Amino acid sequence of oxytocin, identified already in 1906 as the uterotonic component of neurohypophyseal extracts, was established in 1953 by Vincent du Vigneaud in New York and Hans Tuppy in Vienna. Its structure was verified by the total synthesis one year after in the du Vigneaud laboratory. In the following years, simplified synthetic strategies elaborated in a number of laboratories worldwide enabled structural modifications of individual sites in the peptide chain, aiming at a detailed elucidation of their influence upon pharmacologic features of oxytocin. Frequently, these peptide analogues opened the way to new, clinically useful drugs. The research on vasopressin, the other main peptide hormone of posterior pituitary, underwent a similar development. Among the first who elaborated a more flexible alternative to du Vigneaud protocol was the peptide group at the Institute of Organic Chemistry and Biochemistry, Czechoslovak Academy of Sciences (ÚOCHB) in Prague, chaired by Josef Rudinger. Its research activities were broadly supported – sometimes even enabled – by František Šorm, director of the Institute. This opened a way to an easier synthesis of oxytocin analogues. Design strategy in Prague was focused on oxytocin analogues with an enhanced metabolic stability (prolongation of half-life in vivo), and on analogues acting as inhibitors to its uterotonic/galactobolic response. In the former case, design strategy has originated from studies of enzymatic stability of oxytocin, accomplished in the biochemical laboratories at the ÚOCHB, or reported in earlier communications. Doseresponse and time-response behaviour of analogues in which potential sites of enzymatic attacks were replaced by resistant sequences, and modified peptides investigated in a number of in situ and/or ex vivo pharmacological experiments. Of particular interest were analogues in which one or both sulphur atoms in the –S-S– bridge were replaced by the methylene group (–CH2–), the so-called carba-analogues. Individual analogues of this series possessed, in various degrees, biological activities of oxytocin but not a prolongation of their responses in pharmacological models or in their physiological clearance. Thus, the carba analogues document, firstly, that the integrity of the disulfide bridge in not a necessary condition of oxytocin (or vasopressin) activity, and secondly, that the –S-S– bridge is not the rate determining site of neurohypophyseal hormone inactivation in vivo. In an attempt to prolong the action of oxytocin, its N-a-group was acylated by an additional amino acid or a short peptide, in expectation that such analogues would act as prohormones: splitting of additional substituent by tissue aminopeptidases would in vivo produce “free” oxytocin (therapeutically, the analogues would act as oxytocin depots). A number of in vivo experiments verified this “hormonogen” model and brought forth some clinically interesting substances; some of them are in use until now. In the latter case, the search for structural modifications potentially leading to antagonism indeed brought some new antagonists but, in particular, contributed to the notion of continuous change from “full” agonism via partial agonism to antagonism, according to the tissue conditions. Such a change could have been achieved for uterotonic response of several analogues by changing calcium and magnesium concentrations in the tissue medium. Ideas originated by Rudinger’s group brought about several clinically useful peptides like Carbetocin, Atosiban, Glypressin, Terlipressin. Very successful was the Prague vasopressin analogue dDAVP (Desmopressin) licensed to the Swedish pharmaceutical company Ferring Läkemedel AB. Josef Rudinger left Czechoslovakia in 1968 and became a professor of molecular biology at the Swiss Federal Institute of Technology (ETH). He passed away, 51 years old, in 1975.

• MeSH
• biomedicínský výzkum * dějiny   MeSH
• dějiny 20. století MeSH
• desmopresin dějiny   MeSH
• lidé MeSH
• neurohypofyzární hormony dějiny   MeSH
• oxytocin * dějiny   MeSH
• vasopresiny dějiny   MeSH
• Check Tag
• dějiny 20. století MeSH
• lidé MeSH
• Publikační typ
• biografie MeSH
• historické články MeSH
• Geografické názvy
• Česká republika MeSH

• O autorovi
• Šorm, František, 1913-1980 Autorita
• Rudinger, Josef, 1924-1975 Autorita

Cíl: Shrnutí nových poznatků v oblasti implantace embrya v závislosti na kvalitě endometria. Metodika: Rešerše literatury publikované do srpna 2022 v databázích WoS, Scopus, PubMed/Medline se zaměřením na „endometrial receptivity“, „polycystic ovary syndrome“, „endometriosis“, „SARS-CoV-2“. Výsledky: Receptivní stav endometria je výsledkem fyziologické remodelace, činnosti imunity modulované mikrobiomem. Tuto rovnováhu narušují myomy, polypy, saktosalpingy, adenomyóza, endometrióza, syndrom polycystických vaječníků, infekce. Diskutuje se dopad infekce SARS-CoV-2. Pro úspěšnou implantaci je klíčové časování embryotransferu. Konvenčně se pro tyto účely využívá ultrazvuk. Ve specifických případech hysteroskopie a biopsie endometria. Vzorek se hodnotí histologicky, imunohistochemicky, vyšetřuje se mikrobiom anebo transkriptom. Jako podpora implantace jsou využívány gestageny, u syndromu polycystických ovarií metformin. U opakovaného selhání implantace intrauterinní infuze mononukleárů, plazmy bohaté na destičky, subkutánní aplikace granulocyty stimulujícího růstového faktoru, intravenózní podání atosibanu, intrauterinní aplikace choriogonadotropinu. Závěr: Nejnovější výzkumy na poli transkriptomiky, proteomiky a reprodukční imunologie hlouběji odkrývají implantaci a otvírají novou etapu asistované reprodukce.

Objective: A summary of new knowledge on embryo implantation in dependence on quality of the endometrium. Methods: Literature review from August 2022 of the relevant publications in Web of Science, Scopus and PubMed/Medline databases, focused on “endometrial receptivity”, “polycystic ovary syndrome”, “endometriosis”, “SARS-CoV-2”. Results: The receptive state of the endometrium is a result of physiological remodeling and immune system activity modulated by the microbiome. This balance can be disturbed by myomas, polyps, sactosalpings, adenomyosis, endometriosis, polycystic ovary syndrome, infections. The effect of SARS-CoV-2 infection is being discussed. For a successful implantation, timing of transfer is crucial. The ultrasound examination is used conventionally. In specific cases, hysteroscopy and endometrium biopsy are recommended. Histological and immunohistochemical evaluation is performed together with examination of microbiome or transcriptome. To support the implantation, gestagenes are used, or metformin in the patients with polycystic ovary syndrome. In cases of a repeated implantation failure, the intrauterine infusion of mononuclear cells or platelet rich plasma is used, subcutaneous application of granulocyte colony stimulating growth factor, intravenous application of atosiban or intrauterine application of human chorionic gonadotropin. Conclusion: Recent research in the field of transcriptomics, proteomics and reproductive immunology uncovers the process of implantation more deeply and opens a new stage of the assisted reproduction.

• MeSH
• choriogonadotropin MeSH
• COVID-19 metabolismus   MeSH
• endometrióza MeSH
• implantace embrya * fyziologie   MeSH
• lidé MeSH
• syndrom polycystických ovarií MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• přehledy MeSH

