Search

Introduction Thromboembolic events occur due to an imbalance in the hemostasis and some factors associated with this condition can be inherited. In order to evaluate the frequency of genotypes considered to be common hereditary risk factors for thrombophilia associated with venous thrombosis (g.1691G > A and g.20210G > A) and hyperhomocysteinemia (g.677C > T and g.1298A > C), samples from voluntary healthy blood donors at the Hospital de Clinicas de Porto Alegre were tested. Methods We examined 325 blood samples from blood donors collected from October 2017 to July 2018. Blood was collected on filter paper and the DNA was extracted for single nucleotide polymorphisms (SNPs) analysis using the qualitative real time polymerase chain reaction. Results The calculated frequencies of each genetic variant in heterozygosity were 4% for the FV gene (g.1691G > A), 4% for the F2 gene (g.20210G > A) and 42% and 39% for methylenetetrahydrofolate reductase (MTHFR), g.677C > T and g.1298A > C, respectively. Only the genetic variants of MTHFR were found in homozygosity, with frequencies of 14% and 6% (g.677C > T and g.1298A > C), respectively. Discussion Altogether, these results describe the frequencies of genetic variants associated with venous thrombosis and hyperhomocysteinemia in the analyzed group and are important to enhance our current knowledge about the genetic profiles of Brazilian blood donors.

In vitro and animal model studies have shown that vitamin B (VB) deficiency has negative consequences on bone as a result of direct or mediated activity of hyperhomocysteinemia. However, there are still no precise indications regarding a possible VB role in order to maintain bone health. So, the aim of this narrative review was to consider state of the art correlation between VB dietary intake, blood levels and supplementation and bone health (bone mineral density (BMD), bone turnover markers and fractures risk) in humans. This review includes 29 eligible studies. Considering VB blood levels, the 14 studies considered have shown that low serum folate can be a risk factor for reduced BMD and fractures in the elderly, particularly women; no independent association was found for other VB. Studies that evaluate the relationship between VB dietary intake and BMD are only 2; one, conducted on 1869 women, demonstrated a positive effect of folate intake on BMD. Another demonstrated a dose-dependent inverse relationship between vitamin B6 dietary intake and risk of hip fracture, but only for 35298 female participants. Regarding the relationship between BV supplementation and bone health (9 studies with only VB and 4 with other nutrients), all studies that considered patients with hyperhomocysteinemia or with low folate blood levels, are in agreement in demonstrating that folate supplementation (500mcg- 5mg) is useful in improving BMD. In conclusion, a request for folate and homocysteine blood levels in elderly patients with osteopenia/osteoporosis is mandatory. For patients with hyperhomocysteinemia or with low folate blood levels, folate supplementation (500mcg-5mg) is crucial.

Актуальність. Важливе питання профілактики ішемічного інсульту можна реалізувати шляхом поліпшення надання медичної допомоги хворим і проведення профілактичних заходів, спрямованих на запобігання виникненню захворювання. Окремим питанням профілактики повторних тромбозів церебральних судин є медикаментозна профілактика гіпергомоцистеїнемії, що призводить до ряду фізіологічних патологій, серед яких можна назвати атеросклероз, атеротромбоз та венозний тромбоз. Мета роботи — розробка з урахуванням генетичних критеріїв більш досконалого й ефективного способу медикаментозної профілактики повторного мозкового ішемічного інсульту. Матеріали та методи. Нами було обстежено 150 пацієнтів, які перенесли ішемічний інсульт (чоловіків було 86, жінок — 64), віком від 45 до 84 років (середній вік — 65,2 ± 9,7 року) на базі нейрохірургічного відділення № 2 клінічної міської лікарні швидкої медичної допомоги м. Києва. Всім пацієнтам проводилося генетичне тестування у вигляді забору венозної крові та виявлення характеру мутації гена MTHFR C677T (СС, СТ або ТТ варіанти). Результати. Пацієнтів було розподілено на групи згідно з виявленими мутаціями гена MTHFR C677T та призначеним профілактичним лікуванням. У групу СС1 (n = 45) було включено пацієнтів із мутацією MTHFR C677T типу СС, яким призначався додатково до основного профілактичного лікування препарат фолієвої кислоти (вітамін В9) у дозі 1 мг (оптимізована профілактика). Пацієнти групи СС2 (n = 45) мали таку саму мутацію, але отримували лише основне профілактичне лікування (еналаприл 20 мг 2 р/д, аспірин 100 мг 1 р/д та розувастатин 20 мг 1 р/д). Так само були розподілені пацієнти груп СТ1 (n = 21), СТ2 (n = 21), ТТ1 (n = 9) та ТТ2 (n = 9). За умови призначення оптимізованої медикаментозної профілактики ризик інсульту серед пацієнтів із мутаціями СС та СТ вірогідно не відрізнявся (р > 0,1). Проте в разі мутації ТТ дані показали як високий ризик повторного інсульту через генетично обумовлену гіпергомоцистeїнемію, так і значну різницю в частоті повторної церебральної події на тлі лікування фолієвою кислотою (0 та 33,3 % відповідно). Висновки. Таким чином, оптимізована методика медикаментозної профілактики гострого ішемічного інсульту дозволяє ефективно запобігати виникненню повторного ішемічного інсульту залежно від генетичних особливостей пацієнта.

Aims: Hyperhomocysteinemia (HHcy) has been considered as a risk factor for cardiovascular disease (CVD), Alzheimer's disease (AD), nonalcoholic fatty liver (NAFL) and many other pathological condit...

Nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (DM) are the components of metabolic syndrome, the incidence of which is increasing in the world every year. The article presents the results of treatment of 110 patients with NAFLD and its combination with type 2 DM. Patients were divided into two groups: I group — 63 patients with isolated NAFLD, II group — 47 patients with comorbidity (NAFLD and type 2 DM). During a month, all patients received vitamins B6, B12 and folic acid. As a result, patients reported reduction in homocysteine content in blood plasma, normalization of lipid metabolism and the level of liver enzymes.

Background/purpose Our previous study found significantly lower serum hematinic levels and higher serum homocysteine level as well as higher frequencies of serum hematinic deficiencies and hyperhomocysteinemia in oral leukoplakia (OL) patients than in healthy control subjects. This study evaluated whether carcinoembryonic antigen (CEA)-positive or squamous cell carcinoma-antigen (SCC–Ag)-positive OL patients had significantly lower serum hematinic levels and higher serum homocysteine level as well as significantly higher frequencies of hematinic deficiencies and hyperhomocysteinemia than CEA-negative or SCC-Ag-negative OL patients or healthy control subjects. Methods The complete blood count, serum iron, vitamin B12, folic acid, and homocysteine levels in 184 OL patients including 85 CEA-positive, 99 CEA-negative, 25 SCC-Ag-positive, and 159 SCC-Ag-negative OL patients and in 184 age- and sex-matched healthy control subjects were measured and compared. Results We found that the 85 CEA-positive or 25 SCC-Ag-positive OL patients had a significantly lower mean serum folic acid level and a significantly higher mean serum homocysteine level as well as significantly higher frequencies of serum folic acid deficiency and hyperhomocysteinemia than 184 healthy control subjects. Moreover, the 25 SCC-Ag-positive OL patients had a significantly higher mean serum homocysteine level than the 159 SCC-Ag-negative OL patients. The 85 CEA-positive OL patients had a higher mean serum homocysteine level and a higher frequency of hyperhomocysteinemia than 99 CEA-negative OL patients (marginally significant, P = 0.060). Conclusion CEA-positive or SCC-Ag-positive OL patients tend to have a higher mean serum homocysteine level and a higher frequency of hyperhomocysteinemia than CEA-negative or SCC-Ag-negative OL patients, respectively.

A 50-year-old woman was incidentally diagnosed to have unilateral disc oedema during comprehensive ophthalmological evaluation. She had a prior history of ulcerative colitis. She had normal visual function and was initially diagnosed to have incipient non-arteritic anterior ischaemic optic neuropahty. Risk factor evaluation revealed hyperhomocysteinaemia. She was asked to come for a follow-up in 2 months. However, she was lost to follow-up and returned to the clinic for the evaluation for headaches, 23 months later. Her ocular examination was stable and she had persistent unilateral disc oedema unchanged from the prior visit. Repeat MRI brain and MR venogram brain with contrast-established diagnosis of cerebral sinus venous thrombosis (CSVT). She denied any neurological symptoms. Later on, she was diagnosed to have hyperhomocysteinaemia with methyl tetrahydrofolate reductase gene mutation. This case highlights the importance of recognising although rare, unilateral disc oedema secondary to elevated intracranial pressure from CSVT.

