The Association of Serum Profile of Transferrin Isoforms with COVID-19 Disease Severity.

Background/Objective: Bearing in mind the relationship of transferrin (TRF) microheterogeneity with the biological activity of its isoforms, we propose, in this study, to determine the association of the profile of TRF isoforms with COVID-19 disease severity and to compare this profile to the profiles of other diseases. Methods: The disease group consisted of 96 patients from whom blood was collected twice, upon admission to the ward and after treatment (on average on the ninth day). TRF isoforms were separated by capillary electrophoresis. The analysis included disease severity, cytokine storm, comorbidities, patient survival, oxygen therapy, and modified early warning scores (MEWSs). Results: The concentration of 5-sialoTRF was higher in patients compared to controls at the beginning and during COVID-19 treatment. The concentration of this isoform varies with the severity of disease and was higher in critical patients than those with a moderate condition. Additionally, the level of 5-sialoTRF was lower and the level of 4-sialoTRF was higher in patients with comorbidities than that in patients without them. The concentration of 5-sialoTRF was lower and the concentration of 4-sialoTRF was higher in surviving patients than in non-surviving patients. There were no statistical changes in TRF isoforms according to presence of cytokine storm, MEWS, and oxygen therapy. Conclusions: We conclude that the profile of TRF isoforms in COVID-19 patients differs from that in other diseases. An increase in the concentration of a sialic acid-rich isoform, 5-sialoTRF, may be a compensatory mechanism, the goal of which is to increase oxygen delivery to tissues and is dependent on the severity of the disease. Additionally, the concentration of 5-sialoTRF may be a prognostic marker of the survival of COVID-19 patients.

The Diagnostic Value of FibroTest and Hepascore as Non-Invasive Markers of Liver Fibrosis in Primary Sclerosing Cholangitis (PSC).

The aim of this study was to evaluate the diagnostic usefulness of two non-invasive, validated, and patented markers of liver fibrosis, the Hepascore and FibroTest, in patients with primary sclerosing cholangitis (PSC). The study group consisted of 74 PSC patients and 38 healthy subjects. All patients had a liver biopsy. The Hepascore and FibroTest were calculated using specific algorithms. The ANOVA rank Kruskal-Wallis test revealed differences in the Hepascore and FibroTest between patients divided according to histological stage (p < 0.001 for both comparisons). The Hepascore and FibroTest had significantly higher results in patients with significant fibrosis (F ≥ 2) in comparison to those with no significant fibrosis (F1) (p < 0.001 for both tests) and higher values in patients with cirrhosis (F4) when compared to those without cirrhosis (F1-F3) (p < 0.001 for both comparisons). The Hepascore test showed a diagnostic sensitivity of 96.8%, a specificity of 100% for fibrosis (at cut-off 0.52) and a diagnostic sensitivity of 95.2%, and a specificity also of 100% for cirrhosis (at 0.80). The FibroTest in point 0.51 for the diagnosis of fibrosis obtained the following values: 58.6%, 90%, 89.5%, and 60%, respectively, and in point 0.73 for the diagnosis of cirrhosis: 42.9%, 100%, 100%, and 45.5, respectively. The Hepascore test reached an excellent diagnostic power in identifying both fibrosis and cirrhosis (AUC = 1.0). The FibroTest and Hepascore are highly valuable for the evaluation of the severity of liver fibrosis and cirrhosis in PSC patients and can be used as a primary screening method, allowing for a significant reduction in the need for liver biopsy. Both markers have the required sensitivity and specificity to detect liver fibrosis and cirrhosis and can be equally used in clinical practice, although the Hepascore seems to be a better test because it is more specific.

The Serum Profile of Transferrin Isoforms in Pancreatitis.

Total transferrin concentration changes in acute-phase reactions. Additionally, the alteration of transferrin glycosylation in inflammations can occur. The aim of this study is to evaluate the effect of pancreatitis on the serum profile of transferrin isoforms. The tested groups consisted of 84 patients with acute pancreatitis and 42 patients with chronic hepatitis. Transferrin isoforms were analyzed by capillary electrophoresis on a MINICAP electrophoretic system (Sebia, France). There was a significant decrease in the concentration of pentasialotransferrin in both acute and chronic pancreatitis, and a significant increase in tetrasialotransferrin in the acute pancreatitis group when compared to the control group. There were no significant changes in transferrin isoforms between the acute and chronic pancreatitis groups, and between the edematous and necrotizing forms of the disease. Considering the etiology of acute pancreatitis, we noticed higher values of bile acids and γ-glutamyltransferase in acute pancreatitis of alcoholic etiology than that in pancreatitis of other etiologies. In conclusion, the alterations in transferrin isoform profile in acute and chronic pancreatitis are not organ specific. Because similar changes were observed in hepatitis, we can conclude that the serum profile of transferrin isoforms is involved in the pathogenesis of the disease.

