BACKGROUND: Identifying modifiable risk factors for cognitive decline can reduce burden of dementia. OBJECTIVE: We examined whether homocysteine was associated with memory performance, mediated by entorhinal volume, hippocampal volume, total gray matter volume, or white matter lesions, and moderated by APOE ɛ4 allele, B vitamins, creatinine, total cholesterol, or triglycerides. METHODS: All 204 members of the Czech Brain Aging Study with subjective cognitive decline (SCD; n = 60) or amnestic mild cognitive impairment (aMCI; n = 144) who had valid data were included. Linear regression was used, followed by conditional process modeling to examine mediation and moderation. RESULTS: Controlling for age, sex, and education, higher homocysteine was related to poorer memory performance overall (b = -0.03, SE = 0.01, p = 0.017) and in participants with SCD (b = -0.06, SE = 0.03, p = 0.029), but less so in aMCI (b = -0.03, SE = 0.02, p = 0.074); though sensitivity analyses revealed a significant association when sample was reduced to aMCI patients with more complete cognitive data (who were also better functioning; b = -0.04, SE = 0.02, p = 0.022). Results were unchanged in fully adjusted models. Neither mediation by markers of brain integrity nor moderation by APOE ɛ4, B vitamins, creatinine, and cardiovascular factors were significant. Memory sub-analyses revealed that results for SCD were likely driven by non-verbal memory. The homocysteine-memory relationship was significant when hippocampal volume was below the median (b = -0.04, SE = 0.02, p = 0.046), but not at/above the median (p = 0.247). CONCLUSION: Higher homocysteine levels may adversely influence memory performance, which appears particularly apparent in those without cognitive impairment. Results appear to be independent of brain health, suggesting that homocysteine may represent a good target for intervention.
- MeSH
- bílá hmota diagnostické zobrazování MeSH
- hipokampus diagnostické zobrazování MeSH
- homocystein krev MeSH
- lidé středního věku MeSH
- lidé MeSH
- magnetická rezonanční tomografie MeSH
- neuropsychologické testy MeSH
- paměť fyziologie MeSH
- šedá hmota diagnostické zobrazování MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- velikost orgánu fyziologie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Homocysteínový konsenzus odráža súčasné poznanie, že homocysteín (HCY) je pravdepodobnejšie rizikový marker ako faktor a paušálna liečba hyperhomocysteínémie neprináša očakávané zníženie morbidity a mortality kardiovaskulárnych ochorení. Panel odborníkov zastáva nasledujúce stanovisko do praxe pre liečbu a prevenciu kardiovaskulárnych ochorení: A. Paušálna terapeutická intervencia podľa súčasných poznatkov EBM nie je paušálne indikovaná.B. Paušálny skríning homocysteínu neprináša klinický prínos pre všeobecnú populáciu ani pre pacientov s kardiovaskulárnymi ochoreniami. Preventívne podávanie multivitamínov skupiny B pre zníženie hladiny homocysteínu podľa doterajších vedomostí založených na EBM vo všeobecnej populácii nemá podporu. Populačný skríning nie je indikovaný – trieda odporučení III, úroveň dôkazov IA. Terapeutické podávanie multivitamínov skupiny B pre zníženie hladiny homocysteínu podľa doterajších vedomostí založených na EBM v populácii pacientov v sekundárnej i terciárnej prevencii nemá význam. Populačný skríning nie je indikovaný – trieda odporučení III, úroveň dôkazov A. Nebol dostatočne preskúmaný prínos stanovenia HCY pri rozhodovaní o začatí antihypertenzívnej alebo hypolipidemickej liečby. Populačný skríning nie je indikovaný, iba vyšetrenie u individuálneho pacienta – trieda odporučení IIb, úroveň dôkazov A.
Homocysteine consensus reflects current knowledge that homocysteine is rather a risk marker then a factor and treatment of hyperhomocysteinemia does not reduce cardiovascular morbidity and mortality. Panel of experts state this position to approach cardiovascular prevention and treatment in praxis.A. General therapeutic intervention is not generally indicated based on current EBM data. B. General screening of homocysteine is not clinically beneficial in both general population and in patients with cardiovascular disease. Preventive administration of B group vitamins to reduce plasma homocysteine level in general population is not supported based on current EBM data. Population screening is not indicated – class III, level A. Therapeutic administration of B group vitamins to reduce plasma homocysteine level in patients in secondary or tertiary prevention is not supported based on current EBM data. Population screening is not indicated – class III, level A. There are no sufficient data on effect of measuring homocysteine on decision to start treating hypertension or dyslipidemias. Population screening is not indicated, only individual patients ́ examination – class IIb, level A.
