Stable Metabolites Of Nitric Oxide Research Articles

#1073 Changes in endothelial function in patients with impaired central and renal hemodynamics respiratory pathology

Abstract Background and Aims To determine the degree of influence of endothelial dysfunction on the hemodynamics of renal and central vessels in respiratory pathology, as well as to determine the effectiveness of complex therapy regimens with carvedilol. Method Studies were conducted in 26 patients with chronic obstructive pulmonary disease (COPD) of II- III severity (group 1, in whom the level of glomerular filtration rate of the kidneys eGFR CKD-EPI ≥6 ml/min/1.73 m2 was determined) and 32 patients with COPD of IV severity (group 2, they were determined e GFR CKD-EPI ≥60 ml/min/1.73 m2). Patients received one course of ten-day standard therapy (GOLD, 2020) in combination with a beta–blocker drug, T. carvedilol 5 mg (Vertex). Doppler echocardiographic examination of peripheral vessels, heart and renal vessels of patients was performed. Stable metabolites of nitric oxide (Cm NO) in blood plasma, ventilation and perfusion state of the lungs were determined. Results A significant decrease in the functional state of the respiratory system was parallel with a decrease in Cm NO synthesis, which was clearly reflected in the second group (by 11%) compared with the first group (by 7%). Pronounced structural changes with remodeling of the right parts of the heart, as well as a pronounced degree of pancreatic hypertrophy in the second group were accompanied by a sharp change in renal filtration function (eGFR ≤60 ml/min/1.73 m2). When measuring the state of diastolic dysfunction of the right parts of the heart, a decrease in E/As well as an increase in the circulatory vascular resistance index and mean blood pressure were significantly higher in the first group of patients (where еGFR ≥6 ml/min/1.73 m2). After a course of treatment with t. carvedilol, based on basic treatment, normalization of endothelial function was determined, reflected in an increase in the concentration of stable metabolites of nitric oxide by 1.05 and 1.5 times (p<0.05) in the biological fluid, respectively, in the first and second groups. In the dynamics of the course of therapy in groups of patients with 75% and 35% decrease in lung ventilation capacity, mean pulmonary arterial pressure decreased by 18.1 and 14.3%, respectively, and the hemodynamic resistance index decreased by 7.9% and 5.7% in parallel (p<0.05). Conclusion When monitoring the functional state of central and renal hemodynamics and ventilation-perfusion function of the bronchopulmonary system after complex treatment with carvedilol, a long-term hypotensive effect, a decrease in endothelial dysfunction, respectively, and an improvement in central and renal hemodynamics were determined.

Effect of per os administration of fucoxanthin alcoholic and oil extracts to Balb/c mice on biochemical parameters and serum cytokine level

Microalgae are a source of various biologically active substances, including carotenoids. One of the carotenoids of diatom microalgae is fucoxanthin, which has antioxidant, antimicrobial, antitumour and anti-inflammatory properties that can be used in the treatment of a wide range of human and animal pathologies. The aim of the study was to investigate the effect of alcohol and oil extract of fucoxanthin on biochemical parameters and levels of serum cytokines in mice during intragastric administration. Material and methods. Fucoxanthin extracts from the microalga Nanofrustulum shiloi were used. Mice of Balb/c strain were intragastrically administrated with 0.5 ml of oil (500 μg/ml) or alcoholic extract of fucoxanthin (187.5 μg/ml), mice in the comparison group were given 0.5 ml of olive oil or 45% ethyl alcohol once a day within 5 days. On the 8th day, blood serum was obtained and the level of albumin, triglycerides, cholesterol, low (LDL) and high density lipoproteins (HDL), urea, uric acid, creatinine, aspartate (AST) and alanine aminotransferases (ALT), lactate, stable nitric oxide (NO) metabolites (nitrites), cytokines (IL-1β, IL-6, IL-10, TNF-α, IFN-γ) was determined using ELISA with photometric detection. Results and discussion. In the comparison group, ethyl alcohol promoted an increase in serum triglyceride, cholesterol, LDL, HDL, ALT, AST, nitrite, IL-10, IFN-γ and TNF-α content compared to intact animals. Fucoxanthin alcoholic extract administration increased the level of LDL, HDL, uric acid, TNF-α and decreased albumin, cholesterol, uric acid, creatinine, ALT, AST, IL-6 content compared to control. The olive oil group showed a decrease in serum triglycerides, cholesterol, urea, uric acid, ALT and AST content but an increase in LDL, HDL, nitrite level compared to the control. Administration of fucoxanthin oil extract to animals decreased albumin, triglycerides, cholesterol, HDL, uric acid, ALT, AST, lactate, IL-6, IL-10 compared to control. Conclusions. Thus, it was discovered that fucoxanthin in Balb/c mice contributes to a decrease in hepatic synthetic function, as evidenced by the change in the concentration of albumin, triglycerides, uric acid), influences energy metabolism (creatinine, lactate), cell membrane stability (cholesterol, LDL, HDL), serum transaminase activity, pro- and anti-inflammatory cytokines content.