Accumulated evidence demonstrated that an elevated plasma homocysteine level, hyperhomocysteinemia, induced cognitive impairment in animals, elderly and the patients with neurodegenerative diseases. To date, the underlying cellular and molecular mechanisms by which hyperhomocysteinemia induces cognitive impairment has not been clearly defined. The purpose of this study was to investigate the possible cellular and molecular mechanisms behind hyperhomocysteinemia signaling in rat memory impairment. The results from this study demonstrated that hyperhomocysteinemia induced neuronal damage and loss in hippocampal CA3 region and downregulated the cAMP response element-binding protein (CREB) phosphorylation. The findings of this study provide evidence that hyperhomocysteinemia induces rat memory impairment via injuring hippocampal CA3 neurons and downregulating CREB phosphorylation.

Background. In recent years, there have been increasing reports of vitamin B12 deficiency in patients with vasovagal syncope. Therefore, homocysteine levels in these patients may also differ from those in the healthy population. The purpose of the research was to study the peculiarities of serum homocysteine concentration in children with vasovagal syncope. Materials and methods. The main group consisted of 28 children aged 8–17 years with a diagnosis of vasovagal syncope. The control group included 23 apparently healthy children of the same age who had no signs of chronic diseases. The determination of vitamin B6, B12, folic acid, and homocysteine in the blood serum was performed by means of a colorimetric enzyme-linked immunosorbent assay using the Monobind test system. Hyperhomocysteinemia was diagnosed at the level of serum homocysteine above 15 μmol/l. Results. There were decreased serum levels of vitamins B6 and B12 with unchanged folic acid levels in children with vasovagal syncope compared to healthy respondents. In the vasovagal syncope group, an increased level of homocysteine was observed compared to the controls (13.86 ± 0.97 μmol/l; 7.81 ± 0.36 μmol/l; p = 0.000003). The prevalence of hyperhomocysteinemia among children with vasovagal syncope was 46.4 %, whereas in the control group it was not recorded at all (χ2 = 14.33; p = 0.0002). Homocysteine correlates with P-Q interval (moda and mean), Q-T interval (moda), vitamin B6 (p < 0.05). An increase in serum homocysteine concentration is accompanied by deterioration of some quality of life indicators according to the PedsQLTM (general well-being scale, multifactorial fatigue scale, family impact module). Conclusions. Vasovagal syncope in childhood is associated with increased serum homocysteine. The prevalence of hyperhomocysteinemia among children with vasovagal syncope is 46.4 %., Актуальность. В последние годы появляется все больше сообщений о развитии дефицита витамина B12 среди пациентов с вазовагальными обмороками, следовательно, уровень гомоцистеина у этих пациентов тоже может отличаться от показателей в здоровой популяции. Цель: изучить особенности концентрации гомоцистеиина в сыворотке крови детей с вазовагальными обмороками. Материалы и методы. Основную группу составили 28 детей в возрасте 8–17 лет с диагнозом вазовагального обморока, контрольную — 23 практически здоровых ребенка аналогичного возраста, не имевших признаков хронических заболеваний. Уровни витаминов В6, В12, фолиевой кислоты и гомоцистеина в сыворотке крови определяли с помощью колориметрического метода иммуноферментного анализа с использованием тест-системы Monobind. Гипергомоцистеинемию диагностировали при уровне гомоцистеина в крови выше 15 мкмоль/л. Результаты. У детей с вазовагальными обмороками были обнаружены сниженные показатели витаминов В6 и В12 при неизменном уровне фолиевой кислоты по сравнению со здоровыми респондентами. В группе вазовагальных обмороков регистрировался повышенный уровень гомоцистеина по сравнению с контролем (13,86 ± 0,97; 7,81 ± 0,36 мкмоль/л; р = 0,000003). Распространенность гипергомоцистеинемии среди детей с вазовагальными синкопе составила 46,4 %, тогда как в контрольной группе не регистрировалась (χ2 = 14,33; р = 0,0002). Показатель гомоцистеина коррелирует с модой и средним значением интервала P-Q, модой интервала Q-T, витамином В6 (р < 0,05). Увеличение концентрации сывороточного гомоцистеина сопровождается ухудшением отдельных показателей качества жизни по данным опросников PedsQLTM (шкала общего благополучия, многофакторная шкала усталости, модуль влияния на семью). Выводы. Вазовагальные синкопе в детском возрасте ассоциируются с повышенной концентрацией гомоцистеина в сыворотке крови. Распространенность гипергомоцистеинемии среди детей с вазовагальным синкопе составляет 46,4 %., Актуальність. Останніми роками з’являється все більше повідомлень щодо розвитку дефіциту вітаміну B12 серед пацієнтів із вазовагальними синкопе, а отже, рівень гомоцистеїну у цих пацієнтів теж може відрізнятися від показників у здоровій популяції. Мета: вивчити особливості концентрації гомоцистеіїну у сироватці крові дітей із вазовагальними синкопе. Матеріали та методи. Основну групу становили 28 дітей віком 8–17 років із діагнозом вазовагального синкопе, контрольну — 23 практично здорові дитини аналогічного віку, які не мали ознак хронічних захворювань. Рівні вітамінів В6, В12, фолієвої кислоти та гомоцистеїну у сироватці крові визначали за допомогою колориметричного методу імуноферментного аналізу з використанням тест-системи Monobind. Гіпергомоцистеїнемію діагностували у разі, якщо рівень гомоцистеїну в крові був вище 15 мкмоль/л. Результати. У дітей із вазовагальними синкопе виявлено знижені показники вітамінів В6 та В12 при незміненому рівні фолієвої кислоти порівняно зі здоровими респондентами. У групі вазовагальних синкопе реєструвався підвищений рівень гомоцистеїну проти групи контролю (13,86 ± 0,97; 7,81 ± 0,36 мкмоль/л; р = 0,000003). Поширеність гіпергомоцистеїнемії серед дітей із вазовагальними синкопе становила 46,4 %, тоді як у контрольній групі жодного випадку не реєструвалося (χ2 = 14,33; р = 0,0002). Показник гомоцистеїну корелює з модою та середнім значенням інтервалу P-Q, модою інтервалу Q-T, вітаміном В6 (р < 0,05). Зростання концентрації сироваткового гомоцистеїну супроводжується погіршенням окремих показників якості життя за даними опитувальників PedsQLTM (шкала загального благополуччя, багатофакторна шкала втомлюваності, модуль впливу на родину). Висновки. Вазовагальні синкопе у дитячому віці асоціюються з підвищеною концентрацією гомоцистеїну у сироватці крові. Поширеність гіпергомоцистеїнемії серед дітей із вазовагальними синкопе становить 46,4 %.

Homocysteine is a sulfur-containing non-proteinogenic amino acid that is an intermediate product of methionine metabolism. With excessive accumulation of homocysteine in the body, a state of hyperhomocysteinemia occurs, which has attracted the attention of doctors since the middle of the last century and received a serious impetus for research after the publication of data on the role of hyperhomocysteinemia in the pathogenesis of thromboocclusive diseases. To date, there are more than 7.5 thousand scientific papers devoted to the study of hyperhomocysteinemia, monothematic international conferences on clinical and therapeutic aspects of hypermonocysteinemia are held every year. In the Russian Federation, a detailed study of the role of homocysteine and its side effects in excess is of particular interest due to the prevalence of cardiovascular pathologies (according to statistics of the Ministry of Health of Russia-49.27% of deaths of Russians fall on this cohort of diseases). This is an important fact in Russian medicine, which deserves close attention from researchers and scientists.

