• Klíčová slova
• Kobalamin (vtamin B12),
• MeSH
• anemie * etiologie   metabolismus   MeSH
• biochemické jevy genetika   imunologie   účinky léků   MeSH
• Chlorella MeSH
• farmakologické jevy genetika   imunologie   účinky léků   MeSH
• hematopoéza fyziologie   imunologie   účinky léků   MeSH
• houby MeSH
• lidé MeSH
• masné výrobky MeSH
• mléčné výrobky MeSH
• nervový systém * patologie   účinky léků   MeSH
• Porphyra MeSH
• rybí výrobky MeSH
• sójové potraviny využití   MeSH
• vejce MeSH
• vitamin B 12 * farmakologie   metabolismus   terapeutické užití   MeSH
• vnitřnosti MeSH
• Check Tag
• lidé MeSH

PURPOSE: The aim of this study was to analyze homocysteine, folate and cobalamin in men with normozoospermia, obstructive and non-obstructive azoospermia. METHODS: Analysis of plasma and seminal plasma homocysteine, folate and cobalamin in 72 azoospermic and 62 normozoospermic men. Evaluation of the azoospermic patient included testicular biopsy, endocrine, urological and ultrasound examination. RESULTS: Homocysteine (1.2 μmol/l) and cobalamin (322.05 pmol/l) concentrations (median values) in seminal plasma were significantly lower (p < 0.001) in men with azoospermia than in men with normozoospermia (2.5 μmol/l and 579.0 pmol/l). Folate and cobalamin concentrations were significantly higher in obstructive than in non-obstructive azoospermia. Significant correlations were determined between testis volume and seminal plasma homocysteine in azoospermic men. CONCLUSION: Lower concentrations of homocysteine and cobalamin (but not folate) were found in azoospermic seminal plasma than normozoospermic. Folate and cobalamin were higher in seminal plasma from obstructive azoospermia than in non-obstructive azoospermia patients.

• MeSH
• azoospermie krev   MeSH
• dospělí MeSH
• homocystein krev   MeSH
• kyselina listová krev   MeSH
• lidé MeSH
• luminiscence MeSH
• neparametrická statistika MeSH
• sperma metabolismus   MeSH
• vitamin B 12 krev   MeSH
• vysokoúčinná kapalinová chromatografie MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

AIM: To explore the clinical presentation, course, treatment and impact of early treatment in patients with remethylation disorders from the European Network and Registry for Homocystinurias and Methylation Defects (E-HOD) international web-based registry. RESULTS: This review comprises 238 patients (cobalamin C defect n = 161; methylenetetrahydrofolate reductase deficiency n = 50; cobalamin G defect n = 11; cobalamin E defect n = 10; cobalamin D defect n = 5; and cobalamin J defect n = 1) from 47 centres for whom the E-HOD registry includes, as a minimum, data on medical history and enrolment visit. The duration of observation was 127 patient years. In 181 clinically diagnosed patients, the median age at presentation was 30 days (range 1 day to 42 years) and the median age at diagnosis was 3.7 months (range 3 days to 56 years). Seventy-five percent of pre-clinically diagnosed patients with cobalamin C disease became symptomatic within the first 15 days of life. Total homocysteine (tHcy), amino acids and urinary methylmalonic acid (MMA) were the most frequently assessed disease markers; confirmatory diagnostics were mainly molecular genetic studies. Remethylation disorders are multisystem diseases dominated by neurological and eye disease and failure to thrive. In this cohort, mortality, thromboembolic, psychiatric and renal disease were rarer than reported elsewhere. Early treatment correlates with lower overall morbidity but is less effective in preventing eye disease and cognitive impairment. The wide variation in treatment hampers the evaluation of particular therapeutic modalities. CONCLUSION: Treatment improves the clinical course of remethylation disorders and reduces morbidity, especially if started early, but neurocognitive and eye symptoms are less responsive. Current treatment is highly variable. This study has the inevitable limitations of a retrospective, registry-based design.

• MeSH
• dítě MeSH
• dospělí MeSH
• fenotyp MeSH
• homocystinurie metabolismus   MeSH
• kojenec MeSH
• kyselina methylmalonová moč   MeSH
• lidé MeSH
• methylentetrahydrofolátreduktasa (NADPH2) nedostatek   metabolismus   MeSH
• metylace MeSH
• mladiství MeSH
• mladý dospělý MeSH
• novorozenec MeSH
• předškolní dítě MeSH
• progrese nemoci MeSH
• průřezové studie MeSH
• psychotické poruchy metabolismus   MeSH
• registrace MeSH
• retrospektivní studie MeSH
• svalová spasticita metabolismus   MeSH
• těhotenství MeSH
• věk při počátku nemoci MeSH
• vitamin B 12 metabolismus   MeSH
• vrozené poruchy metabolismu aminokyselin diagnóza   terapie   MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• novorozenec MeSH
• předškolní dítě MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Evropa MeSH

Far from being devoid of life, Antarctic waters are home to Cryonotothenioidea, which represent one of the fascinating cases of evolutionary adaptation to extreme environmental conditions in vertebrates. Thanks to a series of unique morphological and physiological peculiarities, which include the paradigmatic case of loss of hemoglobin in the family Channichthyidae, these fish survive and thrive at sub-zero temperatures. While some of the distinctive features of such adaptations have been known for decades, our knowledge of their genetic and molecular bases is still limited. We generated a reference de novo assembly of the icefish Chionodraco hamatus transcriptome and used this resource for a large-scale comparative analysis among five red-blooded Cryonotothenioidea, the sub-Antarctic notothenioid Eleginops maclovinus and seven temperate teleost species. Our investigation targeted the gills, a tissue of primary importance for gaseous exchange, osmoregulation, ammonia excretion, and its role in fish immunity. One hundred and twenty genes were identified as significantly up-regulated in Antarctic species and surprisingly shared by red- and white-blooded notothenioids, unveiling several previously unreported molecular players that might have contributed to the evolutionary success of Cryonotothenioidea in Antarctica. In particular, we detected cobalamin deficiency signatures and discussed the possible biological implications of this condition concerning hematological alterations and the heavy parasitic loads typically observed in all Cryonotothenioidea.

• MeSH
• aklimatizace * MeSH
• nedostatek vitaminu B12 * genetika   metabolismus   MeSH
• ryby * genetika   metabolismus   MeSH
• transkriptom * MeSH
• vitamin B 12 metabolismus   MeSH
• žábry metabolismus   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH
• Geografické názvy
• Antarktida MeSH

The purpose of the present study was to investigate neutrophil and monocyte cell population data as novel markers of low cobalamin/folate concentrations and influence of renal function on their usefulness. The study included 284 patients older than 60 years or with dyspepsia symptoms with mean corpuscular volume 80–100 fL and C-reactive protein ≤ 50 mg/l. Subjects were divided according to renal function and further classified based on cobalamin and folate levels. Neutrophil and monocyte volume (NeV, MoV), conductivity (NeC, MoC), light scatter (NeS, MoS) and standard deviations (NeV-SD, MoV-SD, NeC-SD, MoC-SD, NeS-SD, MoS-SD), obtained by Coulter LH750® Hematology Analyzer (Beckman Coulter, USA), were evaluated along with white blood cell count, hemoglobin, hematocrit, red cell distribution width and homocysteine relative to renal function and cobalamin/folate status. Neutrophil conductivity standard deviation (NeC-SD) had the largest magnitude of the difference between patients with low and normal vitamin levels, was the strongest predictor of low cobalamin/folate concentrations and had the largest area under the curve in detection of vitamin deficiency. Patients with different renal function status and the same cobalamin/folate status did not differ in NeC-SD. In this selected group of patients, NeC-SD was marker of low cobalamin and folate levels regardless of the renal function.