ENDOTHELIAL DYSFUNCTION AND GASTROESOPHAGEAL REFLUX DISEASE: STUDY OF COMMON PATHOGENETIC MECHANISMS AND WAYS OF CORRECTION

The aim. To determine the role and place of endothelial dysfunction in the pathogenesis of comorbid gastroesophageal reflux disease (GERD) and obesity by studying the levels of nitric oxide (NO) metabolites in blood and urine. To evaluate the efficacy and benefits of the prescribed therapy, which included the additional inclusion of a peptide compound analogous to leu-enkephalin tyrosine-2-alanine-glycine-phenylalanine-leucyl-arginine diacetate (Dalargin).
 Materials and methods. Clinical manifestations were assessed using the GERD-HRQL questionnaire, levels of stable nitric oxide metabolites NO2 and total metabolites NO2 + NO3 were determined by spectrophotometric method, leptin levels were determined by enzyme-linked immunosorbent assay, pH-metry and motor function was studied by ultrasound. 130 patients were examined, including 70 patients with GERD with comorbid obesity of the first degree, 40 patients with GERD without concomitant pathology and 20 healthy individuals. The study was divided into 3 groups.
 Results. It was determined that the levels of stable metabolites NO2, NO2 + NO3 in blood and urine in the group of GERD with obesity are significantly lower than in the group of isolated GERD (p<0.001). A direct correlation between the level of nitric oxide metabolites in blood and urine and acidity in the stomach and oesophagus was established; an inverse relationship between NO metabolites and the degree of gastrointestinal motor and functional disorders, the severity of clinical manifestations, and the level of hormonal secretion by adipocytes. The supplemental inclusion of Dalargin improved the effectiveness and quality of pathogenetic therapy and achieved a more positive disease dynamics and is recommended for prescription in practice.
 Conclusions. Obesity is a predictor of a more severe course of GERD and more severe endothelial dysfunction. There is a correlation between the severity of endothelial dysfunction and the degree of functional, motor and secretory disorders of the stomach and oesophagus.

The Role of the L-Arginine-Nitric Oxide Molecular Pathway in Autosomal Dominant Polycystic Kidney Disease.

Recently, arginine has been proven to play an important role in ADPKD physiopathology. Arginine auxotrophy in ADPKD induces cell hyperproliferation, blocking the normal differentiation of renal tube cells and causing cyst formation. We explored the L-arginine (Arg)-nitric oxide (NO) molecular pathway in ADPKD, a multisystemic arginine auxotrophe disease. We developed a prospective case-control study that included a group of 62 ADPKD subjects with an estimated filtration rate over 60 mL/min/1.73 mp, 26 subjects with chronic kidney disease with an eGFR > 60 mL/min/1.73 mp, and a group of 37 healthy subjects. The laboratory determinations were the serum level of arginine, the enzymatic activity of arginase 2 and inducible nitric oxide synthase, the serum levels of the stable metabolites of nitric oxide (nitrate, direct nitrite, and total nitrite), and the endogenous inhibitors of nitric oxide synthesis (asymmetric dimethylarginine and symmetric dimethylarginine). In the ADPKD group, the levels of the arginine and nitric oxide metabolites were low, while the levels of the metabolization enzymes were higher compared to the control group. Statistical analysis of the correlations showed a positive association between the serum levels of Arg and the eGFR and a negative association between Arg and albuminuria. ADPKD is a metabolic kidney disease that is auxotrophic for arginine. Exploring arginine reprogramming and L-Arg-NO pathways could be an important element in the understanding of the pathogenesis and progression of ADPKD.

EFFECT OF B. SUBTILIS ІМV B-7724 LECTIN ON THE ACTIVITY OF EFFECTORS OF CELLULAR ANTITUMOR IMMUNITY OF MICE WITH LEWIS LUNG CARCINOMA.

To evaluate the effect of B. subtilis IMV B-7724 lectin on the functional activity of macrophages (Mph), natural killer (NK) cells and cytotoxic lymphocytes (CTL) of mice bearing Lewis lung carcinoma (LLC). The studies were performed on C57Bl/6J mice; LLC was used as an experimental transplantable tumor. The lectin from B. subtilis IMV B-7724 was administered to LLC-bearing mice subcutaneously at a dose of 1 mg/kg of body weight for 10 days. The immunological testing was performed on days 14, 21, and 28 after tumor grafting. The cytotoxic activity of Mph, NK, and CTL was estimated in MTT-assay; the content of the stable metabolites of nitric oxide (NO) was measured by a standard Griess reaction; the arginase activity (Arg) was determined based on the measurement of urea. The administration of the B. subtilis IMV B-7724 lectin to LLC-bearing mice exerted its antitumor and antimetastatic effects partially via a significant (p < 0.05) increase of Mph and NK activities after the completion of the treatment. In the group of animals injected with lectin, the NO/Arg ratio increased significantly, indicating the prevalence of Mph with proinflammatory and antitumor properties. The cytotoxic activity of Mph exceeded the indices of untreated mice and intact control by 1.8 times and 5.3 times respectively; of NK - by 2.8 and 1.3 times respectively. The effect of treatment on the CTL activity was less pronounced. Antitumor and antimetastatic activity of the lectin from B. subtilis IMV B-7724 ensured the preservation of the cytotoxic activity of the main effectors of antitumor immunity (Mph, NK, and CTL) throughout LLC growth.