• MeSH
• chemické látky - účinky a užití MeSH
• otrava MeSH
• patologie MeSH

• Konspekt
• Patologie. Klinická medicína
• NLK Obory
• patologie

Amino acid sequence of oxytocin, identified already in 1906 as the uterotonic component of neurohypophyseal extracts, was established in 1953 by Vincent du Vigneaud in New York and Hans Tuppy in Vienna. Its structure was verified by the total synthesis one year after in the du Vigneaud laboratory. In the following years, simplified synthetic strategies elaborated in a number of laboratories worldwide enabled structural modifications of individual sites in the peptide chain, aiming at a detailed elucidation of their influence upon pharmacologic features of oxytocin. Frequently, these peptide analogues opened the way to new, clinically useful drugs. The research on vasopressin, the other main peptide hormone of posterior pituitary, underwent a similar development. Among the first who elaborated a more flexible alternative to du Vigneaud protocol was the peptide group at the Institute of Organic Chemistry and Biochemistry, Czechoslovak Academy of Sciences (ÚOCHB) in Prague, chaired by Josef Rudinger. Its research activities were broadly supported – sometimes even enabled – by František Šorm, director of the Institute. This opened a way to an easier synthesis of oxytocin analogues. Design strategy in Prague was focused on oxytocin analogues with an enhanced metabolic stability (prolongation of half-life in vivo), and on analogues acting as inhibitors to its uterotonic/galactobolic response. In the former case, design strategy has originated from studies of enzymatic stability of oxytocin, accomplished in the biochemical laboratories at the ÚOCHB, or reported in earlier communications. Dose-response and time-response behaviour of analogues in which potential sites of enzymatic attacks were replaced by resistant sequences, and modified peptides investigated in a number of in situ and/or ex vivo pharmacological experiments. Of particular interest were analogues in which one or both sulphur atoms in the –S-S– bridge were replaced by the methylene group (–CH2–), the so-called carba-analogues. Individual analogues of this series possessed, in various degrees, biological activities of oxytocin but not a prolongation of their responses in pharmacological models or in their physiological clearance. Thus, the carba analogues document, firstly, that the integrity of the disulfide bridge in not a necessary condition of oxytocin (or vasopressin) activity, and secondly, that the –S-S– bridge is not the rate determining site of neurohypophyseal hormone inactivation in vivo. In an attempt to prolong the action of oxytocin, its N-α-group was acylated by an additional amino acid or a short peptide, in expectation that such analogues would act as prohormones: splitting of additional substituent by tissue aminopeptidases would in vivo produce "free" oxytocin (therapeutically, the analogues would act as oxytocin depots). A number of in vivo experiments verified this "hormonogen" model and brought forth some clinically interesting substances; some of them are in use until now. In the latter case, the search for structural modifications potentially leading to antagonism indeed brought some new antagonists but, in particular, contributed to the notion of continuous change from "full" agonism via partial agonism to antagonism, according to the tissue conditions. Such a change could have been achieved for uterotonic response of several analogues by changing calcium and magnesium concentrations in the tissue medium. Ideas originated by Rudinger's group brought about several clinically useful peptides like Carbetocin, Atosiban, Glypressin, Terlipressin. Very successful was the Prague vasopressin analogue dDAVP (Desmopressin) licensed to the Swedish pharmaceutical company Ferring Läkemedel AB. Josef Rudinger left Czechoslovakia in 1968 and became a professor of molecular biology at the Swiss Federal Institute of Technology (ETH). He passed away, 51 years old, in 1975.

Entropy (ΔS), enthalpy (ΔH) and heat capacity (ΔCp) changes attending the oxytocin interaction with its two binding sites on myometrial cell membranes in sheep were derived from the temperature dependence of Kd values. The high affinity oxytocin site (Kd on the order of 10(-9)mol l(-1), 25 °C), ascribed to the oxytocin receptor (OXTR), is entropy-driven in the temperature range 0-37 °C. Enthalpy component prevails as a driving force in the binding to the low affinity site (Kd ≈ 10(-7)) within the higher temperature range. ΔCp values in both cases do not differ significantly from zero but become highly relevant in the presence of a GTP analog (10(-4)M GTP-γS). Under these conditions, ΔCp in the low site interaction becomes negative and ΔS is shifted toward negative values (enthalpy drift); ΔCp of the high affinity site rises to a high positive value and the interaction is even more strongly entropy driven. Atosiban, a competitive antagonist of oxytocin at OXTR displays a single significant binding site on myometrial cells (Kd about 10(-7)mol l(-1)). Thermodynamic profiles of atosiban and the low affinity oxytocin site show conspicuous similarities, indicating that the inhibitor is bound to the low affinity site, and not, with a lower affinity, to the putative receptor protein. It is suggested that the interaction of oxytocin with its responding system on myometrial membranes follows in two distinct steps that are likely to be associated with several independent binding domains in the GPCR receptor.