- MeSH
- homocystein * analýza krev MeSH
- kardiovaskulární nemoci * prevence a kontrola MeSH
- lidé MeSH
- plošný screening MeSH
- vitamin B komplex terapeutické užití MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- směrnice pro lékařskou praxi MeSH
Homocysteinemia is a metabolic condition characterized by abnormally high level of homocysteine in the blood and is considered to be a risk factor for peripheral neuropathy. However, the cellular mechanisms underlying toxic effects of homocysteine on the processing of peripheral nociception have not yet been investigated comprehensively. Here, using a rodent model of experimental homocysteinemia, we report the causal association between homocysteine and the development of mechanical allodynia. Homocysteinemia-induced mechanical allodynia was reversed on pharmacological inhibition of T-type calcium channels. In addition, our in vitro studies indicate that homocysteine enhances recombinant T-type calcium currents by promoting the recycling of Cav3.2 channels back to the plasma membrane through a protein kinase C-dependent signaling pathway that requires the direct phosphorylation of Cav3.2 at specific loci. Altogether, these results reveal an unrecognized signaling pathway that modulates the expression of T-type calcium channels, and may potentially contribute to the development of peripheral neuropathy associated with homocysteinemia.
- MeSH
- buněčná membrána metabolismus MeSH
- homocystein krev MeSH
- hyperalgezie etiologie metabolismus MeSH
- hyperhomocysteinemie komplikace MeSH
- krysa rodu rattus MeSH
- modely nemocí na zvířatech MeSH
- nemoci periferního nervového systému etiologie metabolismus MeSH
- nocicepce fyziologie MeSH
- potkani Wistar MeSH
- spinální ganglia metabolismus MeSH
- vápník metabolismus MeSH
- vápníkové kanály - typ T metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Goeckerman therapy (GT) of psoriasis vulgaris is based on the application of crude coal tar and ultraviolet radiation. We investigated DNA damage by the number of micronucleated binucleated cells (MNBC) in lymphocytes, serum homocysteine, vitamin B12, folic acid, and two polymorphisms (C677T and A1298C) in the MTHFR gene in 35 patients with exacerbated psoriasis vulgaris classified according to the psoriasis area and severity index (PASI) score and treated by GT. The median of PASI score decreased from nineteen to five, and MNBC increased from 10 to 18‰ after GT (p < 0.001 in both cases). Correlations of MNBC with homocysteine (Spearman's rho = 0.420, p = 0.012) and vitamin B12 (rho = -0.389, p = 0.021) before the therapy were observed. Hyperhomocysteinemia was an independent predictor of genotoxicity (OR 9.91; 95% CI, 2.09-55.67; p = 0.003). Homocysteine was higher in females than in males (13 vs. 12 µmol/L, p = 0.045). In contrast, vitamin B12 levels in the females were lower than in the males (160 vs. 192 pmol/L, p = 0.047). Vitamin B12 in the females were negatively influenced by smoking status (160 pmol/L in smokers vs. 192 pmol/L in non-smokers, p = 0.025). A significantly higher MNBC was found in CC homozygous patients (A1298C polymorphism) than in AC heterozygotes (32 vs. 16‰, p = 0.005) and AA homozygotes (32 vs. 18‰, p = 0.036). Our data showed that homocysteine participates in the pathogenesis of psoriasis. Its serum levels correlated with MNBC and allowed the prediction of DNA damage to appear within GT. Both micronutrients status and homocysteine metabolic pathway contribute to the genotoxicity of GT.
- MeSH
- dehet uhelný terapeutické užití MeSH
- dospělí MeSH
- homocystein krev MeSH
- jednonukleotidový polymorfismus * MeSH
- keratolytika terapeutické užití MeSH
- kyselina listová krev MeSH
- lidé středního věku MeSH
- lidé MeSH
- methylentetrahydrofolátreduktasa (NADPH2) genetika MeSH
- mikrojaderné testy MeSH
- mikroživiny krev MeSH
- poškození DNA účinky léků účinky záření MeSH
- psoriáza krev genetika patologie terapie MeSH
- terapie ultrafialovými paprsky metody MeSH
- vitamin B 12 krev MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Objectives: Previous research has shown that nutrition can influence cognitive abilities in older adults. We examined whether nutritional factors or inflammatory biomarkers moderate the age-cognition association. Method: Analyses included 1,308 participants (age ≥60) from the National Health and Nutrition Examination Survey III. Macronutrients (% of calories from fat, protein, and carbohydrates), micronutrients/amino acids (blood serum values: Vitamins B12, C, D, E, folate, iron, homocysteine, and β-carotene), and inflammatory biomarkers (serum C-reactive protein, plasma fibrinogen, and serum ferritin) were examined as moderators with cognition. Cognition was measured by six tasks: immediate and delayed story recall, immediate and delayed word memory, digit subtraction, and questions about place/orientation. Results: Higher values of serum folate were significantly associated with better cognitive scores. Specifically, the interaction between age-cognition and folate indicated the associations of higher age and lower global cognition and lower immediate story recall were weaker in those with higher folate values (p's < .05). A significant interaction between age and plasma fibrinogen indicated that the association between age and worse digit subtraction was stronger with values >3.1 g/L. Discussion: Folate and fibrinogen were significant moderators between age and cognition. Further research into the relationship between nutrition, inflammation, and cognitive aging is needed.