Effectiveness of rosuvastatin and pulmonary rehabilitation in patients with concurrent course of asthma, chronic obstructive pulmonary disease and diabetes mellitus type 2

The aim of this study was to assess the effectiveness of rosuvastatin and pulmonary rehabilitation in patients with asthma-COPD overlap (ACO) concurrent with type 2 diabetes (T2D).Material and methods. A total of 26 patients with ACO and T2D were examined, with an average age of 61 [55.6; 67.8]. In addition to standard therapy, patients in the main group were prescribed rosuvastatin and a pulmonary rehabilitation program. Treatment efficacy was assessed using questionnaires (CAT, ACQ, SGRQ), dyspnea severity scale (mMRC), BODE index, pulmonary function, bioimpedance analysis, 6-minute walk test, carbohydrate and lipid metabolism status, levels of 8-isoprostane, sCD14, CRP, stable nitric oxide (NO) metabolites - nitrite and nitrate ions, and endothelin-1 in the blood. Results. In the main group, a significant improvement was observed during the treatment course, including a 40% reduction in the BODE index (p&lt;0.05), a 33.4% decrease in dyspnea on the mMRC scale (p&lt;0.05), a 28.5% reduction in CAT, a 40.8% decrease in ACQ, and a 20.6% decrease in SGRQ. Other notable improvements included a 1.3% decrease in BMI, a 13% reduction in body fat percentage, a 23.5% decrease in visceral fat level, a 16% increase in patients' tolerance to physical activity, a 27.5% increase in FEV1 (p&lt;0.05), an 8.1% decrease in fasting blood glucose (p&lt;0.01), a 20% reduction in triglycerides (p&lt;0.05), a 24.9% decrease in LDL cholesterol, and a 27.2% decrease in total cholesterol (p&lt;0.05). Additionally, there was a 23.8% decrease in CRP levels (p&lt;0.05), a two-fold reduction in blood 8-isoprostane levels (p&lt;0.05), a 58% reduction in serum sCD14 levels, a 59.8% increase in stable nitric oxide metabolites (p&lt;0.05), and a 55% decrease in endothelin-1 levels (p&lt;0.05).Conclusions. The use of rosuvastatin and pulmonary rehabilitation significantly improves the quality of life for patients with the concurrent presentation of COPD, asthma, and T2D. It reduces the severity of dyspnea, enhances tolerance to physical activity, improves pulmonary function, lowers visceral fat levels and body fat percentage, enhances lipid profile, and improves endothelial function, all while concurrently reducing oxidative stress and systemic inflammation without worsening carbohydrate metabolism.

The effect of nitric oxide donation on the severity of mitochondrial disfunction to the renal tissue in cardiopulmonary bypass simulation: an experimental study

INTRODUCTION: Acute kidney injury is one of the common complications in cardiosurgical operations with cardiopulmonary bypass (CPB). A number of studies have shown that donation of exogenous nitric oxide (NO) reduces episodes of аcute kidney injury. However, subcellular mechanisms of realization the nephroprotective properties of NO remain unknown. OBJECTIVE: To study the safety of the technology of plasma-chemical synthesis of nitric oxide and to evaluate the effect of the delivery resulting nitric oxide on mitochondrial damage to the renal tissue in the simulation of cardiopulmonary bypass. MATERIALS AND METHODS: Experiment included 12 rams of the Altai breed. Animals were divided into 2 groups: 6 animals were modeled CPB; 6 animals were simulated CPB with NO delivery. Mitochondrial damage was assessed by calcium-binding capacity and transmembrane potential of mitochondria 1 h after weaning from the CPB. The safety of the NO delivery according to the proposed method was assessed by the concentration of nitrogen dioxide on inspiration, the level of methemoglobin. The efficiency of NO delivery according to the proposed method was assessed by the level of stable NO metabolites: endogenous nitrite, nitrate and total concentration of NO metabolites. RESULTS: In the group of animals with NO delivery the average level of transmembrane potential of mitochondria was (171.66 ± 20.41 vs 126.66 ± 18.61; p = 0.00256) and calcium-binding capacity of mitochondria was (1466.66 ± 216.02 vs 866.66 ± 216.02; p = 0.000712) of renal parenchyma. Methemoglobin levels above the recommended thresholds in clinical practice were not recorded in the CPB+NO group. The values of total concentration of NO metabolites and nitrate in the CPB+NO group compared to the CPB group are statistically significantly higher, p = 0.00006; p = 0.0035, respectively. CONCLUSIONS: Plasma-chemical synthesis of nitric oxide is a safe technology, and the use of the resulting nitric oxide in cardiopulmonary bypass leads to a decrease in the severity of mitochondrial dysfunction in the kidney parenchyma.

