No / Sexual dysfunction is a major, although poorly understood, side-effect of treatment with antipsychotic drugs. We have recently show marked disruption of reproductive function and weight gain in female rats treated subchronically with risperidone and haloperidol. The aim of the present study was to examine further the potential relationship between reproductive dysfunction and weight gain in female rats treated with olanzapine. The effects of olanzapine on weight gain, food and water intake, intra-abdominal fat, the oestrous cycle and uterine weight were assessed in group-housed adult female hooded-Lister rats. Olanzapine (0.5-4.0 mg/kg i.p.) or vehicle was administered once daily for 21 days and body weight, food and water intake measured, with histological examination of vaginal lavage to determine the stage of the oestrous cycle. On day 22, animals were sacrificed and intra-abdominal fat, wet and dry uterine weights measured. Olanzapine induced significant weight gain with concomitant increases in food and water intake and intra-abdominal fat without an effect on the oestrous cycle, wet and dry uterine weights or plasma prolactin levels. These results confirm the ability of olanzapine to induce weight gain in female rats on unrestricted normal diet with a concomitant increase in food and water intake and increased intra-abdominal fat. These effects of olanzapine were produced in the absence of any apparent impairment in reproductive function, in contrast to the substantial disruption of oestrous and uterine atrophy previously shown in rats treated with risperidone and haloperidol.

Drug delivery technology is currently advancing faster than at any time in biotechnology history. The challenge of drug delivery is to achieve a controlled release of therapeutic agents over an extended period. Controlled release potentially offers significant advantages over conventional dosage forms, by eliminating both under- and overdosing while maintaining a desired range of drug concentrations. An existing drug regimen for induced calving produces a declining blood profile that does not mimic the naturally occurring, gradually increasing, cortisol blood level around parturition effectively, causing animal health issues. Likewise, while the existing progesterone controlled release systems for oestrous control successfully synchronise oestrus, it is however, associated with reduced fertility and as such other drugs have to be administered to improve the fertility during oestrus. Therefore, there is a need for a drug delivery system that is capable of delivering multiple drugs at various times and patterns. This research aimed to investigate, characterize, identify steroids with high absorption rates through vaginal mucosa and evaluate the potential of an electronic drug delivery system for the delivery of steroids for either the control of the bovine oestrous cycle or induced calving. In order to identify steroids with high absorption rates across the vaginal mucosa, an in vitro permeation method was developed to screen selected steroids for their ability to permeate artificial and biological membranes. The steroids were pre-formulated to enhance their solubility and permeation through these membranes. Analytical UV and HPLC assays to characterise the pure and formulated steroidal compounds were also developed and validated. An assessment of an intravaginal Electronically Modulated Intravaginal Device (EMID) for the control of the bovine oestrous cycle or induced calving was carried out. Five different release assessment methods were investigated and critically evaluated in order to identify the most appropriate release assessment method for the EMID. These were: 1) the Drug Dissolution Test, 2) a weight loss method, 3) the dispensed weight method, 4) the determination of piston travel distance method, and 5) the rod expulsion from the EMID method. The methods investigated were critically evaluated in terms of ease of use and automation, reproducibility and cost/time savings. Optimisation of various components and construction materials of the EMID were also investigated. Animal trials were carried out using the original EMID (manufactured from polypropylene polymer) and modified inserts (manufactured from high density polyethylene polymer) to determine their retention rate in the animals. Accelerated stability testing of progesterone in suspension, oestradiol-17 tablets, cloprostenol as a powder blend and the driving mechanism of the EMID were examined. The flux of the steroids was evaluated through poly-&-caprolactone and excised cow mucosa membranes using side-by-side permeation cells. Results indicated that progesterone followed by dexamethasone acetate and dexamethasone valerate showed higher permeability values through vaginal mucosa compared to dexamethasone or its other analogues. The weight loss method of the EMID proved to be an easy and appropriate method to measure the release rate from the EMID. A high density polyethylene polymer was identified as the most ideal body material for the insert compared to polypropylene body. Also double O-ring silicone, Elastollan WYO 1388-5 and solid silicone pistons were found to be amongst the best pistons tested and all performed well compared to other piston materials. There was a low retention rate with either the original EMID or the modified inserts. Further modification of retention wings of the EMID did not improve the retention rate, but a good blood profile response was obtained from cows treated with the complete EMID containing formulated progesterone. The formulations and driving mechanism were found to be stable under the tested conditions. Therefore, the EMID has potential for commercial application of induced calving or oestrous control per vaginum administration, reliant on improvement of its retention mechanism.

