AIM: The aim of this study was to investigate the association of serum total Hcy (tHcy) levels with various demographic, clinical and genetic characteristics in healthy Greek adults. METHODS: Anthropometric characteristics (height, weight), systolic and diastolic blood pressure, complete blood count and biochemical assessments, were recorded and measured among 383 Greek adults (199 men). Serum folate, Cobalamin (Cbl) and tHcy levels were determined using immunoassays methods. The MTHFR C677T and A1298C gene polymorphisms were genotyped using polymerase chain reaction and reverse hybridization. RESULTS: MTHFR C677T gene polymorphism, serum folate and Cbl levels were correlated with serum tHcy levels independently. The individuals with 677TT genotype had significantly higher serum tHcy levels than individuals with 677 CC or CT genotypes. Regarding the MTHFR C677T gene polymorphism, the existence of the T allele was associated with statistically significantly lower serum folate and higher serum tHcy levels than C allele. Regarding the MTHFR A1298C gene polymorphism, the existence of the C allele was associated with statistically significant lower serum tHcy levels than A allele. Furthermore, there was no significant correlation between the serum tHcy levels and demographic (except age) or clinical characteristics (sex, BMI, smoking status, SBP, DBP, HGB, HCT, TC, TG, HDL-C, LDL-C, TC/HDL-C). CONCLUSIONS: Serum tHcy levels are influenced by the existence of MTHFR C677T gene polymorphism (mainly 677TT genotype), serum folate and Cbl levels. Individuals with hyperhomocysteinemia should be further investigated for the existence of MTHFR C677T gene polymorphism, with the aim to determine the suitable treatment.
- MeSH
- demografie MeSH
- dospělí MeSH
- genotyp MeSH
- homocystein genetika MeSH
- kyselina listová * MeSH
- lidé MeSH
- methylentetrahydrofolátreduktasa (NADPH2) genetika MeSH
- polymorfismus genetický * MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Řecko MeSH
Elevated total plasma homocysteine (hyperhomocysteinemia) is a marker of cardiovascular, thrombotic, and neuropsychological disease. It has multiple causes, including the common nutritional vitamin B12 or folate deficiency. However, some rare but treatable, inborn errors of metabolism (IEM) characterized by hyperhomocysteinemia can be missed due to variable presentations and the lack of awareness. The aim of this study is to identify undiagnosed IEM in adults with significantly elevated homocysteine using key existing clinical data points, then IEM specific treatment can be offered to improve outcome. We conducted a retrospective study with data mining and chart review of patients with plasma total homocysteine >30 μmol/L over a two-year period. We offer biochemical and genetic testing to patients with significant hyperhomocysteinemia without a clear explanation to diagnose IEM. We identified 22 subjects with significant hyperhomocysteinemia but no clear explanation. Subsequently, we offered genetic testing to seven patients and diagnosed one patient with classic homocystinuria due to cystathionine beta-synthase deficiency. With treatment, she lowered her plasma homocysteine and improved her health. This study stresses the importance of a thorough investigation of hyperhomocysteinemia in adults to identify rare but treatable IEM. We propose a metabolic evaluation algorithm for elevated homocysteine levels.
- MeSH
- dospělí MeSH
- homocystein MeSH
- homocystinurie * diagnóza genetika MeSH
- hyperhomocysteinemie * diagnóza genetika MeSH
- kyselina listová MeSH
- lidé MeSH
- retrospektivní studie MeSH
- vitamin B 12 terapeutické užití MeSH
- vrozené poruchy metabolismu * diagnóza genetika MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
The study was designed to evaluate the medical relevance of total homocysteine (tHcy), total antioxidant capacity (TAC), and malondialdehyde (MDA) before and after chemotherapy for women with breast cancer (BRCA). Blood samples were taken from Oncology Unit in Merjian Teaching hospital in Hilla city (Iraq). Sixty patients suffering from breast cancer (BRCA) were enrolled in this study, and twenty-one apparently healthy subjects were considered as a control group control. We found that significantly increased lipid peroxidation, measured as MDA, was demonstrated in the serum of BRCA patients who were not taken any medication was higher than in the control group (P<0.01) were (25±15) nmol/ml of MDA levels in BRCA patient and (14.5±7.9) nmol/ml of MDA levels in healthy controls. We found that treatment by chemotherapy resulted in a significant increase in MDA levels when compared with MDA levels in patients who were not taken any medication. The tHcy level in BRCA patients before and after treatment were changed. In addition, it is found that the mean serum TAC levels in BRCA patients were significantly less than in the control group. Moreover, a positive correlation was observed between the activity of chemotherapy and MDA levels in the patient and the same correlation between tHcy levels and TAC levels while a negative correlation was observed between TAC levels with MDA levels in the patient group.
