Analysis of profibrogenic microRNAs (miRNAs) expression in urine and serum of chronic kidney disease (CKD) stage 1-4 patients and their relationship with proteinuria and kidney function.

PURPOSE: Besides conventional kidney diseases diagnostics, micro RNAs (miRNAs) assessment in urine and serum is considered to be a promising non-invasive method of diagnostics of renal parenchymal diseases and valuable therapeutic target also. The purpose of the study was to investigate the role of several miRNAs as a markers of kidney damage. METHODS: Assessment of 45 chronic kidney disease (CKD) patients stage 1-4 and 17 healthy control. Sample of urine and blood was taken from each participant for molecular analysis using Real Time PCR method to identify such micro-RNAs as: hsa-miR-155-5p, hsa-miR-214-3p, hsa-miR-200a-5p, hsa-miR-29a-5p, hsa-miR-21-5p, hsa-miR-93-5p, and hsa-miR-196a-5p. Basic biochemical test was done. Analysis was performed in CKD patients group and subgroup with chronic glomerulonephritis (CGN) confirmed by kidney biopsy. Moreover, analysis was performed in subgroup with different estimated glomerular filtration rate (eGFR) (according to CKD-EPI equation: eGFR < 60 ml/min, eGFR > 60 ml/min) and different daily protein excretion (DPE): (DPE < 3.5 g; DPE > 3.5 g). RESULTS: Increased relative expression of hsa-miR-29-5p, hsa-miR-21-5p, and hsa-miR-196a-5p and decreased expression of hsa-miR-155-5p, hsa-miR-214-5p, hsa-miR-200a-5p, and hsa-miR-93-5p was demonstrated in urine of analyzed CKD patients. In subpopulation of chronic glomerulonephritis (CGN) patients, there was higher level of expression in urine of hsa-miR-155-5p, hsa-miR 214-3p, hsa-miR-93-5p, and hsa-miR-196a-5p in CGN with DPE < 3.5 g. CGN patients with eGFR < 60 ml/min showed higher expression level of miRNAs such as hsa-miR-214-3p, hsa-miR-29-5p, hsa-miR-93-5p, and hsa-miR-196-5p in urine. There was increase in hsa-miR 155-5p, hsa-miR-214-3p, and hsa-miR-200a-5p serum expression level in CKD population and reduction of hsa-miR-29a-5p, hsa-miR-21-5p, and hsa-miR-93-5p expression. Increased level of expression of hsa-miR-155-5p; hsa-miR-214-3p, hsa-miR-200a-5p, and hsa-miR-29-5p was found in CGN patients with eGFR > 60 ml/min. CONCLUSION: Increased relative expression of profibrogenic miRNAs in urine or serum of CKD patients with eGFR > 60 ml/min and DPE < 3.5 g may indicate higher degree of fibrosis at early CKD stages.

Assessment of the SFlt-1 and sFlt-1/25(OH)D Ratio as a Diagnostic Tool in Gestational Hypertension (GH), Preeclampsia (PE), and Gestational Diabetes Mellitus (GDM).

BACKGROUND: Placental soluble fms-like tyrosine kinase-1 (sFlt-1), an antagonist of vascular endothelial growth factor, is considered an etiological factor of endothelial damage in pregnancy pathologies. An increase in the sFlt-1 level is associated with alterations of endothelial integrity. In contrast, vitamin D exerts a protective effect and low concentrations of 25(OH)D may have an adverse effect on common complications of pregnancy, such as gestational hypertension (GH), preeclampsia (PE), and gestational diabetes mellitus (GDM). The aim of this study was to analyze the levels of sFlt-1 in Polish women with physiological pregnancies and pregnancies complicated by GH, PE, and GDM. Moreover, we analyzed relationships between the maternal serum sFlt-1 level and the sFlt-1 to 25(OH)D ratio and the risk of GH and PE. MATERIAL AND METHODS: The study included 171 women with complicated pregnancies; among them are 45 with GH, 23 with PE, and 103 with GDM. The control group was comprised of 36 women with physiological pregnancies. Concentrations of sFl-1 and 25(OH)D were measured before delivery, with commercially available immunoassays. RESULTS: Women with GH differed significantly from the controls in terms of their serum sFlt-1 levels (5797 pg/ml vs. 3531 pg/ml, p = 0.0014). Moreover, a significant difference in sFlt-1 concentrations was found between women with PE and those with physiological pregnancies (6074 pg/ml vs. 3531 pg/ml, p < 0.0001). GDM did not exert a statistically significant effect on serum sFlt-1 levels. Both logistic regression and ROC analysis demonstrated that elevated concentration of sFlt-1 was associated with greater risk of GH (AUC = 0.70, p = 0.0001) and PE (AUC = 0.82, p < 0.0001). Also, the sFlt-1 to 25(OH)D ratio, with the cutoff values of 652 (AUC = 0.74, p < 0.0001) and 653 (AUC = 0.88, p < 0.0001), respectively, was identified as a significant predictor of GH and PE. CONCLUSIONS: Determination of the sFlt-1/25(OH)D ratio might provide additional important information and, thus, be helpful in the identification of patients with PE and GH, facilitating their qualification for intensive treatment and improving the neonatal outcomes.