• MeSH
• arginin vasopresin metabolismus   MeSH
• buněčná membrána metabolismus   MeSH
• myometrium metabolismus   MeSH
• ovce MeSH
• oxytocin metabolismus   MeSH
• receptory oxytocinu metabolismus   MeSH
• teplota MeSH
• termodynamika MeSH
• vasotocin analogy a deriváty   metabolismus   MeSH
• vazebná místa MeSH
• zvířata MeSH
• Check Tag
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Učebnice určená pro porodníky, anesteziology, neonatology/dětské lékaře, porodní asistentky a studenty medicíny. Kolektiv autorů, předních českých odborníků, přináší rozsáhlé mezioborové informace a současné poznatky o významné perinatologické problematice – o použití analgezie a anestezie v porodnictví. Současně je kladen důraz na repetitorium základů porodnictví, anesteziologie a neonatologie coby nezbytné podmínky pro bezchybnou a nekonfliktní interdisciplinární spolupráci v péči o matku a dítě.

• MeSH
• porodnická analgezie MeSH
• porodnická anestezie MeSH
• porodnictví MeSH

• Konspekt
• Gynekologie. Porodnictví
• NLK Obory
• gynekologie a porodnictví
• anesteziologie a intenzivní lékařství
• NLK Publikační typ
• kolektivní monografie

• Klíčová slova
• Tractocile (Atosiban),
• MeSH
• agonisté beta-2-adrenergních receptorů aplikace a dávkování   farmakologie   MeSH
• hexoprenalin aplikace a dávkování   MeSH
• léková kontraindikace MeSH
• lidé MeSH
• oxytocin antagonisté a inhibitory   aplikace a dávkování   MeSH
• předčasný porod prevence a kontrola   MeSH
• ritodrin aplikace a dávkování   MeSH
• síran hořečnatý aplikace a dávkování   farmakologie   MeSH
• sympatomimetika aplikace a dávkování   farmakologie   MeSH
• těhotenství MeSH
• tokolytika aplikace a dávkování   farmakologie   MeSH
• tokolýza * metody   MeSH
• Check Tag
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH

Základní a dlouho očekávaná učebnice pro studenty zdravotnických oborů na lékařských a zdravotně sociálních fakultách i vyšších odborných školách. Text je doplněn mnoha grafy a praktickými příklady z praxe. Kniha obsahuje velké množství praktických poznatků, které potřebují členové interdisciplinárního zdravotnického týmu pro předepisování a podávání léků, sledování jejich účinků i edukaci pacienta.

• MeSH
• farmakologie MeSH
• učebnice jako téma MeSH

• NLK Obory
• farmacie a farmakologie

Základní a dlouho očekávaná učebnice pro studenty zdravotnických oborů na lékařských a zdravotně sociálních fakultách i vyšších odborných školách. Text je doplněn mnoha grafy a praktickými příklady z praxe. Kniha obsahuje velké množství praktických poznatků, které potřebují členové interdisciplinárního zdravotnického týmu pro předepisování a podávání léků, sledování jejich účinků i edukaci pacienta.

• Klíčová slova
• Farmacie, farmakologie, Ošetřovatelství - klinické obory,
• MeSH
• farmakologie MeSH

• NLK Obory
• farmacie a farmakologie

Základní a dlouho očekávaná učebnice pro studenty zdravotnických oborů na lékařských a zdravotně sociálních fakultách i vyšších odborných školách. Text je doplněn mnoha grafy a praktickými příklady z praxe. Kniha obsahuje velké množství praktických poznatků, které potřebují členové interdisciplinárního zdravotnického týmu pro předepisování a podávání léků, sledování jejich účinků i edukaci pacienta.

• MeSH
• farmakologie MeSH

• Konspekt
• Farmacie. Farmakologie
• Učební osnovy. Vyučovací předměty. Učebnice
• NLK Obory
• farmacie a farmakologie
• NLK Publikační typ
• učebnice vysokých škol