Background/Purpose: Lacto-vegetarians (LVs) tend to have vitamin B12 deficiency (B12D). This study assessed whether 140 female LVs, including 16 B12D/LVs and 124 non-B12D/LVs, had significantly higher frequencies of microcytosis, macrocytosis, and of blood hemoglobin (Hb), red blood cell (RBC), and serum vitamin B12 deficiencies than 140 healthy control subjects (HCSs). Methods: The complete blood count and serum vitamin B12 level in 140 female LVs and 140 female HCSs were measured and compared. Results: We found that 8.6%, 4.3%, 22.9%, 20.0%, and 11.4% of 140 LVs had microcytosis, macrocytosis, and blood Hb, RBC, and serum vitamin B12 deficiencies, respectively. The 140 LVs, 16 B12D/LVs, and 124 non-B12D/LVs had significantly higher frequencies of microcytosis as well as blood Hb and RBC deficiencies than 140 HCSs (all P-values

Homocysteine (Hcy) metabolism is crucial for regulating methionine availability, protein homeostasis, and DNA-methylation presenting, therefore, key pathways in post-genomic and epigenetic regulation mechanisms. Consequently, impaired Hcy metabolism leading to elevated concentrations of Hcy in the blood plasma (hyperhomocysteinemia) is linked to the overproduction of free radicals, induced oxidative stress, mitochondrial impairments, systemic inflammation and increased risks of eye disorders, coronary artery diseases, atherosclerosis, myocardial infarction, ischemic stroke, thrombotic events, cancer development and progression, osteoporosis, neurodegenerative disorders, pregnancy complications, delayed healing processes, and poor COVID-19 outcomes, among others. This review focuses on the homocysteine metabolism impairments relevant for various pathological conditions. Innovative strategies in the framework of 3P medicine consider Hcy metabolic pathways as the specific target for in vitro diagnostics, predictive medical approaches, cost-effective preventive measures, and optimized treatments tailored to the individualized patient profiles in primary, secondary, and tertiary care.

In this study, we performed a study on 106 children with epilepsy who were treated with sodium valproate (the VPA group, n = 37), oxcarbazepine (the OXC group, n = 34), or levetiracetam (the LEV group, n = 35). In addition, the clinical data of epileptic children who were newly diagnosed in the same period without antiepileptic drug (AED) treatment (the untreated group, n = 35) and normal children who received physical examination in our hospital (the healthy group, n = 35) were selected as controls. We analyzed the efficacy and safety of different AEDs, used blood ammonia and homocysteine levels as the observation indicators, and calculated the incidence of hyperammonemia (VAH) and hyperhomocysteinemia (HHcy) treated with different AEDs. And, based on the effect of epilepsy status on the cognitive function of patients, we also analyzed the effect of different AED treatments on children’s cognitive function. Our results show that sodium valproate, oxcarbazepine, and levetiracetam are all effective in the treatment of children with epilepsy and can be used as the first-line choice of antiepileptic treatment for children with epilepsy. However, compared with sodium valproate, levetiracetam and oxcarbazepine have a lower incidence of adverse drug reactions and do not cause an increase in blood ammonia and Hcy levels, so they have higher safety of drug treatment. In addition, compared with sodium valproate, levetiracetam and oxcarbazepine have better recovery of cognitive function in children with epilepsy and so they have better application value.

Aims: The aims of this study were to explore the left ventricular (LV) structural remodeling and its risk factors in type 2 diabetes mellitus (T2DM) patients with or without hyperhomocysteinemia (h...

Background and aims Hyperhomocysteinemia (HHcy) is an independent risk factor for atherosclerosis and plaque vulnerability. The macrophage apoptosis mediated by endoplasmic reticulum (ER) stress plays an important role in the pathogenesis of HHcy-aggravated atherosclerosis. Endoplasmic reticulum oxidoreductase 1α (Ero1α) is critical for ER stress-induced apoptosis. We hypothesize that Ero1α may contribute to ER-stress induced macrophage apoptosis and plaque stability in advanced atherosclerotic lesions by HHcy. Methods Apoe−/− mice were maintained on drinking water containing homocysteine (Hcy, 1.8 g/L) to establish HHcy atherosclerotic models. The role of Ero1α in the atherosclerotic plaque stability, macrophage apoptosis and ER stress were monitored in the plaque of aortic roots in HHcy Apoe−/− mice with or without silence or overexpression of Ero1α through lentivirus. Mouse peritoneal macrophages were used to confirm the regulation of Ero1α on ER stress dependent apoptosis in the presence of HHcy. Results The atherosclerotic plaque vulnerability and macrophage apoptosis were promoted in Apoe−/− mice by high Hcy diet, accompanied by the upregulation of Ero1α expression and ER stress. Inhibition of Ero1α prevented macrophage apoptosis and atherosclerotic plaque vulnerability, and vice versa. Consistently, in mouse peritoneal macrophages, ER stress and apoptosis were attenuated by Ero1α deficiency, but enhanced by Ero1α overexpression. Conclusions Hcy via upregulating Ero1α expression activates ER stress-dependent macrophage apoptosis, so as to promote vulnerable plaque formation in atherosclerosis. Ero1α may be a potential therapeutic target for atherosclerosis induced by Hcy.

Background/purpose: Our previous study found that 70 of 884 burning mouth syndrome (BMS) patients have serum gastric parietal cell antibody (GPCA) positivity but without thyroglobulin antibody (TGA) and thyroid microsomal antibody (TMA) (so-called GPCA+TGAˉTMAˉBMS patients). This study assessed whether these 70 GPCA+TGAˉTMAˉBMS patients had significantly higher frequencies of macrocytosis, anemia, hematinic deficiencies, and hyperhomocysteinemia than 553 GPCA-negative, TGA-negative, and TMA-negative BMS (GPCAˉTGAˉTMAˉBMS) patients or 442 healthy control subjects. Materials and methods: Complete blood count, serum iron, vitamin B12, folic acid, homocysteine, GPCA, TGA, and TMA levels in 70 GPCA+TGAˉTMAˉBMS patients, 553 GPCAˉTGAˉTMAˉBMS patients, and 442 healthy control subjects were measured and compared. Results: We found that 15.7%, 28.6%, 20.0%, 11.4%, 2.9%, and 25.7% of 70 GPCA+TGAˉTMAˉBMS patients and 3.8%, 17.7%, 15.9%, 3.8%, 2.7%, and 20.1% of 553 GPCAˉTGAˉTMAˉBMS patients had macrocytosis, blood hemoglobin, iron, vitamin B12, and folic acid deficiencies, and hyperhomocysteinemia, respectively. Moreover, both 70 GPCA+TGAˉTMAˉBMS patients and 553 GPCAˉTGAˉTMAˉBMS patients had significantly greater frequencies of macrocytosis, blood hemoglobin, serum iron, vitamin B12, and folic acid deficiencies, and hyperhomocysteinemia than 442 healthy control subjects (all P-values

Background The prevalence of coronary artery disease (CAD) continues to increase among young Chinese adults. Current smoking has been recognized as a major risk factor for premature CAD, and hyperhomocysteinaemia (HHcy) has also been suggested to be associated with CAD progression. However, the combined effect of current smoking and HHcy on the severity of coronary artery stenosis in young adults is still uncertain. Methods We consecutively collected young patients (18–35 years of age), diagnosed with CAD and underwent coronary angiography (CAG) at Anzhen Hospital between January 2013 and May 2020. HHcy was defined as serum homocysteine (Hcy) level > 15 µmol/L. The severity of coronary artery stenosis was evaluated by Gensini Score. The co-effect of current smoking and HHcy on CAD severity as well as the relationship between plasma Hcy, pack-years of smoking and CAD severity were assessed by multivariate linear regression analysis. Results A total of 989 participants (mean age, 33 years; 96.2% male) fulfilling the criteria were enrolled in this study. Patients with both HHcy and current smoking accounted for 39.1% of all the subjects. Multivariate liner analysis indicated both serum Hcy levels (β 0.302; 95% CI 0.141–0.462; P β 0.523; 95% CI 0.265–0.781; P r = 0.116, P = 0.001). Moreover, combination of HHcy and current smoking was suggested to have higher risk for CAD severity (β 17.892; 95% CI 11.314–24.469; P β 7.471; 95% CI 0.009–14.934; P = 0.048) or current smoking (β 7.421; 95% CI 0.608–14.233; P = 0.033) alone. Conclusion Combination of HHcy and smoking is independently associated with the severity of CAD in young patients ≤ 35 years of age.

