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Shokuhin Eiseigaku Zasshi. Journal of... 2024The present study verified that it is possible to analyze melengesterol acetate using the existing multi-residue method. Melengestrol acetate was extracted from...
The present study verified that it is possible to analyze melengesterol acetate using the existing multi-residue method. Melengestrol acetate was extracted from livestock products using acidic acetonitrile acidified with acetic acid in the presence of n-hexane and anhydrous sodium sulfate. The crude extracts were cleaned up using an octadecylsilanized silica gel cartridge column. Separation by HPLC was performed using an octadecylsilanized silica gel column with linear gradient elution of 0.1 vol% formic acid and acetonitrile containing 0.1 vol% formic acid. For the determination of the analyte, tandem mass spectrometry with positive ion electrospray ionization was used. In recovery tests using four livestock products fortified with maximum residue limits levels of melengestrol acetate (0.001-0.02 mg/kg), the truenesses ranged from 82% to 100%, and the repeatabilities for the entire procedure ranged from 0.5 RSD% to 5.6 RSD%. In recovery tests using 11 livestock products fortified with 0.0005 mg/kg of melengestrol acetate, the truenesses ranged from 88% to 99%, and the repeatabilities ranged from 1.3 RSD% to 5.4 RSD%. The limit of quantification for melengestrol acetate in livestock products was 0.0005 mg/kg.
Topics: Animals; Liquid Chromatography-Mass Spectrometry; Melengestrol Acetate; Chromatography, Liquid; Livestock; Silica Gel; Tandem Mass Spectrometry; Acetonitriles; Formates
PubMed: 38432897
DOI: 10.3358/shokueishi.65.15 -
Scientific Reports Oct 2023The present study aimed to test the efficiency of transcervical artificial insemination techniques with cervical immobilization (TCAI-CI) or cervical traction (TCAI-CT),...
The present study aimed to test the efficiency of transcervical artificial insemination techniques with cervical immobilization (TCAI-CI) or cervical traction (TCAI-CT), associated or not with the use of oxytocin (OT) as a protocol for cervical dilation, in the brown brocket deer (Subulo gouazoubira). The study was carried out in a crossover design using four adult females in two replicates with an interval of 60 days. Estrus was synchronized with oral melengestrol acetate (MGA) associated with estradiol benzoate and sodium cloprostenol. TCAI techniques were performed from 18 to 24 h after estrus onset. All females received either an i.v. application of 50 IU of OT (G-OT, n = 4) or 1 mL of saline solution (G-Control, n = 4) 20 min before the TCAI procedure. The TCAIs were performed using frozen-thawed semen motility 40%, vigor 3, acrosome integrity 87%, membrane integrity of 95% and 13% of total post-thaw defects from the same batch. Behavioral estrus was observed in 100% of the females, in both replicates. It was achieved a 50% (4/8) success of cervical transposition with semen deposition in the uterine. Regarding inseminations, most of them (87.5%) were performed using the TCAI-CT technique, and the overall conception rate was 50%. Cervical transposition times (< 1 min) and TCAI procedures (~ 17 min) were considered satisfactory. Thus, the performance of the TCAI-CI and TCAI-CT techniques was successful, regardless of using OT as a cervical dilation protocol. This procedure is proposed as a method of choice for artificial insemination with greater applicability in different conservation centers, compared to more advanced reproductive biotechniques, and with a favorable impact on the conservation of deer species.
Topics: Animals; Female; Male; Cervix Uteri; Deer; Insemination, Artificial; Oxytocin; Semen Preservation; Uterus; Cross-Over Studies
PubMed: 37833322
DOI: 10.1038/s41598-023-43392-4 -
Journal of Agricultural and Food... Jun 2023Gestagens, a class of veterinary drugs also called progestogens, are synthetic hormones used to increase feed efficiency and rate of gain in heifers. The Canadian Food...
Gestagens, a class of veterinary drugs also called progestogens, are synthetic hormones used to increase feed efficiency and rate of gain in heifers. The Canadian Food Inspection Agency analyzes progestogens melengestrol acetate (MGA), megestrol acetate, and chlormadinone acetate using liquid chromatography-mass spectrometry (LC-MS). Our conventional gestagen method for kidney fat has many time-consuming steps, including solid-phase extraction. A sample preparation procedure having fewer clean-up steps was developed for routine diagnostic analysis of kidney fat and provided similar results faster, and at lower cost. A confirmatory liver method for gestagens, developed using salt-assisted extraction, employed minimal clean-up steps that resulted in high chemical background at the desired lower limit of quantification (LLOQ). Differential ion mobility spectrometry, specifically high-field asymmetric waveform ion mobility spectrometry (FAIMS), was used to filter chemical background in the gas phase. The effect of the ionization probe position on FAIMS parameters, including sensitivity, is described. With LC-FAIMS-MS, chemical background for each gestagen was virtually eliminated, resulting in a quantitative liver method having the desired 0.6 ng/g LLOQ and estimated limits of detection (LODs) up to 140 times lower than LC-MS. Incurred MGA samples, analyzed using kidney fat and liver methods from the same animal, show levels within the quantitative ranges of both methods.
Topics: Animals; Cattle; Female; Progestins; Canada; Chromatography, Liquid; Mass Spectrometry; Melengestrol Acetate; Liver
PubMed: 37319426
DOI: 10.1021/acs.jafc.3c01200 -
Animal Reproduction Jan 2021Deer are sensitive to stressful stimuli by handling and their reproductive physiology could be altered by these procedures, making it necessary to develop less invasive...
Deer are sensitive to stressful stimuli by handling and their reproductive physiology could be altered by these procedures, making it necessary to develop less invasive protocols for ART. Melengestrol acetate (MGA), a synthetic progestin administered orally, appears as an alternative for estrous synchronization protocols (ESP), such as reported in cattle. Firstly, we compared two MGA doses (0.5 and 1.0 mg/day/animal), which would have suppression effect in estrous behavior (EB). Eight females were randomly and equally distributed in Group 1 (G1) and Group 2 (G2), which received 0.5 and 1.0 mg/day/animal respectively for 15 days (D1 to D15). Two cloprostenol (CP) applications were performed on D0 and D11. Estrus detection (ED) was performed every day. All females from G1 displayed estrus during treatment period, whereas all females from G2 displayed estrus after treatment, suggesting a suppressive effect of 1.0 mg in the EB. Once the suppressive MGA dose (1.0 mg) was defined, we used this dose for assessing ESP. The same eight females received 1.0 mg/animal for eight days (D-8 to D-1), followed by 0.25 mg of estradiol benzoate on D-8 and 265 μg of CP on D0. Feces for fecal progesterone metabolites (FPM) measurement were collected from D0 until seven days after the last day of estrus. Seven females displayed estrus between 12 and 72 h after CP application, which was followed by a significant increase in FPM levels (except female MG6), suggesting the formation of corpus luteum. After ED, females were placed with a fertile male to assess the fertility of the protocol. Pregnancy was confirmed by ultrasound 30 days after mating in 3/6 individuals. Although the low effectiveness of MGA protocol, it should be considered as a promising alternative in deer ESP since this protocol has less stressful effect on the animal during reproductive management when compared to other ESP.
PubMed: 33791030
DOI: 10.1590/1984-3143-AR2020-0526 -
Environmental Science and Pollution... Jan 2021
PubMed: 33216304
DOI: 10.1007/s11356-020-11617-y -
Environmental Science and Pollution... Nov 2020The toxicity of endocrinologically active pharmaceuticals finasteride (FIN) and melengestrol acetate (MGA) was assessed in freshwater mussels, including acute (48 h)...
The toxicity of endocrinologically active pharmaceuticals finasteride (FIN) and melengestrol acetate (MGA) was assessed in freshwater mussels, including acute (48 h) aqueous tests with glochidia from Lampsilis siliquoidea, sub-chronic (14 days) sediment tests with gravid female Lampsilis fasciola, and chronic (28 days) sediment tests with juvenile L. siliquoidea, and in chronic (42 days) sediment tests with the amphipod Hyalella azteca and the mayfly Hexagenia spp. Finasteride was not toxic in acute aqueous tests with L. siliquoidea glochidia (up to 23 mg/L), whereas significant toxicity to survival and burial ability was detected in chronic sediment tests with juvenile L. siliquoidea (chronic value (ChV, the geometric mean of LOEC and NOEC) = 58 mg/kg (1 mg/L)). Amphipods (survival, growth, reproduction, and sex ratio) and mayflies (growth) were similarly sensitive (ChV = 58 mg/kg (1 mg/L)). Melengestrol acetate was acutely toxic to L. siliquoidea glochidia at 4 mg/L in aqueous tests; in sediment tests, mayflies were the most sensitive species, with significant growth effects observed at 37 mg/kg (0.25 mg/L) (ChV = 21 mg/kg (0.1 mg/L)). Exposure to sublethal concentrations of FIN and MGA had no effect on the (luring and filtering) behaviour of gravid L. fasciola, or the viability of their brooding glochidia. Based on the limited number of measured environmental concentrations of both chemicals, and their projected concentrations, no direct effects are expected by these compounds individually on the invertebrates tested. However, organisms are exposed to contaminant mixtures in the aquatic environment, and thus, the effects of FIN and MGA as components of these mixtures require further investigation.
Topics: Animals; Bivalvia; Ephemeroptera; Female; Finasteride; Invertebrates; Melengestrol Acetate; Pharmaceutical Preparations; Water Pollutants, Chemical
PubMed: 32696412
DOI: 10.1007/s11356-020-10121-7 -
Journal of Animal Science Apr 2018Two experiments were conducted to evaluate the effects of a high concentrate, s.c. PGF2α compared with a conventionally concentrated, i.m. PGF2α in estrus...
Two experiments were conducted to evaluate the effects of a high concentrate, s.c. PGF2α compared with a conventionally concentrated, i.m. PGF2α in estrus synchronization protocols for heifers. In Exp. 1, 869 Angus-based beef heifers were enrolled at 8 locations. All heifers were exposed to the 7-d CO-Synch + controlled internal drug release (CIDR) estrus synchronization protocol. On day 7 of the protocol heifers received 100 µg of GnRH i.m., and a CIDR insert for 7 d. On day 0, at CIDR removal, estrous detection patches were applied to heifers and, within location, heifers randomly received 1 of 2 PGF2α treatments: 5 mL of Lutalyse i.m. (CONTROL; n = 434) or a 2 mL of Lutalyse HighCon s.c. (HiCON; n = 435). A second GnRH injection was administered at 54 ± 2 h and heifers were fixed-time AI (TAI). Heifers were evaluated for estrous activity at TAI by determining the activation of estrous detection patches. Pregnancy rates to AI (PR/AI) were diagnosed by transrectal ultrasonography between 35 and 55 d after TAI. The percentage of heifers exhibiting estrus between day 0 and TAI did not differ (P = 0.68) between CONTROL and HiCON treatments (47 vs. 46 ± 4%, respectively). Additionally, PR/AI were similar (P = 0.65) between CONTROL and HiCON treatments (46 vs. 45 ± 3%). In Exp. 2, 190 Angus-based beef heifers were enrolled at 2 locations. Heifers were exposed to the melengestrol acetate (MGA)-PGF2α protocol where they were offered 0.5 mg MGA per day from days 1 to 14. On day 33, heifers were randomly assigned to receive CONTROL (n = 95) or HiCON (n = 95) treatment, and estrous detection aids were applied. Heifers were exposed to AI 12 h after detection of estrus. Heifers not detected in estrus at location 1 received a second PGF2α injection 6 d after the initial PGF2α injection and were placed with fertile bulls. Heifers at location 2 that did not express estrus were administered 100 µg of GnRH i.m. and exposed to TAI 96 h after the initial PGF2α injection. Transrectal ultrasonography was used to diagnose PR/AI between 51 and 57 d after the initial PGF2α injection. The percentage of heifers exhibiting estrus during the estrus detection period was similar (P = 0.40) between CONTROL and HiCON treatments (82 vs. 87 ± 4%). Furthermore, PR/AI were similar (P = 0.62) between CONTROL and HiCON treatments (60 vs. 65 ± 5%). In summary, the 2 concentrations and corresponding routes of administration of PGF2α were similar in efficacy at synchronizing estrus in beef heifers.
Topics: Animals; Cattle; Delayed-Action Preparations; Dinoprost; Estrus; Estrus Detection; Estrus Synchronization; Female; Fertility; Gonadotropin-Releasing Hormone; Male; Melengestrol Acetate; Oxytocics; Pregnancy; Pregnancy Rate; Ultrasonography
PubMed: 29648600
DOI: 10.1093/jas/sky059 -
Journal of the American Veterinary... Apr 2018
Topics: Animals; Breeding; Calcinosis; Contraceptive Agents; Diagnosis, Differential; Drug Implants; Female; Melengestrol Acetate; Panthera; Ultrasonography; Uterine Diseases
PubMed: 29553900
DOI: 10.2460/javma.252.7.801 -
Food Safety (Tokyo, Japan) Dec 2017Food Safety Commission of Japan (FSCJ) conducted a risk assessment of melengestrol acetate (MGA, CAS No. 2919-66-6), a synthetic hormone, based on results from various...