The effect of a tyrosyl-D-alanyl-glycyl-phenylalanyl-leucyl-arginine diacetate (Dalargin) on oxidative stress in patients with severe combined trauma: a prospective clinical study

INTRODUCTION: Severe combined trauma remains the leading cause of mortality and disability of the workable population. Under damaging factor influence, a whole cascade of pathological processes is triggered, leading to development of multiple organ failure. OBJECTIVE: Exploration of the effects synthetic analogue of tyrosyl-D-alanyl-glycyl-phenylalanyl-leucyl-arginine diacetate (Dalargin) on the dynamics of oxidative stress markers in patients with severe polytrauma and the development of organ dysfunction. MATERIALS AND METHODS: 104 patients with severe combined trauma were included in study. There were 38 patients in the Dalargin group and 66 patients in the control group. Patients from main group received Dalargin in the form of a constant infusion through a syringe dispenser at the dose of 10 mcg/kg/hour at first 12 hours of hospitalization and 5 mcg/kg/hour up to 72 hours from the moment of admission. The control group received standard treatment. Indicators of oxidative stress were evaluated at the time of admission (0 days), 1, 3, 5, 7, 10 and 14 days from the therapy onset. RESULTS: In the main group, there was a significant decrease in oxidative stress markers such as malondialdehyde from the first day of treatment (p &lt; 0.05), normalization of stable nitric oxide metabolites at day 10, and a decrease in total antioxidant activity below normal throughout the observation period. Mortality was comparable in both groups (p &gt; 0.05), but the length of hospital stay was lower in surviving patients in the Dalargin group (p &lt; 0.05). The development of organ dysfunction (acute respiratory distress syndrome, acute kidney injury) was less frequent in the Dalargine group (p &lt; 0.05), but infectious complications (pneumonia, meningitis, wound suppuration) were comparable. CONCLUSIONS: Dalargin leads to a decrease of oxidative stress markers and normalization of endothelial function indicators, which contributes to a decrease of organ dysfunction frequency.

The influence of the degree of activity of rheumatoid arthritis on the parameters of stable metabolites of nitric oxide

Rheumatoid arthritis (RA) is an immunoinflammatory disease characterized by progressive destruction of joints and damage to internal organs, which is based on disturbances in the humoral and cellular immune system [1,2]. In the absence of effective therapy, life expectancy in patients with RA is lower by 3 years in women and 7 years in men, primarily due to the high risk of developing comorbid diseases [5].

The Role of Endothelinergic and Nitroxidergic Reactions in Predicting the Functional Outcome in Patients with Ischemic Stroke of Different Severity

The aim of this study was to assess the value of nitric oxide (NO) and endothelin-1 (ET-1) serum concentrations as potential biomarkers for predicting the functional outcome in patients with acute ischemic stroke. Material and methods. A total of 37 patients diagnosed with ischemic stroke and admitted to a multidisciplinary vascular center were included in the study. The patients were divided into two groups based on the severity of neurological deficits as determined by the National Institutes of Health Stroke Scale (NIHSS): Group 1 consisted of 20 patients with NIHSS scores 15, and Group 2 consisted of 17 patients with NIHSS scores 15. The functional outcome was assessed using the NIHSS absolute values and the degree of disability measured by the Modified Rankin Scale (mRS) by comparing the values before and after baseline treatment. Lab evaluation included quantitative assessment of stable NO and ET-1 metabolites in patient’s serum at admission and on day 10 of hospital stay. The SPSS Statistics V23.0 for Windows software package, Python programming language, and Pandas and SciPy libraries were used for statistical data processing. Results. Group 1 patients demonstrated a statistically significant decrease in NIHSS (P=0.0013) and mRS (P0.0001) scores, which was indicative of a favorable functional outcome. Group 2 patients showed some recovery of only neurological deficit measured by NIHSS scale (P=0.0012), changes in degree of disability by mRS were statistically insignificant. On Day10 of hospital stay, both groups showed a clinically significant increase in ET-1 content, and slight change in NO concentration. NIHSS score demonstrated a significant negative correlation with baseline ET-1 concentrations: R=–0.82, P=0.00023 — in Group 1; R=–0.55, P=0.00075 — in Group 2. Modified RS scores showed negative correlation with NO (R=–0.50, P=0.00044) and ET-1 (R=–1.0, P=0.0074) concentrations in Group 1, and positive correlation with NO (R=0.55, P=0.0023) and ET-1 (R=0.33, P=0.04) concentrations in Group 2. Conclusion. Monitoring of NO and ET-1 serum concentrations provides valuable insights for personalized assessment of the anticipated functional outcome in patients with cerebral ischemia. Further research and the development of prognostic mathematical models are needed to validate the use of endothelial function markers as predictive indicators of patients' recovery potential during the acute phase of ischemic stroke.