Non-Invasive Indirect Markers of Liver Fibrosis after Interferon-Free Treatment for Hepatitis C.

The effectiveness of interferon-free therapy during the course of HCV infection has already been confirmed. Liver fibrosis can be assessed in several ways, from biopsies to imaging tests. The present study evaluates the usefulness of non-invasive indirect biomarkers of liver fibrosis (APRI, GAPRI, FORNS, FIB-4, the AP index and HUI score) as markers of the effective treatment of HCV with the 3D regimen. Blood samples were collected from 70 patients suffering from chronic hepatitis C. Patients received the 3D AbbVie regimen for hepatitis C. All patients had HCV genotype 1b. The APRI, GAPRI, FIB-4, FORNS, HUI and AP index (age-platelet score) values were calculated with their respective algorithms. The stage of fibrosis was evaluated on the basis of a liver biopsy and confirmed by FibroScan-based transient elastography. An undetectable level of HCV RNA after 12 weeks of treatment with the 3D regimen indicates 100% eradication of hepatitis C virus. After the treatment, non-invasive indirect markers of liver fibrosis achieved levels below the limit for significant fibrosis, Thus, non-invasive indirect biomarkers of hepatic fibrosis failed to detect the presence of significant fibrosis, which was proved in histopathological examination. However, the eradication of hepatitis C virus by means of the 3D regimen treatment does not mean that patients were completely cured.

Oxidative Stress and Its Consequences in the Blood of Rats Irradiated with UV: Protective Effect of Cannabidiol.

UVA/UVB radiation disturbs the redox balance of skin cells, and metabolic consequences can be transferred into the blood and internal tissues, especially after chronic skin exposure to UV radiation. Therefore, the aim of this study was to evaluate the effect of cannabidiol (CBD), an antioxidant and anti-inflammatory phytocannabinoid, on oxidative stress and its consequences in the blood of nude rats whose skin was exposed to UVA/UVB radiation for 4 weeks. It was shown that CBD penetrated the blood and in UVB-irradiated rats was preferentially located in the membranes of polymorphonuclear leukocytes, which promoted reduction of ROS generation and up-regulation of antioxidant ability by increasing the activity of glutathione reductase and thioredoxin reductase, while the level of reduced glutathione decreased by UV radiation. Consequently, reduction in UV-induced lipid peroxidation, assessed as 4-hydroxynonenal (4-HNE) and 8-isoprostane (8-isoPGF2α) as well as protein modifications, estimated as 4-HNE-protein adducts and protein carbonyl groups, was observed. CBD, by countering the UV-induced down-regulation of 2-arachidonylglycerol, promoted its antioxidant/anti-inflammatory effects by reducing CB1 and increasing PPARγ receptor activation and consequently ROS and TNF-α down-regulation. The results suggest that CBD applied topically to the skin minimizes redox changes not only at the skin level, but also at the systemic level.

Comparison of hyaluronic acid in patients with rheumatoid arthritis, systemic sclerosis and systemic lupus erythematosus.

