Artificially inseminated pregnant sows (Large White × Landrace) were sourced from a commercial piggery owned by The University of Queensland at Gatton, Australia. All piglets were delivered by cesarean section either preterm at 97 days or term at 113 days (term ≈ 115 days). At 97 days of gestation, piglets are developmentally similar to a human infant born at approximately 27 weeks (Eiby et al. 2013 (link)). An additional group of preterm piglets were exposed to maternally administered glucocorticoids (betamethasone, 0.19 mg/kg body wt, i.m.; Celestone Chronodose; Schering‐Plough, Kenilworth, NJ) at 48 and 24 h prior to delivery. This dose/kg is equivalent to that given to women presenting with threatened preterm labor and has been demonstrated to mature the cardiovascular system of pigs (Eiby et al. 2012 (link); Kim et al. 2014a (link)). In each group, 12–15 piglets were randomly selected from 4 litters. Piglets weighing less than the 10th centile or greater than the 90th centile were excluded.
Celestone chronodose
Manufactured by Merck & Co
Sourced in Australia
Celestone Chronodose is a laboratory product manufactured by Merck & Co. It is a corticosteroid medication used in research and clinical settings. The product's core function is to provide a controlled and consistent delivery of the active ingredient over an extended period.
Automatically generated - may contain errors
8 protocols using celestone chronodose
1
Preterm Piglet Model for Human Prematurity
2
Fetal Lung Development: Betamethasone Effects
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Unoperated ewes (n = 6) were administered a bolus intramuscular dose of betamethasone (11.4 mg: 5.7 mg/ml: Celestone Chronodose, Schering-Plough, Australia) at 36 h and 24 h prior to post-mortem at 124 d GA. Ewes bearing control fetuses (n = 6) were administered the equivalent volume of saline at the same gestational ages and at the same time interval as per betamethasone-treated ewes. All ewes and fetuses were humanely killed at 124d GA (late canalicular/early alveolar stage; canalicular stage last until 26 weeks GA in humans) and fetal lung tissue collected.
3
Preterm Piglet Delivery and Glucocorticoid Treatment
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Large White X Landrace piglets were delivered by caesarean section at two ages, preterm piglets delivered at 91 days gestation (term - 115 days) and term piglets delivered two days before the expected farrowing date. At 91 days, preterm piglets are approximately half of term weight, have very thin translucent skin, thermoregulate very poorly and require similar respiratory and cardiovascular support to a baby born at 25–27 weeks gestation [26] . An additional group of preterm piglets was exposed to maternally administered glucocorticoids (betamethasone, 0.19 mg/kg body weight, given i.m.; Celestone Chronodose; Schering-Plough, USA) given 48 h and 24 h before delivery. The timing and dose/kg are equivalent to that given to women presenting with threatened preterm labour. In each of the three treatment groups, three litters of piglets were studied. Four piglets (similar sex ratios) from each litter were randomly assigned to this experiment and four littermates were randomly assigned to another experiment that investigated cardiac function [8] (link). Piglets with a birth weight below the 10th percentile were excluded from both studies.
4
Preterm Guinea Pig Betamethasone Exposure
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All procedures were approved by the University of Newcastle Animal Care and Ethics Committee and were performed in accordance with the Australian Code of Practice for the Care and Use of Animals for Scientific Purposes. The Research Support Unit of the University of Newcastle supplied time-mated, pregnant outbred, tricolour guinea pigs at 21d gestational age (GA). Normal gestation in this population is 71d [22 (link)]. Dams were handled regularly by research staff from early in the pregnancy to reduce near term animal stress and subsequent cortisol release as a confounding factor.
Guinea pig dams received subcutaneous injections of either vehicle (175μL/kg, 0.9% sodium chloride) or betamethasone (Celestone Chronodose, 1mg/kg, Schering-Plough, Sydney, Australia) 24 and 12 hours prior to preterm (62±1d GA) or term (68/69d GA) caesarean-section delivery. The four resulting fetal groups were defined as control (delivery at 69d GA + vehicle treatment), term betamethasone exposure (delivery at 69d GA + betamethasone treatment), preterm (delivery at 62d GA + vehicle treatment) and preterm betamethasone exposure (delivery at 62d GA + betamethasone treatment). The treatment groups were further subdivided by sex. There were 6–8 dams per group, with only one dam being represented by more than one fetus per sex.
