Sibel Serin Kilicoglu

Ionic High-Osmolar Contrast Medium Causes Oxidant Stress in Kidney Tissue: Partial Protective Role of Ascorbic Acid

It has been known that contrast medium may cause contrast-induced nephropathy in risk groups. This study sought to establish possible effects of ionic high-osmolar contrast medium administration with or without antecedent cisplatin treatment on oxidant/antioxidant status in rat kidney tissues, as well as to investigate a possible protective role of antioxidant ascorbic acid in this regard. Thirty-five female, 14-week-old Wistar-albino rats were used in this study. They were divided into five groups of seven rats (sham, contrast, contrast + ascorbic acid, contrast + cisplatin, and contrast + cisplatin + ascorbic acid). Ascorbic acid was given in a dose of 250 mg/kg/day orally throughout the study period, and cisplatin (10 mg/kg) as a single i.v. dose on the fourth day. Ionic high-osmolar contrast medium (3 gr/kg iodine as a single dose) was administered by i.v. route on the fifth day. After the animals were sacrificed on the sixth day, their kidney tissues were removed surgically to be used in the analyses. Malondialdehyde (MDA) level and activities of antioxidant (superoxide dismutase [SOD], glutathione peroxidase [GSH-Px] and catalase [CAT]) and oxidant (xanthine oxidase [XO]) enzymes were measured in these samples. Serum urea and creatinine levels were measured to evaluate kidney functions. Histopathological investigation of the tissues was also performed. It was observed that contrast medium administration caused increases in MDA levels in the kidney tissues, either alone or together with antecedent cisplatin treatment. However, ascorbic acid prevented the increases in MDA levels in the kidney tissues. Histopathological findings revealed that ionic high-osmolar contrast medium administration alone led to mild acute structural damage, but contrast medium administration together with antecedent cisplatin usage caused severe tubular necrosis. Ascorbic acid supplementation prevented these changes, to a great extent. The results suggest that ionic high-osmolar contrast medium administration, either alone or together with antecedent cisplatin treatment, leads to accelerated oxidative reactions in rat kidney tissues, and ascorbic acid protects in part the kidney tissues against this oxidant stress.

Effect of Propolis on Oxidative Stress and Histomorphology of Liver Tissue in Experimental Obstructive Jaundice

Background: Propolis is a natural product collected by honey bees from various plant sources. We aimed to determine the possible effects of propolis on oxidative stress and hepatocyte apoptosis in experimental obstructive jaundice. Methods:Thirty rats were divided into three groups: group I, sham-operated; group II, ligation and division of the common bile duct (BDL); group III, BDL followed by oral supplementation of propolis in a daily dose of 100 mg/kg. Liver samples were examined under the light microscope and transmission electron microscope. Hepatocyte apoptosis was quantitated using the transferase-mediated uridine nick end labeling (TUNEL) assay. Plasma and liver malondialdehyde (MDA) levels and glutathione peroxidase (GSH-Px) activities were measured. Results: The plasma and liver levels of MDA were significantly lower in the propolis group than in the BDL group (p < 0.05 and 0.014, respectively). Although liver GSH-Px activities were significantly higher in the propolis group than in the BDL group (p < 0.001), there was no significant difference between the plasma GSH-Px activities of these groups (p > 0.05). In the propolis group, the enlargement of hepatocytes, dilatation of canaliculi and the edema regressed. The regenerating and normal hepatocytes were demonstrated. In the TUNEL assay, propolis administration reduced hepatocyte apoptosis. Conclusion: Propolis showed a significant hepatoprotective effect in this experimental obstructive jaundice model.

Effects of different pulmonary surfactants in the prevention of postoperative intraabdominal adhesion formation

BACKGROUND After abdominal surgery, the formation of postoperative adhesion is a serious problem. The aim of the study is to evaluate the efficacy of 2 different pulmonary surfactants, poractant and beractant, on adhesion prevention in an experimental model. MATERIALS AND METHODS An experimental intraabdominal adhesion model was created in 18 adult female rats by cecal abrasion. The rats were randomly assigned to 3 groups. Group I received no further treatment, whereas groups II and III received intraperitoneal poractant and beractant, respectively, before closing the incision. On the 15th postoperative day, all rats underwent relaparotomy, intraabdominal adhesions were scored macroscopically according to Canbaz scoring system, and the cecum in each animal was evaluated microscopically. RESULTS The median adhesion scores of group II and III rats were significantly lower when compared with group I (P = .02). Group III had a lower median adhesion score than did group II, but this did not reach significance (P > .05). CONCLUSION These observations suggest that intraperitoneal instillation of both pulmonary surfactants is associated with lower adhesion scores, higher adhesion-free cases, and improved histologic findings.

A controlled trial of glutamine effects on bone healing

Glutamine is considered a nonessential amino acid, but it may be conditionally essential in patients with catabolic conditions. For centuries, researchers have looked for ways to promote and accelerate fracture healing. This controlled animal study examines the effects of glutamine on fracture healing. The left tibias of 10 standardized albino rats were broken at the distal third to produce a closed fracture. L-glutamine/L-alanyl solution (2.0 mL/kg) was administered through the tail veins of half the rats for the first 7 d, and physiologic serum alone was given to the control group. On the 21 st day, all rats were euthanized and their left legs removed; after histologic observation, the tibias were examined under light microscopy. In the glutamine-injected group, development of primary callus was quicker and more regular than in the control group. The control group produced insufficient fibrous callus, and the glutamine group attained formed cartilaginous callus. Glutamine was noted to have positive effects on healing of traumatically fractured bone through attainment of positive nitrogen balance. This effect was minimal in enhancing the quality of fracture healing under conditions of stress, but some effect was noted on the speed of healing. Further research is needed in this area

Behçet's: A Disease or a Syndrome? Answer from an Expression Profiling Study

Behçet’s disease (BD) is a chronic, relapsing, multisystemic inflammatory disorder with unanswered questions regarding its etiology/pathogenesis and classification. Distinct manifestation based subsets, pronounced geographical variations in expression, and discrepant immunological abnormalities raised the question whether Behçet’s is “a disease or a syndrome”. To answer the preceding question we aimed to display and compare the molecular mechanisms underlying distinct subsets of BD. For this purpose, the expression data of the gene expression profiling and association study on BD by Xavier et al (2013) was retrieved from GEO database and reanalysed by gene expression data analysis/visualization and bioinformatics enrichment tools. There were 15 BD patients (B) and 14 controls (C). Three subsets of BD patients were generated: MB (isolated mucocutaneous manifestations, n = 7), OB (ocular involvement, n = 4), and VB (large vein thrombosis, n = 4). Class comparison analyses yielded the following numbers of differentially expressed genes (DEGs); B vs C: 4, MB vs C: 5, OB vs C: 151, VB vs C: 274, MB vs OB: 215, MB vs VB: 760, OB vs VB: 984. Venn diagram analysis showed that there were no common DEGs in the intersection “MB vs C” ∩ “OB vs C” ∩ “VB vs C”. Cluster analyses successfully clustered distinct expressions of BD. During gene ontology term enrichment analyses, categories with relevance to IL-8 production (MB vs C) and immune response to microorganisms (OB vs C) were differentially enriched. Distinct subsets of BD display distinct expression profiles and different disease associated pathways. Based on these clear discrepancies, the designation as “Behçet’s syndrome” (BS) should be encouraged and future research should take into consideration the immunogenetic heterogeneity of BS subsets. Four gene groups, namely, negative regulators of inflammation (CD69, CLEC12A, CLEC12B, TNFAIP3), neutrophil granule proteins (LTF, OLFM4, AZU1, MMP8, DEFA4, CAMP), antigen processing and presentation proteins (CTSS, ERAP1), and regulators of immune response (LGALS2, BCL10, ITCH, CEACAM8, CD36, IL8, CCL4, EREG, NFKBIZ, CCR2, CD180, KLRC4, NFAT5) appear to be instrumental in BS immunopathogenesis.

C-type lectin domain family 12, member A: A common denominator in Behçet's syndrome and acute gouty arthritis.

C-type lectin domain family 12, member A (CLEC12A) is a C-type lectin-like pattern recognition receptor capable of recognizing monosodium urate crystals. Monosodium urate crystals, the causative agents of gout are also among the danger-associated molecular patterns reflecting cellular injury/cell death. In response to monosodium urate crystals, CLEC12A effectively inhibits granulocyte and monocyte/macrophage functions and hence acts as a negative regulator of inflammation. Behçets syndrome and gout are autoinflammatory disorders sharing certain pathological (neutrophilic inflammation), clinical (exaggerated response to monosodium urate crystals) and therapeutic (colchicine) features. We propose the hypothesis that decreased expression of CLEC12A is a common denominator in the hyperinflammatory responses observed in Behçets syndrome and gout. Major lines of evidence supporting this hypothesis are: (1) Downregulation/deficiency of CLEC12A is associated with hyperinflammatory responses. (2) CLEC12A polymorphisms with functional and clinical implications have been documented in other inflammatory diseases. (3) Colchicine, a fundamental therapeutic agent used both in Behçets syndrome and gout is shown to oppose the downregulation of CLEC12A. (4) Behçets syndrome and gout are characterized by a hyperinflammatory response to monosodium urate crystals and other than gout, Behçets syndrome is the only inflammatory condition exhibiting this exaggerated response. (5) Genomewide linkage and association studies of Behçets syndrome collectively point to 12p12-13, the chromosomal region harboring CLEC12A. (6) Patients with severe forms of Behçets syndrome underexpress CLEC12A with respect to patients with mild forms of the disease. If supported by well-designed, rigorous experiments, the forementioned hypothesis pertinent to CLEC12A will carry important implications for therapy, designing experimental models, and uncovering immunopathogenic mechanisms in Behçets syndrome and gout.