#4542 L-ARGININE-NITRIC OXIDE MOLECULAR PATHWAY IN AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE

Abstract Background and Aims Autosomal Dominant Polycystic Kidney Disease (ADPKD) is an inherited, complex disease, cystogenesis and phenotypic changes in this disorder being not yet fully understood. Recently, arginine, important for renal cells metabolism, was proved to play an important role in ADPKD physiopathology (1). The inability of cells to recycle or synthesize intracellular arginine through the urea cycle is defined as arginine auxotrophy. Arginine auxotrophy in ADPKD induces cell hyperproliferation, and cysts formation (2). We aimed to explore L-Arginine (Arg) - Nitric Oxide (NO) molecular pathway in ADPKD, a multisystemic, arginine auxotrophe disease. Method We developed a prospective, case control study, in Carol Davila Clinical Hospital of Nephrology, Bucharest, Romania. The study included a group of 62 subjects with ADPKD (mean age -54.3years old, men:women 34:28, with 1A and 1B Mayo ADPKD risk classes) and a group of 37 healthy subjects, similar as sex, mean age. ADPKD diagnosis was based on familial history, clinical exam and CT or MRI scan. We excluded from the study subjects that presented cysts in other organs except the kidney, with eGFR&amp;lt;60mL/min/1.73mp, with history of hematuria, cysts infection, urinary tract infection, renal lithiasis, with unstable blood pressure and hypertensive treatment for less than 6 months; metabolic disorders (carbamoyl phosphate synthase 1 and N-acetyl glutamate synthase deficiencies, lack of ornithine transcarbamilase, hyperargininemia, phenylketonuria). Laboratory tests: serum level of arginine, enzymatic activity of arginase 2 (ARG-2) and nitric oxide inducible synthase (NOS-2), serum levels of stable metabolites of nitric oxide (nitrate, direct nitrite, total nitrite), endogenous inhibitors of nitric oxide synthesis (Asymmetric Dimethylarginine -ADMA, Symmetric Dimethylarginine SDMA). Results In ADPKD patients, the serum levels of arginine and of the stable metabolites of nitric oxide had statistically significant lower levels compared with control group (Table 1). The levels of the principal enzymes that metabolizes arginine – arginase 2 and nitric oxide inducible synthase, respectively the endogenous inhibitors of nitric oxide synthesis were statistically significant higher in ADPKD group when compared with control group (Table 1). The ARG2/Arg, NOS2/Arg, Nitrite/Arg, Nitrate/Arg, ADMA/Arg and SDMA/Arg ratios were statistically significant overexpressed in ADPKD group when compared with control group. Conclusion ADPKD is a metabolic kidney disease, auxotrophic for arginine. The metabolic ADPKD phenotype of renal cells with low risk of progression (1A and 1B Mayo) is defined by the alteration of L-Arginine-NO molecular pathway, the significant reduction of systemic arginine, moderately increased enzymatic activities of ARG2 and NOS2, the reduction of the synthesis and bioactivity of NO. Exploring arginine reprogramming and related molecular L-Arg-NO pathways disturbances could offer more information about ADPKD physiopathology.

Electrochemical measurements of the levels of nitric oxide metabolites in the blood serum

Background: Sepsis is a serious clinical condition caused by a dysregulated immune response to infection resulting in multiple organ failure. In the pathogenesis of sepsis, especially that of septic shock, great importance is given to the endothelial marker of vascular regulation, nitric oxide (NO). In septic shock, dysregulation of the vascular tone plays a key role in the development of hypotension. Therefore, the control of the level of nitric oxide and its stable metabolites in critically ill patients is a very important task.&#x0D; Aim: the aim of this study was to evaluate the potential of the electrochemical nitrite detection in the patients blood serum.&#x0D; Methods: The levels of nitric oxide stable metabolites in the blood serum of healthy individuals (n=20) and septic patients (n=25) were studied by the electrochemical method using a composite electrode and by the spectrophotometric method using the Griess reagent.&#x0D; Results: The data in the groups of healthy people and patients with sepsis differ significantly (p 0.00001) both when measured using electrochemical and spectrophotometric methods. The median value of the current response in healthy people was 0.41 A (0.33; 0.55), and the total content of nitric oxide metabolites (NOx) was 26.8 mol/L (20.8; 31.0), while in patients with sepsis, these values were 0.79 A (0.61; 1.28) and 38.89 mol/L (29.64; 57.45), respectively. A negative correlation was found between the data obtained for practically healthy persons (r=-0.696, p=0.0007).&#x0D; Conclusion: The obtained results allow us to conclude that the nitrite measurement in the blood serum by amperometry using a composite electrode is promising as a diagnostic technique.

NITRIC OXIDE IN BLOOD PLASMA OF WISTAR RATS RECEIVING VITAMIN D3

Recently, much data has been published on the correlation between vitamin D and endothelium. Which is known to regulate vascular homeostasis and hemodynamics. Nitric oxide is characterized by a strong vasodilating effect. It is also a powerful inhibitor of platelet aggregation and adhesion to the vascular wall. Vitamin D and its receptors can regulate the nitric oxide synthesis by changing the activity of endothelial NO synthase.&#x0D; The purpose of the study was to examine the effect of vitamin D3 (emulsion) consumption on the level of nitric oxide in the blood of Wistar rats.&#x0D; Materials and Methods. The study was carried out on mature male Wistar rats weighing 200–300 g (aged 2–3 months). The rats were randomly divided into two groups: 1) control (n=6), kept in vivarium during the whole experiment, 2) experimental (n=6), daily receiving vitamin D3 in emulsion for 30 days. The calculation of vitamin D3 dose was based on the recommended daily amount of vitamin D3 for an adult person (4000 IU). A biochemical blood test determined 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D and the level of stable nitric oxide metabolites. Statistica software was used for statistical analysis.&#x0D; Results. The trial study showed that a 30-day intake of vitamin D3 in emulsion increased its concentration and the nitric oxide level in the blood of rats. It may indicate the intensification of the enzymatic nitric oxide synthesis and the improvement in endothelial function.&#x0D; Conclusion. Thus, vitamin D and nitric oxide are important functionally correlated compounds. Adequate vitamin D status can mitigate the development of cardiovascular disease.

