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Pregnant Sheep (pregnant + sheep)
Selected AbstractsTemporal Vulnerability of Fetal Cerebellar Purkinje Cells to Chronic Binge Alcohol Exposure: Ovine ModelALCOHOLISM, Issue 10 2007Jayanth Ramadoss Background: Human magnetic resonance imaging (MRI) and autopsy studies reveal abnormal cerebellar development in children who had been exposed to alcohol prenatally, independent of the exposure period. Animal studies conducted utilizing the rat model similarly demonstrate a broad period of vulnerability, albeit the third trimester-equivalent of human brain development is reported to be the most vulnerable period, and the first trimester-equivalent exposure produces cerebellar Purkinje cell loss only at high doses of alcohol. However, in the rat model, all 3 trimester-equivalents do not occur prenatally, requiring the assumption that intrauterine environment, placenta, maternal interactions, and parturition do not play an important role in mediating the damage. In this study, we utilized the ovine model, where all 3 trimester-equivalents occur in utero, to determine the critical window of vulnerability of fetal cerebellar Purkinje cells. Methods: Four groups of pregnant sheep were used: first trimester-equivalent pair-fed saline control group, first trimester-equivalent alcohol group (1.75 g/kg), third trimester-equivalent pair-fed saline control group, and third trimester-equivalent alcohol group (1.75 g/kg). The alcohol exposure regimen was designed to mimic a human binge pattern. Alcohol was administered intravenously on 3 consecutive days beginning on day 4 and day 109 of gestation in the first and third trimester-equivalent groups, respectively, and the alcohol treatment was followed by a 4-day inter-treatment interval when the animals were not exposed to alcohol. Such treatment episodes were replicated until gestational day 41 and 132 in the first and third trimester-equivalent groups, respectively. All fetal brains were harvested on day 133 and processed for stereological cerebellar Purkinje cell counting. Results: Significant deficits were found in the fetal cerebellar Purkinje cell number and density in the first and third trimester-equivalent alcohol exposed fetuses compared with those in the saline controls. However, there was no difference between the first and third trimester-equivalent alcohol administered groups. When comparing the present findings to those from a previous study where the duration of alcohol exposure was all 3 trimester-equivalents of gestation, we did not detect a difference in fetal cerebellar Purkinje cell number. Conclusions: We conclude that the fetal cerebellar Purkinje cells are sensitive to alcohol exposure at any time during gestation and that women who engage in binge drinking during the first trimester are at a high risk of giving birth to children with cerebellar damage even if drinking ceases after the first trimester. Our findings also support the hypothesis that only a certain population of Purkinje cells are vulnerable to alcohol-induced depletion irrespective of the timing or duration of alcohol exposure. [source] Pharmacokinetics of ivermectin after maternal or fetal intravenous administration in sheepJOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2008R. PÉREZ In pregnant sheep at 120,130 days of gestational age, a study was undertaken in order to characterize the pharmacokinetics and transplacental exchange of Ivermectin after maternal or fetal intravenous administration. Eight pregnant Suffolk Down sheep of 73.2 ± 3.7 kg body weight (bw) were surgically prepared in order to insert polyvinyl catheters in the fetal femoral artery and vein and amniotic sac. Following 48 h of recovery, the ewes were randomly assigned to two experimental groups. In group 1, (maternal injection) five ewes were treated with an intravenous bolus of 0.2 mg ivermectin/kg bw. In group 2, (fetal injection) three ewes were injected with an intravenous bolus of 1 mg of ivermectin to the fetus through a fetal femoral vein catheter. Maternal and fetal blood and amniotic fluid samples were taken before and after ivermectin administration for a period of 144 h post-treatment. Samples were analyzed by liquid chromatography (HPLC). A computerized non-compartmental pharmacokinetic analysis was performed and the results were compared by means of the Student t-test. The main pharmacokinetic changes observed in the maternal compartment were increases in the volume of distribution and in the half-life of elimination (t½,). A limited maternal-fetal transfer of ivermectin was evidenced by a low fetal Cmax (1.72 ± 0.6 ng/mL) and AUC (89.1 ± 11.4 ng·h/mL). While the fetal administration of ivermectin resulted in higher values of clearance (554.1 ± 177.9 mL/kg) and lower values of t½, (8.0 ± 1.4 h) and mean residence time (8.0 ± 2.9 h) indicating that fetal-placental unit is highly efficient in eliminating the drug as well as limiting the transfer of ivermectin from the maternal to fetal compartment. [source] A previous infection with Toxoplasma gondii does not protect against a challenge with Neospora caninum in pregnant sheepPARASITE IMMUNOLOGY, Issue 3 2001E.A. Innes Sheep immunized with Toxoplasma gondii (Toxovax®) prior to pregnancy were tested for their ability to withstand a challenge at 90 days gestation with 107 Neospora caninum (NC1) tachyzoites. The antibody responses in sheep following immunization with T. gondi were specific for T. gondii whereas peripheral blood mononuclear cells responded to both T. gondii and caninum antigen in vitro. This suggested that there was induction of crossreactive immune recognition in the sheep, at least at the cellular level. Following challenge of sheep at mid-gestation with N caninum, no febrile responses were recorded in the group of sheep which had previously received Toxovax® while significant febrile responses were recorded in the group of sheep which received N challenge alone. Antibody responses to N developed in all sheep following challenge and antibody responses to T,gondii were boosted in the group of sheep which had previously been immunized with Toxovax®. No antibodies to were observed in the sheep which received the challenge alone. Peripheral blood mononuclear cells from both groups of sheep responded to T.gondii N.caninum antigen invitro and interferon gamma was present in the cell-free supernatant from activated cells. However despite evidence of the induction of crossreactive immunity between T.gondii N.caninum this was not sufficient to prevent foetal death. The group of sheep which had received Toxovax® prior to pregnancy and the group of sheep which only received the N.caninum challenge experienced 100% foetal death compared with 0% in the unchallenged control group. Vaccination prior to pregnancy with Toxovax® did protect against foetal death following oral challenge at 90 days with 2000 oocysts which caused 100% foetal death in a control challenge group. [source] Effects of fetal growth restriction on lung development before and after birth: A morphometric analysisPEDIATRIC PULMONOLOGY, Issue 3 2001G.S. Maritz PhD Abstract Our aim was to determine the effects of fetal growth restriction (FGR) during late gestation on the structure of the lungs in the fetus near term and at 8 weeks after birth. The studies were performed using two groups of pregnant sheep and their offspring. In both groups, FGR was induced by umbilico-placental embolisation (UPE); for fetal studies, UPE was performed from 120 days of gestation until 140 days (term, ,146 days), when fetuses were killed for tissue analysis. For postnatal studies, UPE continued from 120 days until delivery at term; postnatal lambs were killed at 8 weeks after birth for tissue analysis. UPE led to a thicker pulmonary blood-air barrier at 140 days of gestation and this difference, which was due to a thickened basement membrane, was still present at 8 weeks after birth. At 8 weeks, we also observed a smaller number of alveoli per respiratory unit, thicker interalveolar septa, and a greater volume density of lung tissue in FGR lambs compared to controls. These changes would be expected to impair gas exchange and alter the mechanical properties of the lungs. Our data show that structural alterations in the lungs induced by placental insufficiency were more evident at 8 weeks of postnatal age than near term, indicating that the effects of FGR on the lung may become more serious with age and may affect respiratory health later in life. Pediatr Pulmonol. 2001; 32:201,210. © 2001 Wiley-Liss, Inc. [source] Uterine blood flow responses to ICI 182 780 in ovariectomized oestradiol-17,-treated, intact follicular and pregnant sheepTHE JOURNAL OF PHYSIOLOGY, Issue 1 2005Ronald R. Magness Oestrogen dramatically increases uterine blood flow (UBF) in ovariectomized (Ovx) ewes. Both the follicular phase and pregnancy are normal physiological states with elevated levels of circulating oestrogen. ICI 182 780 is a pure steroidal oestrogen receptor (ER) antagonist that blocks oestrogenic actions in oestrogen-responsive tissue. We hypothesized that an ER-mediated mechanism is responsible for in vivo rises in UBF in physiological states of high oestrogen. The purpose of the study was to examine the effect of an ER antagonist on exogenous and endogenous oestradiol-17, (E2,)-mediated elevations in UBF. Sheep were surgically instrumented with bilateral uterine artery blood flow transducers, and uterine and femoral artery catheters. Ovx animals (n= 8) were infused with vehicle (35% ethanol) or ICI 182 780 (0.1,3.0 ,g min,1) into one uterine artery for 10 min before and 50 min after E2, was given (1 ,g kg,1i.v. bolus) and UBF was recorded for an additional hour. Intact, cycling sheep were synchronized to the follicular phase using progesterone, prostaglandin F2,(PGF2,) and pregnant mare serum gonadotrophin (PMSG). When peri-ovulatory rises in UBF reached near peak levels, ICI 182 780 (1 or 2 ,g (ml uterine blood flow),1) was infused unilaterally (n= 4 sheep). Ewes in the last stages of pregnancy (late pregnant ewes) were also given ICI 182 780 (0.23,2.0 ,g (ml uterine blood flow),1; 60 min infusion) into one uterine artery (n= 8 sheep). In Ovx sheep, local infusion of ICI 182 780 did not alter systemic cardiovascular parameters, such as mean arterial blood pressure or heart rate; however, it maximally decreased ipsilateral, but not contralateral, UBF vasodilatory responses to exogenous E2, by ,55,60% (P < 0.01). In two models of elevated endogenous E2,, local ICI 182 780 infusion inhibited the elevated UBF seen in follicular phase and late pregnant ewes in a time-dependent manner by ,60% and 37%, respectively; ipsilateral , contralateral effects (P < 0.01). In late pregnant sheep ICI 182 780 also mildly and acutely (for 5,30 min) elevated mean arterial pressure and heart rate (P < 0.05). We conclude that exogenous E2,-induced increases in UBF in the Ovx animal and endogenous E2,-mediated elevations of UBF during the follicular phase and late pregnancy are partially mediated by ER-dependent mechanisms. [source] 1141160720 Does the anti-proliferative action of ovine uterine serpin involve apoptosis?AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 6 2006MB Padua Ovine uterine serpin (OvUS) is the major progesterone-induced protein in the uterus of the pregnant sheep. This protein is a member of the serine proteinase inhibitor superfamily and it has been proposed to down-regulate uterine immune function during pregnancy to protect the fetus. In vitro experiments have shown that both the native and the recombinant (r) form of the protein can inhibit mitogen-induced lymphocyte proliferation and growth of canine primary osteogenic sarcoma cells, mouse lymphoma cells, human prostatic adenocarcinoma cells (PC-3 cell line) and bovine preimplantation embryos. The mechanism by which OvUS inhibits cell proliferation is still unknown. Accordingly, experiments were conducted to test whether rOvUS exerts its anti-proliferative action through apoptosis. In the first experiment, the anti-proliferative effect of rOvUS on PC-3 cells was tested to determine the minimal concentration effective at inhibiting proliferation. Proliferation was inhibited by concentrations of OvUS at 8 ,g/mL and higher. The incorporation of [3H]thymidine was 4043, 3998, 3464, 2785, 2827, 2310, and 2332 dpm for 0, 0.5, 2, 8, 32, 125, and 250 ,g/mL, respectively. In the second experiment, PC-3 cells were cultured for 48 hr with 50, 100 and 200 ,g/mL of rOvUS or ovalbumin. Cells were then fixed and apoptotic cells identified using the TUNEL assay to detect DNA fragmentation. There was no effect of OvUS at any concentration tested on the percent of cells that were apoptotic. Percent apoptosis was 1.3% for control cells, 3.8%, 4.8% and 2% for cells cultured with 50, 100 and 200 ,g/mL rOvUS, and 2% for cells cultured with 200 ,g/mL ovalbumin. Results confirm that OvUS inhibits proliferation of PC-3 cells and indicate that inhibition does not involve induction of apoptosis. Further experiments are warranted to elucidate the anti-proliferative mechanism of action of OvUS. [source] Two new approaches in intrauterine tracheal occlusion using an ultrathin fetoscopeTHE LARYNGOSCOPE, Issue 2 2010Michael Tchirikov MD Abstract Objectives/Hypothesis: To introduce and establish a new approach in minimal invasive fetoscopic surgery in order to reduce access trauma and the iatrogenic preterm premature rupture of the membranes (PPROM) as a major complication of intrauterine treatment of congenital diaphragmatic hernia. Methods: In total, 27 pregnant sheep were operated on using fetoscopes with 1.2 and 1.0 mm optics. We used an elliptic sheath alone with a maximum diameter of 2.6/1.3 mm; in these cases the balloon was placed under ultrasound control. In comparison, we placed the balloon under fetoscopic control using the fetoscopic sheath and a 7F (2.3 mm) introducer. Therefore, the maximum access trauma was not bigger than the diameter of sheath of introducer. Results: With this technique we successfully operated on 22 sheep. The use of real time three-dimensional ultrasound control distinctly facilitates the operation procedure. Conclusions: Our preliminary findings show that fetoscopic tracheal occlusion using ultrathin fetoscopes and reducing the access trauma on the level of 4.2 or even 2.65 mm2 could be seen as a method of reducing the rate of PPROM. Laryngoscope, 2010 [source] | ||||||||||