Chem. Listy 2022; 116: 101−109. doi: 10.54779/ chl20220101 vladimir.pliska@biol.ethz.ch, parizek@porodnice.cz Došlo 12. 10. 2021, přijato 1. 11. 2021.
Abstract: Licence agreements between the Institute of Organic Chemistry and Biochemistry, Czechoslovak Academy of Sciences, Prague (IOCB), and the pharmaceutical company Ferring AB Malmö enabled the Swedish company to produce and commercialize worldwide a number of neurohypophyseal peptides designed at the IOCB. Several of them found therapeutic applications. dDAVP: 1-deamino-8-D-arginine-vasopressin was designed in one of the IOCB peptide laboratories (M. Zaoral and F. Šorm) in 1967. It displayed an extremely high antidiuretic activity (various tests indicate a 2- to 50-fold increase, as compared to arginine vasopressin) and a very low pressor activity. The peptide (covered by the U.S. Patent No. 3,497,491, 1970) has been used as a preferred drug in the substitution therapy of the central form of diabetes insipidus (Minirin®, today as Desmopressin INN). Besides, as later discovered (Mannucci et al. 1977), dDAVP increases the plasma concentration of the blood clottiing factor VIII. This fact extended its clinical use as haemostatics in cases of milder forms of haemophilia A, von Willebrand-Jürgens syndrome and some thrombocyte dysfunctions. Despite of the clinical success of dDAVP, a closer look reveals certain inadequacies in the presently available pharmacological data: several reports declare activity values and the prolongation effect (index of persistence) in very broad ranges. Triglycyl-8- -lysine-vasopressin (Terlipressin), a peptide with lysine vasopressin chain extended at the N-terminal by a triglycine residue, acts mainly as a prodrug (releasing lysine vasopressin after aminopeptidase splitting at the Na group). The analogue belongs to the so-called „synthetic hormonogens“; individual peptides carrying various acylating groups were synthesized in the midsixties at the IOCB and legally protected by U.S. Patent No. 3,558,590 (1968). It was a part of the licence agreements mentioned above. The activities of triglycyl-8-lysine-vasopressin (both antidiuretic and vasopressor) are about 100 times lower than those of lysine vasopressin, but its persistence is 5 times longer. As such, it is occasionally used in emergency medicine in cases of esophageal (and other gastroenteral) bleeding, traumatic or septic shock, in cirrhotic patients and patients with portal hypertension. Its use as an early abortion drug was discussed but not pursued. Carbetocin (deaminocarba1-2-O-methyltyrosin-oxytocin) was synthetized in the laboratory of Karel Jošt at the IOCB before 1971; its synthesis was covered by a Czechoslovak patent (CS-149,028 B1) in June 1973 (at that time, Czechoslovak patent law did not provide for the patentability of substances as such) and first published in a biophysical communication by Frič et al., 1974). As a part of the licence agreement, it was included in the production program of Ferring AB, but marketed later also by several other pharmaceutical companies due to an incomplete patent protection. The peptide is a moderately active uterotonic partial agonist and as such has been utilized in veterinary obstetrics for delivery induction in cows and (multiparous) pigs: its milder and better--controlled uterotonic action was found preferential as compared to oxytocin so far used for these purposes. In the last two decades, carbetocin has been commonly used also in the human obstetrics, especially to prevent the peri- and post-partum haemorrhage, from the maternal side the most frequent and most severe delivery complication. It became a life-saving drug in emergency obstetrics.