- MeSH
- beta-karoten krev MeSH
- biologické markery krev MeSH
- C-reaktivní protein analýza MeSH
- dieta statistika a číselné údaje MeSH
- ferritin krev MeSH
- fibrinogen analýza MeSH
- homocystein krev MeSH
- kognice * MeSH
- kognitivní dysfunkce krev etiologie MeSH
- kyselina listová krev MeSH
- lidé středního věku MeSH
- lidé MeSH
- neuropsychologické testy MeSH
- nutriční stav * MeSH
- senioři MeSH
- věkové faktory MeSH
- vitaminy krev MeSH
- výživa - přehledy MeSH
- zánět krev komplikace MeSH
- železo krev MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Za účelem objektivizace změn hladin metabolomu neurosteroidů u dospělých klientů po komplexní lázeňské léčebně rehabilitační péči navázaly v roce 2017 vzájemnou spolupráci Endokrinologický ústav v Praze a Priessnitzovy léčebné lázně a.s. v Jeseníku. Autoři prezentují soubor 70 probandů, kteří absolvovali při nástupu a dimisi baterii klinických a laboratorních vyšetření. První výsledky změn metabolomu neurosteroidů, kineziologického vyšetření diagnostickou části Computer Kinesiology a výsledky Knoblochova dotazníku sebeposuzovací škály N-5 ukazují jednoznačně efekt léčení v lázních.
The Endocrinological Institute in Prague established the cooperation with in Priessnitz's spa a.s. in Jesenik intention to objectify changes in neurosteroid metabolomic biomarkers levels in adult clients after spa treatment, in 2017. The authors present a set of 70 probands. The first results of changes in the levels of neurosteroids, serotonin and homocysteine metabolite clearly demonstrate the effect of treatment in the spa. The kinesiological examination of the diagnostic part of Computer Kinesiology and the numeric outputs of Knobloch questionnaire (N-5 self- -judging scale) correlate with endocrinological results.
- Klíčová slova
- Knoblochův dotazník N-5,
- MeSH
- balneologie * MeSH
- dospělí MeSH
- hodnocení výsledků péče pacientem MeSH
- hodnocení výsledků zdravotní péče MeSH
- homocystein analýza krev MeSH
- kineziologie aplikovaná metody MeSH
- klinická studie jako téma MeSH
- klinické laboratorní techniky metody MeSH
- lidé středního věku MeSH
- lidé MeSH
- neurotransmiterové látky * analýza krev metabolismus MeSH
- průzkumy a dotazníky MeSH
- senioři MeSH
- serotonin analýza krev MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- práce podpořená grantem MeSH
BACKGROUND: Alzheimer's disease (AD) is a progressive neurodegenerative disorder with a complex pathogenesis and a common occurrence of comorbid diseases such as depression. It is accepted that the presence of the ε4 allele of the gene that encodes apolipoprotein E (APOE) is the strongest genetic risk factor for the development of sporadic AD. Melatonin, cortisol, homocysteine, and prolactin are presumed to be risk factors or biomarkers for stress- and age-related disorders. OBJECTIVE: The interplay between the APOE genotype and plasma biomarkers was examined in patients with AD presenting with or without depression to contribute to understanding the interdependence of various molecular mechanisms in the pathophysiology of AD. METHOD: The APOE genotype and morning plasma melatonin, cortisol, homocysteine, and prolactin concentrations were measured in 85 patients with AD and 44 elderly controls. RESULTS: A significant association between AD and the allele (ε4) or genotype (ε3/ε4 or ε4/ε4) frequencies of APOE was confirmed. Plasma homocysteine and cortisol levels were significantly increased in patients with AD compared to those in controls, independent of the presence of comorbid depressive symptoms or the severity of dementia. Significantly lower plasma melatonin concentration was found in patients with AD but not in controls, who were noncarriers of the APOE ε4 allele, regardless of the presence of depression or the severity of dementia in AD. CONCLUSION: Our findings indicate the existence of a little-known specific APOE-mediated mechanism that increases the plasma melatonin level in a subgroup of patients with AD who are carriers of the APOE ε4 allele.