• MeSH
• biologické markery krev   MeSH
• dyspepsie MeSH
• krevní obraz MeSH
• kyselina listová krev   MeSH
• lidé středního věku MeSH
• lidé MeSH
• monocyty cytologie   MeSH
• nedostatek kyseliny listové * krev   MeSH
• neutrofily cytologie   MeSH
• počet buněk MeSH
• renální insuficience * krev   MeSH
• senioři MeSH
• vitamin B 12 * krev   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• práce podpořená grantem MeSH

• MeSH
• hyperhomocysteinemie diagnóza   dietoterapie   krev   MeSH
• lidé MeSH
• vitamin B 12 diagnostické užití   krev   terapeutické užití   MeSH
• ženská infertilita diagnóza   dietoterapie   krev   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH

Methylmalonic acid and total homocysteine belong to useful clinical indicators of cobalamin and folate status and are commonly measured separately. A sensitive and rapid method has been developed for simultaneous determination of both biomarkers and related metabolites in serum or plasma by isotope dilution gas chromatography-mass spectrometry (GC/MS). Thiols bound in disulfide bonds were released with 2,3-dimercapto-1-propanesulfonic acid (DMPS), and after deproteinization, they were phase-transfer derivatized with heptafluorobutyl chloroformate (HFBCF) in a single step. The reducing capability of the DMPS agent was comparable to that of the dithiothreitol, but exceeded the latter in much cleaner extracts obtained. The new method enabled GC/MS screening of amino acidic metabolites, including cystathionine and thiol-containing dipeptides, as their N(S,O)-heptafluorobutoxycarbonyl heptafluorobutyl ester derivatives in serum or plasma. Accurate quantitation of seven biomarkers was accomplished by using deuterated internal standards; the detection limits ranged from 7 to 20 nmol/L, the between-day precision from 1.5 to 8.8%, and the recoveries were between 83 and 103%. The results suggest that the new combined procedure of DMPS reduction and HFBCF derivatization make the method efficient for diagnostics of folate and cobalamin status as well as for screening of amino acidic metabolites in body fluids.

• MeSH
• biologické markery MeSH
• financování organizované MeSH
• formiáty MeSH
• homocystein analýza   MeSH
• kyselina listová krev   MeSH
• kyselina methylmalonová analýza   MeSH
• kyseliny alkansulfonové MeSH
• lidé MeSH
• oxidace-redukce MeSH
• plynová chromatografie s hmotnostně spektrometrickou detekcí metody   normy   MeSH
• sulfhydrylové sloučeniny chemie   MeSH
• vitamin B 12 krev   MeSH
• Check Tag
• lidé MeSH

Vegetarian (VG) and vegan (VN) diets in childhood are of growing interest due to their perceived health and environmental benefits. Concerns remain due to the possible disruption of healthy growth and development of children because of the scarcity of evidence-based studies. Among the nutrients of special concern is vitamin B12. Therefore, the Czech Vegan Children Study (CAROTS) decided to examine the relationship between B12 metabolism parameters and B12 intake through diet and supplementation. We analyzed laboratory parameters within n = 79 VG, n = 69 VN, and n = 52 omnivores (OM) children (0-18 years old). There were no significant differences in levels of holotranscobalamin (aB12), folate, homocysteine (hcys), or mean corpuscular volume. However, there was a significant difference in levels of cyanocobalamin (B12) (p = 0.018), even though we identified only n = 1 VG and n = 2 VN children as B12 deficient. On the other hand, we identified n = 35 VG, n = 28 VN, and n = 9 OM children with vitamin B12 hypervitaminosis (p = 0.004). This finding was related to a high prevalence of over-supplementation in the group (mean dose for VG 178.19 ± 238.5 μg per day; VN 278.35 ± 394.63 μg per day). Additionally, we found a significant (p < 0.05) difference between B12, aB12, and hcys levels of supplemented vs. non-supplemented VG/VN children. This can show that the intake of vitamin B12 via diet in the VG group might not be sufficient. Secondly, we analyzed a relation between supplement use in pregnancy and breastfeeding and its impact on vitamin B12 levels of children aged 0-3 years. Out of n = 46 mothers, only n = 3 (e.g., 6.5%) were not supplemented at all. We have not identified any clinical manifestation of B12 deficiency and only n = 1 child with low serum cobalamin, a child who did not receive vitamin B12 supplementation and whose mother took only low doses of vitamin B12 (25/μg/day).To conclude, we did not observe any life-threatening or severe consequences of laboratory-stated vitamin B12 deficiency; thus, our group was well supplemented. On the other hand, we have identified many subjects with vitamin B12 hypervitaminosis of unknown impact on their health. Further research and new guidelines for B12 supplementation among VG and VN children are needed.

