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C Gobello

Publications and source records attributed to C Gobello.

13 recordsLinked to original sources

Dopamine agonists, anti-progestins, anti-androgens, long-term-release GnRH agonists and anti-estrogens in canine reproduction: a review.

Over the last 10 years, new drugs have been applied to canine reproduction, widening the spectrum of therapeutic possibilities for diseases that were previously surgically treated, and facilitating better control of the estrous cycle and fertility. Some are not approved for use in dogs; their use is experimental and further clinical trials are necessary. Dopamine agonists such as cabergoline, bromocriptine or metergoline are ergoderivative alkaloids that exert an anti-prolactinergic effect via stimulation of D2 pituitary receptors or inhibition of central serotoninergic ones. Their main indication is suppression of lactation. Anti-prolactinergic compounds have also been successfully used for pregnancy termination and shortening of interestrous intervals. Anti-progestins, (e.g. mifepristone and aglepristone) are synthetic steroids that bind with high affinity to progesterone (P4) receptors, preventing P4 from exerting its biological effects. Anti-progestins have been indicated in P4-dependent conditions, such as pregnancy termination, induction of parturition and the medical treatment of pyometra. Several groups of drugs have been described to have anti-androgenic properties through different mechanisms of action: progestins, receptor binding anti-androgens (e.g. flutamide), competitive enzyme inhibitors (e.g. finasteride), aromatase inhibitors, and GnRH agonists. Their main application is medical treatment of benign prostatic hyperplasia. Long-term release formulations of GnRH agonists (e.g. leuprolide or deslorelin acetate) postponed puberty and reversibly suppressed reproductive function in male and female dogs for periods exceeding 1 year. Anti-estrogens (e.g. clomiphene and tamoxifen citrate) are synthetic non-steroidal type I anti-estrogenic compounds that competitively block estrogen receptors with a combined antagonist-agonistic effect. In dogs, their action is more agonistic than antagonistic.

Androgen Antagonists↗

Combination dopamine agonist and prostaglandin agonist treatment of cystic endometrial hyperplasia-pyometra complex in the bitch.

Cystic endometrial hyperplasia-pyometra (CEH-P) complex is a progesterone-dependent disease that requires medical treatment in bitches intended for breeding. To test the efficacy and safety of a combined protocol and to assess the effect of age, stage of cycle, previous steroid hormone administration and parity on treatment, 29 bitches diagnosed with CEH-P complex were treated daily with cabergoline 5 microg/kg PO and cloprostenol 1 microg/kg SC for 7-14 days, along with supportive antibiotic and hydration therapies. Before treatment, and on Days 3, 7 and 14, all bitches were evaluated clinically and uterine horn diameter measured during trans-abdominal ultrasonography. Twenty-four of 29 bitches were cured by either Day 7 or 14. Nine bitches had mild digestive side effects. Clinical signs related to pyometra began to improve markedly as early as Day 2 of treatment. Uterine diameters decreased (P < 0.05) by Day 3 of treatment, and continued to gradually decrease, reaching normal size by Day 14. Relapses occurred in 6 of 29 cases. Pregnancy was achieved in one of the two young bitches bred after treatment. No significant relationships were found between success rate and age, stage of the estrous cycle, previous hormone administration or parity. Although no variables affecting treatment results could be identified, this combination of compounds was found to be an efficient and safe for treatment of CEH-P.

Animals↗

Short-term progestin treatments prevent estrous induction by a GnRH agonist implant in anestrous bitches.

