Diabetic Nephropathy: Significance of Determining Oxidative Stress and Opportunities for Antioxidant Therapies.

Diabetes mellitus (DM) belongs to the category of socially significant diseases with epidemic rates of increases in prevalence. Diabetic nephropathy (DN) is a specific kind of kidney damage that occurs in 40% of patients with DM and is considered a serious complication of DM. Most modern methods for treatments aimed at slowing down the progression of DN have side effects and do not produce unambiguous positive results in the long term. This fact has encouraged researchers to search for additional or alternative treatment methods. Hyperglycemia has a negative effect on renal structures due to a number of factors, including the activation of the polyol and hexosamine glucose metabolism pathways, the activation of the renin-angiotensin-aldosterone and sympathetic nervous systems, the accumulation of advanced glycation end products and increases in the insulin resistance and endothelial dysfunction of tissues. The above mechanisms cause the development of oxidative stress (OS) reactions and mitochondrial dysfunction, which in turn contribute to the development and progression of DN. Modern antioxidant therapies for DN involve various phytochemicals (food antioxidants, resveratrol, curcumin, alpha-lipoic acid preparations, etc.), which are widely used not only for the treatment of diabetes but also other systemic diseases. It has also been suggested that therapeutic approaches that target the source of reactive oxygen species in DN may have certain advantages in terms of nephroprotection from OS. This review describes the significance of studies on OS biomarkers in the pathogenesis of DN and analyzes various approaches to reducing the intensity of OS in the prevention and treatment of DN.

Receiver Operator Characteristic (ROC) Analysis of Lipids, Proteins, DNA Oxidative Damage, and Antioxidant Defense in Plasma and Erythrocytes of Young Reproductive-Age Men with Early Stages of Type 1 Diabetes Mellitus (T1DM) Nephropathy in the Irkutsk Region, Russia.

Oxidative stress plays a leading role in the pathogenesis of diabetic nephropathy. However, many aspects of oxidative stress reactions in the initial stages of this disease are not fully understood. The men cohort is of particular interest because of the severe effects of diabetes on their urogenital system. The aim of this study is to assess the intensity of lipids, proteins, DNA oxidative damage, blood antioxidant defense enzymatic, and activity of non-enzymatic components in men with type 1 diabetes mellitus (T1DM) in the early stages of diabetic nephropathy using receiver operator characteristic (ROC) analysis. This study included eighty-nine reproductive-age men in the initial stages of diabetic nephropathy (DN) and thirty-nine age- and sex-matched individuals not suffering from glycemic disorders. The DN patients were divided into two subgroups: stage 1 patients (urinary albumin < 30 mg/day and albumin/creatinine ratio < 3 mg/mmol (n = 45)) and stage 2 patients (urinary albumin 30−300 mg/day and albumin/creatinine ratio 3−30 mg/mmol (n = 44)). Levels of oxidative damage products (conjugated dienes (CDs), thiobarbituric acid reactants (TBARs), methylglyoxal (MGO), and 8-hydroxy-2'-deoxyguanosine (8-OHdG)) and antioxidants (glutathione peroxidase (GPx), glutathione S-transferases π (GSTp), glutathione reductase (GR), copper and zinc-containing superoxide dismutase 1 (SOD-1), total antioxidant status (TAS), α-tocopherol, retinol, reduced glutathione (GSH), and oxidative glutathione (GSSG)) were estimated in plasma and erythrocytes. Oxidative damage to cellular structures (higher values of median CDs (1.68 µmol/L; p = 0.003), MGO (3.38 mg/L; p < 0.001) in the stage 1 group and CDs (2.28 µmol/L; p < 0.0001), MGO (3.52 mg/L; p < 0.001), 8-OHdG (19.44 ng/mL; p = 0.010) in the stage 2 group) and changes in the antioxidant defense system (lower values of TAS (1.14 units; p = 0.011), α-tocopherol (12.17 µmol/L; p = 0.009), GPx (1099 units; p = 0.0003) and elevated levels of retinol (1.35 µmol/L; p < 0.001) in the group with stage 1; lower values of α-tocopherol (12.65 µmol/L; p = 0.033), GPx (1029.7 units; p = 0.0001) and increased levels of GR (292.75 units; p < 0.001), GSH (2.54 mmol/L; p = 0.010), GSSG (2.31 mmol/L; p < 0.0001), and retinol (0.81 µmol/L; p = 0.005) in the stage 2 group) were identified. The ROC analysis established that the following indicators have the highest diagnostic significance for stage 1 diabetic nephropathy: CDs (AUC 0.755; p < 0.0001), TBARs (AUC 0.748; p = 0.0001), MGO (AUC 0.720; p = 0.0033), retinol (AUC 0.932; p < 0.0001), GPx (AUC 0.741; p = 0.0004), α-tocopherol (AUC 0.683; p = 0.0071), and TAS (AUC 0.686; p = 0.0052) and the following for stage 2 diabetic nephropathy: CDs (AUC 0.714; p = 0.001), TBARs (AUC 0.708; p = 0.001), 8-OHdG (AUC 0.658; p = 0.0232), GSSG (AUC 0.714; p = 0.001), and GSH (AUC 0.667; p = 0.0108). We conclude that changes in indicators of damage to lipids, proteins, DNA, and the insufficiency of antioxidant defense factors already manifest in the first stage of diabetic nephropathy in men with T1DM. The ROC established which parameters have the greatest diagnostic significance for stages 1 and 2 of diabetic nephropathy, which may be utilized as additional criteria for defining men with T1DM as being in the risk group for the development of initial manifestations of the disease and thus allow for substantiating appropriate approaches to optimize preventive measures.

Detailed dynamics of direct three-body recombination of singly charged ions.

We consider the main aspects of detailed dynamics of the reactions of direct three-body ion-ion recombination Cs+ + X- + R → CsX + R (X- = F-, I- and R = Ar, Xe) for non-central encounters of the ions. The reactions are simulated by the quasiclassical trajectory method using diabatic semiempirical potential energy surfaces proposed previously. The recombination mechanisms are studied via visualization of randomly selected trajectories for each of the four systems. Comparison of trajectories for different systems with identical sets of initial conditions is carried out. For most of the presented trajectories, the ion encounter energy and the third body energy are equal to 1 eV. The characteristic function of recombination is defined, this function depends on 13 arguments including eight kinematic parameters. It is shown that the transfer of excess energy from the ion pair to the neutral atom can occur, in particular, via an encounter of the R atom with the Cs+ ion, via an encounter of the R atom with the X- ion, or via successive encounters of the R atom with both the ions, as well as via an "insertion" of the R atom between the ions.

Sleep Apnea and Serum Serotonin Level Pre- and Post-PAP Therapy: A Preliminary Study.

INTRODUCTION: The high prevalence of obstructive sleep apnea (OSA), which impairs quality of life for numerous patients and leads to various OSA complications, has contributed to the continued interest in this disorder. The role of serotonin (5-HT) in many physiological processes, studies on its connection with the circadian system, and relationship to changes in sleep architecture are insufficient to assess the interaction of this neurotransmitter with nocturnal hypoxia. The aim of this study was to determine changes in sleep patterns and serum serotonin levels before and after positive airway pressure (PAP) therapy in patients with OSA. METHODS: The study involved 30 OSA patients (27 men and 3 women) who were treated with PAP for 3 months. Polysomnography using the GRASS TELEFACTOR (USA) and blood collection were conducted before and after PAP courses. Determination of serum serotonin was performed by high-performance liquid chromatography (HPLC). PAP therapy was performed using an automatic Prisma 20A (Germany) continuous positive airway pressure (CPAP) device. RESULTS: The use of PAP for 3 months revealed a significant improvement as measured by sleep data and serotonin levels (before: apnea index [AI] 17.2 eV/h, after: 2.4 eV/h p = 0.001; SpO2 < 90% - 45.7 min vs. 6.2 min p = 0.001; serotonin 20.3 ng/mL vs. 26.03 ng/mL p = 0.036]. CONCLUSION: Our results demonstrate an improvement in sleep patterns. There was an increase in serum serotonin levels in OSA patients following PAP therapy, which could be an effect of intermittent hypoxia decline, and could be used as criteria for the effectiveness of PAP and an improvement in sleep quality.

Dynamics of third order direct three-body recombination of heavy ions.

The direct three-body recombination reactions Cs+ + X- + R → CsX + R (X = F, I and R = Ar, Xe) are studied within the quasiclassical trajectory method using diabatic semiempirical potential energy surfaces, the encounters of the ions being non-central. The collision energies range between 1 and 10 eV (values typical for low temperature plasma), while the so-called delay parameter, which characterizes the delay in the arrival of the neutral atom R in relation to the time instant when the distance between the ions attains its minimum, is equal to 0 or 20%. The calculation results include the recombination excitation functions, the opacity functions, and the vibrational and rotational energy distributions of the recombination products. All the four reactions considered exhibit similar overall statistical dynamics, but each process has its own features. On the whole, for both the recombining pairs Cs+ + F- and Cs+ + I-, xenon is more effective than argon as an acceptor of excess energy from the ion pair. The rotational energy distributions of the salt molecules CsF and CsI are almost equilibrium, whereas the vibrational energy distributions are strongly non-equilibrium.

CLOCK 3111TT Genotype Is Associated with Increased Total Cholesterol and Low-Density Lipoprotein Levels in Menopausal Women with a Body Mass Index of at Least 25 kg/m2.

Lipid profile comparative analysis was performed to reveal the interdependence of lipids with Circadian locomoter output cycles protein kaput (CLOCK) 3111T/C gene polymorphism in menopausal women with/without a body mass index (BMI) of ≥25 kg/m2. Methods: A total of 193 female volunteers aged 45 to 60 years were divided into two groups: Those with BMI < 25 kg/m2 (control) and those with BMI ≥ 25 kg/m2. Each group was then divided into two subgroups: Those with the CLOCK TT-genotype and those with the CLOCK TC-, CC-genotypes. Lipid metabolism parameters were determined by the enzymatic method. Single-nucleotide polymorphisms (SNPs) were detected via polymerase chain reaction-restriction fragment length polymorphism technology. Results: There were no differences in CLOCK 3111T/C genotypes or allele frequency between the control and main groups. In addition, there were no differences in lipid profile parameters between women of the control group and different CLOCK 3111T/C genotypes. The total cholesterol (p = 0.041) and low-density lipoprotein cholesterol (p = 0.036) levels were higher in the subgroup of women with a BMI ≥ 25 kg/m2 and CLOCK TT-genotype as compared to the subgroup with a BMI ≥ 25 kg/m2 and minor allele 3111C. Conclusions: SNP 3111T/C of the CLOCK gene is not associated with BMI however, data suggest that the minor allele of the CLOCK 3111T/C gene polymorphism may have a protective role in atherogenic lipid levels in women with a BMI greater than or equal to 25 kg/m2.

Molecular & genetic characteristics of Mycobacterium tuberculosis strains circulating in the southern part of West Siberia.

BACKGROUND & OBJECTIVES: A complicated epidemiological situation characterized by significantly high tuberculosis (TB) morbidity is observed in West Siberia. This study was aimed to investigate the genetic characteristics of Mycobacterium tuberculosis circulating in the southern part of West Siberia (in the Omsk region). METHODS: From March 2013 to January 2015, 100 isolates of M. tuberculosis were obtained from patients with pulmonary TB living in the Omsk region. Drug susceptibility testing was performed on Lowenstein-Jensen medium (absolute concentration method). Genetic typing of isolates was carried out by variable number tandem repeats of mycobacterial interspersed repetitive units (MIRU-VNTR) typing and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. The genetic types and characteristics of cluster strains were determined using 15 MIRU-VNTR loci. RESULTS: Thirty six VNTR types were found. Twenty six (26.0%) isolates had a unique profile, and the remaining 74 were grouped in 10 clusters containing from 2 to 23 isolates. The Beijing genotype was found in 72 isolates, 61 (85.0%) of which were part of five clusters that included two large clusters containing 23 isolates. Other genetic families, such as Latin-American Mediterranean (LAM, 11.0%), S family (2.0%) and Haarlem (4.0%), were also detected. The genetic family of 11 isolates could not be determined. Six different VNTR profiles were found in these non-classified isolates. Only 16 per cent of isolates were sensitive to anti-TB drugs. The katG315 (94.8%) and rpoB531 (92.2%) mutations were identified in 77 multidrug-resistant M. tuberculosis isolates. INTERPRETATION & CONCLUSIONS: This study showed that the M. tuberculosis population in the Omsk region was heterogeneous. The Beijing genotype predominated and was actively spreading. The findings obtained point to the need for the implementation of more effective preventive measures to stop the spread of drug-resistant M. tuberculosis strains.