Recently identified soluble circulating osteoprotegerin (OPG), a member of tumor necrosis factor receptor family, is the osteoclastogenesis inhibitory factor (OCIF). It acts as a "decoy" receptor for receptor activator of NF-kappaB ligand (RANKL) and antagonises RANKL/RANK activity. This way OPG exerts the protective effect on bone, which is also important in hyperparathyroidism. The studies measuring OPG levels in secondary hyperparathyroidism have shown contradictory results and inconsistent conclusions. The aim of our work was to evaluate OPG levels in hemodialysis patients and their correlation with the intensity of bone turnover, bone formation and bone resorption. Serum OPG levels, bone alkaline phosphatase activity (bALP) and beta-CrossLaps (CTx) were measured in a control group (n = 20, age 30+/-6.7 years) and in two groups of dialysis patients: the first group with serum intact parathyroid hormone (iPTH) concentration below 200 pg/ml (n = 28, age 62.6+/-14.8 years) and the second group with iPTH concentration above 200 pg/ml (n = 16, age 63.7+/-14.8 years). Compared to controls, serum OPG levels were 6.4-fold higher in dialysis patients. OPG levels in patients with high PTH were approximately 1.2-fold higher than in the low-PTH group. OPG correlated weakly with bALP (r = 0.277, p = 0.153), as well as with CTx (r = 0.018, p = 0.929) in the low-PTH group, and there was an insignificant negative correlation in the high-PTH group (r = -0.145, p = 0.593 and r = -0.219, p = 0.416, respectively). In conclusion, 6.4-fold increase in OPG might protect bone against intensive bone loss in hemodialysis patients, but this increase is probably not mediated by the increased bone formation; rather, it seems to be the consequence of the imbalance of bone kinetics in renal disease. The precise role of OPG in the pathogenesis of renal osteodystrophy remains unknown and establishing it requires further studies.
Serum RANKL levels were significantly higher in HD patients than in healthy age-matched controls. Moreover, RANKL levels were significantly higher in the upper PTH tertile, indicating enhanced RANKL synthesis in a PTH-dependent fashion. Thus, our clinical findings clearly support published in vitro studies that demonstrated a stimulating effect of PTH on RANKL synthesis. Therefore, the hypothesis that PTH increases bone resorption in HD patients through RANKL appears valid.
Postmenopausal women have slightly higher bone turnover. Since LS and FN BMD were not significantly lower in our group of healthy postmenopausal women, but BALP and CTx were markedly higher, we suggest that measurements of BALP and CTx might be useful as early markers of higher bone turnover. Finally, our results did not show any differences between the clinical utility of BALP activity and BALP mass concentration measurements.
An increase in the carbonyl content along with increased immunoreactivity after oxidation suggests modifications of the IgM paratopes. These results point towards possible modifications of native IgMs to their autoimmune state despite the fact that IgMs were less susceptible to oxidation than IgGs. The importance of an individual's redox status in maintenance of autoimmune reactions was emphasized by in vitro diagnostic tests.
Izhodišče: test ELF (angl. enhanced liver fibrosis test) predstavlja kombinacjo direktnih označevalcev fibroze jeter, ki tvorijo algoritem, s katerim je mogoče oceniti prisotnost in blago, zmerno ter težjo stopnjo fibroze jeter. Test vključuje tri biološke označevalce: hialuronsko kislino (HA), amino-terminalni del prokolagena tipa III (PIIINP) in tkivni inhibitor metaloproteinaze-1 TIMP-1). HA in PIIINP sta označevalca nastajanja depozitov matriksa – fibrogeneze, TIMP-1 pa predstavlja razgradnjo matriksa – fibrolizo. Raziskave so pokazale, da lahko našteti trije označevalci ali test ELF služijo kot uporaben presejalni test pri zgodnjem diagnosticiranju biokemične poškodbe jeter pri avtoimunskih hepatitisih, pri hepatitisu C in drugih okvarah jeter, npr. okvarah zaradi alkoholizma. Namen naše raziskave je bil določiti vrednosti testa ELF pri treh različnih skupinah preiskovancev: kontrolni skupini, pri skupini s potrjeno diagnozo alkoholizma in pri skupini, ki akutno pije alkohol. Rezultate meritev ELF testa smo primerjali z rezultati uveljavljenih biokemičnih označevalcev alkoholizma. Metode: V raziskavo smo vključili 113 preiskovancev, (71 moških, 42 žensk). Povprečna starost preiskovancev je znašala 43 let. Razdelili smo jih v tri skupine: MDPŠ so predstavljali preiskovanci (N = 39), ki so prišli na pregled v ambulanto medicine dela, prometa in športa, AZA je bila skupina 31 preiskovancev z akutnim alkoholnim opojem in DOA skupina 43 preiskovancev, ki so se zdravili zaradi diagnoze odvisnosti od alkohola. V serumskih vzorcih vseh treh skupin preiskovancev smo izmerili povprečni volumen eritrocitov (MCV), katalitične aktivnosti aspartat amino transferaze (AST), alanin amino transferaze (ALT), gama glutamilne transferaze (GGT) in parametre novejšega testa ELF za oceno stopnje z alkoholom povzročene jetrne fibroze. Blaga stopnja jetrne fibroze je pri vrednostih ELF pod 7,7, zmerna pri vrednostih od 7,7 do 9,8 in huda stopnja fibroze pri vrednostih nad 9,8. Za statistično analizo podatkov smo uporabili program SPSS 21.0 za Windowsovo okolje (SPSS, Inc. Chicago, USA). Rezultati: Izmerjene povprečne vrednosti uveljavljenjih bioloških označevalcev alkoholizma pri skupinah MDPŠ, AZA in DOA znašajo za MCV : 91,9; 90,9 in 95,3 fL, mediane katalitične aktivnosti za AST pa 0,30; 0,33 in 0,42 µkat/L, za ALT 0,41; 0,34 in 0,56 µkat/L in za GGT 0,37; 0,34 in 0,92 µkat/L. Kruska-Wallisov test je pokazal statistično značilne razlike med skupinami preiskovancev za AST, GGT in MCV (p < 0,002), medtem ko se aktivnost ALT (p = 0,052) med skupinami razlikuje le na meji statistične značilnosti. V skupini MDPŠ je vrednost mediane testa ELF znašala 7,99 (6,99–10,18), v skupini DOA pa 9,47 (6,98–14,73). V skupini DOA smo dokazali statistično značilno korelacijo med AST, ALT, GGT in testom ELF (r = 0,524; 0,306 in 0,632), v skupini MDPŠ pa je bila statistično značilna samo za MCV (r = 0,327). Zaključek: Rezultati meritev so pokazali, da so v skupini DOA statistično značilno višje vrednosti uveljavljenih bioloških označevalcev alkoholizma (MCV, AST, ALT in GGT) kot v kontrolni skupini MDPŠ. Mediana testa ELF pri skupini DOA kaže na prisotnost zmerne fibroze jeter, ob tem da območje vrednosti od 6,98 do 14,73 kaže, da so v skupini tudi posamezniki s hudo fibrozo. Iz rezultatov je razvidno, da povišane vrednosti jetrnih encimov AST, ALT in GGT ter korelacije med njimi kažejo na poškodbo hepatocitov, vrednosti testa ELF pa opredeljujejo stopnjo in obseg fibroze jeter. Za oceno fibroze jeter se uporabljajo različni indeksi, med katerimi ima test ELF po izsledkih tujih raziskovalcev visoko diagnostično uporabnost. ELF ima kot neinvazivni test tudi vse možnosti za uporabo na primarni ravni zdravstvene obravnave bolnikov z alkoholno in nealkoholno okvaro jeter.
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