The objective of this study was to test the efficacy and safety of a short-term progestin treatment administered at two different times to prevent estrous induction in response to the administration of an implant releasing the GnRH agonist, deslorelin acetate (DA), in anestrous bitches. Interestrous intervals (IEI) observed prior to and post DA were compared. Forty-two anestrous bitches, with previous IEI history, were randomly allocated to one of the following treatments: PL: placebo sc (n = 12); MA: megestrol acetate 2mg/kg po for 8 days (n = 4); DA: 10mg sc (n = 8); MA&DA-1: MA beginning the day before DA (n = 8); and MA&DA-4: MA beginning 4 days before DA (n = 10). The dose of MA was identical for each treatment. All bitches were examined daily for 1 month and then every 3 months until the next spontaneous post-treatment estrous cycle. Post-GnRH estrous response occurred in 0, 0, 100, 50, and 10% of the PL, MA, DA, MA&DA-1, MA&DA-4, groups, respectively (<0.01). There was an interaction between the treatment and period for the duration of the IEI (< 0.01). Changes in IEI were different among treatments (p<0.01); the three DA-treated groups (147.5% +/- 10.3, 161.3% +/- 14.1, 148.6% +/- 19.2) differed from both the MA (12.9% +/- 17.6) and PL (8.1% +/- 7.8), but not among themselves. It is concluded that an 8 days megestrol protocol and DA on Day 4 was better than DA on Day 1 to prevent estrous response in anestrous bitches and that both protocols significantly increased the IEI.

Anestrus↗

Decrease of body temperature after aglepristone treatment in bitches.

Body temperature responses and the timing of abortions were evaluated in pregnant bitches with the anti-progestin aglepristone. Fifteen purebred and crossbred, 25-45 days pregnant, were included in this study and seven untreated bitches at the same stage of pregnancy served as controls. Treated bitches were administered two applications of aglepristone (10 mg/kg SC) 24 h apart for pregnancy termination. Pregnancy termination was confirmed by ultrasonographic assessment. Body temperature was rectally measured three times a day for 6 days beginning 24 h before treatment or pregnancy diagnosis in the treated and control bitches, respectively. Additionally, serum progesterone concentrations were assessed at time points during the study in the treated bitches. Pregnancy was terminated in 14 treated bitches in a mean+/-S.E.M. of 4.3+/-0.7 days after treatment. Control bitches remained pregnant. In the treated bitches, but not in the controls, body temperature significantly decreased 24 h after the beginning of the treatments (P < 0.01) and then gradually returned to pre-treatment values. Correlation between the day of mean minimum body temperature and the day of pregnancy termination was low (0.07; > 0.05). Progesterone did not show significant change throughout the study. Body temperature does not seem to be a suitable variable to clinically monitor the aborting effect of aglepristone. Decrease of body temperature after aglepristone treatment could represent further evidence of its hypothalamic effects.

Abortifacient Agents, Steroidal↗

Effect of tamoxifen citrate on reproductive parameters of male dogs.

Tamoxifen is a synthetic, nonsteroidal Type I antiestrogenic compound that competitively blocks estrogen receptors with a mixed antagonist-agonist effect. The manifestation of these different actions depends on each species, organ, tissue and cell type considered. Very little is known about the effect of antiestrogens in dogs. The objectives of this study were to determine the effects of tamoxifen citrate on some testis, prostate, hormone, and semen parameters in seven Beagle dogs with uncomplicated spontaneous benign prostatic hyperplasia. Two dogs were normospermic, four were oligozoospermic, and one was azoospermic. The dogs were allocated to a control pre-treatment period, followed by a treatment period, and five post-treatment periods (the duration of each period was 4 weeks). During the treatment period, 2.5mg tamoxifen citrate was given p.o. daily for 28 days to all the dogs. Maximum scrotal width, testicular consistency, libido semen parameters, prostatic volume, serum testosterone concentrations, and side effects were assessed. Tamoxifen negatively affected testis size and libido (P<0.01), and decreased prostatic volume (P<0.01) and testosterone concentrations during treatment. Semen quality deteriorated to nadir values (P<0.01) approximately one spermatic cycle after treatment and returned to pre-treatment values on the second cycle after treatment in all the dogs, except one young oligoazoospermic dog, in which the sperm count was higher ( P<0.01 ) at that time. No side effects were observed and fertility was conserved at the end of the study. Tamoxifen acted more like an agonist than antagonist on the gonadal axis and, therefore, upon both the prostate and testis. Therefore, tamoxifen may have therapeutic applications in dogs.

Animals↗

Secretory patterns of prolactin in dogs: circannual and ultradian rhythms.