Aldosterone antagonist therapy and its relationship with inflammation, fibrosis, thrombosis, mineral-bone disorder and cardiovascular complications in peritoneal dialysis (PD) patients.

BACKGROUND: High aldosterone level may contribute to pathogenesis of hypertension, vessels damage and cardiovascular system deterioration in chronic kidney disease patients. Besides its classical action via mineralocorticoid receptor, aldosterone is also involved in cell growth, inflammation, oxidative stress, endothelial dysfunction and exerts fibroproliferative effects. The aim of the study was to assess whether aldosterone antagonist treatment may influence serum level of inflammatory, fibrosis, thrombosis and mineral-bone metabolism markers in peritoneal dialysis (PD) patients and blood pressure, aortic stiffness, echocardiographic indices after 12 months of treatment. METHODS: Twenty-two patients on PD were assigned to spironolactone treatment in dose of 50 mg daily during 12 months. Fifteen PD patients were assigned to control group. Echocardiographic indices, PVW, SBP, DBP (mean values from ABPM) and biochemical parameters such as: aldosterone, osteopontin, IL-6, selectin-P, TGF-ß, PTH, MMP-2 were performed at the beginning and after 12 months in spironolactone and control group. RESULTS: There were no statistically significant differences in echocardiographic indices, PWV, BP (ABPM readings) and biochemical markers: MMP-2, serum aldosterone, TGF-ß, IL-6, selectin-P, PTH level after 12 months of spironolactone treatment. There was statistically significant rise in osteopontin level after 12 months of spironolactone treatment. Episodes of life-threatening hyperkalemia were not reported. CONCLUSIONS: Aldosterone antagonists use in PD patients seems to be safe. Longer duration or higher dosage of spironolactone seems to be more effective in improving cardiovascular system status in PD patients. Further studies are required to determine relationship between mineralocorticoid receptor blockade and mineral-bone disturbances in PD patients.

Dopamine-Induced Changes in Serum Erythropoietin and Creatinine Clearance Reflect Risk Factors for Progression of IgA Nephropathy.

INTRODUCTION: The infusion of low-dose dopamine is normally associated with an increase in creatinine clearance, thereby allowing one to assess renal functional reserve. Increased renal blood flow is also associated with a reduction in erythropoietin (EPO) levels. OBJECTIVES: We evaluated the use of dopamine infusion in subjects with IgA nephropathy to determine if these functional changes correlate with risk factors for progression and compared this to the renal biopsy findings. PATIENTS AND METHODS: Changes in creatinine clearance and EPO levels were determined in 46 non-nephrotic IgA patients with relative preserved renal function after the infusion of low dose dopamine. Control subjects (n = 15) were evaluated using similar protocols. RESULTS: Subjects with IgA nephropathy could be separated into those who showed a fall in EPO levels (n = 24) and those who showed no change or a rise in EPO levels (n = 22). Subjects showing the expected fall in EPO demonstrated a higher increase in creatinine clearance, similar to that observed in control subjects. Most importantly, subjects who showed a fall in EPO had less proteinuria, less N-acetyl-ß-D-glucosaminidase excretion, lower serum uric acid, blood pressure, and less features of metabolic syndrome despite similar inflammation and fibrosis on biopsy as compared to the others. CONCLUSIONS: A decrease in EPO in response to dopamine is associated with a clinical phenotype that is less likely to develop progressive renal disease. These studies suggest that a fall in EPO in response to dopamine likely reflects preserved tubulointerstitial function that cannot be assessed by renal biopsy alone.