Food Safety Commission of Japan (FSCJ) conducted a risk assessment of melengestrol acetate (MGA, CAS No. 2919-66-6), a synthetic hormone, based on results from various studies. MGA was recognized to have no genotoxicity relevant to human health, and it enabled FSCJ to specify an acceptable daily intake (ADI) in the assessment. studies using various human hormone-receptors showed that MGA exerts biological action primarily as progestogens and secondarily as glucocorticoids. Major adverse effects of MGA observed were mammary gland hyperplasia, endometrial hyperplasia, and a lack of corpora lutea, accompanying the elevated level of serum prolactin. Increased incidence of mammary gland tumor was observed in C3Han/f mice at the dose of 1.5 mg/kg bw/day in a carcinogenicity study. The increase was presumably due to MGA-induced hyperprolactinemia, but not a direct effect of MGA from the experiment, using a prolactin inhibitor. Inhibitions of estrus and ovulation, in addition to dystocia, were observed in female animals in the reproductive and developmental toxicity studies. Malformations such as cleft palate, clubfoot, umbilical hernia, and defective skeletal ossification were observed in rabbits at doses of 0.8 and 1.6 mg/kg bw/day in a developmental toxicity study. However, these were likely due to the corticosteroidal (glucocorticoid) action of MGA. The no-observed-adverse-effect level (NOAEL) was obtained from a rhesus monkey study given orally 1.5 µg/kg bw/day of MGA over the one menstrual-cycle. The value was, however, the result of the study using the large common ratio of 10. In another study, the lowest-observed-adverse-effect level (LOAEL) of 5 µg/kg bw/day, obtained from a cynomolgus monkey given MGA over the three menstrual-cycles. The LOAEL value was estimated close to the biological threshold, because of no obvious hormonal disorders despite of minimal change of menstrual cycle. Therefore, FSCJ considered it appropriate to specify an ADI on the basis of the LOAEL obtained from a cynomolgus monkey study over the three menstrual-cycles, and to add an additional safety factor of 2. Consequently, FSCJ specified the ADI of 0.025 µg/kg bw/day by applying a safety factor of 200 to the LOAEL of 5 µg/kg bw/day in a cynomolgus monkey study over the three menstrual-cycles.
PubMed: 32231940
DOI: 10.14252/foodsafetyfscj.2017009s -
Antimicrobial Agents and Chemotherapy 2014Candida species are the cause of 60% of all mycoses in immunosuppressed individuals, leading to ∼150,000 deaths annually due to systemic infections, whereas the...
Candida species are the cause of 60% of all mycoses in immunosuppressed individuals, leading to ∼150,000 deaths annually due to systemic infections, whereas the current antifungal therapies either have toxic side effects or are insufficiently efficient. We performed a screening of two compound libraries, the Enzo and the Institute for Molecular Medicine Finland (FIMM) oncology collection library, for anti-Candida activity based on the European Committee on Antimicrobial Susceptibility Testing (EUCAST) guidelines. From a total of 844 drugs, 26 agents showed activity against Candida albicans. Of those, 12 were standard antifungal drugs (SADs) and 7 were off-target drugs previously reported to be active against Candida spp. The remaining 7 off-target drugs, amonafide, tosedostat, megestrol acetate, melengestrol acetate, stanozolol, trifluperidol, and haloperidol, were identified with this screen. The anti-Candida activities of the new agents were investigated by three individual assays using optical density, ATP levels, and microscopy. The antifungal activities of these drugs were comparable to those of the SADs found in the screen. The aminopeptidase inhibitor tosedostat, which is currently in a clinical trial phase for anticancer therapy, displayed a broad antifungal activity against different Candida spp., including Candida glabrata. Thus, this screen reveals agents that were previously unknown to be anti-Candida agents, which allows for the design of novel therapies against invasive candidiasis.
Topics: Antifungal Agents; Antineoplastic Agents; Candida; Clinical Trials as Topic; Drug Discovery; Drug Repositioning; Drug Resistance, Fungal; Glycine; High-Throughput Screening Assays; Humans; Hydroxamic Acids; Microbial Sensitivity Tests; Small Molecule Libraries
PubMed: 24277040
DOI: 10.1128/AAC.01087-13