Interrelation between the parameters of endogenous vascular regulation, oxidative stress and the markers of inflammatory response in COVID-19 patients while on extracorporeal membrane oxygenation

Introduction. Extracorporeal membrane oxygenation has found wide application in clinical practice during the COVID-19 pandemic. Oxidative stress, endothelial dysfunction, and systemic inflammatory response syndrome play an important role in the pathogenesis of COVID-19. Our research was designed to study correlations in-between those factors and the impact of extracorporeal membrane oxygenation on them.Aim. The study of systemic inflammatory response and endothelial function in patients with COVID-19 during extracorporeal membrane oxygenation.Material and methods. In the course of a prospective study, we examined 100 COVID-19 patients aged 26 to 75 years, median 55 years [47;60], who were treated at the N.V. Sklifosovsky Research Institute for Emergency Medicine, using extracorporeal membrane oxygenation. As a control group (normal), 25 practically healthy people whose median age was 32 years [25;39] were examined. The function of the vascular endothelium was assessed by the content of nitric oxide stable metabolites in the blood serum and the level of angiotensin-converting enzyme. Next, the ratio of nitric oxide metabolite to angiotensin-converting enzyme level was calculated, reflecting the imbalance between endotheliumdependent vasodilation and vasoconstriction. To assess the severity of oxidative stress in blood serum, malondialdehyde was determined as a marker of lipid peroxidation. The state of the antioxidant system was assessed in terms of total antioxidant status of blood serum. The presence of an imbalance in the system of lipid peroxidation and the antioxidant system total antioxidant status was judged by the oxidative stress coefficient, i.e. the ratio of malondialdehyde to the total antioxidant activity.Results. The analysis showed the presence and progression of endothelial dysfunction, impaired vascular regulation, activation of free radical processes, the presence of an imbalance in the prooxidant/antioxidant system, as well as the progression of the inflammatory process with a decrease in the level of markers of the COVID-19 severity.Conclusion. Further studies of the correlation between endothelial damage and the severity of the systemic inflammatory response syndrome may be of fundamental importance for explaining the pathophysiological mechanisms of COVID-19 course and developing new treatments for such patients.

Metabolic indicators in diagnostics and prediction of course of subclinical and clinical mastitis in goats after parturition

The symptom complex of the inflammatory process in the udder was established in the process of clinical examination in 27.69±1.79 percentage of goats at the beginning of lactation. In the early postpartum period, in sick goats with catarrhal or serous mastitis, a decrease in buffer bases, glucose concentration, and the VH/AcAc coefficient were found. The content of total protein is reduced by 1.22 times, and the level of albumin is reduced by 1.51 times. The indices of AST and ALT, CHF, with catarrhal mastitis are reduced, and the indices of LDH are increased relative to other groups of animals studied, which indicates that the destabilization of metabolite metabolism during the functioning of the liver is included in the pathological process. The level of ceruloplasmin ranged from 7.97 to 141.6 mg / dl, in the blood of goats with clinical mastitis, while with subclinical mastitis from 6.74 to 89.14 mg / dl, and in the control group (clinically healthy) was in range from 9.32 to 46.137 mg/dL. Significant differences were obtained in a positive test for the level of ceruloplasmin and Creactive protein in goats with mastitis. In goats with subclinical mastitis, the level of the studied hormones was within the confidence interval, which allows us to consider hormonal imbalance as a proven cause of subclinical, catarrhal, serous mastitis and the likelihood of hormone dependence of udder inflammation in goats shortly after birth. In animals with subclinical mastitis and with clinical signs of catarrhal or serous mastitis, an increase in the level of diene conjugates by 1.87 times, and the concentration of intermediate products of ketodienes and conjugated triune’s by 1.75 times. By 38.0% of the concentration of stable metabolites of nitric oxide and a decrease of 13.1% in the content of vitamin E. In the blood of progesterone and estradiol, as well as the LPO-AOD systems, have a sufficiently high diagnostic value, allowing monitoring the course of the pathological process in the udder of goats and monitoring the treatment protocol.

The effect of antioxidant therapy on some pathogenetic factors of primary open-angle glaucoma