This study aims to evaluate the level of plasma homocysteine in patients with acute post-resection hepatic failure, depending on the degree of the disease. Materials and Methods. The article presents the results of a study of plasma homocysteine levels in 40 patients with c different classes of acute post-resection liver failure. Indications for liver resection were: primary liver cancer 11 (27%), metastatic liver lesions 21 (53%), parasitic liver diseases 3 (7%), benign liver formations 5 (13%). Patients were divided into 3 groups - Patients with Post hepatectomy liver failure (PHLF) class developed in the postoperative period A, B and C. Results. Analysis of the data showed that the initially normal level of plasma homocysteine before liver resection (surgical treatment) and after has different developmental options. Depending on the class of post-resection hepatic failure, the level of plasma homocysteine changes and has deviations from the reference values. In a comparative analysis of the average homocysteine values in the group of patients with post-resection hepatic insufficiency of class A, after surgical treatment, they were significantly lower than in patients with PHLF B and C. In particular, in patients with class B and C PNF, there is a significant trend towards an increase in homocysteine levels after surgery. Hyperhomocysteinemia may be a risk factor for the development of acute liver failure after surgical treatment for focal liver disease. Possibly, its adverse effect on the function and restoration of the liver parenchyma, which requires further targeted study.

Background. Identification of risk factors and preliminary assessment of overall cardiovascular risk in patients with hypertension is the most important task in clinical practice. Most patients, in addition to high blood pressure (BP), have other cardiovascular risk factors that aggravate each other, leading to an increase in overall cardiovascular risk. One of the cardiovascular risk factors is an increased arterial stiffness. Arterial stiffness is evaluated using pulse wave velocity (PWV). The other independent risk factor for cardiovascular diseases is elevated level of total homocysteine in the blood. The purpose was to evaluate the relationship between hyperhomocysteinemia (HHc) and vascular stiffness in patients with hypertension. Materials and methods. Our research was carried out as a part of the ХІПСТЕР trial in Ukraine. The study included 40 patients with hypertension stage 1 and 2 (average office systolic (SBP)/diasto-lic blood pressure (DBP) was 155.88/92.60 ± 1.63/1.43 mmHg, heart rate — 71.40 ± 1.29 bpm). The average age of the patients was 55.85 ± 2.09 (26–74) years. Individuals with homocysteine levels ≥ 10 μmol/l were referred to as those with HHc (H-type hypertension). Arterial stiffness was determined by PWV. Results. We found that at the beginning of the study, 75 % of patients (30 individuals with mild and moderate hypertension) had H-type hypertension with an increased level of homocysteine. Patients with H-type hypertension (HHc) and hypertension without HHc did not differ in terms of age, duration of hypertension. At the same time, patients with H-type hypertension had higher body weight and body mass index. Office SBP in patients with H-type hypertension at baseline and after 6 months of treatment was higher compared to patients without HHc (156.45 ± 1.04 mmHg and 152.55 ±1.41 mmHg (p < 0.05) at baseline vs 130.65 ± 0.96 mmHg and 126.97 ± 1.08 mmHg (p

Повышенная частота сердечно-сосудистых событий и субклинического атеросклероза, подтвержденная методами визуализации и сосудистой функции, является доказанным фактом при системной красной волчанке (СКВ). Хотя традиционные факторы сердечно-сосудистых заболеваний, такие как курение, дислипидемия, сахарный диабет, артериальная гипертензия, центральное ожирение и гипергомоцистеинемия, распространены у больных СКВ, они не в полной мере объясняют высокий уровень ишемических событий, о которых сообщается в настоящий момент, что подразумевает, что другие факторы, которые присущи самой болезни, могут способствовать повышенному риску, включая продолжительность болезни, активность и хроническое течение, психосоциальные факторы, лекарственные препараты, генетические нарушения и измененные иммунологические механизмы. Хотя точный патогенез атеросклероза при СКВ остается плохо изученным, дисбаланс между повреждением эндотелия и атеропротекцией, по-видимому, является центральным механизмом. К факторам, приводящим к повреждению эндотелия при СКВ, относятся окисленные липопротеиды низкой плотности (ЛПНП), аутоантитела к эндотелиальным клеткам и фосфолипидам, интерфероны (ИФН) I типа и внеклеточные нейтрофильные ловушки, которые действуют непосредственно или через активацию пути ИФН I типа. Повышенный окислительный стресс, пониженные уровни антиоксидантных липопротеидов высокой плотности (ЛПВП), повышенные уровни провоспалительных ЛПВП и пониженная параоксоназная активность связаны с повышенными уровнями окисленных ЛПНП. С другой стороны, нарушения атеропротективных механизмов при СКВ включают снижение способности эндотелиальной репарации, частично опосредованной через ИФН I типа, и уменьшение продукции атеропротективных аутоантител. В настоящем обзоре суммированы традиционные и связанные с заболеванием факторы риска сердечно-сосудистых заболеваний при хронических аутоиммунных расстройствах, в частности, при СКВ.

Актуальность. В условиях оксидантного и нитрозативного стресса мозг уязвим для окислительного повреждения вследствие высокого потребления кислорода, большого количества железа, относительно низкого уровня экспрессии антиоксидантов, высокого содержания полиненасыщенных жирных кислот. Один из маркеров нитрозативного стресса — нитротирозин. Высокие концентрации нитротирозина в ликворе связаны с неблагоприятным течением заболевания. В качестве индикатора интенсивности оксидантного стресса используется также гомоцистеин. Повышенные концентрации гомоцистеина имеют цитотоксическое действие, что приводит к гибели клетки. Цель исследования: изучение показателей нитрозативного и оксидантного стресса при бактериальных менингитах у недоношенных детей. Материалы и методы. Обследовано 52 новорожденных. Основная группа — 14 недоношенных детей (средний срок гестации 31,7 ± 0,9 недели), больных бактериальным менингитом. Группа сравнения — 20 новорожденных с перинатальными поражениями ЦНС (10 недоношенных детей со средним сроком гестации 32,3 ± 0,4 недели и 10 доношенных новорожденных). Контрольная группа — 18 здоровых доношенных детей. Проводили оценку анамнеза, соматического и неврологического статуса новорожденных, данных нейросонографии. Методом иммуноферментного анализа было исследовано содержание нитротирозина в сыворотке крови. Результаты. Установлено, что содержание нитротирозина в сыворотке крови новорожденных основной группы было достоверно ниже, чем в группе сравнения и контрольной группе (1,38 ± 0,06 против 1,53 ± 0,07 ммоль/л и 1,61 ± 0,04 ммоль/л соответственно; р < 0,05), зависело от гестационного возраста ребенка (r = +0,63; p

Background. Whether holotranscobalamin (holoTC) indicates B12 deficiency more sensitively than total vitamin B12 (B12) is unclear. This study is aimed at determining the impact of serum holoTC level as a risk factor for ischemic stroke and investigating its association with disease severity and short-term outcomes. Methods. Serum holoTC, total B12, and homocysteine levels were compared between 130 stroke patients and 138 healthy controls. Biomarker level correlations with disease severity and stroke functional outcomes were investigated. Results. holoTC levels were lower and homocysteine levels were higher in stroke patients than in healthy controls ( P < 0.05 ). The holoTC/total B12 ratio and homocysteine level significantly predicted ischemic stroke in the multivariable regression analysis ( P < 0.05 ). Along with hyperhomocysteinemia, patients more often had holoTC than total B12 deficiency (6.2% vs. 3.1%). holoTC levels negatively correlated with homocysteine levels (partial R -0.165, P < 0.05 ) in stroke patients in multiple linear regression analyses, but not total B12 levels. The holoTC level and holoTC/total B12 ratio, but not homocysteine and total B12 levels, negatively correlated with the National Institute of Health Stroke Scale (partial R , -0.405 and -0.207, respectively, P < 0.01 ). Conclusions. Measurements of serum holoTC levels combined with total B12 and homocysteine levels may provide valuable information for predicting ischemic stroke and its severity and short-term outcomes of ischemic stroke patients.

The hyperhomocysteinemia (HHcy) is toxic to the cells and associated with several diseases. Clinical studies have shown changes in plasma concentrations of Hcy after physical exercise. This study aimed to assess the effect of HHcy on testis, epididymis and sperm quality and to investigate whether voluntary exercise training protects this system against damage caused by HHcy in Swiss mice. In this study, 48 mice were randomly distributed in the control, HHcy, physical exercise, and HHcy combined with physical exercise groups. HHcy was induced by daily administration of dl-homocysteine thiolactone via gavage throughout the experimental period. Physical exercise was performed through voluntary running on the exercise wheels. The plasma concentrations of homocysteine (Hcy) and testosterone were determined. The testes and epididymis were used to assess the sperm count, histopathology, lipoperoxidation, cytokine levels, testicular cholesterol, myeloperoxidase, and catalase activity. Spermatozoa were analyzed for morphology, acrosome integrity, mitochondrial activity, and motility. In the testes, HHcy increased the number of abnormal seminiferous tubules, reduced the tubular diameter and the height of the germinal epithelium. In the epididymis, there was tissue remodeling in the head region. Ultimately, voluntary physical exercise training reduced plasma Hcy concentration but did not attenuate HHcy-induced testicular and epididymal disturbances.

