In Europe, the first case of coronavirus disease (COVID-19) and the first COVID-19-related death were reported in France on January 24th and February 15th, 2020, respectively. Officially, the first case of COVID-19 infection in the Republic of Serbia was registered on March 6th. Herein, we presented the first case of retrospective detection of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in the post-mortem-obtained vitreous humor (VH), which took place on February 5th, 2020. This is the first death in Europe proven to be caused by COVID-19 by means of post-mortem histopathological and molecular analyses. Based on this finding, it appears that SARS-CoV-2 has been spreading faster and started spreading much earlier than it had been considered and that COVID-19 was probably the cause of the much-reported pneumonia of unknown origin in January and February 2020.
Itraconazole is a triazole antifungal agent with highly variable pharmacokinetics, with not yet fully identified factors as the source of this variability. Our study aimed to examine the influence of body mass index, gender, and age on the first dose pharmacokinetics of itraconazole in healthy subjects, using pharmacokinetic modeling, non-compartmental versus compartmental ones. A total of 114 itraconazole and hydroxy-itraconazole sets of plasma concentrations of healthy subjects of both genders, determined using a validated liquid chromatographic method with mass spectrometric detection (LC-MS), were obtained for pharmacokinetic analyses performed by the computer program Kinetica 5®. Genetic polymorphism in CYP3A4, CYP3A5, CYP1A1, CYP2C9, and CYP2C19 was analyzed using PCR-based methods. Multiple linear regression analysis indicated that gender had a significant effect on AUC as the most important pharmacokinetics endpoint, whereas body mass index and age did not show such an influence. Therefore, further analysis considered gender and indicated that both geometric mean values of itraconazole and hydroxy-itraconazole plasma concentrations in men were prominently higher than those in women. A significant reduction of the geometric mean values of Cmax and AUC and increment of Vd in females compared with males were obtained. Analyzed genotypes and gender differences in drug pharmacokinetics could not be related. Non-compartmental and one-compartmental models complemented each other, whereas the application of the two-compartmental model showed a significant correlation with the analysis of one compartment. They indicated a significant influence of gender on itraconazole pharmacokinetics after administration of the single oral dose of the drug, given under fed conditions. Women were less exposed to itraconazole and hydroxy-itraconazole than men due to poorer absorption of itraconazole, its more intense pre-systemic metabolism, and higher distribution of both drug and its metabolite.
Nowadays, illegal trafficking and smuggling of animals are among the greatest threats to many avian species. Most commonly smuggled birds belong to parrots, song birds, raptor species and owls. All of these species are protected by national and international legislations. In order to prevent and reduce wildlife trafficking, DNA methods have become an important forensic tool in species and sex identification. In this study, CHD1R/CHD1F primer pair was used to amplify a part of the CHD1 gene from 65 birds that belong to 43 species. For 36 species this is the first time that the length of CHD1 amplicons was measured for the purpose of species determination. The results were visualized using capillary electrophoresis and enabled simultaneous determination of sex and species. Based on the number of amplicons (two in females, one in males) sex was successfully determined in all species, even in cases where gel electrophoresis failed to give results. Moreover, the species was successfully determined in most bird species based on the species-specific sizes of CHD1 amplicon. The method used in this study is of great importance for veterinary forensic medicine and the prevention of wildlife smuggling. Still, further work is necessary to confirm the effectiveness of the method in all bird species.
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