BACKGROUND: Plasma sulfur amino acids (SAAs), i.e., methionine, total cysteine (tCys), total homocysteine (tHcy), cystathionine, total glutathione (tGSH), and taurine, are potential risk factors for obesity and cardiometabolic disorders. However, except for plasma tHcy, little is known about how dietary intake modifies plasma SAA concentrations. OBJECTIVE: To investigate whether the intake of SAAs and proteins or diet quality is associated with plasma SAAs. METHODS: Data from a cross-sectional subset of The Maastricht Study (n = 1145, 50.5% men, 61 interquartile range: [55, 66] y, 22.5% with prediabetes and 34.3% with type 2 diabetes) were investigated. Dietary intake was assessed using a validated food frequency questionnaire. The intake of SAAs (total, methionine, and cysteine) and proteins (total, animal, and plant) was estimated from the Dutch and Danish food composition tables. Diet quality was assessed using the Dutch Healthy Diet Index, the Mediterranean Diet Score, and the Dietary Approaches to Stop Hypertension score. Fasting plasma SAAs were measured by liquid chromatography (LC) tandem mass spectrometry (MS) (LC/MS-MS). Associations were investigated with multiple linear regressions with tertiles of dietary intake measures (main exposures) and z-standardized plasma SAAs (outcomes). RESULTS: Intake of total SAAs and total proteins was positively associated with plasma tCys and cystathionine. Associations were stronger in women and in those with normal body weight. Higher intake of cysteine and plant proteins was associated with lower plasma tHcy and higher cystathionine. Higher methionine intake was associated with lower plasma tGSH, whereas cysteine intake was positively associated with tGSH. Higher intake of methionine and animal proteins was associated with higher plasma taurine. Better diet quality was consistently related to lower plasma tHcy concentrations, but it was not associated with the other SAAs. CONCLUSION: Targeted dietary modifications might be effective in modifying plasma concentrations of tCys, tHcy, and cystathionine, which have been associated with obesity and cardiometabolic disorders.
- MeSH
- aminokyseliny sírové * MeSH
- cystathionin MeSH
- cystein MeSH
- diabetes mellitus 2. typu * MeSH
- dieta MeSH
- homocystein MeSH
- kardiovaskulární nemoci * MeSH
- lidé MeSH
- methionin MeSH
- obezita MeSH
- průřezové studie MeSH
- taurin MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Erdostein patří mezi běžně používaná mukolytika. Mechanismus účinku této látky spočívá v ovlivnění viskozity hlenu, jeho tvorby a také mukociliárního transportu. Zvláštností erdosteinu je ale také antioxidační, protizánětlivé či antibakteriální působení. Článek zmíněné charakteristiky diskutuje v kontextu aktuálních informací s cílem zaměřit se i na dětskou populaci.
Erdosteine belongs to the commonly used mucolytic. The mechanism of action of this substance lies in regulating the mucus viscosity, its formation and also mucociliary transport. However, the peculiarity of erdosteine consists in its antioxidant, anti-inflammatory and antibacterial effect. The article discusses these characteristics in the context of current information with a focus also on the paediatric population.