Alpha-methylacyl-CoA racemase and hepsin as urinary prostate cancer markers.

BACKGROUND: Because of the numerous limitations of prostate-specific antigen (PSA), α-methylacyl-CoA racemase (AMACR) and hepsin have recently been suggested as potential biomarkers in prostate cancer (PC). This report presents a comparison study of the presence of AMACR and hepsin in urine collected before and after digital rectal examination (DRE) as a previously suggested diagnostic marker for PC. METHODS: Seventy-six urine samples (38 before and 38 after prostate massage) from patients with benign prostate hyperplasia (BPH) and 66 urine samples (33 before and 33 after prostate massage) from patients with PC were analyzed. PC was confirmed by prostate biopsy. Urinary levels of AMACR and hepsin were determined by ELISA and related to the tumor stage, Gleason score and PSA level. RESULTS: AMACR and hepsin levels in urine collected after prostate massage were higher only in the PC group. There were no correlations between AMACR levels, hepsin levels, tumor stage and Gleason score. AMACR and hepsin did not differentiate between BPH and PC with better true positive and false negative rates than serum PSA. CONCLUSIONS: AMACR and hepsin were unable to diagnose PC with better true positive and false negative rates than PSA. An additional procedure combined with other markers should be applied for the reliable diagnosis of PC.

The employment of IVF techniques for establishment of sodium, copper and selenium impact upon human sperm quality.

We analysed sodium (Na), copper (Cu) and selenium (Se) levels in human semen and glutathione peroxidase activity (GPx) in seminal plasma and examined their relationships with sperm quality. Semen samples were obtained from men (n=168) undergoing routine infertility evaluation. The study design included two groups based on standard ejaculate parameters: Group I (n=39) with normal ejaculates (normozoospermia) and Group II (n=129) with a pathological spermiogram. Se concentration (but not Na or Cu) and GPx activity were significantly higher in normozoospermic males than in those with a pathological spermiogram and also in males with correct sperm motility and normal sperm morphology than in asthenozoospermic and teratozoospermic males. There were significant correlations between sperm motility, Se and GPx, between rapid progressive motility and Cu, between sperm motility and Na, between normal sperm morphology and Se and Cu and between sperm concentration and Cu and GPx. Significant correlations were found between Na and Cu, between Na and Se and between Cu and Se in human semen in relation to alcohol consumption and tobacco use. Na, Cu, Se and GPx are related to sperm characteristics and male fertility and their survey could improve male infertility diagnosis.

Engrailed-2 protein as a potential urinary prostate cancer biomarker: a comparison study before and after digital rectal examination.

This study was designed to compare and evaluate the presence of engrailed-2 (EN2) protein in urine collected before and after prostate massage as a diagnostic marker for prostate cancer (PCa). We analysed and compared 76 urine samples (38 before and 38 after prostate massage) from the benign group (BPH) and 66 urine samples (33 before and 33 after prostate massage) from patients with PCa confirmed by prostate biopsy. EN2 levels from the PCa and men with BPH (age range 50-82) were related to the tumour stage, Gleason score and prostate-specific antigen. EN2 levels were determined by enzyme-linked immunosorbent assay in urine. The median EN2 levels in urine after prostate massage were significantly different from those determined in urine before prostate massage (1.25 ng/ml in the PCa group and 0.34 ng/ml in the BPH). The mean EN2 levels in PCa patients were 3.76-fold higher than those in non-PCa patients after prostate massage. The distinct influence of prostate massage on EN2 levels was found to be related to the Gleason score and tumour stage. EN2 may be considered a marker of PCa with certain limitations, such as those related to tumour staging. The specificity and sensitivity of the protocol are highly dependent on prostate massage.

Analysis of relative expression level of VEGF ( vascular endothelial growth factor ), HIF-1α ( hypoxia inducible factor 1α ) and CTGF ( connective tissue growth factor ) genes in chronic glomerulonephritis (CGN) patients.

BACKGROUND/AIMS: Analysis of gene expression in renal tissue is considered to be a diagnostic tool predicting the clinical course of glomerulonephritis. The present study quantified the relative transcript levels of VEGF, CTGF and HIF-1α in renal tissue to establish their relationship with some clinical variables in patients suffering from chronic glomerulonephritis (CGN). METHODS: 28 patients (6F and 22M, mean age 51.2±15.0) with CGN were enrolled. Type of CNG recognized by kidney biopsy (histopatological evaluation) was as follows: minimal change disease (MCD)-3pts, IgA nephropathy-5pts, FSGS-3pts, membranous nephropathy-4pts, mesangio-proliferative glomerulonephritis-3pts; MPGN-1pts, lupus nephritis-6pts, granulomatosis with polyangitis-2 pts; hypertensive nephropathy- 3pts. Renal tissue from 3 individuals with normal eGFR and histology was taken as control. Mean clinical follow-up of patients was 12 months after biopsy eGFR and daily urinary protein excretion (DPE) was assessed at the time of biopsy and then in 6 months intervals. Real-time PCR was used to determine relative gene expression. The housekeeping gene GAPDH was used as normalization control. RESULTS: At the time of the biopsy relative expression of 3 analyzed genes was diminished in comparison to control. There were statistically significant differences in VEGF gene relative expression level in patients which varied according to eGFR and tendency in patients which varied according to DPE. HIF-alfa and CTGF gene showed only a tendency. CONCLUSIONS: Overexpression of the VEGF gene in subjects with DPE>3,5 g may point to insufficient oxygen supply in renal tissue which may result in tubulointerstitial fibrosis with further functional renal impairment and decline of eGFR.

The concentration of thiobarbituric acid reactive substances (TBARS) and paraoxonase activity in blood of patients with osteoarthrosis after endoprosthesis implantation.

BACKGROUND: The aim of this study was to evaluate the concentration of malondialdehyde (MDA) in erythrocytes and in blood plasma and the activity of blood paraoxonase (PON1) of patients with osteoarthrosis (OA) submitted to endoprosthesis implantation for evaluating oxidative stress. MATERIAL/METHODS: Study was conducted on 55 patients with OA and on 54 total movement-efficient volunteers. The material for the study was venous blood plasma, serum and erythrocytes. RESULTS: Increased concentration of MDAe before surgery was observed in the group of men and in patients with a degenerative process affecting hip joints. After an implantation of endoprosthesis, MDAe decreased to the level observed in the control groups. In the study group MDA concentration in plasma was slightly lower before surgery, and after an operation it reached the value of the parameter of the reference groups. Regardless of sex or age, paraoxonase activity was almost twice as high in almost all subgroups as in the reference group. A positive correlation between PON 1 activity and MDAe concentration was demonstrated both before and after surgery in the group of men. CONCLUSIONS: The increase of PON1 activity in patients' serum in relation to the control groups indicates a probable pathogenic role of the increased formation of reactive oxygen species in the course of OA and may suggest acute inflammation of the synovial joint. The high level of PON 1 activity after endoprosthesis implantation indicates that surgical treatment may additionally stimulate ROS generation. MDAe concentration indicate more intensive process of lipid peroxidation in the elderly.

High incidence of nephropathy in neurosurgical patients after intra-arterial administration of low-osmolar and iso-osmolar contrast media.

BACKGROUND: Percutaneous endovascular examinations and interventions require significant amounts of iodinated contrast media (CM) and have been reported to be complicated by an increased incidence of post-contrast nephropathy. PURPOSE: To evaluate renal function, the incidence of post-contrast nephropathy, and risk factors after interventional procedures in neurosurgical patients after intra-arterial administration of a low-osmolar contrast medium (LOCM) versus an iso-osmolar contrast medium (IOCM). MATERIAL AND METHODS: This single-center, prospective, randomized, double-blinded study included 92 patients in its final analysis (mean age 49.6 ± 12.6 years, 29.3% men, mean eGFR 97.8 ± 26.3 mL/min/1.73 m(2)). LOCM was used in 48 patients (52.2%) and IOCM in 44 patients (47.8%). The patients were given an average of 151.2 ± 52.1 mL of contrast medium intra-arterially. Serum creatinine (SCr), urinary N-acetyl-ß-glucosaminidase (NAG) excretion, and creatinine clearance (CCr) were measured at baseline, and on days 1 and 3 after the procedure. RESULTS: Baseline risk factors, renal functional parameters, and average CM doses were not statistically different between the two groups. SCr, NAG, and CCr values did not differ significantly between the LOCM and IOCM groups on days 1 and 3 after CM administration. Nephropathy developed in 21 cases (22.8%): 13 (27.1%) after LOCM use and 8 (18.2%) after IOCM; (P = NS). The only significant risk factors of CIN were the diabetes (P = 0.0466) and atherosclerosis (P = 0.0498). CONCLUSION: We found a high incidence of nephropathy in neurosurgical patients after intra-arterial CM administration. The renal function values and incidence of nephropathy following LOCM administration were not statistically different from those following IOCM administration.

Zinc and iron concentration and SOD activity in human semen and seminal plasma.

The aim of the present study was to measure zinc (Zn) and iron (Fe) concentration in human semen and superoxide dismutase (SOD) activity in seminal plasma and correlate the results with sperm quality. Semen samples were obtained from men (N = 168) undergoing routine infertility evaluation. The study design included two groups based on the ejaculate parameters. Group I (n = 39) consisted of males with normal ejaculate (normozoospermia), and group II (n = 129) consisted of males with pathological spermiogram. Seminal Zn and Fe were measured in 162 samples (group I, n = 38; group II, n = 124) and SOD activity in 149 samples (group I, n = 37; group II, n = 112). Correlations were found between SOD activity and Fe and Zn concentration, and between Fe and Zn concentration. SOD activity was negatively associated with volume of semen and positively associated with rapid progressive motility, nonprogressive motility, and concentration. Negative correlation was stated between Fe concentration and normal morphology. Mean SOD activity in seminal plasma of semen from men of group I was higher than in seminal plasma of semen from men of group II. Fe concentration was higher in teratozoospermic males than in males with normal morphology of spermatozoa in group II. Our results suggest that Fe may influence spermatozoa morphology.

Influence of different stages of experimental chronic kidney disease on rats locomotor and postural skeletal muscles microcirculation.

BACKGROUND: Chronic kidney disease (CKD) is associated with muscle excess fatigue and diminished maximal whole body oxygen consumption, which in part could be depended on poor muscle microcirculatory network. The aim of this study was to assume the influence of different stages of CKD on microcirculation vessels in functionally different skeletal muscles--locomotor, the gastrocnemius muscle, and postural, the longissimus thoracis muscle. METHODS: Male Wistar rats underwent sham operation (CON), uninephrectomy (CKD 1/2) and subtotal nephrectomy (CKD 5/6). Muscle samples were stained for an alkaline phosphatase to differentiate capillaries. The number of capillaries was estimated by a single observer in 10 microm transverse sections by point counting at a magnification of x 125 using an Image Analysis System Q 500 MC of Leica. Blood pressure and serum creatinine, haptoglobin, MCP-1, VEGF, and PDGF were measured. RESULTS: There were significant differences (p < 0.05) in CD (number of capillaries per 1 mm(2) of muscle tissue), C:F (capillary to fiber ratio), and CC/F (capillary contact per fiber). The CKD 1/2 group in gastrocnemius and longissimus muscle had 53% and 33% lower C:F; 56% and 33% lower CD; and 44% and 20% less CC/F than CON, respectively. The CKD 5/6 group in gastrocnemius and longissimus muscle had 46% and 20% lower C:F; 47% and 11% lower CD; and 48% and 25% less CC/F versus control, respectively. Blood pressure was higher in CKD 5/6 vs. CKD 1/2 and CON (145/95 vs. 107/87 and 119/77 mmHg, p < 0.05, respectively). CKD 5/6 had higher creatinine than CKD 1/2 and CON (1.22 vs. 0.83 and 0.74 mg/dL, p < 0.05, respectively). Haptoglobin was higher in CKD 1/2 and CKD 5/6 versus CON (1.68 and 1.63 vs. 0.70 mg/mL, p < 0.05, respectively). MCP-1 was higher in CKD 5/6 and CKD 1/2 versus CON (609 and 489 vs. 292 pg/mL, p < 0.05, respectively). There were no significant differences in serum growth factors concentration between groups. CONCLUSION: Capillary rarefaction is present in early stages of CKD. These changes are independent of blood pressure and progression of CKD. We suspected that muscle function has a big impact on microvasculature as capillaries rarefaction has been reduced more in locomotor than postural skeletal muscle.

[The influence of sex and age on the osteoprotegerin level in the blood]. / Wplyw plci i wieku na stezenie osteoprotegeryny we krwi.

The exploration and description of the new cytokine system of tumor necrosis factor (TNF) superfamily contributed to different look on the biology of the bone tissue cells. The OPG/RANKL/RANK system constitutes the important element of controlling the number of active osteoclasts by the osteoblasts. It is essential to determine the influence of age and dependence among osteoprotegerin (OPG) and the level of sex hormones, biochemical markers of bone turnover and other factors in the metabolism of bone tissue in the state of physiology and pathophysiology.

[Some metabolic and genetic risk factors and the progression of IgA nephropathy--preliminary report]. / Wybrane czynniki metaboliczne i genetyczne a progresja nefropatii IgA--doniesienie wstepne.

IgA nephropathy is currently the most frequently occurring type of primary glomerulonephritis. Studies aimed at determining the factors of favorable and unfavorable prognosis in the progression of the disease are conducted. Apart from the above renal disease progression factors, it seems that renal functional reserve (RFR), indirectly indicating the functional status of intrarenal vessels can be a marker assisting in determining prognosis and effectiveness of applied treatment. Decrease in RFR is one of the first symptoms of renal damage, since it precedes decrease in GFR assessed in resting condition. The aim of our study was to assess selected functional (RFR), metabolic, and genetic parameters of renal disease progression in patients with IgA nephropathy, as well as to determine their effect on clinical progression of the disease. Material and methods. The study comprised 30 patients with renal biopsy proven IgA nephropathy, aged 35,2 +/- 8,9, 12 women and 18 men, who had conducted a 12-month period of observation and treatment. The patients' RFR was measured and the following parameters in blood pressure samples were established: creatinine, BUN, uric acid, total cholesterol (TCH), HDL and LDL and TG, homocysteine, endothelium functional indicators: vWF:Ag, TPA:Ag, PAI-1, polymorphism of the human angiotensin converting enzyme gene and endothelial nitric oxide synthase gene. In 24-hour urine collection N-acetylglucosaminidase excretion and daily protein loss were measured. Results. During treatment, changes in some biochemical indicators were observed (uric acid, TCH, LDL, DUB, NAG, erythrocyturia, homocysteine), while others remained stable. Statistically significant differences in concentrations of endothelial antigens: vWF:Ag and PAI-1 were found. Conclusions. Based on the analysis of the results it was concluded that functional status of intrarenal vessels is related to functional status of endothelium and renal tubulae, and also that it probably affects the response to treatment. Decrease of proteinuria during treatment is, among others, related to decrease of metabolic disorders, while the initial results of analysis of polymorphism of the human angiotensin converting enzyme gene and endothelial nitric oxide synthase gene suggest that it may affect the decrease of proteinuria and concentration of homocysteine in the blood.

Cardiac valve calcifications and left ventricular hypertrophy in hemodialysis patients.

Cardiac valve calcification (VC) is a common finding in end-stage renal disease patients. It was shown recently that VC is an independent predictor for all-cause and cardiovascular mortality in peritoneal dialysis patients. In hemodialysis (HD) patients, VC was associated with all-cause and cardiovascular mortality, but after adjusting for other cardiovascular risk factors and complications, as well as left ventricular mass index (LVMI), it lost significance. The aim of the study was to assess the relationship between VC and left ventricular hypertrophy in hemodialysis patients. Echocardiographic examination with mitral and aortic valves assessment and LVMI calculation was performed in 65 HD patients ages 49+/-12, with duration of HD therapy 38+/-32 months. VC were found in 32 of 65 patients (49%)-Group VC(+), mitral valve calcifications (MVC) in 10, aortic valve calcifications (AVC) in 9, and both valves calcifications (MVC+AVC) in 13 patients. Patients with VC were older, on HD therapy were longer, had higher systolic and pulse pressure, and had higher LVMI. Patients with both VCs had the highest LVMI. No significant differences were found with respect to Ca, P, PTH, and mean Ca x P product, but the incidence of Ca x P product above 4.43 mmol2/L2 was higher in VC(+) compared with those without VCs. VC coexists with left ventricular hypertrophy, particularly when both valves are calcified. Even short-lasting incidents of increased Ca x P product may lead to cardiac VC.

[Evaluation of IGF-1 concentration in serum and synovial fluid in women with different type coxarthrosis]. / Ocena stezenia IGF-1 w surowicy krwi i plynie stawowym u kobiet ze zmianami zwyrodnieniowymi stawu biodrowego o róznej etiologii.

Osteoarthritis is the greatest problem of aging population. It concerns particularly women over 65 years of age, in considerable degree limiting their locomotion activity. In recent years many different opinions on pathogenesis of osteoarthritis were presented, among them on the role of some growth factors like IGF-1 and TGF-beta playing an anabolic role in cartilage metabolism. The aim of our study was to compare the concentration of IGF-1 in clinically healthy women and women with coxarthrosis and to evaluate the association between IGF-1 in the serum and synovial fluid in relation to disease etiology. We found that in coxarthrosis of either idiopathic, necrotic or dysplastic etiology serum IGF-1 level was significantly lower than in control women (84.4; 76.1; 86.7 vs. 147.7 microg/ml). Concentration of IGF-1 in different groups of patients was similar or lower in synovial fluid than in the serum. Consistently decreased IGF-1 was found in synovial fluid (42.3 microg/ml) of patients with coxarthosis of necrotic origin. Our results suggest that low IGF-1 values, especially in synovial fluid, are in association with type of osteoarthritic changes within the joint, independently on age.

Role of cathepsin K in the pathogenesis of degenerative changes in joints.

Primary osteoarthritis is one of the oldest known joint diseases. The damage to the joint involves all its structures, and leads to considerable discomfort in daily life and limitations on patient activity. Degenerative changes within the joint were described in ancient time, but the mechanism has not yet been fully elucidated. Cleavage of collagens in the organic matrix of subchondral bone and cartilage by cysteine proteases, such as cathepsin K, may be one possible mechanism.

Clinical Utility of Anti-Tissue Transglutaminase Antibodies for Diagnosis and Monitoring of Coeliac Disease in Children and Adolescents.

Identification of tissue transglutaminase (tTG) as a major target antigen of IgA anti-endomysial antibodies and detection of auto-antibodies against tTG in the serum pointed out a new direction in the serologic diagnosis of coeliac disease. Clinical utility of determination of anti-tTGIgA antibodies, with recombinant human tTG used as antigen, was evaluated for the diagnosis of coeliac disease and monitoring the adherence to the diet in children and adolescents. PATIENTS: The study was performed in 169 patients aged 2-24 years, including 42 children (26 girls, 16 boys, mean age 8.01 ± 5.69, range 2-18) with newly diagnosed coeliac disease (CD) (group I), 60 patients (39 females, 21 males, mean age 15.68 ± 4.74, range 5-24) with CD recognized at least 3 years before entering the study, non-compliants with gluten-free diet (group II) and 67 children (34 girls, 33 boys, mean age 6,28± 4.48, range 2-16) suspected of malabsorption, in whom diagnosis of CD had been excluded. METHODS: Serum samples were taken from all patients and tested for total IgA, anti-endomysial IgA (IgAEmA) or IgG autoantibodies (IgGEmA), only in cases with IgA deficiency, by indirect immunofluorescence method and anti-tTGIgA antibodies by ELISA. RESULTS: [Table: see text] Strong significant associations between anti-tTGIgA present in the serum and IgAEmA (Kendall τ 0.7748, p<0.0001) and good correlation between the levels of anti-tTGIgA and IgAEmA (r=0,488, p=0.001) were found in group I. We have not shown the relationship between the presence of both types of antibodies in patients of group II (Kendall τ 0.2102, p=0.0937). However, a good significant correlation between the levels of these parameters was observed (r=0,813, p<0,0001). Anti-tTGIgA concentration was nificantly higher in patients of group I compared to group II (38.35 U/ml v. 23.13 U/ml, p=0,0356). The sensitivity of anti- tTGIgA test in group I was 88.1%, in group II - 91.7% while specificity reached 97%. CONCLUSIONS: Determination of anti-tTGIgA shows high sensitivity (88.1%) and specificity (97%) for the detection of coeliac disease. This test can be used alternatively with the immunofluorescent IgAEmA in diagnosis of coeliac disease, and also as a marker of compliance with gluten-free diet. However, both IgAEmA and anti-tTGIgA tests do not reach 100% sensitivity and specificity for diagnosis and nitoring of celiac disease. Therefore small intestinal biopsy is still recommended as a ? gold standard?.

[Assessment of serum levels of some angiogenic factors in healthy children]. / Ocena stezen wybranych czynników angiogennych u zdrowych dzieci.

Angiogenesis is defined as a development of new blood vessels. This process is required for many physiological and pathological conditions. Vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) are the most important cytokines stimulating angiogenesis. The purpose of this work was to evaluate serum levels of VEGF and bFGF in healthy children. 39 girls and 31 boys aged 3-18 years were included in the study.