increased significantly. Administration of rikkunshito (an endogenous ghrelin enhancer) or a serotonin 2C receptor antagonist reversed the decrease in hypothalamic ghrelin secretion and food intake 24 h after cisplatin treatment. Cisplatin-induced anorexia is mediated through reduced hypothalamic ghrelin secretion. Cerebral serotonin 2C receptor activation partially induces decrease in hypothalamic ghrelin secretion, and rikkunshito suppresses cisplatin-induced anorexia by enhancing this secretion.

  9. Early puberty in internationally adopted girls: hormonal and clinical markers of puberty in 276 girls examined biannually over two years

    DEFF Research Database (Denmark)

    Teilmann, Grete; Petersen, Jørgen H; Gormsen, Magdalena

    2009-01-01

    Retrospective studies have indicated that internationally adopted girls are at high risk of developing precocious puberty. Hypothetically, this could be due to selection bias. The aim of this study was to determine age at reaching pubertal milestones in healthy internationally adopted girls...

  10. Psychological Support, Puberty Suppression, and Psychosocial Functioning in Adolescents with Gender Dysphoria

    OpenAIRE

    Costa, Rosalia; Dunsford, Michael; Skagerberg, Elin; Holt, Victoria; Carmichael, Polly; Colizzi, Marco

    2015-01-01

    INTRODUCTION: Puberty suppression by gonadotropin-releasing hormone analogs (GnRHa) is prescribed to relieve the distress associated with pubertal development in adolescents with gender dysphoria (GD) and thereby to provide space for further exploration. However, there are limited longitudinal studies on puberty suppression outcome in GD. Also, studies on the effects of psychological support on its own on GD adolescents' well-being have not been reported.AIM: This study aimed to assess GD ado...

  11. Early Treatment of radiation-Induced Heart Damage in Rats by Caffeic acid phenethyl Ester

    International Nuclear Information System (INIS)

    Tawfik, S.S.; Mansour, H. H.

    2012-12-01

    The study designed to determine the therapeutic effect of caffeic acid phenethyl ester (CAPE) in minimising radiation-induced injuries in rats. Rats were exposed to 7 Gy γ-rays, 30 minutes later; rats were injected with CAPE (10μmol/ kg body, i.p.) for 7 consecutive days. Rats were sacrificed at 8 and 15 days after starting the experiment. Gamma-irradiation induced significant increase in malonaldehyde (MDA) level and xanthine oxidase (XO) and adenosine deaminase (ADA) activities, and significant decrease in total nitrate/nitrate (NO (x)) level and glutathione peroxidise (Gpx), superoxide dismutase (SOD)and catalase (CAT) activities in heart tissue and augmented activities of lactate dehydrogenase (LDH), creatine phosphokinase (CPK) and aspartate transaminase (AST) in serum. Irradiated rats early treated with CAPE showed significant decrease in MDA, XO and ADA and significant increase in group. Cardiac enzymes were restored. Conclusion, CAPE could exhibits curable effect on gamma irradiation-induced cardiac-oxidative impairment in rats. (Author)

  12. Oral intake of hydrogen-rich water ameliorated chlorpyrifos-induced neurotoxicity in rats

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Tingting; Zhao, Ling; Liu, Mengyu; Xie, Fei; Ma, Xuemei, E-mail: xmma@bjut.edu.cn; Zhao, Pengxiang; Liu, Yunqi; Li, Jiala; Wang, Minglian; Yang, Zhaona; Zhang, Yutong

    2014-10-01

    Chronic exposure to low-levels of organophosphate (OP) compounds, such as chlorpyrifos (CPF), induces oxidative stress and could be related to neurological disorders. Hydrogen has been identified as a novel antioxidant which could selectively scavenge hydroxyl radicals. We explore whether intake of hydrogen-rich water (HRW) can protect Wistar rats from CPF-induced neurotoxicity. Rats were gavaged daily with 6.75 mg/kg body weight (1/20 LD{sub 50}) of CPF and given HRW by oral intake. Nissl staining and electron microscopy results indicated that HRW intake had protective effects on the CPF-induced damage of hippocampal neurons and neuronal mitochondria. Immunostaining results showed that the increased glial fibrillary acidic protein (GFAP) expression in astrocytes induced by CPF exposure can be ameliorated by HRW intake. Moreover, HRW intake also attenuated CPF-induced oxidative stress as evidenced by enhanced level of MDA, accompanied by an increase in GSH level and SOD and CAT activity. Acetylcholinesterase (AChE) activity tests showed significant decrease in brain AChE activity after CPF exposure, and this effect can be ameliorated by HRW intake. An in vitro study demonstrated that AChE activity was more intense in HRW than in normal water with or without chlorpyrifos-oxon (CPO), the metabolically-activated form of CPF. These observations suggest that HRW intake can protect rats from CPF-induced neurotoxicity, and the protective effects of hydrogen may be mediated by regulating the oxidant and antioxidant status of rats. Furthermore, this work defines a novel mechanism of biological activity of hydrogen by directly increasing the AChE activity. - Highlights: • Hydrogen molecules protect rats from CPF-induced damage of hippocampal neurons. • The increased GFAP expression induced by CPF can also be ameliorated by hydrogen. • Hydrogen molecules attenuated the increase in CPF-induced oxidative stress. • Hydrogen molecules attenuated AChE inhibition in vivo

  13. Oral intake of hydrogen-rich water ameliorated chlorpyrifos-induced neurotoxicity in rats

    International Nuclear Information System (INIS)

    Wang, Tingting; Zhao, Ling; Liu, Mengyu; Xie, Fei; Ma, Xuemei; Zhao, Pengxiang; Liu, Yunqi; Li, Jiala; Wang, Minglian; Yang, Zhaona; Zhang, Yutong

    2014-01-01

    Chronic exposure to low-levels of organophosphate (OP) compounds, such as chlorpyrifos (CPF), induces oxidative stress and could be related to neurological disorders. Hydrogen has been identified as a novel antioxidant which could selectively scavenge hydroxyl radicals. We explore whether intake of hydrogen-rich water (HRW) can protect Wistar rats from CPF-induced neurotoxicity. Rats were gavaged daily with 6.75 mg/kg body weight (1/20 LD 50 ) of CPF and given HRW by oral intake. Nissl staining and electron microscopy results indicated that HRW intake had protective effects on the CPF-induced damage of hippocampal neurons and neuronal mitochondria. Immunostaining results showed that the increased glial fibrillary acidic protein (GFAP) expression in astrocytes induced by CPF exposure can be ameliorated by HRW intake. Moreover, HRW intake also attenuated CPF-induced oxidative stress as evidenced by enhanced level of MDA, accompanied by an increase in GSH level and SOD and CAT activity. Acetylcholinesterase (AChE) activity tests showed significant decrease in brain AChE activity after CPF exposure, and this effect can be ameliorated by HRW intake. An in vitro study demonstrated that AChE activity was more intense in HRW than in normal water with or without chlorpyrifos-oxon (CPO), the metabolically-activated form of CPF. These observations suggest that HRW intake can protect rats from CPF-induced neurotoxicity, and the protective effects of hydrogen may be mediated by regulating the oxidant and antioxidant status of rats. Furthermore, this work defines a novel mechanism of biological activity of hydrogen by directly increasing the AChE activity. - Highlights: • Hydrogen molecules protect rats from CPF-induced damage of hippocampal neurons. • The increased GFAP expression induced by CPF can also be ameliorated by hydrogen. • Hydrogen molecules attenuated the increase in CPF-induced oxidative stress. • Hydrogen molecules attenuated AChE inhibition in vivo and in

  14. Antihyperglycemic and antidyslipidemic activity of Musa paradisiaca-based diet in alloxan-induced diabetic rats.

    Science.gov (United States)

    Ajiboye, Basiru O; Oloyede, Hussein O B; Salawu, Musa O

    2018-01-01

    This study was aimed at investigating the antihyperglycemic and antidyslipidemic activity of Musa paradisiaca -based diets in alloxan-induced diabetic mellitus rats. Diabetes was induced by a single intraperitoneal injection of alloxan (150 mg/kg b.w) in 48 randomly selected rats. The rats were randomly grouped into four as follows: normal rats fed Dioscorea rotundata -based diet, diabetic control rats fed D. rotundata -based diet, diabetic rats fed D. rotundata -based diet and administered metformin (14.2 mg/kg body weight) orally per day, and diabetic rats fed M. paradisiaca -based diet. Body weight and fasting blood glucose level were monitored, on 28th days the rats were sacrificed, liver was excised. Thereafter, the hyperglycemic and dyslipidemic statii of the induced diabetic animals were determined. The M. paradisiaca -based diet significantly ( p  paradisiaca -based diet demonstrated significant reduction ( p  paradisiaca -based diet significantly ( p  <   .05) reversed the activities of aspartate aminotransferase and alanine aminotransferase when compared with diabetic control animals. The consumption of this diet may be useful in ameliorating hyperglycemia and dyslipidemia in diabetes mellitus patients.

  15. Andrographis paniculata leaf extract prevents thioacetamide-induced liver cirrhosis in rats.

    Directory of Open Access Journals (Sweden)

    Daleya Abdulaziz Bardi

    Full Text Available This study investigated the hepatoprotective effects of ethanolic Andrographis paniculata leaf extract (ELAP on thioacetamide-induced hepatotoxicity in rats. An acute toxicity study proved that ELAP is not toxic in rats. To examine the effects of ELAP in vivo, male Sprague Dawley rats were given intraperitoneal injections of vehicle 10% Tween-20, 5 mL/kg (normal control or 200 mg/kg TAA thioacetamide (to induce liver cirrhosis three times per week. Three additional groups were treated with thioacetamide plus daily oral silymarin (50 mg/kg or ELAP (250 or 500 mg/kg. Liver injury was assessed using biochemical tests, macroscopic and microscopic tissue analysis, histopathology, and immunohistochemistry. In addition, HepG2 and WRL-68 cells were treated in vitro with ELAP fractions to test cytotoxicity. Rats treated with ELAP exhibited significantly lower liver/body weight ratios and smoother, more normal liver surfaces compared with the cirrhosis group. Histopathology using Hematoxylin and Eosin along with Masson's Trichrome stain showed minimal disruption of hepatic cellular structure, minor fibrotic septa, a low degree of lymphocyte infiltration, and minimal collagen deposition after ELAP treatment. Immunohistochemistry indicated that ELAP induced down regulation of proliferating cell nuclear antigen. Also, hepatic antioxidant enzymes and oxidative stress parameters in ELAP-treated rats were comparable to silymarin-treated rats. ELAP administration reduced levels of altered serum liver biomarkers. ELAP fractions were non-cytotoxic to WRL-68 cells, but possessed anti-proliferative activity on HepG2 cells, which was confirmed by a significant elevation of lactate dehydrogenase, reactive oxygen species, cell membrane permeability, cytochrome c, and caspase-8,-9, and, -3/7 activity in HepG2 cells. A reduction of mitochondrial membrane potential was also detected in ELAP-treated HepG2 cells. The hepatoprotective effect of 500 mg/kg of ELAP is proposed

  16. Andrographis paniculata leaf extract prevents thioacetamide-induced liver cirrhosis in rats.

    Science.gov (United States)

    Abdulaziz Bardi, Daleya; Halabi, Mohammed Farouq; Hassandarvish, Pouya; Rouhollahi, Elham; Paydar, Mohammadjavad; Moghadamtousi, Soheil Zorofchian; Al-Wajeeh, Nahla Saeed; Ablat, Abdulwali; Abdullah, Nor Azizan; Abdulla, Mahmood Ameen

    2014-01-01

    This study investigated the hepatoprotective effects of ethanolic Andrographis paniculata leaf extract (ELAP) on thioacetamide-induced hepatotoxicity in rats. An acute toxicity study proved that ELAP is not toxic in rats. To examine the effects of ELAP in vivo, male Sprague Dawley rats were given intraperitoneal injections of vehicle 10% Tween-20, 5 mL/kg (normal control) or 200 mg/kg TAA thioacetamide (to induce liver cirrhosis) three times per week. Three additional groups were treated with thioacetamide plus daily oral silymarin (50 mg/kg) or ELAP (250 or 500 mg/kg). Liver injury was assessed using biochemical tests, macroscopic and microscopic tissue analysis, histopathology, and immunohistochemistry. In addition, HepG2 and WRL-68 cells were treated in vitro with ELAP fractions to test cytotoxicity. Rats treated with ELAP exhibited significantly lower liver/body weight ratios and smoother, more normal liver surfaces compared with the cirrhosis group. Histopathology using Hematoxylin and Eosin along with Masson's Trichrome stain showed minimal disruption of hepatic cellular structure, minor fibrotic septa, a low degree of lymphocyte infiltration, and minimal collagen deposition after ELAP treatment. Immunohistochemistry indicated that ELAP induced down regulation of proliferating cell nuclear antigen. Also, hepatic antioxidant enzymes and oxidative stress parameters in ELAP-treated rats were comparable to silymarin-treated rats. ELAP administration reduced levels of altered serum liver biomarkers. ELAP fractions were non-cytotoxic to WRL-68 cells, but possessed anti-proliferative activity on HepG2 cells, which was confirmed by a significant elevation of lactate dehydrogenase, reactive oxygen species, cell membrane permeability, cytochrome c, and caspase-8,-9, and, -3/7 activity in HepG2 cells. A reduction of mitochondrial membrane potential was also detected in ELAP-treated HepG2 cells. The hepatoprotective effect of 500 mg/kg of ELAP is proposed to result from

  17. Study Of Morphological Changes Of Uterine Horn Of Surri Mouse Depended To Morphine Before Puberty And DuringPuberty

    Directory of Open Access Journals (Sweden)

    Shadkhast M

    2003-11-01

    Full Text Available : Morphine is the most important alkaloid of opium family which is found as much as ten percent in opium, and is in two types the sulfate morphine and the hydrochloride morphine."nMaterials and Methods: In this study morphological changes of uterus of surri mice due to oral consumption of sulfate morphine were studied. It was shown that, female surri mice following gradually increasing of morphine to water (0.1 and 0.01 mg/ml were depended to morphine. Female surri mice were classified in two age groups before puberty and depended to morphine during puberty. Each age group took morphine for 21 days. After finishing the period, the mice anesthetizing were weighted, then were anesthetizing and uterus was studied the length, width and apparent features."nResults&ConcIusion: In this study it was distinguished that length and width of uterine horn, between experimental and control groups, were significant (P< 0.01. Morphological changes such as anemia, the thinness and fragitidily walls of uterus and filiformity of uterine horns were observed."n"n"n"n"n"n 

  18. Establishment of an induced rat model of malignant pleural mesothelioma

    International Nuclear Information System (INIS)

    Han Dan; Wu Beihai; Yang Hongsheng; Song Guangyi

    2004-01-01

    Objective: To establish a convenient and practical malignant pleural mesothelioma (MPM) model induced by crocidolite in Da Yao, which has a high induction rate and can be used for imaging and multiple experimental studies and is similar to human MPM. Methods 40 mg of crocidolite suspension was injected into the right chest cavity in 100 Wistar rats in the test group, while same amount of sterilized saline water was injected in 20 rats in the control group. The animals were observed daily , and weighted once a month. CT scanning was performed regularly. When the rats were dead or dying, they were dissected immediately and pathological changes were recorded after CT examination. The experiment lasted for 2 years. Results: The overall induction rate was 71.6%. The survival time of the first MPM rat was 285 days. The mean living span of rats with MPM was (469 ± 21) days. The pathological features of the induced MPMs were multiple morphologically and there were some CT features in different periods. CT imaging could show some MPM features and find the tumour earlier. Conclusion: The cause, positions, tissues and clinical condition of induced tumors were the same as humans. The model had a higher similarity with human MPM in differentiation degree and histological type, and the model can be used to study the mechanism of MPM, to discuss the measures of prevention, and to guide clinical diagnosis and treatment. Multi-morphology of the history from the induced tumors could make up the shortage, which was the difficulty in getting all periods of tissue samples in clinical research and being used in imaging and many kinds of researches. It was a valuable animal model to study MPM. (authors)

  19. Effects of ginkgo biloba extract on laser-induced choroidal neovascularization in rats

    Directory of Open Access Journals (Sweden)

    Chao Chen

    2013-11-01

    Full Text Available AIM: To investigate the effects of ginkgo biloba extract(EGb 761on laser-induced choroidal neovascularization(CNVin rats.METHODS: Totally 60 BN rats were randomly divided into 4 groups: normal control group, model group, experimental group, physiological saline group with 15 in each group. All CNV models were made by krypton laser. Rats in experimental group were intraperitoneally injected with 0.35% EGb761(100mg/kgevery day after laser exposure until they were sacrificed. Rats in physiological saline group were intraperitoneally injected physiological saline every day after laser exposure until they were sacrificed. Fundus fluorescein angiography(FFAwas performed on every rat on the 7th day, 14th day and the 21st day after laser exposure, then the rats were sacrificed immediately. The eyes were enucleated and processed for histopathologic examination.RESULTS: There was no choroidal fluorescein leakage staining in normal rats. There were obviously less choroidal fluorescein leakage points in experimental groups than that in the corresponding model groups(PCONCLUSION: EGb761 len inhibit the formation of laser-induced CNV in rats. The longer the time, the better curative effect.

  20. Cannabis exacerbates depressive symptoms in rat model induced by reserpine.

    Science.gov (United States)

    Khadrawy, Yasser A; Sawie, Hussein G; Abdel-Salam, Omar M E; Hosny, Eman N

    2017-05-01

    Cannabis sativa is one of the most widely recreational drugs and its use is more prevalent among depressed patients. Some studies reported that Cannabis has antidepressant effects while others showed increased depressive symptoms in Cannabis users. Therefore, the present study aims to investigate the effect of Cannabis extract on the depressive-like rats. Twenty four rats were divided into: control, rat model of depression induced by reserpine and depressive-like rats treated with Cannabis sativa extract (10mg/kg expressed as Δ9-tetrahydrocannabinol). The depressive-like rats showed a severe decrease in motor activity as assessed by open field test (OFT). This was accompanied by a decrease in monoamine levels and a significant increase in acetylcholinesterase activity in the cortex and hippocampus. Na + ,K + -ATPase activity increased in the cortex and decreased in the hippocampus of rat model. In addition, a state of oxidative stress was evident in the two brain regions. This was indicated from the significant increase in the levels of lipid peroxidation and nitric oxide. No signs of improvement were observed in the behavioral and neurochemical analyses in the depressive-like rats treated with Cannabis extract. Furthermore, Cannabis extract exacerbated the lipid peroxidation in the cortex and hippocampus. According to the present findings, it could be concluded that Cannabis sativa aggravates the motor deficits and neurochemical changes induced in the cortex and hippocampus of rat model of depression. Therefore, the obtained results could explain the reported increase in the depressive symptoms and memory impairment among Cannabis users. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Ranitidine reduced levodopa-induced dyskinesia in a rat model of Parkinson’s disease

    Directory of Open Access Journals (Sweden)

    Cui G

    2013-12-01

    Full Text Available Guiyun Cui,1,* Xinxin Yang,1,* Xiaoying Wang,2,* Zunsheng Zhang,1 Xuanye Yue,1 Hongjuan Shi,1 Xia Shen11Department of Neurology, 2Department of Ultrasound, the Affiliated Hospital of Xuzhou Medical College, Jiangsu, People’s Republic of China *These authors contributed equally to this workBackground: Chronic administration of levodopa in Parkinson’s disease leads to debilitating involuntary movements, termed levodopa-induced dyskinesia (LID. The pathogenesis of LID is poorly understood. Previous research has shown that histamine H2 receptors are highly expressed in the input (striatum and output (globus pallidus, substantia nigra regions of the basal ganglia, particularly in the GABAergic striatopallidal and striatonigral pathways. Therefore, a histamine H2 receptor antagonist could be used to reduce LID. In the present work, we investigated whether ranitidine has the potential to diminish LID in rats with dyskinesia and explored the underlying mechanisms involved.Methods: A rat model of PD was induced by 6-hydroxydopamine. Valid PD rats were then treated with levodopa (25 mg/kg, intraperitoneally and benserazide (12.5 mg/kg, intraperitoneally for 21 days to induce a rat model of LID. The acute and chronic effects of administration of ranitidine at different doses (5 mg/kg, 10 mg/kg, and 20 mg/kg on abnormal involuntary movements, levodopa-induced rotations, and the forelimb adjusting steps test were investigated in LID rats. The chronic effect of ranitidine (10 mg/kg on the expression of Arc and proenkephalin was also evaluated.Results: Levodopa elicited increased dyskinesia in PD rats. Acute ranitidine treatment had no effect on LID, but chronic ranitidine administration (10 mg/kg, 20 mg/kg reduced LID in rats with dyskinesia. Importantly, levodopa-induced rotations were not affected by chronic treatment with ranitidine. In addition, chronic ranitidine (10 mg/kg, 20 mg/kg significantly improved stepping of the lesioned forepaw. Real

  2. Effect of irradiation on the dental pulp tissues in streptozotocin-induced diabetic rats

    International Nuclear Information System (INIS)

    Kang, Ho Duk; Hwang, Eui Hwan; Lee, Sang Rae

    2005-01-01

    To observe the histological changes in the pulp tissues of mandibular molars in streptozotocin-induced diabetic rats after irradiation. The male Sprague-Dawley rats weighing approximately 250 gm were divided into four groups : control, diabetes, irradiation, and diabetes-irradiation groups. Diabetes mellitus was induced in the rats by injecting streptozotocin. Rats in control and irradiation groups were injected with citrate buffer only. After 5 days, the head and neck region of the rats in irradiation and diabetes-irradiation groups were irradiated with a single absorbed dose of 10 Gy. All the rats were sacrificed at 3, 7, 14, 21, and 28 days after irradiation. The specimen including the mandibular molars were sectioned and observed using a histopathological method. In the diabetes group, capillary dilatation was observed. However, there was no obvious morphologic alteration of the odontoblasts. In the irradiation group, generalized necrosis of the dental pulp tissues was observed. Vacuolation of the odontoblasts and dilatation of the capillaries were noted in the early experimental phases. In the diabetes-irradiation group, generalized degeneration of the dental pulp tissues was observed. Vacuolation of the dental pulp cells and the odontoblasts was noted in the late experimental phases. This experiment suggest that dilatation of the capillaries in the dental pulp tissue is induced by diabetic state, and generalized degeneration of the dental pulp tissues is induced by irradiation of the diabetic group.

  3. Effects of melatonin on aluminium-induced neurobehavioral and neurochemical changes in aging rats.

    Science.gov (United States)

    Allagui, M S; Feriani, A; Saoudi, M; Badraoui, R; Bouoni, Z; Nciri, R; Murat, J C; Elfeki, A

    2014-08-01

    This study aimed to investigate the potential protective effects of melatonin (Mel) against aluminium-induced neurodegenerative changes in aging Wistar rats (24-28months old). Herein, aluminium chloride (AlCl3) (50mg/kg BW/day) was administered by gavage, and melatonin (Mel) was co-administered to a group of Al-treated rats by an intra-peritoneal injection at a daily dose of 10mg/kg BW for four months. The findings revealed that aluminium administration induced a significant decrease in body weight associated with marked mortality for the old group of rats, which was more pronounced in old Al-treated rats. Behavioural alterations were assessed by 'open fields', 'elevated plus maze' and 'Radial 8-arms maze' tests. The results demonstrated that Mel co-administration alleviated neurobehavioral changes in both old and old Al-treated rats. Melatonin was noted to play a good neuroprotective role, reducing lipid peroxidation (TBARs), and enhancing enzymatic (SOD, CAT and GPx) activities in the brain organs of old control and old Al-treated rats. Mel treatment also reversed the decrease of AChE activity in the brain tissues, which was confirmed by histological sections. Overall, the results showed that Mel administration can induce beneficial effects for the treatment of Al-induced neurobehavioral and neurochemical changes in the central nervous system (CNS). Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. Momordica charantia polysaccharides mitigate the progression of STZ induced diabetic nephropathy in rats.

    Science.gov (United States)

    Raish, Mohammad; Ahmad, Ajaz; Jan, Basit L; Alkharfy, Khalid M; Ansari, Mushtaq Ahmad; Mohsin, Kazi; Jenoobi, Fahad Al; Al-Mohizea, Abdullah

    2016-10-01

    Diabetic nephropathy (DN) has become a primary cause of end-stage kidney disease. Several complex dynamics converge together to accelerate the advancement of DN. The present investigation was postulated to explore the mechanism of reno-protective nature of Momordica Charantia polysaccharides (MCP) by evaluating the anti-hyperglycemic, anti-lipidemic as well as markers for oxidative stress and antioxidant proficiency in streptozotocin (STZ)-induced diabetic rats. The oral administration of MCP showed a significant normalization in the levels of kidney function test in the STZ-induced diabetic rats. The levels of blood urea nitrogen (BUN), urea protein and creatinine increased by 316.58%, 195.14% and 800.97% respectively, in STZ-induced diabetic rats when compared with normal rats. MCP treatment also illustrated a significant improvement in glutathione peroxidase, superoxide dismutase and catalase levels, with a significant decline in MDA in diabetic kidneys. Immunoblots of heme-oxygenase 1 (HO-1) and Nrf2 of MCP treated diabetic rats showed a significant up-regulation of HO-1 and Nrf2 protein. Histological and ultra-structural observations also reveal that MCP efficiently protects the kidneys from hyperglycemia-mediated oxidative damage. These findings illustrate that the reno-protective nature of MCP mitigates the progression of STZ induced DN in rats by suppression of oxidative stress and amelioration of the HO-1/Nrf2 pathway. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Brain Aging and AD-Like Pathology in Streptozotocin-Induced Diabetic Rats

    Directory of Open Access Journals (Sweden)

    Jian-Qin Wang

    2014-01-01

    Full Text Available Objective. Numerous epidemiological studies have linked diabetes mellitus (DM with an increased risk of developing Alzheimer’s disease (AD. However, whether or not diabetic encephalopathy shows AD-like pathology remains unclear. Research Design and Methods. Forebrain and hippocampal volumes were measured using stereology in serial coronal sections of the brain in streptozotocin- (STZ- induced rats. Neurodegeneration in the frontal cortex, hypothalamus, and hippocampus was evaluated using Fluoro-Jade C (FJC. Aβ aggregation in the frontal cortex and hippocampus was tested using immunohistochemistry and ELISA. Dendritic spine density in the frontal cortex and hippocampus was measured using Golgi staining, and western blot was conducted to detect the levels of synaptophysin. Cognitive ability was evaluated through the Morris water maze and inhibitory avoidant box. Results. Rats are characterized by insulin deficiency accompanied with polydipsia, polyphagia, polyuria, and weight loss after STZ injection. The number of FJC-positive cells significantly increased in discrete brain regions of the diabetic rats compared with the age-matched control rats. Hippocampal atrophy, Aβ aggregation, and synapse loss were observed in the diabetic rats compared with the control rats. The learning and memory of the diabetic rats decreased compared with those of the age-matched control rats. Conclusions. Our results suggested that aberrant metabolism induced brain aging as characterized by AD-like pathologies.

  6. Brain Aging and AD-Like Pathology in Streptozotocin-Induced Diabetic Rats

    Science.gov (United States)

    Wang, Jian-Qin; Yin, Jie; Song, Yan-Feng; Zhang, Lang; Ren, Ying-Xiang; Wang, De-Gui; Gao, Li-Ping; Jing, Yu-Hong

    2014-01-01

    Objective. Numerous epidemiological studies have linked diabetes mellitus (DM) with an increased risk of developing Alzheimer's disease (AD). However, whether or not diabetic encephalopathy shows AD-like pathology remains unclear. Research Design and Methods. Forebrain and hippocampal volumes were measured using stereology in serial coronal sections of the brain in streptozotocin- (STZ-) induced rats. Neurodegeneration in the frontal cortex, hypothalamus, and hippocampus was evaluated using Fluoro-Jade C (FJC). Aβ aggregation in the frontal cortex and hippocampus was tested using immunohistochemistry and ELISA. Dendritic spine density in the frontal cortex and hippocampus was measured using Golgi staining, and western blot was conducted to detect the levels of synaptophysin. Cognitive ability was evaluated through the Morris water maze and inhibitory avoidant box. Results. Rats are characterized by insulin deficiency accompanied with polydipsia, polyphagia, polyuria, and weight loss after STZ injection. The number of FJC-positive cells significantly increased in discrete brain regions of the diabetic rats compared with the age-matched control rats. Hippocampal atrophy, Aβ aggregation, and synapse loss were observed in the diabetic rats compared with the control rats. The learning and memory of the diabetic rats decreased compared with those of the age-matched control rats. Conclusions. Our results suggested that aberrant metabolism induced brain aging as characterized by AD-like pathologies. PMID:25197672

  7. ANTI-DIABETIC EFFECTS OF TURMERIC IN ALLOXAN INDUCE D DIABETIC RATS

    OpenAIRE

    Jeevangi; Manjunath; Deepak D; Prakash G; Prashant; Chetan

    2013-01-01

    ABSTRACT: OBJECTIVE AND BACKGROUND: Turmeric (Curcuma longa) is one of the common constituents of our daily food. The present study wa s undertaken to evaluate the anti-diabetic effects of ethanolic extract of Rhizomes of curcuma longa in alloxan induced diabetic rats and compared with of Pioglitazone, which is the standard anti-diabetic agent. METHODS: Alloxan monohydrate is used to induce diabetes mellitus in albino rats in the dose of 120mg/kg i.p. and ...

  8. The effect of puberty on fat oxidation rates during exercise in overweight and normal-weight girls.

    Science.gov (United States)

    Chu, L; Riddell, M C; Schneiderman, J E; McCrindle, B W; Hamilton, J K

    2014-01-01

    Excess weight is often associated with insulin resistance (IR) and may disrupt fat oxidation during exercise. This effect is further modified by puberty. While studies have shown that maximal fat oxidation rates (FOR) during exercise decrease with puberty in normal-weight (NW) and overweight (OW) boys, the effect of puberty in NW and OW girls is unclear. Thirty-three NW and OW girls ages 8-18 yr old completed a peak aerobic capacity test on a cycle ergometer. FOR were calculated during progressive submaximal exercise. Body composition and Tanner stage were determined. For each participant, a best-fit polynomial curve was constructed using fat oxidation vs. exercise intensity to estimate max FOR. In a subset of the girls, IR derived from an oral glucose tolerance test (n = 20), and leptin and adiponectin levels (n = 11) were assessed in relation to FOR. NW pre-early pubertal girls had higher max FOR [6.9 ± 1.4 mg·kg fat free mass (FFM)(-1)·min(-1)] than NW mid-late pubertal girls (2.2 ± 0.9 mg·kg FFM(-1)·min(-1)) (P = 0.002), OW pre-early pubertal girls (3.8 ± 2.1 mg·kg FFM(-1)·min(-1)), and OW mid-late pubertal girls (3.3 ± 0.9 mg·kg FFM(-1)·min(-1)) (P puberty; however, this decrease associated with puberty was blunted in OW girls due to lower FOR in pre-early puberty. The presence of IR due to obesity potentially masks the effect of puberty on FOR during exercise in girls.

  9. Tracing Fasting Glucose Fluxes with Unstressed Catheter Approach in Streptozotocin Induced Diabetic Rats

    Directory of Open Access Journals (Sweden)

    Shichun Du

    2014-01-01

    Full Text Available Objective. Blood glucose concentrations of type 1 diabetic rats are vulnerable, especially to stress and trauma. The present study aimed to investigate the fasting endogenous glucose production and skeletal muscle glucose uptake of Streptozotocin induced type 1 diabetic rats using an unstressed vein and artery implantation of catheters at the tails of the rats as a platform. Research Design and Methods. Streptozotocin (65 mg·kg−1 was administered to induce type 1 diabetic state. The unstressed approach of catheters of vein and artery at the tails of the rats was established before the isotope tracer injection. Dynamic measurement of fasting endogenous glucose production was assessed by continuously infusing stable isotope [6, 6-2H2] glucose, while skeletal muscle glucose uptake by bolus injecting radioactively labeled [1-14C]-2-deoxy-glucose. Results. Streptozotocin induced type 1 diabetic rats displayed polydipsia, polyphagia, and polyuria along with overt hyperglycemia and hypoinsulinemia. They also had enhanced fasting endogenous glucose production and reduced glucose uptake in skeletal muscle compared to nondiabetic rats. Conclusions. The dual catheters implantation at the tails of the rats together with isotope tracers injection is a save time, unstressed, and feasible approach to explore the glucose metabolism in animal models in vivo.

  10. Endocrine studies in ivermectin-treated heifers from birth to puberty.

    Science.gov (United States)

    Lacau-Mengido, I M; Mejía, M E; Díaz-Torga, G S; Gonzalez Iglesias, A; Formía, N; Libertun, C; Becú-Villalobos, D

    2000-04-01

    Continuous treatment with ivermectin from birth to puberty advanced sexual maturation by 3.7 wk in Holstein heifers grazing pastures naturally infected with nematodes. Every 14 d jugular blood samples were taken from birth to 45 wk of age from all heifers. No differences in serum FSH, estradiol, or thyroxine levels were observed during the trial between the treated and untreated group. Mean LH levels were diminished in untreated heifers 4 wk before the first estrus and the amplitude of LH pulses was augmented in treated heifers when puberty was reached. Serum IGF-I levels increased from birth to 22 wk of age and then reached a plateau in both groups, but levels were consistently higher in treated heifers from 26 wk of age onward. Body weight gain was retarded in parasitized heifers and IGF-I values were positively correlated with body weight only during the first 20 wk of life. We suggest that enhanced prepubertal IGF-I levels in conjunction with increased prepubertal LH levels and pubertal LH pulse amplitude might be involved in the accelerated somatic maturation and in puberty advancement observed in ivermectin-treated heifers.

  11. METHOD OF TREATMENT OF CONSTITUTIONAL PUBERTY RETARDATION IN BOYS (CASE HISTORY

    Directory of Open Access Journals (Sweden)

    A. A. Sinitsina

    2012-01-01

    Full Text Available The results of examination of a 15-year-old boy with growth and puberty retardation are analyzed in this article. On the grounds of performed complex examination the patient was found physical development delay, changes at the endocrinal status, as well as pathological signs on X-ray, rheo- and electroencephalography, which are characteristic for functional growth and puberty retardation. In order to correct the found disturbances transcranial magnetotherapy was carried out. During the performed treatment improvement of the physical development characteristics, endocrinal status and data of rheo- and electroencephalography were noted.

  12. Extracellular ATP induces albuminuria in pregnant rats

    NARCIS (Netherlands)

    Faas, M.M.; van der Schaaf, G.; Borghuis, T.; Jongman, R.M.; van Pampus, Maria; de Vos, P.; van Goor, Harry; Bakker, W.W.

    BACKGROUND: As circulating plasma ATP concentrations are increased in pre-eclampsia, we tested whether increased plasma ATP is able to induce albuminuria during pregnancy. METHODS: Pregnant (day 14) and non-pregnant rats were infused with ATP (3000 microg/kg bw) via a permanent jugular vein cannula.

  13. Lesions of the lateral hypothalamus impair pilocarpine-induced salivation in rats.

    Science.gov (United States)

    Renzi, A; De Luca, L A; Menani, J V

    2002-09-15

    In the present study we investigated the effects of electrolytic lesions of the lateral hypothalamus (LH) in the salivation induced by intracerebroventricular (i.c.v.) or intraperitoneal (i.p.) injection of the cholinergic agonist pilocarpine. Rats with sham or LH lesions and stainless steel cannulas implanted into the lateral ventricle (LV) were used. In rats anesthetized with urethane (1.25mg/kg of body weight) saliva was collected using pre-weighed cotton balls inserted in the animal mouth during a period of 7 min following i.c.v. or i.p. injection of pilocarpine. Injection of pilocarpine (1mg/kg of body weight) i.p. in sham-operated rats (6h, 2, 7, and 15 days after the surgery) induced salivation (497+/-24, 452+/-26, 476+/-30, and 560+/-75 mg/7 min, respectively). The effects of i.p. pilocarpine was reduced 6h, 2 and 7 days after LH lesions (162+/-37, 190+/-32, and 229+/-27 mg/7 min, respectively), not 15 days after LH lesions (416+/-89 mg/7 min). Injection of pilocarpine (120 micro g/micro l) i.c.v., in sham-operated rats (6h, 2, 7, and 15 days after the surgery) also produced salivation (473+/-20, 382+/-16, 396+/-14, and 427+/-47 mg/7 min, respectively). The salivation induced by i.c.v. pilocarpine was also reduced 6h, 2 and 7 days after LH lesions (243+/-19, 278+/-24, and 295+/-27 mg/7 min, respectively), not 15 days after LH lesions (385+/-48 mg/7 min). The present results show the participation of the LH in the salivation induced by central or peripheral injection of pilocarpine in rats, reinforcing the involvement of central mechanisms on pilocarpine-induced salivation.

  14. Effects of intra-fourth ventricle injection of crocin on capsaicin-induced orofacial pain in rats.

    Science.gov (United States)

    Tamaddonfard, Esmaeal; Tamaddonfard, Sina; Pourbaba, Salar

    2015-01-01

    Crocin, a constituent of saffron and yellow gardenia, possesses anti-nociceptive effects. In the present study, we investigated the effects of intra-fourth ventricle injection of crocin in a rat model of orofacial pain. The contribution of opioid system was assessed using intra-fourth ventricle injection of naloxone, an opioid receptor antagonist. A guide cannula was implanted into the fourth ventricle of brain in anesthetized rats. Orofacial pain was induced by subcutaneous (s.c.) injection of capsaicin (1.5 µg/20 µl) into the right vibrissa pad. The time spent face rubbing/grooming was recorded for a period of 20 min. Locomotor activity was measured using an open-field test. Intra-fourth ventricle injection of crocin (10 and 40 µg/rat) and morphine (10 and 40 µg/rat) and their co-administration (2.5 and 10 µg/rat of each) suppressed capsaicin-induced orofacial pain. The analgesic effect induced by 10 µg/rat of morphine, but not crocin (10 µg/rat), was prevented by 20 µg/rat of naloxone pretreatment. The above-mentioned chemical compounds did not affect locomotor activity. The results of this study showed that the injection of crocin into the cerebral fourth ventricle attenuates capsaicin-induced orofacial pain in rats. The anti-nociceptive effect of crocin was not attributed to the central opioid receptors.

  15. Effects of intra-fourth ventricle injection of crocin on capsaicin-induced orofacial pain in rats

    Directory of Open Access Journals (Sweden)

    Esmaeal Tamaddonfard

    2015-08-01

    Full Text Available Objectives: Crocin, a constituent of saffron and yellow gardenia, possesses anti-nociceptive effects. In the present study, we investigated the effects of intra-fourth ventricle injection of crocin in a rat model of orofacial pain. The contribution of opioid system was assessed using intra-fourth ventricle injection of naloxone, an opioid receptor antagonist. Materials and Methods: A guide cannula was implanted into the fourth ventricle of brain in anesthetized rats. Orofacial pain was induced by subcutaneous (s.c. injection of capsaicin (1.5 µg/20 µl into the right vibrissa pad. The time spent face rubbing/grooming was recorded for a period of 20 min. Locomotor activity was measured using an open-field test. Results: Intra-fourth ventricle injection of crocin (10 and 40 µg/rat and morphine (10 and 40 µg/rat and their co-administration (2.5 and 10 µg/rat of each suppressed capsaicin-induced orofacial pain. The analgesic effect induced by 10 µg/rat of morphine, but not crocin (10 µg/rat, was prevented by 20 µg/rat of naloxone pretreatment. The above-mentioned chemical compounds did not affect locomotor activity. Conclusion: The results of this study showed that the injection of crocin into the cerebral fourth ventricle attenuates capsaicin-induced orofacial pain in rats. The anti-nociceptive effect of crocin was not attributed to the central opioid receptors.

  16. Dai-Kenchu-To, a Herbal Medicine, Attenuates Colorectal Distention-induced Visceromotor Responses in Rats.

    Science.gov (United States)

    Nakaya, Kumi; Nagura, Yohko; Hasegawa, Ryoko; Ito, Hitomi; Fukudo, Shin

    2016-10-30

    Dai-kenchu-to (DKT), a traditional Japanese herbal medicine, is known to increase gastrointestinal motility and improve ileal function. We tested our hypotheses that (1) pretreatment with DKT would block the colorectal distention-induced visceromotor response in rats, and (2) pretreatment with DKT would attenuate colorectal distention-induced adrenocorticotropic hormone (ACTH) release and anxiety-related behavior. Rats were pretreated with vehicle or DKT (300 mg/kg/5 mL, per os). Visceromotor responses were analyzed using electromyography in response to colorectal distention (10, 20, 40, 60, and 80 mmHg for 20 seconds at 3-minutes intervals). Anxiety-related behavior was measured during exposure to an elevated-plus maze after colorectal distention. Plasma ACTH and serum corticosterone levels were measured after exposure to the elevated-plus maze. Colorectal distention produced robust contractions of the abdominal musculature, graded according to stimulus intensity, in vehicle-treated rats. At 40, 60, and 80 mmHg of colorectal distention, the visceromotor responses of DKT-treated rats was significantly lower than that of vehicle-treated rats. At 80 mmHg, the amplitude was suppressed to approximately one-third in DKT-treated rats, compared with that in vehicle-treated rats. Smooth muscle compliance and the velocity of accommodation to 60 mmHg of stretching did not significantly differ between the vehicle-treated and DKT-treated rats. Similarly, the DKT did not influence colorectal distention-induced ACTH release, corticosterone levels, or anxiety-related behavior in rats. Our results suggest that DKT attenuates the colorectal distention-induced visceromotor responses, without increasing smooth muscle compliance, ACTH release or anxiety-related behavior in rats.

