scholarly journals Hepatosplenomegaly in liver cirrhosis is caused by reactive oxygen species formation, an increase in apoptosis and autophagy, and pronounced autoimmune reactions

2021 ◽  
Vol 12 (3) ◽  
pp. 408-418
Author(s):  
E. M. Klimova ◽  
L. A. Drozdova ◽  
O. V. Lavinska ◽  
E. A. Bychenko ◽  
Y. H. Kot ◽  
...  

Various factors of infectious and toxic genesis can lead to the liver cirrhosis, often accompanied by complications such as recurrent bleeding due to portal hypertension against the background of hepatosplenomegaly. Metabolic changes and disturbances in immunoreactivity occur in the liver and spleen. To substantiate the choice of personalized treatment tactics for patients with hepatosplenomegaly, we investigated individual metabolic predictors and immunopathological processes in patients with: liver cirrhosis and hepatitis B (HBV) and/or hepatitis C (HCV) viruses (I group, n = 52); with herpes viruses CMV (cytomegalovirus) and EBV (Epstein-Barr virus) (II group, n = 48), and with splenomegaly and frequent recurrent bleeding associated with hereditary enzymopathies (III group, n = 15). We used the methods of immunoturbidimetry; enzyme immunoassay; light, fluorescence and confocal microscopy. In group I (HBV/HCV), we revealed a decrease in the C4 component; a significant increase in the phagocytic index and phagocytic number, a reduced number of active phagocytes and the digestion index; a decrease in the IL-1β content and an increase in IL-18 and IL-6. In group II (CMV/EBV), we revealed a high activity of the C3 and a low activity of the C4 component against the background of a high level of ROS in neutrophils; the antineutrophil antibodies (ANCA) formation in 85.7% of patients (71.4% –perinuclear antibodies (pANCA) to myeloperoxidase; 14.3% – cytoplasmic antibodies (CANCA) to proteinase 3). Also, in group II, an increased level of pro-inflammatory cytokines IFN-γ, IL-1β, TNF-α, IL-18 and anti-inflammatory IL-6 was detected. Changes in links of immunity in II group led to the formation of autoimmune reactions in 64.7% of patients, which was expressed in the development of a broad range of antinuclear antibodies ANA (11 specificities, including ANA to chromatin and chromatin-associated proteins, to proteins cytoskeleton, enzymes and enzyme complexes). In group III, we revealed a low absorption capacity of neutrophils, a high frequency of antineutrophil antibodies pANCA occurrence and cANCA (in 67.2% of the examined), and low concentration of TNF-α. The developed model of the stepwise change of immunological markers makes it possible to substantiate the choice of a complex targeted treatment, including antiviral and immunotropic therapy.

The study of the role of the spleen in the pathogenesis of liver cirrhosis is important for treatment. Currently available literature data indicate the role of altered spleen functions in the pathogenesis of liver cirrhosis. The aim of this study was to clarify the features of the etiology and pathogenetic disorders in patients with hepatosplenomegaly. Materials and methods. We investigated the uniform elements of blood and blood serum from 58 patients with hepatosplenomegaly amid cirrhosis, portal hypertension complicated. Patients were divided into two groups depending on the antigenic load: I - patients with liver cirrhosis against the background of hepatitis viruses HBV/HCV and II - patients with autoimmune hepatitis against the background of herpes viruses CMV/VEB. Treatment of patients included the use of antiherpetic immunoglobulins and hematopoietic cord blood progenitor cells. Results. In patients of group I was detected an increase in the spontaneous oxidative activity of neutrophils and depletion of the oxidative reserve in oxygen-dependent phagocytosis. It activated the signaling pathways of pro-inflammatory cytokines IL-6 (an increase of 60 times). We found an increased content of CD22+ -plasma B-lymphocyte that elevated synthesized concentrations of IgA. In patients of group II were found an increase in the activity of C3 and a decrease in the C4-components of complement; thrombocytopenia due to the presence of platelet autoantibodies; increased synthesis of immunoglobulins IgM, IgG, increased synthesis of IFN-. All patients showed disturbances in the metabolism of amino acids in various metabolic cycles - ornithine, which disrupted the formation of urea and indicates the accumulation of ammonia, which can enhance the cytotoxic effect in group I; methionine with a violation of the formation of cystine from cysteine and the accumulation of homocysteine, which enhances the synthesis of IFN-γ, which was increased in group II by 4 times. Conclusions. Some etiological and pathogenetic features of the formation of liver cirrhosis complicated by portal hypertension and recurrent bleeding from varicose veins of the esophagus were revealed. The immunological and metabolic changes verified by us correlated with the disappearance of the clinical manifestations of the disease, improved well-being, and the absence of recurrence of bleeding.


2021 ◽  
Vol 19 (1) ◽  
pp. 58-63
Author(s):  
J.-C. Khakizimana ◽  
◽  
V.N. Timchenko ◽  
V.P. Novikova ◽  
O.P. Gurina ◽  
...  

Objective. To analyze clinical and laboratory parameters, as well as the dynamics of cytokine production in children of different ages with acute infectious mononucleosis caused by Epstein-Barr virus (EBV mononucleosis). Patients and methods. We examined two groups of patients: group I included 20 children aged 1 to 7 years, whereas group II included 29 children aged 8 to 17 years. All study participants were tested in the acute phase of the disease and in early convalescence. We evaluated serum levels of interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor-α (TNF-α), and interferon-α (IFN-α) using enzyme-linked immunosorbent assay (ELISA) (standard Vektor-Best kits, Russia). Data analysis was performed using Microsoft Excel 2019 for Windows and IBM SPSS statistics; we applied the methods of non-parametric statistics. Differences were considered significant at p < 0.05. Results. The majority of children had fever, intoxication, acute tonsillitis, and enlarged cervical lymph nodes. Laboratory makers, such as lymphocytosis, neutropenia, and thrombocytopenia were more pronounced in children from group II. In both groups, the level of cytokines in the acute period of the disease was higher than the discriminatory one. In early convalescence, patients from group I demonstrated more significant reduction in the cytokine level than patients from group II (р < 0.05). In children over 7 years of age, the levels of IL-10 and TNF-α positively correlated with the disease duration (p < 0.01 and p < 0.05, respectively) Conclusion. The level of cytokine production in acute EBV mononucleosis depends on patients’ age. Concentrations of IL-10 and TNF-α can serve as markers reflecting the severity of EBV mononucleosis and can be used for disease prognosis. Key words: EBV mononucleosis, children, cytokines, IL-6, IL-10, TNF-α, IFN-α


Biomedicines ◽  
2019 ◽  
Vol 7 (2) ◽  
pp. 39
Author(s):  
Sahar Youssef ◽  
Marwa Salah

Olanzapine is an antipsychotic drug effective in the treatment of stress-associated psychiatric illnesses, but its effect on the spleen remains unclear. Vitamin C is essential for the optimum function of the immune system. We aim to investigate the effect of Olanzapine on spleen structures and to assess the protective effect of vitamin C. Forty adult male albino rats were divided into four groups: group (I), a control; group (II), rats were given vitamin C at 40 mg/kg body weight; group (III), rats were given Olanzapine at 2 mg/kg body weight; and group (IV), rats were given vitamin C and Olanzapine at the same dose of group (II) and group (III) for one month. The hematoxylin and eosin (H&E) of the olanzapine treated group showed focal areas of cellular depletion and a decrease in the size of the white pulp. The red pulp was expanded and showed marked congestion and dilatation of blood sinusoids. Cluster of differentiation 3 (CD3) was significantly reduced, however both tumor necrosis factor alpha (TNF-α), and vascular endothelial growth factor (VEGF) were significantly higher. The administration of vitamin C repaired structural and immunohistochemical changes via increased CD3 and decreased TNF-α and VEGF. Therefore, the oxidative and the inflammatory pathways may be the possible mechanisms underlying olanzapine immunotoxicity. Vitamin C exerted immune modulator and antioxidant effects against olanzapine.


2019 ◽  
Vol 65 (5) ◽  
pp. 418-423
Author(s):  
A.I. Autenshlyus ◽  
A.A. Studenikina ◽  
A.V. Bernado ◽  
E.S. Mikhailova ◽  
A.V. Proskura ◽  
...  

Breast cancer, in most cases, is a malignant neoplasm associated with infiltration of a tumor with the cells that form its microenvironment and produce various cytokines. The aim of the study was to evaluate the cytokine-producing function of tumor cells and their microenvironment in biopsy specimen of patients with invasive carcinoma of no special type and in patients with benign breast diseases. To assess the cytokine-producing activity of the tumor and its microenvironment, the index of polyclonal activators influence on cytokine production by biopsy specimens of patients with invasive carcinoma of no special type (group I) and in patients with benign breast tumors (group II) was calculated. Group II was further subdivided into group IIa, which included only patients with fibroadenoma, and group IIb, which included the patients with leaf-shaped fibroadenoma, fibroadenomatosis, fibrocystic mastopathy, intraductal papillomatosis, sclerosing adenosis and fibrocystic mastopathy with microcalcifications. The concentrations of IL-2, IL-6, IL-8, IL-10, IL-17, IL-18, IL-1β, IL-1Ra, TNF-α, IFN-γ, G-CSF, GM-CSF, VEGF, and MCP-1 were measured in tumor biopsy supernatants. When comparing groups I and II, higher indices of the polyclonal activators influence on the production of IL-17, IL-18 and TNF-α were observed in patients with benign diseases. Higher indices of the polyclonal activators influence on the production of IL-18, TNF-α, and IL-1β and the ratio of IL1β/IL1Ra were observed in patients with fibroadenoma as compared to those with invasive carcinoma of no special type. There were no significant differences in the indices of the polyclonal activators influence between groups I and IIb. This suggests the existence of changes in the mammary gland in patients of group IIb similar to those present in patients with invasive carcinoma of no special type. Higher indices of polyclonal activators influence on the production of IL-1β, as well as the ratio of IL1β/IL1Ra were observed in the patients of group IIa compared to the patients of group IIb. The results of the study identify the features of the cytokine-producing resource of tumor biopsy specimens in patients with invasive carcinoma of no special type and with benign breast tumors.


2014 ◽  
Vol 60 (3) ◽  
pp. 102-105 ◽  
Author(s):  
Enikő Csifo ◽  
Tímea Katona ◽  
Juliánna Arseni ◽  
E. Nagy ◽  
I. Gergely ◽  
...  

Abstract Objectives: Study of circulating and synovial levels of osteocalcin, osteoprotegerin and tumor necrosis factor-alpha (TNF-α) in patients with different stages of knee osteoarthritis and correlation analysis of these parameters with disease severity. Methods: We enrolled 20 patients with different stages of knee osteoarthritis. The IKDC score (International Knee Documentation Comittee, 2000) was determined for each patient. Based on these data patients were divided into two groups: group I (advanced osteoarthritis) and group II (early osteoarthritis). Serum and synovial fluid levels of osteocalcin, osteoprotegerin, TNF-α were determined. Results: For the entire group the level of osteocalcin in the serum showed higher values than in the synovial fluid. We found statistically significant differences in the serum levels of osteocalcin between the two groups (group I: 2.18 ± 0.54 ng/ml, group II: 6.07 ± 1.98 ng/ml, p = 0.019). Serum and synovial osteocalcin in the whole study lot could not be correlated with the disease score, however we observed a tendency towards significant negative correlation between the serum osteocalcin and IKDC score for group I and between synovial osteocalcin and IKDC score in group II. In the entire group, synovial osteoprotegerin concentration was six times higher than the serum osteoprotegerin level (p <0.0001) and TNF-α showed higher circulating levels than local concentrations. Conclusions: In the advanced osteoarthritis group the serum and synovial osteocalcin show lower values than in the early osteoarthritis group, which means that as the disease progresses, bone anabolism decreases. In the case of osteoprotegerin, no significant difference between the two groups was detected.


2020 ◽  
pp. 64-69
Author(s):  
O. M. Babii ◽  
B. F. Shevchenko ◽  
A. V. Tuzko ◽  
O. M. Tatarchuk ◽  
O. P. Petishko

Summary. Objective. To increase the efficiency of diagnostics in determining the wall formation of the pancreatic pseudocyst and the activity of the inflammatory process. Materials and methods. A total of 99 patients were examined who underwent digestive tract surgery from 2006 to 2019 with pseudocyst that developed on the background of acute and chronic pancreatitis. There were 73 males (73.74 %), 26 females (26.26 %), 21 to 74 years of age (47.55–2.4 years). Based on the morphological data of the biopsy material, pancreatic pseudocyst (PC) wall formation and inflammatory activity in chronic pancreatitis, patients were divided into two representative groups: Group I (n = 41) — patients with formed wall of PC, group II (n=58) — patients with unformed PC wall. Morphology data were compared with the data of immunological parameters and radiation diagnostic methods. Results. The TNF-α/IL-10 ratio was higher (p <0.05) in patients in group II than in group I. To differentiate the activity of inflammation, a threshold value of 1.4 was set (sensitivity — 86.7 %, specificity — 59.1 %). The IL-6/IL-10 ratio was higher (p <0.05) in group II patients, which also indicated an imbalance of pro- and anti-inflammatory mediators and was characteristic of active inflammation. The threshold value of the ratio of IL-6/IL-10, above which patients were diagnosed with active inflammation in the PC wall — less than or equal to 1.1 (sensitivity — 91.7 %, specificity — 84.6 %). In group II patients, the level of PMN-elastase was higher (p<0.05) than in group I, which indicated the activity of inflammation. Threshold of fecal PMN-elastase, above which patients were diagnosed with active inflammation of PC wall less than or equal to 84 ng/ml (sensitivity — 90.9 %, specificity - 66.7 %). 3. According to ultrasound/MSCT, the wall thickness of PC in group I was (4.41±0.49)/(4.27±2.02) mm, in group II (2.50±0.52)/(2.75±1.44) mm, which is probably less than 1.7 times and 1.6 times (p <0.05) with the unformed PC wall. According to SWE, the threshold value of the average stiffness values ​​of the PC wall, above which it was diagnosed, was> 7.6 kPa (sensitivity — 80.0 %, specificity 78.9 %). Conclusions. Indices of TNF-α/IL-10, IL-6/IL-10, PMN-elastase, ultrasound, MSCT, SWE have been determined, which allow to evaluate the formation of PC wall and the activity of the inflammatory process.


Health of Man ◽  
2021 ◽  
pp. 93-98
Author(s):  
Vladyslav Ozhogin

The objective: optimization of approaches to the choice of endoscopic ureterolithorpsy method in the presence of large stones of the proximal ureter. Materials and methods. For the period 2017–2020 y. the study included 136 patients with large stones of the proximal ureter, who were performed one of two methods of ureterolithotripsy: rULT (group I) or m-aULT (group II). In group I 73 (53,7%) patients were operated, in group II – 63 (46,3%) patients. The age of patients ranged from 18 to 81 years, the average age was 52,7 years (54±10,5). The age of patients in group II ranged from 25 to 77 (63±10,5) years; the size of a concrement from 10 to 20 (14±3,5 mm). In group I, the age of patients ranged from 18 to 91 (63,5±10 years); the size of a concrement from 7 to 20 (12±5,5 mm). Results. The average time of m-AULT was 58,5±15,4 min, while the status of stone free was achieved in all 100% of patients. The operation ended with the installation of nephrostomy drainage in 11 (17,5%) cases, nephrostomy drainage and internal ureteral JJ-stent – in 33 (52,4%), in 19 (30,2%) cases – tubeless drainage method with the installation of ureteral stent. And the total percentage of stenting in staghorn stones of the proximal ureter, after lithotripsy and litholapaxy was 82,6% (52 patients). RULT surgery in 92% (67 patients) of cases ended with drainage of the kidney by JJ-stent, in 6 (8%) patients the operation ended without drainage. Conclusions. Analyzing the results, it was noted that the antegrade approach is a safe and effective method of treatment for proximal ureterolithiasis in the group with large stones of the proximal ureter, where the effectiveness of RULT (SFR up to 86,3±3,9%) is significantly inferior to AULT, and minimizing the size of instruments m-aULT) reduces the number and degree of complications associated with the size of the coiled tract, while providing a high level of SFR (96,8±4,4%).


QJM ◽  
2020 ◽  
Vol 113 (Supplement_1) ◽  
Author(s):  
S Abdelhamid ◽  
T M Alsakty ◽  
H H Radwan ◽  
M E Abouelmaaty ◽  
A S Allam ◽  
...  

Abstract Background hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide and it is one of the major causes of death, because of its high frequency and poor prognosis. Hepatocellular carcinoma is now a common malignancy in Egypt which usually develops on top of liver cirrhosis secondary to viral infection, as hepatitis C viruses increased the risk of HCC in the Egyptian patients. Aim of the Work was to verify the possibility of using the plasma squamous cell carcinoma antigen level as a tumor marker for hepatocellular carcinoma and to evaluate its prognostic value in management of HCC. Patients and Methods the study included 60 subjects divided into three groups: group I was 30 patients with hepatocellular carcinomas, group II was 15 patients with liver cirrhosis and group III was 15 normal subjects serving as a control group. Follow up of the patients who had HCC and undergone either RFA or TACE will be done after 1 month by measuring serum level of alfa feto protein & SCCA. Results the plasma SCCA level was significantly higher in group I patients (with HCC), than in the group II patients (cirrhosis) and control group. SCCA showed direct significant correlation with the most of laboratory data specially AST, INR, number and size of lesion and its values were decreased after intervention. Conclusion plasma SCCA is a sensitive and specific serum marker for the diagnosis and prognosis of HCC and combination of AFP and SCCA in screening and diagnosis of HCC yielded a better sensitivity in diagnosis of HCC.


2004 ◽  
Vol 19 (5) ◽  
pp. 264-271 ◽  
Author(s):  
Fevziye Toros ◽  
N. Gamsiz Bilgin ◽  
R. Bugdayci ◽  
T. Sasmaz ◽  
O. Kurt ◽  
...  

AbstractObjectivesThis cross-sectional randomised study involving a predominantly adolescent school population (ranging from the 6th to the 11th grades) was conducted to determine the prevalence and clinical characteristics of depression in adolescents in the city of Mersin, Turkey.Subjects and methodsA stratified sample of 4256 students was selected as representative of the city’s adolescent school population. The students were divided into two groups according to diagnosis (Group I: depressive adolescents; Group II: adolescents without depression). The age range varied between 10 and 20 years, with a mean of 14.53 years (S.D. = 1.89), i.e. a mean of 14.73 years (S.D. = 1.79) for Group I, and 15.5 years (S.D. = 1.9) for Group II. Data was obtained via two structured questionnaires designed to determine the presence and clinical characteristics of depression both in adolescents and in their parents. In addition, the Child Beck Depression Inventory (CBDI) was administered to all students participating in the study. After quality control of data, the study sample was reduced to 4143 adolescents. The mean age of the students was 11.23 ± 6.44 years, and the ratio of boys/girls was 1.19:1.ResultsThe prevalence of depression according to the CBDI (cut-off point: 19) was found to be 12.55% in this study group, with a significantly higher prevalence of depression in girls than in boys. Binary regression analysis demonstrated that the most important factors involved in the onset of depression in adolescents were having problems with parents, staying down a grade, and humiliation at school, and that the most common symptoms were feelings of worthlessness/guilt, sadness, emptiness, irritability and somatic disorders.ConclusionThis cross-sectional prospective randomised school-based study has examined sociodemographic and clinical characteristics of adolescents with depression in a student population. It was found that in this study group there was a relatively high level of depressive symptoms, with a clear predominance of females over males. Other clinical characteristics of adolescents with depression have been discussed in the context of previous investigations.


2008 ◽  
Vol 57 (12) ◽  
pp. 1533-1538 ◽  
Author(s):  
Mohammed Mahmoud El-Naggar ◽  
El-Sayed Abdul-Maksoud Khalil ◽  
Medhat Abdul Massih El-Daker ◽  
Mona Fouda Salama

The detection of bacterial DNA in serum and ascitic fluid (AF) from patients with liver cirrhosis and ascites is interpreted as molecular evidence of intestinal bacterial translocation (BT) and considered sufficient to activate the cellular immune response leading to greater cytokine synthesis. We studied 34 patients with liver cirrhosis and culture-negative, non-neutrocytic ascites [22 patients without bacterial DNA (group I) and 12 patients with bacterial DNA (group II)]. History and clinical examination were done with the following investigations at first admission and followed up for 24 weeks: serum and AF tumour necrosis factor-alpha (TNF-α), AF polymorphonuclear leukocytes, AF cultivation and detection of blood and AF bacterial DNA. Serum and AF TNF-α were significantly higher in patients with bacterial DNA compared to those without bacterial DNA at first admission [54.5±22.56 vs 35.2±17.97 pg ml−1 (P=0.02) and 123.2±49.32 vs 82.6±29.58 pg ml−1 (P <0.005), respectively]. These changes became highly significant at the end of follow-up of both groups [119.3±27.19 vs 40.2±16.08 pg ml−1 (P <0.001) and 518.8±91.11 vs 97.6±17.81 pg ml−1 (P <0.001), respectively]. In group II, there was a significant increase in serum and AF TNF-α at the end of follow-up compared to at first admission (P <0.001). The relative risk of death, hepatorenal syndrome (HRS) and spontaneous bacterial peritonitis (SBP) was higher in patients with bacterial DNA compared to those without bacterial DNA. We conclude that cirrhotic patients with culture-negative, non-neutrocytic ascites and bacterial DNA have a significantly higher level of serum and AF TNF-α and higher risk of HRS, SBP and mortality compared to those without bacterial DNA, suggesting that bacterial DNA and TNF-α are implicated in these complications of liver cirrhosis.


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