Browsing by Author "Tretjakovs, Peteris"
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Item Assessment of ADAMTS-13 Level in Hospitalized Children with Serious Bacterial Infections as a Possible Prognostic Marker(2019-08) Rautiainen, Linda; Cirko, Anna; Pavare, Jana; Balmaks, Reinis; Grope, Ilze; Katirlo, Irina; Gersone, Gita; Tretjakovs, Peteris; Gardovska, Dace; Department of Paediatrics; Department of Human Physiology and BiochemistryBackground and objectives: In children, acute infection is the most common cause of visits in the primary care or emergency department. In 2002, criteria for diagnostics of pediatric sepsis were published, and then revised in 2016 as life-threatening organ dysfunction due to a dysregulated host response to infection. In the pathophysiology of sepsis endothelial dysfunction plays a very important role. Deficient proteolysis of von Willebrand factor, due to reduced ADAMTS-13 activity, results in disseminated platelet-rich thrombi in the microcirculation. ADAMTS-13 deficiency has been detected in systemic inflammation. The clinical relevance of ADAMTS-13 during sepsis is still unclear. We aimed to investigate the possible use of ADAMTS-13 as a prognostic marker in children with serious bacterial infection (SBI). Materials and Methods: Inclusion criteria were hospitalized children with SBI, aged from 1 month to 17 years. SBI was defined based on available clinical, imaging, and later also on microbiological data. Sepsis was diagnosed using criteria by The International Consensus Conference. In all the patients, the levels of ADAMTS-13 were measured at the time of inclusion. Results: Data from 71 patients were analyzed. A total of 47.9% (34) had sepsis, 21.1% (15) were admitted to the ICU, 8.5% (6) had mechanical ventilator support, and 4.2% (3) patients had a positive blood culture. The median level of ADAMTS-13 in this study population was 689.43 ng/mL. Patients with sepsis, patients admitted to the Intensive Care Unit, and patients in need of mechanical ventilator support had significantly lower levels of ADAMTS-13. None of the patients had ADAMTS-13 deficiency. In patients with SBI, the area under the curve (AUC) to predict sepsis was 0.67. A cut-off ADAMTS-13 level of <= 730.49 had 82% sensitivity and 60% specificity for sepsis in patients with SBI. Conclusions: ADATMS-13 levels were lower in patients with SBI and sepsis, but AUC and sensitivity were too low to accept it as a prognostic markerItem Association between inflammatory markers and clinical and metabolic risk factors for cardiovascular diseases(2009) Stuķena, Inga; Kalvelis, Andrejs; Bahs, Guntis; Teibe, Uldis; Tretjakovs, Peteris; Lejnieks, Aivars; Rīga Stradiņš UniversityThe inflammatory reaction plays an important role in the development of atherosclerosis. The clinical significance of the main inflammatory markers - C-reactive protein (CRP), interleukin 6 (IL6), tumour necrosis factor alpha (TNF-α), plasminogen activator inhibitor 1 (PAI1), etc. - has not been fully established. CRP, IL6, TNF-α, and PAI1 were assessed in 100 patients in terms of certain clinical indicators (sex, obesity indicators, blood pressure, and heart rate), total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), triglycerides (TG), glucose, insulin, homeostasis model assessment of insulin resistance (HOMA-IR), adiponectin, and leptin levels. CRP and PAI1 levels were elevated in subjects with increased body mass index (BMI) and waist circumference. CRP correlated positively with indicators of carbohydrate metabolism and negatively with TC, HDL-C, and adiponectin. PAI1 correlated positively with insulin levels, HOMA-IR, leptin, and TG, but negatively with HDL-C. IL6 correlated negatively with TC, but TNF-α correlated negatively with HDL-C. Both IL6 and TNF-α correlated positively with leptin levels. TNF-α correlated with TG levels and the indicators of carbohydrate metabolism only in women. CRP and PAI1 are the most sensitive inflammatory markers; their levels were higher in adipose subjects.Item Biomarker combinations in predicting sepsis in hospitalized children with fever(2022-12) Rautiainen, Linda; Cirko, Anna; Pavare, Jana; Grope, Ilze; Gersone, Gita; Tretjakovs, Peteris; Gardovska, Dace; Department of Paediatrics; Department of Human Physiology and BiochemistrySepsis is among the leading causes of critical illness worldwide. It includes physiologic, pathologic, and biochemical abnormalities, induced by infection. Novel methods for recognizing a dysregulated inflammatory response and predicting associated mortality must be developed. Our aim was to investigate biomarkers that characterize a pro-inflammatory and anti-inflammatory response in patients with fever by comparing predictive validity for sepsis. 