INTRODUCTION: The aim of the present study was to determine and compare the concentration of hyaluronic acid (HA) in rheumatoid arthritis (RA), systemic sclerosis (SSc) and systemic lupus erythematosus (SLE), and its correlation with parameters of disease activity and duration. The hypothesis was that HA should be increased in rheumatic diseases. We also expected that HA could be a marker of disease activity and inflammation in some of these diseases. MATERIALS AND METHODS: The study group comprised 149 patients with RA, SSc and SLE hospitalized in the Department of Rheumatology and Internal Diseases, Medical University of Bialystok (Bialystok, Poland) and 30 healthy controls. The concentrations of HA, C-reactive protein (CRP) and rheumatoid factor (RF) were measured using Architect ci8200; haemoglobin, platelets on Sysmex XS-800i; and erythrocyte sedimentation rate (ESR) on Sediplus S 2000 analysers. Statistical analysis was performed using Statistica 13.3 PL. RESULTS: Hyaluronic acid was increased in RA, SLE and SSc when compared to controls (P < 0.001, P = 0.011, and P = 0.015, respectively). There were no differences in HA between rheumatic diseases (P = 0.840). Hyaluronic acid positively correlated with SLE activity (P = 0.025). In RA, HA positively correlated with ESR (P = 0.028) and CRP (P = 0.009). However, HA was not found to correlate with the duration of rheumatic diseases. CONCLUSIONS: Hyaluronic acid concentration undergoes changes in rheumatic diseases with no difference between RA, SLE and SSc. In RA, HA concentration can be a marker of inflammation, while in SLE patients an indicator of disease activity.

Two SPRi biosensors for the determination of cathepsin S in blood plasma.

Cathepsin S is an emerging marker for ovarian cancer. Two 'analytically specific' SPRi biosensors for the determination of Cath S have been developed. The reception part of one of the biosensors consists of the rat monoclonal antibody specific for cathepsin S attached to the gold surface via covalent bonds with cysteamine linker, while the second biosensor consists of the inhibitor LY3000328 attached via hydrophobic interaction with the 1-octadecanothiol linker. Under optimized conditions, in terms of pH and receptor concentration, both biosensors have linear response ranges between LOQ (0.14 ng mL-1) and 2.5 ng mL-1, which is suitable for the determination of Cath S in blood plasma samples of ovarian cancer patients and healthy individuals, after corresponding dilution with 0.15 M PBS buffer. Precision and recoveries are quite acceptable: below 7% and 98-101% respectively for the biosensor with antibody, and below 12% and 101-103% for the biosensor with inhibitor. The biosensors were validated by the determination of Cath S in series of plasma from ovarian cancer patients and healthy volunteers using both biosensors and ELISA, giving Pearson coefficients close to 1. Plasma Cath S concentration can be used as an ovarian cancer marker, in view of the highly elevated concentrations detected.

Comparison of the interleukin 27 expression for the acute and chronic phase of mononucleosis in children.

BACKGROUND: The objective of the current study was to assess the serum level of interleukin 27 in children with mononucleosis and to compare the expression of this cytokine in the acute and chronic phase of the infection. METHODS: The level of IL-27 was determined using commercial enzyme-linked immunosorbent assay (ELISA) kits (Diaclone SAS, Besancon, France). Other laboratory findings were determined using routine laboratory methods. RESULTS: Serum level of IL-27 was found to be significantly higher in children with mononucleosis in comparison with healthy subjects (almost a 4-fold increase, 15.7 vs. 4.2 pg/mL, p < 0.001). It was also significantly higher in the acute phase compared to the chronic stage of the disease (more than a two-fold increase, 20.7 vs. 9.64 pg/mL, p < 0.001). This cytokine positively correlated with ALT, AST, LDH activity and WBC count (R = 0.498, p < 0.001; R = 0.586, p < 0.001; R = 0.170, p < 0.05, R = 0.329, p < 0.05, respectively) in the whole study, and only with AST activity in the chronic phase subgroup (R = 0.684, p < 0.05). CONCLUSION: In conclusion, this study shows that serum concentration of interleukin 27 in children with mononucleosis is increased, thus confirming the on-going inflammatory process. We also suggest that IL-27 can be a useful indicator to differentiate between the acute and chronic phase of the disease.

Endothelin-1 Serum Concentration in Pediatric Chronic Idiopathic Uveitis.

PURPOSE: The aim of our study was to determine endothelin-1 (ET-1) concentration in chronic idiopathic uveitis in children and adolescents depending on anatomical location and grade of inflammation. METHODS: The cross-sectional study was conducted among 17 patients with chronic idiopathic uveitis and 22 healthy controls. Concentration of ET-1 in serum was determined using a commercially available ELISA kit. The concentration of C reactive protein (CRP) in serum was determined by immunoturbidimetric method using CRP4 reagent kit (Roche Diagnostics GmbH, Mannheim, Germany). RESULTS: Statistically significant difference between ET-1 concentration in patients with chronic idiopathic uveitis and controls was found 1.33 (1.22; 1.48) vs 1.93 (1.1; 3.11), p = 0.008). No correlations were found between ET-1 concentration and age, either in chronic idiopathic uveitis patients or controls. Nine out of 17 patients presented with anterior uveitis, 5 with posterior and 3 with panuveitis. There were no differences in ET-1 concentration between anterior, posterior and panuveitis (p = 0.634), and in terms of grade of inflammation. CONCLUSION: ET-1 expression is disturbed in pediatric chronic idiopathic uveitis irrespective of the anatomical location and grade of inflammation. Lower expression of ET-1 plays a crucial role in disturbed vascular tone control and can result in permanent visual impairment in chronic non-infectious uveitis.

Diagnostic Power of Galectin-3 in Rheumatic Diseases.

BACKGROUND: The purpose of our study was to assess the diagnostic power of galectin-3 and compare its between rheumatic diseases and with routinely used tests such as CRP and ESR. METHODS: Eighty-two patients with rheumatoid arthritis (RA), 49 patients with systemic sclerosis (SSc), and 18 patients with systemic lupus erythematosus (SLE) were enrolled in this study. The control group comprised 30 healthy controls. Serum galectin-3 concentration was measured using immunochemical method. RESULTS: The galectin-3 concentration were significantly elevated in the RA, SSc, and SLE in comparison to the controls (p = 0.000, p = 0.000, p < 0.001; respectively). However, there were no significant differences in the serum galectin-3 levels between rheumatic diseases (H = 0.395, p = 0.821). In RA and SSc patients, galectin-3 positively correlated with erythrocyte sedimentation rate (R = 0.332, p = 0.004; R = 0.384, p = 0.009; respectively). ROC analysis revealed that galectin-3 had an excellent diagnostic power in RA (AUC = 0.911) and SSc (AUC = 0.903) and very good for SLE (AUC = 0.859). CONCLUSION: We concluded that diagnostic power of serum galectin-3 is as great as CRP and ESR in rheumatic diseases and it can be a very good laboratory marker in RA and SSc patients and a useful tool in the diagnosis of SLE.

Changed Profile of Serum Transferrin Isoforms in Primary Biliary Cholangitis.

Liver damage affects the synthesis of proteins and glycoproteins, and alters their posttranslational modification, such as glycosylation changing the serum profile of glycoprotein isoforms. The retention of hydrophobic bile acids in the course of cholestatic liver diseases is a major cause of liver damage in primary biliary cholangitis (PBC). The study objective was to determine the serum profile of transferrin isoforms in primary biliary cholangitis and compare it to transferrin isoforms profile in extrahepatic cholestasis. The study was carried out in 76 patients with PBC and 40 healthy blood donors. Transferrin isoforms were analyzed by the capillary electrophoresis method. The mean relative concentrations of disialotransferrin and trisialotransferrin in PBC were significantly lower than those in the healthy subjects (p < 0.001, p = 0.011; respectively). None of the transferrin isoforms changed according to the disease severity evaluated by the Ludwig scoring system. However, the disease stage affected the activity of alkaline phosphatase (ALP) and γ-glutamyl transferase (GGT), and albumin level (p = 0.002; p = 0.013 and p = 0.005, respectively). Our results indicate that serum profile of transferrin isoforms alters primary biliary cholangitis and differs in comparison to transferrin isoforms profile in extrahepatic cholestasis. The decreased concentrations of lower sialylated isoforms of transferrin (low percentage share in total transferrin level) are not associated with the histological stage of disease.

Modulation of the Paracrine Kynurenic System in Bone as a New Regulator of Osteoblastogenesis and Bone Mineral Status in an Animal Model of Chronic Kidney Disease Treated with LP533401.

An increase in the peripheral synthesis of serotonin and kynurenine, observed during the chronic kidney disease (CKD) course, is negatively associated with bone health. Serotonin and kynurenine are connected by the common precursor, tryptophan. LP533401 is an inhibitor of peripheral serotonin synthesis. This study aimed to establish if the inhibition of serotonin synthesis by LP533401 may affect the kynurenine pathway activity in bone tissue and its potential consequence with regard to osteogenesis and bone mineral status. Nephrectomized rats were treated with LP533401 at a dose of 30 and 100 mg/kg daily for eight weeks. Tryptophan and kynurenine concentrations were determined, and tryptophan 2,3-dioxygenase (TDO) expression was assessed. We discovered the presence of a TDO-dependent, paracrine kynurenic system in the bone of rats with CKD. Its modulation during LP533401 treatment was associated with impaired bone mineral status. Changes in TDO expression affecting the kynurenine pathway activity were related to the imbalance between peripheral serotonin and 25-hydroxyvitamin D. There were also close associations between the expression of genes participating in osteoblastogenesis and activation of the kynurenine pathway in the bones of LP53301-treated rats. Our results represent the next step in studying the role of tryptophan metabolites in renal osteodystrophy.

Transferrin isoforms analysis by capillary electrophoresis in systemic lupus erythematosus and systemic sclerosis.

The systemic lupus erythematosus (SLE) and systemic sclerosis (SSc) are a diseases in which disturbances in plasma proteins glycosylation exist. The aim of the study was to compare the serum profile of transferrin isoforms between SLE and SSc. The study was carried out in 38 patients with SLE and 43 patients with SSc. Transferrin isoforms were analyzed by capillary electrophoresis method. Among the transferrin isoforms only the level of pentasialotransferrin in SLE patients was significantly higher than in SSc patients (p = .014). The median concentrations of trisialotransferrin and pentasialotransferrin were significantly lower in SLE patients (p < .001, p = .042; respectively) and SSc (p = .001, p < .001; respectively) than in the healthy subjects. In contrast, the level of tetrasialotransferrin manifested significant increase in comparison to the controls (p < .001 for all comparisons). The serum profile of transferrin isoforms alters in SLE and SSc but only level of pentasialotransferrin differs between SLE and SSc patients. We confirm that the serum profile of transferrin isoforms in SLE and SSc is unique to these diseases.

The effects of adenoidectomy of serum insulin-like growth factor-1 (IGF-1) and ghrelin in hypertrophied adenoids in children with otitis media with effusion.

<b>Aim:</b> The aim of the current study was to assess the serum levels of insulin-like growth factor-1 (IGF-1) and ghrelin in hypertrophied adenoids in children suffering with or without otitis media with effusion before and after adenoidectomy. <br><b>Material and methods:</b> Serum IGF-1 and ghrelin concentrations were measured with specific enzyme-linked immunoassay (ELISA) methods. The study was carried out in 20 children with otitis media with effusion. The reference group comprised 24 children with hypertrophied adenoid, while control group included 19 children. <br><b>Results:</b> This mean values of IGF-1 in children with otitis media with effusion and children with hypertrophied adenoid before adenoidectomy were significantly lower than those found in healthy children. Serum levels of IGF-1 were higher after adenoidectomy. There was a significant difference of serum ghrelin levels between both examined groups and the control group. <br><b>Conclusion:</b> Our results suggest that adenoidectomy in children with hypertrophied adenoids and in children with otitis media with effusion significantly increases the level of IGF-1 in serum compared to before surgery through the effect of the GH-IGF-1 axis, which could contribute to children's growth.

Thyroid Function in Children with Down Syndrome in the Polish Population: A Case-Control Study.

BACKGROUND: Patients with subclinical thyroid disease have few or no clinical symptoms of thyroid dysfunction and thus, laboratory diagnosis is needed. In this context, the objective of the current study was to analyze the prevalence rate and pattern of thyroid function in children with Down syndrome in the Polish population. METHODS: A total of 30 children, aged 6-12 years, with cytogenetically confirmed Down syndrome were studied. The control group included 27 children. RESULTS: Of the 30 patients with Down syndrome, 14 (46.7%) had abnormal thyroid profiles. Mean thyroid-stimulating hormone (TSH) and fT4 concentrations in children with Down syndrome were found to be significantly increased compared with the controls (4.30 ± 1.9 µIU/mL, 95% CI: 3.55-5.04 µIU/mL vs. 3.10 ± 1.47 µIU/mL, 95% CI: 2.52-3.68 µIU/mL, P = 0.013, 95% CI: 0.26-2.14, and 1.33 ± 0.23 ng/dL, 95% CI: 1.25-1.42 vs. 1.19 ± 0.14 ng/dL, 95% CI: 1.13-1.25, P = 0.008, 95% CI: 0.04-0.24, respectively). In Down syndrome, subclinical hypothyroidism was recognized in 10 children (33.3%) (high TSH and normal fT4 and fT3 levels). Two children (6.67%) had evident hypothyroidism (high TSH and low fT4). In the control group, subclinical hypothyroidism was diagnosed in four (14.8%) children. CONCLUSION: Children with Down syndrome may have increased secretion of TSH, even when thyroid hormone and autoantibodies are normal, suggesting that an isolated increase in TSH does not predispose the patient to the development of thyroid disease. We also recommend that all patients with Down syndrome should be screened for thyroid dysgenesis, since they have thyroid dysfunction more frequently as compared to the general healthy population.

Vascular endothelial growth factor and transforming growth factor ß in hypertrophic adenoids in children suffering from otitis media with effusion.

OBJECTIVES: The study objective was to assess the levels of VEGF-A and TGF-ß cytokines in the children with adenoid hypertrophy concomitant with exudative otitis media (OME) and in children with adenoid hypertrophy (HA) alone. METHODS: The study material consisted of hypertrophic adenoids removed during adenoidectomy from 39 children (20 girls and 19 boys), aged 2-7 years suffering from OME. The reference group included 41 children (19 girls and 22 boys), aged from 3 to 9 years with adenoid hypertrophy. The levels of VEGF-A and TGF-ß were determined in supernatants obtained from phytohemagglutinin-stimulated cell cultures of the adenoids using a commercial enzyme-linked immunosorbent assay kit. RESULTS: The median VEGF-A and mean TGF-ß concentrations in the study group were significantly higher than those in the reference group (503 pg/mL versus 201 pg/mL, P < 0.001 and 224 pg/mL versus 132 pg/mL, P < 0.001, respectively). ROC analysis revealed that the area under the curve (AUC) for VEGF-A was 0.952 with diagnostic sensitivity and specificity of 95%, whereas for TGF-ß it was 0.902 with 60% sensitivity and the same specificity as for VEGF-A. There was no significant difference between the AUC for VEGF-A and TGF-ß (P = 0.573). CONCLUSIONS: The changes in the levels of VEGF-A and TGF-ß may indicate bacterial pathogen as one of the causes of exudative otitis media in children. Determination of VEGF-A and TGF-ß could be used as additional and objective tests to confirm the clinical diagnosis.

Endothelin-1 Serum Concentration is Lower in Children and Adolescents with High Myopia, a Preliminary Study.

The aim of this study is to evaluate the levels of enothelin-1 (ET-1) in children and adolescents with high myopia and its association with the axial length of the eye and the presence of myopic retinal degeneration. The cross-sectional study was carried out in 57 patients with high myopia and 29 control subjects. Serum concentrations of ET-1 were measured using enzyme-linked immunosorbent assay (ELISA) kit. A significantly lower concentration of ET-1 in highly myopic patients compared to controls was found (1.47 (0.91; 1.87) vs. 1.94 (1.1; 2.69) pg/mL, p = 0.005). In patients with high myopia, a weak negative correlation between ET-1 concentration and the longest axial length out of the two eyes was found (r = -0.255, p = 0.0558). Further analysis revealed statistically significant differences in ET-1 concentration between patients with the axial length of the eye > 26 and ≤ 26 mm (p < 0.041) and patients with the axial length of the eye > 26 mm and controls (p < 0.001). ET-1 expression is disturbed in highly myopic children and adolescents. Lower ET-1 concentration in patients with the axial length of the eye > 26 mm may co-occur with high myopia and should be considered a risk factor in the pathophysiology of high myopia progression.

Selected cytokines in hypertrophic adenoids in children suffering from otitis media with effusion.

OBJECTIVES: The aim of the current study was to assess the levels of MMP-8, MMP-9 and TIMP-1 in the group of children with adenoids who suffered from exudative otitis media. METHODS: The study included 20 patients (10 females and 10 males) with adenoid hypertrophy coexisting with otitis media with effusion. The reference group included 24 patients (10 females and 14 males) with adenoid hypertrophy without otitis media. The levels of MMP-8, MMP-9 and TIMP-1 were determined in supernatants obtained from phytohemagglutinin (PHA)-stimulated cell cultures of the tonsils, using commercial enzyme-linked immunosorbent assay kits (R@D Systems, USA). RESULTS: The median MMP-8, MMP-9 and TIMP-1 concentrations (220.8 ng/mL, 311.1 ng/mL, 53.5 ng/mL, respectively) in the study group were significantly higher (p = 0.000, p = 0.000, p = 0.048, respectively) than those in the reference group (93.5 ng/mL, 112.5 ng/mL, 36.95 ng/mL, respectively). ROC analysis revealed that the area under a curve (AUC) for both metalloproteinases MMP-8 and MMP-9 was 1 with a diagnostic sensitivity of 100% and diagnostic specificity of 95.8%, as compared to 0.690 for TIMP-1. Significant differences were found between the AUC for MMP-8 and TIMP-1 and MMP-9 and TIMP-1 (p < 0.001 for both comparisons). CONCLUSIONS: The changes in the concentrations of MMP-8, MMP-9 and TIMP-1 may indicate an increased remodeling of the extracellular matrix in children with adenoid hypertrophy and otitis media with effusion. The findings can have clinical as well as diagnostic utility. Determination of MMP-8 and MMP-9 may help qualify a child for adenoidectomy and differentiate pediatric patients affected by adenoid hypertrophy with and without otitis media.

Serum profile of transferrin isoforms in rheumatoid arthritis treated with biological drugs.

BACKGROUND: In the chronic inflammation process in the course of rheumatoid arthritis (RA), many alterations in the expression of plasma proteins, as well as their posttranslational modifications (including glycosylation) can occur. Taking into account the disturbances in protein glycosylation and the emerging new treatment regimens, the aim of this study was to assess the serum profile of transferrin isoforms in RA patients treated with biological drugs. METHODS: The study included 20 patients (16 females and 4 males; mean age: 53.4 years; range: 24-67) with rheumatoid arthritis treated with rituximab. Serum samples were taken 3 times: before and 3 and 6 months during treatment. The isoforms of transferrin were separated by capillary electrophoresis (MINICAP electrophoretic system, Sebia, France) into five major fractions: asialo-, disialo-, trisialo-, tetrasialo- and pentasialotransferrin. The results were calculated as relative concentrations of each fraction. RESULTS: The median trisialotransferrin relative concentrations after 3 and 6 months treatment (4.40% and 4.10%, respectively) were significantly higher (p = 0.013, p = 0.009, respectively) than before treatment (3.50%). The levels of serum pentasialotransferrin were also increased 3 and 6 months following treatment (16.5% and 17.7%, p = 0.005 and p = 0.006, respectively) as compared to those before therapy (14.5%), while tetrasialotransferrin concentrations were lower (80.3% and 78.4%, p = 0.009 and p = 0.008, respectively) than before treatment (81.5%). Trisialotransferrin relative concentration correlated with Hb (p = 0.019), whereas pentasialotransferrin with PLT (p = 0.036) after treatment. CONCLUSIONS: This study indicates that treatment with rituximab of RA patients alters the serum profile of transferrin isoforms. Tri-, tetra- and pentasialotransferrin relative concentrations measurements can be a useful tool to monitor therapy.

The influence of different intensity of treatment on hormonal markers of gonadal function in acute lymphoblastic leukemia survivors.

Anti-cancer treatment in children can deteriorate gonadal function and affect future fertility. We analyzed the hormonal markers of gonadal function in adolescent leukemia survivors, treated in childhood with different levels of aggressiveness. We analyzed hormone levels in 69 adolescents and young adults, leukemia survivors stratified into standard (SR), intermediate (IR), and high (HR) risk groups, and in 80 healthy controls (38 men) at a similar age. We assessed follicular stimulating hormone (FSH), luteinizing hormone (LH), and inhibin B in the whole group, testosterone in males, and E2 and anti-Müllerian hormone (AMH) in females. Males classified into HR group presented, in comparison to control, higher levels of FSH, LH, lower inhibin B, and normal testosterone, whereas in SR and IR group, the hormonal values were comparable to the control. In females, in all risk groups, the levels of FSH, LH, E2, and inhibin B were comparable with the control, but the mean AMH levels were slightly lowered. We did not observe the effect of prophylactic cranial irradiation (12 or 18 Gy) or the time of treatment (before vs. during puberty) on hormone levels. In females, a positive correlation was found between the time interval after the end of treatment and AMH levels. Male leukemia survivors having undergone more intensive chemotherapy show the symptoms of disturbed spermatogenesis and need to be followed-up in the future. Women, irrespective of the risk group, can develop the signs of preterm ovarian insufficiency. They should be informed about the impact of the treatment on gonadal function.