- Klíčová slova
- carbetocin,
- MeSH
- desmopresin aplikace a dávkování dějiny farmakologie terapeutické užití MeSH
- lidé MeSH
- neurohypofyzární hormony * dějiny farmakologie klasifikace MeSH
- oxytocin antagonisté a inhibitory dějiny farmakologie MeSH
- poporodní krvácení farmakoterapie MeSH
- terlipresin aplikace a dávkování dějiny farmakologie terapeutické užití MeSH
- uterotonika aplikace a dávkování dějiny farmakologie klasifikace MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
- Geografické názvy
- Česká republika MeSH
- Švédsko MeSH
Arrested or protracted labor in nulliparous women caused by insufficient uterine contractility is a common problem in obstetrics, for which few management guidelines exist. The European Association of Perinatal Medicine nominated an expert panel, consisting of specialists in obstetrics and gynecology and midwives representing their respective professional national societies in nine European countries and patient representatives. The panel developed an evidence-based guideline for clinical practice supported by the Knowledge Institute of the Dutch Association of Medical Specialists. Five priority clinical questions (PICOs) were identified on nulliparous women, at term, with a singleton fetus, in cephalic presentation, and the diagnosis of arrested or protracted labor. For each question relevant outcome measures were defined as well as a minimal clinically important difference for each of them. Five literature searches were performed by an information specialist and articles were selected independently by two panel members. The GRADE methodology was used to write evidence summaries, considerations, and recommendations. The draft guideline was sent out for review to scientific societies involved in perinatal care in 20 European countries. Comments were answered, and the guideline was revised accordingly. The following procedures should be offered to women: 1) Amniotomy alone may be considered. 2) Women should be informed that there is no scientific evidence regarding the beneficial effects of immediate (<1 h) or delayed administration of oxytocin, although the first option may reduce the duration of labor. A joint decision is recommended, based on clinical judgment, and women's values and preferences. 3) A low-dose oxytocin regimen for labor augmentation should be considered. 4) Amniotomy should be considered before the administration of oxytocin infusion during the first stage of spontaneous labor. 5) Oxytocin augmentation for at least four hours with adequate uterine contractions should be considered, before an operative delivery is proposed, provided that fetal and maternal conditions are adequate.
- MeSH
- amniotomie MeSH
- dystokie * terapie diagnóza MeSH
- komplikace porodu * terapie diagnóza MeSH
- lidé MeSH
- oxytocin aplikace a dávkování MeSH
- parita MeSH
- porodní děj MeSH
- těhotenství MeSH
- uterotonika aplikace a dávkování MeSH
- vedení porodu MeSH
- Check Tag
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- směrnice pro lékařskou praxi MeSH
- Geografické názvy
- Evropa MeSH
Úzkostné poruchy jsou v současnosti nejčetnější skupinou duševních poruch, postihují světově více než 300 milionů lidí. Rozpočty směřující na léčení a prevenci těchto poruch jsou velmi omezené. Článek se zaměřuje na soucit se sebou, který je dostupným přístupem snižování úzkostných příznaků i potenciálního léčení úzkostných poruch. Uvedený text se opírá zejména o teorii tří systémů regulace emocí, doplněnou o rešerši studií zaměřujících se na vztah mezi soucitem se sebou, úzkostnými příznaky, citovou vazbou a oxytocinem. Pro budoucí rozvoj tohoto oboru je zapotřebí více randomizovaných kontrolovaných longitudinálních studií a komplexnějších výzkumných modelů, zkoumajících zejména roli mediačních/moderačních faktorů, jako je citová vazba či emoční regulace. Autoři v oboru by také měli zvážit adaptování a validaci většího množství intervencí v rámci klinické populace. Významný potenciál budoucího výzkumu lze spatřit ve zkoumání role oxytocinu, který dle některých studií vykazuje příznivé efekty pro snižování úzkostí. V poslední části jsou prezentována doporučení pro podporu praxe pracovníků v oblasti duševního zdraví.
Anxiety disorders are currently the most common group of mental disorders, affecting more than 300 million people worldwide. Budgets for the treatment and prevention of these disorders are very limited. The article focuses on self-compassion, which is an available approach to reducing anxiety symptoms as well as potentially treating anxiety disorders. The above text is mainly based on the theory of three systems of emotion regulation, as well as studies focusing on the relationship between self-compassion, anxiety symptoms, emotional attachment and oxytocin. Based on this, recommendations for future studies are presented. For the future development of this field, more randomized controlled longitudinal studies and more complex research models are needed, especially investigating the role of mediating/moderating factors such as emotional attachment, personality characteristics or emotional regulation. Authors in the field should also consider adapting and validating more interventions within a clinical population. Significant potential for future research can be seen in examining the role of oxytocin, which according to some studies shows beneficial effects for reducing anxiety. In the last part, recommendations for supporting the practice of mental health workers are presented.
