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
The present study examined the effect of medicinal plants - ginkgo, tribulus (puncture vine), and yucca - on ovarian functions and their response to the toxic influence of toluene. Therefore, we analyzed the effect of toluene with and without these plant extracts on cultured human ovarian granulosa cells. Cell viability and the release of progesterone, insulin-like growth factor I (IGF I), oxytocin, and prostaglandin F (PGF) were analyzed using the trypan blue test, enzyme immunoassay, and enzyme-linked immunosorbent assay, respectively. The ginkgo, tribulus and yucca were able to suppress ovarian cell viability and alter the release of hormones. Toluene suppressed cell viability and the release of PGF, but not of progesterone, IGF-I, or oxytocin. The negative effect of toluene on cell viability was prevented and even reversed by ginkgo and yucca, whereas its effect on PGF was prevented or inverted by all tested plant extracts. These findings (1) demonstrated the direct toxic effect of toluene on ovarian cells, (2) showed the direct effect of some medicinal plants on ovarian cell functions, and (3) demonstrated the ability of these plants to inhibit the effects of toluene and to act as natural protectors against the suppressive effect of toluene on female reproduction.
- MeSH
- léčivé rostliny * MeSH
- lidé MeSH
- oxytocin MeSH
- progesteron MeSH
- rostlinné extrakty farmakologie MeSH
- viabilita buněk MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
From the fifties to the seventies of the last century, the neurohypophyseal peptides oxytocin and vasopressin constituted one of the main research areas at the Institute of Organic Chemistry and Biochemistry in Prague (IOCB). A significant contribution to this area is associated with the names of František Šorm, director of the said institute, and Josef Rudinger, head of the institute’s peptide laboratory. At that time, newly developed research tools enabled to synthesize structural analogues of these hormones in numerous laboratories worldwide and hence to investigate the structure-activity relationships within this peptide group. Contributions of single peptide-chain positions to the respective biological activities were identified which opened a possibility to rationalize a design of peptides with a combination of changes in several positions. Several clinically interesting peptides were synthesized in the late 1960s at the IOCB and employed as therapeutics: [ (Gly) 3-Cys1,Lys8]-vasopressin (Glypressin Ferring®, Terlipressin INN), 1-deamino-8-D-arginine vasopressin (Desmopressin INN, dDAVP), and later the uterotonics carbetocin (INN), widely used in obstetrics to prevent postpartum haemorrhage. Since the industrial production of peptide therapeutics was scarcely possible under the conditions of socialist economy in Czechoslovakia as well as in other countries under the Soviet influence, F. Šorm agreed to use the already established scientific contacts of IOCB with the Swedish pharmaceutical company Ferring AB and to transfer the production licences to Sweden. The license agreements were signed in 1969 and led to a quick spread of dDAVP in the substitution therapy of the central form of diabetes insipidus and, moreover, contributed to a fast upsurge of the Ferring company. Somewhat later, Glypressin was produced as a therapeutic with a prolonged action in cases of cardiovascular collapse. Contacts between Prague peptide chemists and the Ferring company lasted on a rather informal base until the end of the 1980s. After the fall of the totalitarian regime in Czechoslovakia in 1990, Ferring started a joint-venture collaboration with the newly organized Czech company Léčiva st.p. Praha in a newly established group Prague Poly-peptide Institute spol. s. r. o. (later Ferring-Léčiva a. s.). A substantial part of the peptide-production capacities was then transferred to new buildings in Prague.
- MeSH
- dějiny 20. století MeSH
- dějiny lékárnictví MeSH
- lidé MeSH
- neurohypofyzární hormony dějiny MeSH
- oxytocin dějiny MeSH
- vasopresiny dějiny MeSH
- vyvíjení léků * dějiny MeSH
- Check Tag
- dějiny 20. století MeSH
- lidé MeSH
- Publikační typ
- historické články MeSH
- Geografické názvy
- Československo MeSH
- Švédsko MeSH
Migraine is a severe neurovascular disorder of which the pathophysiology is not yet fully understood. Besides the role of inflammatory mediators that interact with the trigeminovascular system, cyclic fluctuations in sex steroid hormones are involved in the sex dimorphism of migraine attacks. In addition, the pituitary-derived hormone prolactin and the hypothalamic neuropeptide oxytocin have been reported to play a modulating role in migraine and contribute to its sex-dependent differences. The current narrative review explores the relationship between these two hormones and the pathophysiology of migraine. We describe the physiological role of prolactin and oxytocin, its relationship to migraine and pain, and potential therapies targeting these hormones or their receptors.In summary, oxytocin and prolactin are involved in nociception in opposite ways. Both operate at peripheral and central levels, however, prolactin has a pronociceptive effect, while oxytocin appears to have an antinociceptive effect. Therefore, migraine treatment targeting prolactin should aim to block its effects using prolactin receptor antagonists or monoclonal antibodies specifically acting at migraine-pain related structures. This action should be local in order to avoid a decrease in prolactin levels throughout the body and associated adverse effects. In contrast, treatment targeting oxytocin should enhance its signalling and antinociceptive effects, for example using intranasal administration of oxytocin, or possibly other oxytocin receptor agonists. Interestingly, the prolactin receptor and oxytocin receptor are co-localized with estrogen receptors as well as calcitonin gene-related peptide and its receptor, providing a positive perspective on the possibilities for an adequate pharmacological treatment of these nociceptive pathways. Nevertheless, many questions remain to be answered. More particularly, there is insufficient data on the role of sex hormones in men and the correct dosing according to sex differences, hormonal changes and comorbidities. The above remains a major challenge for future development.
- MeSH
- analgetika terapeutické užití MeSH
- bolest farmakoterapie MeSH
- lidé MeSH
- migréna * MeSH
- oxytocin * fyziologie MeSH
- pohlavní steroidní hormony MeSH
- prolaktin * fyziologie MeSH
- receptory oxytocinu MeSH
- receptory prolaktinu MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
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
Finding a cure for Alzheimer's disease (AD) has been notoriously challenging for many decades. Therefore, the current focus is mainly on prevention, timely intervention, and slowing the progression in the earliest stages. A better understanding of underlying mechanisms at the beginning of the disease could aid in early diagnosis and intervention, including alleviating symptoms or slowing down the disease progression. Changes in social cognition and progressive parvalbumin (PV) interneuron dysfunction are among the earliest observable effects of AD. Various AD rodent models mimic these early alterations, but only a narrow field of study has considered their mutual relationship. In this review, we discuss current knowledge about PV interneuron dysfunction in AD and emphasize their importance in social cognition and memory. Next, we propose oxytocin (OT) as a potent modulator of PV interneurons and as a promising treatment for managing some of the early symptoms. We further discuss the supporting evidence on its beneficial effects on AD-related pathology. Clinical trials have employed the use of OT in various neuropsychiatric diseases with promising results, but little is known about its prospective impacts on AD. On the other hand, the modulatory effects of OT in specific structures and local circuits need to be clarified in future studies. This review highlights the connection between PV interneurons and social cognition impairment in the early stages of AD and considers OT as a promising therapeutic agent for addressing these early deficits.
- MeSH
- Alzheimerova nemoc * patologie MeSH
- hipokampus patologie MeSH
- interneurony MeSH
- kognice MeSH
- lidé MeSH
- modely nemocí na zvířatech MeSH
- myši transgenní MeSH
- oxytocin MeSH
- parvalbuminy metabolismus MeSH
- prospektivní studie MeSH
- sociální kognice MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
OF RECOMMENDATIONS1. Oxytocin for induction or augmentation of labor should not be started when there is a previous scar on the body of the uterus (such as previous classical cesarean section, uterine perforation or myomectomy when uterine cavity is reached) or in any other condition where labor or vaginal delivery are contraindicated. (Moderate quality evidence +++-; Strong recommendation).2. Oxytocin should not be started before at least 1 h has elapsed since amniotomy, 6 h since the use of dinoprostone (30 min if vaginal insert) and 4 h since the use of misoprostol (Low quality evidence ++- -; Moderate recommendation).3. Cardiotocography (CTG) should be performed and a normal pattern without tachysystole should be documented for at least 30 min before oxytocin is used. Continuous CTG, with adequate monitoring of both fetal heart rate and uterine contractions, should be maintained for as long as oxytocin is used, and thereafter until delivery (Low ++- - to moderate +++- quality evidence; Strong recommendation).4. For labor induction, at least 1-h should be allowed after amniotomy before oxytocin infusion is started, to evaluate whether adequate uterine contractility has meanwhile ensued. For augmentation of labor, if the membranes are intact and there are conditions for a safe amniotomy, the latter should be considered before oxytocin is started (Very low quality evidence +- --; Weak recommendation).5. Oxytocin should be administered intravenously using the following regimen: 5 IU oxytocin diluted in 500 mL of 0.9% normal saline (NaCl) (each mL contains 10 mIU of oxytocin), in an infusion pump at increasing rates, as shown in Table 1, until a frequency of 3-4 contractions per 10 min is reached, a non-reassuring CTG pattern ensues, or maximum rates are reached (Low quality evidence ++ - -; Strong recommendation). If the frequency of contractions exceeds 5 in 10 min, the infusion rate should be reduced, even if a normal CTG pattern is present. With a non-reassuring CTG pattern, urgent clinical assessment by an obstetrician is indicated, and strong consideration should be given to reducing or stopping the oxytocin infusion. The minimal effective dose of oxytocin should always be used. (Low ++- - to Moderate +++- - quality evidence; Strong recommendation).[Table: see text]6. Use of oxytocin for induction and augmentation of labor should be regularly audited (Low quality evidence ++--; Strong recommendation).
- MeSH
- císařský řez MeSH
- indukovaný porod * MeSH
- lidé MeSH
- misoprostol MeSH
- novorozenec MeSH
- oxytocin terapeutické užití MeSH
- perinatální péče MeSH
- těhotenství MeSH
- uterotonika * terapeutické užití MeSH
- Check Tag
- lidé MeSH
- novorozenec MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
The neuropeptide oxytocin (OXT) is suggested to exert an important role in human social behaviors by modulating the salience of social cues. To date, however, there is mixed evidence whether a single dose of OXT can improve the behavioral and neural sensitivity for emotional face processing. To overcome difficulties encountered with classic event-related potential studies assessing stimulus-saliency, we applied frequency-tagging EEG to implicitly assess the effect of a single dose of OXT (24 IU) on the neural sensitivity for positive and negative facial emotions. Neutral faces with different identities were presented at 6 Hz, periodically interleaved with an expressive face (angry, fearful, and happy, in separate sequences) every fifth image (i.e., 1.2 Hz oddball frequency). These distinctive frequency tags for neutral and expressive stimuli allowed direct and objective quantification of the neural expression-categorization responses. The study involved a double-blind, placebo-controlled, cross-over trial with 31 healthy adult men. Contrary to our expectations, we did not find an effect of OXT on facial emotion processing, neither at the neural, nor at the behavioral level. A single dose of OXT did not evoke social enhancement in general, nor did it affect social approach-avoidance tendencies. Possibly ceiling performances in facial emotion processing might have hampered further improvement.
- MeSH
- dospělí MeSH
- dvojitá slepá metoda MeSH
- elektroencefalografie MeSH
- emoce MeSH
- klinické křížové studie MeSH
- lidé MeSH
- oxytocin * farmakologie MeSH
- výraz obličeje * MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