  17. The formation of rats' choroidal neovascularization induced by acrolein

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    Guan-Feng Wang

    2016-04-01

    Full Text Available AIM:To investigate the formation of rats' choroidal neovascularization(CNVinduced by acrolein. METHODS:Twelve Sprague-Dawley rats were randomly divided into three groups. Acrolein 200μL(2.5 mg/kg/dwas poured into the rats' stomach for 4wk as acrolein 4wk and for 8wk as acrolein 8wk group. The same volume of fresh water was also done to the rats as the control group. Remove all eye balls and embed into paraffin with HE staining.RESLUTS:The RPE-Bruch membrane was intact with no obvious abnormality in the control group and acrolein 4wk group. Lost in the continuity of RPE and the movement of choroidal neovascularization were found in the acrolein 8wk. CONCLUSION:The long time use of acrolein can induce the formation of choroial neovascularization in rats.

  18. Maternal Docosahexaenoic Acid Increases Adiponectin and Normalizes IUGR-Induced Changes in Rat Adipose Deposition

    Directory of Open Access Journals (Sweden)

    Heidi N. Bagley

    2013-01-01

    Full Text Available Intrauterine growth restriction (IUGR predisposes to obesity and adipose dysfunction. We previously demonstrated IUGR-induced increased visceral adipose deposition and dysregulated expression of peroxisome proliferator activated receptor-γ2 (PPARγ2 in male adolescent rats, prior to the onset of obesity. In other studies, activation of PPARγ increases subcutaneous adiponectin expression and normalizes visceral adipose deposition. We hypothesized that maternal supplementation with docosahexaenoic acid (DHA, a PPARγ agonist, would normalize IUGR adipose deposition in association with increased PPARγ, adiponectin, and adiponectin receptor expression in subcutaneous adipose. To test these hypotheses, we used a well-characterized model of uteroplacental-insufficiency-(UPI- induced IUGR in the rat with maternal DHA supplementation. Our primary findings were that maternal DHA supplementation during rat pregnancy and lactation (1 normalizes IUGR-induced changes in adipose deposition and visceral PPARγ expression in male rats and (2 increases serum adiponectin, as well as adipose expression of adiponectin and adiponectin receptors in former IUGR rats. Our novel findings suggest that maternal DHA supplementation may normalize adipose dysfunction and promote adiponectin-induced improvements in metabolic function in IUGR.

  19. Maternal docosahexaenoic acid increases adiponectin and normalizes IUGR-induced changes in rat adipose deposition.

    Science.gov (United States)

    Bagley, Heidi N; Wang, Yan; Campbell, Michael S; Yu, Xing; Lane, Robert H; Joss-Moore, Lisa A

    2013-01-01

    Intrauterine growth restriction (IUGR) predisposes to obesity and adipose dysfunction. We previously demonstrated IUGR-induced increased visceral adipose deposition and dysregulated expression of peroxisome proliferator activated receptor- γ 2 (PPAR γ 2) in male adolescent rats, prior to the onset of obesity. In other studies, activation of PPAR γ increases subcutaneous adiponectin expression and normalizes visceral adipose deposition. We hypothesized that maternal supplementation with docosahexaenoic acid (DHA), a PPAR γ agonist, would normalize IUGR adipose deposition in association with increased PPAR γ , adiponectin, and adiponectin receptor expression in subcutaneous adipose. To test these hypotheses, we used a well-characterized model of uteroplacental-insufficiency-(UPI-) induced IUGR in the rat with maternal DHA supplementation. Our primary findings were that maternal DHA supplementation during rat pregnancy and lactation (1) normalizes IUGR-induced changes in adipose deposition and visceral PPAR γ expression in male rats and (2) increases serum adiponectin, as well as adipose expression of adiponectin and adiponectin receptors in former IUGR rats. Our novel findings suggest that maternal DHA supplementation may normalize adipose dysfunction and promote adiponectin-induced improvements in metabolic function in IUGR.

  20. Central precocious puberty in girls

    International Nuclear Information System (INIS)

    Argyropoulou, M.; Malandry, F.; Perignon, F.; Brunelle, F.; Brauner, R.; Rappaport, R.

    1990-01-01

    The treatment of central precocious puberty (CPP) in girls depends on its etiology and evolution, the latter based on the degree of accelerated bone maturation. The goal of this paper is to assess the diagnostic value of MR imaging in studying CPP in girls. Thirty-four girls with CPP were studied with MR imaging. Pituitary gland height (PGH) was measured on a sagittal midline image and compared with normal measurements. Correlations among clinical presentation, PGH, estradiol levels, and LH/FSH ratio were evaluated

  1. A case of late presentation of precocious puberty due to pituitary astrocytoma

    OpenAIRE

    Fahimeh Soheilipour; Hossein Ghalaenov; Seyyed-Hossein Samedanifard; Fatemeh Jesmi

    2015-01-01

    The importance of assessing precocious puberty, especially in boys, is not only due to the great complications it has for the affected patients, but also to the fatal underlying diseases. Therefore, children with central precocious puberty should first undergo neuroimaging. In this case study, we present a 9.5-year-old boy who was referred to Rasoul-e-Akram Medical Center with increased intracranial pressure, nausea/vomiting, and severe headache having begun three months earlier. ...

  2. The changes in running economy during puberty in overweight and normal weight boys

    Directory of Open Access Journals (Sweden)

    Maciejczyk Marcin

    2015-03-01

    Full Text Available Study aim: running economy (RE is important indicator of endurance performance. During puberty dynamic changes in body composition and function are observed, as such RE is also expected to change. The aim of the study was to compare the running economy (RE in overweight and normoweight boys during a running exercise performed with constant velocity, and the assessment of changes in RE during puberty.

  3. Hypothesis: exposure to endocrine-disrupting chemicals may interfere with timing of puberty

    DEFF Research Database (Denmark)

    Mouritsen, A; Aksglaede, L; Sørensen, K

    2010-01-01

    and increasing prevalence of adiposity may contribute, but environmental factors are also likely to be involved. In particular, the widespread presence of endocrine-disrupting chemicals (EDCs) is suspected to contribute to the trend of earlier pubertal onset. The factors regulating the physiological onset...... of normal puberty are poorly understood. This hampers investigation of the possible role of environmental influences. There are many types of EDCs. One chemical may have more than one mode of action and the effects may depend on dose and duration of the exposure, as well as the developmental stage......A recent decline in onset of puberty - especially among girls - has been observed, first in the US in the mid-1990s and now also in Europe. The development of breast tissue in girls occurs at a much younger age and the incidence of precocious puberty (PP) is increasing. Genetic factors...

  4. Neuroprotective effect of curcumin in arsenic-induced neurotoxicity in rats.

    Science.gov (United States)

    Yadav, Rajesh S; Shukla, Rajendra K; Sankhwar, Madhu Lata; Patel, Devendra K; Ansari, Reyaz W; Pant, Aditya B; Islam, Fakhrul; Khanna, Vinay K

    2010-09-01

    Our recent studies have shown that arsenic-induced neurobehavioral toxicity is protected by curcumin by modulating oxidative stress and dopaminergic functions in rats. In addition, the neuroprotective effect of curcumin has been investigated on arsenic-induced alterations in biogenic amines, their metabolites and nitric oxide (NO), which play an important role in neurotransmission process. Decrease in the levels of dopamine (DA, 28%), norepinephrine (NE, 54%), epinephrine (EPN, 46%), serotonin (5-HT, 44%), 3,4-dihydroxyphenylacetic acid (DOPAC, 20%) and homovanillic acid (HVA, 31%) in corpus striatum; DA (51%), NE (22%), EPN (47%), 5-HT (25%), DOPAC (34%) and HVA (41%) in frontal cortex and DA (35%), NE (35%), EPN (29%), 5-HT (54%), DOPAC (37%) and HVA (46%) in hippocampus, observed in arsenic (sodium arsenite, 20 mg/kg body weight, p.o., 28 days) treated rats exhibited a trend of recovery in rats simultaneously treated with arsenic and curcumin (100 mg/kg body weight, p.o., 28 days). Increased levels of NO in corpus striatum (2.4-fold), frontal cortex (6.1-fold) and hippocampus (6.2-fold) in arsenic-treated rats were found decreased in rats simultaneously treated with arsenic and curcumin. It is evident that curcumin modulates levels of brain biogenic amines and NO in arsenic-exposed rats and these results further strengthen its neuroprotective efficacy. Copyright © 2010 Elsevier Inc. All rights reserved.

  5. Hormonal factors and incident asthma and allergic rhinitis during puberty in girls.

    Science.gov (United States)

    Wei, Junxiang; Gerlich, Jessica; Genuneit, Jon; Nowak, Dennis; Vogelberg, Christian; von Mutius, Erika; Radon, Katja

    2015-07-01

    Accumulating evidence is indicating that hormonal factors play a role in new-onset allergic rhinitis and asthma after puberty. To determine whether age at menarche and use of hormonal contraceptives predict new-onset allergic rhinitis and asthma after puberty in young German women. A prospective community-based cohort study followed 1,191 girls 9 to 11 years old to early adulthood (19-24 years old). Self-administrated questionnaires concerning age at menarche, use of hormonal contraceptives, and status and age at onset of physician-diagnosed allergic rhinitis and asthma were collected at 16 to 18 and 19 to 24 years of age. Logistic regression models were used to analyze the incidence of asthma and allergic rhinitis after puberty and pooled estimates were obtained from the final model. Eleven percent of girls developed allergic rhinitis after menarche and 3% reported new-onset asthma. Late menarche (>13 years of age) was statistically significantly inversely related to allergic rhinitis (adjusted odds ratio [OR] 0.32, 95% confidence interval [CI] 0.14-0.74) but did not reach the level of statistical significance for asthma (OR 0.32, 95% CI 0.07-1.42). Use of hormonal contraceptives was inversely associated with new-onset allergic rhinitis (OR 0.14, 95% CI 0.08-0.23) and asthma (OR 0.27, 95% CI 0.12-0.58) after puberty. This study shows that girls with late onset of menarche are less likely to develop allergic rhinitis after puberty compared with those who have menarche at an average age. These findings also suggest that, in addition to endogenous hormones, hormonal contraceptives play a role and might protect young women from allergies and asthma. Copyright © 2015 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  6. Safety assessment of Hibiscus sabdariffa after maternal exposure on male reproductive parameters in rats.

    Science.gov (United States)

    de Arruda, Aline; Cardoso, Claudia Andrea L; Vieira, Maria do Carmo; Arena, Arielle Cristina

    2016-01-01

    Hibiscus sabdariffa L. (Malvaceae) is a species widely used in folk medicine for the treatment of some disorders. This study evaluated the effects of H. sabdariffa (HS) on the development of the male reproductive tract in rats following in utero exposure. Pregnant rats received 250 or 500 mg/kg of HS extract or vehicle from gestational day 12 until day 21 of lactation. Both doses of HS increased the body weight of male offspring at weaning, without compromising the puberty onset parameters. At puberty, there was a significant increase in the vas deferens absolute weight and a significant reduction in the relative weight of kidney at higher dose. These animals also presented a significant reduction in the sperm number in the caput/corpus of epididymis after exposure to both doses and a reduction in the sperm number in the cauda epididymis for the lower dose. At adulthood, the highest dose significantly reduced the sperm production in relation to controls and both doses provoked a reduction in the relative sperm number in the epididymis without affecting the sperm morphology. These findings demonstrated that maternal exposure to H. sabdariffa can adversely influence the male reproductive system in rats.

  7. Association between Small Fetuses and Puberty Timing: A Systematic Review and Meta-Analysis.

    Science.gov (United States)

    Deng, Xu; Li, Wenyan; Luo, Yan; Liu, Shudan; Wen, Yi; Liu, Qin

    2017-11-13

    Background : Epidemiological studies reporting the effect of small fetuses (SF) on puberty development have shown inconsistent results. Objective : To examine current study evidence and determine the strength and direction of the association between SF and puberty timing. Methods : PubMed, OVID, Web of Science, EBSCO, and four Chinese databases were searched from their date of inception to February 2016. All cohort studies that examined the association between SF and puberty timing in children were identified. Two reviewers independently screened the studies, assessed the quality of included studies, and extracted the data. The quality of the included cohort studies was assessed by the Newcastle-Ottawa Scale. Risk ratio (RR), Weighted Mean Difference (WMD), and 95% confidence intervals (CIs) were calculated and pooled by RevMan5.3 (Cochrane Collaboration, London, UK). Results : A total of 10 cohort studies involving 2366 subjects was included in the final analysis. The pooled estimates showed that SF did not significantly increase the number of pubertal children in boys (RR: 0.97; 95% CI: 0.82 to 1.15), or in girls (RR: 0.91; 95% CI: 0.79 to 1.04). Compared with the control group, the SF group had an earlier onset of puberty in girls (WMD: -0.64; 95% CI: -1.21 to -0.06), and in precocious pubarche (PP) girls (WMD: -0.10; 95% CI: -0.13 to -0.07). There was no difference in the onset of puberty in boys (WMD: -0.48; 95% CI: -1.45 to 0.50) between SF and control groups. The pooled result indicated an earlier age at menarche in girls born small for gestational age (WMD: -0.30; 95% CI: -0.58 to -0.03), but no difference in the age at menarche in the SF group of PP girls. Conclusions : SF may be associated with an earlier age of onset of puberty, especially among girls, as well as earlier age at menarche for girls. Well-designed studies with larger sample sizes and long-term follow-up among different countries and ethnicities are needed.

  8. EPIDIDYMIS-SPECIFIC PATHOLOGIC DISORDERS IN RATS EXPOSED TO GOSSYPOL FROM WEANING THROUGH PUBERTY

    Science.gov (United States)

    Previous work in our laboratory revealed that the pubertal period of reproductive development in the male rat was particularly vulnerable to gossypol exposure, with a higher frequency of round structures in the lumen of the cauda epididymidis in the treated rats. Herein, we utili...

  9. Selective inhibition by chloramphenicol of pregnenolone-16 α-carbonitrile-inducible rat liver cytochrome P-450 isozymes

    International Nuclear Information System (INIS)

    Graves, P.E.; Kaminsky, L.S.; Halpert, J.

    1986-01-01

    Pregnenolone-16 α-carbonitrile (PCN) has been shown to induce, in male rats, cytochrome P-450 isozymes responsible for the formation of R-10-hydroxywarfarin and R-dehydrowarfarin. Antibodies to the major PCN-inducible isozyme (PB/PCN-E) inhibit both activities in microsomal preparations. Recently the authors have shown that PCN treatment of female rats also induces the formation of both R-warfarin metabolites. However, in both sexes chloramphenicol (CAP) treatment selectively inhibits only the rate of formation of the R-dehydrowarfarin. A decrease in microsomal P-450 content occurs after in vivo administration of CAP to PCN-treated rats of both sexes. This is in contrast to the lack of effect of CAP on P-450 levels in phenobarbital-treated rats. Covalent binding of 14 C-CAP to microsomal protein in vitro was increased 3 to 4-fold following PCN treatment. Chromatographic evidences suggests the presence of at least two PCN-induced isozymes of similar molecular weights in both male and female rat liver microsomes. These data are consistent with the multiplicity of PCN-inducible P-450 in rat liver

  10. Protective effects of agmatine on doxorubicin-induced chronic cardiotoxicity in rat.

    Science.gov (United States)

    Yarmohmmadi, Fatemeh; Rahimi, Nastaran; Faghir-Ghanesefat, Hedyeh; Javadian, Nina; Abdollahi, Alireza; Pasalar, Parvin; Jazayeri, Farahnaz; Ejtemaeemehr, Shahram; Dehpour, Ahmad Reza

    2017-02-05

    The detrimental cardio-toxic effect of doxorubicin, an effective chemotherapeutic agent, limited its clinical use. It has been claimed that doxorubicin cardio-toxicity occurs through calcium ions (Ca 2+ ) overload and reactive oxygen species production. Agmatine, an endogenous imidazoline receptor agonist, induce uptake of cytosolic Ca 2+ and cause an increase in activity of calcium pumps, including Ca 2+ -ATPase. Also it shows self-scavenging effect against reactive oxygen species production. Therefore, present study was designed to investigate the effects of agmatine against chronic cardio-toxicity of doxorubicin in rats. Male wistar rats were intraperitoneally injected with doxorubicin and agmatine four times a week for a month. Agmatine significantly alleviate the adverse effect of doxorubicin on left ventricular papillary muscle stimulation threshold and contractibility. Chronic co-administration of agmatine with doxorubicin blocked electrocardiographic changes induced by doxorubicin. In addition, agmatine improved body weight and decreased the mortality rate of animals by doxorubicin. Moreover, reversing the doxorubicin induced myocardial lesions was observed in animals treated by agmatine. A significant rise in the total antioxidant capacity of rat plasma was achieved in agmatine-treated animals in comparison to doxorubicin. To conclude, agmatine may improve therapeutic outcomes of doxorubicin since it exerts protective effects against doxorubicin-induced chronic cardiotoxicity in rats. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Antioxidant Potential of Momordica Charantia in Ammonium Chloride-Induced Hyperammonemic Rats

    Directory of Open Access Journals (Sweden)

    A. Justin Thenmozhi

    2011-01-01

    Full Text Available The present study was aimed to investigate the antioxidant potential of Momordica charantia fruit extract (MCE in ammonium chloride-induced (AC hyperammonemic rats. Experimental hyperammonemia was induced in adult male Wistar rats (180–200 g by intraperitoneal injections of ammonium chloride (100 mg kg−1 body weight thrice a week. The effect of oral administration (thrice a week for 8 consecutive weeks of MCE (300 mg kg−1 body weight on blood ammonia, plasma urea, serum liver marker enzymes and oxidative stress biomarkers in normal and experimental animals was analyzed. Hyperammonemic rats showed a significant increase in the activities of thiobarbituric acid reactive substances, hydroperoxides and liver markers (alanine transaminase, aspartate transaminase and alkaline phosphatase, and the levels of glutathione peroxidase, superoxide dismutase, catalase and reduced glutathione were decreased in the liver and brain tissues. Treatment with MCE normalized the above-mentioned changes in hyperammonemic rats by reversing the oxidant-antioxidant imbalance during AC-induced hyperammonemia, and offered protection against hyperammonemia. Our results indicate that MCE exerting the antioxidant potentials and maintaining the cellular integrity of the liver tissue could offer protection against AC-induced hyperammonemia. However, the exact underlying mechanism is yet to be investigated, and examination of the efficacy of the active constituents of the M. charantia on hyperammonemia is desirable.

  12. Evaluation of Lercanidipine in Paclitaxel-Induced Neuropathic Pain Model in Rat: A Preliminary Study

    OpenAIRE

    Saha, Lekha; Hota, Debasish; Chakrabarti, Amitava

    2012-01-01

    Objective. To demonstrate the antinociceptive effect of lercanidipine in paclitaxel-induced neuropathy model in rat. Materials and Methods. A total of 30 rats were divided into five groups of six rats in each group as follows: Gr I: 0.9% NaCl, Gr II: paclitaxel + 0.9% NaCl, Gr III: paclitaxel + lercanidipine 0.5 μg/kg, Gr IV: paclitaxel + lercanidipine 1 μg/kg, and Gr V: paclitaxel + lercanidipine 2.5 μg/kg. Paclitaxel-induced neuropathic pain in rat was produced by single intraperitoneal (i....

  13. Orally administered nicotine induces urothelial hyperplasia in rats and mice

    International Nuclear Information System (INIS)

    Dodmane, Puttappa R.; Arnold, Lora L.; Pennington, Karen L.; Cohen, Samuel M.

    2014-01-01

    Highlights: • Rats and mice orally administered with nicotine tartrate for total of 4 weeks. • No treatment-related death or whole body toxicity observed in any of the groups. • Urothelium showed simple hyperplasia in treated rats and mice. • No significant change in BrdU labeling index or SEM classification of urothelium. - Abstract: Tobacco smoking is a major risk factor for multiple human cancers including urinary bladder carcinoma. Tobacco smoke is a complex mixture containing chemicals that are known carcinogens in humans and/or animals. Aromatic amines a major class of DNA-reactive carcinogens in cigarette smoke, are not present at sufficiently high levels to fully explain the incidence of bladder cancer in cigarette smokers. Other agents in tobacco smoke could be excreted in urine and enhance the carcinogenic process by increasing urothelial cell proliferation. Nicotine is one such major component, as it has been shown to induce cell proliferation in multiple cell types in vitro. However, in vivo evidence specifically for the urothelium is lacking. We previously showed that cigarette smoke induces increased urothelial cell proliferation in mice. In the present study, urothelial proliferative and cytotoxic effects were examined after nicotine treatment in mice and rats. Nicotine hydrogen tartrate was administered in drinking water to rats (52 ppm nicotine) and mice (514 ppm nicotine) for 4 weeks and urothelial changes were evaluated. Histopathologically, 7/10 rats and 4/10 mice showed simple hyperplasia following nicotine treatment compared to none in the controls. Rats had an increased mean BrdU labeling index compared to controls, although it was not statistically significantly elevated in either species. Scanning electron microscopic visualization of the urothelium did not reveal significant cytotoxicity. These findings suggest that oral nicotine administration induced urothelial hyperplasia (increased cell proliferation), possibly due to a

  14. Radiation-induced apoptosis in the neonatal and adult rat spinal cord.

    Science.gov (United States)

    Li, Y Q; Wong, C S

    2000-09-01

    This study was designed to characterize radiation-induced apoptosis in the spinal cord of the neonatal and young adult rat. Spinal cords (C2-T2) of 1-, 2- and 10-week-old rats were irradiated with a single dose of 8, 18 or 22 Gy. Apoptosis was assessed histologically according to its specific morphological features or by using the TUNEL assay. Cell proliferation was assessed immunohistochemically using BrdU. Identities of cell types undergoing apoptosis were assessed using immunohistochemistry or in situ hybridization using markers for neurons, glial progenitor cells, microglia, oligodendrocytes and astrocytes. The time course of radiation-induced apoptosis in 1- or 2-week-old rat spinal cord was similar to that in the young adult rat spinal cord. A peak response was observed at about 8 h after irradiation, and the apoptosis index returned to the levels in nonirradiated spinal cords at 24 h. The neonatal rat spinal cord demonstrated increased apoptosis compared to the adult. Values for total yield of apoptosis over 24 h induced by 8 Gy in the neonatal rat spinal cord were significantly greater than that in the adult. Immunohistochemistry studies using Leu7, galactocerebroside, Rip and adenomatous polyposis coli tumor suppressor protein indicated that most apoptotic cells were cells of the oligodendroglial lineage regardless of the age of the animal. No evidence of Gfap or factor VIII-related antigen-positive apoptotic cells was observed, and there was a small number of apoptotic microglial cells (lectin-Rca1 positive) in the neonatal and adult rat spinal cord. In the neonatal but not adult rat spinal cord, about 10% of the apoptotic cells appeared to be neurons and were immunoreactive for synaptophysin. Labeling indices (LI) for BrdU in nonirradiated 1- and 2-week-old rat spinal cord were 20.0 and 16.3%, respectively, significantly greater than the LI of 1.0% in the 10-week-old rat spinal cord. At 8 h after a single dose of 8 Gy, 13.4% of the apoptotic cells were

  15. Immunohistochemical study on the fetal rat pituitary in hyperthermia-induced exencephaly

    OpenAIRE

    Watanabe, Yuichi G.; 渡辺, 勇一

    2002-01-01

    Hyperthermia of fetal rats is known to cause malformations of various organs including brain. The present study was carried out to investigate the effect of the hyperthermia-induced brain damages on the development of the adenohypophysis. Mother rats of Day 9.5 of pregnancy were anesthetized and immersed in hot water (43℃) for 15 min. At Day 21.5 of gestation, fetuses were removed by caesarian section and examined for exencephaly. Hyperthermal stress induced varying degrees of exencephaly in ...

  16. Sensitivity to apomorphine-induced yawning and hypothermia in rats eating standard or high-fat chow.

    Science.gov (United States)

    Baladi, Michelle G; Thomas, Yvonne M; France, Charles P

    2012-07-01

    Feeding conditions modify sensitivity to indirect- and direct-acting dopamine receptor agonists as well as the development of sensitization to these drugs. This study examined whether feeding condition affects acute sensitivity to apomorphine-induced yawning or changes in sensitivity that occur over repeated drug administration. Quinpirole-induced yawning was also evaluated to see whether sensitization to apomorphine confers cross-sensitization to quinpirole. Drug-induced yawning was measured in different groups of male Sprague Dawley rats (n = 6/group) eating high (34.3%) fat or standard (5.7% fat) chow. Five weeks of eating high-fat chow rendered otherwise drug-naïve rats more sensitive to apomorphine- (0.01-1.0 mg/kg, i.p.) and quinpirole- (0.0032-0.32 mg/kg, i.p.) induced yawning, compared with rats eating standard chow. In other rats, tested weekly with apomorphine, sensitivity to apomorphine-induced yawning increased (sensitization) similarly in rats with free access to standard or high-fat chow; conditioning to the testing environment appeared to contribute to increased yawning in both groups of rats. Food restriction decreased sensitivity to apomorphine-induced yawning across five weekly tests. Rats with free access to standard or high-fat chow and sensitized to apomorphine were cross-sensitized to quinpirole-induced yawning. The hypothermic effects of apomorphine and quinpirole were not different regardless of drug history or feeding condition. Eating high-fat chow or restricting access to food alters sensitivity to direct-acting dopamine receptor agonists (apomorphine, quinpirole), although the relative contribution of drug history and dietary conditions to sensitivity changes appears to vary among agonists.

  17. Efferent pathways in sodium overload-induced renal vasodilation in rats.

    Directory of Open Access Journals (Sweden)

    Nathalia O Amaral

    Full Text Available Hypernatremia stimulates the secretion of oxytocin (OT, but the physiological role of OT remains unclear. The present study sought to determine the involvement of OT and renal nerves in the renal responses to an intravenous infusion of hypertonic saline. Male Wistar rats (280-350 g were anesthetized with sodium thiopental (40 mg. kg(-1, i.v.. A bladder cannula was implanted for collection of urine. Animals were also instrumented for measurement of mean arterial pressure (MAP and renal blood flow (RBF. Renal vascular conductance (RVC was calculated as the ratio of RBF by MAP. In anesthetized rats (n = 6, OT infusion (0.03 µg • kg(-1, i.v. induced renal vasodilation. Consistent with this result, ex vivo experiments demonstrated that OT caused renal artery relaxation. Blockade of OT receptors (OXTR reduced these responses to OT, indicating a direct effect of this peptide on OXTR on this artery. Hypertonic saline (3 M NaCl, 1.8 ml • kg(-1 b.wt., i.v. was infused over 60 s. In sham rats (n = 6, hypertonic saline induced renal vasodilation. The OXTR antagonist (AT; atosiban, 40 µg • kg(-1 • h(-1, i.v.; n = 7 and renal denervation (RX reduced the renal vasodilation induced by hypernatremia. The combination of atosiban and renal denervation (RX+AT; n = 7 completely abolished the renal vasodilation induced by sodium overload. Intact rats excreted 51% of the injected sodium within 90 min. Natriuresis was slightly blunted by atosiban and renal denervation (42% and 39% of load, respectively, whereas atosiban with renal denervation reduced sodium excretion to 16% of the load. These results suggest that OT and renal nerves are involved in renal vasodilation and natriuresis induced by acute plasma hypernatremia.

  18. Ameliorative effect of kaempferol, a flavonoid, on oxidative stress in streptozotocin-induced diabetic rats.

    Science.gov (United States)

    Al-Numair, Khalid S; Chandramohan, Govindasamy; Veeramani, Chinnadurai; Alsaif, Mohammed A

    2015-09-01

    The aim of the present study was to evaluate the protective effect of kaempferol against oxidative stress in streptozotocin (STZ)-induced diabetic rats. Diabetes was induced in male, adult albino rats of the Wistar strain, by intraperitoneal administration of STZ (40 mg/kg body weight (BW)). Kaempferol (100 mg/kg BW) or glibenclamide (600 µg/kg BW) was administered orally once daily for 45 days to normal and STZ-induced diabetic rats. The STZ-induced diabetic rats showed significantly increased levels of plasma glucose, thiobarbituric acid reactive substances, lipid hydroperoxides, and conjugated dienes in plasma, liver, kidney, and heart whereas they showed significantly decreased level of plasma insulin. The levels of non-enzymic antioxidants (vitamin C, vitamin E, reduced glutathione) in plasma, liver, kidney, and heart and the activities of enzymatic antioxidants (superoxide dismutase, catalase, glutathione peroxidase, and glutathione-S-transferase) in liver, kidney, and heart were significantly decreased in diabetic rats. Administration of kaempferol to diabetic rats was showed brought back in plasma glucose, insulin, lipid peroxidation products, enzymatic, and non-enzymatic antioxidants to near normal. The present study indicates that kaempferol has a good antioxidant property, as evidenced by its increase of antioxidant status and decrease of lipid peroxidation markers, thus providing protection from the risks of diabetic complications.

  19. The protective effect of Physalis peruviana L. against cadmium-induced neurotoxicity in rats.

    Science.gov (United States)

    Abdel Moneim, Ahmed E; Bauomy, Amira A; Diab, Marwa M S; Shata, Mohamed Tarek M; Al-Olayan, Ebtesam M; El-Khadragy, Manal F

    2014-09-01

    The present study was carried out to investigate the protective effect of Physalis peruviana L. (family Solanaceae) against cadmium-induced neurotoxicity in rats. Adult male Wistar rats were randomly divided into four groups. Group 1 was used as control. Group 2 was intraperitoneally injected with 6.5 mg/kg bwt of cadmium chloride for 5 days. Group 3 was treated with 200 mg/kg bwt of methanolic extract of Physalis (MEPh). Group 4 was pretreated with MEPh 1 h before cadmium for 5 days. Cadmium treatment induced marked disturbances in neurochemical parameters as indicating by significant (p Physalis has a beneficial effect in ameliorating the cadmium-induced oxidative neurotoxicity in the brain of rats.

  20. Apparent Transition in the Human Height Distribution Caused by Age-Dependent Variation during Puberty Period

    Science.gov (United States)

    Iwata, Takaki; Yamazaki, Yoshihiro; Kuninaka, Hiroto

    2013-08-01

    In this study, we examine the validity of the transition of the human height distribution from the log-normal distribution to the normal distribution during puberty, as suggested in an earlier study [Kuninaka et al.: J. Phys. Soc. Jpn. 78 (2009) 125001]. Our data analysis reveals that, in late puberty, the variation in height decreases as children grow. Thus, the classification of a height dataset by age at this stage leads us to analyze a mixture of distributions with larger means and smaller variations. This mixture distribution has a negative skewness and is consequently closer to the normal distribution than to the log-normal distribution. The opposite case occurs in early puberty and the mixture distribution is positively skewed, which resembles the log-normal distribution rather than the normal distribution. Thus, this scenario mimics the transition during puberty. Additionally, our scenario is realized through a numerical simulation based on a statistical model. The present study does not support the transition suggested by the earlier study.

  1. Impact of basal diet on dextran sodium sulphate (DSS)-induced colitis in rats.

    Science.gov (United States)

    Boussenna, Ahlem; Goncalves-Mendes, Nicolas; Joubert-Zakeyh, Juliette; Pereira, Bruno; Fraisse, Didier; Vasson, Marie-Paule; Texier, Odile; Felgines, Catherine

    2015-12-01

    Dextran sodium sulphate (DSS)-induced colitis is a widely used model for inflammatory bowel disease. However, various factors including nutrition may affect the development of this colitis. This study aimed to compare and characterize the impact of purified and non-purified basal diets on the development of DSS-induced colitis in the rat. Wistar rats were fed a non-purified or a semi-synthetic purified diet for 21 days. Colitis was then induced in half of the rats by administration of DSS in drinking water (4% w/v) during the last 7 days of experimentation. At the end of the experimental period, colon sections were taken for histopathological examination, determination of various markers of inflammation (myeloperoxidase: MPO, cytokines) and oxidative stress (superoxide dismutase: SOD, catalase: CAT, glutathione peroxidase: GPx and glutathione reductase: GRed activities), and evaluation of the expression of various genes implicated in this disorder. DSS ingestion induced a more marked colitis in animals receiving the purified diet, as reflected by higher histological score and increased MPO activity. A significant decrease in SOD and CAT activities was also observed in rats fed the purified diet. Also, in these animals, administration of DSS induced a significant increase in interleukin (IL)-1α, IL-1β and IL-6. In addition, various genes implicated in inflammation were over-expressed after ingestion of DSS by rats fed the purified diet. These results show that a purified diet promotes the onset of a more severe induced colitis than a non-purified one, highlighting the influence of basal diet in colitis development.

  2. Effect of epidermal growth factor against radiotherapy-induced oral mucositis in rats

    International Nuclear Information System (INIS)

    Lee, Sang-wook; Jung, Kwon Il; Kim, Yeun Wha B.S.; Jung, Heun Don; Kim, Hyun Sook; Hong, Joon Pio

    2007-01-01

    Purpose: We tested the efficacy of oral recombinant human epidermal growth factor (rhEGF) against radiation-induced oral mucositis in a rat model. Methods and Materials: Each of 35 Sprague-Dawley rats, 7 to 8 weeks of age and weighing 178 ± 5 grams, was irradiated once in the head region with 25 Gy, using a 4-MV therapeutic linear accelerator at a rate of 2 Gy/min. The irradiated rats were randomly divided into four groups: those receiving no treatment (Group 1), those treated with vehicle only three times per day (Group 2), and those treated with 50 μg/mL (Group 3), or 100 μg/mL (Group 4) rhEGF three times per day. Results: Rats were monitored for survival rate and daily activity, including hair loss, sensitivity, and anorexia. We found that survival rate and oral intake were significantly increased and histologic changes were significantly decreased in the rhEGF-treated rats. There was no difference, however, between rats treated with 50 μg/mL or 100 μg/mL rhEGF. Conclusion: These findings suggest that orally administered rhEGF decreased radiation-induced oral mucositis in rats

  3. The timing of normal puberty and the age limits of sexual precocity

    DEFF Research Database (Denmark)

    Parent, Anne-Simone; Teilmann, Grete; Juul, Anders

    2003-01-01

    During the past decade, possible advancement in timing of puberty has been reported in the United States. In addition, early pubertal development and an increased incidence of sexual precocity have been noticed in children, primarily girls, migrating for foreign adoption in several Western European...... the environment has been considered. These observations urge further study of the onset of puberty as a possible sensitive and early marker of the interactions between environmental conditions and genetic susceptibility that can influence physiological and pathological processes....

  4. Cardio-protective effects of carnitine in streptozotocin-induced diabetic rats

    Directory of Open Access Journals (Sweden)

    Malone Michael A

    2006-01-01

    Full Text Available Abstract Background Streptozotocin-induced diabetes (STZ-D in rats has been associated with carnitine deficiency, bradycardia and left ventricular enlargement. Aim The purpose of this study was to determine whether oral carnitine supplementation would normalize carnitine levels and cardiac function in STZ-D rats. Methods Wistar rats (48 were made hyperglycemic by STZ at 26 weeks of age. Same age normal Wistar rats (24 were used for comparison. Echocardiograms were performed at baseline 2, 6, 10, and 18 weeks after STZ administration in all animals. HbA1c, serum carnitine and free fatty acids (FFA were measured at the same times. Since STZ-D rats become carnitine deficient, 15 STZ-D rats received supplemental oral carnitine for 16 weeks. Results The heart rates for the STZ-D rats (290 ± 19 bpm were less than control rats (324 ± 20 bpm (p Conclusion Thus, supplemental oral carnitine in STZ-D rats normalized serum carnitine, heart rate regulation and left ventricular size. These findings suggest a metabolic mechanism for the cardiac dysfunction noted in this diabetic animal model.

  5. Effect of Bauhinia holophylla treatment in Streptozotocin-induced diabetic rats.

    Science.gov (United States)

    Pinheiro, Marcelo S; Rodrigues, Luhara S; S, Leila; Moraes-Souza, Rafaianne Q; Soares, Thaigra S; Américo, Madileine F; Campos, Kleber E; Damasceno, Débora C; Volpato, Gustavo T

    2017-01-01

    Bauhinia holophylla, commonly known as "cow's hoof", is widely used in Brazilian folk medicine for the diabetes treatment. Therefore, the aim of this study was at evaluating the aqueous extract effect of Bauhinia holophylla leaves treatment on the streptozotocin-induced diabetic rats. Diabetes was induced by Streptozotocin (40 mg/Kg) in female Wistar rats. Oral administration of aqueous extract of Bauhinia holophylla leaves was given to non-diabetic and diabetic rats at a dose of 400 mg/kg during 21 days. On day 17 of treatment, the Oral Glucose Tolerance Test was performed to determine the area under the curve. At the end of the treatment, the animals were anesthetized and blood was collected for serum biochemical parameters analysis. After treatment with Bauhinia holophylla extract, non-diabetic and diabetic rats presented no glycemic changes. On the other hand, the plant treatment decreased body weight and increased ALT and AST activities. In conclusion, the treatment with aqueous extract of B. holophylla leaves given to diabetic rats presented no hypoglycemic effect in nondiabetic animals and no antidiabetic effect in diabetic animals with the doses studied. In addition, the diabetic animals treated with the B. holophylla extract showed inconvenient effects and its indiscriminate consumption requires particular carefulness.

  6. Analgesic effect of Minocycline in rat model of inflammation-induced visceral pain

    Science.gov (United States)

    Kannampalli, Pradeep; Pochiraju, Soumya; Bruckert, Mitchell; Shaker, Reza; Banerjee, Banani; Sengupta, Jyoti N.

    2014-01-01

    The present study investigates the analgesic effect of minocycline, a semi-synthetic tetracycline antibiotic, in a rat model of inflammation-induced visceral pain. Inflammation was induced in male rats by intracolonic administration of tri-nitrobenzenesulphonic acid (TNBS). Visceral hyperalgesia was assessed by comparing the viscero-motor response (VMR) to graded colorectal distension (CRD) prior and post 7 days after TNBS treatment. Electrophysiology recordings from CRD-sensitive pelvic nerve afferents (PNA) and lumbo-sacral (LS) spinal neurons were performed in naïve and inflamed rats. Colonic inflammation produced visceral hyperalgesia characterized by increase in the VMRs to CRD accompanied with simultaneous activation of microglia in the spinal cord and satellite glial cells (SGCs) in the dorsal root ganglions (DRGs). Selectively inhibiting the glial activation following inflammation by araC (Arabinofuranosyl Cytidine) prevented the development of visceral hyperalgesia. Intrathecal minocycline significantly attenuated the VMR to CRD in inflamed rats, whereas systemic minocycline produced a delayed effect. In electrophysiology experiments, minocycline significantly attenuated the mechanotransduction of CRD-sensitive PNAs and the responses of CRD-sensitive LS spinal neurons in TNBS-treated rats. While the spinal effect of minocycline was observed within 5 min of administration, systemic injection of the drug produced a delayed effect (60 min) in inflamed rats. Interestingly, minocycline did not exhibit analgesic effect in naïve, non-inflamed rats. The results demonstrate that intrathecal injection of minocycline can effectively attenuate inflammation-induced visceral hyperalgesia. Minocycline might as well act on neuronal targets in the spinal cord of inflamed rats, in addition to the widely reported glial inhibitory action to produce analgesia. PMID:24485889

  7. Long-term treadmill exercise-induced neuroplasticity and associated memory recovery of streptozotocin-induced diabetic rats: an experimenter blind, randomized controlled study.

    Science.gov (United States)

    You, Joshua Sung H; Kim, Chung-Ju; Kim, Mee Young; Byun, Yong Gwon; Ha, So Young; Han, Bong Suk; Yoon, Bum Chul

    2009-01-01

    We investigated a long-term exercise-induced neuroplasticity and spatial memory recovery in 15 rats in a treadmill as follows: normal control rats (NC), streptozotocin (STZ)-induced diabetic control rats (DC), and STZ-induced diabetic rats exercising in a treadmill (DE). As per the DE group, the running exercise in a treadmill was administered for 30 minutes a day for 6 weeks. Neuronal immediate-early gene (IEG) expression (c-Fos) in the hippocampus and radial arm maze (RAM) tests were measured and revealed that the c-Fos levels in DE were significantly higher than those in NC and DC (p memory performance scores, obtained from the RAM test, were significantly different among the three groups (p memory scores of NC and DE were higher than those of DC (p memory. This is the first experimental evidence in literature that supports the efficacy of exercise-induced neuroplasticity and spatial motor memory in diabetes care.