Nitrous oxide, colloquially known as “whippets,” is a commonly abused inhalant by adolescents and young adults. There are limited data describing the adverse effects of this abuse. We present a 16-year-old girl with no medical history who presented to the emergency department for confusion, hallucinations, weakness, and headaches. Imaging revealed extensive cerebral thrombosis. She had no prior history of venous or arterial thrombosis. Hypercoagulability workup demonstrated an elevated homocysteine level. She was treated with effective anticoagulation and vitamin B12 folate supplementation. To our knowledge, there are a very few cases in the medical literature of cerebral venous thrombosis following the use of nitrous oxide. The pathophysiology of the disorder appears to be linked to the metabolism of vitamin B12 inducing hyperhomocysteinemia and a procoagulant state.

Objective: Increased level of plasma homocysteine (Hcy) is a potential risk factor for several multi-system diseases. The Methylenetetrahydrofolate reductase (MTHFR) gene C677T variant has been established as an important genetic determinant of hyperhomocysteinemia. There are conflicting reports about the effects of physical activity on plasma Hcy. Therefore, the main aim of this study was to investigate whether the MTHFR C677T variant affects elite athletic performance. Methods: This study was carried out on 214 individuals (114 elite athletes and 100 sedentary controls). Genotyping was performed using PCR- RFLP method. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association. Results: There was a significant difference between the athletes and the control group in genotype distribution and allele frequency of the MTHFR C677T variant. MTHFR C677T CC genotype and C allele were more prevalent in elite athletes than those in the sedentary controls (p =0.007, OR: 2.16, 95%:1.26-3.70; p=0.009, OR: 1.84, 95%:1.18-2.89, respectively). The control group had a higher MTHFR C677T CT genotype than the athletes (p=0.019, OR: 0.51, 95%:0.30-0.88). There was no deviation from HWE for the MTHFR C677T variant in the groups. Conclusion: Our findings support that there is an association between the MTHFR C677T C allele and athletic performance among the elite Turkish athletes.

Background and Purpose Previous studies suggest an association between increased homocysteine (Hcy) and risk of ischemic stroke. Yet, it remains unknown whether a dose-response association exists between Hcy levels and risk of ischemic stroke.Methods Systematic literature searches were performed in PubMed, Embase, Scopus, and Web of Science. Inclusion criteria were studies investigating ischemic stroke risk in an adult population with measured Hcy levels. We computed odds ratios (ORs) for a 5 µmol/L increase in Hcy levels using a random effects meta-analysis.Results In total, 108 studies met the inclusion criteria of which 22 were rated as high-quality studies, and 20 studies included a dose-response analysis. Hcy levels were analyzed either as a continuous or categorical variable. The majority of the studies found an increased risk of ischemic stroke when comparing the highest-to-lowest Hcy strata. A graded association was observed over the Hcy strata, indicating a dose-response association, with the most apparent effect when Hcy levels exceeded approximately 15 µmol/L. No studies explored a potential nonlinear association between Hcy levels and ischemic stroke. Six studies were included in a meta-analysis, showing an OR of 1.43 (95% confidence interval [CI]: 1.28–1.61) per 5 µmol/L increase in Hcy levels.Conclusion This review and meta-analysis indicate a dose-response association between Hcy levels and ischemic stroke. An evident increase in effect measures was observed when Hcy levels exceeded 15 µmol/L, indicating a nonlinear association between ischemic stroke and Hcy levels. This nonlinear association warrants further study.This study is registered with clinical trial ( https://www.crd.york.ac.uk/prospero/ ; unique identifier: CRD42019130371).

Background Homocysteine (Hcy) is considered to be a risk factor for cardiovascular and cerebrovascular diseases. Few studies have evaluated the distribution of Hcy on a large-scale health examination. Accordingly, this study aimed to investigate the level and distribution of Hcy in the population with healthy physical examination and the correlation with other biomarkers, and analyzed for cardiovascular and other diseases. Methods Measurements of serum Hcy, TC, TG, LDL-c, HDL-c, ALT, ALP, γ-GT, TBIL, GLU, urea, Cr, UA, and related metabolic risk factors were selected for analysis from 8063 medical examination samples collected from February 2017 to April 2020. The relationship between Hcy and other biochemical indicators were evaluated with the multivariate regression model of age, gender, smoking, drinking, body mass index (BMI), systolic blood pressure (SBP), and diastolic blood pressure (DBP). Results Among 8063 cases, the age, BMI, SBP, and DBP of the high-Hcy group were higher than those of the low-Hcy group, the difference was statistically significant (P P P = 0.002) and the Hcy of abnormal TG and HDL is higher than that of the normal blood lipid group (P P P = 0.007). In multivariate analysis, lnHDL-C was negatively correlated with lnHcy (β = − 0.038, SE = 0.016, P = 0.019), lnCr was positively correlated with lnHcy (β = 0.055, SE = 0.016, P P = 0.022). Conclusion Hcy is closely related to HDL-c, Cr, and UA, which indicates that Hcy may affect the metabolism of HDL-c and UA, and can also be used as an auxiliary diagnostic index for kidney injury.

This study explored the potential effects of mild hyperhomocysteinemia (HHcy) on the blood–brain barrier (BBB) and neuroinflammation. Seven-week-old male wild-type C57BL/6 mice were fed normal mouse chow (the control group) or a methionine-enriched diet (the HHcy group) for 14 weeks. Mice in the HHcy group exhibited a slight increase in serum Hcy levels (13.56 ± 0.61 μmol/L). Activation of the ERK signaling pathway, up-regulation of matrix metalloproteinase-9 (MMP-9), and degradation of tight junction proteins (occludin and claudin-5) were observed in both the cerebral cortex and hippocampus of mice with mild HHcy. However, microglia were not activated and the levels of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were not changed in either the cerebral cortex or hippocampus of mice with mild HHcy. Moreover, the signaling activity of STAT3 also did not differ significantly between the two groups. These findings demonstrate that the BBB is highly vulnerable to homocysteine insult. Even a slight increase in serum homocysteine levels up-regulates MMP-9 expression and disrupts the BBB integrity. Meanwhile, microglia activation or the STAT3 pathway might not contribute to the effects of mild HHcy on the brain.

Polycystic ovary syndrome (PCOS) is associated with an increased risk of cardiovascular disease in women. Hyperhomocysteinemia (H-Hcy) is closely related to arterial stiffness (AS) in patients with cardiovascular disease. This study aimed to investigate the relationship between serum homocysteine(Hcy) level and brachial-ankle pulse wave velocity (baPWV) in Chinese women with PCOS. A total of 124 PCOS women were enrolled and divided into two groups according to their baPWV values: normal, baPWV < 1400 cm/s and high AS, baPWV ≥ 1400 cm/s. Univariate analysis was performed to investigate the relative factors for baPWV, and multiple regression analysis was used to evaluate the association of Hcy with baPWV. The group with high AS (n = 35) had higher Hcy levels than the other group (n = 89; P < 0.05). Moreover, univariate analysis revealed that serum Hcy was positively correlated with baPWV (r = 0.133, P < 0.01). In multiple regression analysis, the age-adjusted serum Hcy level was positively correlated with baPWV (β = 0.201, P < 0.01). It remained positively associated with baPWV (β = 0.145, P < 0.01) after further adjustments for age, BMI, PCOS duration, systolic blood pressure, and homeostasis model assessment-insulin resistance as well as several other factors correlated with baPWV. Our results demonstrated that H-Hcy was significantly and independently related to elevated baPWV, suggesting that Hcy might play a role in the pathologic process of AS in women with PCOS. Further researches with more subjects are needed to explore whether Hcy would be a promising biomarker for the stratification management of PCOS women.

Increased homocysteine has been related to the occurrence of dissections in the coronary circulation, aorta, and cervical arteries. Spontaneous coronary artery dissection (SCAD) is a relatively rare phenomenon, and data on the long-term follow-up of patients with SCAD are extremely limited. Herein, we describe a case of a young male patient with 3-vessel SCAD (presence of radiolucent linear defects indicating the presence of dissections in all three major coronary arteries) who was found to have hyperhomocysteinemia and a concurrent methylenetetrahydrofolate reductase prothrombotic mutation. Despite the presence of multi-vessel SCAD, the patient had clinically stable coronary artery disease for a long period.

