Banu Dogan Gun

The effect of Helicobacter pylori on insulin resistance.

Helicobacter pylori causes a lifelong infection in the stomach after exposure. H. pylorihas been shown to be associated with peptic ulcer and gastric cancer development. Moreover, it is held responsible for some other nongastric diseases. Among them, coronary heart disease attracts much debate. Many studies have demonstrated a close relationship between insulin resistance and atherosclerosis. Chronic inflammation and alterations in counter-regulatory hormones are deemed responsible for the etiology of insulin resistance. We aimed to examine the effect of H. pylori on insulin resistance. Sixty-three patients were enrolled in the study. Patients were divided into two groups according to H. pylori presence. HOMA-IR (homeostasis model assessment of insulin resistance) level was used to assess insülin resistance. Thirty-six patients were H. pylori positive and 27 were H. pylori negative. There was no difference between the two groups with regard to age, gender, or body mass index. HOMA-IR level was 1.73± 1.1 in the H. pylori-negative group, whereas it was 2.56 ± 1.54 in the H. pylori-positive group (P < 0.05). This study provides the first direct evidence for an association between chronic H. pylori infection and insulin resistance.

Intrauterine growth restriction and placental angiogenesis

BackgroundVascular endothelial growth factor (VEGF), basic-fibroblast growth factor (b-FGF), and endothelial nitric oxide synthase (eNOS) are factors that take part in placental angiogenesis. They are highly expressed during embryonic and fetal development, especially in the first trimester. In this study, we aimed to investigate the role of placental angiogenesis in the development of intrauterine growth restriction (IUGR) by comparing the levels of expression of VEGF-A, b-FGF, and eNOS in normal-term pregnancy and IUGR placentas.MethodsThe expression of VEGF-A, b-FGF, and eNOS was studied using the avidin-biotin-peroxidase method in placental tissues diagnosed as normal (n = 55) and IUGR (n = 55). Results were evaluated in a semi-quantitative manner.ResultsThe expression of all the markers was significantly higher (p < 0.001) in cytotrophoblasts, syncytiotrophoblasts, extravillous trophoblasts, vascular smooth muscle cells, chorionic villous stromal cells, and villous vascular endothelial cells of the IUGR placentas when compared with those collected from normal-term pregnancies.ConclusionIncreased expression of VEGF-A, b-FGF, and eNOS may be the result of inadequate uteroplacental perfusion, supporting the proposal that abnormal angiogenesis plays a role in the pathophysiology of IUGR.

Clinicopathological significance of fascin and CD44v6 expression in endometrioid carcinoma

BackgroundFascin and CD44v6 may have significant roles as biomarkers in tumour progression and metastasis. In endometrioid carcinomas, the fascin expression profile is less defined, and the significance of CD44v6 is uncertain. We aimed to investigate the expressions of both fascin and CD44v6 in endometrioid carcinomas and to evaluate their inter-relation with clinicopathological parameters.MethodsFascin and CD44v6 expressions were evaluated, individually and in combination, in a series of 47 endometrioid carcinomas and 10 proliferative endometrium samples. The staining extent and intensity of both markers in tumour cells were scored semiquantitatively. The relationship between immunoexpressions and clinicopathological variables was assessed.ResultsThe expression rates of fascin and CD44v6 in endometrioid carcinoma were 72.34% and 46.80%, respectively. Although these expression rates were higher than those in proliferative endometrial samples, fascin expression showed a statistically significant difference from the normal group (p = 0.02), but CD44v6 did not differ (p = 0.54). Fascin expression was significantly correlated with tumour grade (p = 0.003) and neural invasion (p = 0.036) in a univariate analysis. In contrast, no significant correlation was found between CD44v6 and any of the clinicopathological parameters.ConclusionsOur findings suggest that fascin might be an independent prognostic indicator in the different steps of extracellular matrix invasion. On the other hand, CD44v6 was not a predictive factor in endometrioid cancer.Virtual SlidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/8511594927206899.

Oxidized low-density-lipoprotein accumulation is associated with liver fibrosis in experimental cholestasis