  8. Pathomorphologic observation on treatment of radiation-induced lung damage in rats with

    International Nuclear Information System (INIS)

    Ye Jiangfeng; Qi Haowen; Zhao Feng; Fan Fengyun; Shi Mei; Zhao Yiling; Meng Yulin

    2004-01-01

    Objective: To inquire into the means of preventing lung damage induced by thoracic irradiation. Methods: SD rats were divided randomly into 3 groups: normal control, irradiated control (Group IC) and irradiated and fluvastatin (Flu)-treated group (Group F). The later two groups of rats were irradiated with X-rays at a dose of 20 Gy thoracically. Beginning from the seventh day before irradiation the rats in the Group F were treated with Flu at a dose of 20 mg per day by garaging until the end of the experiment. Animals from each group were sacrificed on days 5, 15, 30, 60 respectively after irradiation. Sections of lung were examined with light microscopy, electron microscopy and morphometry. Results: The rats in the Group IC suffered from typical radiation pneumonitis (P<0.01). Electron microscopy indicated type II pneumonocytes and capillary endothelial cells were injured in rats of Group IC on days 30, 60. There were increase of collagen and a great quantity of mast cells in irradiated control rats. In rats of the Group F there was slight reaction in the lung. Conclusion: Fluvastatin could reduce radiation pneumonitis and inhibit increase of collagen. The treatment and prevention of radiation-induced lung injury in rats with fluvastatin is effective

  9. The significant effects of puberty on the genetic diathesis of binge eating in girls.

    Science.gov (United States)

    Klump, Kelly L; Culbert, Kristen M; O'Connor, Shannon; Fowler, Natasha; Burt, S Alexandra

    2017-08-01

    Recent data show significant phenotypic and genetic associations between ovarian hormones and binge eating in adulthood. Theories of hormonal risk focus on puberty and the possibility that hormone activation induces changes in genetic effects that then lead to differential risk for binge eating in postpuberty and adulthood. Although this theory is difficult to test in humans, an indirect test is to examine whether genetic influences on binge eating increase during the pubertal period in girls. Prior work has shown pubertal increases in genetic influences on overall disordered eating symptoms, but no study to date has examined binge eating. The present study was the first to examine these increases for binge eating. Participants included 1,568 female twins (aged 8-25 years) from the Michigan State University Twin Registry. Binge eating and pubertal development were assessed with self-report questionnaires. Twin moderation models showed significant linear increases in genetic effects from prepuberty (5%) to postpuberty (42%), even after controlling for the effects of age and body mass index. Results provide critical support for increased genetic influences on binge eating during puberty. Additional studies are needed to identify hormonal mechanisms and fully test contemporary models of ovarian hormone risk. © 2017 Wiley Periodicals, Inc.

  10. Serotonergic-postsynaptic receptors modulate gripping-induced immobility episodes in male taiep rats.

    Science.gov (United States)

    Eguibar, José R; Cortés, M C; Ita, M L

    2009-09-01

    The Taiep rat is a myelin mutant with a motor syndrome characterized by tremor, ataxia, immobility, epilepsy, and paralysis. The rat shows a hypomyelination followed by a progressive demyelination. During immobilities taiep rats show a REM-like sleep pattern and a disorganized sleep-wake pattern suggesting taiep rats as a model of narcolepsy-cataplexy. Our study analyzed the role of postsynaptic serotonin receptors in the expression of gripping-induced immobility episodes (IEs) in 8-month-old male taiep rats. The specific postsynaptic serotonin agonist +/-1-(2,5-dimethoxy-4-iodoamphetamine hydrochloride (+/-DOI) decreased the frequency of gripping-induced IEs, but that was not the case with alpha-methyl-serotonin maleate (alpha-methyl-5HT), a nonspecific postsynaptic agonist. Although the serotonin antagonists, ketanserine and metergoline, produced a biphasic effect, first a decrease followed by an increase with higher doses, similar effects were obtained with a mean duration of gripping-induced IEs. These findings correlate with the pharmacological observations in narcoleptic dogs and humans in which serotonin-reuptake inhibitors improve cataplexy, particularly in long-term treatment that could change the serotonin receptor levels. Polysomnographic recordings showed an increase in the awakening time and a decrease in the slow wave and rapid eye movement sleep concomitant with a decrease in immobilities after use of +/-DOI, this being stronger with the highest dose. Taken together, our results show that postsynaptic serotonin receptors are involved in the modulation in gripping-induced IEs caused by the changes in the organization of the sleep-wake cycle in taiep rats. It is possible that specific agonists, without side effects, could be a useful treatment in human narcoleptic patients. 2009 Wiley-Liss, Inc.

  11. What Do Preservice Teachers Want to Learn about Puberty and Sexuality Education? An Australian Perspective

    Science.gov (United States)

    Goldman, Juliette D. G.; Grimbeek, Peter

    2016-01-01

    The processes of puberty are now commonly observed in primary school-aged students. Schools, therefore, need to address puberty and sexuality education for students' health, well-being, safety and pastoral care. Similarly, preservice teacher education needs to address future primary school teachers' unfamiliarity and lack of confidence with these…

  12. Dietary quercetin exacerbates the development of estrogen-induced breast tumors in female ACI rats

    International Nuclear Information System (INIS)

    Singh, Bhupendra; Mense, Sarah M.; Bhat, Nimee K.; Putty, Sandeep; Guthiel, William A.; Remotti, Fabrizio; Bhat, Hari K.

    2010-01-01

    Phytoestrogens are plant compounds that structurally mimic the endogenous estrogen 17β-estradiol (E 2 ). Despite intense investigation, the net effect of phytoestrogen exposure on the breast remains unclear. The objective of the current study was to examine the effects of quercetin on E 2 -induced breast cancer in vivo. Female ACI rats were given quercetin (2.5 g/kg food) for 8 months. Animals were monitored weekly for palpable tumors, and at the end of the experiment, rats were euthanized, breast tumor and different tissues excised so that they could be examined for histopathologic changes, estrogen metabolic activity and oxidant stress. Quercetin alone did not induce mammary tumors in female ACI rats. However, in rats implanted with E 2 pellets, co-exposure to quercetin did not protect rats from E 2 -induced breast tumor development with 100% of the animals developing breast tumors within 8 months of treatment. No changes in serum quercetin levels were observed in quercetin and quercetin + E 2 -treated groups at the end of the experiment. Tumor latency was significantly decreased among rats from the quercetin + E 2 group relative to those in the E 2 group. Catechol-O-methyltransferase (COMT) activity was significantly downregulated in quercetin-exposed mammary tissue. Analysis of 8-isoprostane F 2α (8-iso-PGF 2α ) levels as a marker of oxidant stress showed that quercetin did not decrease E 2 -induced oxidant stress. These results indicate that quercetin (2.5 g/kg food) does not confer protection against breast cancer, does not inhibit E 2 -induced oxidant stress and may exacerbate breast carcinogenesis in E 2 -treated ACI rats. Inhibition of COMT activity by quercetin may expose breast cells chronically to E 2 and catechol estrogens. This would permit longer exposure times to the carcinogenic metabolites of E 2 and chronic exposure to oxidant stress as a result of metabolic redox cycling to estrogen metabolites, and thus quercetin may exacerbate E 2 -induced

  13. Metabolomics of Hydrazine-Induced Hepatotoxicity in Rats for Discovering Potential Biomarkers

    Directory of Open Access Journals (Sweden)

    Zhuoling An

    2018-01-01

    Full Text Available Metabolic pathway disturbances associated with drug-induced liver injury remain unsatisfactorily characterized. Diagnostic biomarkers for hepatotoxicity have been used to minimize drug-induced liver injury and to increase the clinical safety. A metabolomics strategy using rapid-resolution liquid chromatography/tandem mass spectrometry (RRLC-MS/MS analyses and multivariate statistics was implemented to identify potential biomarkers for hydrazine-induced hepatotoxicity. The global serum and urine metabolomics of 30 hydrazine-treated rats at 24 or 48 h postdosing and 24 healthy rats were characterized by a metabolomics approach. Multivariate statistical data analyses and receiver operating characteristic (ROC curves were performed to identify the most significantly altered metabolites. The 16 most significant potential biomarkers were identified to be closely related to hydrazine-induced liver injury. The combination of these biomarkers had an area under the curve (AUC > 0.85, with 100% specificity and sensitivity, respectively. This high-quality classification group included amino acids and their derivatives, glutathione metabolites, vitamins, fatty acids, intermediates of pyrimidine metabolism, and lipids. Additionally, metabolomics pathway analyses confirmed that phenylalanine, tyrosine, and tryptophan biosynthesis as well as tyrosine metabolism had great interactions with hydrazine-induced liver injury in rats. These discriminating metabolites might be useful in understanding the pathogenesis mechanisms of liver injury and provide good prospects for drug-induced liver injury diagnosis clinically.

  14. Antifibrogenic role of valproic acid in streptozotocin induced diabetic rat penis.

    Science.gov (United States)

    Kutlu, O; Karaguzel, E; Gurgen, S G; Okatan, A E; Kutlu, S; Bayraktar, C; Kazaz, I O; Eren, H

    2016-05-01

    We investigated the therapeutic effects of valproic acid (VPA) on erectile dysfunction and reducing penile fibrosis in streptozocin (STZ)-induced diabetic rats. Eighteen male rats were divided into three experimental groups (Control, STZ-DM, STZ-DM plus VPA) and diabetes was induced by transperitoneal single dose STZ. Eight weeks after, VPA and placebo treatments were given according to groups for 15 days. All rats were anesthetised for the measurement of in vivo erectile response to cavernous nerve stimulation. Afterward penes were evaluated histologically in terms of immune labelling scores of endothelial nitric oxide synthase (eNOS), vascular endothelial growth factor (VEGF) and transforming growth factor-β1 (TGF-β1). Slides were also evaluated in terms of collagen/smooth muscle ratio and penile apoptosis. After the treatment with VPA, erectile responses were found as improved when compared with STZ-DM rats but not statistically meaningful. eNOS and VEGF immune expressions diminished in penile corpora of STZ-DM rats and improved with VPA treatment. VPA led to decrease in TGF-β1 expression and collagen content of diabetic rats' penes. Penile apoptosis was not diminished with VPA. In conclusion, VPA treatment seems to be effective for reducing penile fibrosis in diabetic rats and more prolonged treatment period may enhance erectile functions. © 2015 Blackwell Verlag GmbH.

  15. Anti-hyperlipidemic action of Zingiber officinale (Ginger juice in alloxan induced diabetic rats

    Directory of Open Access Journals (Sweden)

    Selima Sultana

    2012-07-01

    Full Text Available Abstract Hyperlipidemia is an important modifiable risk factor contributing to atterosclerosis in diabetes mellitus. Zingiber officinale (ginger widely consumed as spice is known for its hypoglycemic and hypochlosteremic actions. The present study was undertaken to investigate anti-hyperlipidemic action of ginger juice in alloxan-induced diabetic rats. Male Wister rats, 130-150 g wt, fed on standard diet and water ad libitum were divided into 4 groups (n=6 in each group: group I non-diabetic control, group II non-diabetic treated; group III diabetic control and group IV diabetic treated. Diabetes was induced by Inj. alloxan 150 mg Kg–1 b.w., i.p. (group III & IV on Day 2. Rats having blood glucose level of >7 mmol/l on day 5 (72 hrs after alloxan Inj. were considered diabetic and selected for experimentation. Both non-diabetic and diabetic treated groups (Gr II & IV received Zingiber officinale (ginger juice (4 ml Kg–1 b.w., p.o. for 10 days (day 2-day 11 through Ryles tube. On Day 12, animals were sacrificed under light ether anaesthesia, blood was collected by cardiac puncture and serum separated for estimation of lipids. Zingiber officinale (ginger juice significantly (p<0.01 decreased alloxan induced hyperglycemia (group IV, but had no effect on blood glucose level in normal rats (group II; significantly (p<0.001 reduced alloxan induced hyperlipidemia, but produced no significant lipid lowering effects in normal rats (group II. The results suggest a significant anti-hyperlipidemic action of Zingiber officinale (ginger juice in alloxan induced diabetic rats. The findings may be clinically significant and exploited. Ibrahim Med. Coll. J. 2012; 6(2: 55-58

  16. Glucose turnover during insulin-induced hypoglycemia in liver-denervated rats

    DEFF Research Database (Denmark)

    Mikines, K J; Sonne, B; Richter, Erik

    1985-01-01

    The role of hepatic autonomic nerves in glucose production during hypoglycemia was studied. Selective, surgical denervation of the liver was performed in rats, which reduced hepatic norepinephrine concentrations by 96%. Hypoglycemia was induced by 250 mU of insulin intra-arterially in anesthetized...... as well as in chronically catheterized, awake rats. Half of the anesthetized denervated or sham-operated rats had previously been adrenodemedullated. Glucose turnover was measured by primed, constant intravenous infusion of [3-3H]glucose. Before as well as during hypoglycemia the arterial glucose...

  17. A Study To Evaluate The Aetiological Factors And Management of Puberty Menorrhagia

    Directory of Open Access Journals (Sweden)

    Joydeb Roychowdhury

    2008-04-01

    Full Text Available Introduction: This study aims to evaluate the incidence, clinical presentation, etiological factors and treatment outcomes of the patients suffering from puberty menorrhagia. Methods: 65 patients with puberty menorrhagia attending the outpatient as well as indoor department of NRS Medical College, Kolkata during the period from February, 2005 to July,2006 were included in the study. They were prospectively analysed to assess the aetiological factors and the outcome of treatment required to manage these cases.Results – The incidence of puberty menorrhagia was 9.6% in our study. 40%s patients had menarche between 12-13 years. 61.6% had anovulatory dysfunctional uterine bleeding(DUB. 15.4% had hematological causes. Hypothyroidism, endometrial tuberculosis, polycystic ovarian disease were other important causes. 40% were relieved with tranexamic acid, 26% required hormone treatment and 35.3% received blood transfusion.Conclusion: Anovulatory DUB is the cause of menorrhagia in most of the cases .Medical treatment is mostly effective while surgical procedures are limited to few specific cases.

  18. Evaluation of puberty by verifying spontaneous and stimulated gonadotropin values in girls.

    Science.gov (United States)

    Chin, Vivian L; Cai, Ziyong; Lam, Leslie; Shah, Bina; Zhou, Ping

    2015-03-01

    Changes in pharmacological agents and advancements in laboratory assays have changed the gonadotropin-releasing hormone analog stimulation test. To determine the best predictive model for detecting puberty in girls. Thirty-five girls, aged 2 years 7 months to 9 years 3 months, with central precocious puberty (CPP) (n=20) or premature thelarche/premature adrenarche (n=15). Diagnoses were based on clinical information, baseline hormones, bone age, and pelvic sonogram. Gonadotropins and E2 were analyzed using immunochemiluminometric assay. Logistic regression for CPP was performed. The best predictor of CPP is the E2-change model based on 3- to 24-h values, providing 80% sensitivity and 87% specificity. Three-hour luteinizing hormone (LH) provided 75% sensitivity and 87% specificity. Basal LH lowered sensitivity to 65% and specificity to 53%. The E2-change model provided the best predictive power; however, 3-h LH was more practical and convenient when evaluating puberty in girls.

  19. Psychological assessment of mothers and their daughters at the time of diagnosis of precocious puberty.

    Science.gov (United States)

    Schoelwer, Melissa J; Donahue, Kelly L; Bryk, Kristina; Didrick, Paula; Berenbaum, Sheri A; Eugster, Erica A

    2015-01-01

    Concerns about psychological distress are often used to justify treatment of girls with precocious puberty, but there is little evidence to support these concerns. The extent to which psychological problems are associated with central precocious puberty (CPP) compared with other forms of early puberty in girls has likewise not been established. Girls presenting with untreated CPP, premature adrenarche (PA) or early normal puberty (ENP) were recruited from our pediatric endocrine clinic along with their mothers. Child psychological adjustment was assessed by child self-report and parent report. Parent self-reported personality, anxiety, and depression were also assessed. Differences between groups were explored using one-way ANOVA and Dunnett's T3 test. Sixty-two subjects (aged 7.5 ± 1.4 years, range 4.8-10.5) were enrolled, of whom 19 had CPP, 22 had PA, and 21 had ENP. Girls with ENP were significantly older (8.9 ± .9 years) than girls with CPP (6.9 ± 1.1 years, p psychological adjustment. However, mothers of girls with PA scored significantly higher than mothers of girls with ENP on one measure of depression (p = .04) and stress (p = .01). While mothers of girls with PA report increased psychological distress on some measures, no differences in psychological adjustment were found at baseline amongst the girls themselves. Whether these results will change as puberty progresses in the PA and ENP groups or with treatment of CPP is unknown. Long-term prospective studies are needed in order to further investigate psychological correlates of early puberty in girls.

  20. Somatostatin ontogenesis in the gastrointestinal and pancreatic tract: study in normal rats and during a induced diabetes in neonates rats

    International Nuclear Information System (INIS)

    Cunha, M.C.

    1980-01-01

    The ontogenic studies of somatostatin of pancreas, ileum and duodenum of Wistar rats and the rats with induced diabetes were done. The radioimmunologic method to dose the somatostatin was used. (L.M.J.)

  1. High-Throughput Sequencing Reveals Circulating miRNAs as Potential Biomarkers for Measuring Puberty Onset in Chicken (Gallus gallus).

    Science.gov (United States)

    Han, Wei; Zhu, Yunfen; Su, Yijun; Li, Guohui; Qu, Liang; Zhang, Huiyong; Wang, Kehua; Zou, Jianmin; Liu, Honglin

    2016-01-01

    There are still no highly sensitive and unique biomarkers for measurement of puberty onset. Circulating miRNAs have been shown to be promising biomarkers for diagnosis of various diseases. To identify circulating miRNAs that could be served as biomarkers for measuring chicken (Gallus gallus) puberty onset, the Solexa deep sequencing was performed to analyze the miRNA expression profiles in serum and plasma of hens from two different pubertal stages, before puberty onset (BO) and after puberty onset (AO). 197 conserved and 19 novel miRNAs (reads > 10) were identified as serum/plasma-expressed miRNAs in the chicken. The common miRNA amounts and their expression changes from BO to AO between serum and plasma were very similar, indicating the different treatments to generate serum and plasma had quite small influence on the miRNAs. 130 conserved serum-miRNAs were showed to be differentially expressed (reads > 10, P 1.0, P puberty onset. Further quantitative real-time PCR (RT-qPCR) test found that a seven-miRNA panel, including miR-29c, miR-375, miR-215, miR-217, miR-19b, miR-133a and let-7a, had great potentials to serve as novel biomarkers for measuring puberty onset in chicken. Due to highly conserved nature of miRNAs, the findings could provide cues for measurement of puberty onset in other animals as well as humans.

  2. Sex differences in athletic performance emerge coinciding with the onset of male puberty.

    Science.gov (United States)

    Handelsman, David J

    2017-07-01

    Male performance in athletic events begins to exceed that of age-matched females during early adolescence, but the timing of this divergence relative to the onset of male puberty and the rise in circulating testosterone remains poorly defined. This study is a secondary quantitative analysis of four published sources which aimed to define the timing of the gender divergence in athletic performance and relating it to the rise in circulating testosterone due to male puberty. Four data sources reflecting elite swimming and running and jumping track and field events as well as hand-grip strength in nonathletes were analysed to define the age-specific gender differences through adolescence and their relationship to the rising circulating testosterone during male puberty. The onset and tempo of gender divergence were very similar for swimming, running and jumping events as well as the hand-grip strength in nonathletes, and all closely paralleled the rise in circulating testosterone in adolescent boys. The gender divergence in athletic performance begins at the age of 12-13 years and reaches adult plateau in the late teenage years with the timing and tempo closely parallel to the rise in circulating testosterone in boys during puberty. © 2017 John Wiley & Sons Ltd.

  3. Unraveling the mechanism of neuroprotection of curcumin in arsenic induced cholinergic dysfunctions in rats

    Energy Technology Data Exchange (ETDEWEB)

    Srivastava, Pranay [CSIR-Indian Institute of Toxicology Research, Post Box 80, MG Marg, Lucknow 226 001 (India); Yadav, Rajesh S. [CSIR-Indian Institute of Toxicology Research, Post Box 80, MG Marg, Lucknow 226 001 (India); Department of Crimnology and Forensic Science, Harisingh Gour University, Sagar 470 003 (India); Chandravanshi, Lalit P.; Shukla, Rajendra K.; Dhuriya, Yogesh K.; Chauhan, Lalit K.S. [CSIR-Indian Institute of Toxicology Research, Post Box 80, MG Marg, Lucknow 226 001 (India); Dwivedi, Hari N. [Babu Banarasi Das University, BBD City, Faizabad Road, Lucknow 227 015 (India); Pant, Aditiya B. [CSIR-Indian Institute of Toxicology Research, Post Box 80, MG Marg, Lucknow 226 001 (India); Khanna, Vinay K., E-mail: vkkhanna1@gmail.com [CSIR-Indian Institute of Toxicology Research, Post Box 80, MG Marg, Lucknow 226 001 (India)

    2014-09-15

    Earlier, we found that arsenic induced cholinergic deficits in rat brain could be protected by curcumin. In continuation to this, the present study is focused to unravel the molecular mechanisms associated with the protective efficacy of curcumin in arsenic induced cholinergic deficits. Exposure to arsenic (20 mg/kg body weight, p.o) for 28 days in rats resulted to decrease the expression of CHRM2 receptor gene associated with mitochondrial dysfunctions as evident by decrease in the mitochondrial membrane potential, activity of mitochondrial complexes and enhanced apoptosis both in the frontal cortex and hippocampus in comparison to controls. The ultrastructural images of arsenic exposed rats, assessed by transmission electron microscope, exhibited loss of myelin sheath and distorted cristae in the mitochondria both in the frontal cortex and hippocampus as compared to controls. Simultaneous treatment with arsenic (20 mg/kg body weight, p.o) and curcumin (100 mg/kg body weight, p.o) for 28 days in rats was found to protect arsenic induced changes in the mitochondrial membrane potential and activity of mitochondrial complexes both in frontal cortex and hippocampus. Alterations in the expression of pro- and anti-apoptotic proteins and ultrastructural damage in the frontal cortex and hippocampus following arsenic exposure were also protected in rats simultaneously treated with arsenic and curcumin. The data of the present study reveal that curcumin could protect arsenic induced cholinergic deficits by modulating the expression of pro- and anti-apoptotic proteins in the brain. More interestingly, arsenic induced functional and ultrastructural changes in the brain mitochondria were also protected by curcumin. - Highlights: • Neuroprotective mechanism of curcumin in arsenic induced cholinergic deficits studied • Curcumin protected arsenic induced enhanced expression of stress markers in rat brain • Arsenic compromised mitochondrial electron transport chain protected

  4. Unraveling the mechanism of neuroprotection of curcumin in arsenic induced cholinergic dysfunctions in rats

    International Nuclear Information System (INIS)

    Srivastava, Pranay; Yadav, Rajesh S.; Chandravanshi, Lalit P.; Shukla, Rajendra K.; Dhuriya, Yogesh K.; Chauhan, Lalit K.S.; Dwivedi, Hari N.; Pant, Aditiya B.; Khanna, Vinay K.

    2014-01-01

    Earlier, we found that arsenic induced cholinergic deficits in rat brain could be protected by curcumin. In continuation to this, the present study is focused to unravel the molecular mechanisms associated with the protective efficacy of curcumin in arsenic induced cholinergic deficits. Exposure to arsenic (20 mg/kg body weight, p.o) for 28 days in rats resulted to decrease the expression of CHRM2 receptor gene associated with mitochondrial dysfunctions as evident by decrease in the mitochondrial membrane potential, activity of mitochondrial complexes and enhanced apoptosis both in the frontal cortex and hippocampus in comparison to controls. The ultrastructural images of arsenic exposed rats, assessed by transmission electron microscope, exhibited loss of myelin sheath and distorted cristae in the mitochondria both in the frontal cortex and hippocampus as compared to controls. Simultaneous treatment with arsenic (20 mg/kg body weight, p.o) and curcumin (100 mg/kg body weight, p.o) for 28 days in rats was found to protect arsenic induced changes in the mitochondrial membrane potential and activity of mitochondrial complexes both in frontal cortex and hippocampus. Alterations in the expression of pro- and anti-apoptotic proteins and ultrastructural damage in the frontal cortex and hippocampus following arsenic exposure were also protected in rats simultaneously treated with arsenic and curcumin. The data of the present study reveal that curcumin could protect arsenic induced cholinergic deficits by modulating the expression of pro- and anti-apoptotic proteins in the brain. More interestingly, arsenic induced functional and ultrastructural changes in the brain mitochondria were also protected by curcumin. - Highlights: • Neuroprotective mechanism of curcumin in arsenic induced cholinergic deficits studied • Curcumin protected arsenic induced enhanced expression of stress markers in rat brain • Arsenic compromised mitochondrial electron transport chain protected

  5. Crocin attenuates hemorrhagic shock-induced oxidative stress and organ injuries in rats.

    Science.gov (United States)

    Yang, Long; Dong, Xiujuan

    2017-06-01

    We aimed to evaluate the effect of natural antioxidant crocin in alleviating hemorrhagic shock (HS)-induced organ damages. HS rats were treated with crocin during resuscitation. Mortality at 12h and 24h post resuscitation was documented. HS and resuscitation induced organ injuries, as characterized by elevated wet/dry ratio, quantitative assessment ratio, blood urea nitrogen, creatinine, aspartate aminotransferase and alanine aminotransferase, whereas rats received crocin treatment demonstrated improvements in all the above characteristics. This protective effect coincided with reduced malondialdehyde and increased glutathione in both serum and lung tissues, indicating attenuated oxidative stress in crocin-treated rats. Myeloperoxide levels in lung, kidney and liver were also reduced. Crocin can potentially be used to protect organs from HS-induced damages during resuscitation due to its anti-oxidative role. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Comparative proteomic analysis reveals heart toxicity induced by chronic arsenic exposure in rats

    International Nuclear Information System (INIS)

    Huang, Qingyu; Xi, Guochen; Alamdar, Ambreen; Zhang, Jie; Shen, Heqing

    2017-01-01

    Arsenic is a widespread metalloid in the environment, which poses a broad spectrum of adverse effects on human health. However, a global view of arsenic-induced heart toxicity is still lacking, and the underlying molecular mechanisms remain unclear. By performing a comparative quantitative proteomic analysis, the present study aims to investigate the alterations of proteome profile in rat heart after long-term exposure to arsenic. As a result, we found that the abundance of 81 proteins were significantly altered by arsenic treatment (35 up-regulated and 46 down-regulated). Among these, 33 proteins were specifically associated with cardiovascular system development and function, including heart development, heart morphology, cardiac contraction and dilation, and other cardiovascular functions. It is further proposed that the aberrant regulation of 14 proteins induced by arsenic would disturb cardiac contraction and relaxation, impair heart morphogenesis and development, and induce thrombosis in rats, which is mediated by the Akt/p38 MAPK signaling pathway. Overall, these findings will augment our knowledge of the involved mechanisms and develop useful biomarkers for cardiotoxicity induced by environmental arsenic exposure. - Highlights: • Arsenic exposure has been associated with a number of adverse health effects. • The molecular mechanisms involved in arsenic-induced cardiotoxicity remain unclear. • Differential proteins were identified in arsenic-exposed rat heart by proteomics. • Arsenic induces heart toxicity through the Akt/p38 MAPK signaling pathway. - Label-free quantitative proteomic analysis of rat heart reveals putative mechanisms and biomarkers for arsenic-induced cardiotoxicity.

  7. Esculetin reduces leukotriene B4 level in plasma of rats with adjuvant-induced arthritis

    Directory of Open Access Journals (Sweden)

    Przemysław Rzodkiewicz

    2016-10-01

    Full Text Available Objectives : Esculetin (6,7-dihydroxycoumarin is a natural coumarin with anti-oxidant, anti-inflammatory and anti-nociceptive activity. It acts as a potent inhibitor of lipoxygenases (5-LOX and 12-LOX and decreases the production of matrix metalloproteinases (MMP-1, MMP-3 and MMP-9. Because both inhibition of lipoxygenases and inhibition of matrix metalloproteinases are effective strategies in the treatment of rheumatoid arthritis, we investigated whether esculetin may be effective in adjuvant-induced arthritis in rats. Material and methods : The study was performed on male Lewis rats, in the adjuvant-induced arthritis model. Rats were divided into two groups: control (treated with 1% methylcellulose and experimental (treated with esculetin – 10 mg/kg ip.. The tested compound was administered for 5 consecutive days starting on the 21st day after induction of arthritis. Each group consisted of 7 animals. After 5 days of treatment, rats were anesthetized. The concentration of leukotriene B4 (LTB4 in plasma was determined by a competitive enzyme immunoassay. Results : The LTB4 level in plasma of rats with adjuvant-induced arthritis is increased in comparison to rats without inflammation (362 ±34 vs. 274 ±15 pg/ml, p < 0.01, respectively. Five-day treatment with esculetin in adjuvant-induced arthritis rats decreases the LTB4 level to a level comparable with rats without inflammation (284 ±23 pg/ml, p < 0.01. Conclusions : LTB4 is the most potent chemotactic agent influencing neutrophil migration into the joint. It is known that its level in serum of patients with active rheumatoid arthritis is increased and correlates with disease severity. Some other lipoxygenase inhibitors have already been tested as potential drug candidates in clinical and preclinical trials for rheumatoid arthritis (Zileuton, PF-4191834. Because esculetin decreases the LTB4 level in plasma of rats in adjuvant-induced arthritis, it may also be considered as an attractive

  8. Enzymatic and ultrastructural study of lysosomes in rats bearing radiation-induced thyroid follicular carcinoma

    International Nuclear Information System (INIS)

    Starling, J.R.; Clifton, K.H.; Norback, D.H.

    1981-01-01

    Radiation-induced well-differentiated and poorly differentiated follicular thyroid cancers were transplanted into the intrascapular fat pads of male Fisher 144 rats. The tumors grew in the recipient rats and after a time interval were removed and studied along with normal rat thyroids for lysosomal activity and ultrastructural characteristics. Plasma from experimental and control rats was also studied for lysosomal activity. Rats with radiation-induced thyroid carcinoma had a decrease in growth rate compared with normal rats. There was no significant increase in plasma lysosomal enzymes in the experimental rats. Well-differentiated thyroid carcinomatous tissue showed increased total activities of lysosomal enzymes as well as a difference in subcellular distribution compared with normal and poorly differentiated carcinomatous tissue. Electron microscopy of normal and carcinomatous tissue demonstrated the greatest number of lysosomes in the well-differentiated carcinoma and the fewest in the poorly differentiated carcinoma

  9. Prolactin prevents acute stress-induced hypocalcemia and ulcerogenesis by acting in the brain of rat.

    Science.gov (United States)

    Fujikawa, Takahiko; Soya, Hideaki; Tamashiro, Kellie L K; Sakai, Randall R; McEwen, Bruce S; Nakai, Naoya; Ogata, Masato; Suzuki, Ikukatsu; Nakashima, Kunio

    2004-04-01

    Stress causes hypocalcemia and ulcerogenesis in rats. In rats under stressful conditions, a rapid and transient increase in circulating prolactin (PRL) is observed, and this enhanced PRL induces PRL receptors (PRLR) in the choroid plexus of rat brain. In this study we used restraint stress in water to elucidate the mechanism by which PRLR in the rat brain mediate the protective effect of PRL against stress-induced hypocalcemia and ulcerogenesis. We show that rat PRL acts through the long form of PRLR in the hypothalamus. This is followed by an increase in the long form of PRLR mRNA expression in the choroid plexus of the brain, which provides protection against restraint stress in water-induced hypocalcemia and gastric erosions. We also show that PRL induces the expression of PRLR protein and corticotropin-releasing factor mRNA in the paraventricular nucleus. These results suggest that the PRL levels increase in response to stress, and it moves from the circulation to the cerebrospinal fluid to act on the central nervous system and thereby plays an important role in helping to protect against acute stress-induced hypocalcemia and gastric erosions.

  10. Adherence of urease-induced crystals to rat bladder epithelium.

    Science.gov (United States)

    Grenabo, L; Hedelin, H; Pettersson, S

    1988-01-01

    Apart from urine supersaturation with respect to struvite and calcium phosphate caused by urease-producing microorganisms, retention of formed crystals in the urinary tract is necessary for the formation of infection stones. This study was performed to investigate the role of the mucous coat lining the urothelium in the adhesion of urease-induced crystals. Removal of this glycosaminoglycan-containing layer from rat bladders increased the adherence of struvite and calcium phosphate crystals 5-6 times compared to that in intact rat bladders. Heparin completely restored the antiadherence capacity while chondroitin sulphate had a very weak restorative effect and human urine had no restorative effect. These findings support the view that the mucous coat is of importance in preventing retention of urease-induced crystals.

  11. Everything You Wanted to Know about Puberty (For Teens)

    Science.gov (United States)

    ... it's not a pretty one. That smell is body odor, and everyone gets it. As you enter puberty, ... deodorant with antiperspirant) every day can help keep body odor in check, too. There's More? Guys and girls ...

  12. To treat or not to treat: puberty suppression in childhood-onset gender dysphoria

    OpenAIRE

    Costa, Rosalia; Carmichael, Polly; Colizzi, Marco

    2016-01-01

    Puberty suppression using gonadotropin-releasing-hormone analogues (GnRHa) has become increasingly accepted as an intervention during the early stages of puberty (Tanner stage 2-3) in individuals with clear signs of childhood-onset gender dysphoria. However, lowering the age threshold for using medical intervention for children with gender dysphoria is still a matter of contention, and is more controversial than treating the condition in adolescents and adults, as children with gender dysphor...

  13. Involvement of growth factors and their receptors in radon-induced rat lung tumors

    International Nuclear Information System (INIS)

    Leung, F.C.; Dagle, G.E.; Cross, F.T.

    1992-01-01

    In this paper we examine the role of growth factors (GF) and their receptors (GFR) in radon-induced rat lung tumors. Inhalation exposure of radon and its daughters induced lung tumors in rats, but the molecule/cellular mechanisms are not known. Recent evidence suggests that GF/GFR play a critical role in the growth and development of lung cancer in humans and animals. We have developed immunocytochemical methods for identifying sites of production and action of GF/GFR at the cellular level; for example, the avidin-biotin horseradish peroxidase technique. In radon-induced rat epidermoid carcinomas, epidermal growth factor (EGF), EGF-receptors (EGF-R), transforming growth factor alpha (TGF-α), and bombesin were found to be abnormally expressed. These abnormal expressions, mainly associated with epidermoid carcinomas of the lung, were not found in any other lung tumor types. Our data suggest that EGF, EGF-R, TGF-α, and bombesin are involved in radon oncogenesis in rat lungs, especially in epidermoid carcinomas, possibly through the autocrine/paracrine pathway

  14. Dietary fish oil modulates the effect of dimethylhydrazine-induced colon cancer in rats

    Energy Technology Data Exchange (ETDEWEB)

    Rasmy, G. E.; Khalil, W. K. B.; Moharib, S. A.; Kawab, A. A.; Jwanny, E. W.

    2011-07-01

    This study was conducted to examine the efficacy of fish oil supplementation in male wistar rat colon carcinogenesis. In order to induce colon cancer, the rats were given a weekly subcutaneous injection of 1,2-Dimethylhydrazine (DMH) at a dose of 20 mg/kg b.w. for five weeks. Afterwards, some of the rats ingested fish oil for either 4 weeks (DMH-FO4 group), or 17 weeks (DMH-FO17 group). The remaining rats continued without any supplementation for the same 4 weeks (DMH4 group), or 17 weeks (DMH17 group). Another two groups of rats did not receive the DMH and were given fish oil (FO17 group) or a normal diet only and considered as the control group (CN group). At the end of the experiment, the rats were sacrificed; and were subsequently subjected to biochemical and molecular biological analyses as well as histopathological examinations. The results showed increased levels of lactate dehydrogenase (LDH), malondialdehyde (MDA) and alkaline phosphatase (ALP) activities in the DMH rats compared to the control. The liver and colonic changes that were induced by DMH were significantly improved through fish oil supplementation in the DMH-FO17 group. The molecular analysis revealed that DMH treatment induced the expression alterations of genes p53, p27 and p21 and increased DNA band patterns related to cancer, while both FO17 and DMH-FO17 groups showed much better results. A histopathological examination of the DMH17 group revealed colon adenocarcinoma and several lesions in rat liver tissues. An improvement in the histopathological picture was seen in the livers and colons of groups DMHFO17. In conclusion, the present results demonstrated the anti-carciongenic effect of herring fish oil against DMH induced colon carcinogenesis in rats. The inhibitory effect of FO was due to the modulation of elevated biochemical parameters, DNA damage, gene expression and histopathological lesions caused by DMH. (Author) 70 refs.

  15. Pathological and MRI study on experimental heroin-induced brain damage in rats

    International Nuclear Information System (INIS)

    Long Yu; Kong Xiangquan; Xu Haibo; Liu Dingxi; Yuan Ren; Yu Qun; Xiong Yin; Deng Xianbo

    2005-01-01

    Objective: To study the pathological characteristics of the heroin-induced brain damage in rats, and to assess the diagnostic value of MRI. Methods: A total of 40 adult Wistar rats were studied, 32 rats were used for injecting heroin as heroin group and 8 were used for injecting saline as control group. The heroin dependent rat model was established by administering heroin (ip) in the ascending dosage schedule (0.5 mg/kg), three times a day (at 8:00, 12:00, and 18:00). The control group was established by the same way by injection with saline. The withdrawal scores were evaluated with imp roved criterion in order to estimate the degree of addiction after administering naloxone. Based on the rat model of heroin dependence, the rat model of heroin-induced brain damage was established by the same way with increasing heroin dosage everyday. Two groups were examined by using MRI, light microscope, and electron microscope, respectively in different heroin accumulated dosage (918, 1580, 2686, 3064, 4336, and 4336 mg/kg withdrawal after 2 weeks). Results: There was statistically significant difference (t=9.737, P<0.01) of the withdrawal scores between the heroin dependent group and the saline group (23.0 ± 4.4 and 1.4 ± 0.5, respectively). It suggested that the heroin dependent rat model be established successfully. In different accumulated dosage ( from 1580 mg/kg to 4336 mg/kg), there were degeneration and death of nerve cells in cerebrum and cerebellum of heroin intoxicated rats, and it suggested that the rat model of heroin-induced brain damage was established successfully. The light microscope and electron microscope features of heroin-induced brain damage in rats included: (1) The nerve cells of cerebral cortex degenerated and died. According to the heroin accumulated dosage, there were statistically significant difference of the nerve cell deaths between 4336 mg/kg group and 1580 mg/kg group or control group (P=0.024 and P=0.032, respectively); (2) The main

  16. Moringa oleifera Supplemented Diets Prevented Nickel-Induced Nephrotoxicity in Wistar Rats

    Directory of Open Access Journals (Sweden)

    O. S. Adeyemi

    2014-01-01

    Full Text Available Background. The Moringa oleifera plant has been implicated for several therapeutic potentials. Objective. To evaluate whether addition of M. oleifera to diet has protective effect against nickel-induced nephrotoxicity in rats. Methodology. Male Wistar rats were assigned into six groups of five. The rats were given oral exposure to 20 mg/kg nickel sulphate (NiSO4 in normal saline and sustained on either normal diet or diets supplemented with Moringa oleifera at different concentrations for 21 days. 24 hours after cessation of treatments, all animals were sacrificed under slight anesthesia. The blood and kidney samples were collected for biochemical and histopathology analyses, respectively. Results. NiSO4 exposure reduced the kidney-to-body weight ratio in rats and caused significant elevation in the levels of plasma creatinine, urea, and potassium. Also, the plasma level of sodium was decreased by NiSO4 exposure. However, addition of M. oleifera to diets averted the nickel-induced alteration to the level of creatinine and urea. The histopathology revealed damaged renal tubules and glomerular walls caused by NiSO4 exposure. In contrast, the damages were ameliorated by the M. oleifera supplemented diets. Conclusion. The addition of M. oleifera to diet afforded significant protection against nickel-induced nephrotoxicity.

  17. Moringa oleifera Supplemented Diets Prevented Nickel-Induced Nephrotoxicity in Wistar Rats

    Science.gov (United States)

    Adeyemi, O. S.; Elebiyo, T. C.