• MeSH
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• nedostatek vitaminu B12 * epidemiologie   MeSH
• novorozenec MeSH
• potravní doplňky MeSH
• předškolní dítě MeSH
• prevalence MeSH
• průřezové studie MeSH
• těhotenství MeSH
• vegani MeSH
• vegetariáni MeSH
• vitamin B 12 * MeSH
• zvyky MeSH
• Check Tag
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• novorozenec MeSH
• předškolní dítě MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH

The chicken Tva cell surface protein, a member of the low-density lipoprotein receptor family, has been identified as an entry receptor for avian leukosis virus of classic subgroup A and newly emerging subgroup K. Because both viruses represent an important concern for the poultry industry, we introduced a frame-shifting deletion into the chicken tva locus with the aim of knocking-out Tva expression and creating a virus-resistant chicken line. The tva knock-out was prepared by CRISPR/Cas9 gene editing in chicken primordial germ cells and orthotopic transplantation of edited cells into the testes of sterilized recipient roosters. The resulting tva -/- chickens tested fully resistant to avian leukosis virus subgroups A and K, both in in vitro and in vivo assays, in contrast to their susceptible tva +/+ and tva +/- siblings. We also found a specific disorder of the cobalamin/vitamin B12 metabolism in the tva knock-out chickens, which is in accordance with the recently recognized physiological function of Tva as a receptor for cobalamin in complex with transcobalamin transporter. Last but not least, we bring a new example of the de novo resistance created by CRISPR/Cas9 editing of pathogen dependence genes in farm animals and, furthermore, a new example of gene editing in chicken.

• MeSH
• editace genu MeSH
• genový knockout MeSH
• kur domácí virologie   MeSH
• kuřecí embryo MeSH
• kyselina methylmalonová krev   MeSH
• posunová mutace MeSH
• ptačí proteiny genetika   fyziologie   MeSH
• virové receptory genetika   fyziologie   MeSH
• virus ptačí leukózy klasifikace   fyziologie   MeSH
• vitamin B 12 metabolismus   MeSH
• zvířata MeSH
• Check Tag
• kuřecí embryo MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

BACKGROUND: Remethylation defects are rare inherited disorders in which impaired remethylation of homocysteine to methionine leads to accumulation of homocysteine and perturbation of numerous methylation reactions. OBJECTIVE: To summarise clinical and biochemical characteristics of these severe disorders and to provide guidelines on diagnosis and management. DATA SOURCES: Review, evaluation and discussion of the medical literature (Medline, Cochrane databases) by a panel of experts on these rare diseases following the GRADE approach. KEY RECOMMENDATIONS: We strongly recommend measuring plasma total homocysteine in any patient presenting with the combination of neurological and/or visual and/or haematological symptoms, subacute spinal cord degeneration, atypical haemolytic uraemic syndrome or unexplained vascular thrombosis. We strongly recommend to initiate treatment with parenteral hydroxocobalamin without delay in any suspected remethylation disorder; it significantly improves survival and incidence of severe complications. We strongly recommend betaine treatment in individuals with MTHFR deficiency; it improves the outcome and prevents disease when given early.

• MeSH
• homocystein genetika   MeSH
• lidé MeSH
• methionin genetika   MeSH
• methylentetrahydrofolátreduktasa (NADPH2) nedostatek   MeSH
• metylace účinky léků   MeSH
• protoonkogenní proteiny c-cbl nedostatek   MeSH
• vitamin B 12 farmakologie   terapeutické užití   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH