Surrogates
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The piperidine-based Takemoto catalyst has been successfully employed in a novel asymmetric transfer hydroxymethylation of activated isoindolinones, allowing us to prepare the enantioenriched hydroxymethylated adducts in good to excellent yields (48-96%) and enantiopurities (81:19-97:3 e.r.). To increase the reaction rate without compromising the selectivity, carefully optimized formaldehyde surrogates were employed, providing a convenient source of anhydrous formaldehyde with a base-triggered release. The substrate scope, including 34 entries, showed the considerable generality of the asymmetric transformation, and most entries exhibited complete conversions in 24-48 h. A scale-up experiment and multiple enantioselective downstream transformations were also carried out, suggesting the prospective synthetic utility of the products.
- Publikační typ
- časopisecké články MeSH
In the past, selection of intermediate clinical endpoints (ICEs) in prostate cancer (PCa) trials largely depended on qualitative assessments; however, the advancing quality of research necessitates a robust correlation with overall survival (OS). This review summarises the results from several high-quality meta-analyses that explored the validity of ICEs as surrogates for OS. We found strong evidence that metastasis-free survival can serve as an ICE in localized PCa. In advanced disease, valid ICEs were identified only within the context of metastatic hormone-sensitive PCa, including radiological and clinical progression-free survival; however, concerns remain regarding their use owing to the limited generalisability of the data used to validate their surrogacy. PATIENT SUMMARY: Intermediate clinical endpoints can reduce the costs of trials and allow earlier introduction of new treatment methods. This article summarises results from studies verifying the validity of these endpoints as surrogates for overall survival.
- MeSH
- lidé MeSH
- míra přežití MeSH
- nádory prostaty * mortalita terapie patologie MeSH
- stanovení cílového parametru MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Evaluation of circulating tumor cells (CTCs) has demonstrated clinical validity as a prognostic tool based on enumeration, but since the introduction of this tool to the clinic in 2004, further clinical utility and widespread adoption have been limited. However, immense efforts have been undertaken to further the understanding of the mechanisms behind the biology and kinetics of these rare cells, and progress continues toward better applicability in the clinic. This review describes recent advances within the field, with a particular focus on understanding the biological significance of CTCs, and summarizes emerging methods for identifying, isolating, and interrogating the cells that may provide technical advantages allowing for the discovery of more specific clinical applications. Included is an atlas of high-definition images of CTCs from various cancer types, including uncommon CTCs captured only by broadly inclusive nonenrichment techniques.
- MeSH
- arteria brachialis patologie MeSH
- cévní endotel patologie ultrasonografie MeSH
- dospělí MeSH
- lidé MeSH
- reprodukovatelnost výsledků MeSH
- rychlost toku krve fyziologie MeSH
- ultrasonografie metody MeSH
- vazodilatace fyziologie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- Publikační typ
- srovnávací studie MeSH
Fibrate therapy results in elevation of plasma total homocysteine (tHcy), which is known to induce oxidative stress and endothelial dysfunction. We aimed to establish whether fibrate-induced elevation of tHcy has also similar consequences and whether they may be prevented by folate co-administration. Eighteen subjects with hypercholesterolemia were included in an open, prospective, cross-over study. We compared intra-individually the effect of fenofibrate on tHcy, oxidative stress and endothelial dysfunction surrogates, in monotherapy and when combined with 10 mg of folate. These effects were also compared with fluvastatin monotherapy. Fenofibrate in monotherapy significantly decreased LDL cholesterol, increased the tHcy by 39.5 %, while oxidized LDL (oxLDL), malondialdehyde (MDA), von Willebrand factors (vWf) and thrombomodulin (TMD) remained unchanged. When fibrate was co-administered with folate, the tHcy remained on the initial post-diet level, while both the total and oxLDL as well as MDA, vWf and TMD decreased. In contrast to fenofibrate monotherapy, fluvastatin (80 mg) had a similar effect as combined therapy with fenofibrate and folate, while tHcy remained uninfluenced. In conclusion, fenofibrate decreases the LDL cholesterol, but in contrast to fluvastatin, has no significant antioxidative and endothelium-protective potential, probably due to a concomitant increase of tHcy. These effects may be improved by co-administration of folate.