The objectives of the present study were to characterize in dogs circannual and ultradian prolactin (PRL) secretory patterns and also to compare gender differences in the ultradian period of study in the Southern hemisphere. Blood samples were collected at 15-min intervals for 2.5 h from seven male and seven female dogs and a single monthly sampling, over a 1-year time span, from six male dogs for the ultradian and circannual studies, respectively. Plasma PRL was measured by a homologous enzyme immunometric assay. The ultradian study evidenced PRL elevations suggesting pulsatile secretion in both genders. Significantly higher mean smoothed baseline (ng / ml [7.02 +/- 1.2 vs 1.23 +/- 1.0, p < 0.01]) and AUC (ng/ml * 2.5 h [25.2 +/- 3.8 vs 4.4 +/- 3.8, p < 0.01]) were found in females when compared with males. In the circannual study, plasma PRL concentrations did not statistically differ among the months of the year. When grouped together the 3 months with a longer daylight had significantly higher PRL concentrations than the 3 months with the shortest (2.31 +/- 0.37 vs 0.96 +/- 0.37, p < 0.01). The correlation between length of daylight and PRL concentrations was 0.24, p < 0.05. It is concluded that PRL does have a circannual rhythmicity and that there are ultradian gender-related differences in the period under study in these groups of dogs. This study also demonstrates plasma PRL elevations suggesting pulsatile secretion in male dogs.

Animals↗

Coat colour changes associated with cabergoline administration in bitches.

Cabergoline or bromocriptine were administered orally to 60 bitches at doses of 5 microg/kg and 15 microg/kg daily, respectively, for two to 45 days for the treatment of pseudopregnancy or for oestrus induction. Seven of the dogs which received cabergoline for more than 14 days developed coat colour changes from the second week of administration to the next coat shedding. Of these, fawn-coloured bitches developed a yellowish coat colour while Argentine boar hounds became black spotted, mainly on their extremities. In previous untreated oestrous periods, these bitches had shown no coat colour changes. It is concluded that a colour shift in certain haircoats of particular breeds could be mediated through the inhibition of the secretion of melanocyte-stimulating hormone by the administration of the dopaminergic agonist cabergoline for more than two weeks. Transient coat colour changes should be considered a possible side effect when planning long-term treatment with dopaminergic agonists in dogs.

Animals↗

Effects of vincristine treatment on semen quality in a dog with a transmissible venereal tumour.

The effect of vincristine treatment on semen parameters in a male boxer with a genital transmissible venereal tumour are described. The dog was treated with vincristine intravenously at 0.5 to 0.7 mg/m2 body surface area per week for six weeks until complete regression of the tumour occurred. Semen samples were collected before each application and then at weeks 10, 12, 17, 21 and 23 after the start of therapy. There were no alterations in libido or in testicular size and consistency either during or after treatment. Total sperm count decreased to abnormally low values during weeks 4 and 5, and then began to increase up to pretreatment values. No significant alterations in the other semen parameters were found during the study period.

Animals↗

Study of the change of prolactin and progesterone during dopaminergic agonist treatments in pseudopregnant bitches.

In order to clarify the role of prolactin (PRL) and progesterone (P(4)) in the pathophysiology of canine pseudopregnancy (PSP) we designed an experiment, where we induced an abrupt pharmacological blockade of PRL secretion with dopaminergic agonists (DA) or placebo (PL). Thirty overtly pseudopregnant (PSPT) bitches were randomly allocated to three groups of 10 animals each: PL, bromocriptine (BR), and cabergoline (CA), which were treated with PL, 7.5microg/kg BR and 5microg/kg CA, respectively. On days 1, 7 and 14 (day 0: beginning of the treatment) all the animals were classified into grades of intensity of PSP clinical signs, considering serum or milk secretion and enlargement of the mammary glands. Presence or absence of treatment side effects were recorded and blood samples for PRL and P(4) determinations collected. Serum PRL and P(4) concentrations (ng/ml) of all the animals on day 1 were (least squares means [LSM]+/-S.E.M.) 17.70+/-2.05 and 1.13+/-0.13, respectively. During the experiment, serum PRL and P(4) concentrations decreased (day effect, P<0.05). During the experiment, serum PRL concentrations were lower in the DA treated group (BR and CA) compared with PL group (P<0.05). After a week of treatment, the percentage change of PRL was -62.52 versus 102.16+/-46.20 (P<0.01) for the treated (BR and CA) and PL groups, respectively. Conversely, no significant differences were found in the percent change in PRL between the BR and the CA groups nor in P(4) percentage change among all groups for the same week. Significant differences in the achievement of complete remission between treated and PL groups were found on days 7 (40 versus 0%, P<0.05) and 14 (90 versus 0%, P<0.01). No significant correlation between PRL and P(4) was found on day 1 in any of the animals. However, a significant correlation for the same hormones was found on days 7 and 14 for the DA treated groups (r=0.46, P<0.01). While in the PL group, PRL concentrations and intensity of clinical signs were not significantly correlated on days 1, 7 and 14; in the DA treated groups they were significantly correlated on days 7 and 14 (r=0.34, P<0.05). The presence of a positive correlation between PRL concentrations and the grades of intensity of clinical signs in the treated animals indicates the major role of PRL in PSP physiopathology. However, the lack of correlation during spontaneous involution of PSP in the PL group demonstrates that PRL concentrations do not completely explain the problem. In summary, abrupt changes in serum PRL seemed to be more important in ceasing PSP signs than total PRL concentrations in these groups of animals.