Objective Hyperhomocysteinemia (HHcy) and hypertension are associated with cardiovascular events. However, effects of Hcy-lowing interventions on cardiovascular outcome were conflicting. Serum folate level was proposed to be a possible determinant of efficacy of extra folate supplementation on cardiovascular outcome. The aims of the present study were to describe representative information on the levels of serum homocysteine and folate in hypertensive patients, and to explore the major determinants of HHcy. Methods 11,007 participants with hypertension were analyzed in this cross-sectional study. Blood pressure and serum levels of biochemical indicators were measured. Multivariate logistic regression model was used to assess the associated factors of HHcy. Results Geometric mean of serum total homocysteine was 14.1 (95% CI: 13.9, 14.4) μmol/L and prevalence of HHcy was 36.1 (95% CI: 34.0, 38.1) % in hypertensive patients. HHcy was strongly associated with factors including male sex, older age, elevated serum creatinine (SCr), lower serum folate and vitamin B12, and uncontrolled blood pressure in hypertensive patients. Elevated SCr attributed to HHcy with the etiologic fraction of 0.29. The change of the odds ratio of HHcy associated with folate was significantly higher in patients with elevated SCr compared with that of patients with normal SCr. Conclusion The results suggested the protection of female sex and higher levels of folate and vitamin B12 from HHcy and attribution of older age and elevated SCr to HHcy. Restoring renal function deserved attention for hypertensive patients to benefit from Hcy-lowing measures.

Introduction. Among underground miners, the pathology of the cardiovascular system is much more common than among workers on the surface, which indicates the negative role of the impact of harmful production factors. There is evidence of a high prevalence of traditional risk factors for the development of coronary heart disease among miners with dust pathology of the lungs. Preventive measures for coronary heart disease exist for the timely detection and elimination of risk factors. In this regard, it is relevant to optimize methods for predicting the risk of developing coronary heart disease in coal mine workers. The study aims to develop a system for predicting the probability of developing coronary heart disease in miners with anthracosilicosis based on determining the most significant risk factors. Materials and methods. The experts studied the frequency of coronary heart disease and its risk factors in 139 employees of the primary professions of coal mines. The scientists performed daily ECG monitoring, bicycle ergometry according to the Rose questionnaire. They also studied the indicators of lipid metabolism, hemostasis, the level of homocysteine, C-reactive protein, glycemia, the presence of excess body weight, constitutional and morphological types according to Rice-Eysenck and Tanner. The experts developed a predictive system using the Bayes method. We calculated a predictive coefficient for each factor. Scientists determined the probability of coronary heart disease by the value of the sum of prognostic coefficients. Results. Workers aged 45 years and older have the highest risk of developing coronary heart disease. The experience of working in harmful working conditions for 20 years or more, the presence of arterial hypertension, metabolic syndrome, respiratory failure, andromorphic constitutional-morphological type according to the Tanner index, as well as the presence of hyperhomocysteinemia, hyperfibrinogenemia, increased levels of soluble fibrin-monomer complexes and C-reactive protein - all these are the risks of developing coronary heart disease in miners with anthracosilicosis. Conclusions. The developed system of personalized prediction of the probability of developing coronary heart disease in miners with anthracosilicosis allows us to identify a group of high-risk workers for timely treatment and preventive measures for them.

Background Hypertension associated with hyperhomocysteinemia (HHcy) is correlated with a high risk of vascular diseases. Studies found that folic acid (FA) supplementation can reduce the risk of cardiovascular and cerebrovascular events. The aim of the present study was to explore the potential mechanisms of FA attenuating HHcy-related arterial injury in spontaneously hypertensive rats (SHRs). Methods 24 SHRs were randomized into the control group, the HHcy group, and the HHcy + FA group (8 per group). The SHRs in the HHcy group and the HHcy + FA group were given DL-Hcy intraperitoneally to mimic hypertension associated with HHcy. The SHRs in the HHcy + FA group were given FA by gavage to mimic an FA-fortified diet. The histopathology and immunohistochemistry of rat aorta and carotid artery were analyzed, and the relative expression levels of immune/inflammation and oxidative stress molecules in arterial tissue were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot. Results FA significantly reduced the expression levels of nuclear factor-κ-gene binding (NF-κB) p65/Rela and interleukin-6 (IL-6) in rat arterial tissues, as well as the levels of plasma HHcy and serum malondialdehyde (MDA) in hypertension associated with HHcy rats ( p < 0.05). At the same time, FA significantly increased the serum superoxide dismutase (SOD) level in hypertension associated with HHcy rats, and even the SOD level of the HHcy + FA group was higher than that of the control group ( p < 0.05). However, HHcy induced the opposite results of the above indicators in SHRs compared with the control group ( p < 0.05). Conclusions The arterial protection mechanisms of FA are related to reducing the concentration of HHcy to eliminate the tissue toxicity of HHcy, inhibiting NF-κBp65/Rela/IL-6 pathway molecules to regulate inflammatory response, and promoting the potential anti-oxidative stress pathway molecules to reduce oxidative stress level.

The purpose of this study was to evaluate the vitamin B status related to the homocysteine pathway and the prevalence of polymorphisms of the MTHFR gene in infertile women programming homologous or heterologous ART.We investigated 393 consecutive Caucasian women, referred to the Internal Medicine Clinic at the Center for Assisted Reproductive Technology, in order to be framed for their vascular risk before starting homologous or heterologous (oocyte donation) procedures. Total homocysteine, Vitamin B12, folate and vitamin B6 were measured. The women were divided into quartiles of serum concentration of folate, vitamin B12 and vitamin B6. The C677T and A1298C polymorphisms of the MTHFR gene were genotyped by an electronic microchip technology.Sixty-one women (15.5%) had hyperhomocysteinemia, 22.9% had reduced levels of vitamin B12, 4.1% had reduced levels of serum folate and 0.1% had a deficiency of vitamin B6. Women in the highest quartile of vitamin B12 and folates had lower homocysteine ​​levels than women in the first and second quartiles (p 0.0001). The homozygosity for MTHFR C677T polymorphism was detected in 33.3% (131), and heterozygosity for MTHFR C677T polymorphism in 45.3% (178) of women. We observed a significant association between hyperhomocysteinemia and 677T allele, but not 1298C, of the MTHFR polymorphisms (p = 0.04).We found inadequate vitamin B status related to the homocysteine ​​pathway in women planning Assisted Reproductive Technology. Moreover, interesting association was found regarding hyperhomocysteinemia in women carrying T allele of the C677T MTHFR polymorphism. A specific supplementation with 5-MTHF and adequate vitamin B12 concentrations before Assisted Reproductive Technology warrant serious consideration, in particular in women carrying T allele of the C677T MTHFR polymorphism.

The aim of the study was to analyze the microvasculation of the liver in administration of tautomeric forms of orotic acid for a methionine-induced liver pathology to assess the efficacy of the modified drugs and the potentialof their clinical use.Material and methods. The study included 30 white outbred rats, that were simulated methionine induced hyperhomocysteinemia by the administration of methionine, dosage 0.15 g/100 g of the body we ight, via food during 4 weeks. Animals with hyperhomocysteinemia were divided into 4 groups: animals of group 1 received orotic acid (OA) in the initial form (oxo-tautomer), animals of group 2 received hydroxy–tautomer OA after mechanomodification for 1 hour, animals of group 3 received dihydroxy-tautomer OA after mechanomodification for 6 hours. Histological preparations of the liver were used to evaluate the area of hepatocytes; diameters and areas of the central vein, the interlobular vein and artery, the bile duct, and the Visotto coefficient were calculated.Results. Morphometric data of the hepatic microvascular bloodstream with simulated hyperhomocysteinemia evidenced a general increase in the diameter and area of blood vessels, changes affected the system of blood inflow and outflow at the organ level. Administration of OA had a normalizing effect on the liver bloodflow, but the effects were different: the most pronounced effect was detected in administration of the hydroxy-form of the preparation, this can be explained by a modificationin the dispersion of the preparation (without changing the crystal lattice), an increase in the rate of dissolution in water and aqueous solutions, an increasein the number of functionally active groups in the heterocycle of the hydroxy-form of OA. Thus, the hydroxy-tautomer of orotic acid had the greatest efficacy relating to vasodilation of microvessels of the liver bloodstream in hyperhomocysteinemia; the fact suggesting feasibility of its further study in the clinical environment.