- MeSH
- cévní endotel cytologie enzymologie patofyziologie MeSH
- fenofibrát aplikace a dávkování farmakokinetika MeSH
- financování vládou MeSH
- hyperhomocysteinemie enzymologie etiologie MeSH
- kyselina listová aplikace a dávkování farmakokinetika MeSH
- lidé MeSH
- lipoproteiny biosyntéza metabolismus škodlivé účinky MeSH
- oxidační stres genetika účinky léků MeSH
- peroxidace lipidů genetika účinky léků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- srovnávací studie MeSH
The pyridinium-2-carbaldoximes with quinolinium carboxamide moiety were designed and synthesised as cholinesterase reactivators. The prepared compounds showed intermediate-to-high inhibition of both cholinesterases when compared to standard oximes. Their reactivation ability was evaluated in vitro on human recombinant acetylcholinesterase (hrAChE) and human recombinant butyrylcholinesterase (hrBChE) inhibited by nerve agent surrogates (NIMP, NEMP, and NEDPA) or paraoxon. In the reactivation screening, one compound was able to reactivate hrAChE inhibited by all used organophosphates and two novel compounds were able to reactivate NIMP/NEMP-hrBChE. The reactivation kinetics revealed compound 11 that proved to be excellent reactivator of paraoxon-hrAChE better to obidoxime and showed increased reactivation of NIMP/NEMP-hrBChE, although worse to obidoxime. The molecular interactions of studied reactivators were further identified by in silico calculations. Molecular modelling results revealed the importance of creation of the pre-reactivation complex that could lead to better reactivation of both cholinesterases together with reducing particular interactions for lower intrinsic inhibition by the oxime.
- MeSH
- acetylcholinesterasa metabolismus MeSH
- butyrylcholinesterasa metabolismus MeSH
- chinolinové sloučeniny chemická syntéza chemie farmakologie MeSH
- cholinesterasové inhibitory chemická syntéza chemie farmakologie MeSH
- lidé MeSH
- molekulární struktura MeSH
- pyridinové sloučeniny chemická syntéza chemie farmakologie MeSH
- rekombinantní proteiny metabolismus MeSH
- simulace molekulového dockingu MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Náhradní mateřství (NM) je procedura, kdy asistovanou reprodukci, těhotenství a porod podstoupí žena s cílem vzdát se narozeného dítěte a rodičovská práva a povinnosti převést na někoho jiného, předem domluveného. Složitost procedury s sebou přináší mnoho právních problémů; hlavními jsou určení právního rodičovství, vymahatelnost dohod uzavřených před porodem dítěte či před zahájením léčby, kompenzace nákladů, registrace novorozence, cesty hledání náhradní matky, právo dítěte znát své rodiče. Náš článek je reakcí na článek Náhradní mateřství v právní praxi, uveřejněný v Časopise zdravotnického práva a bioetiky (2015, Vol. 5, No. 2), reagujeme především na problematiku hledání náhradní matky.
Surrogate motherhood (SM) is a procedure, when a woman undergoes assisted reproduction, pregnancy and childbirth in order to give up her child and transfer parental rights and obligations someone else, who she previously agreed with. The complexity of the procedure entails many legal problems; the most important are the determination of legal parenthood, enforceability of agreements concluded before the child's birth or before commencement of treatment, compensation of costs, registration of the newborn, the search for a surrogate mother, the right of the child to know her/his parents. Our article is a response to the article Surrogate motherhood in Legal Practice, published in JMLB (2015, Vol. 5, No. 2), and we mainly address the issue of seeking a surrogate mother.
- Klíčová slova
- surogátní mateřství,
- MeSH
- asistovaná reprodukce MeSH
- lidé MeSH
- náhradní matky MeSH
- těhotenství MeSH
- Check Tag
- lidé MeSH
- těhotenství MeSH
- Publikační typ
- přehledy MeSH
- MeSH
- hematinika aplikace a dávkování terapeutické užití MeSH
- hemokoagulace účinky léků MeSH
- kyselina listová aplikace a dávkování terapeutické užití MeSH
- lidé středního věku MeSH
- lidé MeSH
- oxidační stres účinky záření MeSH
- poruchy koagulačních proteinů farmakoterapie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- srovnávací studie MeSH
Cíl studie: Přinést podklady pro debatu o kritériích výběru náhradní matky, pokud by procedura měla být v ČR právně regulována. Typ studie: Kvalitativní obsahová analýza dokumentů. Název a sídlo pracoviště: Zdravotně sociální fakulta, Jihočeská univerzita, České Budějovice; AK Prudil a spol., s.r.o., Brno. Metodika: Využito bylo několik zdrojů dat: 1. Právní dokumenty několika evropských států, v nichž je náhradní mateřství regulováno zákonem: UK, NL, Řecko, Portugalsko. 2. Webové stránky agentur, které náhradní mateřství zprostředkovávají; analyzovali jsme jich 23. Výsledky: Nejčastěji zmiňovaným kritériem pro výběr náhradní matky byl její rodičovský status a gynekologická anamnéza. Dále se požadavky týkaly věku, zdravotního stavu (vylučuje se psychiatrická diagnóza), životního stylu. Méně časté byly požadavky na BMI, občanství, příbuznost se žadateli, rodinný stav, bezúhonnost, finanční stabilitu, počty podstoupených procedur. Dále se požadují obtížně zajistitelné charakteristiky, například ochota k proceduře či podpora rodiny. Závěr: Kritéria formulovaná SAR ČGPS ČLS jsou velmi kvalifikovaná, zohledňují složitost procedury. Doporučujeme zvážit horní věkovou hranici a počty procedur, které může absolvovat jedna adeptka (doporučujeme jedinou). Zásadní osobou bude psycholog – psychodiagnostik. Doporučujeme začít vyjednávat s odbornými psychologickými společnostmi o jeho požadované kvalifikaci. Dále doporučujeme akceptovat tuto proceduru pouze pro páry s trvalým pobytem v ČR.
Objective: Provide background to the debate on the criteria for selecting a surrogate mother, if the procedure should be regulated in the Czech Republic. Design: Qualitative content analysis of documents. Setting: Faculty of Health and Social Studies, University of South Bohemia, České Budějovice; AK Prudil et al., Brno. Methods: Several sources of data have been used: 1. Legal documents of several European countries where surrogate motherhood is regulated by law: UK, NL, Greece, Portugal. 2. The websites of agencies that mediate surrogate motherhood; analysed number: 23. Results: The most frequently mentioned criterion for selection a surrogate mother was her parental status and gynecological history. Further, the requirements related to age, state of health (exclusion of psychiatric diagnosis), lifestyle. Less often, BMI requirements, citizenship, relationship with the applicant, marital status, impeccability, financial stability, number of procedures underwent. In addition, difficult-to-assess features, such as willingness to process or family support, are required. Conclusion: The criteria formulated by the SAR ČGPS ČLS are highly qualified, taking into account the complexity of the procedure. We recommend to reconsider the upper age limit and the number of procedures that an adept can pass (we recommend one). The psychologist should be qualified in psychodiagnostics. We recommend starting negotiations with professional psychological societies about his required qualifications. We also recommend accepting this procedure only for couples residing in the Czech Republic.
- MeSH
- asistovaná reprodukce * normy zákonodárství a právo MeSH
- lidé MeSH
- náhradní matky * zákonodárství a právo MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- práce podpořená grantem MeSH