- MeSH
- Alzheimerova nemoc krev genetika MeSH
- apolipoproteiny E genetika MeSH
- biologické markery krev MeSH
- genotyp MeSH
- homocystein krev MeSH
- hydrokortison krev MeSH
- lidé středního věku MeSH
- lidé MeSH
- melatonin krev MeSH
- prolaktin krev MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Aldosterone plays a key role in maintaining the homeostasis of the whole organism. Under some circumstances, aldosterone can contribute to the progression of cardiovascular diseases, including coronary artery disease. This study demonstrates that aldosterone associates negatively with some lipidogram parameters and positively with the concentration of homocysteine. These associations are characteristic for coronary artery disease and are not present in control subjects. The findings also indicate that in vitro aldosterone stimulates homocysteine production by rat adrenal glands, which may explain the associations observed with coronary artery disease. Moreover, we have found that aldosterone significantly modulates in vitro platelet reactivity to arachidonate and collagen - aldosterone increases the pro-aggregatory action of collagen, but decreases the pro-aggregatory potential of arachidonate. Therefore, the findings of these in vitro and ex vivo experiments indicate the existence of new pathways by which aldosterone modulates lipid- homocysteine- and platelet-dependent atherogenesis.
- MeSH
- agregace trombocytů účinky léků MeSH
- aldosteron krev farmakologie MeSH
- cholesterol krev MeSH
- homocystein biosyntéza krev MeSH
- kolagen metabolismus MeSH
- kreatinin krev MeSH
- krysa rodu rattus MeSH
- kyselina arachidonová metabolismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- nadledviny účinky léků metabolismus MeSH
- nemoci koronárních tepen krev MeSH
- potkani Sprague-Dawley MeSH
- senioři MeSH
- sulfhydrylové sloučeniny krev MeSH
- techniky in vitro MeSH
- trombóza krev MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
The aims of this study were to determine concentrations of total homocysteine, cysteine, cysteinylglycine and glutathione in spermatozoa, seminal fluid and blood plasma and to analyse their relationships with sperm parameters. For this reason, a new highly effective method of spermatozoa lysis was developed, using methanol, freezing and subsequent thawing in ultrasonic bath. An HPLC-FD assay was conducted on thiols concentrations in lysed spermatozoa, seminal fluid and blood plasma. Concentrations of thiols in spermatozoa were significantly lower in men with normozoospermia than in samples with pathological semen parameters. Statistical analysis found significant correlations between thiol concentrations in spermatozoa and semen parameters, while the same analysis with thiol concentrations in seminal fluid was substantially less powerful. Only cysteinylglycine concentrations in seminal fluid significantly correlated with pathological semen parameters. No significant differences or correlations were found with blood plasma concentrations.
- MeSH
- dospělí MeSH
- frakcionace buněk metody MeSH
- homocystein analýza krev MeSH
- intracelulární prostor chemie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mužská infertilita krev metabolismus MeSH
- sperma chemie MeSH
- spermie chemie ultrastruktura MeSH
- sulfhydrylové sloučeniny analýza krev MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: High plasma homocysteine (Hcy) level is related to higher risk of Alzheimer's disease (AD) and lower cognitive performance in older adults. OBJECTIVE: To assess the association between plasma Hcy level and real-space navigation performance and the role of vascular risk and protective factors, APOE status, and white matter lesions (WML) on this association. METHODS: Ninety-two non-demented older adults (29 with amnestic mild cognitive impairment, 46 with subjective cognitive decline, and 17 cognitively normal older adults) underwent spatial navigation testing of egocentric, allocentric, and mixed navigation in a real-space analogue of the Morris water maze, neuropsychological examination, blood collection, and MRI brain scan with evaluation of WML. RESULTS: In the regression analyses controlling for age, gender, education, and depressive symptoms, higher plasma Hcy level was related to worse mixed and egocentric (β= 0.31; p = 0.003 and β= 0.23; p = 0.017) but not allocentric (p > 0.05) navigation performance. Additional controlling for vascular risk and protective factors, WML, and APOE status did not modify the results. High total cholesterol and low vitamin B12 and folate levels increased the adverse effect of Hcy on egocentric and mixed navigation. WML did not explain the association between plasma Hcy level and navigation performance. CONCLUSION: Elevated plasma Hcy level may affect real-space navigation performance above and beyond vascular brain changes. This association may be magnified in the presence of high total cholesterol and low folate or vitamin B12 levels. Attention to the level of plasma Hcy may be a viable intervention strategy to prevent decline in spatial navigation in non-demented older adults.
- MeSH
- bludiště - učení fyziologie MeSH
- diskriminace (psychologie) MeSH
- homocystein krev MeSH
- kognitivní dysfunkce krev patofyziologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- neuropsychologické testy MeSH
- prostorová navigace fyziologie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- sluchová percepce fyziologie MeSH
- stárnutí krev fyziologie MeSH
- studie případů a kontrol MeSH
- záznam o duševním stavu MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH