Due to long-term domestication, breeding and divergent selection, a vast genetic diversity in poultry currently exists, with various breeds being characterized by unique phenotypic and genetic ...features. Assuming that differences between chicken breeds divergently selected for economically and culturally important traits manifest as early as possible in development and growth stages, we aimed to explore breed-specific patterns and interrelations of embryo myogenesis, nitric oxide (NO) metabolism and post-hatch growth rate (GR).
These characteristics were explored in eight breeds of different utility types (meat-type, dual purpose, egg-type, game, and fancy) by incubating 70 fertile eggs per breed. To screen the differential expression of seven key myogenesis associated genes (
,
,
,
,
,
, and
), quantitative real-time PCR was used.
We found that myogenesis associated genes expressed in the breast and thigh muscles in a coordinated manner showing breed specificity as a genetic diversity signature among the breeds studied. Notably, coordinated ("accord") expression patterns of
,
, and
were observed both in the breast and thigh muscles. Also, associated expression vectors were identified for
and
in the breast muscles and for
and
genes in the thigh muscles. Indices of NO oxidation and post-hatch growth were generally concordant with utility types of breeds, with meat-types breeds demonstrating higher NO oxidation levels and greater GR values as compared to egg-type, dual purpose, game and fancy breeds.
The results of this study suggest that differences in early myogenesis, NO metabolism and post-hatch growth are breed-specific; they appropriately reflect genetic diversity and accurately capture the evolutionary history of divergently selected chicken breeds.
Nirmatrelvir is an antiviral drug that, in combination with ritonavir, is an effective agent for the etiotropic therapy of patients with mild to moderate COVID-19.
The aim
of the study was to ...evaluate bioequivalence of the generic drug nirmatrelvir Аrpaxel in combination with ritonavir and the original drug Paxlovid, which is a combination of nirmatrelvir/ritonavir, in a single dose administration to healthy volunteers.
Materials and methods.
This research was an open-label, randomized, two-period crossover bioequivalence study. It included 2 periods, in each of which the volunteers received either a test drug (nirmatrelvir at the dose of 300 mg) in combination with ritonavir (100 mg), or a reference drug (a combination of nirmatrelvir 300 mg and ritonavir 100 mg), given as a single dose. A wash-out period between each of the administrations was 7 days. The blood sampling to determine the concentration of nirmatrelvir was carried out in the range from 0 to 36 h in each of the study periods. A nirmatrelvir concentration was determined by a validated HPLC-MS/MS method with a lower quantitation limit of 10 ng/mL. Bioequivalence was assessed by comparing 90% confidence intervals (CIs) for the ratio of geometric means of AUC
(0–16)
and C
max
of the test drug and reference drugs with the established equivalence limits of 80.00–125.00%.
Results.
In
the study were included 68 healthy volunteers, 67 participants of which were included in the bioequivalence population. The pharmacokinetic parameters of the drugs were comparable to each other. The 90% confidence interval for the ratio of the geometric mean of the maximum drug concentration in the blood plasma and the area under the pharmacokinetic curve «concentration-time» from zero to the last blood draw within 36 hours of nirmatrelvir was 87.26–100.83 and 93.27–103.74%, which meets the criteria for assessing bioequivalence. The test drugs were well tolerated by the volunteers. The incidence of adverse events was similar for the test and reference drugs. No serious adverse events were recorded during the entire study.
Conclusion.
As a result of this study, bioequivalence of the test and reference drugs has been established.
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