Altered BANKL/OPG system in hepatic osteodystrophy

The coexistence of liver disease and metabolic bone disease has been recognized for many years and is now the subject of increasing attention. Hepatic Osteodystrophy was established in patients with cholestatic liver disease, but new research suggests that it is prevalent in patients with other chronic liver diseases. Its etiology is complex and multifactorial. Receptor activator of nuclear factor Kb ligand [RANKL] plays a role in the differentiation and activation of bone resorbing osteoclasts by binding to its high affinity receptor [RANK] located on the surface of osteoclasts. This effect is counterbalanced by osteoprotegren [OPG], which acts as a decoy receptor competing with RANKL for RANK. To evaluate bone mineral density [BMD] and OPG/RANKL system in cirrhotic patients with backache. This study included 50 subjects suffering from backache, divided into 4 groups as follows: Group I: 10 subjects with normal BMD, Group II: 10 patients with pathological BMD but otherwise healthy considered as control, Group III: 15 patients with cirrhosis and normal BMD, Group IV: 15 patients with cirrhosis and pathological BMD. All patients underwent clinical examination, routine liver function tests, alkaline phosphatase, total calcium, serum OPG, serum RANKL, added to BMD. The lowest BMD values are estimated at the lumber spine, femoral neck, and lastly lower end of radius. There was a significant decrease in OPG in osteopenic/ osteoporotic non cirrhotic patients compared to control group, while it is significantly higher than control in both osteopenic/osteoporotic and patients with normal BMD of cirrhotic groups. RANKL, was significantly higher in non cirrhotic patients with pathological BMD compared to control group, but lower than control in cirrhotic groups both with normal and pathological BMD, with significant difference in cirrhotic with pathological BMD and non significant in those with normal BMD compared to controls. Serum OPG was negatively correlated to serum calcium, albumin, and International Normalized Ratio [INR], but positively correlated to bone alkaline phosphatase, and AST in cirrhotic patients of both groups. In cirrhotic patients, low BMD has tendency to affect axial bone early, which is similar to postmenopausal osteoporosis. On the contrary, higher OPG and lower RANKL levels are opposite to postmenopausal osteoporosis. This difference indicates that: OPG/RANKL system is activated in a different way in cirrhosis, suggesting a role for OPG/RANKL system in pathogenesis of hepatic osteodystrophy

Expression of interleukin[il]-18and il-6 in gastric cancer :diagnostic and prognostic role

Gastric cancer is the second most common cancer worldwide. The purpose of this study was to compare the recently identified interleukin [IL]-18, as well as IL-6 values in patients with gastric ulcer and gastric cancer to assess their diagnostic and prognostic values in patients with gastric cancer. The study comprised 40 patients attended for diagnostic upper gastrointestinal [GIT] endoscopy; 14 with histopathologically proven gastric cancer [Group I], 16 patients with gastric ulcer [Group II] and 10 patients with normal upper GIT endoscopy who served as controls [Group III]. All involved individuals were subjected to clinical examination, liver and renal function tests, complete blood picture, ESR, C-reactive protein, plain chest X-ray, abdominal ultrasound, urease test and gram staining of mucosal biopsies for Helicobacter pylori detection. Additionally chest,abdominal CT and bone scanning for group I gastric cancer were done to detect any metastasis. IL-18 and IL-6 gastric muscosal mRNA expression was assessed by quantitative real time-PCR [QRT-PCR] and their serum levels were estimated by ELISA. Gastric mucosal mRNA expression in parallel to serum values of IL-18 and IL-6 showed significant highly in-creased values in gastric cancer group compared to gastric ulcer and control groups [P<0.001] with elevated values in gastric ulcer group than those in controls. In gastric ulcer group, a positive relation was found between the studied cytokines and the histologically graded precancerous gastric lesions; gastric glandular atrophy grade was correlated with ser-um IL-18 [r=0.77; P < 0.001], gastric mRNA expression of IL-18 [ r= 0.603;P < 0.01] and IL-6 [r = 0.457;P <0.05], also intestinal metaplasia was positively related to IL-18 serum [t=-2.977; P < 0.01] and gastric mRNA expression [t =-2.365; P < 0.05] values. Higher cytokine values were related to H pylori infection in gastric ulcer [P < 0.01] not in gastric cancer group. In gastric cancer group a significant positive correlation was found between the cellular differentiation grade and IL-18 serum [r = 0.712; P <0.01] and gastric mRNA expression [ r = 0.658;P < 0.01] values, while IL-6 serum [r = 0.817; P <0.01] and gastric mRNA expression [r=0.844; P <0.01] values were positively correlated with the gastric cancer stage. Also patients with distant metastasis showed significantly higher IL-6 serum[t=-6.218 ; p < 0.001] and gastric mRNA expression [t = -2.47; P < 0.01]values compared to those without metastasis

In conclusion: IL-18 as a recently identified cytokine as well as IL-6 suggested to be vitally involved in gastric cancer pathogenesis. Serum IL-18 and IL-6 may be useful diagnostic markers for patients with gastriccancer. IL-18 may be used as a predictive marker of tumor grade and serum IL-6 could be used as a tumor marker for advanced gastric cancerstage and metastasis

Factors associated with fibrosis progression in HCV infected children in Egypt

This study aimed at identification of factors that could be associated with development of hepatic fibrosis in children with HCV infection. The study was carried out at the Pediatric Hepatology Unit, Cairo University Children's Hospital, Egypt. Liver biopsies were obtained from 43 children with HCV infection after having informed consent from their parents in the period "1995-2002". Their mean age at liver biopsy was and 8.67 +/- 4.3 years. Boys: girls ratio was 1.3:1. The results proved that, by examining the 43 patients' biopsies, 12 were having no fibrosis, 20 were having mild fibrosis and 11 were having moderate to severe fibrosis. The median time for development of fibrosis was estimated to be 5.5 years. Developing fibrosis was significantly associated with shorter duration from first detected ALT elevation to biopsy [P =0.015] and having higher levels of direct serum bilirubin [P Value=0.048]. Unexpectedly, development of fibrosis was slower in the group with co- morbid conditions compared to the group with no co-morbid conditions [P =0.04]. The development of hepatic fibrosis in children with HCV infection was associated with shorter duration of first detected ALT elevation to biopsy and higher direct serum bilirubin levels and it was progressing more slowly in the group having co-morbid conditions

Rankl/OPG system is altered in hepatic osteodystrophy

The coexistence of liver disease and metabolic bone disease has been recognized for many years and is now the subject of increasing attention. Hepatic Osteodystrophy has been established in patients with cholestatic liver disease, but new research suggests that it is prevalent in patients with other chronic liver diseases. Its etiology is complex and multifactorial. The Receptor activator of nuclear factor Kb ligand [RANKL] plays a role in the differentiation and activation of bone resorbing osteoclasts by binding to its high affinity receptor [RANK] located on the surface of osteoclasts. This effect is counterbalanced by osteoprotegren [OPG], which acts as a decoy receptor competing with RANKL for RANK. In this study we aim to evaluate OPG/RANKL system in cirrhotic patients with backache. This study includes 50 subjects suffering backache, divided into 4 groups as follows: Group I:10 subjects with normal bone mineral density [BMD] as control, Group II: 10 patients with pathological BMD but who are otherwise healthy, Group III: 15 patients with cirrhosis and normal BMD, Group IV: 15 patients with cirrhosis and pathological BMD. All patients underwent clinical examination, routine liver function tests, alkaline phosphatase, total calcium, serum OPG, serum RANKL, added to BMD estimation. The lowest BMD values were estimated at the lumber spine, then femoral neck, and lastly lower end of radius. There was a significant decrease in OPG in osteopenic non cirrhotic patients compared to the control group, while it was significantly higher than controls in both osteopenic and non osteopenic patients of the cirrhotic groups. SRANKL was significantly higher in non cirrhotic patients with pathological BMD compared to the control group, but lower than controls in cirrhotic groups both with normal and pathological BMD, with a significant difference in cirrhotics with pathological BMD, and a non significant difference in those with normal BMD compared to controls. Serum OPG was negatively correlated to serum calcium, albumin, and INR, but positively correlated to bone alkaline phosphatase, and AST in cirrhotic patients of both groups. OPG/RANKL system plays a role in the pathogenesis of hepatic Osteodystrophy. In cirrhotic patients, low BMD has a tendency to affect axial bone earlier, which is similar to postmenopausal osteoporosis. However in cirrhosis there are higher OPG and lower sRANKL levels which are opposite to postmenopausal osteoporosis. This difference indicates that: either OPG/RANKL system is working in a different way in cirrhosis, which might be due to an increased RANK/RANKL affinity which is not measurable, and consumes part of total RANKL leaving a smaller amount of measurable soluble RANKL to be assessed, which would explain its lower level in serum despite increased osteoporotic changes in bone, or there are other factors associated with this process to make their mechanism of action different than in postmenopausal osteoporosis

correlative study of angiogenesis extent and expression of matrix metalloproteinase-9 with upgrading and myometrial invasion in endometrial endometrioid carcinoma

Changes in angiogenesis and expression of extracellular matrix-degrading enzymes have been substantiated during tumor changeover and progression. This study was carried out on 60 retrospective endometrial endometrioid carcinoma [EEC] cases in addition to 15 normal endometrial biopsies as controls. EEC cases were grouped according to both histological grade [G], from G1 to G3, and the depth of myometrial [M] invasion, from M1 to M3. The study investigated all cases immunohistochemically to determine their microvessel number and the expression of matrix metalloproteinase-9 [MMP-9] and showed significantly high counts in EEC as a whole over the control endometria [P < 0.001]. Moreover counts of the G1 group overlapped those of the control endometra, increased significantly [P < 0.01] in the G2 and even more in the G3 group. G3 cases, in particular, displayed most microvessels widely scattered in the tumor tissue, in close association with tumor cells and as winding and arborized tubes, often dilated in microaneurysmatic segments. The counts also increased in M2 and M3 [P < 0.001] while those of the M1 group overlapped the counts of control endometria. Expression of MMP-9, evaluated as percentages of positive cases, revealed that the overall EEC cases gave a significant increase [P < 0.01] over the normal control endometria. Also, the frequencies of expression were significantly increased with the histologic grade [P = 0.01] and with the depth of myometrial invasion [P = 0.08]. The increases for MMP-9 were more evident on transition from G2 to G3 than from G1 to G2. The relationship to the depth of invasion revealed that the increases for MMP-9 were found at each depth, mostly on transition from M2 to M3. By contrast, only two of the control biopsies [13.5%] expressed few MMP-9. In EEC, MMP-9, as well, was, expressed by the host stromal cells. These data suggest that angiogenesis and degradation of extracellular matrix occur simultaneously with EEC upgrading and advancing depth of invasion. Also, they suggest that EEC cells and some host stromal cell populations cooperate in the tumor progression