Homocysteine (Hcy) is an excitatory amino acid that contains thiol group and derives from the methionine metabolism. It increases vulnerability of the neuronal cells to excitotoxic and oxidative damage. This study aimed to investigate the hyperhomocysteinemia (hHcy) effects on rat cerebellum and the possible protective role of quercetin administration in Hcy-treated rats, using behavioral and biochemical analyzes. To this end, the adult male rats were divided randomly into the control group that received vehicle, Hcy group received Hcy (400 μg/kg), Hcy + Que group received Hcy + quercetin (50 mg/kg), quercetin group received quercetin for 14 days. On Day 14 after the final treatment, lipid peroxidation level, the superoxide dismutase (SOD), and glutathione peroxidase (GPx) activities were evaluated in the cerebellum. After completion of treatment, the rat’s performance on rotarod and locomotor activity was evaluated. The results showed that Hcy treatment elicited cerebellar lipid peroxidation, impaired locomotor activity and increased latency to fall on the rotarod. Quercetin failed to attenuate significantly motoric impairment, increased significantly the cerebellar lipid peroxidation and GPx activity in the Hcy + Que group. Our results suggest that Hcy induced cerebellar toxicity and quercetin had no significant protective effects against Hcy toxicity in the cerebellum of adult rats.

Introduction. Prolonged exposure to coal-rock dust affects the formation of the pathology of the bronchopulmonary and cardiovascular systems. Pneumoconiosis occupies one of the leading places among occupational diseases. On the other hand, arterial hypertension occupies a top place among production-related diseases. Timely identification and correction of traditional and professional risk factors is a main point in preventing diseases of the circulatory system in workers in harmful working conditions. Thus, identifying the most significant risk factors for the development of arterial hypertension of miners with anthracosilicosis is an urgent task. The study aims to identify the most significant professional and non-professional risk factors for the development of arterial hypertension in miners with anthracosilicosis. Materials and methods. We examined 269 miners working in underground dust conditions: 139 miners with a previously established diagnosis of anthracosilicosis and 130 miners of the control group without dust pathology of the lungs. The researchers conducted a comprehensive laboratory and clinical and instrumental examination to detect arterial hypertension and risk factors for the development of cardiovascular pathology. Results. Arterial hypertension among miners with anthracosilicosis is two times more common (42.4%) than in the control group (20.8%). Miners aged 50 years and older have the greatest risk of developing arterial hypertension. Also, the presence of fasting hyperglycemia, hyperhomocysteinemia, abdominal type of obesity, hypersthenic constitutional-morphological type according to the Rice–Eysenck index, blood group AB (IV). We identified professional risk factors for the development of arterial hypertension: work experience in harmful working conditions of 25 years or more, the level of the dustiness of the active area exceeding the maximum permissible concentrations by ten or more times. Conclusions. In coal mine workers with anthracosilicosis, arterial hypertension is more common than in the control group, which may indicate that this occupational pathology is an independent risk factor for the development of arterial hypertension. Scientists identified the most significant professional and non-professional risk factors, the elimination of which will reduce the likelihood of developing arterial hypertension in miners with anthracosilicosis.

One-carbon metabolism is crucial for the maintenance of healthy pregnancy and alterations in this pathway have been associated with various pregnancy-related complications. Therefore, the present study was conducted to test the hypothesis that the altered folic acid, vitamin B12 and homocysteine levels are associated with the risk of early pregnancy loss (EPL). Plasma folic acid, vitamin B12 and homocysteine levels were analyzed in 83 females with EPL and 70 healthy pregnant females in their first trimester. Further, meta-analyses of folic acid, vitamin B12 and homocysteine were also performed involving various eligible studies. Results from our case-control study and meta-analysis showed that folic acid deficiency is not associated with the risk of EPL. On the other hand, low vitamin B12 and hyperhomocysteinemia were individually found to be significant risk factors for EPL in the present study (P.01, P.05, respectively) and meta-analysis as well (P.001, P.05, respectively). Vitamin B12 deficiency in combination with hyperhomocysteinemia was a more serious risk factor for EPL (Odds Ratio = 4.98, P = 0.002). Therefore, we conclude that vitamin B12 deficiency and elevated homocysteine levels are independent risk factors for EPL, and of higher risk when combined. The assessment of vitamin B12 and homocysteine levels may serve as a good screening marker for EPL risk.

Background/purpose Our previous study found that 222 of 884 burning mouth syndrome (BMS) patients have thyroglobulin antibody (TGA) positivity and/or thyroid microsomal antibody (TMA) positivity but without gastric parietal cell antibody positivity (GPCAˉTGA+/TMA+BMS patients). This study mainly assessed whether the serum TGA/TMA positivity was significantly associated with anemia, hematinic deficiencies, and hyperhomocysteinemia in GPCAˉTGA+/TMA+BMS patients. Materials and methods The complete blood count, iron, vitamin B12, folic acid, and homocysteine levels were measured and compared between 222 GPCAˉTGA+/TMA+BMS patients and 553 GPCA-negative, TGA-negative, and TMA-negative BMS patients (GPCAˉTGAˉTMAˉBMS patients) or 442 healthy control subjects. Results We found that 222 GPCAˉTGA+/TMA+BMS patients had significantly lower mean corpuscular volume (MCV) and lower blood Hb and serum iron levels than 442 healthy control subjects and significantly lower MCV and lower serum homocysteine levels than 553 GPCAˉTGAˉTMAˉBMS patients. Moreover, 222 GPCAˉTGA+/TMA+BMS patients had significantly greater frequencies of microcytosis, macrocytosis, blood Hb and serum iron deficiencies, and hyperhomocysteinemia than 442 healthy control subjects and significantly higher frequency of microcytosis but significantly lower frequency of hyperhomocysteinemia than 553 GPCAˉTGAˉTMAˉBMS patients. However, no significant differences in the frequencies of macrocytosis, blood Hb, serum iron, vitamin B12, and folic acid deficiencies were discovered between 222 GPCAˉTGA+/TMA+BMS patients and 553 GPCAˉTGAˉTMAˉBMS patients. Conclusion We conclude that the disease of BMS itself does play a significant role in causing macrocytosis, anemia, hematinic deficiencies, and hyperhomocysteinemia in GPCAˉTGA+/TMA+BMS patients. However, the serum TGA/TMA-positivity is not significantly associated with anemia and serum iron, vitamin B12, and folic acid deficiencies in GPCAˉTGA+/TMA+BMS patients.

Homocysteine (Hcy) is considered as a modifiable risk factor for vascular disease. This study was aimed to explore the association between serum concentration and the severity of primary chronic venous disease (CVD).Clinical data of 582 patients diagnosed with primary CVD were collected and analyzed retrospectively. The Clinical Etiology Anatomy Pathophysiology classification system was used to grade the severity of chronic venous disease. Patients were divided into 2 groups (group A: C1-C3; group B: C4-C6). The association between serum homocysteine levels and the severity of primary chronic venous disease was investigated using rank sum test and logistic regression.The difference between the level of homocysteine in each grade has statistical significance. Group A has higher median Hcy concentrations than Group B (15.40 μmol/L vs. 14.05 μmol/L, P0.01). Further binary logistic regression showed no statistical significance among the level of Hcy (11.00-14.75 μmol/L [OR 0.66, 95% CI 0.40-1.11, P= 0.12], 14.75-20.38μmol/L [OR 0.97, 95% CI 0.59-1.69, P = 0.89], ≥20.38 μmol/L [OR 0.67, 95% CI 0.41-1.10, P = 0.11]), but age (OR 1.03, 95% CI 1.01-1.04, P0.01) and female (OR 0.41, 95% CI 0.28-0.59, P0.01) are associated with more severe stages of CVD.Higher level of Hcy is associated with more severe stages of CVD, but it not an independent risk factor. However, Advanced age and female are risk factors for CVD development based on logistic regression analysis.

