scholarly journals Effects of a non-steroidal aromatase inhibitor on ovarian function in cattle

2012 ◽  
Vol 24 (4) ◽  
pp. 631 ◽  
Author(s):  
M. Jimena Yapura ◽  
Reuben J. Mapletoft ◽  
Jaswant Singh ◽  
Roger Pierson ◽  
Jonathan Naile ◽  
...  
Keyword(s):  
Aromatase Inhibitor ◽  
High Performance ◽  
Ovarian Function ◽  
Plasma Concentrations ◽  
Dominant Follicle ◽  
Follicular Wave ◽  
Chromatography Tandem Mass Spectrometry ◽  
Liquid Chromatography Tandem Mass ◽  
Arrest Growth ◽  
Phosphate Buffered Saline

Effects of the non-steroidal aromatase inhibitor letrozole on ovarian function in cattle were determined. The hypothesis that letrozole would arrest growth of the dominant follicle, resulting in emergence of a new follicular wave at a predictable post-treatment interval, was tested. Heifers were assigned randomly to four groups 4 days after follicular ablation (~2½ days after wave emergence) and given intravenous doses of 500 (n = 9), 250 (n = 10), or 125 µg kg–1 (n = 10) letrozole or phosphate-buffered saline (controls; n = 10). Blood was collected and ovarian structures were monitored daily by transrectal ultrasonography. Plasma concentrations of LH and FSH were measured by radioimmunoassay; plasma concentrations of letrozole were determined by high-performance liquid chromatography tandem mass spectrometry. A single intravenous dose of letrozole did not induce regression of the dominant follicle present at the time of treatment, nor did it directly affect FSH release. Conversely, treatment with letrozole increased endogenous concentrations of LH and extended the lifespan of the dominant follicle, which delayed the next FSH surge and subsequent follicular wave emergence. Letrozole continues to have potential as a non-steroidal treatment for controlling ovarian function in cattle.

scholarly journals Relationship between metabolic hormones and ovulation of dominant follicle during the first follicular wave post-partum in high-producing dairy cows

Reproduction ◽  
2007 ◽  
Vol 133 (1) ◽  
pp. 155-163 ◽  
Author(s):  
Chiho Kawashima ◽  
Saori Fukihara ◽  
Mayumi Maeda ◽  
Etsushi Kaneko ◽  
Carlos Amaya Montoya ◽  
...  
Keyword(s):  
Blood Flow ◽  
Dairy Cows ◽  
Ovarian Function ◽  
Post Partum ◽  
Plasma Concentrations ◽  
Reproductive Hormones ◽  
Follicular Growth ◽  
Dominant Follicle ◽  
Follicular Wave ◽  
Igf I

Recent studies suggest that IGF-I is a crucial regulatory factor in follicular growth during earlypost-partumperiod. The aim of the present study was to determine in detail the changing profiles of metabolic and reproductive hormones in relation to ovulation of the dominant follicle (DF) of the first follicular wavepost-partumin high-producing dairy cows. Plasma concentrations of related hormones in 22 multiparous Holstein cows were measured from 4 weeks pre-partum to 3 weekspost-partum, and the development of DF was observed with colour Doppler ultrasound. Thirteen cows showed ovulation by 15.2 dayspost-partum. Anovulatory cows showed higher GH and lower IGF-I levels than those in ovulatory cows during the peri-partum period. Each DF developed similarly, and a clear blood flow in the follicle wall was observed despite ovulation or anovulation. In addition, detailed endocrine profiles were analyzed in 9 out of the 22 cows. Five cows showed an increase in plasma oestradiol-17β (E2) with follicular growth followed by E2 peak, LH surge and ovulation. In these cows, plasma IGF-I concentrations remained high until 10 dayspost-partumfollowed by a gradual decrease. Subsequently, the insulin level increased together with the E2 peak towards ovulation. These profiles were not observed in anovulatory cows. In conclusion, our data strongly support the concept that IGF-I and insulin represent ‘metabolic signals’ of the resumption of ovarian functionpost-partumin high-producing dairy cows. Moreover, we provide the first visual evidence that both ovulatory and anovulatory DFs of the first follicular wavepost-partumare similarly supplied with active blood flow.

scholarly journals NAT2 Gene Polymorphisms and Plasma Isoniazid Concentration in Vietnamese Tuberculosis Patients

2021 ◽  
Vol 18 (2) ◽  
Author(s):  
Tuan Anh LE ◽  
Nhung Hong Thi PHAM ◽  
Long Doan DINH ◽  
Luyen Thi LE ◽  
Thom Thi VU
Keyword(s):  
Gene Polymorphisms ◽  
High Performance ◽  
Sanger Sequencing ◽  
Plasma Concentrations ◽  
Tuberculosis Patients ◽  
Rapid Acetylators ◽  
Chromatography Tandem Mass Spectrometry ◽  
Liquid Chromatography Tandem Mass ◽  
Nat2 Gene ◽  
Study Population