Transrectal ovarian ultrasonography and hormone measurements were used to study ovarian antral follicular dynamics and development of luteal structures during the middle portion of the breeding season in non-prolific cross-bred Western white-faced ewes and prolific Finn sheep. Studies were also done on ovarian activity in Western white-faced ewes during the transition to seasonal anoestrus and at the onset of the breeding season. Lastly, two experiments were carried out to examine ovulatory responses and subsequent luteal function in Western white-faced ewes treated with luteolysin (PgF 2á) and progestogen (medroxyprogesterone acetate-MAP) during the luteal phase of the oestrous cycle and after ovulation induction with gonadotrophin-releasing hormone (GnRH) in mid-anoestrus. The results of the present experiments showed that the growth of ovine antral follicles reaching ovulatory sizes of >=5 mm in diameter occurred in a wave-like pattern throughout the oestrous cycle in both breeds of sheep under study. There were typically 3 or 4 waves of follicle production throughout the 17-day interovulatory period. Ovarian follicular emergence, or beginning of growth from the pool of 3-mm follicles, appeared to be primarily controlled by changes in circulating concentrations of follicle-stimulating hormone (FSH). In cyclic ewes, the largest ovarian follicles acquired the ability to secrete oestradiol from the day of emergence and a peak of oestradiol secretion occurred about the time they reached their maximum diameter. The high ovulation rate in prolific Finn sheep appeared to be achieved mainly by the ovulation of follicles emerging in the last two waves of the interovulatory interval. Interestingly, prolific Finn ewes produced more but smaller corpora lutea (CL) and had lower serum concentrations of progesterone during the luteal phase of the oestrous cycle as compared to non-prolific Western white-faced ewes. During the transition into seasonal anoestrus in Western white-faced ewes, FSH secretion resembled that during the breeding season but the pattern of emergence of sequential follicular waves was dissociated from FSH and oestradiol secretion. Prior to the first ovulation of the breeding season, there was a distinct elevation in circulating concentrations of progesterone produced by luteinized unovulated follicles and/or interstitial tissue of unknown origin. This increase in serum levels of progesterone, heralding the resumption of ovulatory cycles, did not alter the rhythmic pattern FSH secretion or follicular wave emergence. Treatment of non-prolific Western white-faced ewes with PgF2á and MAP applied late in the oestrous cycle changed follicular dynamics and increased ovulation rate to resemble that in prolific Finn sheep. Effects of MAP on the recruitment and growth of ovulatory follicles in Western white-faced ewes did not have a clear gonadotrophic dependancy, suggesting a possible local regulation of ovarian activity by progestins in ewes. Following the induction of ovulation with GnRH in anoestrous Western white-faced ewes, an array of ovarian responses were detected with ultrasonography, including failure of ovulation of large antral follicles, normal (fall-lifespan) and short-lived CL post-ovulation, and luteinized cystic-like follicles. The normal luteinization of ovulated follicles appeared to be related to the amplitude of episodic elevations in daily serum FSH concentrations before induction of ovulation and characteristics of the preovulatory LH surge.

Veterinært speciale, 27 ECTS point. / Haves kun i elektronisk udg.

Diss. (sammanfattning) Uppsala : Sveriges lantbruksuniv., 2007. / Härtill 4 uppsatser.

MSCAGR / Department of Animal Science

Submitted by Mario BC (mario@bc.ufrpe.br) on 2017-05-05T14:30:11Z No. of bitstreams: 1 Marquiliano Farias de Moura.pdf: 1343014 bytes, checksum: 18474259144cdf58c8045b49e60f7998 (MD5) / Made available in DSpace on 2017-05-05T14:30:11Z (GMT). No. of bitstreams: 1 Marquiliano Farias de Moura.pdf: 1343014 bytes, checksum: 18474259144cdf58c8045b49e60f7998 (MD5) Previous issue date: 2014-08-04 / It was carried out a morphological study on Oocyte Cumulus Complex of sheep (COCs), in order to characterize them quantitatively, both during the proestrus and diameter phases of the estrous cycle, as during different periods of the gestation. COCs were collected from antral follicles (3-6 mm) with regular, slightly grainy and multiple layers of cumulus cytoplasm (COC Grade I) fixed on glutaraldehyde and embedded in paraffin, as well as sectioned into sections of 5 μm. The principle of the nucleator was used to estimate average volumes of oocytes, cumulus cells and their nuclei. The thicknesses of the pellucida zone, as well as the numerical percentages of different types of cumulus cells were evaluated. There was a synchronous increase of the volume of the oocyte and its nucleus from diestrus to proestrus phases. Concerning the ones collected in the gestation stages, there was a parameter volume reduction as the pregnancy progresses. The thickness of the pellucida zone was reduced during the periods approaching ovulation. Three types of cumulus cells were observed (C1-C3). The results suggest that cumulus cells respond to circulating hormone levels during the estrous cycle and gestation. / Um estudo morfológico foi realizado em complexos cumulus oophorus de ovinos (CCOs), a fim de caracterizá-los durante as fases de proestro e dietro do ciclo estral, e durante diferentes períodos de gestação. CCOs foram colhidos a partir de folículos antrais (3-6 mm) com citoplasma regular, levemente granulado e com múltiplas camadas de células do cúmulus (CCO Grau I). Fixados em glutaraldeído e incluso em parafina, e seccionado em cortes de 5 μm. O volume médio dos oócitos com e sem zona pelúcida foram maiores nas fases de proestro, havendo redução desses volumes nas fases de diestro, G30 e G60, respectivamente. No entanto, foi observado que na fase de proestro o volume do núcleo foi inferior quando comparado aos núcleos das fases de diestro, G30 e G60. A zona pelúcida apresentou-se mais delgada à medida que no volume do oócito aumentou. As células do cumulus e seus respectivos núcleos mantiveram os volumes inalterados durante todas as fases estudadas. Houve diferença significativa quando comparado o volume dos tipos de células do cumulus em todas as fases. Também foram observados e classificados vários tipos (C1, C2 e C3) de células do cumulus, na fase de proestro houve uma maior proporção de células do tipo C3, seguido de significativa redução desse tipo de célula nas fases de diestro, G30 e G60. Já o tipo de célula C1 e C2 foram mais frequentes no grupo G60. Conclui-se que a morfologia das células do cumulus, da zona pelúcida, do citoplasma e do núcleo de complexo cumulus oophorus de folículos antrais ovinos apresenta-se morfologicamente distinta de acordo com as fases do ciclo estral e gestação.