    2014-01-01

    Background. The Moringa oleifera plant has been implicated for several therapeutic potentials. Objective. To evaluate whether addition of M. oleifera to diet has protective effect against nickel-induced nephrotoxicity in rats. Methodology. Male Wistar rats were assigned into six groups of five. The rats were given oral exposure to 20 mg/kg nickel sulphate (NiSO4) in normal saline and sustained on either normal diet or diets supplemented with Moringa oleifera at different concentrations for 21 days. 24 hours after cessation of treatments, all animals were sacrificed under slight anesthesia. The blood and kidney samples were collected for biochemical and histopathology analyses, respectively. Results. NiSO4 exposure reduced the kidney-to-body weight ratio in rats and caused significant elevation in the levels of plasma creatinine, urea, and potassium. Also, the plasma level of sodium was decreased by NiSO4 exposure. However, addition of M. oleifera to diets averted the nickel-induced alteration to the level of creatinine and urea. The histopathology revealed damaged renal tubules and glomerular walls caused by NiSO4 exposure. In contrast, the damages were ameliorated by the M. oleifera supplemented diets. Conclusion. The addition of M. oleifera to diet afforded significant protection against nickel-induced nephrotoxicity. PMID:25295181

  18. Low-dose acute vanillin is beneficial against harmaline-induced tremors in rats.

    Science.gov (United States)

    Abdulrahman, Al Asmari; Faisal, Kunnathodi; Meshref, Ali Al Amri; Arshaduddin, Mohammed

    2017-03-01

    To study the effect of pretreatment with low doses of vanillin, a flavoring agent used as a food additive, on harmaline-induced tremor in rats. Sprague Dawley rats (110 ± 5 g) were divided into groups of six animals each. Vanillin (6.25 mg, 12.5 mg, and 25 mg/kg) was administered by gavage to different groups of rats, 30 minutes before the induction of tremor. Harmaline (10 mg/kg, i.p.) was used for the induction of tremor. The latency of onset, duration, tremor intensity, tremor index, and spontaneous locomotor activity were recorded. A separate batch of animals was used for the determination of serotonin (5HT) and 5 hydroxyindole acetic acid (5HIAA) levels in the brain. Harmaline treatment resulted in characteristic tremor that lasted for more than 2 hours and decreased the locomotor activity of rats. Pre-treatment with vanillin significantly reduced the duration, intensity, and tremor index of harmaline-treated animals. Vanillin treatment also significantly attenuated harmaline-induced decrease in the locomotor activity. An increase in 5HT levels and the changes in 5HIAA/5HT ratio observed in harmaline treated rats were significantly corrected in vanillin pretreated animals. Vanillin in low doses reduces harmaline-induced tremor in rats, probably through its modulating effect on serotonin levels in the brain. These findings suggest a beneficial effect of vanillin in essential tremor.

  19. Atrazine-induced reproductive tract alterations after transplacental and/or lactational exposure in male Long-Evans rats

    International Nuclear Information System (INIS)

    Rayner, Jennifer L.; Enoch, Rolondo R.; Wolf, Douglas C.; Fenton, Suzanne E.

    2007-01-01

    Studies showed that early postnatal exposure to the herbicide atrazine (ATR) delayed preputial separation (PPS) and increased incidence of prostate inflammation in adult Wistar rats. A cross-fostering paradigm was used in this study to determine if gestational exposure to ATR would also result in altered puberty and reproductive tissue effects in the male rat. Timed-pregnant Long-Evans (LE) rats were dosed by gavage on gestational days (GD) 15-19 with 100 mg ATR/kg body weight (BW) or 1% methylcellulose (controls, C). On postnatal day (PND)1, half litters were cross-fostered, creating 4 treatment groups; C-C, ATR-C, C-ATR, and ATR-ATR (transplacental-milk as source, respectively). On PND4, male offspring in the ATR-ATR group weighed significantly less than the C-C males. ATR-ATR male pups had significantly delayed preputial separation (PPS). BWs at PPS for C-ATR and ATR-ATR males were reduced by 6% and 9%, respectively, from that of C-C. On PND120, lateral prostate weights of males in the ATR-ATR group were significantly increased over C-C. Histological examination of lateral and ventral prostates identified an increased distribution of inflammation in the lateral prostates of C-ATR males. By PND220, lateral prostate weights were significantly increased for ATR-C and ATR-ATR, but there were no significant changes in inflammation in either the lateral or ventral prostate. These results suggest that in LE rats, gestational ATR exposure delays PPS when male offspring suckle an ATR dam, but leads to increased lateral prostate weight via transplacental exposure alone. Inflammation present at PND120 does not increase in severity with time

  20. Preventive effects of β-cryptoxanthin against cadmium-induced oxidative stress in the rat testis

    Directory of Open Access Journals (Sweden)

    Xiao-Ran Liu

    2016-01-01

    Full Text Available β-cryptoxanthin (CRY, a major carotenoid of potential interest for health, is obtained naturally from orange vegetables and fruits. A few research studies have reported that CRY could decrease oxidative stress and germ cell apoptosis. The purpose of this study was to examine the effects of CRY on acute cadmium chloride (CdCl 2 -induced oxidative damage in rat testes. For this study, 24 rats were divided into four groups, one of which serves as a control group that received intraperitoneal (i.p. injections of corn oil and physiological saline. The other rats were i.p. injected with CRY (10 μg kg−1 every 8 h, beginning 8 h before CdCl 2 (2.0 mg kg−1 treatment. The pathological and TUNEL findings revealed that CRY ameliorated the Cd-induced testicular histological changes and germ cell apoptosis in the rats. Furthermore, the Cd-induced decrease in the testicular testosterone (T level was attenuated after CRY administration (P < 0.05. The administration of CRY significantly reversed the Cd-induced increases in the lipid peroxide (LPO and malondialdehyde (MDA levels (P < 0.01. The testicular antioxidants superoxide dismutase (SOD, catalase (CAT and glutathione (GSH were decreased by treatment with Cd alone but were restored by CRY co-treatment. These results demonstrated that the application of CRY can enhance the tolerance of rats to Cd-induced oxidative damage and suggest that it has promised as a pharmacological agent to protect against Cd-induced testicular toxicity.

  1. Neuroprotective efficacy of curcumin in arsenic induced cholinergic dysfunctions in rats.

    Science.gov (United States)

    Yadav, Rajesh S; Chandravanshi, Lalit P; Shukla, Rajendra K; Sankhwar, Madhu L; Ansari, Reyaz W; Shukla, Pradeep K; Pant, Aditya B; Khanna, Vinay K

    2011-12-01

    Our recent studies have shown that curcumin protects arsenic induced neurotoxicity by modulating oxidative stress, neurotransmitter levels and dopaminergic system in rats. As chronic exposure to arsenic has been associated with cognitive deficits in humans, the present study has been carried out to implore the neuroprotective potential of curcumin in arsenic induced cholinergic dysfunctions in rats. Rats treated with arsenic (sodium arsenite, 20mg/kg body weight, p.o., 28 days) exhibited a significant decrease in the learning activity, assessed by passive avoidance response associated with decreased binding of (3)H-QNB, known to label muscarinic-cholinergic receptors in hippocampus (54%) and frontal cortex (27%) as compared to controls. Decrease in the activity of acetylcholinesterase in hippocampus (46%) and frontal cortex (33%), staining of Nissl body, immunoreactivity of choline acetyltransferase (ChAT) and expression of ChAT protein in hippocampal region was also observed in arsenic treated rats as compared to controls. Simultaneous treatment with arsenic and curcumin (100mg/kg body weight, p.o., 28 days) increased learning and memory performance associated with increased binding of (3)H-QNB in hippocampus (54%), frontal cortex (25%) and activity of acetylcholinesterase in hippocampus (41%) and frontal cortex (29%) as compared to arsenic treated rats. Increase in the expression of ChAT protein, immunoreactivity of ChAT and staining of Nissl body in hippocampal region was also observed in rats simultaneously treated with arsenic and curcumin as compared to those treated with arsenic alone. The results of the present study suggest that curcumin significantly modulates arsenic induced cholinergic dysfunctions in brain and also exhibits neuroprotective efficacy of curcumin. Copyright © 2011 Elsevier Inc. All rights reserved.

  2. Curcumin Attenuates Hepatotoxicity Induced by Zinc Oxide Nanoparticles in Rats

    Directory of Open Access Journals (Sweden)

    Layasadat Khorsandi

    2016-06-01

    Full Text Available Background: Zinc oxide nanoparticles (NZnO are increasingly used in modern life. Most metal nanoparticles have adverse effects on the liver. Aims: To explore the protective action of curcumin (Cur against hepatotoxicity induced by NZnO in rats. Study Design: Animal experimentation. Methods: Control group animals received normal saline, while the Cur group animals were treated with 200 mg/kg of Cur orally for 21 days. NZnO-intoxicated rats received 50 mg/kg of NZnO for 14 days by gavage method. In the NZnO+Cur group, rats were pretreated with Cur for 7 days before NZnO administration. Plasma activities of Alanine aminotransferase (ALT, aspartate aminotransferase (AST and alkaline phosphatase (ALP were measured as biomarkers of hepatotoxicity. Hepatic levels of malondialdehyde (MDA and superoxide dismutase (SOD and glutathione peroxidase (GPx activities were measured for detection of oxidative stress in liver tissue. Histological changes and apoptosis in liver tissue were studied by using Hematoxylin-eosin staining and the transferase dUTP nick end labeling (TUNEL method. Results: NZnO induced a significant increase in plasma AST (2.8-fold, ALT (2.7-fold and ALP (1.97-fold activity in comparison to the control group (p<0.01. NZnO increased MDA content and reduced SOD and GPx activities. NZnO caused liver damage including centrilobular necrosis and microvesicular steatosis. The percentage of apoptosis in hepatocytes was increased in NZnO-treated rats (p<0.01. Pre-treatment of Cur significantly reduced lipid peroxidation (39%, increased SOD (156% and GPx (26% activities, and attenuated ALT (47%, AST (41% and ALP (30% activities. Pre-treatment with Cur also decreased the histology changes and apoptotic index of hepatocytes (p<0.05. Conclusion: These findings indicate that Cur effectively protects against NZnO-induced hepatotoxicity in rats. However, future studies are required to propose Cur as a potential protective agent against hepatotoxicity

  3. PC Greyling CH van Niekerk* Most investigators determine puberty ...

    African Journals Online (AJOL)

    progesterone concentrations, cyclic activity for kids weaned in December and April on a high- or ... goats had an effect upon synchronization and timing of puberty, entrained by ... research done on ewe lambs is much more comjJrehensive.

  4. Enhanced cocaine-induced locomotor sensitization and intrinsic excitability of NAc medium spiny neurons in adult but not adolescent rats susceptible to diet-induced obesity

    Science.gov (United States)

    Oginsky, Max F.; Maust, Joel D.; Corthell, John T.; Ferrario, Carrie R.

    2015-01-01

    Rationale Basal and diet-induced differences in mesolimbic function, particularly within the nucleus accumbens (NAc), may contribute to human obesity; these differences may be more pronounced in susceptible populations. Objectives We determined whether there are differences in cocaine-induced behavioral plasticity in rats that are susceptible vs. resistant to diet-induced obesity, and basal differences in the striatal neuron function in adult and adolescent obesity-prone and obesity-resistant rats. Methods Susceptible and resistant outbred rats were identified based on “junk-food” diet-induced obesity. Then, the induction and expression of cocaine-induced locomotor sensitization, which is mediated by enhanced striatal function and is associated with increased motivation for rewards and reward-paired cues, were evaluated. Basal differences in mesolimbic function were examined in selectively bred obesity-prone and obesity-resistant rats (P70-80 and P30-40) using both cocaine induced locomotion and whole-cell patch clamping approaches in NAc core medium spiny neurons (MSNs). Results In rats that became obese after eating “junk-food”, the expression of locomotor sensitization was enhanced compared to non-obese rats, with similarly strong responses to 7.5 and 15 mg/kg cocaine. Without diet manipulation, obesity-prone rats were hyper-responsive to the acute locomotor-activating effects of cocaine, and the intrinsic excitability of NAc core MSNs was enhanced by ~60% at positive and negative potentials. These differences were present in adult, but not adolescent rats. Post-synaptic glutamatergic transmission was similar between groups. Conclusions Mesolimbic systems, particularly NAc MSNs, are hyper-responsive in obesity-prone individuals; and interactions between predisposition and experience influence neurobehavioral plasticity in ways that may promote weight gain and hamper weight loss in susceptible rats. PMID:26612617

  5. Immune responses induced by co-infection with Capillaria hepatica in Clonorchis sinensis-infected rats.

    Science.gov (United States)

    Moon, E-K; Lee, S-H; Goo, T W; Quan, F-S

    2018-07-01

    Clonorchis sinensis and Capillaria hepatica are zoonotic parasites that mainly infect the liver and cause serious liver disorders. However, immunological parameters induced by co-infection with these parasites remain unknown. In this study, for the first time, we investigated immunological profiles induced by co-infection with C. hepatica (CH) in C. sinensis (CS)-infected rats (Sprague-Dawley). Rats were infected primarily with 50 metacercariae of C. sinensis; 4 weeks later, they were subsequently infected with 1000 infective C. hepatica eggs. Significantly higher levels of C. sinensis- or C. hepatica-specific IgG antibodies were found in the sera of rats. Interestingly, no cross-reacting antibody was observed between C. sinensis and C. hepatica infections. Significantly raised eosinophil levels were found in the blood of C. sinensis/C. hepatica co-infected rats (CS + CH) compared to the blood of rats infected singly with C. sinensis. Co-infected rats showed significantly higher levels of lymphocyte proliferation and cytokine production compared to a single C. sinensis infection. The worm burden of C. sinensis was significantly reduced in co-infected rats compared to the single C. sinensis infection. These results indicate that the eosinophils, lymphocyte proliferation and cytokine production induced by subsequent infection with C. hepatica in C. sinensis-infected rats might contribute to the observed C. sinensis worm reduction.

  6. Protective effect of selenium against aluminium chloride induced cardiotoxicity in rats

    Directory of Open Access Journals (Sweden)

    Imen Ghorbel

    2017-08-01

    Full Text Available Our study pertains to evaluate the protective effect of selenium (Se, used as a nutritional supplement, against aluminium chloride induced cardiotoxicity in rats. Rats have received during 21 days either AlCl3 (400 ppm via drinking water, AlCl3 associated with Na2SeO3 (0.5 mg/kg of diet or only Na2SeO3. Co-administration of Se to AlCl3 treated rats alleviated heart oxidative stress objectified by a decrease of malondialdehyde, hydrogen peroxide and protein carbonyls levels. An improvement in antioxidant redox status, enzymatic (catalase, superoxide dismutase and glutathione peroxidase and non enzymatic (reduced glutathione, non protein thiols and vitamin C was also observed in Se treated rats.  LDH and CK activities, TC, LDL-C levels, TC/HDL-C and LDL-C/HDL-C ratios were increased, while HDL-C and TG decreased in rats treated with AlCl3. Cardiac biomarkers and lipid profile were restored to near control values by the supplementation of Se. Our results revealed that Se, a trace element with antioxidant properties, was effective in preventing heart damage induced by aluminium chloride.

  7. FORMALDEHYDE-INDUCED GENE EXPRESSION IN F344 RAT NASAL RESPIRATORY EPITHELIUM.

    Science.gov (United States)

    Formaldehyde-induced gene expression in F344 rat nasal respiratory epithelium ABSTRACTFormaldehyde, an occupational and environmental toxicant used extensively in the manufacturing of many household and personal use products, is known to induce squamous cell carci...

  8. Protective effect of mulberry flavonoids on sciatic nerve in alloxan-induced diabetic rats

    Directory of Open Access Journals (Sweden)

    Ma Song-Tao

    2014-12-01

    Full Text Available Mulberry leaves (Morus alba L. are a traditional Chinese medicine for blood serum glucose reduction. This study evaluated the protective effects of mulberry flavonoids on sciatic nerve in alloxan-induced diabetic rats. In this study, 80 Sprague-Dawley rats were divided into five groups: A (control, B (diabetic treated with saline, C-D (diabetic treated with 0.3, 0.1 g/kg mulberry flavonoids once a day for 8 weeks and E (diabetic treated with 0.3 mg/kg methycobal. The diabetic condition was induced by intraperitoneal injection of 200 mg/kg alloxan dissolved in saline. At the end of the experimental period, blood, and tissue samples were obtained for biochemical and histopathological investigation. Treatment with 0.3 g/kg mulberry flavonoids significantly inhibited the elevated serum glucose (P< 0.01. The increased myelin sheath area (P< 0.01, myelinated fiber cross-sectional area and extramedullary fiber number (P< 0.05 were also reduced in alloxan-induced rats treated with 0.3 g/kg mulberry flavonoids. 0.3 g/kg mulberry flavonoids also markedly decreased onion-bulb type myelin destruction and degenerative changes of mitochondria and Schwann cells. These findings demonstrate that mulberry flavonoids may improve the recovery of a severe peripheral nerve injury in alloxan-induced diabetic rats and is likely to be useful as a potential treatment on peripheral neuropathy (PN in diabetic rats.

  9. Islet transplantation in diabetic rats normalizes basal and exercise-induced energy metabolism

    NARCIS (Netherlands)

    Houwing, Harmina; Benthem, L.; Suylichem, P.T.R. van; Leest, J. van der; Strubbe, J.H.; Steffens, A.B.

    Transplantation of islets of Langerhans in diabetic rats normalizes resting glucose and insulin levels, but it remains unclear whether islet transplantation restores resting and exercise-induced energy metabolism. Therefore, we compared energy metabolism in islet transplanted rats with energy

  10. Mixed organic solvents induce renal injury in rats.

    Science.gov (United States)

    Qin, Weisong; Xu, Zhongxiu; Lu, Yizhou; Zeng, Caihong; Zheng, Chunxia; Wang, Shengyu; Liu, Zhihong

    2012-01-01

    To investigate the injury effects of organic solvents on kidney, an animal model of Sprague-Dawley (SD) rats treated with mixed organic solvents via inhalation was generated and characterized. The mixed organic solvents consisted of gasoline, dimethylbenzene and formaldehyde (GDF) in the ratio of 2:2:1, and were used at 12,000 PPM to treat the rats twice a day, each for 3 hours. Proteinuria appeared in the rats after exposure for 5-6 weeks. The incidences of proteinuria in male and female rats after exposure for 12 weeks were 43.8% (7/16) and 25% (4/16), respectively. Urinary N-Acetyl-β-(D)-Glucosaminidase (NAG) activity was increased significantly after exposure for 4 weeks. Histological examination revealed remarkable injuries in the proximal renal tubules, including tubular epithelial cell detachment, cloud swelling and vacuole formation in the proximal tubular cells, as well as proliferation of parietal epithelium and tubular reflux in glomeruli. Ultrastructural examination found that brush border and cytoplasm of tubular epithelial cell were dropped, that tubular epithelial cells were partially disintegrated, and that the mitochondria of tubular epithelial cells were degenerated and lost. In addition to tubular lesions, glomerular damages were also observed, including segmental foot process fusion and loss of foot process covering on glomerular basement membrane (GBM). Immunofluorescence staining indicated that the expression of nephrin and podocin were both decreased after exposure of GDF. In contrast, increased expression of desmin, a marker of podocyte injury, was found in some areas of a glomerulus. TUNEL staining showed that GDF induced apoptosis in tubular cells and glomerular cells. These studies demonstrate that GDF can induce both severe proximal tubular damage and podocyte injury in rats, and the tubular lesions appear earlier than that of glomeruli.

  11. Mixed organic solvents induce renal injury in rats.

    Directory of Open Access Journals (Sweden)

    Weisong Qin

    Full Text Available To investigate the injury effects of organic solvents on kidney, an animal model of Sprague-Dawley (SD rats treated with mixed organic solvents via inhalation was generated and characterized. The mixed organic solvents consisted of gasoline, dimethylbenzene and formaldehyde (GDF in the ratio of 2:2:1, and were used at 12,000 PPM to treat the rats twice a day, each for 3 hours. Proteinuria appeared in the rats after exposure for 5-6 weeks. The incidences of proteinuria in male and female rats after exposure for 12 weeks were 43.8% (7/16 and 25% (4/16, respectively. Urinary N-Acetyl-β-(D-Glucosaminidase (NAG activity was increased significantly after exposure for 4 weeks. Histological examination revealed remarkable injuries in the proximal renal tubules, including tubular epithelial cell detachment, cloud swelling and vacuole formation in the proximal tubular cells, as well as proliferation of parietal epithelium and tubular reflux in glomeruli. Ultrastructural examination found that brush border and cytoplasm of tubular epithelial cell were dropped, that tubular epithelial cells were partially disintegrated, and that the mitochondria of tubular epithelial cells were degenerated and lost. In addition to tubular lesions, glomerular damages were also observed, including segmental foot process fusion and loss of foot process covering on glomerular basement membrane (GBM. Immunofluorescence staining indicated that the expression of nephrin and podocin were both decreased after exposure of GDF. In contrast, increased expression of desmin, a marker of podocyte injury, was found in some areas of a glomerulus. TUNEL staining showed that GDF induced apoptosis in tubular cells and glomerular cells. These studies demonstrate that GDF can induce both severe proximal tubular damage and podocyte injury in rats, and the tubular lesions appear earlier than that of glomeruli.

  12. Possible mechanism of PNS protection against cisplatin-induced nephrotoxicity in rat models.

    Science.gov (United States)

    Liu, Xinwen; Huang, Zhenguang; Zou, Xiaoqin; Yang, Yufang; Qiu, Yue; Wen, Yan

    2015-01-01

    This study investigates the mechanism of the protective effect of Panax notoginsenosides (PNS) against cisplatin-induced nephrotoxicity via the hypoxia inducible factor 1 (HIF-1)/Bcl-2/adenovirus E1B 19 kDa-interacting protein 3 (BNIP3) pathway of autophagy. The rats underwent intraperitoneal injection with a single dose of cisplatin and a subset of rats were also intraperitoneally injected with 31.35 mg/kg PNS once a day. After 24 h exposure to cisplatin, the concentrations of urinary N-acetyl-β-D-glucosaminidase (NAG), blood urea nitrogen (BUN) and serum creatinine (Scr) were determined. The rat renal tissue was examined using H&E-staining, and the mitochondria of renal tubular epithelial cells were observed using transmission electron microscopy. The expressions of microtubule-associated protein-1 light chain (LC)3, autophagy-related gene (Atg)5, Beclin-1 and BNIP3 in rat renal tissue were detected using western blotting. The expression of HIF-1 was detected by immunohistochemistry. The results showed that PNS significantly protected against cisplatin-induced nephrotoxicity, as evidenced by decreasing the concentration of blood BUN and Scr, the attenuation of renal histopathological changes and the mitochondrial damages of renal cells, and the increase of mitochondria autophagosome in renal tubular epithelial cells. Additionally, PNS significantly increased the expression of LC3 and the ratio of LC3II/LC3I in rat renal tissue. Moreover, PNS significantly increased the expression of HIF-1α, BNIP3, Atg5 and Beclin-1 in rat renal tissue. In conclusion, the protective effect of PNS on cisplatin-induced nephrotoxicity was mainly due to its ability to enhancing the mitochondrial autophagy of renal tissue via the HIF-1α/BNIP3 pathway, and here is the first demonstration about it.

  13. Effects of sleeve gastrectomy in neonatally streptozotocin-induced diabetic rats.

    Directory of Open Access Journals (Sweden)

    Yan Wang

    Full Text Available BACKGROUND: Sleeve gastrectomy (SG has emerged recently as a stand-alone bariatric procedure to treat morbid obesity and enhance glucose homeostasis. The aim of the study was to evaluate its effects in neonatally streptozotocin (STZ-induced diabetic rats (n-STZ diabetic rats. METHODOLOGY AND PRINCIPAL FINDINGS: To induce diabetes, STZ (90 mg/kg was administered intraperitoneally to 2-day-old male pups. When 12 weeks old, diabetic rats were randomized into sleeve operation group (SLG, n = 6 and sham operation group (SOG, n = 6. Body weights were monitored weekly, and daily consumption of water and food were followed for eight consecutive weeks postoperatively. Serum glucose levels were measured periodically at the 4th and 8th week after surgery. Insulin, ghrelin, glucose-dependent insulinotropic polypeptide (GIP and Glucagon-like peptide-1 (GLP-1 levels were assayed at the end of the study. Our data showed that SLG rats exhibited significantly lower body weight gain in addition to reduced food and water intakes postoperatively compared to their sham-operation counterparts. However, resolution of diabetes was not observed in our study. Correspondingly, there were no significant differences between SOG rats and SLG rats in glucose metabolism-associated hormones, including insulin, GIP and GLP-1. In contrast, ghrelin level significantly decreased (P<0.01 in SLG group (58.01 ± 3.75 pg/ml after SG surgery compared to SOG group (76.36 ± 3.51 pg/ml. CONCLUSIONS: These observations strongly suggest that SG is effective in controlling body weight. However, SG did not achieve resolution or improvement of diabetes in n-STZ diabetic rats.

  14. Oxytocin mediates copulation-induced hypoalgesia of male rats.

    Science.gov (United States)

    Futagami, Hiroko; Sakuma, Yasuo; Kondo, Yasuhiko

    2016-04-08

    Copulatory behavior has been reported to raise the pain threshold in male rats. In this study, we examined the effect of copulatory behavior with or without ejaculation on pain threshold measured by electrical shock via an electrode attached to the tail. It was demonstrated that ejaculation is not necessary to raise the pain threshold in male rats. In addition, we examined whether oxytocin, a hypothalamic neuropeptide, was involved in copulation-induced hypoalgesia. Sexually experienced males were subjected to stereotaxic implantation of a guide cannula targeting the lateral ventricle. After the recovery period, half of the males were intracerebroventricularly treated with an oxytocin antagonist (OTA, 100ng d(CH2)51,Tyr(Me)2,Thr4, Orn8,Tyr-NH29]-vasotocin/1μL saline) and the remaining half were administered saline without anesthesia. Fifteen minutes later, half of each group were given sexual behavior with receptive females. We found no effect of OTA on sexual activity. Immediately after ejaculation, pain threshold was measured. While raised pain threshold was observed after sexual behavior in saline-treated males, no change in pain threshold was found in OTA-treated males even after copulation. The results suggest that central oxytocin mediates copulation-induced hypoalgesia in male rats. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  15. Oxidative stress induces the decline of brain EPO expression in aging rats.

    Science.gov (United States)

    Li, Xu; Chen, Yubao; Shao, Siying; Tang, Qing; Chen, Weihai; Chen, Yi; Xu, Xiaoyu

    2016-10-01

    Brain Erythropoietin (EPO), an important neurotrophic factor and neuroprotective factor, was found to be associated with aging. Studies found EPO expression was significantly decreased in the hippocampus of aging rat compared with that of the youth. But mechanisms of the decline of the brain EPO during aging remain unclear. The present study utilized a d-galactose (d-gal)-induced aging model in which the inducement of aging was mainly oxidative injury, to explore underlying mechanisms for the decline of brain EPO in aging rats. d-gal-induced aging rats (2months) were simulated by subcutaneously injecting with d-gal at doses of 50mg·kg(-1), 150mg·kg(-1) and 250mg·kg(-1) daily for 8weeks while the control group received vehicle only. These groups were all compared with the aging rats (24months) which had received no other treatment. The cognitive impairment was assessed using Morris water maze (MWM) in the prepared models, and the amount of β-galactosidase, the lipid peroxidation product malondialdehyde (MDA) level and the superoxide dismutase (SOD) activity in the hippocampus was examined by assay kits. The levels of EPO, EPOR, p-JAK2 and hypoxia-inducible factor-2α (HIF-2α) in the hippocampus were detected by western blot. Additionally, the correlation coefficient between EPO/EPOR expression and MDA level was analyzed. The MWM test showed that compared to control group, the escape latency was significantly extended and the times of crossing the platform was decreased at the doses of 150mg·kg(-1) and 250mg·kg(-1) (paging rats, the expressions of EPO, EPOR, p-JAK2, and HIF-2αin the brain of d-gal-treated rats were significantly decreased (paging could result in the decline of EPO in the hippocampus and oxidative stress might be the main reason for the decline of brain EPO in aging rats, involved with the decrease of HIF-2α stability. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Both hypothyroidism and hyperthyroidism increase atrial fibrillation inducibility in rats.

    Science.gov (United States)

    Zhang, Youhua; Dedkov, Eduard I; Teplitsky, Diana; Weltman, Nathan Y; Pol, Christine J; Rajagopalan, Viswanathan; Lee, Bianca; Gerdes, A Martin

    2013-10-01

    Evidence indicates that cardiac hypothyroidism may contribute to heart failure progression. It is also known that heart failure is associated with an increased risk of atrial fibrillation (AF). Although it is established that hyperthyroidism increases AF incidence, the effect of hypothyroidism on AF is unclear. This study investigated the effects of different thyroid hormone levels, ranging from hypothyroidism to hyperthyroidism on AF inducibility in thyroidectomized rats. Thyroidectomized rats with serum-confirmed hypothyroidism 1 month after surgery were randomized into hypothyroid (N=9), euthyroid (N=9), and hyperthyroid (N=9) groups. Rats received placebo, 3.3-mg l-thyroxine (T4), or 20-mg T4 pellets (60-day release form) for 2 months, respectively. At the end of treatment, hypothyroid, euthyroid, and hyperthyroid status was confirmed. Hypothyroid animals showed cardiac atrophy and reduced cardiac systolic and diastolic functions, whereas hyperthyroid rats exhibited cardiac hypertrophy and increased cardiac function. Hypothyroidism and hyperthyroidism produced opposite electrophysiological changes in heart rates and atrial effective refractory period, but both significantly increased AF susceptibility. AF incidence was 78% in hypothyroid, 67% in hyperthyroid, and the duration of induced AF was also longer, compared with 11% in the euthyroid group (all Phyperthyroidism lead to increased AF vulnerability in a rat thyroidectomy model. Our results stress that normal thyroid hormone levels are required to maintain normal cardiac electrophysiology and to prevent cardiac arrhythmias and AF.

  17. Amelioration of azoxymethane induced-carcinogenesis by reducing oxidative stress in rat colon by natural extracts.

    Science.gov (United States)

    Waly, Mostafa I; Al-Rawahi, Amani S; Al Riyami, Marwa; Al-Kindi, Mohamed A; Al-Issaei, Halima K; Farooq, Sardar A; Al-Alawi, Ahmed; Rahman, Mohammad S

    2014-02-18

    Azoxymethane (AOM) is a potent carcinogenic agent commonly used to induce colon cancer in rats; the cytotoxicity of AOM is considered to mediate oxidative stress. This study investigated the chemopreventive effect of three natural extracts [pomegranate peel extract (PomPE), papaya peel extract (PapPE) and seaweed extract (SE)] against AOM-induced oxidative stress and carcinogenesis in rat colon. Eighty Sprague-Dawley rats (aged 4 weeks) were randomly divided into 8 groups (10 rats/group). Control group was fed a basal diet; AOM-treated group was fed a basal diet and received AOM intraperitonial injections for two weeks at a dose of 15 mg/kg bodyweight, whereas the other six groups were received oral supplementation of PomPE, PapPE or SE, in the presence or absence of AOM injection. All animals were continuously fed ad-libitum until aged 16 weeks, then all rats were sacrificed and the colon tissues were examined microscopically for pathological changes and aberrant crypt foci (ACF) development, genotoxicity (induced micronuclei (MN) cells enumeration), and glutathione and lipid peroxidation. Our results showed that AOM-induced ACF development and pathological changes in the colonic mucosal tissues, increased bone marrow MN cells and oxidative stress (glutathione depletion, lipid peroxidation) in rat colonic cells. The concomitant treatment of AOM with PomPE, PapPE or SE significantly ameliorated the cytotoxic effects of AOM. The results of this study provide in-vivo evidence that PomPE, PapPE and SE reduced the AOM-induced colon cancer in rats, through their potent anti-oxidant activities.

  18. Increase in first morning voided urinary luteinizing hormone levels precedes the physical onset of puberty

    DEFF Research Database (Denmark)

    Demir, Ahmet; Voutilainen, R; Juul, A

    1996-01-01

    Determinations of serum gonadotropin concentrations by ultra-sensitive methods have improved the diagnosis of pubertal disorders. The onset of puberty can be estimated by measuring serum gonadotropin pulsation, but as this requires serial nocturnal blood sampling, it is not a routine investigation...... before clinical signs of puberty can be detected. The correlation between FMV urine and S-LH values was good (r = 0.64; P ... for S-LH. A significant increase in FMV U-LH concentration occurs before the first clinical signs of puberty in a sex-independent fashion. Our data indicate that FMV U-LH measurement is a clinically relevant, noninvasive method for the evaluation of pubertal development, and it may be helpful...

  19. Feeding blueberry diets in early life prevent senescence of osteoblasts and bone loss in ovariectomized adult female rats.

    Directory of Open Access Journals (Sweden)

    Jian Zhang

    Full Text Available Appropriate nutrition during early development is essential for maximal bone mass accretion; however, linkage between early nutrition, childhood bone mass, peak bone mass in adulthood, and prevention of bone loss later in life has not been studied.In this report, we show that feeding a high quality diet supplemented with blueberries (BB to pre-pubertal rats throughout development or only between postnatal day 20 (PND20 and PND34 prevented ovariectomy (OVX-induced bone loss in adult life. This protective effect of BB is due to suppression of osteoblastic cell senescence associated with acute loss of myosin expression after OVX. Early exposure of pre-osteoblasts to serum from BB-fed rats was found to consistently increase myosin expression. This led to maintenance osteoblastic cell development and differentiation and delay of cellular entrance into senescence through regulation of the Runx2 gene. High bone turnover after OVX results in insufficient collagenous matrix support for new osteoblasts and their precursors to express myosin and other cytoskeletal elements required for osteoblast activity and differentiation.These results indicate: 1 a significant prevention of OVX-induced bone loss from adult rats can occur with only 14 days consumption of a BB-containing diet immediately prior to puberty; and 2 the molecular mechanisms underlying these effects involves increased myosin production which stimulates osteoblast differentiation and reduces mesenchymal stromal cell senescence.

  20. Lipid profile of alloxan-induced diabetic wistar rats treated with ...

    African Journals Online (AJOL)

    weeks; Group 2, diabetes control rats, induced with 150 mg/kg b.w., i.p. administration of alloxan and thereafter given 0.2 ml distilled water throughout the study period; Groups 3, 4 and 5, diabetic (i.p., 150 mg/kg b.w. alloxan) rats were given single oral dose of MAD (100, 200 and 300 mg/kg b.w. respectively) for 4 weeks; ...

  1. Disrupting circadian rhythms in rats induces retrograde amnesia

    NARCIS (Netherlands)

    Fekete, Mátyás; Ree, J.M. van; Niesink, Raymond J.M.; Wied, D. de

    1985-01-01

    Disrupting circadian organization in rats by phase-shifting the illumination cycle or by exposure to a reversed day/night cycle or to continuous light, resulted in retrograde amnesia for passive avoidance behavior. This retrograde amnesia induced by phase-shifting lasted at least 2 days, and

  2. Validation of infrared thermography in serotonin-induced itch model in rats

    DEFF Research Database (Denmark)

    Dagnæs-Hansen, Frederik; Jasemian, Yousef; Gazerani, Parisa

    The number of scratching bouts is generally used as a standard method in animal models of itch. The aim of the present study was to validate the application of infrared thermography (IR-Th) in a serotonin-induced itch model in rats. Adult Sprague-Dawley male rats (n = 24) were used in 3 consecuti...

  3. A novel model for NSAID induced gastroenteropathy in rats.

    Science.gov (United States)

    Singh, Devendra Pratap; Borse, Swapnil P; Nivsarkar, Manish

    2016-01-01

    Progress in management of Nonsteroidal anti-inflammatory drug (NSAID) induced gastrointestinal toxicity requires the availability of appropriate experimental animal models that are as close to humans as feasible. Our objective was to develop a rat model for NSAID-induced gastroenteropathy and also to simulate the common clinical scenario of co-administration of NSAID and proton pump inhibitor (PPI) to explore if PPI contribute to exacerbation of NSAID-enteropathy. Rats were treated twice daily with pantoprazole sodium (PTZ; 10mg/kg peroral) or vehicle for a total of 10days. In some experiments, Diclofenac sodium (DCF; 9mg/kg) or vehicle was administered orally twice daily for the final 5days of PTZ/vehicle administration. After the last dose on 9th day, rats in all the groups were fasted but water was provided ad libitum. 12h after the last dose on 10th day, rats in all the groups were euthanized and their gastrointestinal tracts were assessed for haemorrhagic lesions, lipid peroxidation, intestinal permeability and gastrointestinal luminal pH alterations. Changes in haemoglobin, haematocrit and serum levels of albumin, total protein, ALT and bilirubin were calculated. The macroscopic and histological evidence suggested that administration of DCF resulted in significant gastroenteropathic damage and co-administration of PTZ resulted in significant exacerbation of NSAID enteropathy, while attenuation of NSAID induced gastropathy was observed. Our results were further supported by the significant decrease in haemoglobin and haematocrit levels and serum levels of albumin and total proteins, an increase in oxidative stress and intestinal permeability with the use of DCF either alone or in combination with PTZ. This model was developed to simulate the human clinical situation during NSAID therapy and indeed the present DCF regimen caused both gastric and small bowel alterations, such as multiple erosive lesions, together with a decrease in haemoglobin, haematocrit

  4. Influence of dietary iodine on drug-induced hypothyrodism in the rat.

    Science.gov (United States)

    Beyssen, M L; Lagorce, J F; Cledat, D; Buxeraud, J

    1999-06-01

    Several compounds of pharmaceutical importance from a variety of chemical families, for example chlorpromazine and clomipramine, have been found to form charge-transfer complexes with iodine. We have investigated the influence of dietary iodine on thyroid-gland dysfunction induced by clomipramine, chlorpromazine or 2-thiazoline-2-thiol. We suggest that iodine is partly diverted from its metabolic pathway by complexation with drugs, and so the urinary concentration of iodide is increased. Both chlorpromazine and clomipramine, at doses which do not inhibit thyroperoxidase, enhanced urinary iodine excretion when dietary iodine was restricted (3.944+/-0.96 microg/day for chlorpromazine-tested rats, 3.43+/-1.33 microg/day for clomipramine-tested rats, compared with 2.34+/-0.11 microg/day in control rats). Concurrently, these pharmaceutical compounds increased the level of free thyroid-stimulating hormone (TSH) in comparison with controls and induced histological modifications in, and enlargement of, the thyroid gland. We have demonstrated that drug-induced loss of iodine in the urine was associated with antithyroid action when iodine intake was limited.

  5. Antihypertensive Effect of Radix Paeoniae Alba in Spontaneously Hypertensive Rats and Excessive Alcohol Intake and High Fat Diet Induced Hypertensive Rats

    Directory of Open Access Journals (Sweden)

    Chen Su-Hong

    2015-01-01

    Full Text Available Radix Paeoniae Alba (Baishao, RPA has long been used in traditional Chinese medicine formulation to treat hypertension by repression the hyperfunction of liver. However, whether the RPA itself has the antihypertensive effect or not is seldom studied. This study was to evaluate the protective effect of RPA on hypertensive rats. Alcohol in conjunction with a high fat diet- (ACHFD- induced hypertensive rats and spontaneously hypertensive rats (SHR was constantly received either RPA extract (25 or 75 mg/kg or captopril (15 mg/kg all along the experiments. As a result, RPA extract (75 mg/kg could significantly reduce systolic blood pressure of both ACHFD-induced hypertensive rats and SHR after 9-week or 4-week treatment. In ACHFD-induced hypertensive rats, the blood pressure was significantly increased and the lipid profiles in serum including triglyceride, total cholesterol, LDL-cholesterol, and HDL-cholesterol were significantly deteriorated. Also, hepatic damage was manifested by a significant increase in alanine transaminase (ALT and aspartate transaminase (AST in serum. The RPA extract significantly reversed these parameters, which revealed that it could alleviate the liver damage of rats. In SHR, our result suggested that the antihypertensive active of RPA extract may be related to its effect on regulating serum nitric oxide (NO and endothelin (ET levels.

  6. Anti-asialo GM1 antibodies prevents guanethidine-induced sympathectomy in athymic rats

    DEFF Research Database (Denmark)

    Thygesen, P; Hougen, H P; Christensen, H B

    1992-01-01

    Guanethidine sulphate induces destruction of peripheral sympathetic neurons and infiltration of mononuclear cells in rat sympathetic ganglia. The effect of guanethidine is believed to be an autoimmune reaction. In order to determine the effect of anti-asialo GM1, an antibody that binds to the gly......Guanethidine sulphate induces destruction of peripheral sympathetic neurons and infiltration of mononuclear cells in rat sympathetic ganglia. The effect of guanethidine is believed to be an autoimmune reaction. In order to determine the effect of anti-asialo GM1, an antibody that binds...... to the glycolipid asialo GM1 expressed on rodent natural killer cells, athymic Lewis rats received guanethidine 40 mg/kg i.p. daily from day 1 to 14 and anti-asialo GM1 i.p. 1 mg/rat on day -2, 0, 2, 6, and 10 in the study period. Saline and anti-asialo GM1 were given alone in the same doses as control. The number...... of neurons in the sympathetic ganglia were counted and the ganglionic volume determined. The presence of natural killer cells in the ganglia were determined by immunohistochemical methods. Our results shows that anti-asialo GM1 can prevent guanethidine-induced reduction of sympathetic neurons...

  7. Antidiabetic and Antioxidant Properties of Triticum aestivum in Streptozotocin-Induced Diabetic Rats

    Directory of Open Access Journals (Sweden)

    Yogesha Mohan

    2013-01-01

    Full Text Available The antidiabetic and antioxidant potential of Triticum aestivum were evaluated by using in vivo methods in normal and streptozotocin-induced diabetic rats. Diabetes was induced in the Wistar strain albino rats by injecting streptozotocin at a dose of 55 mg/kg body weight. Ethanolic extracts of Triticum aestivum at doses of 100 mg/kg body weight were administered orally for 30 days. Various parameters were studied and the treatment group with the extract showed a significant increase in the liver glycogen and a significant decrease in fasting blood glucose, glycosylated hemoglobin levels, and serum marker enzyme levels. The total cholesterol and serum triglycerides levels, low density lipoprotein, and very low density lipoprotein were also significantly reduced and the high density lipoprotein level was significantly increased upon treatment with the Triticum aestivum ethanol extract. A significant decrease in the levels of lipid peroxides, superoxide dismutase, and glutathione peroxidise and increase in the levels of vitamin E, catalase, and reduced glutathione were observed in Triticum aestivum treated diabetic rats. Thus, from this study we conclude that ethanolic extract of Triticum aestivum exhibited significant antihyperglycemic, hypolipidemic, and antioxidant activities in streptozotocin-induced diabetic rats.

  8. Effects of maternal exposure to cow´s milk high or low in isoflavones on carcinogen-induced mammary tumorigenesis among rat offspring

    DEFF Research Database (Denmark)

    Nielsen, Tina Skau; Purup, Stig; Warri, A

    2011-01-01

    We investigated whether maternal exposure during pregnancy to cow's milk containing endogenous estrogens and insulin like growth factor 1 (IGF-1) and either high or low levels of isoflavones from dietary legumes (HIM and LIM, respectively) affected carcinogen-induced mammary carcinogenesis....... No differences in maternal serum estradiol (P = 0.19) and IGF-1 levels (P = 0.15) at GD 19 or birth weight among the milk and water groups were seen, but estradiol, and IGF-1 levels and birth weight were numerically higher in the LIM than in the HIM group. Puberty onset occurred earlier in the LIM offspring than...... in controls (P = 0.03). Although the high isoflavone content seemed to prevent the effect on circulating estradiol and IGF-1 levels and advanced puberty onset seen in the LIM group, HIM increased DMBA-DNA adducts in the mammary gland and tended to increase mammary tumorigenesis. In contrast, offspring exposed...

  9. Protective effects of Ginkgo biloba extract on the ethanol-induced gastric ulcer in rats

    Science.gov (United States)

    Chen, Sheng-Hsuan; Liang, Yu-Chih; Chao, Jane CJ; Tsai, Li-Hsueh; Chang, Chun-Chao; Wang, Chia-Chi; Pan, Shiann

    2005-01-01

    AIM: To evaluate the preventive effect of Ginkgo biloba extract (GbE) on ethanol-induced gastric mucosal injuries in rats. METHODS: Female Wistar albino rats were used for the studies. We randomly divided the rats for each study into five subgroups: normal control, experimental control, and three experimental groups. The gastric ulcers were induced by instilling 1 mL 50% ethanol into the stomach. We gave GbE 8.75, 17.5, 26.25 mg/kg intravenously to the experimental groups respectively 30 min prior to the ulcerative challenge. We removed the stomachs 45 min later. The gastric ulcers, gastric mucus and the content of non-protein sulfhydryl groups (NP-SH), malondialdehyde (MDA), c-Jun kinase (JNK) activity in gastric mucosa were evaluated. The amount of gastric juice and its acidity were also measured. RESULTS: The findings of our study are as follows: (1) GbE pretreatment was found to provide a dose-dependent protection against the ethanol-induced gastric ulcers in rats; (2) the GbE pretreatment afforded a dose-dependent inhibition of ethanol-induced depletion of stomach wall mucus, NP-SH contents and increase in the lipid peroxidation (increase MDA) in gastric tissue; (3) gastric ulcer induced by ethanol produced an increase in JNK activity in gastric mucosa which also significantly inhibited by pretreatment with GbE; and (4) GbE alone had no inhibitory effect on gastric secretion in pylorus-ligated rats. CONCLUSION: The finding of this study showed that GbE significantly inhibited the ethanol-induced gastric lesions in rats. We suggest that the preventive effect of GbE may be mediated through: (1) inhibition of lipid peroxidation; (2) preservation of gastric mucus and NP-SH; and (3) blockade of cell apoptosis. PMID:15968732

  10. Andrographolide reorganise hyperglycaemia and distorted antioxidant profile in streptozotocin-induced diabetic rats.

    Science.gov (United States)

    Naik, Ramavat Ravindhar; Munipally, Praveen Kumar; Nagaraju, Turlapati

    2017-10-26

    Diabetes mellitus (DM) is a constant and illimitable metabolic disorder that can happen even at a young age due to the virtual absence of naturally acting insulin, which uptakes and accumulates glucose; thereby reduce the use of glucose. In the present study, we evaluated the neuroprotective efficacy of andrographolide on streptozotocin (STZ) induced diabetic Sprague dawley rats. Diabetes was induced by intraperitonial injection of STZ (45 mg/kg B.W) in Sprague dawley rats. Andrographolide (2.5 mg/kg B.W) was administered orally to diabetic rats and Glibenclamide (25mg/kg B.W) as control for 30 days to assess its effects on blood glucose, insulin, insulin resistance and antioxidant profiles such as superoxide dismutase, catalase, glutathione peroxidase, reduced glutathione and lipid peroxidation in various regions of brain namely hypothalamus, cerebellum, hippocampus and brain cerebral cortex. Oral supplementation of andrographolide extensively diminished the blood glucose levels than diabetic control. There was noteworthy reduction in the CAT, SOD and GPx activities in the hippocampus, hypothalamus and cerebral cortex cerebellum of the DM rat brain. However, andrographolide supplementation drastically reverses the CAT, GPx and SOD back to normal levels. In conclusion, the results revealed that andrographolide shown beneficial potentiality against neuropathy in STZ induced diabetic rats. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  11. Antidiabetic effect of Chloroxylon swietenia bark extracts on streptozotocin induced diabetic rats

    Directory of Open Access Journals (Sweden)

    B. Jayaprasad

    2016-03-01

    Full Text Available Diabetes has been increasing at an alarming rate around the world, and experts have relied on remedies from the utilization of ancient drugs that are essentially derived from plants. The present study aimed to evaluate the antidiabetic potential of Chloroxylon swietenia bark extracts on streptozotocin induced diabetic rats. Diabetes was induced in male albino Wistar rats by single intraperitoneal injection of streptozotocin (STZ (50 mg/kg b.w.. The diabetic rats were administered orally with C. swietenia bark (CSB methanolic (CSBMEt and aqueous (CSBAEt (250 mg/kg b.w. extracts and glibenclamide (600 µg/kg b.w. by intragastric intubation for 45 days. The result showed a heavy loss in weight, increase in blood glucose and glycosylated hemoglobin level, and decline in plasma insulin and total hemoglobin content. Furthermore, glucose-6-phosphatase and fructose-1,6-bis phosphatase were found to be increased whereas hexokinase and glycogen contents were decreased in STZ induced diabetic rats. CSBAEt, CSBMEt and glibenclamide treated diabetic rats showed moderate reduction in blood glucose and glycosylated hemoglobin levels; in addition, plasma insulin and hemoglobin levels were elevated. The altered activities of carbohydrate metabolizing enzymes and liver glycogen were improved remarkably. CSBMEt results were comparable to the standard drug glibenclamide. The present findings support the usage of the plant extracts for the traditional treatment of diabetes.

  12. Effect of physical and psychological puberty training on general well being and its dimensions in girl students

    Directory of Open Access Journals (Sweden)

    Shahrban Mehrabi

    2018-03-01

    Full Text Available Transition through puberty is marked by an increased risk for the onset of a range of health problems, particularly those related to the control of behavior and emotion. The aim of this study was to determine the effectiveness of training puberty (physical and psychological matters in general well being and its dimensions in girl adolescents. This was a quasi-experimental study in which the target population included all girl students at the first grade of high school in Jiroft, Iran. 40 students (20 in the experimental group and 20 in the control group was selected using multi stage sampling method. The experimental group was educated in twelve-90- minute sessions. The content of the educational course included physical signs of puberty, physiologic change in menstrual period, hygiene, nutrition, and psychological changes of puberty. The participants completed the Skehill's general well being questionnaire before and after the intervention. Covariance analysis revealed the efficacy of education on the enhancement of psychological well being and psychological distress reduction. Therefore, it is recommended to implement health educational programs about physical and psychological matters during puberty to elementary and secondary school students to improve their mental health

  13. Combination of Erythromycin and Curcumin Alleviates Staphylococcus aureus Induced Osteomyelitis in Rats

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    Zubin Zhou

    2017-08-01

    Full Text Available Osteomyelitis is commonly caused by Staphylococcus aureus. Both erythromycin and curcumin can suppress S. aureus growth, but their roles in osteomyelitis are barely studied. We aim to explore the activities of erythromycin and curcumin against chronical osteomyelitis induced by methicillin-resistant S. aureus (MRSA. Chronicle implant-induced osteomyelitis was established by MRSA infection in male Wistar rats. Four weeks after bacterial inoculation, rats received no treatment, erythromycin monotherapy, curcumin monotherapy, or erythromycin plus curcumin twice daily for 2 weeks. Bacterial levels, bone infection status, inflammatory signals and side effects were evaluated. Rats tolerated all treatments well, with no death or side effects such as, diarrhea and weight loss. Two days after treatment completion, erythromycin monotherapy did not suppress bacterial growth and had no effect in bone infection, although it reduced serum pro-inflammatory cytokines tumor necrosis factor (TNF-α and interleukin (IL-6. Curcumin monotherapy slightly suppressed bacterial growth, alleviated bone infection and reduced TNF-α and IL-6. Erythromycin and curcumin combined treatment markedly suppressed bacterial growth, substantially alleviated bone infection and reduced TNF-α and IL-6. Combination of erythromycin and curcumin lead a much stronger efficiency against MRSA induced osteomyelitis in rats than monotherapy. Our study suggests that erythromycin and curcumin could be a new combination for treating MRSA induced osteomyelitis.

  14. Radiation-induced cognitive dysfunction: an experimental model in the old rat

    Energy Technology Data Exchange (ETDEWEB)

    Lamproglou, Ioannis; Chen, QI Ming; Boisserie, Gilbert; Mazeron, Jean-Jacques; Poisson, Michel; Baillet, Francois; Le Poncin, Monique; Delattre, Jean-Yves

    1995-01-01

    Purpose: To develop a model of radiation-induced behavioral dysfunction. Methods and Materials: A course of whole brain radiation therapy (30 Gy/10 fractions/12 days) was administered to 26 Wistar rats ages 16-27 months, while 26 control rats received sham irradiation. Sequential behavioral studies including one-way avoidance, two-way avoidance, and a standard operant conditioning method (press-lever avoidance) were undertaken. In addition, rats were studied in a water maze 7 months postradiation therapy. Results: Prior to radiation therapy, both groups were similar. No difference was found 1 and 3 months postradiation therapy. At 6-7 months postradiation therapy, irradiated rats had a much lower percentage of avoidance than controls for one-way avoidance (23% vs. 55%, p {<=} 0.001) and two-way avoidance (18% vs. 40%, p {<=} 0.01). Seven months postradiation therapy the reaction time was increased (press-lever avoidance, 11.20 s vs. 8.43 s, p {<=} 0.05) and the percentage of correct response was lower (water maze, 53% vs. 82%) in irradiated rats compared with controls. Pathological examination did not demonstrate abnormalities of the irradiated brains at the light microscopic level. Conclusion: Behavioral dysfunction affecting mainly memory can be demonstrated following conventional radiation therapy in old rats. This model can be used to study the pathogenesis of radiation-induced cognitive changes.

  15. Radiation-induced cognitive dysfunction: an experimental model in the old rat

    International Nuclear Information System (INIS)

    Lamproglou, Ioannis; Chen, QI Ming; Boisserie, Gilbert; Mazeron, Jean-Jacques; Poisson, Michel; Baillet, Francois; Le Poncin, Monique; Delattre, Jean-Yves

    1995-01-01

    Purpose: To develop a model of radiation-induced behavioral dysfunction. Methods and Materials: A course of whole brain radiation therapy (30 Gy/10 fractions/12 days) was administered to 26 Wistar rats ages 16-27 months, while 26 control rats received sham irradiation. Sequential behavioral studies including one-way avoidance, two-way avoidance, and a standard operant conditioning method (press-lever avoidance) were undertaken. In addition, rats were studied in a water maze 7 months postradiation therapy. Results: Prior to radiation therapy, both groups were similar. No difference was found 1 and 3 months postradiation therapy. At 6-7 months postradiation therapy, irradiated rats had a much lower percentage of avoidance than controls for one-way avoidance (23% vs. 55%, p ≤ 0.001) and two-way avoidance (18% vs. 40%, p ≤ 0.01). Seven months postradiation therapy the reaction time was increased (press-lever avoidance, 11.20 s vs. 8.43 s, p ≤ 0.05) and the percentage of correct response was lower (water maze, 53% vs. 82%) in irradiated rats compared with controls. Pathological examination did not demonstrate abnormalities of the irradiated brains at the light microscopic level. Conclusion: Behavioral dysfunction affecting mainly memory can be demonstrated following conventional radiation therapy in old rats. This model can be used to study the pathogenesis of radiation-induced cognitive changes

  16. Radiation-induced cognitive dysfunction: An experimental model in the old rat

    International Nuclear Information System (INIS)

    Lamproglou, I.; Chen, Q.M.; Poisson, M.

    1995-01-01

    To develop a model of radiation-induced behavioral dysfunction. A course of whole brain radiation therapy (30 Gy/10 fractions/12 days) was administered to 26 Wistar rats ages 16-27 months, while 26 control rats received sham irradiation. Sequential behavioral studies including one-way avoidance, two-way avoidance, and a standard operant conditioning method (press-lever avoidance) were undertaken. In addition, rats were studied in a water maze 7 months postradiation therapy. Prior to radiation therapy, both groups were similar. No difference was found 1 and 3 months postradiation therapy. At 6-7 months postradiation therapy, irradiated rats had a much lower percentage of avoidance than controls for one-way avoidance (23% vs. 55%, p ≤ 0.001) and two-way avoidance (18% vs. 40%, p ≤ 0.01). Seven months postradiation therapy the reaction time was increased (press-lever avoidance, 11.20 s vs. 8.43 s, p ≤ 0.05) and the percentage of correct response was lower (water maze, 53% vs. 82%) in irradiated rats compared with controls. Pathological examination did not demonstrate abnormalities of the irradiated brains at the light microscopic level. Behavioral dysfunction affecting mainly memory can be demonstrated following conventional radiation therapy in old rats. This model can be used to study the pathogenesis of radiation-induced cognitive changes. 15 refs., 3 figs., 1 tab

  17. Spontaneous and x-irradiation induced carcinomas of small intestine in Wistar-Furth rats

    Energy Technology Data Exchange (ETDEWEB)

    Maeura, Y; Kosaki, G; Kitamura, H [Osaka Univ. (Japan). Faculty of Medicine; Nagatomo, T

    1980-04-01

    Spontaneous carcinoma of the small intestine in Wistar-Furth (WF) rats and carcinoma of the small intestine induced by local x-ray irradiation to the abdomen of WF rats without carcinoma were observed, and x-ray sensitivity of the small intestine mucosa was reported. Out of 19 rats with spontaneous carcinoma of the small intestine, 18 also had carcinoma of the colon, and 4 also had gastric cancer. They already had spontaneous carcinoma of the small intestine within 2 weeks after their birth, and the ratio of female and male was 13 : 6. Histological type of this carcinoma in all 19 rats was highly differentiated adenocarcinoma, and small intestine epithelium around carcinoma presented atypical epithelium. As to mice without carcinoma, x-ray, 1,000 R, 1,500 R, and 2,000 R, was irradiated to the abdomen of Sprague-Dawley (SD) and WF rats. In the irradiation with 1,000 R, carcinogenesis was not found in rats of both strains. In the irradiation with 1,500 R, carcinogenesis was hardly found, but in the irradiation with 2,000 R, carcinoma of small intestine occurred in 5 of 17 rats 15 weeks after the irradiation, 9 of 19 rats 25 weeks after the irradiation, and 9 of 14 rats 35 weeks after the irradiation. Histological type of carcinoma in irradiated rats was highly differentiated adenocarcinoma. The incidence of carcinoma in irradiated rats was higher in WF rats than SD rats through the course after the irradiation, which suggested that x-ray sensitivity of WF rats was higher than that of SD rats. Therefore, carcinoma of the small intestine in irradiated mice seemed to be induced by x-ray.

  18. A terrified-sound stress induced proteomic changes in adult male rat hippocampus.

    Science.gov (United States)

    Yang, Juan; Hu, Lili; Wu, Qiuhua; Liu, Liying; Zhao, Lingyu; Zhao, Xiaoge; Song, Tusheng; Huang, Chen

    2014-04-10

    In this study, we investigated the biochemical mechanisms in the adult rat hippocampus underlying the relationship between a terrified-sound induced psychological stress and spatial learning. Adult male rats were exposed to a terrified-sound stress, and the Morris water maze (MWM) has been used to evaluate changes in spatial learning and memory. The protein expression profile of the hippocampus was examined using two-dimensional gel electrophoresis (2DE), matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, and bioinformatics analysis. The data from the MWM tests suggested that a terrified-sound stress improved spatial learning. The proteomic analysis revealed that the expression of 52 proteins was down-regulated, while that of 35 proteins were up-regulated, in the hippocampus of the stressed rats. We identified and validated six of the most significant differentially expressed proteins that demonstrated the greatest stress-induced changes. Our study provides the first evidence that a terrified-sound stress improves spatial learning in rats, and that the enhanced spatial learning coincides with changes in protein expression in rat hippocampus. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. Ectopic Liver Tissue Formation in Rats with Induced Liver Fibrosis

    Directory of Open Access Journals (Sweden)

    Bauyrzhan Umbayev

    2014-12-01

    Full Text Available Introduction: The possible alternative approach to whole-organ transplantation is a cell-based therapy, which can also be used as a "bridge" to liver transplantation.  However, morphological and functional changes in the liver of patients suffering from chronic liver fibrosis and cirrhosis restrict the effectiveness of direct cell transplantation. Therefore, extra hepatic sites for cell transplantation, including the spleen, pancreas, peritoneal cavity, and subrenal capsule, could be a useful therapeutic approach for compensation of liver functions. However, a method of transplantation of hepatocytes into ectopic sites is needed to improve hepatocyte engraftment. Previously published data has demonstrated that mouse lymph nodes can support the engraftment and proliferation of hepatocytes as ES and rescue Fah mice from lethal liver failure. Thus, the aim of the study was to evaluate the engraftment of i.p. injected allogeneic hepatocytes into extra hepatic sites in albino rats with chemically induced liver fibrosis (LF. Materials and methods: Albino rats were randomly divided into 4 groups: (1 intact group (n = 18; (2 rats with induced LF (n = 18; (3 rats with induced LF and transplanted with hepatocytes (n = 18; (4 as a control, rats were treated with cyclosporine A only (n = 18. In order to prevent an immune response, groups 2 and 3 were subjected to immunosuppression by cyclosporine A (25 mg/kg per day. LF was induced using N-nitrosodimethylamine (NDMA, i.p., 10 mg/kg, three times a week for 4 weeks and confirmed by histological analysis of the liver samples. Hepatocytes transplantation (HT was performed two days after NDMA exposure cessation by i.p. injection of 5×106 freshly isolated allogeneic hepatocytes. Liver function was assessed by quantifying blood biochemical parameters (ALT, AST, GGT, total protein, bilirubin, and albumin at 1 week, 1 month, and 2 months after hepatocytes transplantation (HT. To confirm a hepatocytes

  20. Peritoneal lavage with povidone-iodine solution in colorectal cancer-induced rats.

    Science.gov (United States)

    Song, Hua-Li; Zhang, Dong-Mei; Wen, Heng; Wang, Meng; Zhao, Na; Gao, Yu-Hua; Ding, Ni

    2018-08-01

    Although peritoneal lavage with povidone-iodine (PVPI) is frequently performed after surgery on the gastrointestinal tract, the effects of PVPI on the intestinal epithelial barrier are unknown. The purpose of this study was to investigate the effects of abdominal irrigation with PVPI on the intestinal epithelial barrier in a colorectal cancer (CRC)-induced rat model. The CRC model was induced in rats with azoxymethane and dextran sodium sulfate. Next, a total of 24 male CRC-induced rats were randomly divided into three groups (n = 8): (1) a sham-operated group, (2) an NS group (peritoneal lavage 0.9% NaCl), and (3) a PVPI group (peritoneal lavage with 0.45%-0.55% PVPI). The mean arterial pressure was continuously monitored throughout the experiment. The levels of plasma endotoxin and D-lactate, blood gases, and protein concentration were measured. The ultrastructural changes of the epithelial tight junctions were observed by transmission electron microscopy. The mean arterial pressure after peritoneal lavage was lower in the PVPI group than that in the NS group. The protein concentration and levels of endotoxin and D-lactate were higher in the PVPI group than they were in the PVPI group. In addition, PVPI treatment resulted in a markedly severe metabolic acidosis and intestinal mucosal injury compared with NS rats. Peritoneal lavage with PVPI dramatically compromises the integrity of the intestinal mucosa barrier and causes endotoxin shock in CRC rats. It is unsafe for clinical applications to include peritoneal lavage with PVPI in colorectal operations. Copyright © 2018 Elsevier Inc. All rights reserved.

  1. The roles of age at puberty and energy restriction in sow reproductive longevity: a genomic perspective

    Science.gov (United States)

    Approximately 50% of sows are culled annually with more than one third due to poor fertility. Our research demonstrated that age at puberty is an early pre-breeding indicator of reproductive longevity. Age at puberty can be measured early in life, has a moderate heritability and is negatively correl...

  2. Is puberty a risk factor for back pain in the young? a systematic critical literature review

    DEFF Research Database (Denmark)

    Lardon, A.; Leboeuf-Yde, C.; Le Scanff, C.

    2014-01-01

    the increasing stages of puberty and the subsequent prevalence of back pain? 4) Is there a temporal link between puberty and back pain? DESIGN: A systematic critical literature review. METHODS: Systematic searches were made in March 2014 in PubMed, Embase, CINAHL and PsycINFO including longitudinal or cross...

  3. Effect of irradiation on the periodontal tissues in streptozotocin-induced diabetic rats

    International Nuclear Information System (INIS)

    Park, Dong Sin; Hwang, Eui Hwan; Lee, Sang Rae

    2005-01-01

    To observe the histopathological changes in the periodontal tissues of mandibular molars in streptozotocin-induced diabetic rats after irradiation. The male Sprague-Dawley rats weighing approximately 250 gm were divided into four groups; control, diabetes, irradiation, and diabetes - irradiation groups. Diabetes mellitus was induced in the rats by injecting streptozotocin. Rats in the control and irradiation groups were injected with citrate buffer only. After 5 days, the head and neck region of the rats in irradiation and diabetes - irradiation groups were irradiated with a single absorbed dose of 10 Gy. All the rats were sacrificed at 3, 7, 14, 21, and 28 days after irradiation. The specimen including the mandibular molars were sectioned and observed using a histopathological method. In the diabetes group, osteoclastic activity was observed in the alveolar bone and the root throughout the period of experiment. Also, osteoblastic and fibroblastic activities were markedly decreased. In the irradiation group, the osteoclasts were observed in the alveolar bone and the dilated capillaries were increased in the early experimental phases. However, vigorous osteoblastic activity was noted in the late experimental phases. In the diabetes- irradiation group, osteoblastic activity in the alveolar bone and the root was observed in the early experimental phases. However, there were no resorption and osteoblastic activity in the alveolar bone and the root in the late experimental phases, and obvious atrophic change of fibrous tissues was noted. This experiment suggests that osteoblastic activity was caused by irradiation in the late experimental phases, but atrophic change of the periodontal ligament tissues was induced after irradiation in diabetic state.

  4. Effect of irradiation on the temporomandibular joint in streptozotocin-induced diabetic rat

    Energy Technology Data Exchange (ETDEWEB)

    Ahn, Ki Dong; Hwang, Eui Hwan; Lee, Sang Rae [Kyunghee University College of Medicine, Seoul (Korea, Republic of)

    2004-06-15

    To investigate the histopathological changes in the temporomandibular joint in streptozotocin-induced diabetic rat following irradiation. Sprague-Dawley rats weighing about 250 gm were divided into three groups: control, diabetic, and diabetic-irradiated groups. Diabetes mellitus was induced in the rats by injecting streptozotocin. Rats in the control group were injected with citrate buffer only. After 5 days, the head and neck region of the rats in diabetic-irradiated group were irradiated with single absorbed dose of 10 Gy. The rats were killed at 1, 3, 7, 14, 21, and 28 days after irradiation. The specimen including the temporomandibular joint were sectioned and observed using a histopathological method. In the diabetic group, severe bone resorption in the mandibular condyle was observed throughout the period of experiment. Necrosis of bone marrow and trabeculae was observed at 28 days after diabetic state. Atrophy and fibrosis in the retrodiscal tissue was gradually progressed during the time of the experiment. In the diabetic-irradiated group, severe bone resorption in the mandibular condyle was observed during the early experimental phases, but regeneration of bone marrow was initiated at 14 days after diabetic state and irradiation. Also, calcification of abnormal trabeculae was observed at 28 days after diabetic state and irradiation. The retrodiscal tissue was degenerated in the early experimental phases, but it had been gradually regenerated during the experimental time. This experiment suggests that bone resorption and degeneration in the mandibular condyle are caused by the induction of diabetes, and abnormal bone formation is induced after irradiation in diabetic state.

  5. Effect of irradiation on the temporomandibular joint in streptozotocin-induced diabetic rat

    International Nuclear Information System (INIS)

    Ahn, Ki Dong; Hwang, Eui Hwan; Lee, Sang Rae

    2004-01-01

    To investigate the histopathological changes in the temporomandibular joint in streptozotocin-induced diabetic rat following irradiation. Sprague-Dawley rats weighing about 250 gm were divided into three groups: control, diabetic, and diabetic-irradiated groups. Diabetes mellitus was induced in the rats by injecting streptozotocin. Rats in the control group were injected with citrate buffer only. After 5 days, the head and neck region of the rats in diabetic-irradiated group were irradiated with single absorbed dose of 10 Gy. The rats were killed at 1, 3, 7, 14, 21, and 28 days after irradiation. The specimen including the temporomandibular joint were sectioned and observed using a histopathological method. In the diabetic group, severe bone resorption in the mandibular condyle was observed throughout the period of experiment. Necrosis of bone marrow and trabeculae was observed at 28 days after diabetic state. Atrophy and fibrosis in the retrodiscal tissue was gradually progressed during the time of the experiment. In the diabetic-irradiated group, severe bone resorption in the mandibular condyle was observed during the early experimental phases, but regeneration of bone marrow was initiated at 14 days after diabetic state and irradiation. Also, calcification of abnormal trabeculae was observed at 28 days after diabetic state and irradiation. The retrodiscal tissue was degenerated in the early experimental phases, but it had been gradually regenerated during the experimental time. This experiment suggests that bone resorption and degeneration in the mandibular condyle are caused by the induction of diabetes, and abnormal bone formation is induced after irradiation in diabetic state.

  6. Antihypertensive effect of rhizome part of Acorus calamus on renal artery occlusion induced hypertension in rats

    Directory of Open Access Journals (Sweden)

    Pinal Patel

    2012-05-01

    Full Text Available Objective: The rhizomes part of Acorus calamus (AC having the calcium inhibitory effect and diuretic activity which may potentiate Na+ excretion in hypertension induced by occlusion of renal artery. Therefore this study was aimed to investigate the effect of AC on experimentally induced hypertension. Methods: Hypertension in rats was induced by clamping the left renal artery for 4h by arterial clamp (2K1C. At the end of experiment animal were anesthetized with ketamine (50 mg/kg. Carotid artery was cannulated which was connected to pressure transducer for estimation of blood pressure. Results: Ethyl acetate extract of Acorus calamus rhizomes (EAAC treated rats that underwent hypertension, demonstrated significant (P < 0.01 lower systolic blood pressure and diastolic blood pressure when compared with 2K1C rats indicated blood pressure lowering activity. Plasma renin activity was significantly (P < 0.05 decreased in EAAC treated rats compared to 2K1C rats. EAAC treated rats that underwent hypertension demonstrated significant (P < 0.01 lower mean blood urea nitrogen and creatinine when compared with 2K1C rats. Lipid peroxidation was significantly (P < 0.001 decreased, where as nitric oxide level in tissue was significantly elevated in EAAC treated rats. Antioxidant enzymes like glutathione, superoxide dismutase and catalase were significantly (P < 0.05, P < 0.01, P < 0.001 increased in EAAC treated rats when compared to 2K1C rats. Conclusions: In conclusions, EAAC treatment attenuated renal artery occlusion induced hypertension via nitric oxide generation and decreases the plasma renin activity.

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

    Science.gov (United States)

    Linares, Rosa; Hernández, Denisse; Morán, Carolina; Chavira, Roberto; Cárdenas, Mario; Domínguez, Roberto; Morales-Ledesma, Leticia

    2013-07-17

    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. 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. 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. 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.

  8. Metabolic enhancer piracetam attenuates rotenone induced oxidative stress: a study in different rat brain regions.

    Science.gov (United States)

    Verma, Dinesh Kumar; Joshi, Neeraj; Raju, Kunumuri Sivarama; Wahajuddin, Muhammad; Singh, Rama Kant; Singh, Sarika

    2015-01-01

    Piracetam is clinically being used nootropic drug but the details of its neuroprotective mechanism are not well studied. The present study was conducted to assess the effects of piracetam on rotenone induced oxidative stress by using both ex vivo and in vivo test systems. Rats were treated with piracetam (600 mg/kg b.w. oral) for seven constitutive days prior to rotenone administration (intracerebroventricular, 12 µg) in rat brain. Rotenone induced oxidative stress was assessed after 1 h and 24 h of rotenone administration. Ex vivo estimations were performed by using two experimental designs. In one experimental design the rat brain homogenate was treated with rotenone (1 mM, 2 mM and 4 mM) and rotenone+piracetam (10 mM) for 1 h. While in second experimental design the rats were pretreated with piracetam for seven consecutive days. On eighth day the rats were sacrificed, brain homogenate was prepared and treated with rotenone (1 mM, 2 mM and 4mM) for 1h. After treatment the glutathione (GSH) and malondialdehyde (MDA) levels were estimated in brain homogenate. In vivo study showed that pretreatment of piracetam offered significant protection against rotenone induced decreased GSH and increased MDA level though the protection was region specific. But the co-treatment of piracetam with rotenone did not offer significant protection against rotenone induced oxidative stress in ex vivo study. Whereas ex vivo experiments in rat brain homogenate of piracetam pretreated rats, showed the significant protection against rotenone induced oxidative stress. Findings indicated that pretreatment of piracetam significantly attenuated the rotenone induced oxidative stress though the protection was region specific. Piracetam treatment to rats led to its absorption and accumulation in different brain regions as assessed by liquid chromatography mass spectrometry/mass spectrometry. In conclusion, study indicates the piracetam is able to enhance the antioxidant capacity in brain cells

  9. Phosphorus-31 magnetic resonance spectroscopy of experimentally induced arthritis in rats

    International Nuclear Information System (INIS)

    Blatter, D.D.

    1987-01-01

    Phosphorus-31 magnetic resonance spectroscopy (MRS) of the hind paws of rats was performed at 1.5 Tesla before and during the course of an experimentally-induced inflammatory arthritis. Arthritis was induced by daily subcutaneous administration of 6-sulfanilamidoindazole, an antibacterial sulfa known to produce an acute, self-limited arthritis and periarthritis in the hind paws of rats. Phosphorus-31 spectra obtained after the development of clinical arthritis showed a significant (p 31 P MRS may permit evaluation of the severity of an inflammatory arthritis with greater accuracy than the bony changes definable by plain roentgenograms. (orig.)

  10. Vitamin-C protect ethanol induced apoptotic neuro degeneration in postnatal rat brain

    International Nuclear Information System (INIS)

    Naseer, M.I.; Najeebullah; Ikramullah; Zubair, H.; Hassan, M.; Yang, B.C.

    2010-01-01

    Objective: To evaluate ethanol effects to induced activation of caspsae-3, and to observe the protective effects of Vitamin C (vit-C) on ethanol-induced apoptotic neuro degeneration in rat cortical area of brain. Methodology: Administration of a single dose of ethanol in 7-d postnatal (P7) rats triggers activation of caspase-3 and widespread apoptotic neuronal death. Western blot analysis, cells counting and Nissl staining were used to elucidate possible protective effect of vit-C against ethanol-induced apoptotic neuro degeneration in brain. Results: The results showed that ethanol significantly increased caspase-3 expression and neuronal apoptosis. Furthermore, the co-treatment of vit-C along with ethanol showed significantly decreased expression of caspase-3 as compare to control group. Conclusion: Our findings indicate that vit-C can prevent some of the deleterious effect of ethanol on developing rat brain when given after ethanol exposure and can be used as an effective protective agent for Fetal Alcohol Syndrome (FAS). (author)

  11. Serum glucose and lipid levels in alloxan-induced diabetic rats ...

    African Journals Online (AJOL)

    Effect of Aloe barbadensis Miller juice extract on serum glucose and lipids in alloxan-induced diabetic rats was investigated. Diabetes was induced by intraperitoneal injection of 150mg/kg alloxan in 5% solution. Diabetes was confirmed 72 hours after alloxan injection, if fasting blood glucose (FBG) was equal to or greater ...

  12. Lycopene Protects the Diabetic Rat Kidney Against Oxidative Stress-mediated Oxidative Damage Induced by Furan

    Directory of Open Access Journals (Sweden)

    Dilek Pandir

    2016-01-01

    Full Text Available Furan is a food and environmental contaminant and a potent carcinogen in animals. Lycopene is one dietary carotenoid found in fruits such as tomato, watermelon and grapefruit. The present study was designed to explore the protective effect of lycopene against furan-induced oxidative damage in streptozotocin (STZ-induced diabetic rat kidney. At the end of the experimental period (28 days, we found that lycopene markedly decreased the malondialdehide (MDA levels in the kidney, urea, uric acid and creatinine levels in the serum of furan-treated rats. The increase of histopathology in the kidney of furan-treated rats were effectively suppressed by lycopene. Furthermore, lycopene markedly restored superoxide dismutase (SOD, catalase (CAT, glutathione peroxidase (GPx and glutathione-S-transferase (GST activities in the kidney of furan-treated rats. In conclusion, these results suggested that lycopene could protect the rat kidney against furan-induced injury by improving renal function, attenuating histopathologic changes, reducing MDA production and renewing the activities of antioxidant enzymes.

  13. Exogenous agmatine has neuroprotective effects against restraint-induced structural changes in the rat brain

    Science.gov (United States)

    Zhu, Meng-Yang; Wang, Wei-Ping; Cai, Zheng-Wei; Regunathan, Soundar; Ordway, Gregory

    2009-01-01

    Agmatine is an endogenous amine derived from decarboxylation of arginine catalysed by arginine decarboxylase. Agmatine is considered a novel neuromodulator and possesses neuroprotective properties in the central nervous system. The present study examined whether agmatine has neuroprotective effects against repeated restraint stress-induced morphological changes in rat medial prefrontal cortex and hippocampus. Sprague-Dawley rats were subjected to 6 h of restraint stress daily for 21 days. Immunohistochemical staining with β-tubulin III showed that repeated restraint stress caused marked morphological alterations in the medial prefrontal cortex and hippocampus. Stress-induced alterations were prevented by simultaneous treatment with agmatine (50 mg/kg/day, i.p.). Interestingly, endogenous agmatine levels, as measured by high-performance liquid chromatography, in the prefrontal cortex and hippocampus as well as in the striatum and hypothalamus of repeated restraint rats were significantly reduced as compared with the controls. Reduced endogenous agmatine levels in repeated restraint animals were accompanied by a significant increase of arginine decarboxylase protein levels in the same regions. Moreover, administration of exogenous agmatine to restrained rats abolished increases of arginine decarboxylase protein levels. Taken together, these results demonstrate that exogenously administered agmatine has neuroprotective effects against repeated restraint-induced structural changes in the medial prefrontal cortex and hippocampus. These findings indicate that stress-induced reductions in endogenous agmatine levels in the rat brain may play a permissive role in neuronal pathology induced by repeated restraint stress. PMID:18364017

  14. Effect of Saraca asoca (Asoka) on estradiol-induced keratinizing metaplasia in rat uterus.

    Science.gov (United States)

    Shahid, Adangam Purath; Salini, Sasidharan; Sasidharan, Nanu; Padikkala, Jose; Raghavamenon, Achuthan Chathrattil; Babu, Thekkekara Devassy

    2015-09-01

    Estrogen-mediated uterus endometrium instability is considered as one of the etiological factors in dysfunctional uterine bleeding (DUB) and uterine cancer. Saraca asoca (Family: Fabaceae) and its fermented preparation, Asokarishta, are extensively used as uterine tonic to treat gynecological disorders in Ayurveda. The present study evaluated the effect of S. asoca (Asoka) on estrogen-induced endometrial thickening of rat uterus. Endometrial thickening was induced by intraperitoneal injection of estradiol (20 μg/kg b.wt) to 8-day-old immature rats for alternate 5 days. Methanolic extract (200 mg/kg b. wt) from S. asoca bark was given orally along with estradiol. Uterus endometrial thickening was analyzed histopathologically and serum estrogen level by radioimmunoassay (RIA). Cyclooxygenase (COX-2) expression in rat uterus was also estimated by Western blot. Anti-inflammatory activity of the extract was analyzed by formalin- and carrageenan-elicited paw edema models in mouse. Uterus endometrium proliferation and keratinized metaplasia with seven to eight stratified epithelial layers on day 16 was observed in rats administered with estradiol. Treatment with S. asoca reduced the thickening to two to four layers and the serum estrogen level diminished significantly to 82.9±12.87 pg/mL compared to rats administered with estrogen alone (111.2±10.68 pg/mL). A reduction of formalin- and carrageenan-induced paw edema in mouse by S. asoca extract was observed. Lower level of lipopolysaccharides (LPS)-induced COX-2 enzyme in rat uterus by the extract further confirms its anti-inflammatory activity. Present study reveals the antiproliferative and antikeratinizing effects of S. asoca in uterus endometrium possibly through its anti-estrogenic and anti-inflammatory properties.

  15. Autophagy in muscle of glucose-infusion hyperglycemia rats and streptozotocin-induced hyperglycemia rats via selective activation of m-TOR or FoxO3.

    Directory of Open Access Journals (Sweden)

    Pengfei Lv

    Full Text Available Autophagy is a conserved process in eukaryotes required for metabolism and is involved in diverse diseases. To investigate autophagy in skeletal muscle under hyperglycemia status, we established two hyperglycemia-rat models that differ in their circulating insulin levels, by glucose infusion and singe high-dose streptozotocin injection. We then detected expression of autophagy related genes with real-time PCR and western blot. We found that under hyperglycemia status induced by glucose-infusion, autophagy was inhibited in rat skeletal muscle, whereas under streptozotocin-induced hyperglycemia status autophagy was enhanced. Meanwhile, hyperglycemic gastrocnemius muscle was more prone to autophagy than soleus muscle. Furthermore, inhibition of autophagy in skeletal muscle in glucose-infusion hyperglycemia rats was mediated by the m-TOR pathway while m-TOR and FoxO3 both contributed to enhancement of autophagy in gastrocnemius muscle in streptozotocin-induced hyperglycemia rats. These data shows that insulin plays a relatively more important role than hyperglycemia in regulating autophagy in hyperglycemia rat muscle through selectively activating the m-TOR or FoxO3 pathway in a fiber-selective manner.

  16. Hibiscus sabdariffa calyx palliates insulin resistance, hyperglycemia, dyslipidemia and oxidative rout in fructose-induced metabolic syndrome rats.

    Science.gov (United States)

    Ajiboye, Taofeek O; Raji, Hikmat O; Adeleye, Abdulwasiu O; Adigun, Nurudeen S; Giwa, Oluwayemisi B; Ojewuyi, Oluwayemisi B; Oladiji, Adenike T

    2016-03-30

    The effect of Hibiscus sabdariffa calyx extract was evaluated in high-fructose-induced metabolic syndrome rats. Insulin resistance, hyperglycemia, dyslipidemia and oxidative rout were induced in rats using high-fructose diet. High-fructose diet-fed rats were administered 100 and 200 mg kg(-1) body weight of H. sabdariffa extract for 3 weeks, starting from week 7 of high-fructose diet treatment. High-fructose diet significantly (P Hibiscus extract. Overall, aqueous extract of H. sabdariffa palliates insulin resistance, hyperglycemia, dyslipidemia and oxidative rout in high-fructose-induced metabolic syndrome rats. © 2015 Society of Chemical Industry.

