Selected hormonal and other biochemical parameters in cerebrospinal fluid and serum, along with clinical status will be followed in patients with hydrocephalus treated neurosurgically by sucking off and subsequent channelling an excessive fluid into abdominal cavity. Taking advantage of non-invasive sampling after introduction of shunt and of the aformentioned analyses, we will attempt to find out, why in the most patients after initial improvement the dementia is developed, most frequently of Alzheimer´s type. Following our previous experience enabling us to distinguish Alzheimer´s disease from vascular dementia on the base of chosen laboratory parameters, we are going to establish a predictive mathematical model which would contribute to an early disclosure, why such a fatal reversion occurs in these patients.

Přebytečný mozkomíšní mok (CSF) je odváděn neurochirurgicky zavedením drenážního systému. Odstraněním přebytečného CSF se normalizuje intrakraniální tlak a pacient se dostává do subjektivně dobrého stavu. Odvod CSF se provádí buď nárazově při akutním stavu, nebo kontinuálně zavedením tzv. shuntu, který odvádí přebytečnou tekutinu nejčastěji do dutiny břišní. V takto získaném CSF a v séru budeme analyzovat jak klinické ukazatele, tak vybrané biochemické a hormonální parametry. Na základě těchto analýz sepokusíme zjistit důvod rozvoje mentálních poruch u těchto pacientů, které vznikají v relativně krátkém časovém úseku od operace a prvotního výrazného zlepšení stavu. Na základě předešlých zkušeností s rozlišením Alzheimerovy demence od demence vaskulární se pokusíme pomocí vytipovaných laboratorních parametrů vypracovat matematický predikční model, který by přispěl k včasnému odhalení tohoto fatálního zvratu u pacientů trpících hydrocefalem.

• MeSH
• aldosteron analýza   MeSH
• dehydroepiandrosteron analýza   MeSH
• dehydroepiandrosteronsulfát analýza   MeSH
• drenáž MeSH
• homocystein analýza   MeSH
• hydrokortison analýza   MeSH
• management nemoci MeSH
• metabolomika MeSH
• mozkomíšní mok MeSH
• neurodegenerativní nemoci diagnóza   MeSH
• neurotransmiterové látky diagnostické užití   MeSH
• normotenzní hydrocefalus diagnóza   patofyziologie   terapie   MeSH
• prognóza MeSH
• shunty pro odvod mozkomíšního moku MeSH
• spinální punkce MeSH
• tandemová hmotnostní spektrometrie MeSH
• teoretické modely MeSH
• vysokoúčinná kapalinová chromatografie MeSH

• Konspekt
• Fyziologie člověka a srovnávací fyziologie
• NLK Obory
• endokrinologie
• neurologie
• NLK Publikační typ
• závěrečné zprávy o řešení grantu IGA MZ ČR

Numerous chemicals in the environment have the ability to interact with the endocrine system. These compounds are called endocrine disruptors (EDs). Exposure to EDs represents one of the hypotheses for decreasing fertility, the increased risk of numerous cancers and obesity, metabolic syndrome and type 2 diabetes. There are various mechanisms of ED action, one of which is their interference in the action of 11β-hydroxysteroid dehydrogenase (11βHSD) that maintains a balance between active and inactive glucocorticoids on the intracellular level. This enzyme has two isoforms and is expressed in various tissues. Inhibition of 11βHSD in various tissues can have different consequences. In the case of EDs, the results of exposure are mainly adverse; on the other hand pharmaceutically developed inhibitors of 11βHSD type 1 are evaluated as an option for treating metabolic syndrome, as well as related diseases and depressive disorders. This review focuses on the effects of 11βHSD inhibitors in the testis, colon, adipose tissue, kidney, brain and placenta.

• MeSH
• 11-beta-hydroxysteroiddehydrogenasa typ 1 antagonisté a inhibitory   metabolismus   MeSH
• 11-beta-hydroxysteroiddehydrogenasa typ 2 antagonisté a inhibitory   metabolismus   MeSH
• diabetes mellitus chemicky indukované   enzymologie   patologie   MeSH
• endokrinní disruptory farmakologie   MeSH
• glukokortikoidy metabolismus   MeSH
• inhibitory enzymů farmakologie   MeSH
• kolon účinky léků   enzymologie   MeSH
• lidé MeSH
• metabolický syndrom chemicky indukované   enzymologie   patologie   MeSH
• mozek účinky léků   enzymologie   MeSH
• nádory chemicky indukované   enzymologie   patologie   MeSH
• obezita chemicky indukované   enzymologie   patologie   MeSH
• orgánová specificita MeSH
• placenta účinky léků   enzymologie   MeSH
• těhotenství MeSH
• testis účinky léků   enzymologie   MeSH
• tuková tkáň účinky léků   enzymologie   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

Cytokines are widely known mediators of inflammation accompanying many neurodegenerative disorders including normal pressure hydrocephalus (NPH). NPH is caused by impaired cerebrospinal fluid (CSF) reabsorption and treated by surgical shunt insertion. The diagnostics is still complicated and the shunt effect is not durable; after several years, dementia may develop. In the clinical practice, biomarkers support the diagnostics as well as the further time course of many neurodegenerative diseases. Until recently, no reliable biomarker for NPH was evaluated. The attempt of this review was to make a survey concerning cytokines as possible NPH markers. Among all reviewed cytokines, the most promising are CSF IL-10 and IL-33, enabling to follow-up the disease progression and monitoring the effectiveness of the shunt insertion.

• MeSH
• biologické markery krev   MeSH
• cytokiny krev   MeSH
• lidé MeSH
• mediátory zánětu krev   MeSH
• následné studie MeSH
• normotenzní hydrocefalus krev   diagnóza   chirurgie   MeSH
• shunty pro odvod mozkomíšního moku trendy   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

Normal pressure hydrocephalus (NPH) is one of a few treatable conditions of cognitive decline affecting predominately elderly people. Treatment, commonly based on the ventriculoperitoneal shunt insertion, leads to a partial or complete correction of patient's state, although its effect does not unfortunately always last. The aim of our study was to observe the changes of homocysteine and selected steroids and neurosteroids and follow-up the patients with respect to the duration of the NPH-related dementia improvement. The cerebrospinal fluid and plasma levels of cortisol, cortisone, dehydroepiandrosterone (DHEA), 7alpha-hydroxy-DHEA, 7beta-hydroxy-DHEA, 7-oxo-DHEA, 16alpha-hydroxy-DHEA (all LC-MS/MS), DHEA-sulphate (DHEAS) (radioimmunoassay) and homocysteine (gas chromatography) were determined in NPH-diagnosed subjects before, during and 6, 12 and 24 months after shunt insertion. The cognitive functions ameliorated after shunt insertion and remain improved within 2 years. Changes in cerebrospinal fluid DHEAS, DHEA and its ratio, cortisone/cortisol and 16alpha-hydroxy-DHEA and plasma DHEAS, 7beta-hydroxy-DHEA, cortisone/cortisol and homocysteine were found. Mentioned changes may contribute to the clarification of NPH pathogenesis. Altered neurosteroids levels are possible indicators to be utilized in the follow-up of NPH subjects. Moreover, plasma homocysteine may serve as an early indicator of NPH-related dementia.

• MeSH
• biologické markery krev   MeSH
• dehydroepiandrosteron krev   MeSH
• homocystein krev   MeSH
• hydrokortison krev   MeSH
• kortison krev   MeSH
• lidé MeSH
• neurotransmiterové látky krev   MeSH
• normotenzní hydrocefalus krev   chirurgie   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Hormones exert many actions in the brain, and brain cells are also hormonally active. To reach their targets in brain structures, hormones must overcome the blood-brain barrier (BBB). The BBB is a unique device selecting desired/undesired molecules to reach or leave the brain, and it is composed of endothelial cells forming the brain vasculature. These cells differ from other endothelial cells in their almost impermeable tight junctions and in possessing several membrane structures such as receptors, transporters, and metabolically active molecules, ensuring their selection function. The main ways how compounds pass through the BBB are briefly outlined in this review. The main part concerns the transport of major classes of hormones: steroids, including neurosteroids, thyroid hormones, insulin, and other peptide hormones regulating energy homeostasis, growth hormone, and also various cytokines. Peptide transporters mediating the saturable transport of individual classes of hormones are reviewed. The last paragraph provides examples of how hormones affect the permeability and function of the BBB either at the level of tight junctions or by various transporters.