Animals↗

Twenty-four-hour profiles of serum prolactin and luteinizing hormone in anoestrous crossbred bitches.

The dynamics of prolactin (PRL) and luteinizing hormone (LH) secretion in the anoestrous bitch is poorly known. Therefore, the objective of this study was to characterize the 24 h profiles of serum PRL and LH in crossbred anoestrous bitches and to assess whether a relationship exists between the secretory patterns of these two hormones. Serum PRL and LH concentrations were measured in 10 healthy anoestrous crossbred bitches at 145 min intervals for 24 h. During the experiment the animals received continuous artificial illumination and remained undisturbed except at the time of blood sampling. Serum PRL was measured by a homologous enzyme-linked immunosorbent assay, whereas LH and progesterone (P4) were determined by radioimmunoassay. The anoestrous state of the bitches was assessed by vaginal cytology, vaginoscopy and physical examination. Two groups of animals were identified according to their PRL levels: a high PRL group (n = 3, mean +/- SEM 12.3 +/- 2.7 ng/ml) and a low PRL group (n = 7, mean +/- SEM: 2.5 +/- 0.9 ng/ml). In the low PRL group, the PRL profiles were flat and did not show any significant circadian pattern. Nevertheless, occasional single-point peaks were detected in some of the bitches. In the high PRL group the individual PRL profiles were variable. To detect the presence of a circadian change of PRL concentrations, two different sets of time windows (TW) of sampling were studied. The first set was: day [TW1A, samples 1-5 (0900-1840 h)] and night [TW1B, samples 6-10 (2105-0645 h)]. The second set was chosen after visual inspection of the average PRL profiles for both (high and low) groups: [TW2A, samples 3-7 (1350-2330 h) and TW2B, samples 1-2 and 8-10 (0155-1125 h)]. PRL concentrations were not significantly different between day and night. In the high PRL group, but not in the low PRL group, average serum PRL was significantly (p < 0.01) higher in TW2A than TW2B. In both groups serum LH levels were more homogeneous than PRL levels. Neither TW showed circadian changes in LH patterns of secretion (TW1A versus TW1B, p < 0.69; TW2A versus TW2B, p < 0.88). On the other hand, bitches in the high PRL group showed significantly (p < 0.01) lower serum LH levels than those in the low PRL group of animals. Serum PRL concentrations presented a significant inverse correlation with LH concentrations (r=-0.21, p < 0.03) and a significant positive correlation with P4 concentrations across the study (0.92, p < 0.01). It is concluded that in anoestrous crossbred bitches serum PRL is highly variable and inversely related to LH. No circadian rhythm of PRL secretion appears to exist in most anoestrous bitches.

Anestrus↗

A review of canine pseudocyesis.