  17. Environmental factors and puberty timing: Expert panel research needs

    Science.gov (United States)

    An expert panel reviewed the literature on endocrine disrupting chemicals (EDCs), body size and puberty. The panel concluded that available experimental animal and human data support a possible role of EDCs and body size in relation to alterations in pubertal onset and progressio...

  18. Age and body weight of Moroccan local cattle at puberty: Effect of season

    International Nuclear Information System (INIS)

    Mazouz, A.; Asri, A.

    1988-01-01

    Moroccan local cattle are a distinct breed comprising almost 90% of the total cattle population of 2.5 million. The age and the body weight of some 1662 heifers attaining puberty were determined under two production systems by monitoring plasma progesterone levels as an indicator of the first ovulation. The effect of season on these parameters was also studied. Ovarian cyclicity commenced in 50% of heifers by the age of 16.5 months and at a body weight of 144 kg (70% of the mature body weight). The time of puberty was correlated with both age and body weight and was influenced by both the season of the year at which puberty was reached and the system of rearing. The mean age at which behavioural oestrus was first observed and the heifer inseminated was 26.5 months. Fifty per cent of 546 heifers were pregnant by 27 months of age. (author). 18 refs, 7 figs

  19. Agmatine improves renal function in gentamicin-induced nephrotoxicity in rats.

    Science.gov (United States)

    El-Kashef, Dalia H; El-Kenawi, Asmaa E; Abdel Rahim, Mona; Suddek, Ghada M; Salem, Hatem A

    2016-03-01

    The present study was designed to explore the possible protective effects of agmatine, a known nitric oxide (NO) synthase inhibitor, against gentamicin-induced nephrotoxicity in rats. For this purpose, we quantitatively evaluated gentamicin-induced renal structural and functional alterations using histopathological and biochemical approaches. Furthermore, the effect of agmatine on gentamicin-induced hypersensitivity of urinary bladder rings to acetylcholine (ACh) was evaluated. Twenty-four male Wistar albino rats were randomly divided into 3 groups, namely control, gentamicin (100 mg/kg, i.p.), and gentamicin plus agmatine (40 mg/kg, orally). At the end of the study, all rats were sacrificed and then blood and urine samples and kidneys were taken. Administration of agmatine significantly decreased kidney/body mass ratio, serum creatinine, lactate dehydrogenase (LDH), renal malondialdehyde (MDA), myeloperoxidase (MPO), NO, and tumor necrosis factor-alpha (TNF-α) while it significantly increased creatinine clearance and renal superoxide dismutase (SOD) activity when compared with the gentamicin-treated group. Additionally, agmatine ameliorated tissue morphology as evidenced by histological evaluation and reduced the responses of isolated bladder rings to ACh. Our study indicates that agmatine administration with gentamicin attenuates oxidative-stress associated renal injury by reducing oxygen free radicals and lipid peroxidation, restoring NO level and inhibiting inflammatory mediators such as TNF-α.

  20. Age and radiation sensitivity of rat mammary clonogenic cells

    International Nuclear Information System (INIS)

    Shimada, Yoshiya; Yasukawa-Barnes, J.; Kim, R.Y.; Gould, M.N.; Clifton, K.H.

    1994-01-01

    The relative risk of breast cancer is very high among women who were exposed to ionizing radiation during or before puberty. In the current studies, the surviving fractions of clonogenic mammary cells of groups of virgin rats were estimated after single exposures to 137 Cs γ rays at intervals from 1 to 12 weeks after birth. The radiosensitivity of clonogens from prepubertal rats was high and changed with the onset of puberty at between 4 and 6 weeks of age. By this time, the increase in the size of the clonogenic cell subpopulation was slowing and differentiation of terminal mammary end buds and alveolar structures was occurring. Analysis of the relationship of clonogen survival and radiation dose according to the α/β model showed that the exponential αD term predominated at the second and fourth weeks of age. By the eighth week of age, the βD 2 term had come to predominate and the survival curve had a pronounced initial convex shoulder. Further experiments are required to determine whether there is an association between the high sensitivity of the prepubertal and pubertal mammary clonogens to radiation killing and a high susceptibility to radiogenic initiation of cancer. 24 refs., 4 figs., 1 tab

  1. Putrescine treatment reverses α-tocopherol-induced desynchronization of polyamine and retinoid metabolism during rat liver regeneration

    Directory of Open Access Journals (Sweden)

    Lourdes Sánchez-Sevilla

    2016-10-01

    Full Text Available Abstract Background The pre-treatment with α-tocopherol inhibits progression of rat liver proliferation induced by partial hepatectomy (PH, by decreasing and/or desynchronizing cyclin D1 expression and activation into the nucleus, activation and nuclear translocation of STAT-1 and -3 proteins and altering retinoid metabolism. Interactions between retinoic acid and polyamines have been reported in the PH-induced rat liver regeneration. Therefore, we evaluated the effect of low dosage of α-tocopherol on PH-induced changes in polyamine metabolism. Methods This study evaluated the participation of polyamine synthesis and metabolism during α-tocopherol-induced inhibition of rat liver regeneration. In PH-rats (Wistar treated with α-tocopherol and putrescine, parameters indicative of cell proliferation, lipid peroxidation, ornithine decarboxylase expression (ODC, and polyamine levels, were determined. Results Pre-treatment with α-tocopherol to PH-animals exerted an antioxidant effect, shifting earlier the increased ODC activity and expression, temporally affecting polyamine synthesis and ornithine metabolism. Whereas administration of putrescine induced minor changes in PH-rats, the concomitant treatment actually counteracted most of adverse actions exerted by α-tocopherol on the remnant liver, restituting its proliferative potential, without changing its antioxidant effect. Putrescine administration to these rats was also associated with lower ODC expression and activity in the proliferating liver, but the temporally shifting in the amount of liver polyamines induced by α-tocopherol, was also “synchronized” by the putrescine administration. The latter is supported by the fact that a close relationship was observed between fluctuations of polyamines and retinoids. Conclusions Putrescine counteracted most adverse actions exerted by α-tocopherol on rat liver regeneration, restoring liver proliferative potential and restituting the decreased

  2. Intestinal metaplasia induced by x-irradiation in different strains of rats

    International Nuclear Information System (INIS)

    Watanabe, Hiromitsu; Naito, Masashi; Kawashima, Kengo; Ito, Akihiro

    1985-01-01

    Attempts were made to examine strain differences in the susceptibility of rats to intestinal metaplasia induced by X-irradiation. The gastric regions of 4 inbred male rats (SHR, F344, WKY, and LEW strains) in 5-week-old and 2 random bred male rats (SD, and WIS strains) were irradiated with a total dose of 20 Gy X-ray given in two equal fractions separated by three days. Upon sacrifice at 6 months after the last irradiation, the number of intestinal metaplastic crypts with positive reaction to alkaline phosphatase (ALP) appeared highest in the SHR and lowest in the WIS rats. Morphologically, the number of crypts with intestinal metaplasia in whole glandular stomachs of SHR, WIS, F344, and SD rats were higher than those in WKY and LEW rats. In the pyloric gland, it was highest in WIS rats, while in the fundic gland it was highest in SHR rats. The results show that the appearance and location of intestinal metaplasia by X-irradiation are greatly influenced by the strain of the rat. (author)

  3. Geraniin Protects High-Fat Diet-Induced Oxidative Stress in Sprague Dawley Rats

    Directory of Open Access Journals (Sweden)

    Alexis Panny Y. S. Chung

    2018-03-01

    Full Text Available Geraniin, a hydrolysable polyphenol derived from Nephelium lappaceum L. fruit rind, has been shown to possess significant antioxidant activity in vitro and recently been recognized for its therapeutic potential in metabolic syndrome. This study investigated its antioxidative strength and protective effects on organs in high-fat diet (HFD-induced rodents. Rats were fed HFD for 6 weeks to induce obesity, followed by 10 and 50 mg/kg of geraniin supplementation for 4 weeks to assess its protective potential. The control groups were maintained on standard rat chows and HFD for the same period. At the 10th week, oxidative status was assessed and the pancreas, liver, heart and aorta, kidney, and brain of the Sprague Dawley rats were harvested and subjected to pathological studies. HFD rats demonstrated changes in redox balance; increased protein carbonyl content, decreased levels of superoxide dismutase, glutathione peroxidase, and glutathione reductase with a reduction in the non-enzymatic antioxidant mechanisms and total antioxidant capacity, indicating a higher oxidative stress (OS index. In addition, HFD rats demonstrated significant diet-induced changes particularly in the pancreas. Four-week oral geraniin supplementation, restored the OS observed in the HFD rats. It was able to restore OS biomarkers, serum antioxidants, and the glutathione redox balance (reduced glutathione/oxidized glutathione ratio to levels comparable with that of the control group, particularly at dosage of 50 mg geraniin. Geraniin was not toxic to the HFD rats but exhibited protection against glucotoxicity and lipotoxicity particularly in the pancreas of the obese rodents. It is suggested that geraniin has the pharmaceutical potential to be developed as a supplement to primary drugs in the treatment of obesity and its pathophysiological sequels.

  4. Wheat Germ Oil Attenuates Gamma Radiation- Induced Skeletal Muscles Damage in Rats

    International Nuclear Information System (INIS)

    Said, U.Z.; Saada, H.N.; Shedid, Sh.M.; Mahdy, E.M.E.; Shousha, W.Gh.

    2008-01-01

    Muscular strength is important in sport as well as in daily activities. Exposure to ionizing radiation is thought to increase oxidative stress and damage muscle tissue. Wheat germ oil is a natural unrefined vegetable oil. It is an excellent source of vitamin E, octacosanol, linoleic and linolenic essential fatty acids, which may be beneficial in neutralizing the free oxygen radicals. The present study was designed to investigate the efficacy of wheat germ oil, on radiation-induced oxidative damage in rats skeletal muscle. Wheat germ oil was supplemented orally via gavages to rats at a dose of 54 mg/ kg body weight/day for 14 successive days pre- and 7 post-exposure to 5 Gy (one shot dose) of whole body gamma irradiation. Animals were sacrificed 7, 14 and 21 days post radiation exposure. The results revealed that whole body gamma-irradiation of rats induces oxidative stress in skeletal muscles obvious by significant elevation in the level of thiobarbituric acid reactive substances (TBARS) associated with significant decreases in the content of reduced glutathione (GSE1), as well as decreases in superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) activities. Irradiated rats showed, also, significant decreases in creatine phosphokinase (CPK), glutamate dehydrogenase (GDH) and glucose-6-phosphate dehydrogenase (G-6-PD) activities. Furthermore, total iron, total copper and total calcium levels were significantly increased in skeletal muscles of irradiated rats group compared to control group. Wheat germ oil treated-irradiated rats showed significantly less sever damage and remarkable improvement in all the measured parameters, compared to irradiated rats. It could be concluded that wheat germ oil by attenuating radiation induced oxidative stress might play a role in maintaining skeletal muscle integrity

  5. Moringa oleifera-based diet protects against nickel-induced hepatotoxicity in rats

    Science.gov (United States)

    Stephen Adeyemi, Oluyomi; Sokolayemji Aroge, Cincin; Adewumi Akanji, Musbau

    2017-01-01

    Multiple health-promoting effects have been attributed to the consumption of Moringa oleifera leaves, as part of diet without adequate scientific credence. This study evaluated the effect of M. oleifera-based diets on nickel (Ni) - induced hepatotoxicity in rats. Male rats assigned into six groups were given oral administration of 20 mg/kg body weight nickel sulfate in normal saline and either fed normal diet orM. oleifera-based diets for 21 days. All animals were sacrificed under anesthesia 24 hours after the last treatment. Ni exposure elevated the rat plasma activities of alanine transaminase, aspartate transaminase and alkaline phosphatase significantly. Ni exposure also raised the levels of triglyceride, total cholesterol and low-density lipoprotein cholesterol while depleting the high-density lipoprotein cholesterol concentration. Further, Ni exposure raised rat plasma malondialdehyde but depleted reduced glutathione concentrations. The histopathological presentations revealed inflammation and cellular degeneration caused by Ni exposure. We show evidence thatM. oleifera-based diets protected against Ni-induced hepatotoxicity by improving the rat liver function indices, lipid profile as well as restoring cellular architecture and integrity. Study lends credence to the health-promoting value ofM. oleifera as well as underscores its potential to attenuate hepatic injury. PMID:28808207

  6. Antibiotic suppression of intestinal microbiota reduces heme-induced lipoperoxidation associated with colon carcinogenesis in rats.

    Science.gov (United States)

    Martin, O C B; Lin, C; Naud, N; Tache, S; Raymond-Letron, I; Corpet, D E; Pierre, F H

    2015-01-01

    Epidemiological studies show that heme iron from red meat is associated with increased colorectal cancer risk. In carcinogen-induced-rats, a heme iron-rich diet increases the number of precancerous lesions and raises associated fecal biomarkers. Heme-induced lipoperoxidation measured by fecal thiobarbituric acid reagents (TBARs) could explain the promotion of colon carcinogenesis by heme. Using a factorial design we studied if microbiota could be involved in heme-induced carcinogenesis, by modulating peroxidation. Rats treated or not with an antibiotic cocktail were given a control or a hemoglobin-diet. Fecal bacteria were counted on agar and TBARs concentration assayed in fecal water. The suppression of microbiota by antibiotics was associated with a reduction of crypt height and proliferation and with a cecum enlargement, which are characteristics of germ-free rats. Rats given hemoglobin diets had increased fecal TBARs, which were suppressed by the antibiotic treatment. A duplicate experiment in rats given dietary hemin yielded similar results. These data show that the intestinal microbiota is involved in enhancement of lipoperoxidation by heme iron. We thus suggest that microbiota could play a role in the heme-induced promotion of colorectal carcinogenesis.

  7. Tesofensine induces appetite suppression and weight loss with reversal of low forebrain dopamine levels in the diet-induced obese rat

    DEFF Research Database (Denmark)

    Hansen, Henrik H; Jensen, Majbrit M; Overgaard, Agnete

    2013-01-01

    is not clarified. Tesofensine effectively induces appetite suppression in the diet-induced obese (DIO) rat partially being ascribed to an indirect stimulation of central dopamine receptor function subsequent to blocked dopamine transporter activity. This is interesting, as obese patients have reduced central......Tesofensine is a triple monoamine reuptake inhibitor which inhibits noradrenaline, 5-HT and dopamine reuptake. Tesofensine is currently in clinical development for the treatment of obesity, however, the pharmacological basis for its strong and sustained effects in obesity management...... as compared to age-matched chow-fed rats. DIO rats also exhibited a marked reduction in baseline extracellular dopamine levels in the nucleus accumbens (NAcc) and prefrontal cortex (PFC), as compared to chow-fed rats using microdialysis. While acute administration of tesofensine (2.0mg/kg) normalized accumbal...

  8. Beneficial effect of candesartan and lisinopril against haloperidol-induced tardive dyskinesia in rat.

    Science.gov (United States)

    Thakur, Kuldeep Singh; Prakash, Atish; Bisht, Rohit; Bansal, Puneet Kumar

    2015-12-01

    Tardive dyskinesia is a serious motor disorder of the orofacial region, resulting from chronic neuroleptic treatment of schizophrenia. Candesartan (AT1 antagonist) and lisinopril (ACE inhibitor) has been reported to possess antioxidant and neuroprotective effects. The present study is designed to investigate the effect of candesartan and lisinopril on haloperidol-induced orofacial dyskinesia and oxidative damage in rats. Tardive dyskinesia was induced by administering haloperidol (1 mg/kg i.p.) and concomitantly treated with candesartan (3 and 5 mg/kg p.o.) and lisinopril (10 and 15 mg/kg p.o.) for 3 weeks in male Wistar rats. Various behavioral parameters were assessed on days 0, 7, 14 and 21 and biochemical parameters were estimated at day 22. Chronic administration of haloperidol significantly increased stereotypic behaviors in rats, which were significantly improved by administration of candesartan and lisinopril. Chronic administration of haloperidol significantly increased oxidative stress and neuro-inflammation in the striatum region of the rat's brain. Co-administration of candesartan and lisinopril significantly attenuated the oxidative damage and neuro-inflammation in the haloperidol-treated rat. The present study supports the therapeutic use of candesartan and lisinopril in the treatment of typical antipsychotic-induced orofacial dyskinesia and possible antioxidant and neuro-inflammatory mechanisms. © The Author(s) 2014.

  9. α-fetoprotein involvement during glucocorticoid-induced precocious maturation in rat colon.

    Science.gov (United States)

    Chen, Min; Sun, Peng; Liu, Xiao-Yan; Dong, Dan; Du, Jun; Gu, Luo; Ge, Ying-Bin

    2011-06-28

    To investigate the role of α-fetoprotein (AFP), a cancer-associated fetal glycoprotein, in glucocorticoid-induced precocious maturation in rat colon. Colons from suckling Sprague-Dawley rats were used in this study. Corticosterone acetate at a dose of 100 μg/g body weight was given to normal pups on days 7, 9 and 11 after birth to induce hypercorticoidism. Control animals were injected with identical volumes of normal saline. Some rats receiving corticosterone 7 d after birth were also treated with mifepristone (RU38486), a glucocorticoid cytoplasm receptor antagonist to investigate the effects of glucocorticoids (GCs). The morphological changes of the crypt depth and villous height of the villous zone in colon were observed as indices of colon maturation. Expression levels of AFP in colons were detected by reverse transcriptase polymerase chain reaction and Western blotting. To identify the cellular localization of AFP in developing rat colons, double-immunofluorescent staining was performed using antibodies to specific mesenchymal cell marker and AFP. Corticosterone increased the crypt depth and villous height in the colon of 8- and 10-d-old rats with hypercorticoidism compared with that in the control animals (120% in 8-d-old rats and 118% in 10-d-old rats in villous height, P = 0.021; 145% in 8-d-old rats and 124% in 10-d-old rats in crypt depth, P = 0.017). These increases were accompanied by an increase of AFP expression in both mRNA and protein (2.5-folds in 8-d-old and 2.5-folds in 10-d-old rats higher than in control animals, P = 0.035; 1.8-folds in 8-d-old and 1.3-folds in 10-d-old rats higher than in control animals, P = 0.023). Increased crypt depth and villous height and increased expression of AFP in the colon of rats with hypercorticoidism were blocked by mifepristone. Both had positive staining for AFP or vimentin, and overlapped in mesenchymal cells at each tested colon. GCs promote the development of rat colon. AFP appears to be involved, in

  10. Perinatal testosterone contributes to mid-to-post pubertal sex differences in risk for binge eating in male and female rats.

    Science.gov (United States)

    Culbert, Kristen M; Sinclair, Elaine B; Hildebrandt, Britny A; Klump, Kelly L; Sisk, Cheryl L

    2018-02-01

    Exposure to testosterone early in life may contribute to sex differences and pubertal changes in risk for eating pathology (i.e., females > males, after pubertal onset). Specifically, perinatal testosterone permanently alters brain structure/function and drives the masculinization of several sex-differentiated behaviors. However, the effects of perinatal testosterone are often not evident until puberty when increases in gonadal hormones activate the expression of sex typical behavior, including eating behaviors (e.g., chow intake; saccharin preference) in rodents. Despite perinatal testosterone's masculinizing effects on general feeding behavior, it remains unknown if perinatal testosterone exposure contributes to sex differences in pathological eating. The current study addressed this gap by examining whether perinatal testosterone exposure decreases risk for binge eating proneness after pubertal onset in male and female rats. Sprague-Dawley rats (n = 40 oil-treated control females; n = 39 testosterone-treated females; n = 40 oil-treated control males) were followed longitudinally across pre-to-early puberty, mid-to-late puberty, and adulthood. The binge eating prone (BEP)/binge eating resistant (BER) rodent model was used to identify individual differences in binge eating proneness across the dimensional spectrum. As expected, testosterone-treated females and control males showed masculinized (i.e., lower) risk for binge eating as compared to control females, but only after midpuberty. These animal data are significant in suggesting that perinatal testosterone exposure may protect against binge eating and underlie sex differences in binge eating prevalence during and after puberty. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

  11. Dynamic Aerobic Exercise Induces Baroreflex Improvement in Diabetic Rats

    Directory of Open Access Journals (Sweden)

    Luciana Jorge

    2012-01-01

    Full Text Available The objective of the present study was to investigate the effects of an acute aerobic exercise on arterial pressure (AP, heart rate (HR, and baroreflex sensitivity (BRS in STZ-induced diabetic rats. Male Wistar rats were divided into control (n=8 and diabetic (n=8 groups. AP, HR, and BRS, which were measured by tachycardic and bradycardic (BR responses to AP changes, were evaluated at rest (R and postexercise session (PE on a treadmill. At rest, STZ diabetes induced AP and HR reductions, associated with BR impairment. Attenuation in resting diabetes-induced AP (R: 103±2 versus PE: 111±3 mmHg and HR (R: 290±7 versus PE: 328±10 bpm reductions and BR dysfunction (R: -0.70±0.06 versus PE: -1.21±0.09 bpm/mmHg was observed in the postexercise period. In conclusion, the hemodynamic and arterial baro-mediated control of circulation improvement in the postexercise period reinforces the role of exercise in the management of cardiovascular risk in diabetes.

  12. Dynamic Aerobic Exercise Induces Baroreflex Improvement in Diabetic Rats

    Science.gov (United States)

    Jorge, Luciana; da Pureza, Demilto Y.; Dias, Danielle da Silva; Conti, Filipe Fernandes; Irigoyen, Maria-Cláudia; De Angelis, Kátia

    2012-01-01

    The objective of the present study was to investigate the effects of an acute aerobic exercise on arterial pressure (AP), heart rate (HR), and baroreflex sensitivity (BRS) in STZ-induced diabetic rats. Male Wistar rats were divided into control (n = 8) and diabetic (n = 8) groups. AP, HR, and BRS, which were measured by tachycardic and bradycardic (BR) responses to AP changes, were evaluated at rest (R) and postexercise session (PE) on a treadmill. At rest, STZ diabetes induced AP and HR reductions, associated with BR impairment. Attenuation in resting diabetes-induced AP (R: 103 ± 2 versus PE: 111 ± 3 mmHg) and HR (R: 290 ± 7 versus PE: 328 ± 10 bpm) reductions and BR dysfunction (R: −0.70 ± 0.06 versus PE: −1.21 ± 0.09 bpm/mmHg) was observed in the postexercise period. In conclusion, the hemodynamic and arterial baro-mediated control of circulation improvement in the postexercise period reinforces the role of exercise in the management of cardiovascular risk in diabetes. PMID:22203833

  13. Both Hypothyroidism and Hyperthyroidism Increase Atrial Fibrillation Inducibility in Rats

    Science.gov (United States)

    Zhang, Youhua; Dedkov, Eduard I.; Teplitsky, Diana; Weltman, Nathan Y.; Pol, Christine J.; Rajagopalan, Viswanathan; Lee, Bianca; Gerdes, A. Martin

    2014-01-01

    Background Evidence indicates that cardiac hypothyroidism may contribute to heart failure (HF) progression. It is also known that HF is associated with an increased risk of atrial fibrillation (AF). While it is established that hyperthyroidism increases AF incidence, the effect of hypothyroidism on AF is unclear. This study investigated the effects of different thyroid hormone levels, ranging from hypothyroidism to hyperthyroidism on AF inducibility in thyroidectomized rats. Methods and Results Thyroidectomized rats with serum confirmed hypothyroidism 1 month after surgery were randomized into hypothyroid (n=9), euthyroid (n=9) and hyperthyroid (n=9) groups. Rats received placebo, 3.3mg L-thyroxine (T4), or 20 mg T4 pellets (60 day release form) for 2 months, respectively. At the end of treatment, hypothyroid, euthyroid and hyperthyroid status was confirmed. Hypothyroid animals showed cardiac atrophy and reduced cardiac systolic and diastolic function, while hyperthyroid rats exhibited cardiac hypertrophy and increased cardiac function. Hypothyroidism and hyperthyroidism produced opposite electrophysiological changes in heart rates and atrial effective refractory period, but both significantly increased AF susceptibility. AF incidence was 78% in hypothyroid, 67% in hyperthyroid, and the duration of induced AF was also longer, compared with 11% in the euthyroid group (all phyperthyroidism lead to increased AF vulnerability in a rat thyroidectomy model. Our results stress that normal thyroid hormone levels are required to maintain normal cardiac electrophysiology and prevent cardiac arrhythmias and AF. PMID:24036190

  14. MX-INDUCED URINARY BLADDER EPITHELIAL HYPERPLASIA IN EKER RATS

    Science.gov (United States)

    MX-INDUCED URINARY BLADDER EPITHELIAL HYPERPLASIA IN EKER RATS Epidemiological studies have shown a positive association between chronic exposure to chlorinated drinking water and human cancer, particularly of the urinary bladder. MX (3- chloro-4-(dichloromethyl)-5-hydrox...

  15. Puberty timing associated with diabetes, cardiovascular disease and also diverse health outcomes in men and women: the UK Biobank study.

    Science.gov (United States)

    Day, Felix R; Elks, Cathy E; Murray, Anna; Ong, Ken K; Perry, John R B

    2015-06-18

    Early puberty timing is associated with higher risks for type 2 diabetes (T2D) and cardiovascular disease in women and therefore represents a potential target for early preventive interventions. We characterised the range of diseases and other adverse health outcomes associated with early or late puberty timing in men and women in the very large UK Biobank study. Recalled puberty timing and past/current diseases were self-reported by questionnaire. We limited analyses to individuals of White ethnicity (250,037 women; 197,714 men) and to disease outcomes with at least 500 cases (~ 0.2% prevalence) and we applied stringent correction for multiple testing (corrected threshold P puberty timing was associated with higher risks for angina, hypertension and T2D. Furthermore, compared to the median/average group, earlier or later puberty timing in women or men was associated with higher risks for 48 adverse outcomes, across a range of cancers, cardio-metabolic, gynaecological/obstetric, gastrointestinal, musculoskeletal, and neuro-cognitive categories. Notably, both early and late menarche were associated with higher risks for early natural menopause in women. Puberty timing in both men and women appears to have a profound impact on later health.

  16. Effects of Trigonelline, an Alkaloid Present in Coffee, on Diabetes-Induced Disorders in the Rat Skeletal System.

    Science.gov (United States)

    Folwarczna, Joanna; Janas, Aleksandra; Pytlik, Maria; Cegieła, Urszula; Śliwiński, Leszek; Krivošíková, Zora; Štefíková, Kornélia; Gajdoš, Martin

    2016-03-02

    Diabetes increases bone fracture risk. Trigonelline, an alkaloid with potential antidiabetic activity, is present in considerable amounts in coffee. The aim of the study was to investigate the effects of trigonelline on experimental diabetes-induced disorders in the rat skeletal system. Effects of trigonelline (50 mg/kg p.o. daily for four weeks) were investigated in three-month-old female Wistar rats, which, two weeks before the start of trigonelline administration, received streptozotocin (60 mg/kg i.p.) or streptozotocin after nicotinamide (230 mg/kg i.p.). Serum bone turnover markers, bone mineralization, and mechanical properties were studied. Streptozotocin induced diabetes, with significant worsening of bone mineralization and bone mechanical properties. Streptozotocin after nicotinamide induced slight glycemia increases in first days of experiment only, however worsening of cancellous bone mechanical properties and decreased vertebral bone mineral density (BMD) were demonstrated. Trigonelline decreased bone mineralization and tended to worsen bone mechanical properties in streptozotocin-induced diabetic rats. In nicotinamide/streptozotocin-treated rats, trigonelline significantly increased BMD and tended to improve cancellous bone strength. Trigonelline differentially affected the skeletal system of rats with streptozotocin-induced metabolic disorders, intensifying the osteoporotic changes in streptozotocin-treated rats and favorably affecting bones in the non-hyperglycemic (nicotinamide/streptozotocin-treated) rats. The results indicate that, in certain conditions, trigonelline may damage bone.

  17. Desmodium gangeticum root extract attenuates isoproterenol-induced cardiac hypertrophic growth in rats.

    Directory of Open Access Journals (Sweden)

    Divya Hitler

    2014-10-01

    Full Text Available Context: Desmodium gangeticum (L DC (Fabaceae; DG, a medicinal plant that grows in tropical habitats, is widely used to treat various ailments including digestive and inflammatory disorders. Aims: To investigate the possible cardioprotective activity of a DG root extract against isoproterenol (ISO-induced left ventricular cardiac hypertrophy (LVH in adult Wistar rats. Methods: Daily intraperitoneal administration of ISO (10 mg/kg body weight, single injection for 7 days induced LVH in rats. The LVH rats were post-treated orally with DG (100 mg/kg body weight for a period of 30 days. Thereafter, changes in heart weight (HW and body weight (BW, HW/BW ratio, percent of hypertrophy, collagen accumulation, activities of matrix metalloproteinase (MMP -2 and -9, superoxide dismutase (SOD and catalase (CAT enzymes, and the level of an oxidative stress marker, lipid peroxide (LPO, were determined. Results: HW/BW ratio, an indicator of hypertrophic growth, was significantly reduced in DG root post-treated LVH rats as compared with that for the non-treated LVH rats. The altered levels of ventricular LPO, collagen, MMPs-2 and -9, and antioxidant enzymes in the ISO-treated animals reverted back to near normal upon DG treatment. Further, the anti-hypertrophic activity of DG was comparable to that of the standard drug losartan (10 mg/kg. Conclusions: The results of the present study suggest that the aqueous root extract of DG exhibited anti-hypertrophic activity in-vivo by inhibiting ISO-induced ROS generation and MMP activities.

  18. Naftopidil inhibits 5-hydroxytryptamine-induced bladder contraction in rats.

    Science.gov (United States)

    Sakai, Takumi; Kasahara, Ken-ichi; Tomita, Ken-ichi; Ikegaki, Ichiro; Kuriyama, Hiroshi

    2013-01-30

    Naftopidil is an α(1D) and α(1A) subtype-selective α(1)-adrenoceptor antagonist that has been used to treat lower urinary tract symptoms of benign prostatic hyperplasia. In this study, we investigated the effects of naftopidil on 5-hydroxytryptamine (5-HT)-induced rat bladder contraction (10(-8)-10(-4) M). Naftopidil (0.3, 1, and 3 μM) inhibited 5-HT-induced bladder contraction in a concentration-dependent manner. On the other hand, other α(1)-adrenoceptor antagonists, tamsulosin, silodosin or prazosin, did not inhibit 5-HT-induced bladder contraction. The 5-HT-induced bladder contraction was inhibited by both ketanserin and 4-(4-fluoronaphthalen-1-yl)-6-propan-2-ylpyrimidin-2-amine (RS127445), serotonin 5-HT(2A) and 5-HT(2B) receptor antagonists, respectively. In addition, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) and α-methyl-5-HT, 5-HT(2A) and 5-HT(2) receptor agonists, respectively, induced bladder contraction. The 5-HT-induced bladder contraction was not inhibited by N-[2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl]-N-pyridin-2-yl-cyclohexanecarboxamide (WAY-100635), [1-[2[(methylsulfonyl)amino]ethyl]-4-piperidinyl]methyl-1-methyl-1H-indole-3-carboxylate (GR113808) or (R)-3-[2-[2-(4-methylpiperidin-1-yl)ethyl]pyrrolidine-1-sulphonyl]phenol (SB269970), 5-HT(1A), 5-HT(4) and 5-HT(7) receptor antagonists, respectively. Naftopidil inhibited both the 5-HT(2A) and 5-HT(2) receptor agonists-induced bladder contractions. Naftopidil binds to the human 5-HT(2A) and 5-HT(2B) receptors with pKi values of 6.55 and 7.82, respectively. These results suggest that naftopidil inhibits 5-HT-induced bladder contraction via blockade of the 5-HT(2A) and 5-HT(2B) receptors in rats. Furthermore, 5-HT-induced bladder contraction was enhanced in bladder strips obtained from bladder outlet obstructed rats, with this contraction inhibited by naftopidil. The beneficial effects of naftopidil on storage symptoms such as urinary frequency and nocturia in patients with benign

  19. Modulation of Immune Disorders Induced-Arthritis in γ- Irradiated Rats

    International Nuclear Information System (INIS)

    Thabet, N.M.S.

    2013-01-01

    This study was to evaluate the antioxidant and anti-inflammatory capability of a laboratory preparation mixture Nano Selenium-lovastatin (Lov-Se) against oxidative stress and inflammatory cascade in irradiated and/or adjuvant arthritic rats. The experimental animals were divided into: adjuvant free groups and adjuvant induced groups. Rats were exposed to whole body γ-radiation (2 Gy every 3 days up to total dose of 8 Gy) and received oral administration of 1 ml Lov-Se mixture (≈ 20 mg kg - 1 Lov and 0.1 mg kg - 1 day - 1 Se) for 14 successive days. Animal model of arthritis was organized by subcutaneous injection of complete freund’s adjuvant. The antioxidant parameters (heart GSH-Px, CAT, SOD, XDH, GSH and blood Se), and oxidant markers (heart XO, NO, protein carbonyls and TBARS) and Also, the inflammatory molecules (serum TNF-α, CRP and RF) were determined. In irradiated Lov-Se rats, the results obtained reveals that, TBARS, protein carbonyl, TNF-α, CRP levels, and XO, CAT and SOD activities were significantly ameliorated as compared to irradiated rats. Also, heart GSH, NO levels, XDH, GSH-Px activities and blood Se level were significantly improved. In addition, the administration of Lov-Se to the arthritic and arthritic irradiated rats ameliorates the disturbance occurs in oxidative stress, inflammatory cascades and antioxidant indicators when compared to control rats. In conclusion, the proper administration of Lov-Se mixture might reduce the radiation-induced heart injury via amending the antioxidant molecules and decreasing lipid and protein oxidation. Also, it could be suggested that Lov-Se mixture might posses a considerable anti-inflammatory properties

  20. Prolactin and aging: X-irradiated and estrogen-induced rat mammary tumorigenesis

    International Nuclear Information System (INIS)

    Ito, A.; Naito, M.; Watanabe, H.; Yokoro, K.

    1984-01-01

    Both sexes of inbred WF rats at either 8 or 28-60 weeks of age were exposed to 200 rad whole-body radiation, 2.5 or 5.0 mg 17 beta-estradiol (E2), or both agents The female rats treated with E2 alone or with both X-rays and E2 at 8 weeks of age showed a high incidence of mammary carcinomas (MCA), a large increase in pituitary weight, and a rise in serum prolactin (PRL) levels. However, the same treatments to males did not induce MCA despite a moderate increase in both pituitary weight and serum PRL. Ovariectomy prior to E2 treatment failed to modify the occurrence of MCA or pituitary tumors. When X-rays and E2 were given to female rats at 28-60 weeks of age, pituitary weight, serum PRL levels, and the incidence of MCA were unaffected. When the E2 pellet was kept for the first 24 weeks and withdrawn during the last 12 weeks, the incidence of MCA, pituitary weight, and serum PRL was low. It was concluded that: 1) the pituitary glands of young female rats were susceptible to E2 treatment but were insensitive in older females, and 2) the occurrence of MCA in female rats appeared to be promoted by elevated PRL levels secreted by E2-induced pituitary tumors. Mammary tissue of male rats was less sensitive to PRL levels in the development of MCA

  1. α-Amyrin attenuates high fructose diet-induced metabolic syndrome in rats.

    Science.gov (United States)

    Prabhakar, Pankaj; Reeta, K H; Maulik, Subir Kumar; Dinda, Amit Kumar; Gupta, Yogendra Kumar

    2017-01-01

    This study investigated the effect of α-amyrin (a pentacyclic triterpene) on high-fructose diet (HFD)-induced metabolic syndrome in rats. Male Wistar rats were randomly distributed into different groups. The control group was fed normal rat chow diet. The HFD group was fed HFD (60%; w/w) for 42 days. Pioglitazone (10 mg/kg, orally, once daily) was used as a standard drug. α-Amyrin was administered in 3 doses (50, 100, and 200 mg/kg, orally, once daily along with HFD). Plasma glucose, total cholesterol, triglycerides, and high-density lipoprotein cholesterol (HDL-C) were estimated. Changes in blood pressure, oral glucose tolerance, and insulin tolerance were measured. Hepatic oxidative stress as well as messenger RNA (mRNA) and protein levels of peroxisome proliferator-activated receptor alpha (PPAR-α) were analyzed. A significant increase in systolic blood pressure, plasma glucose, total cholesterol, and plasma triglycerides and a significant decrease in HDL-C were observed in HFD rats as compared with control rats. Glucose tolerance and insulin tolerance were also significantly impaired with HFD. α-Amyrin prevented these changes in a dose-dependent manner. Hepatic oxidative stress as well as micro- and macrovesicular fatty changes in hepatocytes caused by HFD were also attenuated by α-amyrin. α-Amyrin preserved the hepatic mRNA and protein levels of PPAR-α, which was reduced in HFD group. This study thus demonstrates that α-amyrin attenuates HFD-induced metabolic syndrome in rats.

  2. Municipal landfill leachates induced chromosome aberrations in rat ...

    African Journals Online (AJOL)

    Physico-chemical and heavy metal analysis of the test samples showed that they contained high concentrations of toxic anions and cations that are capable of inducing mutation in living cells. The interaction of these constituents with the genetic material in the bone marrow cells of rat caused the observed chromosome ...

  3. Validation of infrared thermography in serotonin-induced itch model in rats

    DEFF Research Database (Denmark)

    Dagnæs-Hansen, Frederik; Jasemian, Yousef; Gazerani, Parisa

    The number of scratching bouts is generally used as a standard method in animal models of itch. The aim of the present study was to validate the application of infrared thermography (IR-Th) in a serotonin-induced itch model in rats. Adult Sprague-Dawley male rats (n = 24) were used in 3 consecutive...... experiments. The first experiment evaluated vasomotor response (IR-Th) and scratching behavior (number of bouts) induced by intradermal serotonin (10 μl, 2%). Isotonic saline (control: 10 μl, 0.9%) and Methysergide (antagonist: 10 μl, 0.047 mg/ml) were used. The second experiment evaluated the dose......-response effect of intradermal serotonin (1%, 2% and 4%) on local temperature. The third experiment evaluated the anesthetized rats to test the local vasomotor responses in absent of scratching. Serotonin elicited significant scratching and lowered the local temperature at the site of injection. A dose...

  4. Chemopreventive effect of artesunate in 1,2-dimethylhydrazine-induced rat colon carcinogenesis

    Directory of Open Access Journals (Sweden)

    Sazal Patyar

    2017-01-01

    Full Text Available Artesunate (ART is a semisynthetic derivative of artemisinin. Artemisinin and its derivatives have shown profound cytotoxicity and antitumor activity in addition to antimalarial activity in various studies. As the in vivo chemopreventive efficacy of ART in colon carcinogenesis has not been investigated so far, the aim of the current study was to study the chemopreventive effect of ART in 1,2-dimethylhydrazine (DMH-induced rat colon carcinogenesis. Animals were divided into four groups (n = 6: Group I - vehicle (1 mM ethylenediaminetetraacetic acid, Group II - DMH (20 mg/kg, Group III - DMH + 5-fluorouracil (81 mg/kg, Group IV - DMH + ART (6.7 mg/kg. After completion of 15 weeks of treatment, rats were sacrificed under ether anesthesia by cervical dislocation for assessment of lipid peroxidation (LPO, antioxidant status, average number of aberrant crypt foci (ACF, and cytokine levels. ART administration significantly decreased the average number of ACF/microscopic field. Similarly, LPO level was decreased and antioxidant activities were enhanced after ART treatment. ART decreased the levels of proinflammatory cytokines and induced apoptosis in the colons of DMH-treated rats. The results of this study suggest that ART has a beneficial effect against chemically induced colonic preneoplastic progression in rats.

  5. Hyperthyroidism enhances 5-HT-induced contraction of the rat pulmonary artery: role of calcium-activated chloride channel activation.

