Preclinical Development Handbook

Gad, Shayne C.

doi:10.1002/9780470249055

Cited by 3 publications

(1 citation statement)

References 295 publications

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“…At the present stage of development of veterinary science, the use of ozone is gaining popularity, both for therapeutic purposes [1][2][3][4][5][6][7][8] and in many preventive measures [8][9][10][11][12][13][14]. The intensive development of ozone therapy opens up more and more prospects for the use of ozone in the treatment of various diseases, both in humans and in animals.…”

Section: Introductionmentioning

confidence: 99%

Determination of inhalation toxicity of the ozone-air mixture

et al. 2020

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The work on the inhalation toxicity of the ozone-air mixture was carried out in two stages. At the first stage, acute inhalation toxicity was studied and the class of toxicity was determined, at the second stage, subchronic inhalation toxicity was determined. The object of the study was an ozone-air mixture. A portable standalone ozone generation device developed by us was used as a source of the mixture. A total of 58 outbred mature white Wistar rats of both sexes were used in the study, where 18 rats participated in the first stage, and 40 rats in the second. The animals were placed in an inhalation chamber. The procedure for testing acute inhalation toxicity was carried out according to the standard method at concentrations of ozone-air mixture of 100, 500, 2500 ppm and an exposure of 4 hours. As a result, the fatal outcome was observed only in 3 groups (2500 ppm), 3 out of 6 individuals were killed, including 2 males and 1 female. In fallen animals, death occurred as a result of respiratory arrest. The surviving animals were monitored for 14 days after the test. During the treatment of animals with ozone-air mixture, a gradual inhibition of the respiratory system was observed, followed by the development of pulmonary edema and respiratory failure. Based on the data obtained, the ozone-air mixture under study was assigned a hazard class 3. In the study of subchronic inhalation toxicity of oats, concentrations of 250, 125, and 50 ppm were studied. The experiment was carried out, according to the standards for determining the subchronic inhalation toxicity of substances, for 90 days. During the experiment, body weight, feed consumption, behavioral activity were recorded, and blood hematological and biochemical parameters were determined. As a result of the study of subchronic inhalation toxicity of the ozone-air mixture, no signs of intoxication were detected in rats, and there were no death cases.

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Section: Introductionmentioning

confidence: 99%

Determination of inhalation toxicity of the ozone-air mixture

et al. 2020

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Characterisation of AMB-FUBINACA metabolism and CB1-mediated activity of its acid metabolite

et al. 2022

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Purpose AMB-FUBINACA is a synthetic cannabinoid receptor agonist (SCRA) which is primarily metabolised by hepatic enzymes producing AMB-FUBINACA carboxylic acid. The metabolising enzymes associated with this biotransformation remain unknown. This study aimed to determine if AMB-FUBINACA metabolism could be reduced in the presence of carboxylesterase (CES) inhibitors and recreational drugs commonly consumed with it. The affinity and activity of the AMB-FUBINACA acid metabolite at the cannabinoid type-1 receptor (CB1) was investigated to determine the activity of the metabolite. Methods The effect of CES1 and CES2 inhibitors, and delta-9-tetrahydrocannabinol (Δ9-THC) on AMB-FUBINACA metabolism were determined using both human liver microsomes (HLM) and recombinant carboxylesterases. Radioligand binding and cAMP assays comparing AMB-FUBINACA and AMB-FUBINACA acid were carried out in HEK293 cells expressing human CB1. Results AMB-FUBINACA was rapidly metabolised by HLM in the presence and absence of NADPH. Additionally, CES1 and CES2 inhibitors both significantly reduced AMB-FUBINACA metabolism. Furthermore, digitonin (100 µM) significantly inhibited CES1-mediated metabolism of AMB-FUBINACA by ~ 56%, while the effects elicited by Δ9-THC were not statistically significant. AMB-FUBINACA acid produced only 26% radioligand displacement consistent with low affinity binding. In cAMP assays, the potency of AMB-FUBINACA was ~ 3000-fold greater at CB1 as compared to the acid metabolite. Conclusions CES1A1 was identified as the main hepatic enzyme responsible for the metabolism of AMB-FUBINACA to its less potent carboxylic acid metabolite. This biotransformation was significantly inhibited by digitonin. Since other xenobiotics may also inhibit similar SCRA metabolic pathways, understanding these interactions may elucidate why some users experience high levels of harm following SCRA use.

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Enviromicsin breeding: applications and perspectives on envirotypic-assisted selection

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Piepho

Silva‐Junior

et al. 2019

Preprint

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Key message:We propose the application of Enviromics to breeding practice, by which the similarity 16 among sites assessed on an "omics" scale of environmental attributes drives the prediction of 17 unobserved genotypes. 18 Abstract. Genotype by Environment interaction (G × E) studies have focused mainly on estimating 19 genetic parameters over a limited number of experimental trials. However, recent Geographic 20 34 when coupled with next-generation genotyping/phenotyping and powerful statistical modeling of 35 genetic diversity. Environmental scenarios can also be improved using information from strategic plans 36 for biodiversity and genetic resources management, especially in the current perspective of dynamic 37 climate change.38

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Preclinical Development Handbook

Cited by 3 publications

References 295 publications

Determination of inhalation toxicity of the ozone-air mixture

Determination of inhalation toxicity of the ozone-air mixture

Characterisation of AMB-FUBINACA metabolism and CB1-mediated activity of its acid metabolite

Enviromicsin breeding: applications and perspectives on envirotypic-assisted selection

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