The study analyzes the vascular remodulation, antioxidant and antihypoxic effects of the drug Mexidol in patients with PAOG. The study included 78 patients with POAG of the early (n=43) and advanced stage (n=35) with average age of 67.8±1.5 years. The main study group consisted of 47 patients who received Mexidol in addition to local hypotensive treatment; 31 patients comprised the control group. In the comparison groups, the degree of ED was determined by the results of reactive hyperemia test, patients' blood plasma was analyzed for levels of stable nitric oxide metabolite (nitrite NO2-) and endothelin-1 (ET-1). General assessment of oxidative stress was carried out by high-performance liquid chromatography. Functional activity of the retina was studied using an electroretinograph and static computer perimetry performed according to the standard technique. The following changes are observed in patients of the main group using Mexidol: the index of oscillatory potentials significantly increases, peak latency decreases, perimeter indices show positive trends, vascular endothelial function improves according to reactive hyperemia test, concentration of vasoconstrictor mediator ET-1 in blood plasma decreases and of nitrite (NO2-) increases moderately, the coefficient of bioeffective vasotonic activity decreases, the level of glutathione peroxidase increases (p<0.05 compared to the baseline value), the level of malonyldialdehyde decreases, lipid metabolism improves (reduction in total cholesterol, low-density lipoprotein-cholesterol, triglycerides, decrease in the Atherogenic Index compared to the initial level). The drug Mexidol proved to be an effective endothelial protector, a powerful antioxidant and antihypoxant, contributed to deceleration of atherogenesis in patients with POAG.

Effect of an herbal formulation containing Peganum harmala L. and Fraxinus excelsior L. on oxidative stress, memory impairment and withdrawal syndrome induced by morphine

Background: Traditional Persian medicine has introduced effective remedies in opioid dependence care. One of the most widely used remedies is an herbal formulation containing Peganum harmala L. and Fraxinus excelsior L. (HF). This study investigated the effects of HF to attenuate the withdrawal signs and rewarding effects in morphine-dependent rats. Methods: Forty-nine male Wistar rats were randomly divided into seven groups. The control and vehicle groups received normal saline and sodium carboxymethyl cellulose, respectively. The morphine group received morphine for one week. The single and daily dose of HF groups received morphine similar to the morphine group, and HF (1.4 and 2.8 g/kg) once a day in the daily dose group and only on the last day of the experiment in the single dose of HF group. Finally, the withdrawal signs as well biochemical tests were evaluated. The behavioral parameters were assessed by conditioned place preference (CPP), elevated plus-maze and Y-maze tests. The antioxidant activity of HF was evaluated by measurement of serum contents of malondialdehyde, stable nitric oxide metabolites and total antioxidant capacity (TAC). Moreover, the protein expression of c-fos was assessed by western blotting. Results: Daily treatment with HF significantly reduced the score of CPP behavioral test, all of the withdrawal signs, TAC and the c-fos protein level. Conclusions: The results indicated that HF might be a promising complementary treatment in reducing morphine-induced physical and psychological dependence probably through modulation of c-fos protein expression.

Динаміка рівнів біомаркерів ендотеліальної функції у хворих на резистентну артеріальну гіпертензію під впливом лікування

The purpose of the study was to determine the biomarker levels dynamics of endothelial function in patients with treatment resistant hypertension under the influence of treatment. Materials and methods. A comprehensive outpatient examination was conducted in 117 patients with a preliminary diagnosis of treatment resistant hypertension. 71 patients with hypertension of the stage II and 35 practically healthy individuals were examined. The quantitative content of endothelin-1 was determined by enzyme immunoassay using a set of reagents Endothelin-1 ELISA kit (Biomedica, Austria). The method for determining stable final metabolites of nitric oxide in the blood is based on the reduction of nitrates to nitrites with the determination of the latter by reaction with the Gris reagent. Results and discussion. The level of endothelin-1 between the groups of patients was significantly higher among patients with treatment resistant hypertension than among patients with hypertension of the stage II – 1.64 [1.16; 2.18] fmol/l versus 0.98 [0.73; 1.02] fmol/l, respectively, (p&lt;0.05). The NO2 index had the lowest value in the group of patients with treatment resistant hypertension 6.00 [5.10; 7.30] mmol/l and was significantly lower by 20.0% compared to the group of patients with hypertension of the stage II – 7.50 [6.80; 9.40] mmol/L. The NO3 level among patients with treatment resistant hypertension was 13.50 [11.20; 14.80] mmol/l, which was significantly lower by 11.8% and 18.2% compared to the group of patients with hypertension of the stage II and the group of practically healthy individuals, respectively (p&lt;0.05). In the first group, blood pressure levels &lt;140/90 mmHg were reached by 29 (56.9%) people, which significantly exceeded the percentage in the second group – 15 (30.6%) patients (p&lt;0.05). Treatment of patients with treatment resistant hypertension should include optimizing dosages and prescribing rational combinations of antihypertensive drugs in order to enhance synergistic effects. Among the measures to overcome low adherence to treatment of hypertension, the following should be recommended: assessment and selection of patients with low compliance (according to the Morisky-Green scale); optimization of pharmacotherapy by prescribing drugs with fixed combinations; control of drug intake. The Morisky-Green scale test should be applied at the beginning of treatment of patients with hypertension, since it allows the doctor to understand how supportive the patient is to treatment and will correctly perform the appointment. After all, only accurate and correct execution of prescriptions can bring the maximum positive effect of therapy and prevent the development of complications. The fixed combination of amlodipine-indapamide-perindopril has one important advantage, which is to increase adherence to treatment due to the principle of "one day – one pill". Conclusion. Among patients with hypertension, the development of endothelial dysfunction is noted, which increases with treatment resistant hypertension. The combination of amlodipine-indapamide-perindopril is effective in reducing blood pressure and correcting endothelial dysfunction. The use of a fixed combination of amlodipine-indapamide-perindopril in the form of a single pill by patients is accompanied by a large percentage of those who have reached blood pressure levels &lt;140/90 mmHg