Isoniazid (INH) is one of the most common drugs for tuberculosis (TB) treatment and INH acetylation catalyzed by non-inducible hepatic enzyme arylamine N-acetyltransferase type 2 (NAT2). The isoniazid acetylation rates, which depend on NAT2 genotypes, is constant in an individual but can changes between patients. Phenotypic groups can be classified based on the genotype: slow, intermediate, and rapid acetylators. This study was performed to identify the relation between NAT2 gene polymorphisms and plasma INH concentrations among the different genotypes of Vietnamese tuberculosis patients. Blood samples of 136 adult TB patients treated with INH were collected and genotyped for NAT2 gene polymorphisms using Sanger sequencing. Two-hour post-dosing INH plasma concentrations were determined by high-performance liquid chromatography/tandem mass spectrometry (HPLC/MS/MS). Among the 136 patients genotyped, there were 43 (31.62 %), 58 (42.65 %), and 35 (25.74 %) of slow, intermediate, and rapid acetylation phenotypes, with two-hour post dosing INH plasma concentrations of 3.4, 2.7, and 2.2 μg/ml, respectively. The differences in INH concentrations among the three genotypes were significant (P < 0.05). Genotyping of TB patients from Vietnam for NAT2 gene polymorphism revealed that 48 percent of the study population comprised slow acetylators. Two-hour INH levels were significantly different among CC and TT homozygous genotypes of NAT2(C282T), as 2.7 μg/ml and 3.9 μg/ml, respectively. This suggests that NAT2(C282T) could play a role in INH metabolism in TB patients. Methods: Blood samples of 136 adult TB patients treated with INH were collected and genotyped for NAT2 gene polymorphisms using Sanger sequencing. Two-hour post-dosing INH plasma concentrations were determined by high-performance liquid chromatography/tandem mass spectrometry (HPLC/MS/MS). Results: Among the 136 patients genotyped, there were 43 (31.62%), 58 (42.65%) and 35 (25.74%) of slow, intermediate and rapid acetylation phenotypes with two-hour post dosing INH plasma concentration of 3.4, 2.7 and 2.2 μg/ml, respectively. The differences in INH concentrations among the three genotypes were significant (P<0.05). Conclusions: Genotyping of TB patients from Vietnam for NAT2 gene polymorphism revealed that 48 per cent of the study population comprised slow acetylators. Two-hour INH levels were significantly different among slow and rapid acetylators.

176 EFFECTS OF VEHICLE AND ROUTE OF ADMINISTRATION OF LETROZOLE ON OVARIAN FUNCTION IN CATTLE

2011 ◽  
Vol 23 (1) ◽  
pp. 190 ◽  
Author(s):  
M. J. Yapura ◽  
R. J. Mapletoft ◽  
J. Singh ◽  
R. A. Pierson ◽  
D. Rogan ◽  
...  
Keyword(s):  
Aromatase Inhibitor ◽  
Benzyl Alcohol ◽  
Canola Oil ◽  
Ovarian Function ◽  
Transvaginal Ultrasound ◽  
Route Of Administration ◽  
Series Data ◽  
Dominant Follicle ◽  
Plasma Progesterone ◽  
Follicular Wave

Treatment with letrozole, a non-steroidal aromatase inhibitor, has been associated with elevated mean plasma LH concentrations, a prolonged period of dominance of the extant dominant follicle, and delayed emergence of the next follicular wave in cattle. As well, a luteotrophic effect was hypothesised by the observation that CL diameter was increased in heifers given 250 μg kg–1 of letrozole divided in a 3-day regimen. The objective of the present study was to determine the effects of vehicle and route of administration of letrozole on ovarian function in sexually mature beef heifers. Ovarian function was synchronized among heifers using transvaginal ultrasound-guided follicular ablation followed by a luteolytic dose of PGF b.i.d. 4 days later. The ovaries were subsequently examined daily by transrectal ultrasonography until ovulation was detected. On Day 3 (Day 0 = ovulation), heifers were assigned randomly to 4 treatment groups and given letrozole at a dose of 1 mg kg–1 intravenously (i.v. in benzyl alcohol, n = 10) or intramuscularly (i.m. in benzyl alcohol plus canola oil 1:1 v/v, n = 10), or given a placebo (i.v. in benzyl alcohol, n = 5) or (i.m. in benzyl alcohol plus canola oil 1:1 v/v, n = 5). The ovaries were monitored daily by ultrasonography, and blood samples collected twice daily by jugular venipuncture from pre-treatment to post-treatment ovulations. Comparisons among groups were made by 1-way ANOVA for single-point measurements and by ANOVA for repeated measures for time-series data. The interovulatory interval did not differ among groups, nor did the day-to-day diameter profile of the dominant follicle of wave 1 (first follicular wave after ovulation). However, the interval between emergence of waves 1 and 2 was longer in heifers treated with letrozole i.m. (11.7 ± 0.3 days) than in controls (10 ± 0.4 and 9.5 ± 0.5 days for i.v. and i.m. controls, respectively; P < 0.05), and intermediate in heifers given letrozole i.v. (10.6 ± 0.30 days). The day-to-day diameter profile of the corpus luteum was greater (P < 0.05), and plasma progesterone concentrations tended to be greater (P < 0.06) in heifers treated i.m. with letrozole v. placebo. Plasma LH concentrations did not differ among groups, whereas plasma FSH concentrations were greater (P < 0.02) in heifers treated i.v. with letrozole v. placebo. In summary, letrozole dissolved in benzyl alcohol and given intravenously at a dose of 1 mg kg–1 on Day 3 did not alter ovarian function in cattle, but the same dose given i.m. in canola oil vehicle resulted in a longer inter-wave interval, a greater CL diameter profile, and greater plasma progesterone concentrations. We conclude that i.m. letrozole in oil is a feasible route of administration and vehicle for the development of an aromatase inhibitor-based treatment for herd synchronization in cattle. Research supported by the Natural Sciences and Engineering Research Council of Canada, Canadian Institutes for Health Research, and Bioniche Life Science Inc.

227 EFFECTS OF A SINGLE DOSE OF A NONSTEROIDAL AROMATASE INHIBITOR ON OVARIAN FUNCTION IN CATTLE

2010 ◽  
Vol 22 (1) ◽  
pp. 271 ◽  
Author(s):  
M. J. Yapura ◽  
R. J. Mapletoft ◽  
J. Singh ◽  
R. A. Pierson ◽  
G. P. Adams
Keyword(s):  
Single Dose ◽  
Aromatase Inhibitor ◽  
Ovarian Function ◽  
T Test ◽  
The Body ◽  
Farm Animals ◽  
Saline Control ◽  
Dominant Follicle ◽  
Follicular Wave ◽  
Treatment Research

Many countries have banned the use of estrogenic products in farm animals. Nonsteroidal aromatase inhibitors prevent the body from producing its own estrogen. The effects on the ovary are thought to be a result of suppression of estrogen-producing follicles and a rebound in endogenous levels of FSH through the removal of the negative feedback effect of estradiol. An experiment was designed to determine the effects of a nonsteroidal aromatase inhibitor, letrozole, on ovarian function in cattle. The specific objective was to test the hypothesis that letrozole will arrest growth of the dominant follicle, resulting in emergence of a new follicular wave at a predictable interval post-treatment. Beef heifers were assigned randomly to 4 groups and given phosphate-buffered saline [control; (n = 10)] or letrozole at a dose of 500 (n = 9), 250 (n = 10), or 125 (n = 10) μgkg-1 i.v. 4 days after follicular ablation (≈ 2.5 days after wave emergence, at the time dominant follicle selection is manifest). Blood samples were collected and ovarian structures were monitored daily by transrectal ultrasonography. Analysis of variance for repeated measures, one-way ANOVA, paired t-test, and 2-sample t-test were applied to the analysis of the data. The diameter profile of the dominant follicle was larger in heifers treated with letrozole than in control heifers (P < 0.05). The intervals from treatment to new wave emergence and from treatment to onset of regression of the extant dominant follicle were longer (P < 0.05) in heifers treated with letrozole than in controls, although variances in the intervals were not different. A small but significant reduction in circulating estradiol concentration was observed, and plasma LH concentrations were higher (P < 0.05) in letrozole-treated heifers than in controls. Lower plasma concentrations of FSH in letrozole-treated heifers than in controls (P < 0.03) was interpreted as an indirect effect resulting from prolonged follicular dominance. In summary, a single dose of letrozole did not induce regression of the extant dominant follicle, nor did it directly affect FSH release. Conversely, letrozole extended the lifespan of the dominant follicle, in association with increased endogenous levels of LH, thereby delaying the next FSH surge and subsequent follicular wave emergence. Results suggest that letrozole has potential as a nonsteroidal method of controlling ovarian function in cattle but further studies are needed to clarify dosage and timing of treatment. Research supported by the Natural Sciences and Engineering Research Council of Canada and Bioniche Life Science Inc.

Study on the relationship between rivaroxaban and factor Xa activity in blood based on HPLC-MS/MS

2021 ◽  
Vol 22 ◽  
Author(s):  
Hongchuan Liu ◽  
Zhixia Zhao ◽  
Yingkai Wang ◽  
Lihong Liu ◽  
Yuanhua Yang ◽  
...  
Keyword(s):  
Plasma Concentration ◽  
High Performance ◽  
Plasma Concentrations ◽  
Factor Xa ◽  
Bleeding Risk ◽  
Tandem Mass ◽  
Chromatography Tandem Mass Spectrometry ◽  
Liquid Chromatography Tandem Mass ◽  
The Relationship

Objective: The aim of the study was to investigate a high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method for the determination of rivaroxaban and evaluate the correlation between plasma concentration and anti-Xa activity in patients using oral rivaroxaban. Methods: In this study, the plasma concentration of rivaroxaban and anti-Xa factor activities was determined in 125 patients, and the relationship between the two variables was analysed by SPSS 21.0 software. Results: The results showed that the plasma concentrations of oral rivaroxaban patients were significantly correlated with the activity of the anti-Xa factor (Spearman’s r = 0.990, p <0.05). Conclusion: The plasma concentrations of rivaroxaban are a potentially useful monitoring indicator to assess the patient’s bleeding risk if testing for plasma anti-Xa activity is not available.

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