ABSTRACT
Erythropoietin [EPO] is a hypoxia-induced cytokine. It is traditionally known to regulate erythropoiesis, but recently its protective effect against Ischemia/Reperfusion injury [I/R] has been studied in cardiovascular and neuronal systems and other tissues. This work was carried out to demonstrate the possible protective role of erythropoietin in ameliorating the effect of experimentally induced intestinal ischemia/reperfusion injury histologically, immunohistochemically and biochemically. Fifty adult albino rats were divided into three groups: Group I [Control Group]; Group II [Ischemia/Reperfusion] and group III [ischemia/reperfusion with erythropoietin]. The superior mesenteric artery was occluded for 60-min to induce ischemia and then the clamp was removed for 120-min for reperfusion. EPO [5000 U/ kg] was administered intraperitoneally at the onset of reperfusion. At the end of the reperfusion period terminal ileum was extracted for histological examination and immunohistochemical detection of the distribution of proliferating cell nuclear antigen [PCNA] from all animals. The levels of malondialdehyde [MDA, a biomarker of oxidative damage], myeloperoxidase [MPO, an index of the degree of neutrophil accumulation] and glutathione [GSH, a biomarker of protective oxidative injury] were also determined in all dissected tissues. In the Ischemia/Reperfusion [I/R] group, the mucosa of the ileum showed shortening and distortion of the villi, erosion of the lining epithelium, degeneration of epithelial cells of the villi and the crypts of Leiberkuhn. Inflammatory cellular infiltration in mucosa was also observed. Ultrastructurally, degenerative changes were observed in the enterocytes in the form of cytoplasamic vacuolation, mitochondrial degeneration and dilatation of rER. The levels of MDA and MPO were significantly increased whereas those of GSH were significantly decreased. Immunohistochemical study revealed a non significant increase in the number of PCNA - positive nuclei in the crypts. On the other hand, when erythropoietin was administrated at the onset of reperfusion [Group III], intestinal morphological changes were alleviated and the levels of MDA and MPO were significantly decreased whereas those of GSH were significantly increased. Immunohistochemical study revealed a significant increase in the PCNA positive nuclei in the crypts of Leiberkuhn. EPO exerts a protective effect against intestinal I/R injury in rats by reducing oxidative stress and promoting enterocytes proliferation. Therefore, erythropoietin may offer a new protective strategy for I/R injury in the field of intestinal surgery and transplantation
ABSTRACT
To evaluate serum and synovial fluid levels of receptor activator of nuclear factor Kappa B ligand [RANKL] and osteoprotegrin [OPG] in patients with rheumatoid arthritis [RA] and to determine the level of osteoclastic bone resorption by the ratio of RANKL to OPG as well as their correlation with the clinical activity, radiological grades and bone mineral density. 45 RA female patients and 15 age-matched healthy females with post traumatic knee effusion [as controls] were subjected to full history taking, complete clinical examination, assessment of disease activity using DAS score, radiological progression assessment using Larsen score, laboratory investigations including ESR, CRP and RF. Also, serum and synovial fluid levels of RANKL and OPG and bone mineral density [BMD] were done. RA patients had significantly higher levels of serum and synovial fluid RANKL, OPG and RANKL/OPG ratio than controls. Levels of RANKL, OPG and RANKL/OPG ratio were significantly higher in SF than in serum and in the active than in non active RA patients. The serum RANKL significantly correlated with disease duration, RF, ESR, DAS score and T- score, with no correlation with CRP or Larsen score. Synovial RANKL did not correlate with any of the previous parameters. As regards to serum OPG, it correlated with disease duration, RF, T-score and Larsen score, while synovial OPG showed correlation only with CRP. The serum RANKL/OPG ratio had significant positive correlation with CRP, DAS score and Larsen score. RANKL has a crucial role in the pathogenesis of bone loss in rheumatoid arthritis and can be used as a marker of bone erosion and disease activity. OPG plays a protective role against bone erosion and joint destruction in RA. RANKL/OPG ratio is more informative about bone resorption than each of RANKL or OPG alone
Subject(s)
Humans , Female , RANK Ligand , Osteoprotegerin , Osteoclasts , Bone Regeneration , Blood Sedimentation , Absorptiometry, PhotonABSTRACT
To investigate the association between serum and synovial fluid levels of both resistin and YKL-40 with markers of inflammation, disease activity and radiographic grading and to determine if they have a role in the pathogenesis of RA. This study was conducted on 30 patients with RA and 15 healthy controls with acute post traumatic knee effusion. Serum and synovial fluid levels of both resistin and YKL-40 were measured in patients and controls using ELISA technique. Plain x-ray of hands, wrists and feet were done for all patients and assessed according to Larsen score. Serum levels of resistin and YKL-40 were significantly higher in RA patients than controls and in active RA than in non active patients. Also, their levels significantly correlated with CRP, ESR, RF, disease activity parameters and Larsen score. Furthermore, synovial levels of resistin and YKL-40 were significantly higher than that of the serum, and synovial YKL-40 levels showed significant correlation with CRP, ESR, RF, disease activity parameters and Larsen score. On the other hand, resistin synovial levels significantly correlated with CRP, ESR, RF and synovial leucocytic count. Resistin and YKL-40 were increased in the serum and synovial fluid of rheumatoid arthritis patients. Their serum levels correlated with markers of inflammation, parameters of disease activity and radiographic progression of joint damage. These results suggested the key roles of resistin and YKL-40 in the pathogenesis of RA and they may be important new therapeutic targets