165 patients with fever were enrolled in this study, 55 of them had sepsis according to pSOFA criteria. All patients had blood samples drawn at the time of inclusion and after 24 h. CRP, PCT and also IL-6, IL-8 and sFAS levels were significantly higher in patients with sepsis. The AUC of CRP to predict sepsis was 0.799, all the other biomarkers had AUC’s lower than that. Cytokines, when used as a single marker, did not show a significant diagnostic performance We analyzed various models of biomarker combinations. CRP combined with sFAS showed increase in sensitivity in predicting sepsis (88% vs. 83%). The highest AUC was achieved, when CRP, IL-6, sFAS and sVCAM-1 markers were combined 0.830 (95% CI 0.762–0.884) with a sensitivity of 70% and specificity of 84%. vs. 0.799 for CRP alone.Item Characteristics of cardiovascular risk factors and their correlation with the sex and age of patients in the Latvian population(2009) Stuķena, Inga; Kalvelis, Andrejs; Bahs, Guntis; Teibe, Uldis; Tretjakovs, Peteris; Lejnieks, Aivars; Rīga Stradiņš UniversityVarious cardiovascular risk factors (RFs) were determined in 773 out-patients (mean age 55.8 ± 14.5 years). Male individuals had a larger waist circumference (WC) than did female patients (99.1 ± 13.6 cm vs 93.3 ± 15.2 cm), higher diastolic blood pressure (DBP) (83.6 ± 9.6 mmHg vs 81.8 ± 9.6 mmHg), and higher levels of blood glucose (5.73 ± 1.4 mmol/L vs 5.49 ± 1.3 mmol/L) and triglycerides (TG) (1.89 ± 1.3 mmol/L vs 1.60 ± 1.0 mmol/L), but lower levels of total cholesterol (TC) (5.54 ± 1.2 mmol/L vs 5.79 ± 1.2 mmol/L) and high-density lipoprotein cholesterol (HDL-C) (1.21 ± 0.4 mmol/L vs 1.44 ± 0.4 mmol/L). Compared with the younger age group (i.e., males, < 7 years; females, < 65 years), patients in the older age group had a larger WC (98.4 ± 14.2 cm vs 92.8 ± 15.1 cm), higher systolic blood pressure (SBP) (144.2 ± 19.2 mmHg vs 131.6 ± 18.5 mmHg), higher DBP (84.5 ± 8.8 mmHg vs 80.9 ± 9.8 mmHg), higher blood glucose level (5.74 ± 1.3 mmol/L vs 5.46 ± 1.3 mmol/L), and higher low-density lipoprotein cholesterol level (LDL-C) (3.68 ± 1.0 mmol/L vs 3.52 ± 1.0 mmol/L), but lower HDL-C level (1.3 ± 0.4 mmol/L vs 1.41 ± 0.4 mmol/L). Age was significantly correlated with all RFs, with the exception of the level of C-reactive protein. In conclusion, analysis of cardiovascular RFs in different age subgroups of both sexes clearly showed individual peculiarities of risk profile. This conclusion challenges the usual way of risk calculation using "universal" markers like adiposity or dyslipidemia in all population. The new approach requires individual attention depending on sex and age also in management of risk.Item Circulating irisin in healthy adults : Changes after acute exercise, correlation with body composition, and energy expenditure parameters in cross-sectional study(2020-06) Lagzdina, Rudite; Rumaka, Maija; Gersone, Gita; Tretjakovs, Peteris; Department of Human Physiology and BiochemistryBackground and Objectives: Skeletal muscles are considered to be the main source of circulating irisin, both at rest and during physical activity. The aim of this study was to investigate the connection between irisin, body composition, and energy metabolism in humans. Materials and Methods: Serum irisin concentrations before and after acute aerobic exercise on a treadmill in 84 healthy adults were measured and their association with body composition and energy expenditure (EE) (obtained from indirect calorimetry) was determined. Results: The total pre-exercise irisin concentrations in males and females were similar, but higher in females when expressed per body mass kg (p <0.001). There was an association between pre-exercise irisin per body mass kg, visceral fat rating (rho = −0.52, p = 0.001), and lean tissue % (rho = 0.41, p <0.05) in males and lean body mass index (LBMI) (rho = −0.59, p <0.001) in females. The pre-exercise irisin concentration correlated with the resting metabolic rate (RMR) in both sexes (rho = 0.44 in males, rho = 0.36 in females; p <0.05), but with walking, running, and the EE difference from RMR in running (∆ running EE) in males only (rho = 0.32 to 0.37, p <0.05). There was no significant change in irisin concentration after exercise in 58% of participants, while it decreased in 23%, and increased in 19%. In male subjects with no change in irisin concentration after exercise, running (p < 0.05) and ∆ running EE per body mass kg (p <0.05) were higher than in those with decreased irisin concentration. Conclusions: These findings indicate that the association of irisin concentration with body composition and EE parameters has sex-dependent differences, and acute exercise can lead to various changes in post-exercise irisin levels.Item Ectopic Adipose Tissue Storage in the Left and the Right Renal Sinus is Asymmetric and Associated With Serum Kidney Injury Molecule-1 and Fibroblast Growth Factor-21 Levels Increase(2016-11-01) Krievina, Gita; Tretjakovs, Peteris; Skuja, Ilze; Silina, Vija; Keisa, Laura; Krievina, Daiga; Bahs, Guntis; Department of Human Physiology and Biochemistry; Department of Family Medicine; Department of Internal DiseasesObjective A potential mechanism by which obesity could promote hypertension and kidney diseases is through accumulation of adipose tissue in the renal sinus (RS). The aim of the study was to quantify RS and abdominal adipose tissue volumes and to evaluate serum kidney injury molecule (sKIM)-1 and fibroblast growth factor (FGF)-21 association with different adipose tissue compartments. Methods The cross-sectional study included 280 and follow-up study-40 asymptomatic participants; aged 38.30 ± 4.10. For all study participants computed tomography examination was performed, sKIM-1 and FGF-21 levels were measured. Results The results indicated asymmetrical deposition of adipose tissue into the RS even after corresponding kidney volume adjustment. The cross-sectional and the follow-up studies showed that sKIM-1 level was positively associated with RS adipose tissue volume increase for both genders. FGF-21 was positively associated with RS and retroperitoneal adipose tissue amount. Conclusions Regardless of gender adipose tissue in RS accumulates asymmetrically–the left RS accumulates a significantly higher amount of adipose tissue. Thus, primarily RS adipose tissue effects should be assessed on the left kidney. Accumulation of adipose tissue in the RS is related with the visceral adipose amount, KIM-1 and FGF-21 concentration increase in the blood serum.Item HDL-C role in acquired aortic valve stenosis patients and its relationship with oxidative stress(2019-08) Hofmanis, Juris; Hofmane, Dace; Svirskis, Simons; Mackevics, Vitolds; Tretjakovs, Peteris; Lejnieks, Aivars; Signorelli, Salvatore Santo; Department of Internal Diseases; Institute of Microbiology and Virology; Department of Human Physiology and BiochemistryBackground and objectives: Mechanical stress is currently considered as the main factor promoting calcific aortic valve stenosis (AS) onset. It causes endothelial damage and dysfunction. The chronic inflammatory process causes oxidative stress. Oxidative stress-induced high-density lipoprotein cholesterol (HDL-C) dysfunction is an important component of the development of AS. The aim of the study was to evaluate the role of HDL-C in AS patients in three severity grades and in relation to the biomarkers of oxidative stress, thioredoxin reductase 1 (TrxR1) and myeloperoxidase (MPO). Materials and Methods: 18 patients with mild, 19 with moderate. and 15 with severe AS were included in the study, and 50 individuals were enrolled in the control group. Stenosis severity was determined by echocardiography. The TrxR1 and MPO were analyzed by ELISA, and HDL-C by commercially available tests. Data were analyzed using GraphPad Prism 8. Results: HDL-C in AS patients vs. control substantially decreases and this decline was observed in all three AS severity groups: mild (p = 0.018), moderate (p = 0.0002), and severe (p = 0.004). In both the control and the stenosis group, the HDL-C was higher in women than in men. In comparison to control, the HDL-C level was lower in the AS group, and more pronounced in women (p = 0.0001) than in men (p = 0.049). A higher TrxR1 level was observed in patients with mild (p = 0.0001) and severe AS (p = 0.047). However, a clear correlation between TrxR1 and HDL-C was not obtained. Analysis of MPO showed differences in all severity grades vs. control (p = 0.024 mild stenosis; p = 0.002 moderate stenosis; p = 0.0015 severe stenosis). A negative correlation (p = 0.047; rp = −0.28) was found between MPO and HDL-C, which confirms the adverse effects of MPO resulting in HDL-C dysfunction. Conclusions: In this study, we justified HDL-C level association with AS development process. The results unequivocally substantiated the association between HDL-C and AS in all severity grades in women, but only in moderate AS for men, which we explained by the small number of men in the groups. The obtained correlation between the HDL-C and MPO levels, as well as the concurrent decrease in the HDL-C level and increase in the TrxR1 level, indicate in general an HDL-C association with oxidative stress in AS patients.Item Increased serum chemerin level to predict early onset of aortic valve stenosis(2018-01) Lurins, Juris; Lurina, Dace; Tretjakovs, Peteris; Mackevics, Vitolds; Lejnieks, Aivars; Rapisarda, Venerando; Baylon, Vincenzo; Department of Human Physiology and Biochemistry; Department of Internal DiseasesInflammation appears to be the cause of aortic valve (AoV) stenosis and identification of predictive biomarkers is therefore imperative. The aim of the current study was to evaluate the potential role of serum chemerin and fibroblast growth factor-21 (FGF-21) in the pathogenesis of the disease. A total of 102 patients were selected based on certain criteria and divided into an aortic stenosis group and a control group. Patients with AoV stenosis were subdivided into three groups depending on the severity according to the echocardiography criteria: Aortic jet velocity, Vmax (m/ sec); mean pressure gradient, PG (mmHg); aortic valve area (AVA), cm2; and indexed AVA, cm2/m2. Patients were graded as: Severe: Vmax >4 m/sec, PG >40 mmHg, AVA <1.0 cm2, indexed AVA <0.6; moderate: Vmax 3.0-4.0 m/sec, PG 20-40 mmHg, AVA 1.0-1.5 cm2, indexed AVA 0.60-0.85; mild: Vmax 2.5-2.9 m/sec, PG <20 mmHg, AVA >1.5 cm2, indexed AVA >0.85. ELISA was used for the detection of chemerin and FGF-21. Post-hoc analysis with Tukey's correction was performed. The highest chemerin levels were found in mild and moderate AoV stenosis and decreased along with the grade of severity, compared with the control group. The FGF-21 level was increased in all the stenosis groups, reaching the highest level at severe stenosis. Receiver-operating characteristic analysis of chemerin in all the AoV stenosis groups without grading the severity included, area under the curve (AUC)=0.76; 0.70-0.80= fair; P<0.001 and for mild AoV stenosis was AUC=0.82; 0.80-0.90= good; P<0.001. In conclusion, chemerin is a good diagnostic biomarker for mild AoV stenosis, while FGF-21 is a moderate diagnostic marker.Item Inflammatory cytokine and chemokine patterns in paediatric patients with suspected serious bacterial infection(2019-01-01) Rautiainen, Linda; Pavare, Jana; Grope, Ilze; Tretjakovs, Peteris; Gardovska, Dace; Department of Paediatrics; Department of Human Physiology and BiochemistryBackground and objectives: In children, acute infection is the most common cause of visits to the emergency department. Although most of them are self-limiting, mortality due to severe bacterial infections (SBI) in developed countries is still high. When the risk of serious bacterial infection is too high to ignore, yet too low to justify admission and hospital observation, clinicians try to improve diagnostic accuracy by performing various laboratory tests. The aim of the study was to investigate whether an early inflammatory cytokine and chemokine panel can add information in diagnostics of SBI and assessment of efficacy of early therapies in hospitalized children with fever. Methods: This study included 51 children with febrile infections that were admitted to the emergency department (ED). Clinical examination and microbiological and radiological tests were used as reference standards for the definition of SBI. Study population was categorized into two groups: (1) patients with SBI (n = 21); (2) patients without SBI (n = 30). Inflammatory cytokine and chemokine panels were analyzed from the first routine blood samples at hospital admission and after 24 h. Results: Out of 12 cytokines and chemokines, only Eotaxin and granulocyte colony-stimulating factor (G-CSF) had statistically significant differences between groups at the time of inclusion. Receiver operator characteristic analysis to predict SBI showed an area under the curve (AUC) of 0.679 for G-CSF. Conclusions: Analysis of inflammatory cytokine profiles may provide additional information in early diagnostics of SBI.Item Influence of Migraine on Axon Reflex-Mediated and Endothelial-Dependent Vasodilatation in the Skin(2021-06-01) Plinta, Aelita; Tretjakovs, Peteris; Logina, Inara; Miķelsone, Indra; Blumfelds, Leons; Bahs, Guntis; Rīga Stradiņš UniversityThe aim of the study was to evaluate the changes in skin blood flow as a result of local heating tests in migraine patients during the interictal period, measured by laser Doppler perfusion imaging (LDI). The aim of the study was also to estimate the correlations between the results of these tests and interleukin (IL)-8 levels. Twelve migraine patients during their interictal period were compared with twelve healthy control subjects. Only women were included in the study. Both groups were matched with regard of their age, body mass index and blood pressure. For the purpose of measuring cutaneous microvascular blood flow, heating (+44 °C) of the dorsal side of the palm as a response to the local LDI was used. IL-8 was measured in serum by ELISA method. The findings suggested that migraine patients have a cutaneous vasomotor dysfunction during the interictal period. The results showed a significant decrease in the initial peak of vasodilation and the second peak of vasodilation (plateau phase). Also there were significant changes observed in the length of the time interval required to reach the first and second vasodilation peak. It is known that migraine patients have a shorter time interval to reach the first perfusion peak (axonal reflex-mediated) and longer time interval to reach the second peak (endothelium-dependent). The results confirmed the correlation between proinflammatory chemokine IL-8 levels, and the time interval till the second peak of blood flow in all study subjects.Item Laboratory Tests in Addition to the Alvarado Score in the Management of Acute Appendicitis in School-Age Children(2019-08-01) Zviedre, Astra; Eņgelis, Arnis; Tretjakovs, Peteris; Zile, Irisa; Petersons, Aigars; Department of Paediatric Surgery; Department of Human Physiology and Biochemistry; Department of Public Health and EpidemiologyThe aim of the study was to determine whether the Alvarado score (AS) together with laboratory tests could be used to distinguish patients with acute appendicitis (AA) from acute mesenteric lymphadenitis (AML). Fifty-seven patients (7-18 years) with suspected AA were included in the prospective study (October 2010 - October 2013). Thirty-one patients underwent surgery for AA and 26 were not treated surgically and were diagnosed AML on ultrasonography. AS, white blood cell count (WBC), C - reactive protein (CRP) and serum cytokines (EGF, IL-10, IL-12(p70), IL-1β, IL-4, IL-6, IL-8, IL-17, MCP-1, TNF-α) were obtained on admission and were compared between groups. Mean age of the 57 patients was 12.9 (SD 3.2). Accuracy (AR) for AS ≥ 7 alone was 73.7% for AA. Modified AS with certain serum cytokines seemed to be a reliable tool for initial differential diagnosis between AA and AML in school-age children. Based on these results, AS ≥ 7, WBC ≥ 10.7 × 103/μL and serum IL-6 ≥ 4.3 pg/mL assessed altogether will yield more sensitivity for AA. Also for further advanced diagnostics, we propose to take into account the serum IL-6, IL-8, MCP-1, CRP cut-off levels in the differential diagnosis between complicated and uncomplicated AA to decide whether the treatment should be conservative or surgical.Item Levels of Inflammatory Cytokines and Chemokines in Hospitalized Children with Sepsis and Pneumonia(2013-12-01) Rautiainen, Linda; Ince, Svetlana; Pavare, Jana; Grope, Ilze; Tretjakovs, Peteris; Gardovska, Dace; Department of Paediatrics; Department of Human Physiology and BiochemistryIntroduction. Pneumonia is a common childhood lower respiratory tract infection, which accounts for large number of hospitalization and death among children; its diagnosis is based mainly on clinical signs.Aim of the study was to measure inflammatory cytokine panels in children with pneumonia, and their correlation with clinically used inflammatory markers. Materials and methods. We included 20 patients, hospitalized in Children’s Clinical University hospital, with systemic inflammatory response syndrome (SIRS) and radiologically confirmed pneumonia from October 2011 to January 2013. In all patients cytokine and chemokine panels and clinical inflammatory markers were measured at the time of admission, after 24 hours and on the time of discharge.Results. 12 different inflammatory cytokines were measured. sFAS, sVCAM1, IL-8, IL-10, TNF alpha, Eotaxin, G-CSF, IL1ra, IP10 and MCP1 showed statistically significant changes between levels of inclusion in the study and levels after 24 hours. G-CSF, IL-8, IFN gamma, TNF alpha and IL-10 showed also medium strong correlation with clinically used inflammatory markers (PCT, CRO, and IL-6).Conclusions. Inflammatory cytokines show statistically significant changes during course of treatment, thus they could be used in diagnostics in septic patients with pneumonia, and also could show patients response to therapy.Item Melatonin concentrations and sleep quality in patients with type 2 diabetes and obesity(2019-05-01) Kalere, Ieva; Konrade, Ilze; Proskurina, Anna; Upmale, Sabine; Zaķe, Tatjana; Limba, Normunds; Krieviņa, Gita; Lejnieks, Aivars; Tretjakovs, Peteris; Department of Human Physiology and Biochemistry; Department of Internal DiseasesThere is a close relationship between melatonin as a circadian regulator and insulin, glucagon and somatostatin production. This study aimed to describe subgroups of type 2 diabetes mellitus (T2DM) patients that may benefit from melatonin clock-targeting properties. The study involved 38 participants: 26 T2DM patients, and 12 participants without diabetes in the control group. Subjects were asked to complete the questionnaire of Pittsburgh Sleep Quality Index (PSQI). Standard biochemical venous sample testing was performed, and a sample of saliva was collected for melatonin testing. Melatonin concentration in participants without obesity (body mass index (BMI) < 30 kg/m 2 ) was significantly higher than in obese participants: 13.2 (6.4; 23.50) pg/ml vs 5.9 (0.78; 13.1) pg/ml, p = 0.035. Subjects with BMI 30 kg/m 2 had a significantly higher PSQI score than non-obese subjects: 7 (4.5; 10) vs 5.5 (3; 7), p = 0.043. T2DM patients showed significantly lower levels of melatonin than the control group: 6.1 (0.78; 12.2) pg/ml vs 17.8 (8.2; 25.5) pg/ml, p = 0.003. T2DM patients using short-acting insulin analogues showed a significantly higher PSQI score than patients not using insulin: 9 (6; 10) vs 6 (3; 8), respectively (p = 0.025). Poor sleep quality was more prevalent in patients with diabetic retinopathy than in those without this complication (p = 0.031). Lower melatonin levels were detected in T2DM and obese patients. Furthermore, poor sleep quality was observed in T2DM patients using short-acting insulin analogues and those with diabetic retinopathy, and obese individuals.Item Prognostic utility of circulating growth factors in aortic valve stenosis : A pilot study(2021-01) Hofmanis, Juris; Tretjakovs, Peteris; Svirskis, Simons; Gersone, Gita; Hofmane, Dace; Rozenberga, Ulla; Blumfelds, Leons; Bahs, Guntis; Lejnieks, Aivars; Mackevics, Vitolds; Faculty of MedicineBackground and Objectives: Aortic valve stenosis (AS) develops with a pronounced local inflammatory response, where a variety of growth factors are involved in the process, and may have a pro-inflammatory and anti-inflammatory effect. The aim of our study was to elucidate whether circulating growth factors: growth differentiation factor 15 (GDF-15), angiopoietin-2 (Ang-2), vascular endothelial growth factor A (VEGF-A), fibroblast growth factor 2 (FGF-2), and fibroblast growth factor 21 (FGF-21) could be proposed as clinically relevant biomarkers to improve risk stratification in AS patients. Materials and Methods: AS patients were classified into three groups: 16 patients with mild AS stenosis; 19 with moderate and 11 with severe AS, and 30 subjects without AS (echocardiographically approved) were selected as a control group. GDF-15, Ang-2, VEGF-A, FGF-2, and FGF-21 were measured in plasma by the ELISA method. Results: GDF-15 levels differed significantly not only when comparing AS patients with control groups (p < 0.0001), but also a statistically significant difference was achieved when comparing AS patients at a mild degree stage with control individuals. We found a strong relationship of GDF-15 levels regarding AS severity degree (p < 0.0001). VEGF-A, FGF-2 and FGF-21 levels were significantly higher in AS patients than in controls, but relationships regarding the AS severity degree were weaker (p < 0.02). ROC analysis of the study growth factors showed that GDF-15 might serve as a specific and sensitive biomarker of AS stenosis (AUC = 0.75, p = 0.0002). FGF-21 correlated with GDF-15, Ang-2, and FGF-2, but it did not reach the level to serve as a clinically relevant biomarker of AS stenosis. Conclusions: AS is associated with significantly increased GDF-15, VEGF-A, FGF-2, and FGF-21 levels in plasma, but only GDF-15 shows a pronounced relationship regarding AS severity degree, and GDF-15 might serve as a specific and sensitive biomarker of AS stenosis.Item Prognostic utility of circulating growth factors in aortic valve stenosis : A pilot study(2021-01) Hofmanis, Juris; Tretjakovs, Peteris; Svirskis, Simons; Gersone, Gita; Hofmane, Dace; Rozenberga, Ulla; Blumfelds, Leons; Bahs, Guntis; Lejnieks, Aivars; Mackevics, Vitolds; Faculty of MedicineBackground and Objectives: Aortic valve stenosis (AS) develops with a pronounced local inflammatory response, where a variety of growth factors are involved in the process, and may have a pro-inflammatory and anti-inflammatory effect. The aim of our study was to elucidate whether circulating growth factors: growth differentiation factor 15 (GDF-15), angiopoietin-2 (Ang-2), vascular endothelial growth factor A (VEGF-A), fibroblast growth factor 2 (FGF-2), and fibroblast growth factor 21 (FGF-21) could be proposed as clinically relevant biomarkers to improve risk stratification in AS patients. Materials and Methods: AS patients were classified into three groups: 16 patients with mild AS stenosis; 19 with moderate and 11 with severe AS, and 30 subjects without AS (echocardiographically approved) were selected as a control group. GDF-15, Ang-2, VEGF-A, FGF-2, and FGF-21 were measured in plasma by the ELISA method. Results: GDF-15 levels differed significantly not only when comparing AS patients with control groups (p < 0.0001), but also a statistically significant difference was achieved when comparing AS patients at a mild degree stage with control individuals. We found a strong relationship of GDF-15 levels regarding AS severity degree (p < 0.0001). VEGF-A, FGF-2 and FGF-21 levels were significantly higher in AS patients than in controls, but relationships regarding the AS severity degree were weaker (p < 0.02). ROC analysis of the study growth factors showed that GDF-15 might serve as a specific and sensitive biomarker of AS stenosis (AUC = 0.75, p = 0.0002). FGF-21 correlated with GDF-15, Ang-2, and FGF-2, but it did not reach the level to serve as a clinically relevant biomarker of AS stenosis. Conclusions: AS is associated with significantly increased GDF-15, VEGF-A, FGF-2, and FGF-21 levels in plasma, but only GDF-15 shows a pronounced relationship regarding AS severity degree, and GDF-15 might serve as a specific and sensitive biomarker of AS stenosis.Item Prognostic utility of novel biomarkers in aortic valve stenosis(2019-05-01) Tretjakovs, Peteris; Hofmanis, Juris; Hofmane, Dace; Krieviņa, Gita; Blumfelds, Leons; Mackevičs, Vitolds; Lejnieks, Aivars; Bahs, Guntis; Faculty of MedicineThe aim of the present study was to evaluate plasma levels of chemerin, myeloperoxidase (MPO), fibroblast growth factor-21 (FGF-21), thioredoxin reductase-1 (TrxR1), and matrix metallopeptidase-9 (MMP-9) in acquired aortic valve (AoV) stenosis patients to determine correlations between the studied cellular factors, and also clarify the predictive values of these factors as biomarkers in AoV stenosis. AoV stenosis patients were classified into three groups: 17 patients with mild AoV stenosis; 19 with moderate and 15 with severe AoV stenosis. Twenty-four subjects without AoV stenosis were selected as a control group. Our findings suggest that AoV stenosis might be associated with increased chemerin, TrxR1, MPO, and FGF-21 levels in plasma. Moreover, these factors and also MMP-9 already reached statistically significantly elevated levels in the early stages of AoV stenosis, but MPO levels were more pronounced in patients with moderate and severe AoV stenosis. Chemerin was correlated with all of the studied cytokines; TrxR1 and MMP-9 were correlated with several other cellular factors. Our findings (by ROC analysis) suggest that MPO and chemerin might serve as specific and sensitive biomarkers for AoV stenosis without grading the severity, but, in relation to mild AoV stenosis, TrxR1, FGF-21, and MMP-9 also reached good or moderate levels as biomarkers. The cellular factors might serve as novel diagnostic and prognostic biomarkers in AoV stenosis patients, while chemerin and MPO may be more powerful.Item Red Beetroot Juice and Stamina: An Experimental Study(2022-09) Smirnova, Galina; Tretjakovs, Peteris; Fedotova, Anna; Simanis, Raimonds; Vasiljeva, Svetlana; Suhorukovs, Olegs; Seglina, Dalija; Krasnova, Inta; Bartkevics, Vadims; Babarykin, Dmitry; Rīga Stradiņš UniversityIntroduction: Red beet juice is increasingly used in sports to enhance the endurance of athletes. To increase the specific efficiency of red beet juice, the method of its fractionation by ultrafiltration was used for the first time. The purpose of the study was to evaluate the effect of fractionated beetroot juice on the strength and endurance of laboratory rats. Methods: Male Wistar rats (6 groups; n = 10) were used in the study. In addition to the standard chow, some groups of rats 2 h before the exercises received 0.5 ml of native (RBJ) or fractionated (FRBJ) per os. Three groups of animals were trained using a motorized wheel with a gradual speed increase over four weeks: 20 min/day for five days a week. Muscle strength of animals in all groups was measured by electronic dynamometry and the endurance of rats was evaluated once a week using electrical stimulation on a racetrack which moved at a speed of 15 m/min. The test was performed an hour after the ingestion of RBJ or FRBJ. At the end of the experiment, biochemical blood indices were determined. FRBJ was prepared by the original method. Results: Most significant differences in the chemical composition of RBJ and FRBJ were found for glutamic acid, of which the content was 67.2% higher than in native juice. The greatest changes during the experiment were in the mass of the rats’ calf muscles. Regular running exercise caused a 29% increase in muscle mass. The additional increase in m. gastrocnemius was also provided y FRBJ – 12%. The combination of physical activity and the introduction of red beet derivate led to the increase of the calf muscle mass by 121% within a month. Assessing the endurance of animals by frequency of falling from the treadmill, we can conclude that compared with untrained animals, trained rats receiving FRBJ had three times higher levels of endurance. Conclusion: Consumption of FRBJ led to increased muscle strength in rats and the ergogenic effect of the product was significantly higher in combination with physical activity.Item Relation of endothelial dysfunction and adipokines levels to insulin resistance in metabolic syndrome patients(2009) Tretjakovs, Peteris; Jurka, Antra; Bormane, Inga; Miķelsone, Indra; Reihmane, Dace; Balode, Liga; Jaunalksne, Inta; Mackevičs, Vitolds; Stuķena, Inga; Bahs, Guntis; Lejnieks, Aivars; Aivars, Juris; Pirags, Valdis; Rīga Stradiņš UniversityObese metabolic syndrome (MS) patients were categorised into three groups: 44 with type 2 diabetes mellitus (T2DM)(D); 20 with T2DM and coronary artery disease (CAD) (DC), and 26 with MS alone (M). Eighteen healthy subjects were selected as controls (C). Insulin resistance (IR) was assessed by HOMA-IR. Adiponectin, tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), and interleukin-8 (IL-8) concentrations were measured by xMAP technology. Endothelin-1 (ET-1) was determined by ELISA. We used laser Doppler imaging for evaluating cutaneous endothelium-dependent vasodilatation in the hand. D and DC groups had significantly elevated IR compared with M or C group (P < 0.01). TNF-α, IL-6, IL-8, MCP-1 and ET-1 levels in DC were significantly elevated compared with other groups (P < 0.001). IL-6, IL-8, MCP-1 and ET-1 in D group were higher than those in C group (P < 0.05). TNF-α, IL-6, IL-8, MCP-1 and ET-1 concentrations were correlated with HOMA-IR indexes and adiponectin levels. All patients had lower adiponectin concentrations than controls (P < 0.001), but there were no differences between the patient groups. Only D and DC groups demonstrated a significant and similar decrease in LDI-Ach marker compared to C group (P < 0.001). LDI-Ach values were significantly correlated with HOMA-IR indexes and adiponectin levels (P < 0.001). Our findings show that obese MS patients have significantly increased HOMA-IR, TNF-α, IL-6, MCP-1 and IL-8 levels, decreased adiponectin concentration, and endothelial dysfunction, but the presence of T2DM and CAD in these patients is associated with more pronounced endothelial dysfunction and increased production of inflammatory cytokines and chemokines.Item Role of serum cytokines in acute appendicitis and acute mesenteric lymphadenitis among children(2016) Zviedre, Astra; Engelis, Arnis; Tretjakovs, Peteris; Jurka, Antra; Zile, Irisa; Petersons, Aigars; Department of Paediatric Surgery; Department of Human Physiology and Biochemistry; Department of Public Health and EpidemiologyBackground and objective The diagnostic role of serum cytokines depends on the etiology and pathogenesis of acute appendicitis (AA) and acute mesenteric lymphadenitis (AML). The aim of this study was to evaluate differences in cytokine levels between AA and AML. Materials and methods Data of 7- to 18-year-old children were collected prospectively from October 2010 to October 2013. There were 31 patients with AA (AA group), 26 with AML (AML group), and 17 with elective non-inflammatory surgical disease (control group). Serum levels of IL-10, IL-12(p70), IL-1β, IL-4, IL-6, IL-8, IL-17, MCP-1, EGF, TNF-α and white blood count (WBC) were measured three times consecutively in each group. Results The level of IL-6 and IL-10 was significantly higher in the AA group than the AML group at the first measurement (8 pg/mL vs. 3.2 pg/mL, P = 0.000; 6.1 pg/mL vs. 3.2 pg/mL, P = 0.005, respectively). There was a significant difference observed in time dynamics of concentration of IL-6 and MCP-1 for AA and AML. The area under the curve (AUC) was 0.77 (95% CI 0.64–0.89; P = 0.001) for IL-6 with a cut-off value of 4.3 pg/mL (67.7% sensitivity and 76.9% specificity) for AA 1 h before surgery. The AUC for WBC was 0.72 (95% CI 0.58.4–0.85; P = 0.005) with a cut-off value of 10.7 × 103/μL (sensitivity 71.0% and specificity 46.2%). Conclusions Serum IL-6 with a cut-off value of 4.3 pg/mL and WBC with a cut-off value of 10.7 × 103/μL assessed together will yield more sensitivity for AA.Item Thioredoxin‐1 and correlations of the plasma cytokines regarding aortic valve stenosis severity(2021-08-18) Tretjakovs, Peteris; Lurins, Juris; Svirskis, Simons; Gersone, Gita; Lurina, Dace; Rozenberga, Ulla; Blumfelds, Leons; Bahs, Guntis; Lejnieks, Aivars; Mackevics, Vitolds; Faculty of MedicineAortic valve stenosis (AS) develops not only with a pronounced local inflammatory re-sponse, but also oxidative stress is involved. The aim of this study was to evaluate the plasma levels of thioredoxin‐1 (TRX1), myeloperoxidase (MPO), chemerin, growth differentiation factor 15 (GDF‐ 15), angiopoietin‐2 (Ang‐2), vascular endothelial growth factor A (VEGF‐A), fibroblast growth factor 2 (FGF‐2), fibroblast growth factor 21 (FGF‐21), and metalloproteinase (MMP)‐1, ‐3, and ‐9 in acquired AS patients as well as to clarify the correlations of TXR1 and the plasma inflammatory biomarkers regarding AS severity. AS patients were classified into three groups: 16 patients with mild AS stenosis, 19 with moderate and 11 with severe AS, and 30 subjects without AS were selected as a control group. AS patients had significantly higher plasma levels of TRX1 compared to controls, but the highest difference was found in mild AS patients compared to the controls. We conclude that AS is associated with significantly increased plasma TRX1 levels, and TRX1 might serve as a specific and sensitive biomarker of AS. TRX1 and also chemerin, GDF‐15, VEGF‐A, FGF‐2 and FGF‐ 21 significantly correlate with AS severity degrees. TRX1 also showed positive association with FGF‐2, VEGF‐A, and MMP‐3 in all AS patients.