Parameters of the Blood Oxidant/Antioxidant System in Elderly Patients with Acute Poisoning

The aim of the study was to assess the oxidant/antioxidant status in elderly patients in the early period of acute poisoning by psychotropic drugs or corrosive substances.Material and methods. An open prospective observational study with retrospective control was conducted in 80 patients (age ≥ 60 years) with acute poisoning, of which 49 patients aged 72.1±9.55 years had psychotropic drug poisoning (PDP) and 31 subjects aged 73.0±10.3 years had corrosive substance poisoning (CSP). Patients with mild poisoning were excluded from the study. The control group consisted of 39 volunteers aged 68.3±6.3 years. Total antioxidant status (TAS), blood levels of malondialdehyde (MDA), stable nitric oxide metabolites (nitrite/nitrate, NOx), and oxidative stress index (MDA/TAS) were measured on days 1, 3 and 5 after hospital admission.Results. When analyzing the changes in the parameters of the oxidant/antioxidant system, we observed lower values of the studied parameters in patients with both PDP and CSP compared to the control group. In patients with PDP, several parameters were reduced: MDA by 1.2 times on days 1 and 3 (P=0.002; P=0.008, respectively), NOx by 1.7 times (P&lt;0.001) at all stages of the study, MDA/TAS by 2.4–2.9 times (P&lt;0.001). In patients with CSP, MDA level decreased by 1.1–1.2 times at all study timepoints (P=0.003; P=0.010; P=0.046, respectively), NOx dropped 1.4–1.6-fold (P=0.012; P=0.004; P=0.023, respectively), and MDA/TAS decreased by 2.3–2.4 times (P&lt;0.001). While comparing patients with favorable and fatal outcome, we found that in survived patients an increase of MDA/TAS along with growing NOx level was seen by day 5 with no significant changes of MDA and TAS, while in non-survivors MDA/TAS dropped continuously due to progressive fall of NOx level, reaching values 2.8–2.9 times (P&lt;0.001) lower than those of the controls.Conclusion. In elderly patients with acute poisonings due to psychotropic drugs or corrosive substances, an inadequate response of the oxidant/antioxidant system occurs manifesting as a reduced blood level of peroxidation products with simultaneous normal or slightly decreased concentration of antioxidant protection system components. Thus, the oxidative stress develops, which contributes to the death of the patients.

The Effect of the Enteral Correction Program on Oxidative Stress Parameters in Patients with Poisoning with Psychopharmacological Agents or Corrosive Substances

RATIONALE Acute exogenous poisonings represent a serious medical problem due to the prevalence, severity of the course and high lethality. In their pathogenesis, an important place is given to oxidative stress (OS). Among modern methods of treatment of acute poisoning, the attention is drawn to approaches aimed at normalizing homeostatic indicators by cleansing the enteric environment, restoration of its barrier function.PURPOSE OF THE STUDY Assess the impact of the enteral correction program (ECP) on the parameters of lipid peroxidation (LPO) and antioxidant systems in acute exogenous poisoning.MATERIAL AND METHODS 119 patients who underwent treatment at the N.V. Sklifosovsky Research Institute for Emergency Medicine, of which 45 were with severe acute poisoning with psychopharmacological agents (PPPA) and 74 with poisoning with corrosive substances (PCS). The two study groups consisted of 40 patients with PCS and 23 patients with PPPA, whose standard therapy was supplemented with ECP. The ECP included making intestinal lavage on admission, the introduction of glucosed saline enteral solution in the following days; and for patients with PCS the treatment also included enteral nutrition and Pektovit.The comparison groups included 56 people (34 with PCS and 22 with PPPA) comparable to the patients of the study groups by sex, age, the type and severity of poisoning poisoning treated with standard therapy The severity of OS was assessed by the KMDA/TAA index which was calculated by means of measuring the concentration of malonic dialdehyde (as an LPO parameter) and total antioxidant activity in the blood plasma of the patients. Serum levels of nitric oxide stable metabolites were also measured.The analysis of the results was performed with the regard to patient’s age.RESULTS In patients of working age, regardless of the toxicant type, LPO activation occurred, which was expressed with an increased KMDA/TAA by 1.4–1.8 times compared to the norm. Using ECP at the study stages contributed to maintaining this balance level between pro- and antioxidants. In patients of comparison groups there was an increase in the LPO system imbalance, while KMDA/TAA exceeded the norm by 2.2–2.4 times that was statistically signifi cantly different from the parameters in the study groups.Older patients showed decreased levels of LPO products, the total antioxidant activity compared to the normal for the age, and, as a result, a decrease in KMDA/TAA by 1.3–1.5 times in PCS and by 2–2.4 times in PPPA. This is due to the low adaptive potential of this category of patients. In this age group, ECP contributed to a moderate activation of LPO, which provided the trend towards normalization of OS parameters.CONCLUSIONS The use of the enterable correction program has a positive impact on the dynamics of oxidative stress parameters, ensuring the maintenance of oxidative processes at the level required for an adequate protective reaction of the body to chemical injury.