OBJECTIVE The aim of the present study was to examine the probable relationship between the accumulation of oxLDL and hepatic fibrogenesis in cholestatic rats. INTRODUCTION There is growing evidence to support the current theories on how oxidative stress that results in lipid peroxidation is involved in the pathogenesis of cholestatic liver injury and fibrogenesis. One of the major and early lipid peroxidation products, OxLDL, is thought to play complex roles in various immuno-inflammatory mechanisms. METHODS A prolonged (21-day) experimental bile duct ligation was performed on Wistar-albino rats. Biochemical analysis of blood, histopathologic evaluation of liver, measurement of the concentration of malondialdehyde (MDA) and superoxide-dismutase (SOD) in liver tissue homogenates, and immunofluorescent staining for oxLDL in liver tissue was conducted in bile-duct ligated (n = 8) and sham-operated rats (n = 8). RESULTS Significantly higher levels of MDA and lower concentrations of SOD were detected in jaundiced rats than in the sham-operated rats. Positive oxLDL staining was also observed in liver tissue sections of jaundiced rats. Histopathological examination demonstrated that neither fibrosis nor other indications of hepatocellular injury were found in the sham-operated group, while features of severe hepatocellular injury, particularly fibrosis, were found in jaundiced rats. CONCLUSION Our results support the finding that either oxLDLs are produced as an intermediate agent during exacerbated oxidative stress or they otherwise contribute to the various pathomechanisms underlying the process of liver fibrosis. Whatever the mechanism, it is clear that an association exists between elevated oxLDL levels and hepatocellular injury, particularly with fibrosis. Further studies are needed to evaluate the potential effects of oxLDLs on the progression of secondary biliary cirrhosis.

Expression of adhesion molecules in first trimester spontaneous abortions and their role in abortion pathogenesis.

Background. Early placental development is associated with complex regulatory mechanisms, and molecular communication problems that arise during the developmental process are dangerous for continuation of the pregnancy. As studies on the process of invasion and migration of trophoblast cells have shown the importance of cell–cell and cell–matrix interactions, we examined the effects of adhesion molecules on the mechanism(s) of spontaneous abortions and compared them to elective abortion materials using histopathological and immunohistochemical methods. To the best of our knowledge, this is the first study to investigate adhesion molecules in spontaneous abortions. Methods. Curettage materials from abortions were examined retrospectively in the Department of Pathology, Zonguldak Karaelmas University School of Medicine, Zonguldak, Turkey. CD31/PECAM‐1 (endothelial cell marker), CD44v (variant 3), E‐cadherin, CD54/ICAM‐1, and CD106/VCAM‐1 expression profiles were evaluated by immunohistochemistry, and cellular localization was determined under light microscopy. The results of spontaneous abortions were compared to those of elective abortions. Results. The staining percentages of CD31, CD44, CD106, and E‐cadherin decreased in cases of spontaneous abortion, but CD54 (ICAM‐1) expression increased. Statistically significant differences were detected between spontaneous and elective abortion materials with regard to cytotrophoblasts (CTs), syncytiotrophoblasts (STs), and extravillous trophoblasts (EVTs) with the anti‐CD31 antibody (p = 0.0001). In addition, CD54 (p = 0.007 and p = 0.002) and E‐cadherin (p = 0.002 and p = 0.02) expression in CTs and STs, respectively, were significantly different. Furthermore, CD44 expression (p = 0.003) in decidual (D) cells and CD106 (p = 0.0001) expression in vessels of endometrial (E) and villous tissues were also significantly different. Conclusions. Decreased CD31 expression in CTs that invade the spiral arterioles and mimic E cells in spontaneous abortion cases suggests that CD31/PECAM‐1 is an important molecule in uteroplacental adequacy. Moreover, diminished expression of CD44 in D cells caused impaired stroma–villous connections. Enhancement of ICAM‐1 in placental and invading STs may be useful as a diagnostic marker for patients who may have a tendency to have spontaneous abortions. A down‐regulation of E‐cadherin was observed, which may be responsible for impaired CT differentiation and loss of the pregnancy. Furthermore, decreased VCAM‐1 expression in spontaneous abortions may be consistent with the importance of VCAM‐1 in trophoblast–endothelial cell interactions. Many adhesion molecules are known to be effective in the normal development of a pregnancy, and the analysis of adhesion molecules in spontaneous abortions will provide useful information for clarifying the physiopathology of spontaneous abortions.

Expression of heat shock protein 70 and endothelial nitric oxide synthase in placental tissue of preeclamptic and intrauterine growth-restricted pregnancies

Ischemia, hypoxia, and elevated vascular resistance disturb placental functions by increasing oxidative stress. Heat shock protein 70 (HSP70) is an oxidative stress marker. Endothelial nitric oxide synthase (eNOS) is a nitric oxide enzyme with a key role in pathologic and physiologic angiogenesis and vasculogenesis. This study was performed to investigate the role of oxidative stress in the pathogenesis of preeclampsia and intrauterine growth-restricted (IUGR) pregnancies by comparing the levels of HSP70 and eNOS in placentas from women with these diseases and those with healthy pregnancies. HSP70 and eNOS were examined using the streptavidin-biotin-peroxidase complex technique on formalin-fixed, paraffin-embedded sections from 135 placental villous tissues obtained from normal pregnancies (n=45) and pregnancies complicated with preeclampsia (n=45) and IUGR (n=45). The intensity of labeling in placental tissues with antibodies to HSP70 and eNOS was scored between 0 and 3, using a semiquantitative scale. HSP70 and eNOS levels were increased in the syncytiotrophoblasts, cytotrophoblasts, and extravillous trophoblast cells of preeclamptic and IUGR placentas (P<0.001), compared with normal pregnancies. However, their levels were increased only in the villous endothelial cells of IUGR placentas (P<0.001). Oxidative stress is thought to play an important role in the pathogenesis of preeclampsia and IUGR pregnancies.