    Science.gov (United States)

    Oriowo, Mabayoje A; Oommen, Elsie; Khan, Islam

    2011-11-01

    Experimentally-induced hyperthyroidism in rodents is associated with signs and symptoms of pulmonary hypertension. The main objective of the present study was to investigate the effect of thyroxine-induced pulmonary hypertension on the contractile response of the pulmonary artery to 5-HT and the possible underlying signaling pathway. 5-HT concentration-dependently contracted artery segments from control and thyroxine-treated rats with pD(2) values of 5.04 ± 0.19 and 5.34 ± 0.14, respectively. The maximum response was significantly greater in artery segments from thyroxine-treated rats. Neither BW 723C86 (5-HT(2B)-receptor agonist) nor CP 93129 (5-HT(1B)-receptor agonist) contracted ring segments of the pulmonary artery from control and thyroxine-treated rats at concentrations up to 10(-4)M. There was no significant difference in the level of expression of 5-HT(2A)-receptor protein between the two groups. Ketanserin (3 × 10(-8)M) produced a rightward shift of the concentration-response curve to 5-HT in both groups with equal potency (-logK(B) values were 8.1 ± 0.2 and 7.9 ± 0.1 in control and thyroxine-treated rats, respectively). Nifedipine (10(-6)M) inhibited 5-HT-induced contractions in artery segments from control and thyroxine-treated rats and was more effective against 5-HT-induced contraction in artery segments for thyroxine-treated rats. The calcium-activated chloride channel blocker, niflumic acid (10(-4)M) also inhibited 5-HT-induced contractions in artery segments from control and thyroxine-treated rats and was more effective against 5-HT-induced contraction in artery segments for thyroxine-treated rats. It was concluded that hyperthyroidism enhanced 5-HT-induced contractions of the rat pulmonary artery by a mechanism involving increased activity of calcium-activated chloride channels. Copyright © 2011 Elsevier B.V. All rights reserved.

  6. Ultrastructural apoptotic lesions induced in rat thymocytes after borax ingestion.

    Science.gov (United States)

    Sylvain, I C; Berry, J P; Galle, P

    1998-01-01

    Apoptosis has gained increasing attention in recent years. Several chemical compounds induce apoptotic lesions in the thymus. Male Wistar rats received 2000 ppm of borax (Na2B4O7.10H2O) in their food for 16 days. The rats were sacrificed 2, 5, 9, 12, 19, 21, 26 and 28 days after the beginning of treatment. Thymus samples of all rats were taken. A Philips EM 300 electron microscopy was used to study the ultrastructural morphology. Serious nuclear and cytoplasmic lesions were observed. Moreover, numerous macrophages containing apoptotic cells were present in the thymus. The alterations were observed from the 2nd to the 28th day. The extent of damage was much more important in the rats sacrificed 21, 26 and 28 days after borax ingestion.

  7. Bacterial Flora Changes in Conjunctiva of Rats with Streptozotocin-Induced Type I Diabetes.

    Science.gov (United States)

    Yang, Chao; Fei, Yuda; Qin, Yali; Luo, Dan; Yang, Shufei; Kou, Xinyun; Zi, Yingxin; Deng, Tingting; Jin, Ming

    2015-01-01

    The microbiota of both humans and animals plays an important role in their health and the development of disease. Therefore, the bacterial flora of the conjunctiva may also be associated with some diseases. However, there are no reports on the alteration of bacterial flora in conjunctiva of diabetic rats in the literature. Therefore, we investigated the changes in bacterial flora in bulbar conjunctiva of rats with streptozotocin (STZ)-induced type I diabetes. A high dose of STZ (60 mg/kg, i.p.) was injected into Sprague-Dawley (SD) rats to induce type I diabetes mellitus (T1DM). The diabetic rats were raised in the animal laboratory and at 8 months post-injection of STZ swab samples were taken from the bulbar conjunctiva for cultivation of aerobic bacteria. The bacterial isolates were identified by Gram staining and biochemical features. The identified bacteria from both diabetic and healthy rats were then compared. The diabetic and healthy rats had different bacterial flora present in their bulbar conjunctiva. In total, 10 and 8 bacterial species were found in the STZ and control groups, respectively, with only three species (Enterococcus faecium, Enterococcus gallinarum and Escherichia coli) shared between the two groups. Gram-positive bacteria were common in both groups and the most abundant was Enterococcus faecium. However, after the development of T1DM, the bacterial flora in the rat bulbar conjunctiva changed considerably, with a reduced complexity evident. STZ-induced diabetes caused alterations of bacterial flora in the bulbar conjunctiva in rats, with some bacterial species disappearing and others emerging. Our results indicate that the conjunctival bacterial flora in diabetic humans should be surveyed for potential diagnostic markers or countermeasures to prevent eye infections in T1DM patients.

  8. Antioxidants as recipes for efavirenz-induced liver damage: A study in albino rats

    Directory of Open Access Journals (Sweden)

    Elias Adikwu

    2018-03-01

    Full Text Available Objective: Hepatotoxicity is a clinical challenge associated with the use of efavirenz (EFV. This study investigated the effects of n-acetylcysteine (NAC, vitamins C and E on EFV-induced hepatotoxicity in albino rats. Methods: Rats were divided into groups and administered with NAC (20mg/kg, Vit C (50mg/kg, Vit  E (50mg/kg, Vit C+ E and 60mg/kg of EFV respectively. Rats were also divided into groups and pretreated with NAC, Vit C, E, and combined doses of Vit C+E prior to treatment with EFV for 15 days respectively. After drug administration rats were sacrificed and serum was collected and evaluated for liver function parameters. Rats were dissected, liver was collected weighed and evaluated for alkaline phosphatase (ALP, alanine aminotransferase (AST, aspartate aminotransferase (ALT, gamma glutamyl transferase (GGT, lactate dehydrogenase (LDH, malondialdehyde (MDA, super oxide dismutase (SOD, catalase (CAT, glutathione (GSH, gluthatione peroxidase (GPX levels and pathological damage. Results: Effects were not significant (p>0.05 on body and liver weights, however, the levels of AST, ALT, AST, GGT, LDH, CB, TB and MDA were increased significantly (p<0.05 whereas SOD, CAT, SOD, GSH and GPX were decreased significantly (p<0.05 in EFV-treated rats in comparison to control. The liver of EFV-treated rats showed necrosis of hepatocytes. Nevertheless, EFV-induced alterations in the above parameters were significantly (p<0.05 ameliorated in antioxidants pretreated rats.  The combined doses of Vit C and E produced the best and significant (p<0.05 ameliorative effects in comparison to their individual doses. Conclusion: This study shows the prospects of antioxidants as candidates for the treatments of efavirenz-induced hepatotoxicity.

  9. Sildenafil Ameliorates Gentamicin-Induced Nephrotoxicity in Rats: Role of iNOS and eNOS

    Directory of Open Access Journals (Sweden)

    Mohamed A. Morsy

    2014-01-01

    Full Text Available Gentamicin, an aminoglycoside antibiotic, is used for the treatment of serious Gram-negative infections. However, its usefulness is limited by its nephrotoxicity. Sildenafil, a selective phosphodiesterase-5 inhibitor, was reported to prevent or decrease tissue injury. The aim of this study is to evaluate the potential protective effects of sildenafil on gentamicin-induced nephrotoxicity in rats. Male Wistar rats were injected with gentamicin (100 mg/kg/day, i.p. for 6 days with and without sildenafil. Sildenafil administration resulted in nephroprotective effect in gentamicin-intoxicated rats as it significantly decreased serum creatinine and urea, urinary albumin, and renal malondialdehyde and nitrite/nitrate levels, with a concomitant increase in renal catalase and superoxide dismutase activities compared to gentamicin-treated rats. Moreover, immunohistochemical examination revealed that sildenafil treatment markedly reduced inducible nitric oxide synthase (iNOS expression, while expression of endothelial nitric oxide synthase (eNOS was markedly enhanced. The protective effects of sildenafil were verified histopathologically. In conclusion, sildenafil protects rats against gentamicin-induced nephrotoxicity possibly, in part, through its antioxidant activity, inhibition of iNOS expression, and induction of eNOS production.

  10. Hemodynamic and neuropathological analysis in rats with aluminum trichloride-induced Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Szu-Ming Chen

    Full Text Available BACKGROUND AND AIMS: Hemodynamic normality is crucial to maintaining the integrity of cerebral vessels and, therefore, preserving the cognitive functions of Alzheimer's disease patients. This study investigates the implications of the hemodynamic changes and the neuropathological diversifications of AlCl3-induced AD. METHODS: The experimental animals were 8- to 12-wk-old male Wistar rats. The rats were randomly divided into 2 groups: a control group and a (+control group. Food intake, water intake, and weight changes were recorded daily for 22 wk. Synchronously, the regional cerebral blood flow (rCBF of the rats with AlCl3-induced AD were measured using magnetic resonance imaging (MRI. The hemorheological parameters were analyzed using a computerized auto-rotational rheometer. The brain tissue of the subjects was analyzed using immunohistological chemical (IHC staining to determine the beta-amyloid (Aβ levels. RESULTS: The results of hemodynamic analysis revealed that the whole blood viscosity (WBV, fibrinogen, plasma viscosity and RBC aggregation index (RAI in (+control were significantly higher than that of control group, while erythrocyte electrophoresis (EI of whole blood in (+control were significantly lower than that of control group. The results of acetylcholinesterase-RBC (AChE-RBCin the (+control group was significantly higher than that of the control group. The results also show that the reduction of rCBF in rats with AlCl3-induced AD was approximately 50% to 60% that of normal rats. IHC stain results show that significantly more Aβ plaques accumulated in the hippocampus and cortex of the (+control than in the control group. CONCLUSION: The results accentuate the importance of hemorheology and reinforce the specific association between hemodynamic and neuropathological changes in rats with AlCl3-induced AD. Hemorheological parameters, such as WBV and fibrinogen, and AChE-RBC were ultimately proven to be useful biomarkers of the

  11. Attenuation of cigarette smoke-induced airway mucus production by hydrogen-rich saline in rats.

    Directory of Open Access Journals (Sweden)

    Yunye Ning

    Full Text Available BACKGROUND: Over-production of mucus is an important pathophysiological feature in chronic airway disease such as chronic obstructive pulmonary disease (COPD and asthma. Cigarette smoking (CS is the leading cause of COPD. Oxidative stress plays a key role in CS-induced airway abnormal mucus production. Hydrogen protected cells and tissues against oxidative damage by scavenging hydroxyl radicals. In the present study we investigated the effect of hydrogen on CS-induced mucus production in rats. METHODS: Male Sprague-Dawley rats were divided into four groups: sham control, CS group, hydrogen-rich saline pretreatment group and hydrogen-rich saline control group. Lung morphology and tissue biochemical changes were determined by immunohistochemistry, Alcian Blue/periodic acid-Schiff staining, TUNEL, western blot and realtime RT-PCR. RESULTS: Hydrogen-rich saline pretreatment attenuated CS-induced mucus accumulation in the bronchiolar lumen, goblet cell hyperplasia, muc5ac over-expression and abnormal cell apoptosis in the airway epithelium as well as malondialdehyde increase in the BALF. The phosphorylation of EGFR at Tyr1068 and Nrf2 up-regulation expression in the rat lungs challenged by CS exposure were also abrogated by hydrogen-rich saline. CONCLUSION: Hydrogen-rich saline pretreatment ameliorated CS-induced airway mucus production and airway epithelium damage in rats. The protective role of hydrogen on CS-exposed rat lungs was achieved at least partly by its free radical scavenging ability. This is the first report to demonstrate that intraperitoneal administration of hydrogen-rich saline protected rat airways against CS damage and it could be promising in treating abnormal airway mucus production in COPD.

  12. Hypospermatogenesis and spermatozoa maturation arrest in rats induced by mobile phone radiation.

    Science.gov (United States)

    Meo, Sultan Ayoub; Arif, Muhammad; Rashied, Shahzad; Khan, Muhammad Mujahid; Vohra, Muhammad Saeed; Usmani, Adnan Mahmood; Imran, Muhammad Babar; Al-Drees, Abdul Majeed

    2011-05-01

    To determine the morphological changes induced by mobile phone radiation in the testis of Wistar albino rats. Cohort study. Department of Physiology, College of Medicine, King Saud University, Riyadh, Saudi Arabia, from April 2007 to June 2008. Forty male Wistar albino rats were divided in three groups. First group of eight served as the control. The second group [group B, n=16] was exposed to mobile phone radiation for 30 minutes/day and the third group [group C, n=16] was exposed to mobile phone radiation for 60 minutes/day for a total period of 3 months. Morphological changes in the testes induced by mobile phone radiations were observed under a light microscope. Exposure to mobile phone radiation for 60 minutes/day caused 18.75% hypospermatogenesis and 18.75% maturation arrest in the testis of albino rats compared to matched controls. However, no abnormal findings were observed in albino rats that were exposed to mobile phone radiation for 30 minutes/day for a total period of 3 months. Long-term exposure to mobile phone radiation can cause hypospermatogenesis and maturation arrest in the spermatozoa in the testis of Wistar albino rats.

  13. Edaravone protects neurons in the rat substantia nigra against 6-hydroxydopamine-induced oxidative stress damage.

    Science.gov (United States)

    Liu, Xiqi; Shao, Rushing; Li, Meng; Yang, Guofeng

    2014-11-01

    To investigate the mechanism of the neuroprotective effect of edaravone in substantia nigra (SN) of the 6-OHDA-induced rat model of Parkinson's disease. Animal model of Parkinson's disease was induced in male Sprague-Dawley rats by injecting 6-OHDA into the left medial forebrain bundle. Subsequently, rats were intraperitoneally injected with 0.3, 1, or 3 mg/kg of edaravone for 14 days or with 3 mg/kg edaravone for 14 days followed by 14 days of no treatment. We evaluated the effect of edaravone on the rotational and normal behavior of the rats, and on the number of tyrosine hydroxylase (TH)-positive cells, the amount of Nissl bodies, and the levels of glutathione (GSH), and malondialdehyde (MDA) in the SN. Edaravone treatment at 3 mg/kg significantly reduced apomorphine-induced rotational behavior (P Edaravone exerted a long-term neuroprotective effects in 6-OHDA-induced PD animal model by attenuating changes in the levels of GSH and MDA in SN, caused by oxidative stress. Edaravone prevented 6-OHDA-induced behavioral changes and de-pigmentation of SN that results from the loss of dopaminergic neurons.

  14. Mucus reduction promotes acetyl salicylic acid-induced small intestinal mucosal injury in rats.

    Science.gov (United States)

    Suyama, Yosuke; Handa, Osamu; Naito, Yuji; Takayama, Shun; Mukai, Rieko; Ushiroda, Chihiro; Majima, Atsushi; Yasuda-Onozawa, Yuriko; Higashimura, Yasuki; Fukui, Akifumi; Dohi, Osamu; Okayama, Tetsuya; Yoshida, Naohisa; Katada, Kazuhiro; Kamada, Kazuhiro; Uchiyama, Kazuhiko; Ishikawa, Takeshi; Takagi, Tomohisa; Konishi, Hideyuki; Itoh, Yoshito

    2018-03-25

    Acetyl salicylic acid (ASA) is a useful drug for the secondary prevention of cerebro-cardiovascular diseases, but it has adverse effects on the small intestinal mucosa. The pathogenesis and prophylaxis of ASA-induced small intestinal injury remain unclear. In this study, we focused on the intestinal mucus, as the gastrointestinal tract is covered by mucus, which exhibits protective effects against various gastrointestinal diseases. ASA was injected into the duodenum of rats, and small intestinal mucosal injury was evaluated using Evans blue dye. To investigate the importance of mucus, Polysorbate 80 (P80), an emulsifier, was used before ASA injection. In addition, rebamipide, a mucus secretion inducer in the small intestine, was used to suppress mucus reduction in the small intestine of P80-administered rats. The addition of P80 reduced the mucus and exacerbated the ASA-induced small intestinal mucosal injury. Rebamipide significantly suppressed P80-reduced small intestinal mucus and P80-increased intestinal mucosal lesions in ASA-injected rats, demonstrating that mucus is important for the protection against ASA-induced small intestinal mucosal injury. These results provide new insight into the mechanism of ASA-induced small intestinal mucosal injury. Mucus secretion-increasing therapy might be useful in preventing ASA-induced small intestinal mucosal injury. Copyright © 2018 Elsevier Inc. All rights reserved.

  15. Infrared Thermography in Serotonin-Induced Itch Model in Rats

    DEFF Research Database (Denmark)

    Jasemian, Yousef; Gazerani, Parisa; Dagnæs-Hansen, Frederik

    2012-01-01

    The study validated the application of infrared thermography in a serotonin-induced itch model in rats since the only available method in animal models of itch is the count of scratching bouts. Twenty four adult Sprague-Dawley male rats were used in 3 experiments: 1) local vasomotor response...... with no scratching reflex was investigated. Serotonin elicited significant scratching and lowered the local temperature at the site of injection. A negative dose-temperature relationship of serotonin was found by thermography. Vasoregulation at the site of serotonin injection took place in the absence of scratching...

  16. Bioavailability of andrographolide and protection against carbon tetrachloride-induced oxidative damage in rats

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Haw-Wen [Department of Nutrition, China Medical University, Taichung, Taiwan (China); Huang, Chin-Shiu [Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan (China); Li, Chien-Chun [School of Nutrition, Chung Shan Medical University, Taichung, Taiwan (China); Department of Nutrition, Chung Shan Medical University Hospital, Taichung, Taiwan (China); Lin, Ai-Hsuan; Huang, Yu-Ju [Department of Nutrition, China Medical University, Taichung, Taiwan (China); Wang, Tsu-Shing [Department of Biomedical Science, Chung Shan Medical University, Taichung, Taiwan (China); Yao, Hsien-Tsung [Department of Nutrition, China Medical University, Taichung, Taiwan (China); Lii, Chong-Kuei [Department of Nutrition, China Medical University, Taichung, Taiwan (China); Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan (China)

    2014-10-01

    Andrographolide, a bioactive diterpenoid, is identified in Andrographis paniculata. In this study, we investigated the pharmacokinetics and bioavailability of andrographolide in rats and studied whether andrographolide enhances antioxidant defense in a variety of tissues and protects against carbon tetrachloride-induced oxidative damage. After a single 50-mg/kg administration, the maximum plasma concentration of andrographolide was 1 μM which peaked at 30 min. The bioavailability of andrographolide was 1.19%. In a hepatoprotection study, rats were intragastrically dosed with 30 or 50 mg/kg andrographolide for 5 consecutive days. The results showed that andrographolide up-regulated glutamate cysteine ligase (GCL) catalytic and modifier subunits, superoxide dismutase (SOD)-1, heme oxygenase (HO)-1, and glutathione (GSH) S-transferase (GST) Ya/Yb protein and mRNA expression in the liver, heart, and kidneys. The activity of SOD, GST, and GSH reductase was also increased in rats dosed with andrographolide (p < 0.05). Immunoblot analysis and EMSA revealed that andrographolide increased nuclear Nrf2 contents and Nrf2 binding to DNA, respectively. After the 5-day andrographolide treatment, one group of animals was intraperitoneally injected with carbon tetrachloride (CCl{sub 4}) at day 6. Andrographolide pretreatment suppressed CCl{sub 4}-induced plasma aminotransferase activity and hepatic lipid peroxidation (p < 0.05). These results suggest that andrographolide is quickly absorbed in the intestinal tract in rats with a bioavailability of 1.19%. Andrographolide protects against chemical-induced oxidative damage by up-regulating the gene transcription and activity of antioxidant enzymes in various tissues. - Highlights: • The bioavailability of andrographolide is 1.19% in rats. • Plasma concentration reaches 1 μM after giving 50 mg/kg andrographolide. • Andrographolide up-regulates Nrf2-dependent antioxidant genes. • Andrographolide increases antioxidant defense

  17. Bioavailability of andrographolide and protection against carbon tetrachloride-induced oxidative damage in rats

    International Nuclear Information System (INIS)

    Chen, Haw-Wen; Huang, Chin-Shiu; Li, Chien-Chun; Lin, Ai-Hsuan; Huang, Yu-Ju; Wang, Tsu-Shing; Yao, Hsien-Tsung; Lii, Chong-Kuei

    2014-01-01

    Andrographolide, a bioactive diterpenoid, is identified in Andrographis paniculata. In this study, we investigated the pharmacokinetics and bioavailability of andrographolide in rats and studied whether andrographolide enhances antioxidant defense in a variety of tissues and protects against carbon tetrachloride-induced oxidative damage. After a single 50-mg/kg administration, the maximum plasma concentration of andrographolide was 1 μM which peaked at 30 min. The bioavailability of andrographolide was 1.19%. In a hepatoprotection study, rats were intragastrically dosed with 30 or 50 mg/kg andrographolide for 5 consecutive days. The results showed that andrographolide up-regulated glutamate cysteine ligase (GCL) catalytic and modifier subunits, superoxide dismutase (SOD)-1, heme oxygenase (HO)-1, and glutathione (GSH) S-transferase (GST) Ya/Yb protein and mRNA expression in the liver, heart, and kidneys. The activity of SOD, GST, and GSH reductase was also increased in rats dosed with andrographolide (p < 0.05). Immunoblot analysis and EMSA revealed that andrographolide increased nuclear Nrf2 contents and Nrf2 binding to DNA, respectively. After the 5-day andrographolide treatment, one group of animals was intraperitoneally injected with carbon tetrachloride (CCl 4 ) at day 6. Andrographolide pretreatment suppressed CCl 4 -induced plasma aminotransferase activity and hepatic lipid peroxidation (p < 0.05). These results suggest that andrographolide is quickly absorbed in the intestinal tract in rats with a bioavailability of 1.19%. Andrographolide protects against chemical-induced oxidative damage by up-regulating the gene transcription and activity of antioxidant enzymes in various tissues. - Highlights: • The bioavailability of andrographolide is 1.19% in rats. • Plasma concentration reaches 1 μM after giving 50 mg/kg andrographolide. • Andrographolide up-regulates Nrf2-dependent antioxidant genes. • Andrographolide increases antioxidant defense in

  18. Exercise attenuates intermittent hypoxia-induced cardiac fibrosis associated with sodium-hydrogen exchanger-1 in rats

    Directory of Open Access Journals (Sweden)

    Tsung-I Chen

    2016-10-01

    Full Text Available Purpose: To investigate the role of sodium–hydrogen exchanger-1 (NHE-1 and exercise training on intermittent hypoxia-induced cardiac fibrosis in obstructive sleep apnea (OSA, using an animal model mimicking the intermittent hypoxia of OSA. Methods: Eight-week-old male Sprague–Dawley rats were randomly assigned to control (CON, intermittent hypoxia (IH, exercise (EXE or IH combined with exercise (IHEXE groups. These groups were randomly assigned to subgroups receiving either a vehicle or the NHE-1 inhibitor cariporide. The EXE and IHEXE rats underwent exercise training on an animal treadmill for 10 weeks (5 days/week, 60 minutes/day, 24–30 m/minute, 2–10% grade. The IH and IHEXE rats were exposed to 14 days of IH (30 seconds of hypoxia - nadir of 2-6% O2 - followed by 45 seconds of normoxia for 8 hours/day. At the end of 10 weeks, rats were sacrificed and then hearts were removed to determine the myocardial levels of fibrosis index, oxidative stress, antioxidant capacity and NHE-1 activation. Results: Compared to the CON rats, IH induced higher cardiac fibrosis, lower myocardial catalase and superoxidative dismutase activities, higher myocardial lipid and protein peroxidation and higher NHE-1 activation (p < 0.05 for each, which were all abolished by cariporide. Compared to the IH rats, lower cardiac fibrosis, higher myocardial antioxidant capacity, lower myocardial lipid and protein peroxidation and lower NHE-1 activation were found in the IHEXE rats (p < 0.05 for each. Conclusion: IH-induced cardiac fibrosis was associated with NHE-1 hyperactivity. However, exercise training and cariporide exerted an inhibitory effect to prevent myocardial NHE-1 hyperactivity, which contributed to reduced IH-induced cardiac fibrosis. Therefore, NHE-1 plays a critical role in the effect of exercise on IH-induced increased cardiac fibrosis.

  19. Hormonal changes during GnRH analogue therapy in children with central precocious puberty

    DEFF Research Database (Denmark)

    Müller, J; Juul, A; Andersson, A M

    2000-01-01

    Gonadotropin releasing hormone analogues (GnRHa) have been used for treatment of central precocious puberty (CPP) for more than 15 years. They are generally considered safe although data on potential long-term side effects are scarce. However, GnRHa therapy has profound effects on both the hypoth......Gonadotropin releasing hormone analogues (GnRHa) have been used for treatment of central precocious puberty (CPP) for more than 15 years. They are generally considered safe although data on potential long-term side effects are scarce. However, GnRHa therapy has profound effects on both...

  20. Neuroprotective influence of taurine on fluoride-induced biochemical and behavioral deficits in rats.

    Science.gov (United States)

    Adedara, Isaac A; Abolaji, Amos O; Idris, Umar F; Olabiyi, Bolanle F; Onibiyo, Esther M; Ojuade, TeminiJesu D; Farombi, Ebenezer O

    2017-01-05

    Epidemiological and experimental studies have demonstrated that excessive exposure to fluoride induced neurodevelopmental toxicity both in humans and animals. Taurine is a free intracellular β-amino acid with antioxidant and neuroprotective properties. The present study investigated the neuroprotective mechanism of taurine by evaluating the biochemical and behavioral characteristics in rats exposed to sodium fluoride (NaF) singly in drinking water at 15 mg/L alone or orally co-administered by gavage with taurine at 100 and 200 mg/kg body weight for 45 consecutive days. Locomotor behavior was assessed using video-tracking software during a 10-min trial in a novel environment while the brain structures namely the hypothalamus, cerebrum and cerebellum of the rats were processed for biochemical determinations. Results showed that taurine administration prevented NaF-induced locomotor and motor deficits namely decrease in total distance travelled, total body rotation, maximum speed, absolute turn angle along with weak forelimb grip, increased incidence of fecal pellets and time of grooming, immobility and negative geotaxis. The taurine mediated enhancement of the exploratory profiles of NaF-exposed rats was supported by track and occupancy plot analyses. Moreover, taurine prevented NaF-induced increase in hydrogen peroxide and lipid peroxidation levels but increased acetylcholinesterase and the antioxidant enzymes activities in the hypothalamus, cerebrum and cerebellum of the rats. Collectively, taurine protected against NaF-induced neurotoxicity via mechanisms involving the restoration of acetylcholinesterase activity and antioxidant status with concomitant inhibition of lipid peroxidation in the brain of rats. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  1. Puberty suppression in gender identity disorder: the Amsterdam experience

    NARCIS (Netherlands)

    Kreukels, B.P.C.; Cohen-Kettenis, P.T.

    2011-01-01

    The use of gonadotropin-releasing hormone analogs (GnRHa) to suppress puberty in adolescents with gender dysphoria is a fairly new intervention in the field of gender identity disorders or transsexualism. GnRHa are used to give adolescents time to make balanced decisions on any further treatment

  2. Lives in a chiaroscuro. Should we suspend the puberty of children with gender identity disorder?

    Science.gov (United States)

    Giordano, S

    2008-08-01

    Transgender children who are not treated for their condition are at high risk of violence and suicide. As a matter of survival, many are willing to take whatever help is available, even if this is offered by illegal sources, and this often traps them into the juvenile criminal system and exposes them to various threats. Endocrinology offers a revolutionary instrument to help children/adolescents with gender identity disorder: suspension of puberty. Suspension of puberty raises many ethical issues, and experts dissent as to when treatment should be commenced and how children should be followed up. This paper argues that suspension of puberty is not only not unethical: if it is likely to improve the child's quality of life and even save his or her life, then it is indeed unethical to defer treatment.

  3. Renal and endocrine changes in rats with inherited stress-induced arterial hypertension (ISIAH)

    DEFF Research Database (Denmark)

    Amstislavsky, Sergej; Welker, Pia; Frühauf, Jan-Henning

    2006-01-01

    Hypertensive inbred rats (ISIAH; inherited stress-induced arterial hypertension) present with baseline hypertension (>170 mmHg in adult rats), but attain substantially higher values upon mild emotional stress. We aimed to characterize key parameters related to hypertension in ISIAH. Kidneys, adre...

  4. ZINC-INDUCED HYPERLEPTINEMIA IN RATS RELATED TO THE AMELIORATION OF SUCROSE-INDUCED OBESITY WITH ZINC REPLETION

    International Nuclear Information System (INIS)

    HEIBASHY, M.I.; EL-NAHLA, A.M.; ASHOUR, I.; SALEH, SH.Y.A.

    2008-01-01

    Thirty adult albino rats (Rattus rattus) at 6 weeks of age were divided into three groups (ten for each). The first group was fed a standard laboratory diet for 8 weeks (control). The second group was made obese by giving them 32% sucrose solution in addition to the standard laboratory diet .The third group was received zinc supplementation (50 mg zinc acetate/ litre) with their sucrose solution. Body weight of all rats was measured weekly for 8 weeks. At 14 weeks of age, rats were killed and fasting blood samples were obtained. Serum glucose, insulin, cholesterol, triglyceride, leptin, tumour necrosis factor-α and zinc were measured.Results showed remarkable changes in body weights in sucrose fed rats only when compared to control and supplemented zinc rats group. Serum glucose, insulin, cholesterol and triglycerides were significantly increased in sucrose fed rats than both control and sucrose with zinc group. Serum leptin showed significant increase in sucrose fed rats than control and also showed higher significant value in sucrose fed rats supplemented with zinc comparing with sucrose fed rats and control ones. Tumour necrosis factor-? did not show any significant difference between all groups. Serum zinc concentration was decreased significantly in sucrose fed rats as compared to control. On the other hand, it was increased significantly in sucrose fed rats supplemented with zinc than other both groups. It could be concluded that zinc supplementation induced hyperleptinemia caused ameliorating effects in obese rats

  5. Protective Effect of Piper aduncum Capsule on DMBA-induced Breast Cancer in Rats.

    Science.gov (United States)

    Arroyo-Acevedo, J; Chávez-Asmat, R J; Anampa-Guzmán, A; Donaires, R; Ráez-Gonzáles, José

    2015-01-01

    The possible protective effect of Piper aduncum capsule on DMBA (dimethylbenz[α]anthracene)-induced breast cancer in rats was assessed by monitoring the tumor and lung metastases incidence and recording hematological and biochemical parameters and frequency of micronuclei. Mammary carcinogenesis was induced in 36 female Holtzman rats by providing a single subcutaneous injection of DMBA. Oral administration of P. aduncum capsule lowered adenocarcinoma and lymph node metastases incidence. Pulmonary metastasis was significantly lowered (P < 0.05). Hematological indicators showed that the triglyceride level was significantly lowered (P < 0.01) and high-density lipoprotein (HDL) level was significantly increased (P < 0.01). Also, P. aduncum capsule significantly lowered the C reactive protein (CRP) level (P < 0.01) and malondialdehyde level (P < 0.05). There was a significant decrease in the frequency of DMBA-induced micronucleated polychromatic erythrocyte (P < 0.01). Considering the antitumorigenic, hypolipidemic, anti-inflammatory, antioxidant, and antigenotoxic properties of P. aduncum capsule, we conclude that it has a protective effect on DMBA-induced breast cancer in rats.

  6. Masked rat: an x-ray-induced mutant with chronic blepharitis, alopecia, and pasteurellosis

    International Nuclear Information System (INIS)

    Kent, R.L.; Lutzner, M.A.; Hansen, C.T.

    1976-01-01

    An autosomal recessive mutation had been previously x-ray-induced in the rat and named the masked rat (genotype mk/mk). This study describes the mutant's appearance, histology, and microflora. The rat's eyelids were swollen, often to the point of closure, and its face was partially covered by a brownish crust, giving the mutant a mask-like appearance. The chronic blepharitis was also accompanied by alopecia that appeared as bare patches across the mutant's back. Pasteurella pneumotropica was found in eyelids and on skin from all masked rats. The normal rat demonstrated a resistance to Pasteurella pneumotropica infection, or, conversely, the masked rat appeared to be genetically predisposed to pasteurellosis

  7. Cardioprotective effect of Erythrina stricta leaves on isoproterenol-induced myocardial infarction in rat

    Directory of Open Access Journals (Sweden)

    Asokkumar Kuppusamy

    2010-03-01

    Full Text Available The cardioprotective activity of Erythrina stricta leaves against isoproterenol- induced myocardial infarction was studied. Wistar albino rats were pretreated with leaf extract (200 mg/kg daily for 28 days. After treatment, isoproterenol (8.5 mg/kg body weight, orally was injected to rats at an interval of 24 hours for two days to induce myocardial injury. Cardioprotection was investigated by estimating the activities of serum aminotransferase, lactate dehydrogenase and creatinine kinase. Antioxidant enzymes such as superoxide dismutase, catalase, glutathione peroxidase, reduced glutathione and thiobarbituric acid reactive substances were determined. The activities of serum marker enzymes were increased significantly (p<0.05 in isoproterenol-induced rats. E. stricta leaf extract showed a decrease in serum enzyme levels and increase of antioxidant status. The results were confirmed by histopathological evidences. The present study concludes that E. stricta leaf extract has a prophylactic value in myocardial infarction.

  8. Cardioprotective effect of Erythrina stricta leaves on isoproterenol-induced myocardial infarction in rat

    Directory of Open Access Journals (Sweden)

    Divia Chirakkan

    2010-06-01

    Full Text Available The cardioprotective activity of Erythrina stricta leaves against isoproterenol- induced myocardial infarction was studied. Wistar albino rats were pretreated with leaf extract (200 mg/kg daily for 28 days. After treatment, isoproterenol (8.5 mg/kg body weight, orally was injected to rats at an interval of 24 hours for two days to induce myocardial injury. Cardioprotection was investigated by estimating the activities of serum aminotransferase, lactate dehydrogenase and creatinine kinase. Antioxidant enzymes such as superoxide dismutase, catalase, glutathione peroxidase, reduced glutathione and thiobarbituric acid reactive substances were determined. The activities of serum marker enzymes were increased significantly (p<0.05 in isoproterenol-induced rats. E. stricta leaf extract showed a decrease in serum enzyme levels and increase of antioxidant status. The results were confirmed by histopathological evidences. The present study concludes that E. stricta leaf extract has a prophylactic value in myocardial infarction.

  9. Speman®, A Proprietary Ayurvedic Formulation, Reverses Cyclophosphamide-Induced Oligospermia In Rats.

    Directory of Open Access Journals (Sweden)

    Mohd. Azeemuddin Mukram

    2013-04-01

    Full Text Available Background: This investigation was aimed to evaluate the effect of Speman®, a well known ayurvedic proprietary preparation, in an experimental model of cyclophosphamide-(CP induced oligospermia in rats.Materials and Methods: Thirty male rats were randomized in to five, equally-sized groups. Rats in group 1 served as a normal control; group 2 served as an untreated positive control; groups 3, 4, 5 received  Speman® granules  at doses of 300, 600, and 900mg/kg body weight p.o. respectively, once daily for 13 days. On day four, one hour after the respective treatment, oligospermia was induced by administering a single dose of CP (100mg/kg body weight p.o.  to all the groups except group1. At the end of the study period the rats were euthanised and accessory reproductive organs were weighed and subjected to histopathological examination. The semen samples were subject to enumeration of sperms.  Weight of the reproductive organs, histopathological examination of the tissues, and sperm count were the parameters studied to understand the effect of Speman® on rats with CP-induced oligospermia.Results: Changes that occurred due to the administration of CP at a dose of 100 mg/kg body weight were dose dependently reversed with Speman® at a dose of 300, 600, and 900 mg/kg body weight. There was a statistically significant increase in sperm count and the weight of the seminal vesicle, epididymis, and prostate.Conclusion: Findings of this investigation indicate that Speman® dose dependently reversed the CP-induced derangement of various parameters pertaining to the reproductive system.  This could explain the total beneficial actions of Speman® reported in several other clinical trials.

  10. Crocin Improved Learning and Memory Impairments in Streptozotocin-Induced Diabetic Rats

    Directory of Open Access Journals (Sweden)

    Esmaeal Tamaddonfard

    2013-01-01

    Full Text Available Objective(s: Crocin influences many biological functions including memory and learning. The present study was aimed to investigate the effects of crocin on learning and memory impairments in streptozotocine-induced diabetic rats. Materials and Methods: Diabetes was induced by intraperitoneal (IP injection of streptozotocin (STZ, 45 mg/kg. Transfer latency (TL paradigm in elevated plus-maze (EPM was used as an index of learning and memory. Plasma levels of total antioxidant capacity (TAC and malondialdehyde (MDA, blood levels of glucose, and serum concentrations of insulin were measured. The number of hippocampal neurons was also counted. Results: STZ increased acquisition transfer latency (TL1 and retention transfer latency (TL2, and MDA, decreased transfer latency shortening (TLs and TCA, produced hyperglycemia and hypoinsulinemia, and reduced the number of neurons in the hippocampus. Learning and memory impairments and blood TCA, MDA, glucose, and insulin changes induced by streptozotocin were improved with long-term IP injection of crocin at doses of 15 and 30 mg/kg. Crocin prevented hippocampal neurons number loss in diabetic rats. Conclusion: The results indicate that oxidative stress, hyperglycemia, hypoinsulinemia, and reduction of hippocampal neurons may be involved in learning and memory impairments in STZ-induced diabetic rats. Antioxidant, antihyperglycemic, antihypoinsulinemic, and neuroprotective activities of crocin might be involved in improving learning and memory impairments.

  11. Lithium induces microcysts and polyuria in adolescent rat kidney independent of cyclooxygenase‐2

    Science.gov (United States)

    Kjaersgaard, Gitte; Madsen, Kirsten; Marcussen, Niels; Jensen, Boye L.

    2014-01-01

    Abstract In patients, chronic treatment with lithium leads to renal microcysts and nephrogenic diabetes insipidus (NDI). It was hypothesized that renal cyclooxygenase‐2 (COX‐2) activity promotes microcyst formation and NDI. Kidney microcysts were induced in male adolescent rats by feeding dams with lithium (50 mmol/kg chow) from postnatal days 7–34. Lithium treatment induced somatic growth retardation, renal microcysts and dilatations in cortical collecting duct; it increased cortical cell proliferation and inactive pGSK‐3β abundance; it lowered aquaporin‐2 (AQP2) protein abundance and induced polyuria with decreased ability to concentrate the urine; and it increased COX‐2 protein level in thick ascending limb. Concomitant treatment with lithium and a specific COX‐2 inhibitor, parecoxib (5 mg/kg per day, P10–P34), did not prevent lithium‐induced microcysts and polyuria, but improved urine concentrating ability transiently after a 1‐desamino‐8‐D‐arginine vasopressin challenge. COX‐2 inhibition did not reduce cortical lithium‐induced cell proliferation and phosphorylation of glycogen synthase kinase‐3β (GSK‐3β). COX‐1 protein abundance increased in rat kidney cortex in response to lithium. COX‐1 immunoreactivity was found in microcyst epithelium in rat kidney. A human nephrectomy specimen from a patient treated for 28 years with lithium displayed multiple, COX‐1‐immunopositive, microcysts. In chronic lithium‐treated adolescent rats, COX‐2 is not colocalized with microcystic epithelium, mitotic activity, and inactive pGSK‐3β in collecting duct; a blocker of COX‐2 does not prevent cell proliferation, cyst formation, or GSK‐3β inactivation. It is concluded that COX‐2 activity is not the primary cause for microcysts and polyuria in a NaCl‐substituted rat model of lithium nephropathy. COX‐1 is a relevant candidate to affect the injured epithelium. PMID:24744881

  12. An experimental study on choroidal neovascularization induced by Krypton laser in rat model.

    Science.gov (United States)

    Cui, Jing; Liu, Yuanyuan; Zhang, Jingkai; Yan, Hua

    2014-01-01

    The purpose of this work was to study the efficacy and safety of choroidal neovascularization (CNV) formation induced by Krypton laser in Brown Norway (BN) rats, and observe the trend of the change of CNV after laser photocoagulation. Twenty-five male BN rats were involved in this study. Two eyes of one rat without any laser photocoagulation were randomly selected as the control group, and the other 48 eyes of 24 rats were selected as the experimental group. Eight eyes of four rats were randomly selected to receive the examinations of fundus fluorescein angiography (FFA), histopathology, and transmission electron microscopy 3, 7, 14, 21, 28, and 56 days after laser photocoagulation. After laser photocoagulation, the leakage appeared in burns on day 7 (59%), reached the peak on day 21 (84%), (p0.05). The thickness of CNV increased from day 7 to day 21 (p0.05). The experimental model of CNV can be successfully induced by Krypton laser in rats with a stable, long-lasting, and high success rate. After laser photocoagulation, the leakages appear on day 7, reach the peak on day 21, and remain stable after day 21.

  13. Gamma-aminobutyric acid aggravates nephrotoxicity induced by cisplatin in female rats.

    Science.gov (United States)

    Peysepar, Elham; Soltani, Nepton; Nematbakhsh, Mehdi; Eshraghi-Jazi, Fatemeh; Talebi, Ardeshir

    2016-01-01

    Cisplatin (CP) is a major antineoplastic drug for treatment of solid tumors. CP-induced nephrotoxicity may be gender-related. This is while gamma-aminobutyric acid (GABA) is an inhibitory neurotransmitter in the central nervous system that has renoprotective impacts on acute renal injury. This study was designed to investigate the protective role of GABA against CP-induced nephrotoxicity in male and female rats. Sixty Wistar male and female rats were used in eight experimental groups. Both genders received GABA (50 μg/kg/day; i. p.) for 14 days and CP (2.5 mg/kg/day; i. p.) was added from day 8 to the end of the study, and they were compared with the control groups. At the end of the study, all animals were sacrificed and the serum levels of blood urea nitrogen (BUN), creatinine (Cr), nitrite, malondialdehyde (MDA), and magnesium (Mg) were measured. The kidney tissue damage was also determined via staining. CP significantly increased the serum levels of Cr and BUN, kidney weight, and kidney tissue damage score in both genders (PGABA did not attenuate these markers in males; even these biomarkers were intensified in females. Serum level of Mg, and testis and uterus weights did not alter in the groups. However, the groups were significantly different in terms of nitrite and MDA levels. It seems that GABA did not improve nephrotoxicity induced by CP-treated rats, and it exacerbated renal damage in female rats.