• MeSH
• endoteliální buňky metabolismus   MeSH
• hematoencefalická bariéra cytologie   metabolismus   MeSH
• hormony metabolismus   MeSH
• lidé MeSH
• mozek cytologie   metabolismus   MeSH
• permeabilita MeSH
• Check Tag
• lidé MeSH

Normal pressure hydrocephalus (NPH) is a treatable neurological disorder affecting elderly people with the prevalence increasing with age. NPH is caused by abnormal cerebrospinal fluid (CSF) reabsorption and manifested as a balance impairment, urinary incontinence and dementia development. These symptoms are potentially reversible if recognized early. Diagnosis of NPH is difficult and can be easily mistaken for other neurodegenerative disorders, which makes NPH one of the major misdiagnosed diseases worldwide. The aim of the study was to find out the appropriate combination of indicators, based on CSF steroids, which would contribute to a clearer NPH diagnosis. The levels of CSF cortisol, cortisone, dehydroepiandrosterone (DHEA), 7α-OH-DHEA, 7β-OH-DHEA, 7-oxo-DHEA, 16α-OH-DHEA and aldosterone (all LC-MS/MS) were determined in our patients (n=30; NPH, 65-80 years) and controls (n=10; 65-80 years). The model of orthogonal projections to latent structures (OPLS) was constructed to predict NPH. Cortisone, 7α-OH-DHEA, 7β-OH-DHEA, 7-oxo-DHEA, aldosterone, 7α-OH-DHEA /DHEA, 7-oxo-DHEA/7α-OH-DHEA, 7β-OH-DHEA/7-oxo-DHEA and 16α-OH-DHEA/DHEA in the CSF were identified as the key predictors and the model discriminated patients from controls with 100% sensitivity and 100% specificity. The suggested model would contribute to early and accurate NPH diagnosis, enabling promptly treatment of the disease.

• MeSH
• aldosteron MeSH
• chromatografie kapalinová MeSH
• dehydroepiandrosteron analogy a deriváty   MeSH
• hmotnostní spektrometrie MeSH
• hormony kůry nadledvin MeSH
• hydrokortison MeSH
• kortison MeSH
• lidé MeSH
• normotenzní hydrocefalus diagnóza   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• MeSH
• aktivní transport fyziologie   MeSH
• cytokiny metabolismus   MeSH
• glukosa metabolismus   MeSH
• hematoencefalická bariéra * fyziologie   MeSH
• lidé MeSH
• neuroendokrinní buňky * metabolismus   účinky léků   MeSH
• neuropeptidy metabolismus   MeSH
• steroidy metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• práce podpořená grantem MeSH

Dehydroepiandrosterone (DHEA) and its 7-oxo- and 7-hydroxy-metabolites occurring in the brain are considered neurosteroids. Metabolism of the latter is catalysed by 11β-hydroxysteroid dehydrogenase (11β-HSD) which also interconverts cortisol and cortisone. The concurrent metabolic reaction to DHEA 7-hydroxylation is the formation of 16α-hydroxy-DHEA. The LC-MS/MS method using triple stage quadrupole-mass spectrometer was developed for simultaneous quantification of free DHEA, 7α-hydroxy-DHEA, 7β-hydroxy-DHEA, 7-oxo-DHEA, 16α-hydroxy-DHEA, cortisol and cortisone in human plasma and cerebrospinal fluid (CSF). The method employs 500 μL of human plasma and 3000 μL of CSF extracted with diethyl ether and derivatized with 2-hydrazinopyridine. It has been validated in terms of sensitivity, precision and recovery. In plasma, the following values were obtained: limit of detection: 2-50p g/mL; limit of quantification: 5-140 pg/mL; within-day precision 0.58-14.58%; between-day precision: 1.24-13.89% and recovery: 85-113.2%). For CSF, the values of limit of detection: 2-28 pg/mL; limit of quantification: 6-94 pg/mL; within-day precision; 0.63-5.48%; between-day precision: 0.88-14.59% and recovery: 85.1-109.4% were acquired. Medians and concentration ranges of detected steroids in plasma and CSF are given in subjects with excluded normal pressure hydrocephalus (n=37; 65-80 years). The method enables simultaneous quantification of steroids important for the estimation of 11β-HSD activity in human plasma and CSF. It will be helpful in better understanding various degenerative diseases development and progression.

