Associations of circulating biomarkers with the presence and severity of coronary, carotid and femoral arterial atherosclerosis

Aim. To identify and characterize the associations of the presence and severity of atherosclerosis of various localization with the blood level of biochemical parameters, as well as to assess the potential of their use as markers of metabolic disorders with increased atherogenic potential.Material and methods. The study included 216 patients (men, 53%) aged 24-87 years (mean age, 61,5±10,73 years). All patients underwent coronary angiography, carotid (CA) and femoral arterial (FA) duplex ultrasound to assess the presence and severity of atherosclerosis. In blood serum/plasma, biochemical parameters were analyzed using standard methods.Results. Based on the analysis of circulating biomarker profile, diagnostic complexes have been established that allow assessing atherosclerosis of different localization. According to the data obtained, the determinants of coronary and CA atherosclerosis are endothelial dysfunction (concentration of nitric oxide metabolites <36,0 μmol/L) and an increased level of creatinine (≥73,0 μmol/L). The specific markers associated with severe atherosclerosis of coronary and FAs (but not CA) were low high-density lipoprotein cholesterol (≤1,0/1,2 μmol/L for male/ female, respectively) and an increased C-reactive protein level (≥1,0 mg/l). Severe peripheral atherosclerosis (CA and FA involvement) was associated with hyperglycemia (glucose ≥6,1 μmol/L), while severe FA atherosclerosis — with hyperinsulinemia (insulin ≥14,0 μU/ml).Conclusion. The analysis of associations of circulating biochemical parameters with atherosclerosis localization and severity revealed a number of metabolic markers associated with the increased atherogenic potential. It is possible to distinguish both universal parameters that are associated with atherosclerosis, regardless of its localization and/or severity, and specific biomarkers that characterize either the localization or the severity of atherosclerosis, or both.

Influence of antidepressants on plasma levels of nitric oxide metabolites in patients with major depressive disorder

The impairment of endothelial function by reduced endothelial production of nitric oxide (NO) may contribute to the increased risk of developing cardiovascular disease in patients with depression. NO also plays an essential role in the efficacy of antidepressants. The present study aimed to confirm our previous preliminary findings using a larger sample and different antidepressants. We enrolled 100 patients with major depressive disorder (MDD) and 50 healthy controls. Patients were administered sertraline, duloxetine or mirtazapine and were followed up for 8 weeks. We also compared the rate of increase in plasma levels of metabolites of NO (NOx) among the three antidepressant treatments. Baseline plasma NOx levels were significantly lower in the MDD group than in the control group. A negative correlation was found between plasma NOx levels and the severity of MDD. Treatment with duloxetine significantly increased plasma NOx levels, whereas sertraline treatment caused no significant increase.

Biochemical criteria for the development mechanisms of various reproduction disorders in dairy cows

Ventsova I, Safonov V. 2021. Biochemical criteria for the development mechanisms of various reproduction disorders in dairy cows. Biodiversitas 22: 4997-5002. The article presents the evaluation of peroxide, antioxidant, and hormonal conditions of high-producing red-and-white dairy cows in the physiological and pathological course of pregnancy and the postpartum period. The blood concentration of malonic dialdehyde, stable nitric oxide metabolites, S-nitrosothiols, vitamins E and C, carotin, gonadal, corticosteroid, and thyroid hormones, as well as activity of GPx, GR, SOD, catalase, and ceruloplasmin, were estimated to define major disorder-provoking factors. Analysis of the data shows that ketosis-gestosis syndrome during pregnancy, postpartum metritis, and gonadal dysfunction occur mainly because of oxidative stress in the context of unbalanced peroxide responses and antioxidant protection. Levels of malonic dialdehyde compared to healthy animals increased by 42.3%, 75%, 56.6%, respectively, as also enzyme activities of GR by 26%, 68.1%, 30.1% and catalase by 17.3%, 45.1%, and 23.9%, correspondingly. The endocrine status indicators in the animals with ketosis-gestosis syndrome changed as follows: progesterone levels were 29.5% lower in cows, 17?-estradiol and cortisol were 20.8% and 14.7% lower, respectively. In animals with inflammatory uterine diseases and depressing reproductive glands, progesterone level was 2 and 3 times lower than in healthy animals, the content of cortisol was 17.6% and 25.1% lower, and testosterone decreased by 21.4% and 75.1%, respectively.