  14. Effects of betaine supplementation and choline deficiency on folate deficiency-induced hyperhomocysteinemia in rats.

    Science.gov (United States)

    Liu, Ying; Liu, Yi-qun; Morita, Tatsuya; Sugiyama, Kimio

    2012-01-01

    The effect of betaine status on folate deficiency-induced hyperhomocysteinemia was investigated to determine whether folate deficiency impairs homocysteine removal not only by the methionine synthase (MS) pathway but also by the betaine-homocysteine S-methyltransferase (BHMT) pathway. For this purpose, we investigated the effect of dietary supplementation with betaine at a high level (1%) in rats fed a folate-deprived 10% casein diet (10C) and 20% casein diet (20C). We also investigated the effect of choline deprivation on folate deficiency-induced hyperhomocysteinemia in rats fed 20C. Supplementation of folate-deprived 10C and 20C with 1% betaine significantly suppressed folate deprivation-induced hyperhomocysteinemia, but the extent of suppression was partial or limited, especially in rats fed 10C, the suppression of plasma homocysteine increment being 48.5% in rats fed 10C and 69.7% in rats fed 20C. Although betaine supplementation greatly increased hepatic betaine concentration and BHMT activity, these increases did not fully explain why the effect of betaine supplementation was partial or limited. Folate deprivation markedly increased the hepatic concentration of N,N-dimethylglycine (DMG), a known inhibitor of BHMT, and there was a significant positive correlation between hepatic DMG concentration and plasma homocysteine concentration, suggesting that folate deficiency increases hepatic DMG concentration and thereby depresses BHMT reaction, leading to interference with the effect of betaine supplementation. Choline deprivation did not increase plasma homocysteine concentration in rats fed 20C, but it markedly enhanced plasma homocysteine concentration when rats were fed folate-deprived 20C. This indicates that choline deprivation reinforced folate deprivation-induced hyperhomocysteinemia. Increased hepatic DMG concentration was also associated with such an effect. These results support the concept that folate deficiency impairs homocysteine metabolism not only

  15. Controlled-release levodopa methyl ester/benserazide-loaded nanoparticles ameliorate levodopa-induced dyskinesia in rats

    Directory of Open Access Journals (Sweden)

    Yang X

    2012-04-01

    Full Text Available Xinxin Yang1*, Ruiyuan Zheng2*, Yunpeng Cai2, Meiling Liao2, Weien Yuan1,2, Zhenguo Liu11Department of Neurology, Xinhua Hospital (affiliated to Shanghai Jiaotong University School of Medicine, 2School of Pharmacy, Shanghai Jiaotong University, Shanghai, People's Republic of China*Xinxin Yang and Ruiyuan Zheng contributed equally to this workBackground: Levodopa remains the most effective drug in the treatment of Parkinson's disease. However, long-term administration of levodopa induces motor complications, such as levodopa-induced dyskinesia. The mechanisms underlying levodopa-induced dyskinesia are not fully understood.Methods: In this study, we prepared levodopa methyl ester (LDME/benserazide-loaded nanoparticles, which can release LDME and benserazide in a sustained manner. Dyskinesia was induced in rats by repeated administration of levodopa then treated with LDME plus benserazide or the same dose of LDME/benserazide-loaded nanoparticles. Apomorphine-induced rotations and abnormal involuntary movements (AIMs were measured on treatment days 1, 5, 10, 15, and 20. In addition, the levels of phosphorylated dopamine- and cyclic adenosine monophosphate-regulated phosphoprotein of 32 kDa, extracellular signal-regulated kinases 1/2, and ΔfosB were determined by Western blot. Tau levels were determined by Western blot and immunohistochemistry. Dynorphin levels in the striatum and cortex of rats were measured using enzyme-linked immunosorbent assay.Results: Over the course of levodopa treatment, the rats developed abnormal AIMs, classified as locomotive, axial, orolingual, and forelimb dyskinesia. The degree of reduction of apomorphine-induced rotations was comparable in dyskinetic rats treated with LDME plus benserazide or LDME/benserazide-loaded nanoparticles. The axial, limb, and orolingual (ALO AIMs of dyskinetic rats treated with LDME/benserazide-loaded nanoparticles were 14 ± 2.5, 9 ± 2.0, and 10 ± 2.1 on treatment days 10, 15, and 20

  16. Final height in central precocious puberty after long term treatment with a slow release GnRH agonist

    NARCIS (Netherlands)

    Oostdijk, W; Rikken, B; Schreuder, S; Otten, Barto; Odink, R; Rouwe, C; Jansen, M; Gerver, WJ; Waelkens, J; Drop, S

    1996-01-01

    Objective-To study the resumption of puberty and the final height achieved in children with central precocious puberty (CPP) treated with the GnRH agonist triptorelin. Patients-31 girls and five boys with CPP who were treated with triptorelin 3.75 mg intramuscularly every four weeks. Girls were

  17. Camel Milk Beneficial Effects on Treating Gentamicin Induced Alterations in Rats

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    Abdulrahman K. Al-Asmari

    2014-01-01

    Full Text Available The potential effect of camel milk (CM against gentamicin (GM induced biochemical changes in the rat serum was evaluated. Four groups of six albino rats were used for control, CM fed, injected with GM(i.p., and then fed and injected with GM. The results showed that the administration of GM significantly altered the levels of aspartate aminotransferase (AST, alanine aminotransferase (ALT, alkaline phosphatase (ALP, and lactate dehydrogenase (LDH activity in rat serum. CM restored these parameters to almost their normal range in group IV. Additionally, the present study showed that injection of rats with gentamicin caused an increase in malondialdehyde (MDA and myeloperoxidase (MPO activity while the antioxidant enzymes like superoxide dismutase (SOD and glutathione s-transferase (GST activity decreased significantly (P≤0.05. Administration of CM significantly (P≤0.05 inhibited the formation of MDA and activity of MPO and upregulated the antioxidant enzymes (SOD and GST activity. The overall findings of this study demonstrated that pretreatment with CM gave protection against GM induced hepatic damage possibly by inhibiting oxidative stress and inflammation, and hence camel milk can be identified as a new therapeutic agent.

  18. Hypolipidemic activity of Piper betel in high fat diet induced hyperlipidemic rat

    OpenAIRE

    Thirunavukkarasu Thirumalai; Narayanaswamy Tamilselvan; Ernest David

    2014-01-01

    Objective: To evaluate the hypolipidemic effect of Piper betel (P. betel) in high fat diet induced hyperlipidemia rat. Methods: The methanol leaf extract was tested for hypolipidemic effect in the albino rats at the selected optimum dosage of 250 mg/kg body weight and administered orally. Adult male albino rats of six numbers in each group were undertaken study and evaluated. Results: In group II animals, the activity levels of serum total cholesterol (TC), triglycerides (TG), low densi...

  19. A case of late presentation of precocious puberty due to pituitary astrocytoma

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    Fahimeh Soheilipour

    2015-08-01

    Full Text Available The importance of assessing precocious puberty, especially in boys, is not only due to the great complications it has for the affected patients, but also to the fatal underlying diseases. Therefore, children with central precocious puberty should first undergo neuroimaging. In this case study, we present a 9.5-year-old boy who was referred to Rasoul-e-Akram Medical Center with increased intracranial pressure, nausea/vomiting, and severe headache having begun three months earlier. The development of secondary sexual changes had started two years earlier, and had been neglected. His testes, penis, and pubic hair were at the fourth Tanner stage. He had elevated luteinizing and follicle stimulating hormones. Microscopic evaluation confirmed low-grade pilocytic astrocytoma WHO grade 1. Emergency brain surgery was conducted in which the brain was decompressed, and chemotherapy was started postoperatively. Two years after the surgery, he remains under chemotherapy, with obvious sexual maturation and a height of 154 cm. Training families and medical staff efficiently can help prevent the late diagnosis and treatment of precocious puberty and, as a result, help patients in their social life.

  20. Hormone-induced protection against mammary tumorigenesis is conserved in multiple rat strains and identifies a core gene expression signature induced by pregnancy.

    Science.gov (United States)

    Blakely, Collin M; Stoddard, Alexander J; Belka, George K; Dugan, Katherine D; Notarfrancesco, Kathleen L; Moody, Susan E; D'Cruz, Celina M; Chodosh, Lewis A

    2006-06-15

    Women who have their first child early in life have a substantially lower lifetime risk of breast cancer. The mechanism for this is unknown. Similar to humans, rats exhibit parity-induced protection against mammary tumorigenesis. To explore the basis for this phenomenon, we identified persistent pregnancy-induced changes in mammary gene expression that are tightly associated with protection against tumorigenesis in multiple inbred rat strains. Four inbred rat strains that exhibit marked differences in their intrinsic susceptibilities to carcinogen-induced mammary tumorigenesis were each shown to display significant protection against methylnitrosourea-induced mammary tumorigenesis following treatment with pregnancy levels of estradiol and progesterone. Microarray expression profiling of parous and nulliparous mammary tissue from these four strains yielded a common 70-gene signature. Examination of the genes constituting this signature implicated alterations in transforming growth factor-beta signaling, the extracellular matrix, amphiregulin expression, and the growth hormone/insulin-like growth factor I axis in pregnancy-induced alterations in breast cancer risk. Notably, related molecular changes have been associated with decreased mammographic density, which itself is strongly associated with decreased breast cancer risk. Our findings show that hormone-induced protection against mammary tumorigenesis is widely conserved among divergent rat strains and define a gene expression signature that is tightly correlated with reduced mammary tumor susceptibility as a consequence of a normal developmental event. Given the conservation of this signature, these pathways may contribute to pregnancy-induced protection against breast cancer.

  1. Quercetin Attenuates Vascular Calcification through Suppressed Oxidative Stress in Adenine-Induced Chronic Renal Failure Rats.

    Science.gov (United States)

    Chang, Xue-Ying; Cui, Lei; Wang, Xing-Zhi; Zhang, Lei; Zhu, Dan; Zhou, Xiao-Rong; Hao, Li-Rong

    2017-01-01

    This study investigated whether quercetin could alleviate vascular calcification in experimental chronic renal failure rats induced by adenine. 32 adult male Wistar rats were randomly divided into 4 groups fed normal diet, normal diet with quercetin supplementation (25 mg/kg·BW/d), 0.75% adenine diet, or adenine diet with quercetin supplementation. All rats were sacrificed after 6 weeks of intervention. Serum renal functions biomarkers and oxidative stress biomarkers were measured and status of vascular calcification in aorta was assessed. Furthermore, the induced nitric oxide synthase (iNOS)/p38 mitogen activated protein kinase (p38MAPK) pathway was determined to explore the potential mechanism. Adenine successfully induced renal failure and vascular calcification in rat model. Quercetin supplementation reversed unfavorable changes of phosphorous, uric acid (UA) and creatinine levels, malonaldehyde (MDA) content, and superoxide dismutase (SOD) activity in serum and the increases of calcium and alkaline phosphatase (ALP) activity in the aorta ( P chronic renal failure rats, possibly through the modulation of oxidative stress and iNOs/p38MAPK pathway.

  2. Quercetin Attenuates Vascular Calcification through Suppressed Oxidative Stress in Adenine-Induced Chronic Renal Failure Rats

    Science.gov (United States)

    Chang, Xue-ying; Cui, Lei; Wang, Xing-zhi; Zhang, Lei; Zhu, Dan

    2017-01-01

    Background This study investigated whether quercetin could alleviate vascular calcification in experimental chronic renal failure rats induced by adenine. Methods 32 adult male Wistar rats were randomly divided into 4 groups fed normal diet, normal diet with quercetin supplementation (25 mg/kg·BW/d), 0.75% adenine diet, or adenine diet with quercetin supplementation. All rats were sacrificed after 6 weeks of intervention. Serum renal functions biomarkers and oxidative stress biomarkers were measured and status of vascular calcification in aorta was assessed. Furthermore, the induced nitric oxide synthase (iNOS)/p38 mitogen activated protein kinase (p38MAPK) pathway was determined to explore the potential mechanism. Results Adenine successfully induced renal failure and vascular calcification in rat model. Quercetin supplementation reversed unfavorable changes of phosphorous, uric acid (UA) and creatinine levels, malonaldehyde (MDA) content, and superoxide dismutase (SOD) activity in serum and the increases of calcium and alkaline phosphatase (ALP) activity in the aorta (P chronic renal failure rats, possibly through the modulation of oxidative stress and iNOs/p38MAPK pathway. PMID:28691026

  3. Peripubertal castration of male rats, adult open field ambulation and partner preference behavior.

    Science.gov (United States)

    Brand, T; Slob, A K

    1988-09-15

    The validity of the hypothesis put forward earlier, that testicular secretions during puberty have an organizing effect on open field ambulation was examined. Male rats were castrated or sham-operated at days 21, 43 or 70. At the age of 17 weeks the males were tested in an automated, octagonal open field (3 consecutive days, 3 min/day) for locomotor activity. Male rats castrated at day 21 or day 43 ambulated more than sham-castrated controls. Males castrated at day 70 did not differ from sham-castrated controls. It thus appears that pubertal testicular secretion(s) organize adult open field locomotor activity in male rats. From 18 weeks of age partner preference behavior was tested in the same open field apparatus with one adjacent cage containing an ovariectomized female and an opposite one containing an ovariectomized female brought into heat. The females in the adjacent cages were separated from the experimental males in the octagonal cage by wire mesh. Peripubertally castrated males did not show a clear-cut partner preference, whereas the intact males preferred the vicinity of the estrous female. There were no differences among the males castrated either before, during or after puberty. Testosterone treatment (crystalline T in silastic capsules) caused peripubertally castrated males to prefer the estrous female. Thus, adult partner preference behavior does not seem to be organized by peripubertal testicular androgens.

  4. Structural and numerical chromosome aberration inducers in liver micronucleus test in rats with partial hepatectomy.

    Science.gov (United States)

    Itoh, Satoru; Hattori, Chiharu; Nagata, Mayumi; Sanbuissho, Atsushi

    2012-08-30

    The liver micronucleus test is an important method to detect pro-mutagens such as active metabolites not reaching bone marrow due to their short lifespan. We have already reported that dosing of the test compound after partial hepatectomy (PH) is essential to detect genotoxicity of numerical chromosome aberration inducers in mice [Mutat. Res. 632 (2007) 89-98]. In naive animals, the proportion of binucleated cells in rats is less than half of that in mice, which suggests a species difference in the response to chromosome aberration inducers. In the present study, we investigated the responses to structural and numerical chromosome aberration inducers in the rat liver micronucleus test. Two structural chromosome aberretion inducers (diethylnitrosamine and 1,2-dimethylhydrazine) and two numerical chromosome aberration inducers (colchicine and carbendazim) were used in the present study. PH was performed a day before or after the dosing of the test compound in 8-week old male F344 rats and hepatocytes were isolated 4 days after the PH. As a result, diethylnitrosamine and 1,2-dimethylhydrazine, structural chromosome aberration inducers, exhibited significant increase in the incidence of micronucleated hepatocyte (MNH) when given either before and after PH. Colchicine and carbendazim, numerical chromosome aberration inducers, did not result in any toxicologically significant increase in MNH frequency when given before PH, while they exhibited MNH induction when given after PH. It is confirmed that dosing after PH is essential in order to detect genotoxicity of numerical chromosome aberration inducers in rats as well as in mice. Regarding the species difference, a different temporal response to colchicine was identified. Colchicine increased the incidence of MNH 4 days after PH in rats, although such induction in mice was observed 8-10 days after PH. Copyright © 2012 Elsevier B.V. All rights reserved.

  5. Experimental research on recombinant human endostatin-induced cardiomyocyte apoptosis in rats

    Directory of Open Access Journals (Sweden)

    Jing QIN

    2014-03-01

    Full Text Available Objective To explore the recombinant human endostatin (rh-ES-induced cardiotoxicity in rats and its mechanism. Methods Twenty four female Wistar rats were randomly divided into four groups (6 each. Rats in low, moderate and high dose group received rh-ES with a dosage of 3, 6 and 12mg/(kg·d, respectively, by intraperitoneal injection, and rats in control group received the same amount of normal saline alone. Half of rats in each group were sacrificed by spinal dislocation after 4 weeks and 8 weeks of the treatment. Pathomorphologic and ultrastructural changes in rat's myocardial tissue were evaluated by light microscopy and transmission electron microscopy. Cardiomyocyte apoptosis was detected with TdT-mediated dUTP nick end labeling (TUNEL assay. Microvessel density (MVD in myocardial tissue was measured by immunohistochemically marking endothelial cell with CD34. Results No pathomorphologic and ultrastrucural changes were found under light microscope and transmission electron microscope in the low dose and moderate dose groups, but cardiomyocyte damage were found in the high dose group. TUNEL assay revealed more apoptotic cells in high and moderate (only 8 weeks dose groups than in control group (P=0.033, P=0.000, and the apoptosis index was highest in the high dose group at 8 weeks. In addition, compared with the control group, MVD significantly increased in high dose groups at 4 weeks and 8 weeks (P<0.05. Conclusions rh-ES induces the cardiotoxicity in rats, and cardiomyocyte apoptosis is involved in the pathological course of cardiac toxicity. DOI: 10.11855/j.issn.0577-7402.2014.01.02

  6. Curcumin loaded solid lipid nanoparticles ameliorate adjuvant-induced arthritis in rats.

    Science.gov (United States)

    Arora, R; Kuhad, A; Kaur, I P; Chopra, K

    2015-08-01

    Rheumatoid arthritis (RA), a chronic and systemic inflammation, results in destruction of joints and cartilages. Effectiveness of curcumin has been established in a wide variety of inflammatory disorders, but its utility as a therapeutic agent is limited by its poor absorption, rapid metabolism and fast systemic elimination. To apprehend these limitations, we propose to use highly bioavailable curcumin loaded solid lipid nanoparticles (C-SLNs) for the treatment of RA. In the present study, the protective effect of curcumin and its SLNs was evaluated in complete Freund's adjuvant (CFA)-induced arthritis in rats. Arthritic rats exhibited marked decrease in paw withdrawal threshold in Randall-Selitto and von Frey hair test along with decreased reaction time in hot plate. Arthritic rats also showed significant joint hyperalgesia, joint stiffness and increased paw volume along with marked decrease in mobility score. Arthritic rats showed a significant increase in blood leukocyte count, oxidative-nitrosative stress, tumour necrosis factor-α, C-reactive protein, cyclic citrullinated peptide antibody levels and radiological alterations in tibiotarsal joint. C-SLN administration (10 and 30 mg/kg), when compared with free curcumin (10 and 30 mg/kg), significantly and dose dependently ameliorated various symptoms of arthritis in rats, improved biochemical markers and preserved radiological alterations in joints of arthritic rats. The current findings suggest the protective potential of curcumin-SLNs in ameliorating CFA-induced arthritis in rats through attenuation of oxido-inflammatory and immunomodulatory cascade. Further, the results emphasize that SLNs are a novel approach to deliver curcumin into the inflamed joints and improve its biopharmaceutical performance. © 2014 European Pain Federation - EFIC®

  7. Profile of blood glucose and ultrastucture of beta cells pancreatic islet in alloxan compound induced rats

    Directory of Open Access Journals (Sweden)

    I Nyoman Suarsana

    2010-06-01

    Full Text Available Diabetes is marked by elevated levels of blood glucose, and progressive changes of the structure of pancreatic islet histopathology. The objective of this research was to analyse the glucose level and histophatological feature in pancreatic islet in alloxan compound induced rats. A total of ten male Spraque Dawley rats of 2 months old were used in this study. The rats were divided into two groups: (1 negative control group (K-, and (2 positif induced alloxan group (diabetic group =DM. The rats were induced by a single dose intraperitonial injection of alloxan compound 120 mg/kg of body weight. The treatment was conducted for 28 days. Blood glucose levels of rats were analysed at 0, 4, 7, 14, 21, and 28 days following treatment. At the end of the experiment, rats were sacrificed by cervical dislocation. Pancreas was collected for analysis of histopathological study by Immunohistochemical technique, and ultrastructural study using transmission electron microscope (TEM. The result showed that Langerhans islet of diabetic rat (rat of DM group showed a marked reduction of size, number of Langerhans islet of diabetic rat decrease, and characterized by hyperglycemic condition. By using TEM, beta cells of DM group showed the rupture of mitochondrial membrane, the lost of cisternal structure of inner membrane of mitocondria, reduction of insulin secretory granules, linkage between cells acinar with free Langerhans islet, and the caryopicnotic of nucleus.

  8. Effects of Streptococcus thermophilus TH-4 in a rat model of doxorubicin-induced mucositis.

    Science.gov (United States)

    Wang, Hanru; Brook, Caitlin L; Whittaker, Alexandra L; Lawrence, Andrew; Yazbeck, Roger; Howarth, Gordon S

    2013-08-01

    Mucositis is a debilitating intestinal side effect of chemotherapeutic regimens. Probiotics have been considered a possible preventative treatment for mucositis. Streptococcus thermophilus TH-4 (TH-4), a newly identified probiotic, has been shown to partially alleviate mucositis induced by administration of the antimetabolite chemotherapy drug, methotrexate in rats; likely mediated through a mechanism of folate production. However, its effects against other classes of chemotherapy drug have yet to be determined. The authors investigated the effects of TH-4 in a rat model of mucositis induced by the anthracycline chemotherapy drug, doxorubicin. Gastrointestinal damage was induced in female Dark Agouti rats (148.3 ± 1.5 g) by intraperitoneal injection of doxorubicin (20 mg/kg). Animals recieved a daily oral gavage of TH-4 at 10(9) cfu/ml or skim milk (vehicle) from days 0 to 8. At day 6, rats were injected with either saline or doxorubicin. At kill, small intestinal tissues were collected for determination of sucrase and myeloperoxidase (MPO) activities and histological assessment. Body weight was significantly decreased by doxorubicin compared with normal controls (p TH-4 partially prevented the loss of body weight induced by doxorubicin (2.3% compared with 4%), but provided no further therapeutic benefit. The minimal amelioration of doxorubicin-induced mucositis by TH-4 further supports folate production as a likely mechanism of TH-4 action against methotrexate-induced mucositis. Further studies into TH-4 are required to confirm its applicability to other conventional chemotherapy regimens.

  9. Normalized Urinary Flow at Puberty after Tubularized Incised Plate Urethroplasty for Hypospadias in Childhood.

    Science.gov (United States)

    Andersson, Marie; Doroszkiewicz, Monika; Arfwidsson, Charlotte; Abrahamsson, Kate; Sillén, Ulla; Holmdahl, Gundela

    2015-11-01

    An obstructive urinary flow pattern is frequently seen after tubularized incised plate urethroplasty for hypospadias. However, the significance of this finding has not been determined and long-term results are few. We describe postoperative long-term uroflowmetry results after puberty in males who underwent tubularized incised plate urethroplasty in childhood. A total of 126 boys underwent tubularized incised plate urethroplasty for distal penile to mid shaft hypospadias at Queen Silvia Children's Hospital in Gothenburg between 1999 and 2003. Of the patients 48 were toilet trained at surgery. We report on 40 patients who had data available at 2 and 12 months postoperatively, 7 years postoperatively and at puberty (median age 15.0 years, range 13.7 to 17.1). Of the patients 31 had distal and 9 had mid penile hypospadias. Clinical examination, urinary medical history, uroflowmetry and ultrasound measuring residual urine were performed. Maximum urinary flow was correlated to age and voided volume, using Miskolc nomograms for comparison of percentiles. At 1 year postoperatively 15 boys (37.5%) had normal urinary flow (above 25th percentile), compared to 16 (40%) at 7 years and 38 (95%) at puberty (p puberty for boys with hypospadias treated with tubularized incised plate urethroplasty. Unless symptoms occur, a conservative approach seems preferable. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  10. Effect of Urtica dioica L. (Urticaceae) on testicular tissue in STZ-induced diabetic rats.

    Science.gov (United States)

    Ghafari, S; Balajadeh, B Kabiri; Golalipour, M J

    2011-08-15

    Urtica dioica L. (Stinging nettle) has already been known for a long time as a medicinal plant in the world. This histopathological and morphometrical study was conducted to determine the effects of the hydroalcoholic extract of Urtica dioica leaves on testis of streptozotocin-induced diabetic rats. Eighteen male Wistar rats were allocated to equally normal, diabetic and treatment groups. Hyperglycemia was induced by Streptozotocin (80 mg kg(-1)) in animals of diabetic and treatment groups. One week after STZ injection (80 mg kg(-1)), the rats of treatment group received the extract of U. dioica (100 mg/kg/day) IP for 28 days. After 5 weeks of study, all the rats were sacrificed and testes were removed and fixed in bouin and after tissue processing stained with H and E technique. Tubular cell disintegration, sertoli and spermatogonia cell vacuolization and decrease in sperm concentration in seminiferous tubules were seen in diabetic and treatment groups group in comparison with control. External Seminiferous Tubular Diameter (STD) and Seminiferous Epithelial Height (SEH) significantly reduced (p < 0.05) in the diabetic rats compared with controls and these parameters in the treatment group were similar to diabetics animals. This study showed that hydroalcoholic extract of Urtica dioica leaves, after induction of diabetes; has no treatment effect on seminiferous tubules alterations in streptozotocin-induced diabetic rats.

  11. Ketamine-induced apoptosis in cultured rat cortical neurons

    International Nuclear Information System (INIS)

    Takadera, Tsuneo; Ishida, Akira; Ohyashiki, Takao

    2006-01-01

    Recent data suggest that anesthetic drugs cause neurodegeneration during development. Ketamine is frequently used in infants and toddlers for elective surgeries. The purpose of this study is to determine whether glycogen synthase kinase-3 (GSK-3) is involved in ketamine-induced apoptosis. Ketamine increased apoptotic cell death with morphological changes which were characterized by cell shrinkage, nuclear condensation or fragmentation. In addition, insulin growth factor-1 completely blocked the ketamine-induced apoptotic cell death. Ketamine decreased Akt phosphorylation. GSK-3 is known as a downstream target of Akt. The selective inhibitors of GSK-3 prevented the ketamine-induced apoptosis. Moreover, caspase-3 activation was accompanied by the ketamine-induced cell death and inhibited by the GSK-3 inhibitors. These results suggest that activation of GSK-3 is involved in ketamine-induced apoptosis in rat cortical neurons

  12. Amnesia induced by morphine in spatial memory retrieval inhibited in morphine-sensitized rats.

    Science.gov (United States)

    Farahmandfar, Maryam; Naghdi, Nasser; Karimian, Seyed Morteza; Kadivar, Mehdi; Zarrindast, Mohammad-Reza

    2012-05-15

    The present study investigated the effect of morphine sensitization on the impairment of spatial memory retrieval induced by acute morphine in adult male rats. Spatial memory was assessed by 2-day Morris water maze task which included training and test day. On the training day, rats were trained by a single training session of 8 trials. On the test day, a probe trial consisting of 60s free swim period without a platform and the visible test were administered. Morphine sensitization was induced by subcutaneous (s.c.) injection of morphine, once daily for 3 days followed by 5 days without drug treatment before training. The results indicated that acute administration of morphine (7.5mg/kg, s.c.) before testing impaired spatial memory on the test day. Pre-test morphine-induced amnesia decreased in morphine-sensitized (15 and 20mg/kg, s.c.) rats. Improvement in spatial memory retrieval in morphine-sensitized rats was inhibited by once daily administration of naloxone (1 and 2mg/kg, s.c.) 30 min prior to the injection of morphine for three days. The results suggest that morphine sensitization reverses the impairment of spatial memory retrieval induced by acute morphine and it is implied that mu-opioid receptors may play an important role in this effect. Copyright © 2012 Elsevier B.V. All rights reserved.

  13. Bees’ Honey Attenuation of Metanil-Yellow-Induced Hepatotoxicity in Rats

    Directory of Open Access Journals (Sweden)

    Abdulrahman L. Al-Malki

    2013-01-01

    Full Text Available The present study aims to investigate the protective effect of bees’ honey against metanil-yellow-induced hepatotoxicity in rats. Rats were divided into 7 groups: control group; three groups treated with 50, 100, and 200 mg/kg metanil yellow, and three groups treated with metanil yellow plus 2.5 mg·kg-1·day-1 bees’ honey for 8 weeks. The obtained data showed that the antioxidant/anti-inflammatory activity of bees’ honey reduced the oxidative stress in the liver tissue and downregulated the inflammatory markers. In addition, the elevated levels of AGE and the activated NF-κB in the metanil-yellow-treated animals were significantly attenuated. Moreover, the levels of TNF-α and IL-1β were significantly attenuated as a result of bees’ honey administration. Furthermore, the histopathological examination of the liver showed that bees’ honey reduced fatty degeneration, cytoplasmic vacuolization, and necrosis in metanil-yellow-treated rats. In conclusion, the obtained data suggest that bees’ honey has hepatoprotective effect on acute liver injuries induced by metanil-yellow in vivo, and the results suggested that the effect of bees’ honey against metanil yellow-induced liver damage is related to its antioxidant/anti-inflammatory properties which attenuate the activation of NF-κB and its controlled genes like TNF-α and IL-1β.

  14. Food Color Induced Hepatotoxicity in Swiss Albino Rats, Rattus norvegicus.

    Science.gov (United States)

    Saxena, Beenam; Sharma, Shiv

    2015-01-01

    Certain dietary constituents can induce toxicity and play a critical role in the development of several hepatic disorders. Tartrazine, metanil yellow and sunset yellow are widely used azo dyes in food products, so the present study is aimed to investigate the food color induced hepatotoxicity in Swiss albino rats. Swiss albino rats were divided into four groups, each group having six animals. Group I served as control, Group II, Group III and Group IV were administered with 25, 50 and 75 mg/kg body weight blend of sunset yellow, metanil yellow and tartrazine for 30 days. Hepatotoxicity in rats treated with a blend of these food colors was studied by assessing parameters such as serum total protein, serum albumin, serum alkaline phosphatase (ALP) as well as hepatic malondialdehyde (MDA). The activity of superoxide dismutase (SOD), reduced glutathione (GSH) and catalase (CAT) were assessed. Significantly increased concentrations of serum total protein, serum albumin, serum ALP and hepatic MDA and significantly lowered levels of SOD, reduced GSH and CAT in the liver tissue of treated animals were observed when compared with control animals. The alteration in the liver includes necrosis of hepatocytes, infiltration and vacuolation. The result indicates that consumption of food color in diet induces liver tissue damage. The used doses of food color were mostly attributable to hepatocellular damage and drastic alteration in antioxidant defense system.

  15. Virilizing adrenocortical carcinoma advancing to central precocious puberty after surgery.

    Science.gov (United States)

    Kim, Min Sun; Yang, Eu Jeen; Cho, Dong Hyu; Hwang, Pyung Han; Lee, Dae-Yeol

    2015-05-01

    Adrenocortical carcinoma (ACC) in pediatric and adolescent patients is rare, and it is associated with various clinical symptoms. We introduce the case of an 8-year-old boy with ACC who presented with peripheral precocious puberty at his first visit. He displayed penis enlargement with pubic hair and facial acne. His serum adrenal androgen levels were elevated, and abdominal computed tomography revealed a right suprarenal mass. After complete surgical resection, the histological diagnosis was ACC. Two months after surgical removal of the mass, he subsequently developed central precocious puberty. He was treated with a gonadotropin-releasing hormone agonist to delay further pubertal progression. In patients with functioning ACC and surgical removal, clinical follow-up and hormonal marker examination for the secondary effects of excessive hormone secretion may be a useful option at least every 2 or 3 months after surgery.

  16. Fluoride-elicited developmental testicular toxicity in rats: Roles of endoplasmic reticulum stress and inflammatory response

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Shun [Department of Environmental Health and MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Hangkong Road 13, Wuhan 430030, Hubei (China); Jiang, Chunyang [Department of Environmental Health and MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Hangkong Road 13, Wuhan 430030, Hubei (China); Department of Thoracic Surgery, Tianjin Union Medicine Centre, 190 Jieyuan Road, Hongqiao District, Tianjin 300121, Tianjin (China); Liu, Hongliang [Tianjin Center for Disease Control and Prevention, Huayue Road 6, Hedong Region, Tianjin 300011, Tianjin (China); Guan, Zhizhong [Department of Pathology, Guiyang Medical College, Guiyang 550004, Guizhou (China); Zeng, Qiang [Tianjin Center for Disease Control and Prevention, Huayue Road 6, Hedong Region, Tianjin 300011, Tianjin (China); Zhang, Cheng; Lei, Rongrong; Xia, Tao; Gao, Hui; Yang, Lu; Chen, Yihu; Wu, Xue; Zhang, Xiaofei [Department of Environmental Health and MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Hangkong Road 13, Wuhan 430030, Hubei (China); Cui, Yushan; Yu, Linyu [Tianjin Center for Disease Control and Prevention, Huayue Road 6, Hedong Region, Tianjin 300011, Tianjin (China); Wang, Zhenglun [Department of Environmental Health and MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Hangkong Road 13, Wuhan 430030, Hubei (China); Wang, Aiguo, E-mail: wangaiguo@mails.tjmu.edu.cn [Department of Environmental Health and MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Hangkong Road 13, Wuhan 430030, Hubei (China)

    2013-09-01

    Long-term excessive fluoride intake is known to be toxic and can damage a variety of organs and tissues in the human body. However, the molecular mechanisms underlying fluoride-induced male reproductive toxicity are not well understood. In this study, we used a rat model to simulate the situations of human exposure and aimed to evaluate the roles of endoplasmic reticulum (ER) stress and inflammatory response in fluoride-induced testicular injury. Sprague–Dawley rats were administered with sodium fluoride (NaF) at 25, 50 and 100 mg/L via drinking water from pre-pregnancy to gestation, birth and finally to post-puberty. And then the testes of male offspring were studied at 8 weeks of age. Our results demonstrated that fluoride treatment increased MDA accumulation, decreased SOD activity, and enhanced germ cell apoptosis. In addition, fluoride elevated mRNA and protein levels of glucose-regulated protein 78 (GRP78), inositol requiring ER-to-nucleus signal kinase 1 (IRE1), and C/EBP homologous protein (CHOP), indicating activation of ER stress signaling. Furthermore, fluoride also induced testicular inflammation, as manifested by gene up-regulation of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), in a nuclear factor-κB (NF-κB)-dependent manner. These were associated with marked histopathological lesions including injury of spermatogonia, decrease of spermatocytes and absence of elongated spermatids, as well as severe ultrastructural abnormalities in testes. Taken together, our results provide compelling evidence that ER stress and inflammation would be novel and significant mechanisms responsible for fluoride-induced disturbance of spermatogenesis and germ cell loss in addition to oxidative stress. - Highlights: • We used a rat model to simulate the situations of human fluoride (F) exposure. • Developmental F exposure induces testicular damage related with oxidative stress.

  17. Fluoride-elicited developmental testicular toxicity in rats: Roles of endoplasmic reticulum stress and inflammatory response

    International Nuclear Information System (INIS)

    Zhang, Shun; Jiang, Chunyang; Liu, Hongliang; Guan, Zhizhong; Zeng, Qiang; Zhang, Cheng; Lei, Rongrong; Xia, Tao; Gao, Hui; Yang, Lu; Chen, Yihu; Wu, Xue; Zhang, Xiaofei; Cui, Yushan; Yu, Linyu; Wang, Zhenglun; Wang, Aiguo

    2013-01-01

    Long-term excessive fluoride intake is known to be toxic and can damage a variety of organs and tissues in the human body. However, the molecular mechanisms underlying fluoride-induced male reproductive toxicity are not well understood. In this study, we used a rat model to simulate the situations of human exposure and aimed to evaluate the roles of endoplasmic reticulum (ER) stress and inflammatory response in fluoride-induced testicular injury. Sprague–Dawley rats were administered with sodium fluoride (NaF) at 25, 50 and 100 mg/L via drinking water from pre-pregnancy to gestation, birth and finally to post-puberty. And then the testes of male offspring were studied at 8 weeks of age. Our results demonstrated that fluoride treatment increased MDA accumulation, decreased SOD activity, and enhanced germ cell apoptosis. In addition, fluoride elevated mRNA and protein levels of glucose-regulated protein 78 (GRP78), inositol requiring ER-to-nucleus signal kinase 1 (IRE1), and C/EBP homologous protein (CHOP), indicating activation of ER stress signaling. Furthermore, fluoride also induced testicular inflammation, as manifested by gene up-regulation of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), in a nuclear factor-κB (NF-κB)-dependent manner. These were associated with marked histopathological lesions including injury of spermatogonia, decrease of spermatocytes and absence of elongated spermatids, as well as severe ultrastructural abnormalities in testes. Taken together, our results provide compelling evidence that ER stress and inflammation would be novel and significant mechanisms responsible for fluoride-induced disturbance of spermatogenesis and germ cell loss in addition to oxidative stress. - Highlights: • We used a rat model to simulate the situations of human fluoride (F) exposure. • Developmental F exposure induces testicular damage related with oxidative stress.

  18. Mechanisms of phytoestrogen biochanin A-induced vasorelaxation in renovascular hypertensive rats

    Directory of Open Access Journals (Sweden)

    Seok Choi

    2014-12-01

    Conclusion: These results suggest that the enhanced relaxation caused by biochanin A in aortic rings from hypertensive rats is endothelium dependent. Vascular smooth muscle K+ channels may be involved in biochanin A-induced relaxation in aortae from hypertensive and normotensive rats. In addition, an endothelium-derived activation of voltage-dependent K+ channels contributes, at least in part, to the relaxant effect of biochanin A in renovascular hypertension.

  19. Puberty and Perimenopause: Reproductive Transitions and their Implications for Women's Health

    Science.gov (United States)

    Hoyt, Lindsay T.; Falconi, April

    2015-01-01

    This scoping review synthesizes existing research on two major transitions in females’ lives: puberty and perimenopause. These two periods of vast physiological change demarcate the beginning and the end of the reproductive life cycle and are associated with major neuroendocrine reorganization across two key systems, the hypothalamic-pituitary-gonadal (HPG) axis the hypothalamus-pituitary-adrenal (HPA) axis. Despite growing evidence suggesting that the timing and experience of puberty and perimenopause are related to various physical and mental health outcomes (e.g., mood disorders, metabolism, cardiovascular health, autoimmune conditions and cancer), these two processes are rarely examined together. In this paper, we bridge these disparate literatures to highlight similarities, isolate inconsistencies, and identify important areas for future research in women’s health. PMID:25797100

  20. Antioxidant activity of citrullus colocynthis pulp extract in the RBC's of alloxan-induced diabetic rats

    International Nuclear Information System (INIS)

    Dallak, M.; Jaliah, B.I.

    2010-01-01

    Previous studies in our laboratory showed that Citrullus colocynthis pulp seedless extract have antihyperglycemic and insulinotropic effects in alloxan induced diabetes. Reactive oxygen species have been implicated in the mechanism of damage of red blood cells and anaemia in diabetic patients. So the current study was carried out to investigate the protective role of citrullus colocynthis against oxidative stress in the RBC's of alloxan induced diabetic rats. Methods: Rats were divided into four groups each of ten rats, the first group was normal non diabetic rats given normal saline orally and was named control group, the second group was diabetic rats given normal saline orally and were named normal saline treated-diabetic rats, the third and fourth group were diabetic rats treated with the pulp extract or glibenclamide (a positive control) orally. Evaluations were made for haematological parameters in the blood and for lipid peroxidation and oxidative stress enzymes activities in the RBC's of all experimental rats. Results: The diabetic rats had a significant decrease (p<0.05) in total erythrocytes count and Packed Cell Volume (PCV) and a normal Haemoglobin (Hb) value in the blood. They also showed decreased levels of Thiobarbituric Acid Reactive Substances (TBARS) and decreased activities of Superoxide Dismutase (SOD) and Catalase (CAT) in the RBC's hemolysate. On other hand, oral administration of citrullus colocynthis or glibenclamide alleviated these altered parameters in the treated rats, they resulted in a significant increase (p<0.05) in the in total erythrocytes count and PCV (Haematocrit) values in the blood and caused a significant decreased levels of TBARS and increased activities of SOD and CAT in the RBC's of those diabetic treated rats when compared to diabetic rats given normal saline. The effect was more profound in citrullus colocynthis treated diabetic rats. Conclusion: Citrullus colocynthis pulp extract possesses a potent antioxidant property