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Novel biochemical markers for the prediction of renal injury in beta-thalassemia major pediatric patients

A. J. Shwayel1*, A. M. Jewad1, M. Q. Abdulsattar2

1Department of Medical Laboratory Technology, Health and Medical Technical College,
Southern Technical University, Basrah, Iraq;
2Thi-Qar Health Directorate, Iraq;
*е-mail: ameeralzaidy6@gmail.com

Received: 07 June 2023; Revised: 14 August 2023;
Accepted: 27 October 2023; Available on-line: 06 November 2023

Beta-thalassemia major is a severe inherited disorder characterized by inadequate production of hemoglobin beta chains, ineffective erythropoiesis, chronic hemolysis and necessitates lifelong transfusions, which lead to iron overload. The disease manifests itself in early childhood and persists throughout an individual’s life with a high risk of developing renal impairment, which cannot be reliably determined using routine markers. The objective of this research was to apply biomarkers to the evaluation of renal injury in pediatric­ patients within the age range of 1–14 years diagnosed with beta-thalassemia major. In the case-control study, the blood samples obtained in the Genetic Hematology Center in Thi-Qar Iraq Province were used: 60 samples from healthy individuals and 60 samples from the patients with beta-thalassemia, subdivided into 1-7 and 8-14 years old groups. The levels of hemoglobin, ferritin, creatinine and potassium were estimated with standard tests, enzyme-linked immunoassay was used to determine the level of neutrophil gelatinase-associated lipocalin (NGAL) and beta-2-microglobulin (β2M) as novel markers of tubular and glomerular dysfunctions. The study revealed a statistically significant decrease in hemoglobin, serum potassium levels and an increase in ferritin, NGAL and β2M levels in the patients from both groups compared to controls and elevation of creatinine level in the 8–14-year-old group. It was concluded that NGAL and β2M levels may be considered indicators for the early diagnosis of renal injury in pediatric patients with beta-thalassemia, as these biomarkers exhibit elevated levels before an increase in creatinine is observed.

Assessment of urinary podocalyxin as a biomarker of early diagnosis of hypertensive nephropathy

I. Kostovska*, K. Tosheska-Trajkovska, D. Labudovic,
S. Cekovska, O. Kostovski, G. Spasovski

Faculty of Medicine, Ss. Cyril and Methodius University in Skopje, North Macedonia;
*e-mail: irenakostovska22@yahoo.com

Received: 31 August 2023; Revised: 28 September 2023;
Accepted: 27 October 2023; Available on-line: 06 November 2023

Chronically high blood pressure-related kidney injury is known as hypertensive nephropathy (HN). Podocyte damage in the pathogenesis of this disease can result in the release of the sialoglycoprotein podocalyxin into the urine, so podocalyxin may be useful in the early diagnosis of HN. The purpose of the study was to examine the relationships between urine podocalyxin level and clinical and biochemical parameters in individuals with HN and to assess the diagnostic utility of urinary podocalyxin as an early marker of HN. Participants (114 individuals) were enrolled in this cross-sectional study, including 30 healthy controls and 84 patients with clinically proven chronic hypertension (CH). Biochemical tests were performed on the blood samples. Urinary microalbumin and creatinine levels were measured using immunoturbidimetric and spectrophotometric methods, respectively; urinary podocalyxin level was estimated with ELISA. All CH patients were classified into subgroups according to urine microalbumin/creatinine ratio (UM/CR) and the stage of chronic kidney disease (CKD). The results obtained showed that urinary podocalyxin level was significantly increased in both UM/CR and CKD staging subgroups compared with the healthy control group. A gradual increase in urinary podocalyxin level with CKD stage, especially in IV and V stages, and the higher sensitivi­ty of urinary podocalyxin as compared to UM/CR ratio in early detection of HN was demonstrated. It was concluded that urinary podocalyxin may be an important and highly sensitive marker for early diagnosis of hypertensive nephropathy in patients with chronic hypertension.

Assessing the relationship between organ function test results and COVID-19 severity

A. K. Yadav1, M. K. Mishra2*, S. Prasad3, S. Singh4

1Department of Biochemistry, Heritage Institute of Medical Science, Varanasi, U.P., India;
2Department of Biochemistry, GMERS Medical College & Hospital, Vadnagar, Gujarat, India;
3Department of Biochemistry, K. J. Somaiya Medical College & Research Centre, Mumbai, India;
4Department of Microbiology, Integral Institute of Medical Science and Research, Lucknow, U.P., India;
*e-mail: mritunjaymishra007@gmail.com

Received: 25 July 2023; Revised: 12 October 2023;
Accepted: 27 October 2023; Available on-line: 06 November 2023

