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.

• Klíčová slova
• Hippocampus, magnetic resonance imaging, mild cognitive impairment, neuropsychological tests,
• 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
• Názvy látek
• homocystein 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
• Názvy látek
• homocystein MeSH
• vápník MeSH
• vápníkové kanály - typ T 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.

• Klíčová slova
• Goeckerman therapy, folic acid, genotoxicity, homocysteine, psoriasis, vitamin B12,
• 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
• Názvy látek
• dehet uhelný MeSH
• homocystein MeSH
• keratolytika MeSH
• kyselina listová MeSH
• methylentetrahydrofolátreduktasa (NADPH2) MeSH
• mikroživiny MeSH
• MTHFR protein, human MeSH Prohlížeč
• vitamin B 12 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
• Názvy látek
• beta-karoten MeSH
• biologické markery MeSH
• C-reaktivní protein MeSH
• ferritin MeSH
• fibrinogen MeSH
• homocystein MeSH
• kyselina listová MeSH
• vitaminy MeSH
• železo 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.

• Klíčová slova
• Alzheimer's disease, apolipoprotein E, cortisol, homocysteine, melatonin, prolactin.,
• 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
• Názvy látek
• apolipoproteiny E MeSH
• biologické markery MeSH
• homocystein MeSH
• hydrokortison MeSH
• melatonin MeSH
• prolaktin 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
• Názvy látek
• aldosteron MeSH
• cholesterol MeSH
• homocystein MeSH
• kolagen MeSH
• kreatinin MeSH
• kyselina arachidonová MeSH
• sulfhydrylové sloučeniny 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.

• Klíčová slova
• APOE, Alzheimer’s disease, homocysteine, mild cognitive impairment, spatial navigation, subjective cognitive decline, vascular factors,
• 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
• Názvy látek
• homocystein 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.

• Klíčová slova
• glutathione, homocysteine, seminal plasma, spermatozoa, thiols,
• 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
• Názvy látek
• homocystein MeSH
• sulfhydrylové sloučeniny MeSH

UNLABELLED: Moderate regular consumption of alcoholic beverages is believed to protect against atherosclerosis but can also increase homocysteine or dimethylglycine, which are putative risk factors for atherosclerosis. We aimed (1) to investigate the effect of alcohol consumption on vitamins and several metabolites involved in one-carbon metabolism; and (2) to find the most effective way of decreasing homocysteine during moderate alcohol consumption. METHODS: Male volunteers (n = 117) were randomly divided into five groups: the wine-only group (control, 375 mL of white wine daily for one month) and four groups combining wine consumption with one of the supplemented substances (folic acid, betaine, and vitamins B12 or B₆). Significant lowering of homocysteine concentration after the drinking period was found in subjects with concurrent folate and betaine supplementation. Vitamin B12 and vitamin B₆ supplementation did not lead to a statistically significant change in homocysteine. According to a multiple linear regression model, the homocysteine change in the wine-only group was mainly determined by the interaction between the higher baseline homocysteine concentration and the change in dimethylglycine levels. Folate and betaine can attenuate possible adverse effects of moderate alcohol consumption. Dimethylglycine should be interpreted together with data on alcohol consumption and homocysteine concentration.

• Klíčová slova
• B-vitamins, betaine, dimethylglycine, homocysteine, moderate alcohol consumption,
• MeSH
• ateroskleróza etiologie   prevence a kontrola   MeSH
• dospělí MeSH
• homocystein krev   MeSH
• kyselina listová farmakologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lineární modely MeSH
• pití alkoholu škodlivé účinky   krev   MeSH
• potravní doplňky * MeSH
• sarkosin analogy a deriváty   krev   MeSH
• senioři MeSH
• víno škodlivé účinky   MeSH
• vitamin B 12 farmakologie   MeSH
• vitamin B komplex farmakologie   MeSH
• vitamin B6 farmakologie   MeSH
• zdraví dobrovolníci pro lékařské studie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• dimethylglycine MeSH Prohlížeč
• homocystein MeSH
• kyselina listová MeSH
• sarkosin MeSH
• vitamin B 12 MeSH
• vitamin B komplex MeSH
• vitamin B6 MeSH

Hyperhomocysteinemia is a common occurrence in many neurodegenerative diseases, including tauopathies. We developed and validated a simple and sensitive liquid chromatography-tandem mass spectrometry method for the analysis of homocysteine (Hcy) in rat plasma. Hcy was analyzed using ultra-performance liquid chromatography on a C8 column with detection by positive ESI tandem mass spectrometry. For optimal retention and separation, we used ion-pair reagent-heptafluorobutyric acid. The method utilizes heavy labeled internal standard and does not require any derivatization or extraction step. The procedure was validated in compliance with the European Medicines Agency guideline. The limit of detection was 0.15 µmol/L and the limit of quantification was 0.5 µmol/L. The method showed excellent linearity with regression coefficients higher than 0.99. The accuracy was in the range of 93-98%. The inter-day precision (n = 5 days), expressed as % relative standard deviation, was in the range 3-8%. Using this method, we analyzed plasma samples from two transgenic lines of the rat model for tauopathies.

• MeSH
• chromatografie kapalinová metody   MeSH
• homocystein krev   MeSH
• krysa rodu Rattus MeSH
• limita detekce MeSH
• lineární modely MeSH
• potkani inbrední SHR MeSH
• potkani transgenní MeSH
• potkani Wistar MeSH
• reprodukovatelnost výsledků MeSH
• stabilita léku MeSH
• studie případů a kontrol MeSH
• tandemová hmotnostní spektrometrie metody   MeSH
• tauopatie krev   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• homocystein MeSH