Anti-Müllerian hormone in queens: Serum concentrations and total ovarian follicle population.

The objectives of this study were: a) To report anti-Müllerian hormone (AMH) serum concentrations in neonatal, pre and postpubertal female cats. b) To establish the relationship between serum AMH with either age and estrous cycle c) To correlate the total number of different ovarian follicle types with AMH in adult queens. A single blood sample was collected from 10 neonates (including 5 male), 15 prepubertal and 48 postpubertal female cats to measure AMH. Eight, 10, and 18 of this latter group were in follicular (FP), luteal phase (LP), and anestrus (AN), respectively. The total number of each follicle type was histologically counted using the Gougeon and Chainy (1987) formula in a subgroup of 10 adult queens. Overall AMH mean of these the female cats was 6.31 ± 0.54 ng/mL. The neonatal females had lower AMH serum concentrations than their male littermates (2.56 ± 0.49 vs. >23 ng/mL; P < 0.01). Concentrations were also higher in prepubertal than in neonatal and postpubertal cats (11.79 ± 1.36 vs. 2.56 ± 0.49 vs. 4.87 ± 0.38 ng/mL; P < 0.01). Queens below 12 mo of age had the highest AMH levels (10.41 ± 1.16; P < 0.01). Age was inversely correlated with AMH (r = -0.5; P < 0.01). Animals in FP had lower AMH concentrations than AN females (2.51 ± 0.33 vs. 5.46 ± 0.76 ng/mL; P < 0.05). No difference in the total number of each follicle type were found between either ovary (P > 0.05). A high correlation was only found between small antral follicles and AMH concentrations (r = 0.85; P < 0.01). It was concluded, that AMH can provide an indirect, reliable marker for the assessment of ovarian follicle size and functionality. Age as well as pubertal state should be considered when evaluating AMH concentrations in this species.

The specific inhibition of the cardiac electrogenic sodium/bicarbonate cotransporter leads to cardiac hypertrophy.

Two alkalinizing mechanisms coexist in cardiac myocytes to maintain intracellular pH: sodium/bicarbonate cotransporter (electroneutral isoform NBCn1 and electrogenic isoform NBCe1) and sodium/proton exchanger (NHE1). Dysfunction of these transporters has previously been reported to be responsible for the development of cardiovascular diseases. The aim of this study was to evaluate the contribution of the downregulation of the NBCe1 to the development of cardiac hypertrophy. To specifically reduce NBCe1 expression, we cloned shRNA into a cardiotropic adeno-associated vector (AAV9-shNBCe1). After 28 days of being injected with AAV9-shNBCe1, the expression and the activity of NBCe1 in the rat heart were reduced. Strikingly, downregulation of NBCe1 causes significant hypertrophic heart growth, lengthening of the action potential in isolated myocytes, an increase in the duration of the QT interval and an increase in the frequency of Ca2+ waves without any significant changes in Ca2+ transients. An increased compensatory expression of NBCn1 and NHE1 was also observed. We conclude that reduction of NBCe1 is sufficient to induce cardiac hypertrophy and modify the electrical features of the rat heart.

Non-invasive cardiovascular assessment of pregnancy in healthy female cats.

INTRODUCTION: The aim of this study was to evaluate cardiac morphology, indices of systolic and diastolic function, systolic blood pressure (SBP), and uterine artery resistance index (RI) during normal feline pregnancy. ANIMALS; MATERIALS AND METHODS: Twenty domestic short-hair pregnant queens, weighing 2.4-3.9 kg. Animals were assessed by two-dimensional, M-mode, and Doppler echocardiography, non-invasive SBP measurement, and uterine Doppler ultrasound every 10 days from mating to parturition. RESULTS: Interventricular septal thickness at end-diastole and end-systole, left ventricular internal dimension at end-diastole, left ventricular free wall thickness at end-diastole and end-systole, fractional shortening, stroke volume, cardiac output (CO), heart rate, and peak velocities of early and late diastolic transmitral flow increased during the second half of gestation, while SBP and RI decreased during the same period (p < 0.01). DISCUSSION AND CONCLUSIONS: Cardiac structure and function varied during normal pregnancy in these queens. Eccentric hypertrophy, increased indices of systolic function, and increased measurements of CO seem to be the consequences of the hemodynamic modifications occurring during pregnancy. The assessment of maternal cardiovascular function may prove a useful screening tool to detect pregnancy complications in feline species.

Reference range of gestational uterine artery resistance index in small canine breeds.

The objectives of this study were to evaluate the uterine artery blood flow during the second half of normal pregnancy in small breed dogs and to determine the RI reference values of this artery in these bitches. Fifty-two, 1.5-6.5 kg, purebred healthy pregnant bitches were included in this study. Doppler ultrasonographic examinations of the uterus were performed every 10 days from Day 30 of the estrous cycle to parturition. Peak systolic velocity (PSV) and end diastolic velocity (EDV) of the uterine artery were measured while RI [(PSV-EDV)/PSV] was automatically calculated. Values of PSV, EDV and RI were analyzed by repeated measures ANOVA followed by Tukey test using age, body weight, litter size and parity as covariates. Resistance index reference ranges were constructed by regressing this index on gestational age. Equation of the polynomial regression curves was used to calculate the mean, 95th and 5th centiles for each gestational age (GA). A gradual increase of PSV (P < 0.01) and EDV (P < 0.01) and a decrease in RI (P < 0.01) were found throughout the study period. PSV and EDV were influenced by litter size (P < 0.05), while RI was not. None of the Doppler parameters were influenced by age, body weight or parity. A second-degree polynomial described the relationship between RI of uterine artery and GA in the different time points: [RI = 0.993 + 8.4x10-5 x GA2- 0.0117 x GA]. It is concluded that uterine artery blood flow progressively increased throughout normal pregnancy in small breed bitches. In addition, reference ranges of uterine artery RI were 0.64-0.79, 0.57 to 0.75, 0.53 to 0.71 and 0.52 to 0.66 on Days 30, 40, 50 and 60 of gestation, respectively.

Echocardiographic and electrocardiographic parameters during the normal postpartum period in toy breeds of dogs.

The aim of this study was to evaluate echocardiographic and electrocardiographic parameters during the normal canine postpartum period. Twenty clinically healthy pregnant bitches of toy breeds (11 Miniature poodles, five Yorkshire terriers, two Maltese terriers and two Bichons Frises) were evaluated on days -3, 3, 10, 17, 24, 38, 52 and 80 relative to parturition (day 0). During the first postpartum week, the width of the interventricular septum in systole, the shortening fraction and the left atrium size decreased, while the left ventricle internal diameter in systole and end systolic stress increased. There were progressive decreases in the velocity of circumferential fibre shortening, stroke volume, cardiac output, and mitral E and A wave values. Systolic blood pressure increased markedly during the first postpartum week to gradually increase thereafter. Heart rate and corrected QT interval progressively decreased, while P wave amplitude increased. QRS complex amplitude decreased in the second week after parturition and then increased during the following weeks. In conclusion, there were changes in systolic function and some structural adaptive changes in the bitch during the first 80days postpartum. In addition, maternal heart rate and corrected QT interval decreased, while P wave and QRS amplitudes increased.

Evaluation of feline uterine and umbilical arteries blood flow in a pharmacologically induced abnormal gestation model.

The aim of this study was to describe resistance index (RI) and systolic/diastolic ratio (S/D ratio) of uterine and umbilical arteries in an experimental model of abnormal pregnancy in felids. On days 30 to 35 (32 ± 2.9) after mating, 20 domestic short-hair pregnant queens were randomly assigned to one of the following treatment groups: a treated group (TG; n = 8), which received 10 mg/kg of aglepristone subcutaneously twice, 24 hours apart, and a control nontreated group (CG; n = 12). M-mode and Doppler ultrasonographic evaluations were performed at the initiation of the treatment (Day 0) and then every other day during 8 days. In both groups, uterine and umbilical arteries were evaluated by Doppler ultrasound, whereas fetal heart rate was assessed by M-mode ultrasound. Resistance index of uterine artery augmented in TG from Day 2 onward, conversely it decreased in CG (P < 0.01). On Day 8, RI values were 0.64 ± 0.05 vs 0.37 ± 0.01 for TG and CG, respectively. Additionally, S/D ratio of the same artery presented an increase in TG, whereas this ratio diminished in CG (P < 0.01). On Day 8, this parameter showed values of 2.98 ± 0.4 vs 1.62 ± 0.06 for TG and CG, respectively. Resistance index of umbilical artery remained almost unchanged in TG from Day 6 onward, whereas it progressively decreased in CG throughout the course of the study (P < 0.05). On Day 8, RI were 0.89 ± 0.04 and 0.82 ± 0.01, for TG and CG, respectively. Furthermore, on Day 8, S/D ratio of umbilical artery progressively diminished in CG but not in TG (P < 0.01), being 14.7 ± 9.1 vs 5.9 ± 0.3 for TG and CG, respectively. Fetal heart rate was higher in TG than in CG (P < 0.05). Group differences in Doppler parameters appeared on Day 2, when the other clinical or ultrasonographic signs were still absent. It is concluded that blood flow of the uterine and umbilical arteries differed between these normal and abnormal gestations predicting an adverse obstetric outcome.

Uterine blood flow evaluation in bitches suffering from cystic endometrial hyperplasia (CEH) and CEH-pyometra complex.

Doppler ultrasound is a useful diagnosis tool to evaluate uterine blood flow in different canine reproductive states. The aim of this study was to describe and compare uterine blood flow in bitches suffering from cystic endometrial hyperplasia (CEH) and CEH-pyometra complex (CEH-P). Ninety diestrous bitches were clinically, hematologically, and ultrasonographically classified into four groups: (1) clinical signs, leukocytosis, CEH, and uterine luminal contents (CEH-P, n = 31); (2) asymptomatic bitches with CEH and uterine contents (CEH-C, n = 15); (3) asymptomatic bitches with CEH without uterine contents (CEH, n = 16); and (4) normal diestrous bitches (ND, n = 28). The widest cross-sectional diameter and uterine wall thickness (W) of uterine horns were measured using two-dimensional ultrasound. Peak systolic velocity and end diastolic velocity of uterine arteries were measured by Doppler ultrasound in all the bitches. Peak systolic velocity and end diastolic velocity were higher in CEH-P than in CEH-C, CEH, and ND (P < 0.01); although both parameters did not show differences among the latter three groups (P > 0.1). Conversely, resistance index (RI) reported lower values in CEH-P than that in the other three groups (P < 0.01), being ND higher (P < 0.01) than both CEH-C and CEH which did not differ between themselves (P > 0.1). When all the bitches were considered, correlation between RI and cross-sectional diameter was r = -0.69 (P < 0.01) and between RI and uterine wall thickness was r = -0.02 (P > 0.1). It is concluded that the uterine artery blood flow velocity of bitches suffering from pyometra was higher, not only from normal bitches, but also from females with endometrial hyperplasia. Furthermore, endometrial hyperplasia, accompanied or not by luminal contents, had a higher blood flow velocity than normal uterus. Hemodynamic parameters appear as useful markers to differentiate uterine pathologic conditions.

Failure of a single dose of medroxyprogesterone acetate to induce uterine infertility in postnatally treated domestic cats.

In mice and sheep, neonatal administration of progesterone or progestins inhibited development of uterine glands. The aims of the present study were (1) to describe uterine gland development on postnatal Days 6 to 8 and (2) to evaluate the effects of a single postnatal administration of a progestin on reproduction and adult uterine glands morphology and function in domestic cats. Necropsy was performed on three 1-week-old female cats which had died unrelated to this study. Ten female kittens were randomly assigned within the first 24 hours of birth to: medroxyprogesterone acetate 10 mg/animal subcutaneously (MPA; n = 6) or placebo (PLC; n = 4) and followed up until puberty when they were mated. Twenty-four days after the end of estrus, ovulation and pregnancy were diagnosed by serum progesterone measurement and ultrasonography, respectively. Then, all the cats were ovariohysterectomized. After necropsy or surgery, the excised organs were histologically evaluated. Seven queens ovulated (4 of 6 MPA and 3 of 4 PLC; P > 0.1) and were pregnant (P > 0.1). Four MPA cats presented endometrial hyperplasia and one of them developed a pyometra. The 1-week-old females presented uterine glands in the stage of budding and incipient penetration of the glandular epithelium into the underlying stroma. The MPA-treated queens revealed that the area occupied by uterine glands per square-micrometer (0.55 ± 0.2 vs. 0.49 ± 0.2; P > 0.1) and the height of the glandular epithelium (µm; 24.5 ± 6.7 vs. 24.4 ± 7.2; P > 0.1) did not differ from those of the PLC group. Neither significant gross nor microscopical differences were also found for ovaries (P > 0.1). It is concluded that 1-week-old kittens had an incipient stage of uterine gland development and that a single postnatal supraphysiological dose of MPA did not alter uterine adenogenesis in this species. Furthermore, this treatment seemed to predispose to uterine disease without prevention of fertility.