Annotation. Defeat of the respiratory system is a common phenomenon in today's conditions. Elevated levels of homocysteine (Hz) are one of the predictors of bronchopulmonary pathology. In recent years, there has been an association between its concentration in blood plasma and the risk of developing COPD, bronchial asthma, lung cancer. The pathogenesis of respiratory damage in hyperhomocysteinemia (GHz) is still being studied, but it is known to be the cause of endothelial dysfunction, oxidative stress, endoplasmic reticulum stress, which underlie lung tissue damage. The aim of the study is to establish a comparative characterization of histological changes in the lung tissue of rats of different ages at GHz. The experimental study was performed on 64 white nonlinear male rats. During the experiment, the animals were divided into two groups – control and experimental, each of which is divided into subgroups depending on age – young (1-2 months), mature (6-8 months), old (24-26 months). Simulation of the stable GHz state was achieved by administering to rats the experimental group thiolactone Hz at a dose of 200 mg/kg body weight intragastrically for 60 days. Histological specimens were studied using an SEO CCAN light microscope and photo-documented using a Vision CCD Camera with an image output system from histological specimens. Histological examinations of the lungs of young animals under GHz conditions revealed moderate destructive changes of vessels, bronchi, components of the respiratory department, which were compensatory-adaptive and reversible. Adaptive-compensatory and destructive changes of the organ were found in adult rats at experimental GHz. Older animals develop the most significant destructive-degenerative changes compared with studies of the lungs of groups of young and mature rats. The defining feature for this age group was excessive activation of fibroblasts and the development of perivascular, peribronchial, interstitial sclerosis.

The new coronavirus infection COVID-19 has highlighted the importance of ongoing support for innate antiviral immunity systems. The aim. Conduct a systematic review of publications on the research of the use of B vitamins to support immunity and rehabilitation of patients with COVID-19. Methods. Intelligent analysis of so-called Big Data and special computational methods for analyzing Big Data of biomedical publications, based on the topological theory of sentiment analysis of medical texts from PubMed/MEDLINE. Results. Low levels of B vitamins contribute to chronic comorbidities and aggravate the clinical course of COVID-19 significantly. Increasing the supply of B vitamins in COVID-19 patients is essential for the maintenance of energy and oxygen metabolism; the direct antiviral effects of vitamins (reduction of SARS-CoV-2 replication); compensation of chronic comorbidities (thromboembolism, impaired liver and kidney functions, diabetes mellitus, polyneuropathy), which aggravate the course of COVID-19; reducing hyperhomocysteinemia and chronic aseptic inflammation; inhibiting carbonic anhydrases to improve oxygen metabolism in the lungs, and increasing the clearance of lactate from the blood and preventing sepsis. Conclusion. By improving myelination of the olfactory sensory neurons, vitamin B 12 can help overcome anosmia, which occurs in 80% of COVID-19 patients. Short courses (up to 2 – 3 weeks) of high-dose parenteral therapy with thiamine, pyridoxine, and cyanocobalamin can be used as a part of a complex of therapeutic measures to improve clinical outcomes in patients with COVID-19, especially in elderly patients with polyhypovitaminosis, diabetes mellitus, hyperhomocysteinemia, thrombophilia, and high risk of sepsis. Oral therapy with thiamine, pyridoxine, and cyanocobalamin is justified as a part of rehabilitation measures after COVID-19 in patients who have faced its consequences in the form of clinical signs of vitamin B vitamin deficiency.

Background: Alzheimer’s disease (AD) may be a vascular disorder with neurodegenerative consequences opening possibility of preventing AD by targeting vascular risk factors including homocysteine. Objective: The study aims were to assess homocysteine distribution in different forms and severity of cognitive impairment (CogI) [mild cognitive impairment (MCI), probable AD (Prob-AD), possible AD (Poss-AD), and vascular dementia (VaD)] and in NoCogI, and to estimate possible association between hyperhomocysteinemia levels with functional deficit severity and psychobehavioral complications. Methods: In total, 929 (M = 366, F = 563; mean age of 72.55±6.24 years) patients were evaluated with cognitive, neuropsychiatric, affective, and functional assessment scales. Homocysteine serum was set on two levels: between 0 and 10μmol/L and > 10μmol/L. For each patient, blood concentration of folate, vitamin B12, hemoglobin, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), cholesterol, triglycerides, and glycemia were measured. Results: CogI patients demonstrated significantly a higher frequency of homocysteine > 10 (p = 0.003), than NoCogI patients. Patients with moderate and severe dementia had a higher frequency of homocysteine > 10 (p 10 (p = 0.003), than Prob-AD patients. Homocysteine > 10 frequency is directly proportional to increased neuropsychiatric symptom severity (p

Resume Introduction La maladie thromboembolique veineuse a une incidence de 1,57/1000. Chez les patients de moins de 50 ans, le bilan de thrombophilie est realise, dont les indications sont de plus en plus strictes. La place du dosage de l’homocysteine plasmatique est incertaine. Observation Notre cas est un patient de 42 ans ayant une embolie pulmonaire, associee a une macrocytose, nous faisant decouvrir une carence en B12 secondaire a une maladie de Biermer. Dans la litterature, les patients sont principalement des hommes, ayant un âge moyen limite a la realisation du bilan de thrombophilie. Tous ces patients n’avaient pas d’autres etiologies que l’hyperhomocysteinemie secondaire a une maladie de Biermer. La prise en charge est peu detaillee. Conclusion L’hyperhomocysteinemie n’est probablement pas le seul facteur thromboembolique. Le patient a beneficie d’une anticoagulation et d’une supplementation en cobalamine. Une bonne lecture de la NFS est un point essentiel.

The article presents current views on maternal hyperhomocysteinemia (HHcy) as an important factor causing prenatal stress and impaired nervous system development in fetuses and newborns in early ontogenesis, as well as complications in adulthood. Experimental data demonstrate that prenatal HHcy (PHHcy) affects the morphological maturation of the brain and activity of its neurotransmitter systems. Cognitive deficit observed in the offspring subjected to PHHcy in experimental studies can presumably cause the predisposition to various neurodegenerative diseases, as the role of maternal HHcy in the pathogenesis such diseases has been proven in clinical studies. The review also discusses molecular mechanisms of the HHcy neurotoxic action on the nervous system development in the prenatal and early postnatal periods, which include oxidative stress, apoptosis activation, changes in the DNA methylation patterns and microRNA levels, altered expression and processing of neurotrophins, and neuroinflammation induced by an increased production of pro-inflammatory cytokines. Special attention is given to the maternal HHcy impact on the placenta function and its possible contribution to the brain function impairments in the offspring. Published data suggest that some effects of PHHcy on the developing fetal brain can be due to the disturbances in the transport functions of the placenta resulting in an insufficient supply of nutrients necessary for the proper formation and functioning of brain structures.

Stroke is a common neurological emergency. Almost 80% of strokes are due to arterial occlusion. Venous thrombosis comprises less than 1–2% of all strokes. Involvement of the deep cerebral venous system is still rare and accounts for about 10.9% of all cerebral venous thromboses (CVT). CVT diagnosis is often delayed or missed, because of its variable clinical manifestations. We retrospectively (2015–18) and prospectively (2018–20) reviewed all the cases of CVT in a tertiary care center in south India. Out of a total of 52 CVT cases, 12 were due to the involvement of deep cerebral venous system. Their clinical presentation, imaging characteristics, and outcomes were assessed. The most frequent presentation was headache followed by seizures. Hyperhomocysteinemia was the most common risk factor noted. Imaging characteristics were variable, and a high index of suspicion was required for early diagnosis. All patients had favorable outcome in our study, and except one, all were treated conservatively.

Ligustrazine, an alkaloid extracted from the traditional Chinese herbal medicine Ligusticum Chuanxiong Hort, has been clinically applied to treat the cerebrovascular diseases. Hyperhomocysteinemia (Hhcy) is an independent risk factor for Alzheimer's disease (AD). Memory deficits can be caused by Hhcy via pathologies of AD-like tau and amyloid-β (Aβ) in the hippocampus. Here, we investigated whether homocysteine (Hcy) can induce AD-like pathologies and the effects of ligustrazine on these pathologies. The Hcy rat model was constructed by 14-day Hcy injection via vena caudalis, and rats were treated with daily intragastric administration of ligustrazine at the same time. We found that the pathologies of tau and Aβ were induced by Hcy in the hippocampus, while the Hcy-induced tau hyperphosphorylation and Aβ accumulation could be markedly attenuated by simultaneous ligustrazine treatment. Our data demonstrate that ligustrazine may be used as a promising neuroprotective agent to treat the Hcy-induced AD-like pathologies.