Metabolic syndrome risk factors and estimated glomerular filtration rate among children and adolescents

The aim of this study was to seek the possible relationship between estimated glomerular filtration rate (e-GFR) and anthropometric indexes, lipids, insulin sensitivity, and metabolic syndrome risk factors among healthy children and adolescents. Sufficient evidence suggest that obesity is related with a novel form of glomerulopathy named obesity-related glomerulopathy (ORG) among adults, children, and adolescents. Glomerular filtration rate was estimated from serum creatinine in 166 healthy children and adolescents [79 males, 87 females; age 10.6 ± 3.3 (3–18) years]. Anthropometric indexes and systolic and diastolic blood pressure were measured. Fasting insulin, glucose, creatinine, uric acid, total cholesterol, high-density lipoprotein (HDL)-cholesterol, low-density lipoprotein (LDL)-cholesterol, and triglycerides were estimated. Insulin sensitivity was estimated from known formulas. The presence of certain metabolic syndrome risk factors was checked among the studied population. Boys showed higher e-GFR rates than girls (f = 8.49, p = 0.004). We found a strong positive correlation between e-GFR and body weight (r = 0.415), body mass index (BMI) (r = 0.28), waist circumference (r = 0.419), hip circumference (r = 0.364), birth weight (r = 0.164), systolic blood pressure (SBP) (r = 0.305), and mean arterial pressure (MAP) (r = 0.207). A negative correlation was found between e-GFR and fasting glucose (r = -0.19), total cholesterol (r = -0.27) and LDL-cholesterol (r = -0.26). Clustering of metabolic syndrome risk factors among certain individuals was correlated with higher e-GFR rates (f = 3.606, p = 0.007). The results of this study suggest that gender, anthropometric indexes, and SBP are strong positive determinants of e-GFR among children and adolescents. Waist circumference is the most powerful determinant of e-GFR. Fasting glucose and lipid abnormalities are negative determinants of e-GFR among the studied population. Clustering of metabolic syndrome risk factors is coupled with higher e-GFR rates.     

Matrix metalloproteinase‐9‐mediated type III collagen degradation as a novel serological biochemical marker for liver fibrogenesis

Background: During fibrogenesis in the liver, in which excessive remodelling of the extracellular matrix (ECM) occurs, both the quantity of type III collagen (CO3) and levels of matrix metalloproteinases (MMPs), including MMP‐9, increase significantly. MMPs play major roles in ECM remodelling, via their activity in the proteolytic degradation of extracellular macromolecules such as collagens, resulting in the generation of specific cleavage fragments. These neo‐epitopes may be used as markers of fibrosis. Aims: The current study investigated whether a novel enzyme‐linked immunosorbent assay (ELISA) assay specifically measuring an MMP‐9‐cleaved sequence of type III collagen located at position 610 (CO3‐610C) may be used as a marker of liver fibrosis. Material and methods: Bile duct ligation (BDL) was performed in 20 rats, with sham operations performed on another 20 rats. Serum levels of the neo‐epitope CO3‐610C (MMP‐mediated type III collagen degradation) were determined with an ELISA at 14 and 28 days post‐surgery. Liver fibrosis was evaluated by quantitative digital image analysis of Sirius red‐stained formalin‐fixed and paraffin‐embedded sections. Western blot and densitometry were performed to confirm the CO3‐610C ELISA data. Results: CO3‐610C levels in serum increased significantly in BDL rats compared with those undergoing sham operations (% increase: 14 days=153%, P<0.0001; 28 days=134%, P=0.0014). This increase was confirmed by Western blot and densitometry of the identified bands. The CO3‐610C levels correlated to liver fibrosis (R²=0.23 and P=0.01), as evaluated by quantitative digital histology. Discussion and conclusion: The data suggest that MMP‐9‐mediated CO3 turnover is a central event in the pathogenesis of fibrosis, and that the neo‐epitope generated may be a novel biochemical marker.     

Advances in prognostic factors in acute pancreatitis: a mini-review

BACKGROUND:Early assessment of the severity of acute pancreatitis is essential to the proper management of the disease.It is dependent on the criteria of the Atlanta classification system.DATA SOURCES:PubMed search of recent relevant articles was performed to identify information about the severity and prognosis of acute pancreatitis.RESULTS:The scoring systems included the Ranson's or Glasgow's criteria ≥3,the APACHE II classification system ≥8,and the Balthazar's criteria ≥4 according to the computed tomography enhanced scanning findings.The single factors on admission included age 65 years,obesity,hemoconcentration(44%),abnormal chest X-ray,creatinine 2 mg/dl,C-reactive protein150 mg/dl,procalcitonin 1.8 ng/ml,albumin 2.5 mg/dl,calcium 8.5 mg/dl,early hyperglycemia,increased intra-abdominal pressure,macrophage migration inhibitory factor,or a combination of IL-10 50 pg/ml with calcium 6.6 mg/dl.CONCLUSION:The prediction of the severity of acute pancreatitis is largely based on well defined multiple factor scoring systems as well as several single risk factors.     

Expression analysis of proteins involved in the non homologous end joining DNA repair mechanism, in the bone marrow of adult de novo myelodysplastic syndromes

Myelodysplastic syndromes (MDS) are characterized by genetic instability which is associated with abnormal DNA repair mechanisms. The most lethal type of DNA damage are double strand DNA breaks (DSBs), which are mainly repaired by Non Homologous End Joining Mechanism (NHEJ), whose core enzyme components include the Ku70/Ku80 heterodimer, DNA–PKcs, XRCC4 and DNA Ligase IV. The aim of the present study was the analysis of expression of proteins required for NHEJ in bone marrow cells of adult de novo MDS and their association with clinical characteristics and prognosis. Our analysis included 48 cases of MDS; 19 RA, 5 RARS, 19 RAEB, 3 RAEB-T, 1 CMML, 1 transformation to AML according to FAB classification. The expression of the enzymes Ku70, Ku80, XRCC4, DNA-PKcs and Ligase IV was determined by Western Blotting. The mean Ligase IV expression value was significantly lower in MDS patients compared to normal controls (0.53 vs. 0.78, p?=?0.03). A negative correlation was found between karyotype risk group and Ligase IV values. (p?=?0.05). Moreover, Ku70 expression levels were significantly lower in patients with a good prognosis karyotype (p?=?0.04). Furthermore, a negative correlation between Ku70 expression values and Hb levels was observed (p?=?0.04). Finally, a positive correlation was observed between enzyme Ku70 expression values and level of blasts (p?=?0.04). Our findings suppor-t a potential role of NHEJ enzyme Ligase IV in the pathogenesis of MDS. Larger numbers of cases need to be screened in order to draw definite conclusion.     

Prophylactic antibiotics for the prevention of neutropenic fever in patients undergoing autologous stem-cell transplantation: results of a single institution, randomized phase 2 trial

One hundred and fifty-seven patients undergoing high-dose chemotherapy (HDT) and autologous stem-cell transplantation (ASCT) for hematopoietic malignancies and solid tumors were randomly assigned to receive (Group A) or not (Group B) prophylaxis with ciprofloxacin, orally, and vancomycin, intravenously. Prophylactic antibiotics were given from day 0 until resolution of neutropenia or the appearance of a febrile event. Furthermore, patients in both groups received once a day fluconazole, orally. The primary end-point of our study was the incidence of neutropenic febrile episodes attributed to infection. One hundred and twelve (71.3%) patients developed neutropenic fever, 50 (56.2%) in Group A and 62 (91.2%) in Group B (P < 0.001) with the majority (82%) of patients developing fever of unknown origin. Patients on prophylactic antibiotics had a significantly lower rate of bacteremias (5.6%) than did those randomized to no prophylaxis (29.4%) (P = 0.005) and, when developing neutropenic fever, they had a lower probability of response to first-line empirical antibiotics (P = 0.025). Prophylactic administration of ciprofloxacin and vancomycin reduced the incidence of neutropenic fever in patients receiving HDT with ASCT, however, without affecting the total interval of hospitalization, time to engraftment, or all-cause mortality. Therefore, our results do not support the use of antibiotic prophylaxis for patients undergoing HDT and ASCT.