Bidimensional and Doppler ultrasonographic evaluation of postpartum uterine involution in the queen.

The aim of this study was to describe bidimensional and Doppler ultrasonographic changes of uterine involution during normal feline puerperium. Secondary, the postpartum vaginal discharge was described. Twelve pregnant female cats were included in this study. After queening, vulvar discharge was grossly and microscopically examined daily. Bidimensional and Doppler ultrasonographic examinations of the uterus were performed on Days -4 to -2, 4, 11, 18, and 25 from parturition. Total uterine diameter, uterine wall thickness, uterine lumen contents, peak systolic velocity, end diastolic velocity, and resistance index of uterine arteries were measured. The cats presented serosanguineous vulvar discharge for a mean of 3 ± 1 days after parturition, and the cytology revealed 70% to 80% of erythrocytes, which progressively decreased up to Day 13. Immediately after parturition, there were less than 20% neutrophils, and this percentage gradually diminished to 0% to 1% at the end of the study. Uterine total diameter diminished up to Day 25 (P < 0.01), when ultrasonographic uterine dimensions were similar to that of anestrus. A progressive decrease of uterine wall thickness (P < 0.05), uterine lumen contents (P < 0.01), peak systolic velocity (P < 0.01), and end diastolic velocity (P < 0.01) was found throughout the study period. Conversely, resistance index increased during the first week after parturition (P < 0.01). It is concluded that the uterine artery blood flow progressively decreased during the first 25 days after parturition, which was associated with the bidimensional ultrasonographic regression of the organ. Although lochial discharge disappeared far before ultrasonographic involution, cytologic findings further corroborated the duration of this regression process.

Doppler ultrasonographic assessment of maternal and fetal arteries during normal feline gestation.

The aim of this study was to describe Doppler parameters of uterine, umbilical, fetal abdominal aorta, fetal renal and fetal internal carotid arteries, as well as fetal heart rate (FHR), during normal feline gestation. Fifteen, 1-4 years of age, weighing 2.5-3.9kg, domestic short-hair pregnant queens, which were born in our institutional cat colony were included in this study. Color and pulsed-wave Doppler evaluations of uterine arteries were performed every 10 days (Day 0, 10, 20, 30, 40, 50, 60) from mating. Fetal Doppler and M-mode ultrasonography were performed to assess umbilical, fetal abdominal aorta, fetal renal, fetal internal carotid arteries and FHR. Both peak systolic velocity (PSV) and end diastolic velocity (EDV) of uterine artery increased up to parturition (P<0.01), while resistance index (RI) decreased from Day 10 onwards (P<0.01). From Day 40 onwards, RI of umbilical artery diminished, while PSV and EDV augmented (P<0.01). Fetal abdominal aorta (P<0.01), renal (P<0.01) and internal carotid (P<0.01) arteries diminished their RI from Days 40, 60 and 40 onwards, respectively. Both PSV and EDV of these three arteries increased progressively. Fetal heart rate was first registered on Day 20 when it began to increase up to Day 40 and then diminished to the end of gestation (P<0.01). It is concluded that blood flow of uterine, umbilical, fetal abdominal aorta, fetal renal and fetal internal carotid arteries progressively increased during normal feline pregnancy, while FHR rose to mid gestation and then decreased up to parturition.

Doppler ultrasonographic assessment of uterine arteries during normal canine puerperium.

The aim of this study was to describe Doppler ultrasonographic changes of uterine arteries during normal canine puerperium. Eight healthy, pure-bred bitches, were ultrasonographically assessed during the postpartum period on Days -3, 3, 10, 17, 24, 38, 52 and 80 (Day 0 defined as the day of parturition). Total horn diameters (TD) and endometrium thickness (E) were evaluated. Color Doppler was used to localize uterine arteries at both sides of the body and pulsed-wave Doppler was performed to obtain the waveforms. Peak systolic velocity (PSV) and end diastolic velocity (EDV) were measured. Resistance index [(PSV-EDV)/PSV] was automatically calculated. Values of TD, E, PSV, EDV and RI were analyzed by repeated measures ANOVA followed by LSD test (SPSS 18.0; SPSS, Chicago, IL, USA). A correlation analysis was also carried out between RI and TD. A progressive decrease of TD (P<0.01) and E (P<0.01) was found in the course of the study. A gradual diminution of PSV (P<0.01) and EDV (P<0.01) and an increase of RI (P<0.01) were also found throughout the study period. The resistance index negatively correlated with TD (r=-0.46; P<0.01) and E (r=-0.44; P<0.01) while the ultrasonographic and vascular changes in this period are concurrent with regenerative changes in the glandular and epithelial structures of the uterus. It is concluded that uterine artery RI progressively increased during normal canine puerperium, associated to the two-dimensional ultrasonographic regression of the organ.

Echocardiographic and Doppler assessment of maternal cardiovascular function in normal and abnormal canine pregnancies.

The objective was to verify maternal hemodynamic differences between normal and abnormal pregnancies in dogs. Brucella-negative pregnant bitches (n = 31) were retrospectively classified into abnormal (which had either their pregnancy interrupted between Days 52 and 60 or perinatal death of more than 50% of the litter; n = 14) and normal (which had delivered healthy puppies at term; n = 17). These dogs were evaluated with echocardiography every 10 days from Days 0 to 60 of gestation (Day 0 = estimated day of LH peak). Systolic blood pressure was also assessed. At Day 50 of gestation, left ventricular free wall in systole increased in the normal but not in the abnormal group (P < 0.01). In contrast, end systolic stress (P < 0.01) and systolic blood pressure (P < 0.01) diminished only in normal animals. We concluded that signs of altered maternal cardiovascular adaptation to pregnancy may be predictors of obstetrical complications in dogs.

The safety and efficacy of oral docosahexaenoic acid supplementation for the treatment of primary sclerosing cholangitis - a pilot study.

BACKGROUND: Primary sclerosing cholangitis (PSC) is characterised by progressive inflammatory and fibrotic destruction of the biliary ducts. There are no effective medical therapies and presently high dose ursodeoxycholic acid is no longer recommended due to significant adverse events in a recent clinical trial. Cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction is associated with PSC in both children and adults. Since CFTR dysfunction leads to altered fatty acid metabolism, specifically reduced docosahexaenoic acid (DHA), we hypothesised that DHA supplementation might be an effective therapy for patients with PSC. AIM: To determine the safety and efficacy of oral DHA supplementation for the treatment of PSC. METHODS: We conducted a 12 month open-label pilot study to evaluate safety of oral DHA and its effects on serum alkaline phosphatase as a primary outcome measure in 23 patients with PSC. DHA was administered orally at 800 mg twice per day. Secondary outcomes included changes in other liver function tests and fibrosis biomarkers. RESULTS: A 1.7-fold increase in serum DHA levels was observed with supplementation. The mean alkaline phosphatase level (±S.E.) at baseline was 357.8 ± 37.1 IU compared to 297.1 ± 23.7 IU (P < 0.05) after 12 months of treatment. There were no changes in other liver function tests and fibrosis biomarkers. No adverse events were reported. CONCLUSIONS: Oral DHA supplementation is associated with an increase in serum DHA levels and a significant decline in alkaline phosphatase levels in patients with PSC. These data support the need for a rigorous trial of DHA therapy in PSC.

Electrocardiographic changes in normal and abnormal canine pregnancy.

The aim of this study was to describe the canine electrocardiographic changes in the course of normal and abnormal pregnancy. Twenty-three Brucellosis-negative pregnant bitches were retrospectively classified as normal (n = 12) or abnormal (n = 11). A control group of non-pregnant dioestrous bitches (n = 10) was also included. Normal pregnant females delivered healthy puppies at term while abnormal animals interrupted their pregnancy between days 52-60 (from estimated luteinizing hormone peak) or presented perinatal litter death higher than 60%. All the bitches were electrocardiographically evaluated every 10 days from day 0 to day 65 of the oestrous cycle, to parturition or abortion. Percentage heart rate change increased 31.3% from day 40 to 60 in normal gestation while it decreased -1.8% in dioestrous bitches, although it did not change in the abnormal group (p < 0.01). In the abnormal pregnant group but not in the others, percentage QRSa change fell to -34% on day 60 (p < 0.01). At the same time point, percentage QRSd change was 6.2% vs -4.9% in normal gestations and dioestrous animals, respectively (p < 0.05). Corrected QT interval augmented from day 40 onwards up to 9.9% and 4.3% in the normal pregnant and dioestrous groups, respectively, while it remained unchanged in abnormal gestations (p < 0.05). It is concluded that during normal canine pregnancy, some electrocardiographic parameters begin changing from day 40 onwards, and that pathological gestations differ from normality from day 30. The use of electrocardiography in canine obstetrics might contribute to identify abnormal outcomes before they become clinically evident.

Doppler ultrasonographic assessment of maternal and fetal blood flow in abnormal canine pregnancy.

The aim of this study was to describe the changes of uterine artery, umbilical artery and fetal abdominal aorta, renal and internal carotid arteries blood flow in abnormal canine pregnancy. Twenty-two, Brucella-negative pregnant bitches were retrospectively classified into abnormal (which had either interrupted their pregnancy between days 52 and 60 or had perinatal death >60% of the litter; n=11) and normal (which had delivered healthy puppies at term; n=11). In all the animals, color and pulsed-wave Doppler examinations of uterine artery were conducted every 10 days from Day 20 to 50 from estimated luteinizing hormone peak. Doppler ultrasonography was also conducted in the fetuses to assess umbilical artery, abdominal aorta, renal and internal carotid arteries from Day 40 to 60 of gestation. Throughout the study, resistance index (RI) of uterine, umbilical and fetal renal arteries decreased up to -15% compared to -36% (P<0.01), -11% compared to -23% (P<0.05) and 2% compared to -13% (P<0.05), respectively in the abnormal and normal bitches. Fetal abdominal aorta and internal carotid did not differ between groups (P>0.05). It is concluded that in dogs, uterine artery, umbilical artery and fetal renal artery RI differ between normal and abnormal gestation being useful for the prediction of adverse obstetric outcome.

The GnRH antagonist acyline prevented ovulation, but did not affect ovarian follicular development or gestational corpora lutea in the domestic cat.

Two experiments were conducted to investigate the effects of the GnRH antagonist acyline (330 microg/kg, given sc) on ovarian follicular development and ovulation, as well as on pregnancy maintenance in domestic cats. In the first experiment, seven queens in proestrus (total of 24 proestrus periods), were randomly assigned to treatment with either acyline (ACY; n=17) or a placebo (PLC; n=7). All queens were mated with a fertile tomcat. In the ACY and PLC groups, cessation of estrus occurred (mean+/-SEM) 7.0+/-1.3 and 7.0+/-1.7 d after treatment (P>0.1), ovulation occurred in 2 of 17 and all seven estrus periods (P<0.05), and pregnancy rates were 1 of 16 and 7 of 7 (P<0.05), respectively. In the ACY and PLC groups, intervals from treatment to the onset of the ensuing proestrus were 18.4+/-1.7 and 120+/-17.2 d. In the second experiment, 14 pregnant queens were randomly allocated, according to their mating date, to treatment with acyline in early pregnancy (from 20 to 25 d, n=3), mid pregnancy (from 26 to 45 d; n=4), late pregnancy (> 45 d; n=3), or injection of a placebo in early (n=1), mid (n=2), or late pregnancy (n=1). Ultrasonographic assessments of the uterus were done every second day for 2 wk post treatment, and serum progesterone (P(4)) concentrations were determined before treatment, and at 7 and 14 d after treatment. No pregnancies were prematurely terminated and post-treatment P(4) concentrations did not differ among treatment groups (P>0.1). In conclusion, in the domestic cat, GnRH withdrawal by acyline prevented ovulation when given in early follicular phase (proestrus), but did not significantly affect luteal function during pregnancy.

Comparison of two doses of the GnRH antagonist, acyline, for pregnancy termination in bitches.

Gonadotropin-releasing hormone (GnRH) antagonists are particularly useful when a rapid inhibitory effect on the gonadal axis is required. The aim of this study was to test the efficacy and clinical safety of a low and high dose of the third generation GnRH antagonist, acyline, on pregnancy termination in female dogs. The effect of the antagonist on the progesterone (P(4)) serum concentration was also described. Twenty-one mid-pregnant bitches were randomly assigned to a single subcutaneous (SC) dose of a placebo (PLACE; n = 7), a low (ACY-L; 110 microg/kg; n = 6) or high (ACY-H; 330 microg/kg; n = 8) dose of acyline. The animals were followed up for 15 days. All ACY treated but no placebo-treated animals terminated their pregnancy by abortion (p < 0.01). The ACY-L and ACY-H groups interrupted their pregnancy 7 +/- 1.9 and 6.4 +/- 1.3 days after treatment, respectively (p = 0.7). A significant interaction between treatment and day was found (p < 0.01) for P(4) serum concentrations when PLACE was compared with both ACY groups. No difference was found for this hormone between both ACY groups (p > 0.05) where P(4) diminished throughout the study. The decreasing rate varied among animals and was closely related to the time of abortion when P(4) reached basal concentrations. In PLACE animals, gestation progressed normally and P(4) did not change throughout the study (p > 0.05). None of the bitches presented side effects. It was concluded that acyline safely terminated mid-pregnancy by permanently decreasing P(4) serum concentrations.

An experimental model to study resistance index and systolic/diastolic ratio of uterine arteries in adverse canine pregnancy outcome.

The aim of this study was to describe the changes in the resistance index (RI) and systolic/diastolic ratio (S/D) of the uterine arteries during mid-pregnancy abortion induction in the dog. Sixteen 30-35 day pregnant bitches were randomly assigned to either a pharmacological protocol to interrupt gestation (n = 8) or were used as untreated control group (n = 8). Doppler assessments of uterine arteries blood flow were carried out before the initiation of the protocol and then every other day up to abortion (treated group) or parturition (control group). All treated bitches aborted 6 +/- 1.2 days after initiation of the treatment (while none of the non-treated bitches aborted). Pre-treatment RI and S/D did not differ between groups (p > 0.2) while average post-treatment indexes were (mean +/- SD): 0.62 +/- 0.1 vs 0.53 +/- 0.1 (p < 0.01) and 2.96 +/- 0.9 vs 2.23 +/- 0.3 (p = 0.01), for the treated and non-treated group respectively. Correlations between days to abortion and RI or S/D were 0.75 (p < 0.01) and 0.79 (p < 0.01) and, -0.78 (p < 0.01) and -0.73 (p < 0.01) for the treated and non-treated groups respectively. In the treated group, correlations between serum progesterone (P(4)) concentrations and RI and S/D were -0.76 (p < 0.01) and -0.59 (p < 0.01) respectively. It is concluded that, during induction of abortion, RI and S/D of uterine arteries progressively increased while P(4) decreased.

Fatty acids in cystic fibrosis.

Cystic fibrosis (CF) is associated with deficiencies in certain essential fatty acids. These deficiencies have been studied in plasma, red blood cells, and mucus and were previously thought to be a result of malnutrition or malabsorption. More recent studies have indicated that these deficiencies are independent of nutritional status. However, these studies examined fatty acids in plasma but not in CF-regulated tissues. In the pancreas, lungs, and ileum of CF knock-out mice, membrane-bound arachidonic acid levels have been shown to be increased while docosahexaenoic acid levels are decreased. This lipid abnormality is reversed following oral administration of docosahexaenoic acid (DHA). In addition, DHA therapy reverses the increased neutrophil infiltration in the lungs of CF knock-out mice. Further studies are required to determine the mechanism by which CF gene mutations lead to this lipid abnormality.