Репозиторий Университета

© 2019 The Author(s). Background: Cobalamin metabolism disorders are rare, inherited diseases which cause megaloblastic anaemia and other clinical manifestations. Early diagnosis of these conditions is essential, in order to allow appropriate treatment as early as possible. Case presentation: Here we report the case of a patient who was apparently healthy until the age of 20, when she presented with impaired renal function and normocytic anaemia. At the age of 34, when her first pregnancy resulted in an intrauterine death of a morphologically normal growth-restricted foetus, she was diagnosed with homocystinuria and methylmalonic aciduria due to cyanocobalamin C (cblC) defect, which was confirmed by molecular investigation. Consequently, hydroxocobalamin was administered to correct homocysteine plasma levels. This treatment was efficacious in lowering homocysteine plasma levels and restored anaemia and renal function. During a second pregnancy, the patient was also administered a prophylactic dose of low molecular -weight heparin. The pregnancy concluded with a full-term delivery of a healthy male. Conclusions: This case emphasises the importance of awareness and appropriate management of rare metabolic diseases during pregnancy. We suggest that women with late-onset cblC defect can have a positive pregnancy outcome if this metabolic disease is treated adequately.

© 2019 Elsevier B.V. A validated approach to determine various methionine cycle metabolites (S-adenosylmethionine, S-adenosylhomocysteine, and methylthioadenosine) in human blood plasma is offered. The approach is based on solid-phase extraction (with grafted phenylboronic acid) and derivatization with chloroacetaldehyde followed by ultra-performance liquid chromatography with fluorescence detection. We used a 100 × 2.1 mm × 1.8 μm C18 column for the selective separation of analytes. Chromatographic separation was achieved with gradient elution of acetonitrile (flow rate 0.2 mL/min) from 2 to 20%. The eluent was initially composed of 10 mM KH2PO4 with 10 mM acetic acid and 25 μM heptafluorobutyric acid. The total analysis time was 11 min. Validation of the method included detection of the limit of detection (2 nM), limit of quantification (5 nM), accuracy (97.2–101%), and intra- and interday precision (2.2–9.0%). Analysis of plasma samples from healthy volunteers revealed that the average levels of S-adenosylmethionine, S-adenosylhomocysteine, and methylthioadenosine were 93.6, 20.9 and 14.8 nM, respectively.

© 2019, Springer Science+Business Media, LLC, part of Springer Nature. A model of moderate hyperhomocysteinemia associated with mechanical injury of the musculoskeletal system was developed and experimentally substantiated. The adequacy of this model for studies of morphological and functional regularities is verified. This model can be used for the development of a new concept of evaluation of thrombotic complications of mechanical injury.

© 2018 Vserossiiskoe Obshchestvo Kardiologov. All rights reserved. Aim. Assessment of the markers levels of endothelial dysfunction (ED): stable metabolites of nitric oxide (NOx), endothelin-1 (E1), homocysteine (HC), von Willebrand factor (vWF) and tissue plasminogen activator (tPA) in blood plasma of smoker and nonsmoker patients with arterial hypertension (AH) of low and moderate risk, not taking antihypertension therapy regularly. Material and methods. Totally, 124 AH patients included, 45 males and 79 females, mean age 51,4±6,5 y. O., mean AH duration 7,9±7,3 y. Controls included 35 healthy volunteers (20 males, 15 females). Concentration of NOx in plasma was measured with spectrophotometry, and of vWF, HC, E1 and tPA-with immune enzyme assay. Results. To evaluate the relation of smoking and ED markers levels, AH patients and controls were selected to subgroups according to smoking status: smoker (35,5%) and non-smoker (64,5%) AH patients; smoker (38%) and non-smoker (62%) controls. In smoker AH patients comparing to non-smoking there were significantly higher concentrations of NOx-48,2±18,8 mcM/L and 40,3±21,2 mcM/L, respectively (p<0,05), E1-1,2±0,16 and 0,6±0,2 fM/L, resp. (p<0,05), HC-25,7±6,04 and 16,2±6,5 mcM/L, resp. (p<0,05), vWF-1,39±0,7 and 1,1±0,6 mg/dL, resp (p<0,05) and tPA-13,05±6,2 and 8,5±6,2 mcM/L, resp. (p<0,05). There was correlation in the AH group, of NOx concentration and smoking (r=0,46, p<0,05), and tobacco smoking duration (r=0,83, p<0,05). Also, there were positive correlations of HC and smoking (r=0,4, p<0,05). In control group smokers had higher HC-20,7±5,3 and 17,2±4,7 mcM/L, resp. (p<0,05), vWF-1,3±0,8 and 0,8±0,6 mg/dL, resp. (p<0,05) and tPA-11,1±6,5 and 6,6±5,2 mcM/L, resp. (p<0,05). There were no significant changes in NOx and E1. Conclusion. In smokers of both AH and control groups the levels of HC, vWF and tPA were significantly higher in comparison with nonsmokers. In smoker AH patients the mean concentrations of NOx and E1 are higher than in non-smoker patients. Levels of ED are related with not only the fact of smoking itself (p<0,05), but smoking duration (p<0,05).

© 2018, Canadian Science Publishing. All rights reserved. The aim of this study was to assess the impact of atorvastatin and simvastatin on myocardial contractility during the different degrees of hyperhomocysteinemia (HHcy) in rats. Study was conducted on adult male Wistar albino rats (n = 90; 4 weeks old; 100 ± 15 g body mass) in which HHcy was achieved by dietary manipulation. Animals were exposed to pharmacology treatment with atorvastatin in dose of 3 mg/kg per day i.p. or simvastatin in dose of 5 mg/kg per day i.p. at the same time every day, according to equivalent therapeutic doses of these statins (10 mg atorvastatin = 20 mg simvastatin). After the dietary manipulation and pharmacological treatment and confirmation of HHcy, all animals were sacrificed, hearts were isolated, and cardiac function was tested according to the Langendorff technique. Size of recovery of maximum rate of left ventricular development (dp/dtmax), minimum rate of left ventricular development (dp/dtmin), systolic left ventricular development, diastolic left ventricular development, heart rate, and coronary flow at the 40, 60, 80, 100, and 120 cmH2O coronary perfusion pressure were measured in state of physiological condition (homocysteine less than 15 μmol/L), mild HHcy, and moderate HHcy. Atorvastatin treatment significantly attenuated homocysteine-induced impairment of myocyte contractility and dominantly decreased dp/dtmax, dp/dtmin, and heart rate and induced greater changes in systolic left ventricular development compared with simvastatin. Treatment with atorvastatin seems able to revert systolic abnormalities and improve contractility during the different degrees of HHcy.

© 2018, Canadian Science Publishing. All rights reserved. Homocysteine, an amino acid containing a sulfhydryl group, is an intermediate product during metabolism of the amino acids methionine and cysteine. Hyperhomocysteinemia is used as a predictive risk factor for cardiovascular disorders, the stroke progression, screening for inborn errors of methionine metabolism, and as a supplementary test for vitamin B12 deficiency. Two organic systems in which homocysteine has the most harmful effects are the cardiovascular and nervous system. The adverse effects of homocysteine are achieved by the action of several different mechanisms, such as overactivation of N-methyl-D-aspartate receptors, activation of Toll-like receptor 4, disturbance in Ca2+ handling, increased activity of nicotinamide adenine dinucleotide phosphate-oxidase and subsequent increase of production of reactive oxygen species, increased activity of nitric oxide synthase and nitric oxide synthase uncoupling and consequent impairment in nitric oxide and reactive oxygen species synthesis. Increased production of reactive species during hyperhomocysteinemia is related with increased expression of several proinflammatory cytokines, including IL-1α, IL-6, TNF-α, MCP-1, and intracellular adhesion molecule-1. All these mechanisms contribute to the emergence of diseases like atherosclerosis and related complications such as myocardial infarction, stroke, aortic aneurysm, as well as Alzheimer disease and epilepsy. This review provides evidence that supports the causal role for hyperhomocysteinemia in the development of cardiovascular disease and nervous system disorders.

© 2017, Springer Science+Business Media, LLC. Considering the well-known antioxidant properties of statins, it seems important to assess their impact on major markers of oxidative stress (superoxide anion radical, nitric oxide, and index of lipid peroxidation) to compare the antioxidative potentials of atorvastatin and simvastatin during the different degrees of hyperhomocysteinemia (HHcy) in rats. This study was conducted on adult male Wistar albino rats (n = 90; 4 weeks old; 100 ± 15 g body mass) in which HHcy was achieved by dietary manipulation. For 4 weeks, the animals were fed with one of the following diets: standard rodent chow, diet enriched in methionine with no deficiency in B vitamins (folic acid, B6, and B12), or diet enriched in methionine and deficient in B vitamins (folic acid, B6, and B12). At the same time, animals were treated with atorvastatin at doses of 3 mg/kg/day i.p. or simvastatin at doses of 5 mg/kg/day i.p. Levels of superoxide anion radical and TBARS were significantly decreased by administration of simvastatin in normal and high-homocysteine (Hcy) groups (p < 0.05). At 4 weeks after feeding with purified diets, the concentrations of the GSH, CAT, and SOD antioxidants were significantly affected among all groups (p < 0.05). Our results indicated that statin therapy had variable effects on the redox status in hyperhomocysteinemic rats, and simvastatin demonstrated stronger antioxidant effects than did atorvastatin.

© 2018 by the Serbian Biological Society. The aim of this study was to assess the effects of DL-homocysteine (DL-Hcy) and DL-homocysteine thiolactone (DL-Hcy TLHC) on selected serum biochemical parameters, markers of oxidative stress and the activities of antioxidant enzymes (catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD)) in the plasma, as well as on acetylcholinesterase (AChE) activity in the cardiac tissue homogenate in the rat. Male Wistar rats were divided into three groups as follows: control group (1 mL 0.9% NaCl, intraperitoneal (i.p.) injection), DL-Hcy group (8 mmol/kg body mass (b.m.), i.p.) or DL-Hcy TLHC group (8 mmol/kg b.m., i.p.). One hour after administration, the rats were euthanized, whole blood was collected for biochemical analysis, and the heart was excised. Following the i.p. administration of DL-Hcy and DL-Hcy TLHC, the activities of antioxidant enzymes were mostly significantly increased, while plasma malondialdehyde (MDA) was decreased. Administration of DL-Hcy and DL-Hcy TLHC significantly inhibited AChE activity in rat cardiac tissue. Our findings suggest that DL-Hcy and DL-Hcy TLHC exerted prooxidant effects; however, the decrease in MDA points to an inverse response to the increase in antioxidant enzyme activities. While both substances inhibited AChE activity in rat cardiac tissue, DL-Hcy TLHC induced stronger effects than DL-Hcy.

Considering the well-known antioxidant properties of statins, it seems important to assess their impact on major markers of oxidative stress (superoxide anion radical, nitric oxide, and index of lipid peroxidation) to compare the antioxidative potentials of atorvastatin and simvastatin during the different degrees of hyperhomocysteinemia (HHcy) in rats. This study was conducted on adult male Wistar albino rats (n = 90; 4 weeks old; 100 ± 15 g body mass) in which HHcy was achieved by dietary manipulation. For 4 weeks, the animals were fed with one of the following diets: standard rodent chow, diet enriched in methionine with no deficiency in B vitamins (folic acid, B6, and B12), or diet enriched in methionine and deficient in B vitamins (folic acid, B6, and B12). At the same time, animals were treated with atorvastatin at doses of 3 mg/kg/day i.p. or simvastatin at doses of 5 mg/kg/day i.p. Levels of superoxide anion radical and TBARS were significantly decreased by administration of simvastatin in normal and high-homocysteine (Hcy) groups (p < 0.05). At 4 weeks after feeding with purified diets, the concentrations of the GSH, CAT, and SOD antioxidants were significantly affected among all groups (p < 0.05). Our results indicated that statin therapy had variable effects on the redox status in hyperhomocysteinemic rats, and simvastatin demonstrated stronger antioxidant effects than did atorvastatin.

Considering the well-known antioxidant properties of statins, it seems important to assess their impact on major markers of oxidative stress (superoxide anion radical, nitric oxide, and index of lipid peroxidation) to compare the antioxidative potentials of atorvastatin and simvastatin during the different degrees of hyperhomocysteinemia (HHcy) in rats. This study was conducted on adult male Wistar albino rats (n = 90; 4 weeks old; 100 ± 15 g body mass) in which HHcy was achieved by dietary manipulation. For 4 weeks, the animals were fed with one of the following diets: standard rodent chow, diet enriched in methionine with no deficiency in B vitamins (folic acid, B6, and B12), or diet enriched in methionine and deficient in B vitamins (folic acid, B6, and B12). At the same time, animals were treated with atorvastatin at doses of 3 mg/kg/day i.p. or simvastatin at doses of 5 mg/kg/day i.p. Levels of superoxide anion radical and TBARS were significantly decreased by administration of simvastatin in normal and high-homocysteine (Hcy) groups (p < 0.05). At 4 weeks after feeding with purified diets, the concentrations of the GSH, CAT, and SOD antioxidants were significantly affected among all groups (p < 0.05). Our results indicated that statin therapy had variable effects on the redox status in hyperhomocysteinemic rats, and simvastatin demonstrated stronger antioxidant effects than did atorvastatin.