- Klíčová slova
- ERDOSTEIN,
- MeSH
- dítě MeSH
- expektorancia * terapeutické užití MeSH
- homocystein analogy a deriváty farmakologie terapeutické užití MeSH
- infekce dýchací soustavy farmakoterapie MeSH
- klinické zkoušky jako téma MeSH
- lidé MeSH
- thiofeny * farmakologie terapeutické užití MeSH
- thioglykoláty * farmakologie terapeutické užití MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
Regulation of H2S homeostasis in humans is poorly understood. Therefore, we assessed the importance of individual enzymes in synthesis and catabolism of H2S by studying patients with respective genetic defects. We analyzed sulfur compounds (including bioavailable sulfide) in 37 untreated or insufficiently treated patients with seven ultrarare enzyme deficiencies and compared them to 63 controls. Surprisingly, we observed that patients with severe deficiency in cystathionine β-synthase (CBS) or cystathionine γ-lyase (CSE) - the enzymes primarily responsible for H2S synthesis - exhibited increased and normal levels of bioavailable sulfide, respectively. However, an approximately 21-fold increase of urinary homolanthionine in CBS deficiency strongly suggests that lacking CBS activity is compensated for by an increase in CSE-dependent H2S synthesis from accumulating homocysteine, which suggests a control of H2S homeostasis in vivo. In deficiency of sulfide:quinone oxidoreductase - the first enzyme in mitochondrial H2S oxidation - we found normal H2S concentrations in a symptomatic patient and his asymptomatic sibling, and elevated levels in an asymptomatic sibling, challenging the requirement for this enzyme in catabolizing H2S under physiological conditions. Patients with ethylmalonic encephalopathy and sulfite oxidase/molybdenum cofactor deficiencies exhibited massive accumulation of thiosulfate and sulfite with formation of large amounts of S-sulfocysteine and S-sulfohomocysteine, increased renal losses of sulfur compounds and concomitant strong reduction in plasma total cysteine. Our results demonstrate the value of a comprehensive assessment of sulfur compounds in severe disorders of homocysteine/cysteine metabolism and provide evidence for redundancy and compensatory mechanisms in the maintenance of H2S homeostasis.
- MeSH
- cystein MeSH
- homeostáza MeSH
- homocystein MeSH
- lidé MeSH
- síra MeSH
- sulfan * metabolismus MeSH
- sulfidy metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
To investigate the influence of beer consumption on levels of homocysteine (HCY), vitamin B6, B12, folic acid (FA), dimethylglycine (DMG), betaine (BET) and other selected markers. One hundred and sixteen male volunteers were enrolled in the study. A one-month period of alcohol abstinence was followed by a one month when participants drank 830 mL of alcoholic beer every day. After that phase, one month of alcohol abstinence followed. At the beginning and after every phase blood samples were taken and analysed. Ninety-three participants completed the study. After the phase of alcohol consumption, uric acid (UA) (p<0.0001), antioxidative capacity (AOC) (p=0.02), superoxide dismutase (SOD) (0.025), glutathione reductase (GRH) (0.0001), total cholesterol (p<0.0001), HDL-cholesterol (p<0.0001), Apolipoprotein-AI (ApoAI) (p<0.0001), LDL-cholesterol (p<0.039) and Apolipoprotein B (ApoB) (p<0.009) increased, while vitamin B12 (p=0.0001) and fibrinogen (p<0.0001) decreased. Other tested parameters (DMG, BET, vitamin B6 and FA) did not show any significant changes. UA changes and changes in AOC were statistically significantly correlated (r=0.52, p<0.0001). HCY, DMG and BET levels did not show any statistically significant changes after beer consumption, whereas some markers of redox metabolism increased (UA, AOC, SOD and GRH). A statistically significant correlation denotes the dependence of UA and AOC changes in connection with beer consumption.