Guinea pig dams received subcutaneous injections of either vehicle (175μL/kg, 0.9% sodium chloride) or betamethasone (Celestone Chronodose, 1mg/kg, Schering-Plough, Sydney, Australia) 24 and 12 hours prior to preterm (62±1d GA) or term (68/69d GA) caesarean-section delivery. The four resulting fetal groups were defined as control (delivery at 69d GA + vehicle treatment), term betamethasone exposure (delivery at 69d GA + betamethasone treatment), preterm (delivery at 62d GA + vehicle treatment) and preterm betamethasone exposure (delivery at 62d GA + betamethasone treatment). The treatment groups were further subdivided by sex. There were 6–8 dams per group, with only one dam being represented by more than one fetus per sex.
5
Glucocorticoid-induced Ocular Hypertension
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OH was induced in ten eyes, five eyes G1, and five eyes G3. Topical prednisolone acetate drops (10 mg/mL Prednefrin Forte Eye drops, Allergan, Brazil) were used twice a day to raise and maintain elevated IOP. This was associated with weekly subconjunctival injections of 0.5 mL betamethasone acetate (Celestone Chronodose, 3 + 3 mg/mL disodium phosphate, Schering-Plough, Mexico) [12 (link), 13 ] in the right eye for 5 weeks, with the left eye used as the control.
6
Antenatal Corticosteroid Randomization
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Staff who enrolled eligible women at participating hospitals randomly assigned women (1:1) to receive either dexamethasone or betamethasone by contacting a central randomisation service, to determine the treatment pack to be given. An investigator (who was not involved with clinical care and is not a coauthor) used computergenerated random numbers and balanced variable blocks to produce a randomisation schedule, which was stratified by hospital, gestational age (<28 weeks or ≥28 weeks of gestation), and number of fetuses (ie, a singleton or twin pregnancy). At randomisation, the central randomisation service allocated a study number to each woman, which corresponded to a treatment pack. Treatment packs all looked identical and contained two opaque studylabelled syringes, which contained either 12 mg dexamethasone (as dexa methasone sodium phosphate, a nonsulphite containing preparation) or 11•4 mg betamethasone (Celestone Chronodose; ScheringPlough, Sydney, Australia) to be administered to participating women. We masked participants, clinical staff, study investigators, and those assessing outcomes to treatment allocations.
7
Fetal Arterial Pressure and Betamethasone
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Fetal arterial and amniotic catheters were connected to pressure transducers ("DTX Plus" transducer, Becton Dickinson, Singapore, Malaysia), and data were recorded digitally (PowerLab8/30 using LabChart, ADInstruments, Bella Vista, Australia). Fetal arterial pressure and HR were recorded for 1 h on 131 and 132 DG. Following the recording of fetal arterial pressure at 131 DG, betamethasone (5.7 mg i.m., Celestone Chronodose; Schering-Plough, Baulkham Hills, Australia) was administered to the ewe.
8
Fetal Monitoring and Preterm Delivery
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For 3 consecutive days after surgery, antibiotics (ampicillin and Engemycin; Austrapen; CSL) were administered intravenously to the ewe. Fetal blood samples were taken daily for assessment of fetal well-being, until 10 days postsurgery. The partial pressures of arterial oxygen (Pa O 2 ), carbon dioxide (Pa CO 2 ), oxygen saturation (Sa O 2 ), pH, hematocrit, glucose, HCO 3 Ϫ , and lactate were measured (ABL 700 blood gas analyzer; Radiometer, Copenhagen, Denmark). At fetal gestational age 123 and 124 days, betamethasone (Celestone Chronodose; Schering Plough) was administered to the ewe to mature the lungs before planned preterm delivery, as previously described (49) (link); this is equivalent to that used in human preterm pregnancies (2 doses of 11.4 mg im 24 h apart).
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