Entry
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Journal of molecular and cellular cardiology, ISSN 0022-2828 vol. 16, suppl. 3, September 1984
Nestr. ; 24 cm
- MeSH
- blokátory kalciových kanálů terapeutické užití farmakologie MeSH
- kardiovaskulární nemoci farmakoterapie MeSH
- Publikační typ
- abstrakty MeSH
- kongresy MeSH
- Konspekt
- Patologie. Klinická medicína
- NLK Obory
- kardiologie
- farmacie a farmakologie
American journal of cardiology, ISSN 0002-9149 vol. 56, no. 16, December 1985
111H s. : tab., grafy ; 30 cm
- MeSH
- antihypertenziva MeSH
- blokátory kalciových kanálů MeSH
- hypertenze MeSH
- Publikační typ
- kongresy MeSH
- Konspekt
- Farmacie. Farmakologie
- NLK Obory
- farmacie a farmakologie
- angiologie
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is an RNA virus responsible for coronavirus disease 2019 (COVID-19). While SARS-CoV-2 primarily targets the lungs and airways, it can also infect other organs, including the central nervous system (CNS). The aim of this study was to investigate whether the choroid plexus could serve as a potential entry site for SARS-CoV-2 into the brain. Tissue samples from 24 deceased COVID-19-positive individuals were analyzed. Reverse transcription real-time PCR (RT-qPCR) was performed on selected brain regions, including the choroid plexus, to detect SARS-CoV-2 viral RNA. Additionally, immunofluorescence staining and confocal microscopy were used to detect and localize two characteristic proteins of SARS-CoV-2: the spike protein S1 and the nucleocapsid protein. RT-qPCR analysis confirmed the presence of SARS-CoV-2 viral RNA in the choroid plexus. Immunohistochemical staining revealed viral particles localized in the epithelial cells of the choroid plexus, with the spike protein S1 detected in the late endosomes. Our findings suggest that the blood-cerebrospinal fluid (B-CSF) barrier in the choroid plexus serves as a route of entry for SARS-CoV-2 into the CNS. This study contributes to the understanding of the mechanisms underlying CNS involvement in COVID-19 and highlights the importance of further research to explore potential therapeutic strategies targeting this entry pathway.
- MeSH
- COVID-19 * virologie MeSH
- dospělí MeSH
- fosfoproteiny * metabolismus MeSH
- glykoprotein S, koronavirus * genetika metabolismus MeSH
- hematoencefalická bariéra * virologie MeSH
- internalizace viru MeSH
- koronavirové nukleokapsidové proteiny MeSH
- lidé středního věku MeSH
- lidé MeSH
- plexus chorioideus * virologie MeSH
- RNA virová * genetika MeSH
- SARS-CoV-2 * fyziologie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
In several species, including Xenopus, mouse and human, two members of cyclin A family were identified. Cyclin A2, which is ubiquitously expressed in dividing cells and plays role in DNA replication, entry into mitosis and spindle assembly, and cyclin A1, whose function is less clear and which is expressed in spermatocytes, leukemia cells and in postmitotic multiciliated cells. Deletion of the gene showed that cyclin A1 is essential for male meiosis, but nonessential for female meiosis. Our results revealed, that the cyclin A1 is not only dispensable in oocytes, we show here that its expression is in fact undesirable in these cells. Our data demonstrate that the APC/C and proteasome in oocytes are unable to target sufficiently cyclin A1 before anaphase, which leads into anaphase arrest and direct inhibition of separase. The cyclin A1-induced cell cycle arrest is oocyte-specific and the presence of cyclin A1 in early embryos has no effect on cell cycle progression or chromosome division. Cyclin A1 is therefore not only an important cell cycle regulator with biased expression in germline, being essential for male and damaging for female meiosis, its persistent expression during anaphase in oocytes shows fundamental differences between APC/C function in oocytes and in early embryos.
- MeSH
- anafáze * MeSH
- cyklin A1 fyziologie MeSH
- cyklin A2 fyziologie MeSH
- fluorescenční mikroskopie MeSH
- meióza MeSH
- metafáze MeSH
- mikroinjekce MeSH
- myši MeSH
- oocyty cytologie MeSH
- proteasomový endopeptidasový komplex fyziologie MeSH
- segregace chromozomů * MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Táto štúdia poskytuje nové empirické dôkazy o zmenách v intenzite konkurencie a štruktúre trhu lekární po deregulácii vstupných podmienok. Štúdia skúma vývoj maloobchodného trhu lekární v Portugalsku, ktorý prešiel regulačnými zmenami v rokoch 2004 a 2007. V dôsledku týchto zmien boli predaj voľne predajných liekov a vlastníctvo lekární liberalizované, avšak obmedzenia vstupu súvisiace s veľkosťou trhu a umiestnením nových lekární ostali v platnosti v nezmenenej podobe. Empirická stratégia vychádza z modelov vstupu, ktoré umožňujú porovnanie nevyhnutnej veľkosti trhu pre vstup tej-ktorej lekárne na trh pred a po zmenách v regulácii. Takéto porovnanie umožňuje zistiť, či sa konkurencia zintenzívnila s deregulovanými OTC liekmi. Zo štúdie vyplynuli tri hlavné zistenia. Po prvé, nevyhnutná veľkosť trhu sa znížila bez ohľadu na počet lekární na tomto trhu, čo naznačuje, že priestor na realizáciu ziskov je širší ako pred dereguláciou. Po druhé, hoci vstupné prahy mali nižšiu hodnotu, ich relatívny nárast s každým ďalším konkurentom vstupujúcim na trh bol v roku 2020 strmší ako v roku 2004, čo naznačuje zintenzívnenie cenovej konkurencie. Po tretie, súčasné pravidlo 3500 pacientov na lekáreň je pravdepodobne príliš reštriktívne a lekárne by sa vedeli presadiť aj na menších trhoch.
This study provides new empirical evidence on the changes in competition and entry decisions of pharmacies after regulatory changes. It investigates the development of the retail pharmacy market in Portugal, which underwent major regulatory changes in 2004 and 2007. Sale of OTC drugs and ownership of pharmacies were liberalized while entry restrictions related to market size and the location of new pharmacies prevailed. Our empirical strategy was based on entry models and provided indirect information on the toughness of competition and entry decisions of firms in the market. We estimated and compared the entry thresholds and their ratios before and after liberalization. Such a comparison allows to see if competition got tenser with OTC drugs deregulated. There were three main findings from the study. First, the entry thresholds decreased regardless of the number of pharmacies in the market, suggesting that room for the realization of profits is broader than it was in the past. Second, although the entry thresholds were lower in value, their increase was steeper with each incumbent in 2020, suggesting harsher price competition with new entrants. Third, the current rule of 3,500 patients per pharmacy is likely overly restrictive, pharmacies could break-even even in smaller markets.