• MeSH
• 11-beta-hydroxysteroiddehydrogenasy metabolismus   MeSH
• dehydroepiandrosteron analogy a deriváty   MeSH
• imunologické faktory MeSH
• lidé MeSH
• neurotransmiterové látky MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Increased homocysteine levels in serum are typical features of neurodegenerative brain diseases including hydrocephalus. The most frequent therapeutic approach consists of the insertion of a shunt, connecting the brain ventricles to an alternative drainage site. To decide whether the patient should undergo this, the lumbar drainage test is usually carried out to distinguish patients who can benefit from the shunt insertion. In searching for other potential biochemical markers for shunt indication we determined homocysteine levels in CSF during the lumbar drainage test. Homocysteine in CSF was measured during the 5-day lumbar drainage test in 27 patients with normal-pressure hydrocephalus (NPH) and in 25 patients with excluded hydrocephalus. A novelized gas chromatography method with flame ionization detection (GC-FID) was developed and evaluated. During the first two days of lumbar drainage, the levels of CSF homocysteine in NPH patients were significantly higher compared to the controls, while on the fifth day, the homocysteine levels in patients with hydrocephalus reached the level of controls. Determination of CSF homocysteine in patients with confirmed or suspected hydrocephalus may serve as an independent marker for deciding on their further treatment strategy.

• MeSH
• biologické markery MeSH
• chromatografie plynová metody   MeSH
• homocystein MeSH
• hydrocefalus chirurgie   MeSH
• kalibrace MeSH
• lidé MeSH
• limita detekce MeSH
• plamínková ionizace MeSH
• reprodukovatelnost výsledků MeSH
• shunty pro odvod mozkomíšního moku MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

OBJECTIVES: Normal pressure hydrocephalus (NPH) is a treatable neurological syndrome developing in the elderly. It is characterized by balance impairment, urinary incontinence and dementia development caused by disorders in the cerebrospinal fluid (CSF) circulation. The diagnosis can be easily mistaken for other neurodegenerative diseases, which are often accompanied by inflammation and the production of cytokines. The aim of our study was to determine and compare selected CSF and plasma cytokines with respect to their informative value for laboratory diagnostics of NPH. METHODS: The levels of IL-1β, IL-4, IL-6, IL-10, IL-17A, IL-17F, IL-21, IL-22, IL-23, IL-25, IL-31, IL-33, INF-γ, sCD40L and TNF-α were measured in the CSF and plasma in age-matched subjects with NPH (n=20) and controls (n=20) by multiplex assay. RESULTS: CSF IL-1β, IL-6 and IL-10 were significantly increased on the 1st day of lumbar drainage in NPH (p<0.01). No significant changes were observed in the plasma. The CSF cytokines were one to three orders of magnitude higher compared to the plasma. CONCLUSION: CSF can better show the neurodegenerative changes in the brain. The cytokines IL-1β, IL-6 and IL-10 may be helpful in NPH diagnostics.

• MeSH
• biologické markery MeSH
• cytokiny imunologie   MeSH
• demence diagnóza   imunologie   MeSH
• inkontinence moči diagnóza   imunologie   MeSH
• lidé MeSH
• normotenzní hydrocefalus diagnóza   imunologie   MeSH
• posturální rovnováha MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• stárnutí imunologie   MeSH
• Check Tag
• lidé MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH