Ageing is accompanied by deterioration in physical condition and a number of physiological processes and thus a higher risk of a range of diseases and disorders. In particular, we focused on the changes associated with aging, especially the role of small molecules, their role in physiological and pathophysiological processes and potential treatment options. Our previously published results and data from other authors lead to the conclusion that these unwanted changes are mainly linked to the hypothalamic-pituitary-adrenal axis can be slowed down, stopped, or in some cases even reversed by an appropriate treatment, but especially by a life-management adjustment.

• MeSH
• hormony metabolismus   MeSH
• knihovny malých molekul MeSH
• lidé MeSH
• receptory buněčného povrchu metabolismus   MeSH
• stárnutí účinky léků   metabolismus   patologie   MeSH
• systém hypofýza - nadledviny účinky léků   fyziologie   MeSH
• systém hypotalamus-hypofýza účinky léků   fyziologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Testing of the adrenal function with ACTH 1-24 (Synacthen test) or insulin (insulin tolerance test-ITT) is commonly used. The question of ongoing debate is the dose of Synacthen. Moreover, it may be important from the physiological point of view besides measurement of cortisol levels and 17α-hydroxy-progesterone to know also the response of other steroids to these test. The plasma levels of 24 free steroids and their polar conjugates were followed after stimulation of 1 μg, 10 μg and 250 μg of ACTH 1-24 and after insulin administration in thirteen healthy subjects. The study aimed to describe a response of steroid metabolome to various doses of ACTH 1-24 and to find the equivalency of these tests. The additional ambition was to contribute to understanding of physiology of these stimulation tests and suggest an additional marker for HPA axis evaluation. No increase of most conjugated steroids and even decrease of some of them during all of the Synacthen tests and ITT at 60th min were observed. The levels of steroid conjugates decreased in ITT but did not during all of the Synacthen tests by 20 min of each test. Testosterone and estradiol did not increase during the Synacthen tests or ITT as expected. The results suggest that the conjugated steroids in the circulation can serve as reserve stock for rapid conversion into free steroids in the first minutes of the stress situation. Various doses of ACTH 1-24 used in the Synacthen tests implicate earlier or later occurrence of maximal response of stimulated steroids. The equivalent dose to ITT and standard 250 μg of ACTH 1-24 seemed to be dose of 10 μg ACTH 1-24 producing the similar response in all of the steroids in the 60th min of the test.

• MeSH
• dospělí MeSH
• estradiol krev   MeSH
• hydrokortison krev   MeSH
• inzulin aplikace a dávkování   MeSH
• kosyntropin aplikace a dávkování   MeSH
• lidé MeSH
• metabolom MeSH
• nadledviny metabolismus   patologie   MeSH
• steroidy metabolismus   MeSH
• systém hypofýza - nadledviny účinky léků   patologie   MeSH
• systém hypotalamus-hypofýza metabolismus   patologie   MeSH
• testosteron krev   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zdraví dobrovolníci pro lékařské studie MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Criteria for the evaluation of the insulin tolerance test (ITT) and Synacthen test are still a matter of debate. The objective of the study was to make a comparison of serum and salivary cortisol during four stimulation tests. Sixty four healthy volunteers underwent the ITT, the Synacthen test with 1 (LDST), 10 (MDST) and 250 (HDST) microg dose of ACTH. Maximum serum cortisol response was observed at the 90 min of the ITT (49 %), HDST (89 %) and MDST (56 %) and at the 40 min of the LDST (44 %). Results expressed as 95 % confidence intervals: 408.0-843.6 and 289.5-868.1 nmol/l in the IIT at 60 and 90 min. In the HDST and the MDST serum cortisol reached the maximum at 90 min 542.6-1245.5 and 444.2-871.3 nmol/l. Levels of salivary cortisol followed the same pattern as serum cortisol. Salivary cortisol reached the maximum response in the HDST and the MDST at 90 min and at 40 min in the LDST. We confirmed good reliability of all tests with respect to timing of response and maximum response compared to the ITT. We proved that the MDST test can provide the similar response in serum cortisol to the HDST. Measuring either salivary cortisol or ACTH levels did not provide any additional benefit then measuring serum cortisol by itself.

• MeSH
• dospělí MeSH
• hydrokortison analýza   krev   MeSH
• inzulin aplikace a dávkování   normy   MeSH
• inzulinová rezistence fyziologie   MeSH
• kosyntropin aplikace a dávkování   normy   MeSH
• lidé MeSH
• referenční standardy MeSH
• reprodukovatelnost výsledků MeSH
• sliny chemie   metabolismus   MeSH
• systém hypofýza - nadledviny účinky léků   metabolismus   MeSH
• systém hypotalamus-hypofýza účinky léků   metabolismus   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH
• srovnávací studie MeSH

• MeSH
• adrenální insuficience * chemicky indukované   MeSH
• chronická bolest * farmakoterapie   komplikace   MeSH
• hydrokortison krev   MeSH
• index tělesné hmotnosti MeSH
• lidé středního věku MeSH
• lidé MeSH
• opioidní analgetika * škodlivé účinky   terapeutické užití   MeSH
• průřezové studie MeSH
• systém hypofýza - nadledviny účinky léků   MeSH
• systém hypotalamus-hypofýza účinky léků   MeSH
• věkové faktory MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• souhrny MeSH

This introductory chapter provides an overview of the levels and sites at which endocrine disruptors (EDs) affect steroid actions. In contrast to the special issue of Journal of Steroid Biochemistry and Molecular Biology published three years ago and devoted to EDs as such, this paper focuses on steroids. We tried to point to more recent findings and opened questions. EDs interfere with steroid biosynthesis and metabolism either as inhibitors of relevant enzymes, or at the level of their expression. Particular attention was paid to enzymes metabolizing steroid hormones to biologically active products in target cells, such as aromatase, 5α-reductase and 3β-, 11β- and 17β-hydroxysteroid dehydrogenases. An important target for EDs is also steroid acute regulatory protein (StAR), responsible for steroid precursor trafficking to mitochondria. EDs influence receptor-mediated steroid actions at both genomic and non-genomic levels. The remarkable differences in response to various steroid-receptor ligands led to a more detailed investigation of events following steroid/disruptor binding to the receptors and to the mapping of the signaling cascades and nuclear factors involved. A virtual screening of a large array of EDs with steroid receptors, known as in silico methods (≡computer simulation), is another promising approach for studying quantitative structure activity relationships and docking. New data may be expected on the effect of EDs on steroid hormone binding to selective plasma transport proteins, namely transcortin and sex hormone-binding globulin. Little information is available so far on the effects of EDs on the major hypothalamo-pituitary-adrenal/gonadal axes, of which the kisspeptin/GPR54 system is of particular importance. Kisspeptins act as stimulators for hormone-induced gonadotropin secretion and their expression is regulated by sex steroids via a feed-back mechanism. Kisspeptin is now believed to be one of the key factors triggering puberty in mammals, and various EDs affect its expression and function. Finally, advances in analytics of EDs, especially those persisting in the environment, in various body fluids (plasma, urine, seminal fluid, and follicular fluid) are mentioned. Surprisingly, relatively scarce information is available on the simultaneous determination of EDs and steroids in the same biological material. This article is part of a Special Issue entitled 'Endocrine disruptors & steroids'.

• MeSH
• 17-hydroxysteroidní dehydrogenasy genetika   metabolismus   MeSH
• 3-oxo-5-alfa-steroid-4-dehydrogenasa genetika   metabolismus   MeSH
• dějiny 20. století MeSH
• dějiny 21. století MeSH
• endokrinní disruptory dějiny   farmakologie   MeSH
• globulin vázající pohlavní hormony genetika   metabolismus   MeSH
• lidé MeSH
• pohlavní steroidní hormony dějiny   metabolismus   MeSH
• regulace genové exprese MeSH
• rychlé screeningové testy MeSH
• signální transdukce MeSH
• simulace molekulového dockingu MeSH
• steroidní receptory genetika   metabolismus   MeSH
• systém hypofýza - nadledviny účinky léků   metabolismus   MeSH
• systém hypotalamus-hypofýza účinky léků   metabolismus   MeSH
• transkortin genetika   metabolismus   MeSH
• vztahy mezi strukturou a aktivitou MeSH
• Check Tag
• dějiny 20. století MeSH
• dějiny 21. století MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• historické články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

• Klíčová slova
• substituční léčba pumpou,
• MeSH
• adrenální insuficience * farmakoterapie   patofyziologie   MeSH
• adrenokortikotropní hormon fyziologie   krev   sekrece   MeSH
• cirkadiánní rytmus MeSH
• cykly aktivity * fyziologie   MeSH
• glukokortikoidy fyziologie   MeSH
• hormonální substituční terapie * metody   MeSH
• hydrokortison * aplikace a dávkování   farmakokinetika   fyziologie   krev   MeSH
• infuzní pumpy MeSH
• léky s prodlouženým účinkem MeSH
• lidé MeSH
• odběr vzorku krve metody   MeSH
• subkutánní infuze MeSH
• systém hypofýza - nadledviny * fyziologie   patofyziologie   účinky léků   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• práce podpořená grantem MeSH
• přehledy MeSH

Narcolepsy with cataplexy is caused by a deficiency in the production of hypocretin/orexin, which regulates sleep and wakefulness, and also influences appetite, neuroendocrine functions and metabolism. In this case-control study, 11 patients with narcolepsy with cataplexy and 11 healthy adults underwent an oral glucose tolerance test, and dexamethasone suppression/corticotropin-releasing hormone stimulation test. The average age of patients and controls was 35.1 ± 13.2 and 41.0 ± 2.9 years, respectively, body mass index was 28.1 ± 6.6 and 25.5 ± 4.7 kg m(-2) . We did not find evidence of a significantly increased prevalence of disturbed glucose tolerance in patients with narcolepsy. After hypothalamo-pituitary-adrenal axis suppression, the number of non-suppressors did not differ between the groups, indicating normal negative feedback sensitivity. The level of cortisol after dexamethasone suppression was significantly lower in patients with narcolepsy, suggesting a slight basal downregulation and/or a slightly increased negative feedback sensitivity of the major endocrine stress system in narcolepsy. Following corticotropin-releasing hormone stimulation, there were no significant differences in levels of adrenocorticotropic hormone or cortisol, and in adrenocortical responsivity to adrenocorticotropic hormone. Finally, patients with narcolepsy displayed significantly higher plasma levels of tumour necrosis factor alpha, soluble tumour necrosis factor receptor p55, soluble tumour necrosis factor receptor p75 and interleukin 6 after adjustment for body mass index. The present study confirms that narcolepsy by itself is not associated with disturbances of glucose metabolism, but goes along with a subtle dysregulation of inflammatory cytokine production. We also found that dynamic hypothalamo-pituitary-adrenal system response is not altered, whereas negative feedback to dexamethasone might be slightly enhanced.

• MeSH
• adrenokortikotropní hormon krev   MeSH
• dexamethason farmakologie   MeSH
• dospělí MeSH
• glukózový toleranční test MeSH
• hormon uvolňující kortikotropin farmakologie   MeSH
• hydrokortison krev   MeSH
• index tělesné hmotnosti MeSH
• interleukin-6 metabolismus   MeSH
• kataplexie krev   komplikace   metabolismus   MeSH
• krevní glukóza metabolismus   MeSH
• lidé MeSH
• narkolepsie krev   komplikace   metabolismus   MeSH
• studie případů a kontrol MeSH
• systém hypofýza - nadledviny účinky léků   metabolismus   MeSH
• systém hypotalamus-hypofýza účinky léků   metabolismus   MeSH
• TNF-alfa krev   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

V klinickej praxi je častou komorbiditou drogovej závislosti depresia, hlavne v prípade sekundárnej drogovej závislosti u depresívnych pacientov. Vysoká úroveň komorbidity v populácii (30 – 50 %) sa dá vysvetliť zdieľanými neurobiologickými abnormalitami a aberantnou neuroadaptáciou na akútny efekt drogy vedúcej k neurochemickým zmenám, ktoré majú spoločné prvky s abnormalitami vyskytujúcimi sa pri depresii. Článok poskytuje prehľad neurobiologického podkladu drogovej závislosti a depresie so zameraním na amfetamínové psychostimulanciá.

Drug addiction and depression is the most common comorbidity, especially in case of secondary drug addiction of patients with depression. High comorbidity in population (30 – 50 %) may reflect shared neurobiogical abnormalities, aberrant neuroadaptation to acute drug effect leading to neurochemical changes, which have common elements with abnormalities connected to depression. Article presents review of neurobiological background of drug addiction and depression focused on amphetamine-like psychostimulants.

• MeSH
• deprese * patofyziologie   MeSH
• endokanabinoidy MeSH
• GABA MeSH
• glutamáty MeSH
• inhibitory vychytávání neurotransmiterů MeSH
• komorbidita MeSH
• lidé MeSH
• methamfetamin * farmakokinetika   MeSH
• modely u zvířat MeSH
• neurobiologie * MeSH
• noradrenalin MeSH
• nucleus accumbens fyziologie   účinky léků   MeSH
• receptory neurotransmiterů fyziologie   účinky léků   MeSH
• serotonin fyziologie   MeSH
• systém hypofýza - nadledviny fyziologie   účinky léků   MeSH
• systém hypotalamus-hypofýza fyziologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• práce podpořená grantem MeSH
• přehledy MeSH

Deprese (D) je závažné, chronické onemocnění mozku postihující až 10 % populace, přičemž celoživotní prevalence je 17 %. D je porucha, která je spojena s nejnižší mírou sociálního uplatnění a fyzické výkonnosti při srovnání s cukrovkou, hypertenzí či artritidou. D vyžaduje pokračovací a udržovací léčbu, přesto bývá nedostatečně diagnostikována a léčena. S depresí je spojena i vysoká mortalita, dále dochází k narušení kognitivních funkcí, dochází ke změnám endokrinním a snížení imunity. D se vyskytuje u celé řady somatických onemocnění, přičemž její rozpoznání a léčení zlepšuje prognózu jak léčebnou, tak i vitální. Je popsáno místo tianeptinu (Coaxilu) jako účinného antidepresiva s anxiolytickým účinkem, s velmi dobrou snášenlivostí a širokým indikačním spektrem.

Depression (D) is serious, chronic disease of the brain, affecting 10% of the population. At the same time full life prevalence is 17%. D is the disorder, which is combined with the lowest level of social position and physical performance as compared to diabetes, hypertension or arthritis. D requires continuous and supportive treatment, however it is often insufficiently diagnosed and treated. There is a big mortality combined with depression, additionally cognitive functions are affected as well as endocrine changes are present and immunological response is decreased. D occurs with big range of different somatic diseases, and diagnosing it improves patient’s health and life prognosis. Tianeptin (Coaxil) was described as effective antidepressive and anxiolytic agent, with very good tolerance and wide spectrum of indications.

• Klíčová slova
• Coaxil,
• MeSH
• antidepresiva terapeutické užití   MeSH
• deprese diagnóza   epidemiologie   farmakoterapie   MeSH
• komorbidita MeSH
• lidé MeSH
• systém hypofýza - nadledviny účinky léků   MeSH
• systém hypotalamus-hypofýza účinky léků   MeSH
• Check Tag
• lidé MeSH

Objective: Proinflammatory cytokines IL-1ß, and IL-6 are synthesized in the brain, where they exert local regulatory functions. Our aim was to find out whether, along with the activation of hypothalamo-pituitary-adrenocortical (HPA) axis and prolactin (PRL), the acute systemic enhancement of IL-1ß affects its own production in the hypothalamus as well as that of IL-6. Method: Forty five minutes after a single i.p. administration of recombinant rat IL-1ß (5 μg/kg) to male Long Evans rats we estimated the expression of IL-1ß and IL-6 mRNA in the hypothalamus by real time PCR, ACTH, corticosterone (CORT), and PRL by RIA Results: IL-1ß administration stimulated the expression of IL-1ß mRNA in the hypothalamus by 99 %, but not that of IL-6. It also significantly activated plasma levels of ACTH, PRL, CORT, and CORT production in adrenal gland. Conclusion: These results indicate that acute peripheral enhancement of IL-1ß may induce neuroendocrine changes also via the immediate activation of its own expression in the hypothalamus, but not that of IL-6 expression in the hypothalamus was found.

• MeSH
• adrenokortikotropní hormon krev   MeSH
• hypothalamus * metabolismus   účinky léků   MeSH
• interleukin-1beta farmakologie   metabolismus   MeSH
• interleukin-6 metabolismus   MeSH
• messenger RNA metabolismus   MeSH
• potkani Long-Evans MeSH
• prolaktin * krev   metabolismus   MeSH
• systém hypofýza - nadledviny metabolismus   účinky léků   MeSH
• systém hypotalamus-hypofýza účinky léků   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• práce podpořená grantem MeSH