COMPARATIVE EFFECTIVENESS OF VARIOUS SCHEMES OF IMMUNOREHABILITATION IN INFERTILITY OF TUBOPERITONEAL GENESIS

The study aimed to compare the effectiveness of various pharmacotherapy regimens for infertility of tubo-peritoneal genesis. Under constant supervision were 96 patients referred to the hospital for diagnostic laparoscopy for infertility of tubo-peritoneal genesis, divided equally into 4 groups depending on the pharmacological treatment methods: the 1st group received basic pharmacotherapy (BPT) after endoscopic surgery (antibacterial, antifungal, vitamin therapy). Patients of groups 2-4, in addition to BPT, received Hepon, Cycloferon or Lavomax, respectively. The control group consisted of 38 gynecologically healthy women. Laboratory examination was performed within 24 hours after the operation and on the 30th day after BPT. Vaginocervical lavage and plasma were assayed for the activity of lipid peroxidation processes, the state of the antioxidant system, the level of stable nitric oxide metabolites, neopterin, C-reactive protein, cytokines (TNFα, IL-1β, IL-8, IFNγ, IL-18, G-CSF, IL-4, IL-10), immunoglobulins (IgM, IgG, IgA, sIgA), components of the complement system (C3, C4, C5, C5А), phagocytic and oxygen-dependent activity of polymorphonuclear leukocytes. It was established that the use of immunomodulatory and antiviral activity medication with BPT according to the degree of increasing efficiency in the correction of immunometabolic laboratory parameters at the systemic and local level in infertility of tuboperitoneal genesis is as the following sequence: basic pharmacotherapy < basic pharmacotherapy + Hepon < basic pharmacotherapy + Cycloferon < basic pharmacotherapy + Lavomax.

Nitric oxide metabolites in complications after open reconstructive procedures in patients with peripheral atherosclerosis

BACKGROUND: Assessing the severity of endothelial dysfunction (ED) and making a prognosis after open reconstructive interventions in patients with peripheral atherosclerosis is complicated due to a limited number of conventional routine methods, including laboratory ones, available for establishing associations between biochemical markers and disease outcomes. AIM: This work is dedicated to the evaluation of nitric oxide (II) metabolites (nitrates and nitrites) in patients with complications following open bypass procedures on the lower extremity arteries using synthetic grafts in order to assess the severity of endothelial dysfunction and its negative sequalae. MATERIALS AND METHODS: The study involved 60 subjects with stage IIb–III chronic lower limb ischemia according to A. V. Pokrovsky–Fontaine classification (categories 3–5 Rutherford) due to atherosclerotic peripheral artery disease. Median age of the subjects was 65 (60–67); the majority of the patients were male (51 (85%). Median value of ankle-brachial index at baseline was 0.32 (0.19–0.42). All participants underwent open bypass grafting procedures using synthetic vascular grafts. Nitric (II) oxide (NO) metabolites level (nitrites and nitrates) was measured before the intervention and three months afterwards by spectrophotocolorimetry using an ELISA analyzer Stat Fax 3200 (Awareness Techonology, Inc., USA) and Griess reagent. The subjects were followed up for a year to determine the rate of development of complications such as restenosis, graft thrombosis, limb loss (major amputation), lethal outcomes, as well as disease progression, myocardial infarction, oncology, and stroke. RESULTS: Performance of a reconstructive procedure on lower extremity arteries was followed by a decrease in NO metabolites level from initial median 76.3 mcmol/ml (48–100.7) to 52.4 mcmol/ml (36.1–93.8) at three months after the intervention (р = 0.015). There was a positive correlation between the NO metabolites level at baseline (0 months) and follow-up visit (3 months) (r = +0.573). Complications within one year after bypass procedures were detected in 66.64% subjects. Baseline level of NO metabolites in patients who required an amputation within one year after the procedure was markedly elevated and reached 116.3 mcmol/ml (90–130.5) (p = 0.025); development of restenosis and lethal outcomes within one year were associated with initially low NO metabolites levels, 35.6 mcmol/ml (p = 0.036) and 33 mcmol/ml (30–36), accordingly (р = 0.043). CONCLUSIONS: Both markedly high and low levels of nitric oxide metabolites (nitrates and nitrites) levels are associated with development of severe complications after open reconstructive procedures in patients with peripheral atherosclerosis. Quantitative determination of the NO metabolites level in serum is a relatively easy and reliable method allowing for the determination of the severity of endothelial dysfunction and its sequalae in subjects after open bypass reconstructive procedures on lower extremity arteries.

Sample stacking – Capillary electrophoretic determination of nitrate and nitrite contents as nitric oxide metabolites in honey varieties originated from Anatolia

Nitrate and nitrite ions taken from food are the sources of bioavailable nitric oxide (NO) in the nitrogen cycle. Some beneficial effects of honey on health are attributed to the ability of honey to increase NO production. The variation of nitrate and nitrite levels of honey samples collected from different Anatolia regions were clarified using capillary electrophoresis technique. The sensitivities of both anions were improved with the application of the sample stacking method. Separation buffer consisted of 30 mmol L−1 formic acid and 30 mmol L−1 sodium sulfate at a pH of 4.0. The CE technique revealed that 18 honey samples contained nitrate anion ranged between 2.53 and 31.8 mg kg−1. Nitrite amounts were found in lower amounts in the honey samples as between non-detected and 0.533 mg kg−1. The observed differences in nitrate levels between honey varieties may be a way to determine honey's origin.

The effects of long-term moderate exercise and Western-type diet on oxidative/nitrosative stress, serum lipids and cytokines in female Sprague Dawley rats

Purpose Regular exercise reduces obesity and the risk of cardiovascular disease. However, health-promoting benefits of physical activity are commonly associated with increased inflammation and oxidative stress. Here, we tested whether constant moderate exercise is able to prevent or attenuate the oxidative/nitrosative stress, inflammation, and serum lipids in lean and obese rats. Methods Four-month-old female Sprague Dawley rats received standard or a high-fat diet. Animals were subjected to a physical activity protocol, consisting of 30 min forced treadmill exercise for 5 consecutive days per week during 10 months. Baseline and sedentary (non-exercised) rats were used as controls. Lipids, oxidized low-density lipoprotein cholesterol, nitric oxide metabolites, and pro- and anti-inflammatory markers were measured in blood collected upon euthanasia. Results At variance to young baseline control rats, 14-month-old animals fed normal diet had increased plasma lipid levels, including total cholesterol and triglycerides, which were further elevated in rats that consumed a high-fat diet. While treadmill exercise did not lower the amount of serum lipids in standard diet group, forced physical activity reduced non-high-density lipoprotein cholesterol in response to high-fat diet feeding. Exercised rats fed standard diet or high-fat diet had lower abundancy of nitric oxide metabolites, which coincided with increased levels of oxidized low-density lipoprotein cholesterol. Accordingly, the amount of nitric oxide metabolites correlated inversely with oxidized low-density lipoprotein cholesterol and homo-arginine. Exercise significantly reduced inflammatory cytokines in high-fat diet fed rats only. Conclusion Our study suggests that regular exercise alters the equilibrium between oxidative and anti-oxidative compounds and reduces pro-inflammatory cytokines.

Red Blood Cell and Endothelial eNOS Independently Regulate Circulating Nitric Oxide Metabolites and Blood Pressure

Background: Current paradigms suggest that nitric oxide (NO) produced by endothelial cells (ECs) via endothelial nitric oxide synthase (eNOS) in the vessel wall is the primary regulator of blood flow and blood pressure. However, red blood cells (RBCs) also carry a catalytically active eNOS, but its role is controversial and remains undefined. This study aimed to elucidate the functional significance of red cell eNOS compared to EC eNOS for vascular hemodynamics and NO metabolism. Methods: We generated tissue-specific "loss-" and "gain-of-function" models for eNOS by using cell-specific Cre-induced gene inactivation or reactivation. We created two founder lines carrying a floxed eNOS (eNOS flox/flox ) for Cre-inducible knock out (KO), as well as gene construct with an inactivated floxed/inverted exon (eNOS inv/inv ) for a Cre-inducible knock in (KI), which respectively allow targeted deletion or reactivation of eNOS in erythroid cells (RBC eNOS KO or RBC eNOS KI mice) or endothelial cells (EC eNOS KO or EC eNOS KI mice). Vascular function, hemodynamics, and NO metabolism were compared ex vivo and in vivo . Results: The EC eNOS KOs exhibited significantly impaired aortic dilatory responses to acetylcholine, loss of flow-mediated dilation (FMD), and increased systolic and diastolic blood pressure. RBC eNOS KO mice showed no alterations in acetylcholine-mediated dilation or FMD but were hypertensive. Treatment with the NOS inhibitor L-NAME further increased blood pressure in RBC eNOS KOs, demonstrating that eNOS in both ECs and RBCs contributes to blood pressure regulation. While both EC eNOS KOs and RBC eNOS KOs had lower plasma nitrite and nitrate concentrations, the levels of bound NO in RBCs were lower in RBC eNOS KOs as compared to EC eNOS KOs. Crucially, reactivation of eNOS in ECs or RBCs rescues the hypertensive phenotype of the eNOS inv/inv mice, while the levels of bound NO were restored only in RBC eNOS KI mice. Conclusions: These data reveal that eNOS in ECs and RBCs contribute independently to blood pressure homeostasis.