Clinical and prognostic significance of the soluble form of the VISTA immunity control point in patients with primary bone tumors

2021 ◽  
Vol 66 (9) ◽  
pp. 533-538
Author(s):  
N. E. Kushlinskii ◽  
Olga Vladimirovna Kovaleva ◽  
Yu. B. Kuzmin ◽  
E. A. Korotkova ◽  
E. S. Gershtein ◽  
...  

The data of a comparative enzyme-linked immunosorbent assay of the content of the soluble form of the immunity checkpoint VISTA in the blood serum of 30 healthy donors (control group), 79 patients with primary malignant (osteosarcoma - 30, chondrosarcoma - 31, chordoma - 14) and 14 borderline (giant cell tumor) bone neoplasms are presented. In the general group of patients with malignant neoplasms of bones, the median sVISTA content in blood serum is statistically significant lower than in the control (p = 0.040). In patients with bone tumors and healthy donors over 18 years of age, there was a decrease with age in serum sVISTA levels. There were no significant differences in sVISTA concentration between patients with osteosarcoma, chondrosarcoma and healthy donors. Only in patients with chordoma were sVISTA levels statistically significant lower than in controls (p = 0.013). In the groups of patients with chondrosarcoma and osteosarcoma of the bone, there were no significant associations between the serum sVISTA content and the main clinical and morphological characteristics of the disease. In patients with osteosarcoma, no relationship was found between sVISTA levels and overall survival rates, while in patients with bone chondrosarcoma, there was a tendency towards a favorable prognosis with a high content of the marker in the blood serum.

Author(s):  
Babaeva T.N. ◽  
Seregina O.B. ◽  
Pospelova T.I.

At present, the serum ferritin level is not included in the list of prognostic factors; however, it is known that its increased serum level in patients with malignant neoplasms relates with the tumor burden, the degree of disease activity and correlates with a worse prognosis in patients with hematologic malignancies.The normalization of serum ferritin level during remission period confirms the involving of hyperferritinemia in mechanisms of tumor progression and may testify for clinical importance of measurement of serum ferritin level in patients, including those with malignant lymphomas. Objective:The aim of this study was to assess of the prognostic significance of high ferritin levels at the onset of the disease in patients with malignant lymphomas. Materials and methods:98 patients with malignant lymphomaswere enrolled in this study, including 72 patients (73.5%) with non-Hodgkins lymphomas (NHL) and 26 patients (26.5%) with Hodgkin’s lymphoma (HL). The increased serum ferritin level (more than 350 ng/ml) was found in 53 (54.2%) patients with malignant lymphomas at the onset of disease and its average concentration was 587,62±131,6 ng/ml (8.3 times higher values of control group, p<0.001).Also the positive statistical correlationsbetween increased ferritin level and increased level of LDH (r=0.47, p<0.001, n=98) and C-reactive protein (r=0.41, p<0.001, n=98) as well as the presence of B-symptomswere found. The median OS was significantly shorter in the group of patients with increased ferritin level (more than 350 ng/ml) at the onset of disease in comparison with group of patients with normal ferritin level, where the median OS was not reach during the observation period. Patients with increased ferritin level before starting chemotherapy also showed worse results of overall survival and increased mortality risk (OR 8.122; 95% CI, 1.764-37.396;р<0.05) compare with a group of patients with ferritin level ˂350 hg/ml at the onset of disease. Conclusion:These results make it possible to include lymphomas’s patients with increased ferritin level at the onset of disease in the group with poor prognosis and lower OS, while the increased ferritin level in patients without previous blood transfusions should be considered as a significant prognostic factor.


2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Fengzhi Wu ◽  
Yuehan Song ◽  
Feng Li ◽  
Xin He ◽  
Jie Ma ◽  
...  

Wen-Dan Decoction (WDD), a formula of traditional Chinese medicine, has been clinically used for treating insomnia for approximately 800 years. However, the therapeutic mechanisms of WDD remain unclear. Orexin-A plays a key role in the sleep-wake cycle, while leptin function is opposite to orexin-A. Thus, orexin-A and leptin may be important factors in sleep disorders. In this study, 48 rats were divided into control, model, WDD-treated, and diazepam-treated groups. The model of insomnia was produced by sleep deprivation (SD) for 14 days. The expressions of orexin-A, leptin, and their receptors in blood serum, prefrontal cortex, and hypothalamus were detected by enzyme-linked immunosorbent assay, immunohistochemistry, and real time PCR. Open field tests showed that SD increased both crossing movement (Cm) and rearing-movement (Rm) times. Orexin-A and leptin levels in blood serum increased after SD but decreased in brain compared to the control group. mRNA expressions of orexin receptor 1 and leptin receptor after SD were decreased in the prefrontal cortex but were increased in hypothalamus. WDD treatment normalized the behavior and upregulated orexin-A, leptin, orexin receptor 1 and leptin receptor in brain. The findings suggest that WDD treatment may regulate SD-induced negative emotions by regulating orexin-A and leptin expression.


2021 ◽  
pp. 34-37
Author(s):  
B. Yu. Kuzmichev ◽  
O. S. Polunina ◽  
L. P. Voronina ◽  
T. V. Prokofieva ◽  
E. A. Polunina

Objective. To create a personalized mathematical model of the development of complications – cardiogenic shock and pulmonary edema in patients with myocardial infarction (MI) with chronic obstructive pulmonary disease (COPD) depending of the homocysteine (HCY) level and the COPD phenotype.Materials and methods. The study included 88 patients with MI and COPD with various phenotypes: 25 patients with emphysematous phenotype, 22 patients with a mixed phenotype, 20 patients with chronic bronchitis phenotype, 21 patients with eosinophilia and bronchial asthma (BA). As a control group, 50 somatically healthy individuals were examined. Gender anamnestic, clinical, and laboratory – instrumental indicators were studied and analyzed to develop a predictive mathematical model. The level of HCY was determined by enzyme-linked immunosorbent assay in all patients.Results. It was found that in patients with MI and COPD with different COPD phenotypes, the level of HCY was statistically significantly higher than in the control group. The highest level of HCY was in patients with the chronic bronchitis phenotype and was 45 [14.1; 51.9] mmol/l, which was statistically significantly higher than in patients with the phenotype with eosinophilia and BA, with emphysematous and mixed phenotypes. Predictor factors were selected using the logit regression method from gender-anamnestic, clinical, and laboratory – instrumental indicators to create a mathematical model with the highest prediction accuracy. HCY level and COPD phenotype were predictors of the mathematical model for predicting the development of complications – cardiogenic shock and pulmonary edema in patients with MI and COPD. It was also found that the threshold value of HCY for predicting the development of cardiogenic shock and pulmonary edema in patients with MI and COPD was 0.82 ± 0.51 confidence interval [0.72–0.91] mmol/l (p < 0.001).Conclusion. The personalized mathematical model initiated for predicting the development of complications-cardiogenic shock and pulmonary edema in patients with MI and COPD, depending of the HCY level and the COPD phenotype, has a high sensitivity (85%) and prognostic significance (92%), which allows us to recommend it for use in clinical practice.


2020 ◽  
Author(s):  
Wioletta Ratajczak-Wrona ◽  
Lukasz Wozniak ◽  
Jan Borys ◽  
Bozena Antonowicz ◽  
Karolina Nowak ◽  
...  

Abstract Background Nitric oxide is a small gaseous molecule with significant bioactivity. It has been observed that NO may have a dual role dependent on its production and concentrations in the bone microenvironment. The objective of the study was to assess the concentration of total nitric oxide malonyldialdehyde, nitrotyrosine, and asymmetric dimethylarginine in the serum of patients with mandibular fractures and to understand the relationship between these compounds, in order to expand the knowledge base of the role of nitric oxide and its activity indicators in the process of bone fracture healing.Material and methods The study included patients with mandibular fractures who were undergoing inpatient and outpatient treatments. Results were analyzed with respect to the measurement time. Total nitric oxide concentration in the blood serum was determined according to the Griess reaction, while the concentration of malonyldialdehyde, nitrotyrosine, and asymmetric dimethylarginine was estimated using the immunoenzymatic method (i.e. enzyme-linked immunosorbent assay).Results Before procedure as well as on the first day and 2 and 6 weeks after the procedure, higher concentrations of total nitric oxide and lower concentrations of malonyldialdehyde were observed in the blood serum of patients with mandibular fractures compared to the control group. No statistically significant differences were found in nitrotyrosine concentrations in the blood serum of patients throughout the measurement period. However, a significantly higher asymmetric dimethylarginine concentration was observed in the patient serum before the procedure and on the first day of operation as compared with the control group. Analysis of the results observed in patient serum with respect to the number of fractures within the mandible demonstrated the same trend of concentrations for the tested compounds for the entire study group.Conclusions In summary, our results revealed that the intensity of local processes resulting from mandibular fractures is associated with the concentration of nitric oxide, confirming its significant role, as well as that of its indicators, in the process of bone fracture healing in this patient population.


2015 ◽  
Vol 18 (1) ◽  
pp. 20
Author(s):  
Ye. N. Berezikova ◽  
M. G. Pustovetova ◽  
S. N. Shilov ◽  
A. V. Yefremov ◽  
A. T. Teplyakov ◽  
...  

The aim of the study was to assess the relationship of homocysteine levels in the blood serum with the severity and nature of chronic heart failure (CHF) in patients with coronary heart disease. 94 patients with CHF were examined. The control group included 32 patients without cardiovascular disorders. At baseline and after 12 months of observation the homocysteine levels in the blood serum were determined by enzyme-linked immunosorbent assay. Correlative relationship of hyperhomocysteinemia with ischemic myocardial remodeling and with reduced inotropic function in CHF patients was observed. The homocysteine level in the blood serum of CHF patients significantly exceeded that of the control group and moderately increased with the progression of the disease severity of functional class. In the group with an unfavorable course of CHF the baseline homocysteine level proved to have the greatest value as compared to that in the group with a favorable course. In patients with a favorable course of CHF the homocysteinemia level tended to decrease towards the end of prospective study, whereas in patients with an unfavorable course, on the contrary, hyperhomocysteinemia persisted (p<0.01). In case the hyperhomocysteinemia baseline exceeds 18.5 mkmol/L (ROC-AreaSE = 0.860.04, sensitivity 71 %, specificity 90%), the severity and characteristics of the ischemic CHF could be most likely predicted. Thus, hyperhomocysteinemia is related with the severity and nature of CHF. Determining the level of homocysteine in the blood serum can be recommended for early prediction of the severity and nature of CHF.


1995 ◽  
Vol 13 (3) ◽  
pp. 575-582 ◽  
Author(s):  
J F Seymour ◽  
M Talpaz ◽  
F Cabanillas ◽  
M Wetzler ◽  
R Kurzrock

PURPOSE Interleukin-6 (IL-6) is a potent immunomodulatory cytokine that may have pathogenetic and prognostic significance in a number of disorders. The objective of this study was to examine the correlation between serum IL-6 levels and phenotypic characteristics, as well as outcome of patients with diffuse large-cell lymphoma (DLCL). PATIENTS AND METHODS Using an enzyme-linked immunosorbent assay (ELISA; lower limit of sensitivity, 0.35 pg/mL), we measured IL-6 levels in frozen sera from 33 healthy controls and 58 untreated patients with DLCL who were enrolled onto a single combination chemotherapy protocol. Serum IL-6 levels were correlated with clinical and laboratory features at diagnosis and with failure-free and overall survival. RESULTS Serum IL-6 levels in the lymphoma patients (median, 4.37 pg/mL; range, < 0.35 to 110 pg/mL) were significantly higher than in the control group (median, < 0.35 pg/mL; range, < 0.35 to 1.87 pg/mL) (P < .0001). Serum IL-6 levels were higher in patients with B symptoms (P = .012), an elevated beta 2-microglobulin level (> or = 3.0 mg/L) (P = .017), and a poor performance status (P = .02). Direct linear correlations with the erythrocyte sedimentation rate (ESR), platelet count, and total WBC count, and an inverse linear correlation with the serum albumin level, were observed (all P < .02). Patients with elevated serum IL-6 levels had inferior failure-free (P = .042) and overall survival (P = .05) compared with those with normal serum IL-6 levels. CONCLUSION In patients with DLCL, elevated serum levels of IL-6 at diagnosis are frequent, strongly associated with many adverse disease features, and predictive of a poor failure-free and overall survival.


2018 ◽  
Vol 22 (4) ◽  
pp. 81-89
Author(s):  
O. V. Semeshina ◽  
V. N. Luchaninova ◽  
A. Nee ◽  
E. V. Markelova ◽  
N. V. Gorelik ◽  
...  

THE AIM: to study diagnostic and prognostic significance of blood serum cytokine status evaluation in children with different nosological forms of kidney diseases.PATIENTS AND METHODS. The study included 255 children with various kidney diseases (kidney stone disease (KSD) – 16, with  infectious kidney diseases (IKD) – 174, with a glomerulopathy (GP)  – 65). In all study groups were dominant children with 1st and 2nd  stage of CKD (100%, 97,5% and 95,4% respectively). The control group included 50 virtually healthy children. All patients  determined level of TNF-α, TNF-RI and TNF-RII, IL-10, TGF-β1 and TGF-β3, IL2, IL2-SR in blood serum.RESULTS.Increase of TNF-α level in blood serum can be considered as a highly specific marker of acute pielonephritis chronization, as  well as decrease of TNF-RII concentration can be considered as a  marker of full clinical and laboratory pielonephritis remission. The  increase in TNF-α and TNF-RI can also be considered as a marker of autoimmune inflammation. Deficiency of IL-2, IL-10 and TGF-β3  with an increase in IL-2 R in blood should be used as a marker of  bacterial-inflammatory and autoimmune kidney diseases, and TGF- β1 increase as an early marker of nephrosclerosis, especially in  patients with glomerulonephritis. The increase of the inflammatory  index TNF-α / IL-10 more than 4 times, gives us  the opportunity to  position it as an additional diagnostic criterion for infectious and  autoimmune process in the kidneys. The increase in urinary  excretion of TNF-α with the decrease of IL-10 by maintaining  consistently high concentrations of TGF-β1 is a marker of  inflammation and fibrosis in infectious kidney diseases and  glomerulonephritis. Modern nephroprotection therapy directed at  slowing progression of CKD and its complications should include  modulation of cytokine status.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 455.2-456
Author(s):  
Y. Akhverdyan ◽  
В. Zavodovsky ◽  
E. Papichev ◽  
J. Polyakova ◽  
L. Seewordova

Background:In recent years, the systemic effects of a number of cytokines have been actively studied, in particular, fetuin-A is considered a negative protein of the acute phase response, and visfatin, on the contrary, affects the activation of the cytokine cascade and has a pro-inflammatory effect. Taking into account that women suffer from rheumatoid arthritis (RA) more often, we investigated the levels of fetuin-A and visfatin in the blood serum of females in comparison with a group of healthy individuals and depending on the activity of the disease.Objectives:to study the levels of fetuin-A and visfatin in the blood serum of women suffering from RA, depending on the activity of the diseaseMethods:The study included 110 women with RA and 30 apparently healthy individuals. The inclusion criteria were: a diagnosis of RA verified based on the criteria of the American College of Rheumatology/European Anti-Rheumatic League (ACR/EULAR) 2010. The patients’ age ranged from 18 to 90 years. The control group included 30 conventionally healthy individuals. Serum fetuin-A and visfatin levels were determined by indirect enzyme-linked immunosorbent assay using commercial kits. RA activity was determined by the DAS28-CRP index. Activity 0-I was in 33 (30%) patients, grade II in 67 (60.9%), grade III in 10 (9.09%) patients.Results:The normal level of fetuin-A was calculated using the formula M±2σ in the group of conventionally healthy individuals and ranged from 653.55 to 972.19 μg/ml. In patients with grade 0-I RA activity according to DAS28, the mean serum fetuin-A level was 843.92±130.73 μg/ml, in patients with grade II activity - 742.37±98.85 μg / ml, with III the degree of activity - 663.9±123.7 μg/ml (p<0.001).The average level of visfatin in the blood serum in healthy individuals was 2.43±0.17 ng/ml. The level of normal values of visfatin in healthy individuals, defined as M±2σ, ranged from 0 to 5.07 ng/ml. The average level of visfatin in patients with RA was 6.27±0.18 ng/ml, which is significantly higher than in healthy individuals (p<0.001).In patients with 0-I degree of RA activity according to DAS28, the average level of visfatin in blood serum was 4.94±0.02 ng/ml, in patients with degree II activity - 5.08±0.02 ng/ml, with III degree of activity - 6.82±0.23 ng/ml (p<0.001).Conclusion:Thus, the level of fetuin-A in the blood serum of patients with RA is significantly lower in the case of a high degree of disease activity. The level of visfatin in the blood serum in women with RA is significantly higher in patients with a higher degree of disease activity. Therefore, the concentration values of fetuin-A and visfatin in the blood serum of patients with RA can be used in an integrated assessment of the prognosis of disease activity.References:[1]Inoue K, Ikeda Y, Yamanaka S, et al. Serum fetuinA levels in patients with rheumatoid arthritis [abstract]. Atherosclerosis. 2002;9(Suppl 1):233. doi: 10-1016/s1567-5688(08)70930-9[2]Janssens K, ten Dijke P, Janssens S, et al. Transforming growth factor-beta1 to the bone. Endocrine Reviews. 2005;26(6):743-74. doi:10.1210/er.2004-0001[3]Polyakova J, Korolik O, Papichev E, et al. The role of «new» cytokines in the pathogenesis rheumatoid arthritis. Ann Rheum Dis. 2018; 78(2): 1497Disclosure of Interests:None declared


2004 ◽  
Vol 3 (4) ◽  
pp. 21-25
Author(s):  
N. A. Trofimenko ◽  
V. N. Zorina ◽  
S. V. Arkhipova ◽  
Ya. A. Gorbatovsky ◽  
R. M. Zorina

Concentrations of cytokines (IL-1β, IL-6, TNF-α) of α2-macroglobulin (MG), α1-antitrypsin (AT) plasminogen (PL), whole protein, albumin and uric acid in blood serum of patients with collagenosis have been investigated aiming the study of their complex interaction and the possibility of their use during differential diagnostics. The blood serum of 60 healthy donors, 53 patients with rheumatoid arthritis (RA), 15 patients with reactive arthritis (REA) and 16 patients with systemic lupus erythematosus (SLE) has been studied. IL-1β, IL-6 and TNF-α concentrations have been defined by ELISA, MG, AT and PL-rocket immunoelectrophoresis, the whole protein, albumin and uric acid — by biochemical methods. The albumin level decreased in all groups of patients. The whole protein concentration decreased at the first RA activity degree. MG, AT and PL levels had no difference at all diseases as compared to the control group. IL-6 concentration increased significantly at all patients groups. TNF-α increased with the RA severity but differed statistically significantly from REA and SLE only at the most severe degree. Analogous trends in IL-1β concentration have been found in cases of RA and SLE but at REA great individual fluctuations with the high average level have been found. Synchronous change of the studied cytokine concentrations without associated MG level change is evidence of the damage of traffic and regulatory functions of this protein. The uric acid can be used for SLE diagnostics and the dynamic supervision of IL-1β and TNF-α can be a prognostic criterion at RA.


2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
Y Sibagatullina ◽  
M Pugina ◽  
I Voronkina ◽  
E Zhiduleva ◽  
P Evstigneeva ◽  
...  

Abstract Background The main mechanism of aortic valve (AV) calcification is not yet known. One of the possibility pathway responsible for AV calcification (AVC) includes osteoprotegerin (OPG), receptor activator of nuclear factor kappa-B ligand (RANKL) – the parts of the RANKL-RANK-OPG system and fetuin-A: cysteine protease inhibitors. Aim Evaluation of OPG, sRANKL, fetuin-A in blood serum and tissues in patients with varying severity of aortic stenosis (AS) to establish potential methods of estimation AVC depending on the presence of congenital heart disease: bicuspid AV (BAV) or its absence. Materials and methods The study involved 285 patients with AS (59.06±6.95 years, m:f – 1.1:1): 163 with (BAV) and 122 with tricuspid AV (TAV). The control group 53 patients (48.31±9.04 years, m:f-1:1) without valvular pathology, connective tissue dysplasia and coronary heart disease. ECHO (Vivid 7, GE, USA) was performed in all patients. The expression of OPG, RANKL, fetuin-A in homogenates of aortic valve were determined by immunoblotting. Serum concentration of OPG, RANKL, fetuin were performed in all pts by enzyme-linked immunosorbent assay. Results In the control group the concentration of fetuin-A in the blood serum was significantly higher than in TAV and BAV subgroups (446.66 [293.63; 619.19] vs 319.9 [239.6; 400.2] vs 315.6 [245.6; 385.6] pmol/l, p=0.ehab724.1560001). In all groups of patients with AS an increased level of sRANKL in the blood serum was revealed compared to the control group (TAV=0.39 [0.25; 0.53] vs BAV=0.38 [0.21; 0.55] vs control group 0.31 [0.18; 0.44] pmol/l; p&lt;0.005). OPG level in serum was increased in patients with TAV: 8.1 [4.3; 11.9] pmol/l compared to BAV: 6.8 [3.9; 9.7] pmol/l, p=0.003, as well as the control group: 6.15 [3.41; 8.89] pmol/L, p=0.001. RANKL expression in AV tissue was significantly lower in patients in the control group: 2119,06 [1990.94; 2554.11] as compared with AS pts: 4273.03 [2887.620; 4956], p=0.001, and in subgroups with TAV: 4273.08 [2887.620; 5285], p=0.002 or BAV: 4272.99 [2884.430; 4847], p&lt;0.01. In addition, a positive correlation of moderate strength was found between the RANKL in the blood serum and the expression of RANKL in the AV tissue in patients with BAV (r=0.357, p=0.04). OPG expression in the AV tissue was higher in patients in the control group: 3949,953 [1931.88; 6447.67], while significant only in comparison with the BAV subgroup: 2599.28 [1066.38; 4132.18], p=0.02. A positive correlation of moderate strength was found between the OPG in the blood serum and the expression of OPG in the AV tissue in TAV subgroup (r=0.423, p=0.03). Conclusion Different pathogenic mechanisms of AV calcification are accompanied by an increase in various markers of the OPG / RANK / RANKL system: in patients with TAV calcification marker is OPG, in patients with BAV it is RANKL. FUNDunding Acknowledgement Type of funding sources: None.


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