- MeSH
- antioxidancia MeSH
- apolipoproteiny MeSH
- betain MeSH
- homocystein MeSH
- kyselina listová MeSH
- kyselina močová MeSH
- LDL-cholesterol MeSH
- lidé MeSH
- metylace MeSH
- oxidace-redukce MeSH
- pivo * MeSH
- superoxiddismutasa MeSH
- vitamin B6 * MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
MTHFR deficiency is a severe inborn error of metabolism leading to impairment of the remethylation of homocysteine to methionine. Neonatal and early-onset patients mostly exhibit a life-threatening acute neurologic deterioration. Furthermore, data on early-onset patients' long-term outcomes are scarce. The aims of this study were (1) to study and describe the clinical and laboratory parameters of early-onset MTHFR-deficient patients (i.e., ≤3 months of age) and (2) to identify predictive factors for severe neurodevelopmental outcomes in a cohort with early and late onset MTHFR-deficient patients. To this end, we conducted a retrospective, multicentric, international cohort study on 72 patients with MTHFR deficiency from 32 international metabolic centres. Characteristics of the 32 patients with early-onset MTHFR deficiency were described at time of diagnosis and at the last follow-up visit. Logistic regression analysis was used to identify predictive factors of severe neurodevelopmental outcome in a broader set of patients with early and non-early-onset MTHFR deficiency. The majority of early-onset MTHFR-deficient patients (n = 32) exhibited neurologic symptoms (76%) and feeding difficulties (70%) at time of diagnosis. At the last follow-up visit (median follow-up time of 8.1 years), 76% of treated early-onset patients (n = 29) exhibited a severe neurodevelopmental outcome. Among the whole study population of 64 patients, pre-symptomatic diagnosis was independently associated with a significantly better neurodevelopmental outcome (adjusted OR 0.004, [0.002-0.232]; p = 0.003). This study provides evidence for benefits of pre-symptomatic diagnosis and appropriate therapeutic management, highlighting the need for systematic newborn screening for MTHFR deficiency and pre-symptomatic treatment that may improve outcome.
- MeSH
- homocystein MeSH
- homocystinurie * diagnóza farmakoterapie MeSH
- kohortové studie MeSH
- lidé MeSH
- methylentetrahydrofolátreduktasa (NADPH2) nedostatek genetika MeSH
- novorozenec MeSH
- psychotické poruchy MeSH
- retrospektivní studie MeSH
- svalová spasticita diagnóza MeSH
- Check Tag
- lidé MeSH
- novorozenec MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Patient registries for rare diseases enable systematic data collection and can also be used to facilitate postauthorization safety studies (PASS) for orphan drugs. This study evaluates the PASS for betaine anhydrous (Cystadane), conducted as public private partnership (PPP) between the European network and registry for homocystinurias and methylation defects and the marketing authorization holder (MAH). Data were prospectively collected, 2013-2016, in a noninterventional, international, multicenter, registry study. Putative adverse and severe adverse events were reported to the MAH's pharmacovigilance. In total, 130 individuals with vitamin B6 nonresponsive (N = 54) and partially responsive (N = 7) cystathionine beta-synthase (CBS) deficiency, as well as 5,10-methylenetetrahydrofolate reductase (MTHFR; N = 21) deficiency and cobalamin C (N = 48) disease were included. Median (range) duration of treatment with betaine anhydrous was 6.8 (0-9.8) years. The prescribed betaine dose exceeded the recommended maximum (6 g/day) in 49% of individuals older than 10 years because of continued dose adaptation to weight; however, with disease-specific differences (minimum: 31% in B6 nonresponsive CBS deficiency, maximum: 67% in MTHFR deficiency). Despite dose escalation no new or potential risk was identified. Combined disease-specific treatment decreased mean ± SD total plasma homocysteine concentrations from 203 ± 116 to 81 ± 51 μmol/L (p < 0.0001), except in MTHFR deficiency. Recommendations for betaine anhydrous dosage were revised for individuals ≥ 10 years. PPPs between MAH and international scientific consortia can be considered a reliable model for implementing a PASS, reutilizing well-established structures and avoiding data duplication and fragmentation.
- MeSH
- betain škodlivé účinky MeSH
- cystathionin-beta-synthasa MeSH
- homocystein MeSH
- homocystinurie * farmakoterapie MeSH
- lidé MeSH
- methylentetrahydrofolátreduktasa (NADPH2) nedostatek genetika MeSH
- psychotické poruchy * MeSH
- svalová spasticita MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