The purpose of this article is to review the most relevant features of the physiology, clinical signs, diagnosis, treatment and prevention of canine pseudocyesis (PSC). This is a physiological syndrome, characterized by clinical signs such as: nesting, weight gain, mammary enlargement, lactation and maternal behaviour, which appears in non-pregnant bitches at the end of metaoestrus. PSC is a frequent finding in domestic dogs. Although it is generally admitted that prolactin (PRL) plays a central role in the appearance of PSC, its precise aetiophysiology is not completely understood yet. A number of clinical studies suggest that at some point of metaoestrus circulating PRL levels rise in overtly pseudopregnant bitches. Individual differences in sensitivity to PRL as well as the existence of molecular variants of canine PRL with different bioactivity versus immunoreactivity ratios may help clarify the aetiopathology of PSC. Diagnosis of PSC is based on the presence of typical clinical signs in metaoestrous non-pregnant bitches. Considering that PSC is a self limiting physiological state, mild cases usually need no treatment. Discouraging maternal behaviour and sometimes fitting Elizabethan collars to prevent licking of the mammary glands may suffice in these cases. Sex steroids (oestrogens, progestins and androgens) have been traditionally used to treat PSC but the side-effects usually outweigh the benefits of these medications. Inhibition of PRL release by ergot derivatives [bromocriptine (10-100 microg/kg per day for 10-14 days], cabergoline (5 microg/kg per day during 5-10 days), metergoline (0.2 mg/kg per day during 8-10 days) has proved to be effective for the treatment of canine PSC. Although some of these ergot derivatives present some untoward side-effects, they are transient and can usually be managed. Predisposed bitches not intended for breeding should be spayed as ovariectomy is the only permanent preventive measure.

Animals↗

Dioestrous ovariectomy: a model to study the role of progesterone in the onset of canine pseudopregnancy.

It has been suggested that overt pseudopregnancy in bitches is caused by an increase in the concentration of serum prolactin as a result of an abrupt decrease in progesterone concentration in the late luteal phase. This hypothesis was tested by using ovariectomy at dioestrus as an experimental model. A total of 18 intact cross- and purebred bitches were used. Eleven animals were ovariectomized (day 0) between day 25 and day 40 of the oestrous cycle, and seven intact bitches were used as controls. Blood samples for determination of prolactin and progesterone concentrations were collected on days -1, 1, 2, 3 and 7 in the ovariectomized group, and on day 1 and day 7 in the control group. On day 7, the presence or absence of overt pseudopregnancy was recorded. The four ovariectomized bitches with a history of pseudopregnancy showed signs of overt pseudopregnancy (P < 0.01). On day 7, progesterone concentrations were significantly higher in the control than in the ovariectomized bitches (P < 0.01). The expected decrease in serum progesterone concentration after ovariectomy was similar in pseudopregnant bitches and non-pseudopregnant bitches. However, in pseudopregnant bitches, but not in non-pseudopregnant bitches, there was a marked increase (expressed as percentage change) in the concentration of prolactin between day -1 and day 7 (P < 0.01). It was concluded that the abrupt decrease in progesterone concentrations does not lead systematically to pseudopregnancy. Only in bitches predisposed to pseudopregnancy would an abrupt decrease in progesterone concentrations induce a substantial increase in prolactin concentrations, which in turn would trigger the typical signs of pseudopregnancy.

Animals↗

Heterogeneity of circulating prolactin in the bitch.

Different molecular forms of circulating prolactin (PRL) are known to occur in several species. As no such information was available in dogs, we assessed the molecular profile of circulating PRL in bitches. Pooled sera from covertly (CTRL) and overtly pseudopregnant (PSPT) diestrous bitches with high or low (> 10 or < 10 ng x mL(-1), respectively) serum PRL (measured by ELISA) were analyzed by Sephadex G-100 and Concanavalin A-Sepharose column chromatography. Four serum PRL fractions were identified and termed big-big, big (> 67 kDa), native (23 kDa) and fragmented (< 20) kDa) PRL. The percentages of these fractions were roughly similar in CTRL and PSPT animals, irrespective of their serum PRL levels (higher in PSPT than in CTRL bitches). A large proportion of glycosylated PRL (between 69 and 100%) was also detected in these sera. We conclude that in dogs, circulating PRL occurs in multiple molecular forms, whose relative abundance is comparable in covertly and overtly pseudopregnant bitches.

Animals↗