Ectopic pancreas associated with choledochal cyst and multiseptate gallbladder.

Congenital choledochal cyst is a rarely seen malformation of childhood, particularly when associated with multiseptate gallbladder or ectopic pancreas. The current case represents a 15-day-old boy with jaundice. Ultrasonography suggested a cystic lesion, probably of the common bile duct. The patient underwent a total excision of type I choledochal cyst and gallbladder with Roux-en-Y anastomosis, and a wedge biopsy from the liver. Gross examination revealed multiple septa dividing the gallbladder into multiple compartments. The outer and inner surfaces of the choledochal cyst were unremarkable. Microscopically, the cyst wall was composed of dense fibrous tissue with a single layer of cubic to columnar cells constituting the overlying epithelium. Serial sections incidentally revealed ectopic pancreatic tissue lying along the cyst wall characterized by acini, islets, and ductal structures with endocrine cells reactive for chromogranin A. Septa dividing the gallbladder were composed of fibrotic stalks containing smooth muscle fibers. Areas of papillary hyperplasia and intestinal metaplasia of gallbladder epithelium were also noted. The liver biopsy specimen demonstrated the presence of intrahepatic bile ducts, subsequently confirmed by cytokeratin 7. To our knowledge, this case represents the 1st one associated with these 3 entities and only the 2nd choledochal cyst with ectopic pancreatic tissue in its wall.

The effect of atorvastatin and its role on systemic cytokine network in treatment of acute experimental colitis

Inflammatory bowel diseases are characterized by disabilities in gastrointestinal system and defects in mucosal immune system. Statins are 3-hydroxy-3-methyl glutaryl coenzyme A reductase inhibitor and are used to treat hypercholesterolemia in patients with coronary artery and atherosclerotic diseases. Recent studies have demonstrated that statins have immunomodulatory role by effecting different pathways in immune system. In this study, we investigated the effect of atorvastatin and its mechanism on systemic immune response in treatment of trinitrobenzene sulfonic acid (TNBS)-induced colitis mice. We observed that atorvastatin significantly suppressed the severity of TNBS-induced colitis in BALB/c mice. This was manifested in reduced rectal bleeding, decrease in colon length, reduction of histological damage, and improved survival. Concurrently, we investigated the immunomodulatory role of atorvastatin on systemic immune system. We investigated the proinflammatory (IL-1α, IL-6, TNF-α), Th1 (IFN-γ, IL-2), Th2 (IL-4, IL-5, IL-10), and Th17 (IL-17, IL-23) cytokine levels in serum samples of colitis and atorvastatin-administered mice. We discovered that administration of atorvastatin significantly down-regulates systemic TNF-α level and Th17 cytokine levels. Furthermore, atorvastatin treatment switches Th1 type T-cell response toward/to Th2 (IL-4, IL-10) type response.

Primary Stromal Tumor of the Omentum: Report of a Case

We report the case of a primary extragastrointestinal stromal tumor (EGIST) found in the omentum of a 65-year-old woman. The resected specimen, which measured 6 cm at its largest point, consisted of an outer solid part and inner uniloculated cysts. Microscopically, the tumor was characterized by interlacing bundles of elongated spindle cells, with the nuclei showing a focal palisading pattern; however, skenoid fibers were not observed anywhere and mitoses were absent. Immunohistochemically, the tumor was negative for smooth-muscle actin, desmin, and S-100 protein, but it was positive for CD117 and CD34. The microscopic features were consistent with a gastrointestinal stromal tumor.

Elastofibroma: a clinicopathologic and immunohistochemical study of seven cases and literature review

Elastofibroma is a rare fibrous lesion characterized by accumulated abnormal elastic fibers whose etiology remains largely unknown. In this study, we analyzed seven cases of elastofibroma to further explore the characteristics of its cellular composition. Immunohistochemistry was performed for mast cell tryptase, S‐100 protein, vimentin, CD34, smooth muscle actin, desmin and collagen type IV. Histochemical staining methods for Gomoris trichrome and Verhoeff elastica‐van Gieson were also evaluated. Histopathologically, a haphazard array of collagen, eosinophilic amorphous fibers, and globules in a fibrous tissue was seen. The elastic nature of the fibers was confirmed by elastic stain, and with Gomoris trichrome collagen fibers were also demonstrated. The interspersed spindle or stellate cells were almost consistently positive for vimentin and frequently positive for CD34. Mast cell tryptase‐positive cells were present in five of the cases. Collagen type IV immunoreactivity was seen in two cases. No staining was observed with smooth muscle actin, desmin or S‐100 protein. Our findings suggest that CD34‐positive mesenchymal cells are an integral component of elastofibroma.