A number of recent reports have indicated the association of COVID-19 with multiple organ failure and the need to clarify the relationship between organ testing parameters and disease progression. Therefore, this study aimed to determine the degree of abnormal organ function test parameters and its correlation with COVID-19 severity. A cross-sectional study was conducted among COVID-19 patients admitted at Sanaka hospital, India, from August to September 2020. A total of 100 qRT-PCR-confirmed COVID-19 patients divided into groups with mild or severe cases were enrolled. The data from venous blood samples for liver, renal, cardiac and inflammatory test parameters were included from the Sanaka hospital laboratory database. Biochemical prognostic tests were carried out using a clinical automated ERBA analyzer, cardiac markers were estimated with Enzyme Linked Fluorescent Assay. The Pearson correlation analysis was used to analyze the data. Aspartate/Alanine aminotransferases and alkaline phosphatase activity, creatinine, urea and troponin levels were higher in the confirmed positive cases of COVID-19. Significantly higher levels of troponin, D-dimer and C reactive protein (CRP) were found in patients with severe COVID form compared to a mild one. A strong positive correlation between elevated D-dimer and Ferritin with CRP level was revealed in this group of patients. It was concluded that the positive relationship between serum D-dimer, ferritin levels and CRP level in patients can be considered a stable indicator of disease severity.

A new affine inhibitor of sodium pump thiacalix[4]arene С-1193 increases the intracellular concentration of Ca ions and modifies myometrium contractility

Т. О. Veklich1*, S. О. Cherenok2, О. V. Tsymbalyuk3, О. A. Shkrabak1,
S. O. Karakhim1, A. I. Selihova2, V. І. Kalchenko2, S. O. Kosterin1

1Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;
*e-mail: veklich@biochem.kiev.ua;
2Institute of Organic Chemistry, National Academy of Sciences of Ukraine, Kyiv;
3Educational and Scientific Institute of High Technologies,
Taras Shevchenko National University of Kyiv, Ukraine

Received: 16 June 2023; Revised: 31 September 2023;
Accepted: 27 October 2023; Available on-line: 06 November 2023

The methods of enzymatic and kinetic analysis were used to demonstrate that thiacalix[4]arene-bis-hydroxymethylphosphonic acid С-1193 had the inhibitory effect (І0.5 = 42.1 ± 0.6 nM) on Na+,K+-ATPase activity in the plasma membrane of myometrium cells with no effect on the relative activity of other ATPases localized in this subcellular structure. The method of confocal microscopy and Са2+-sensitive fluorescent probe fluo-4 were used to demonstrate that thiacalix[4]arene С-1193 increased the intracellular concentration of Ca ions in the immobilized uterine myocytes. The tenzometric studies proved that С-1193 (10 and 100 μМ) increased the isometric phasic contractions, induced via the paths of both electromechanical (depolarization with high-potassium solution) and pharmacomechanical (application of uterotonic hormone oxytocin, neurotransmitter acetylcholine or selective agonist of muscarinic acetylcholine receptors cevimeline) coupling. Application of thiacalix[4]arene С-1193 as a selective and effective inhibitor of Nа+,K+-ATPase may be useful both for studyng the regulation of ion homeostasis in smooth muscle cells and creation of new uterotonics based on the calixarene core.

Contents UBJ, 2023, Volume 95, Issue 4

Serhiy Komisarenko. On the 80th birthday

Undecylenic acid and N,N-dibutylundecenamide as effective antibacterials against antibiotic-resistant strains

Y. D. Startseva*, D. M. Hodyna, I. V. Semenyuta,
O. P. Tarasyuk, S. P. Rogalsky, L. O. Metelytsia

V.P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry,
National Academy of Sciences of Ukraine, Kyiv;
*e-mail: startseva1991@gmail.com

Received: 25 April 2023; Revised: 03 July 2023;
Accepted: 7 September 2023; Available on-line: 12 September 2023

Evaluation of undecylenic acid (UA) and its tertiary amide N,N-dibutylundecenamide (DBUA) activity­ in vitro against the standard and antibiotic-resistant Escherichia coli and Staphylococcus aureus strains was carried out. The antibacterial potential of the acid and its amide at 2.5 and 5.0 μM concentration both against gram-positive bacteria (S. aureus) and gram-negative (E. coli) cultures was confirmed by monitoring the diameter of the bacterial growth inhibition zones. The docking study identified methionine aminopeptidase (MAP) as the most energy-favorable potential biotarget associated with the drug resistance of E. coli and S. aureus with a binding energy in the range from -8.0 to -8.5 kcal/mol. The ligands complexation was due to the formation of hydrogen bonds with ASP108, HIS171, HIS178, GLU204, GLU235, HIS76, ASP104, GLU233, ASP93 and metal-acceptor interactions with Co2+. Overall, the results indicated that UA and DBUA activity against antibiotic-resistant strains creates prospects for the development of new antibacterial formulations.

The influence of coordination compounds with malatogermanate/stannate anions and 1,10-phenanthroline cations of 3D metals on α-L-rhamnosidase activity of Penicillium tardum, Penicillium restrictum and Eupenicillium erubescens

O. V. Gudzenko1*, N. V. Borzova1, L. D. Varbanets1,
I. I. Seifullina2, O. E. Martsinko2, E. V. Afanasenko2

1D.K. Zabolotny Institute of Microbiology and Virology, National Academy of Siences of Ukraine, Kyiv;
2I.I. Mechnikova Odesa National University, Odesa, Ukraine;
*e-mail: alena.gudzenko81@gmail.com

Received: 01 May 2023; Revised: 15 July 2023;
Accepted: 7 September 2023; Available on-line: 12 September 2023

The search for effectors capable of influencing the catalytic activity of enzymes is an important area of modern enzymology. The aim of the study was to investigate the ability of 6 coordination compounds with malatogermanate/stannate anions and 1,10-phenanthroline cations of 3d metals to modify α-L-rhamnosidase activity of Penicillium tardum, Penicillium restrictum and Eupenicillium еrubescens strains. α-L-Rhamnosidase activity was determined by the Davis method using naringin as a substrate. It was demonstrated­ that [Ni(phen)3]2[{Sn(HMal)2(Mal)}Cl]•14H2O) in 0.1% concentration had the most pronounced activating effect on α-L-rhamnosidase activity of all strains studied. Noncompetitive inhibition of α-L-rhamnosidase in E. еrubescens by [Cu(phen)3]2[{Sn(HMal)2(Mal)}Cl]•10H2O was shown. The obtained results expand the idea of glycosidases possible activators and inhibitors and indicate the perspective of their use in modern biotechnological processes.

Hepatoprotective effect of 2,6-dimethylpyridine N-oxide (Ivin) in experimental model of CCl(4)-induced hepatitis of rats

O. P. Vasetska*, V. S. Lisovska, M. H. Prodanchuk, P. H. Zhminko

SE “L. I. Medved’s Research Center of Preventive Toxicology,
Food and Chemical Safety, Ministry of Health, Ukraine”, Kyiv;
*e-mail: o.vasetska.medved@gmail.com

Received: 20 April 2023; Revised: 12 June 2023;
Accepted: 7 September 2023; Available on-line: 12 September 2023

The effect of concomitant pesticides and plant growth regulators on humans is still not well understood. N-oxide-2,6-dimethylpyridine (Ivin) is the plant growth regulator known to reduce the acute toxicity of pesticides, but its protective mechanisms need to be investigated. The aim of the study was to assess the hepatoprotective ability of 2,6-dimethylpyridine N-oxide (Ivin) using a model of acute CCl4-induced hepatitis. Male Wistar Han rats received two subcutaneous CCl4 injections (0.8 ml/100 g b.w.). Oral Ivin (13 or 0.13 mg/kg) and hepatoprotector “Silybor-35” (5 mg/kg) as reference substances were administered orally one hour pre- and 2 hours post-CCl4 injection. The biochemical assay of blood plasma, estimation of lipid peroxidation products in the liver tissue and histological liver analysis were done. The results of functional tests and histomorphological studies of liver tissue demonstrated that Ivin exhibited a pronounced hepatoprotective effect, more pronounced when it was administered at a low 0.13 mg/kg dose. Calculation of the hepatoprotection efficiency index for Ivin showed that it was comparable to that for “Silybor-35”.

Nitric oxide cycle activity in rat biceps femoris muscle under conditions of bacterial lipopolysaccharide influence, experimental metabolic syndrome and their combination

O. Ye. Akimov1*, A. O. Mykytenko2, V. O. Kostenko1

1Department of Pathophysiology, Poltava State Medical University, Poltava, Ukraine;
*e-mail: o.akimov@pdmu.edu.ua;
2Department of Biological and Bioorganic Chemistry, Poltava State Medical University, Poltava, Ukraine

Received: 22 April 2023; Revised: 05 June 2023;
Accepted: 7 September 2023; Available on-line: 12 September 2023

There is evidence that long-term organism stimulation with bacterial lipopolysaccharides (LPS), which promotes the secretion of pro-inflammatory cytokines and nitric oxide, may play an important role in metabolic syndrome (MetS) development. Changes in NO production under conditions of MetS have different directions and depend on a specific organ. The purpose of this work was to study the production of nitric oxide and its metabolites in the biceps femoris muscle of rats under conditions of lipopolysaccharide stimulation of the organism, metabolic syndrome and their combination. The study was conducted for 60 days on 24 male Wistar rats divided into control, MetS, LPS and LPS+MetS groups. MetS was reproduced by adding 20% fructose solution to food, LPS stimulation was carried out by intraperitoneal injection of S. typhi LPS. It was demonstrated that stimulation of the rat organism with LPS under conditions of experimental metabolic syndrome increased the production of nitric oxide by L-arginine-dependent pathway, but limited metabolic syndrome-induced increase in nitric oxide production by L-arginine-independent pathway, reduced the concentration of S-nitrosothiols, while increasing the concentration of peroxynitrites and nitrites in the biceps femoris muscle of rats.