- MeSH
- lidé MeSH
- oxytocin fyziologie MeSH
- psychoterapie MeSH
- soucit se sebou * MeSH
- úzkost psychologie MeSH
- úzkostné poruchy * patologie psychologie terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
Fibrilácia predsiení (FP) je najčastejšia arytmia v klinickej praxi prispievajúca k zvýšenej morbidite a mortalite. Humorálne biomarkery, ako natriuretické peptidy, troponín, aldosterón, kortizol, kopeptín a apelín, zohrávajú čoraz dôležitejšiu úlo- hu v diagnostike, predikcii prognózy a manažmente FP. Zvýšené hladiny týchto biomarkerov naznačujú nielen poruchu funkcie myokardu a remodeláciu predsiení, ale aj zápalové a prokoagulačné stavy, ktoré ovplyvňujú vývoj a komplikácie FP. Sledovanie hladín biomarkerov poskytuje hlbší náhľad na patofyziologické mechanizmy FP a môže pomôcť pri identi- fikácii pacientov so zvýšeným rizikom komplikácií, ako sú tromboembolické príhody alebo progresia ochorenia. Integrácia biomarkerov do klinickej praxe môže výrazne zlepšiť stratifikáciu rizika, umožniť personalizovanejší prístup k liečbe FP a prispieť k efektívnejšiemu monitorovaniu priebehu ochorenia. Dôkazy o spojitosti medzi biomarkermi a FP sú povzbud- zujúce, avšak sú potrebné ďalšie štúdie na potvrdenie ich klinického využitia v štandardnej starostlivosti o pacientov s týmto závažným ochorením.
Atrial fibrillation (AF) is the most common arrhythmia in clinical practice, contributing to increased morbidity and mortality. Humoral biomarkers, such as natriuretic peptides, troponin, aldosterone, cortisol, copeptin, and apelin, are gaining importance in the diagnosis, prognosis, and management of AF. Elevated levels of these biomarkers indicate not only myocardial dysfunction and atrial remodeling but also inflammatory and procoagulant states that influence the progression and complications of AF. Monitoring biomarker levels provides deeper insight into the pathophysiological mechanisms of AF and can aid in identifying patients at higher risk of complications, such as thromboembolic events or disease progression. Integrating biomarkers into clinical practice can significantly improve risk stratification, facilitate a more personalized approach to AF treatment, and contribute to more effective disease monitoring. Evidence linking biomarkers with AF is promising; however, further studies are needed to confirm their clinical utility in standard care for patients with this serious condition.
- MeSH
- aldosteron MeSH
- apelin MeSH
- arginin vasopresin MeSH
- biologické markery MeSH
- fibrilace síní * diagnóza MeSH
- hydrokortison MeSH
- lidé MeSH
- natriuretické peptidy MeSH
- troponin krev MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
Chronic diarrhea is a significant challenge in clinical practice because of its high prevalence and various causes. Comprehensive clinical assessment and stepwise laboratory approach are crucial for an accurate diagnosis. This report presents a case of an adult woman who experienced chronic watery diarrhea, complicated by renal impairment and multiple electrolyte imbalances, including hypokalemia, hypophosphatemia, and metabolic acidosis. The diagnosis of a vasoactive intestinal polypeptide-secreting tumor (VIPoma) with liver metastases was confirmed by elevated serum levels of a vasoactive intestinal polypeptide (VIP) and imaging findings of a pancreatic mass with multiple hepatic lesions. Preoperative management, including fluid rehydration, electrolyte correction, and somatostatin analog therapy, significantly improved her clinical symptoms. Subsequent surgical tumor removal and radiofrequency ablation of the hepatic lesions resulted in complete resolution of symptoms and normalized VIP levels. This case emphasizes the importance of early recognition of this rare tumor in patients with chronic diarrhea to improve clinical outcomes.
- MeSH
- chronická nemoc MeSH
- diareogenní nádor * komplikace diagnóza MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory jater sekundární komplikace MeSH
- nádory slinivky břišní * komplikace MeSH
- průjem * etiologie MeSH
- vazoaktivní intestinální peptid krev MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
AIMS: To investigate the therapeutic potential of visual stimulation (VS) and BDNF in murine experimental autoimmune uveoretinitis (EAU). MAIN METHODS: Mice were immunized by subcutaneous injection of interphotoreceptor retinoid-binding protein in Freund's complete adjuvant and intravenous injection of pertussis toxin, and were then exposed to high-contrast VS 12 h/day (days 1-14 post-immunization). EAU severity was assessed by examining clinical score, visual acuity, inflammatory markers, and immune cells in the retina. The transcriptome of activated retinal cells was determined by RNA-seq using RNA immunoprecipitated in complex with phosphorylated ribosomal protein S6. The retinal levels of protein products of relevant upregulated genes were quantified. The effect of BDNF on EAU was tested in unstimulated mice by its daily topical ocular administration (days 8-14 post-immunization). KEY FINDINGS: VS attenuated EAU development and decreased the expression of pro-inflammatory cytokines/chemokines and numbers of immune cells in the retina (n = 10-20 eyes/group for each analysis). In activated retinal cells of control mice (n = 30 eyes/group), VS upregulated genes encoding immunomodulatory neuropeptides, of which BDNF and vasoactive intestinal peptide (VIP) also showed increased mRNA and protein levels in the retina of VS-treated EAU mice (n = 6-10 eyes/group for each analysis). In unstimulated EAU mice, BDNF treatment mimicked the protective effects of VS by modulating the inflammatory and stem cell properties of Müller cells (n = 5 eyes/group for each analysis). SIGNIFICANCE: VS effectively suppresses EAU, at least through enhancing retinal levels of anti-inflammatory and neuroprotective factors, VIP and BDNF. Our findings also suggest BDNF as a promising therapeutic agent for uveitis treatment.
- MeSH
- autoimunitní nemoci * imunologie metabolismus MeSH
- cytokiny metabolismus MeSH
- modely nemocí na zvířatech MeSH
- mozkový neurotrofický faktor * metabolismus MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- retina metabolismus účinky léků MeSH
- retinitida * farmakoterapie prevence a kontrola imunologie MeSH
- uveitida * metabolismus farmakoterapie imunologie MeSH
- vazoaktivní intestinální peptid farmakologie MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Obavy pacientů z vyšetření a ošetření jsou nedílnou součástí praxe většiny nejen zubních lékařů. Se strachem z ošetření zubním lékařem se potýká až 75 % vyspělé populace. Nepřekonatelným strachem (odontofobií) se všemi sociálními, zdravotními a ekonomickými důsledky zanedbané zubní péče pak trpí kolem 10 % lidí. Toto sdělení přibližuje možnosti léčby dentální fobie. Prvním předpokladem pro zdárné ošetření je podání lokální anestezie. Mírnější formy odontofobie můžeme zvládnout pomocí nefarmakologických metod, jako jsou vlídné vystupování, odvedení pozornosti, vhodné přístrojové vybavení apod. Těžší případy navíc řešíme pomocí farmakoterapie; například je možno použít benzodiazepiny, oxid dusný, dle moderních postupů i oxytocin.
Patients ́ fear of examination and treatment is an integral part of the most physicians ́ routine not only a dentist ́s one. Up to 75% of the population are afraid of being treated by a dentist. About 10% of people suffer from an overwhelming fear (odontophobia) with all the social, health and economical consequences of a neglected dental care. This review article offers an overview of the treatment options of dental phobia. The first prerequisite for a successful treatment is the application of local anesthesia. Milder forms of odontophobia can be managed with non-pharmacological methods, such as a gentle attitude, diversion of attention, and appropriate technical equipment. In addition, more difficult cases are controlled with pharmacotherapy; for example, it is possible to use benzodiazepines, nitrous oxide, and according to modern guidelines, even oxytocin.
Agomelatine is a pharmaceutical compound that functions as an agonist for melatonin receptors, with a particular affinity for the MT1 and MT2 receptor subtypes. Its mode of action is integral to the regulation of diverse physiological processes, encompassing the orchestration of circadian rhythms, sleep-wake cycles, and mood modulation. In the present study, we delve into the intricate interplay between agomelatine and the modulation of estrus cycles, gestation periods, offspring numbers, and uterine contractions, shedding light on their collective impact on reproductive physiology. Both in vivo and in vitro experiments were performed. Wistar Albino rats, divided into four groups: two non-pregnant groups (D1 and D2) and two pregnant groups (G1 and G2). The D1 and G1 groups served as control groups, while the D2 and G2 groups received chronic agomelatine administration (10 mg/kg). Uterine contractions were assessed in vitro using myometrial strips. Luzindole, a melatonin receptor antagonist, was employed to investigate the pathway mediating agomelatine's effects on uterine contractions. In in vivo studies, chronic agomelatine administration extended the diestrus phase (p<0.05) in non-pregnant rats, prolonged the gestational period (p<0.01), and increased the fetal count (p<0.01) in pregnant rats. Additionally, agomelatine reduced plasma oxytocin and prostoglandin-E levels (p<0.01) during pregnancy. In vitro experiments showed that agomelatine dose-dependently inhibited spontaneous and oxytocin-induced myometrial contractions. Luzindole (2 μM) reverse the agomelatine-induced inhibition of myometrial contractions. These findings suggest that agomelatine holds the potential to modulate diverse reproductive parameters during the gestational period, influencing estrus cycling, gestational progression, offspring development, and the orchestration of uterine contractions.
- MeSH
- děložní kontrakce * MeSH
- krysa rodu rattus MeSH
- melatonin * farmakologie MeSH
- melatoninové receptory metabolismus MeSH
- oxytocin MeSH
- potkani Wistar MeSH
- těhotenství MeSH
- tryptaminy * MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
