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Effects of Caffeic acid phenethyl ester (CAPE) and/or PD98059 (PD) on the gene expression of Caveolin-1 (CAV1) and reduced glutathione (GSH), malondialdehyde (MDA), copper-zinc superoxide dismutase (CuZn-SOD), and catalase (CAT) enzyme activities were investigated in an experimental chronic renal failure model in rats. Eighty Wistar rats were divided into eight groups for a 28-day study: Control, CsA (Cyclosporine A), CsA-V (CsA solvent), CsA + PD (CsA + PD98059), CsA + PD + CAPE, CsA + CAPE, CAPE-V (CAPE solvent), and PD-V (PD98059 solvent). Serum blood urea nitrogen and creatinine levels, as well as histopathological findings indicated the development of renal failure in the CsA group. Kidney GSH levels decreased while MDA levels, CuZn-SOD, and CAT activities increased significantly in the CsA group compared to control indicating oxidative stress. CAV1 gene expression significantly decreased in the CsA group compared to the control. PD98059 and CAPE applications made positive improvements in the levels of the parameters investigated. PD98059 and CAPE applications in CsA given animals increased GSH and CAV1 gene expressions and decreased CuZn-SOD and CAT levels compared to the CsA group. In conclusion, it was shown that PD98059 and CAPE could attenuate the effects of chronic renal failure, and CAV1 is suggested as a therapeutic target and the inhibition of the p44/42 MAPK pathway may be a new approach for the treatment of renal degenerations.

Hepatoblastoma is the most common primary liver cancer of childhood, accounting for two-thirds of primary malignant hepatic neoplasms. Radical surgical removal combined with efficient chemotherapy is essential for cure. Despite a complete tumor resection, hepatoblastoma may recur as isolated local disease. Intrahepatic recurrence of hepatoblastoma after liver resection is among the indications for liver transplant. Here, we present a patient who underwent salvage liver transplant for the treatment of local recurrence of hepatoblastoma. A 13-year-old boy who was diagnosed with hepatocellular carcinoma arising from the left liver lobe and who had been treated with surgical resection was admitted to our outpatient oncology clinic for further evaluation because alpha-fetoprotein levels had started to increase after surgery. Histopathological reexamination of hemihepatectomy material showed a histological aspect of an epithelial hepatoblastoma. Magnetic resonance imaging revealed multifocal lesions in the right liver lobe compatible with local recurrence. Despite a favorable initial response to chemotherapy, the tumor showed progression with increased alpha-fetoprotein levels. The patient was deemed a viable candidate for an urgent liver transplant and underwent right lobe living donor liver transplant. He had excellent graft function without any complications or signs of malignancy in the last follow-up visit at 7 months posttransplant. Salvage liver transplant is a lifesaving and sometimes the only treatment option for patients with local recurrence of hepatoblastoma. Although transplant in the salvage setting has been associated with worse outcomes than primary transplant, recent data have indicated more favorable and acceptable outcomes. Further studies are warranted to better understand the role of salvage liver transplant in the treatment of hepatoblastoma. Early consultation with the liver transplant team is critical in children who are most likely to need extreme resection or liver transplant.

Immunosuppressive therapy is a double-edged sword and causes a risk for some complications, such as opportunistic infections and posttransplant lymphoproliferative disease. The most likely risk factors for posttransplant lymphoproliferative disease are Epstein-Barr virus serology mismatch, prolonged and high viral load for Epstein-Barr virus, higher doses of immunosuppressive therapy, and cytomegalovirus infection. Transplant recipients who are seropositive for Epstein-Barr virus show a lower risk for posttransplant lymphoproliferative disease than seronegative recipients. Here, we present a 3.5-year-old boy who was seropositive for Epstein-Barr virus and developed posttransplant lymphoproliferative disease 18 months after liver transplant with a previous history of cytomegalovirus- related pneumatosis intestinalis.

Congenital hepatic fibrosis (CHF) is a developmental liver disease that is caused by mutations in genes that encode for ciliary proteins and is characterized by bile duct dysplasia and portal fibrosis. Recent work has demonstrated that mutations in ANKS6 can cause CHF due to its role in bile duct development. Here, we report a novel ANKS6 mutation, which was identified in an infant presenting with neonatal jaundice due to underlying biliary abnormalities and liver fibrosis. Molecular analysis revealed that ANKS6 liver pathology is associated with the infiltration of inflammatory macrophages to the periportal fibrotic tissue and ductal epithelium. To further investigate the role of macrophages in CHF pathophysiology, we generated a novel liver-specific Anks6 knockout mouse model. The mutant mice develop biliary abnormalities and rapidly progressing periportal fibrosis reminiscent of human CHF. The development of portal fibrosis in Anks6 KO mice coincided with the accumulation of inflammatory monocytes and macrophages in the mutant liver. Gene expression and flow cytometric analysis demonstrated the preponderance of M1- over M2-like macrophages at the onset of fibrosis. A critical role for macrophages in promoting peribiliary fibrosis was demonstrated by depleting the macrophages with clodronate liposomes which effectively reduced inflammatory gene expression and fibrosis, and ameliorated tissue histology and biliary function in Anks6 KO livers. Together, this study demonstrates that macrophages play an important role in the initiation of liver fibrosis in ANKS6-deficient livers and their therapeutic elimination may provide an avenue to mitigate CHF in patients.

Poster-Abstract

Our aim was to investigate the effects of Achillea millefolium on wound healing in second-degree burns formed in diabetic rats. This study was conducted at the Kafkas University Experimental Research Center. 20 Sprague Dawley rats were divided into 2 groups. Group I (n=10 rats) was the Control group and contained the diabetic rats with burn injury. Group II (n=10 rats) was the group where burn injury was created and Achillea millefolium was administered to diabetic rats. The backs of the rats were shaved so as to include 30% of the body area. A 10% lanolin extract was administered for 14 days after the burn injury was created. Tissue was obtained from the burn area of the rats sacrificed. No significant difference was found in Group II in terms of the severity of the dermatitis and inflammatory cell reactions when compared to Group I. No significant difference was observed between FGFR1immunoreactivity in the epidermis and dermis in Group I. While FGFR1immunoreactivity in 3 rats in Group II was similar to Group I, strong immunore activity that was more prominent in the epidermis was found in 7 rats in Group II. We believe that Achillea millefolium contributes to wound healing in burn injury due to its antioxidant and anti-inflammatory properties.

The aim of this study was to investigate whether Helicobacter pylori plays a role in the pathogenesis and severity of non-cystic fibrosis bronchiectasis, and its relationship with gastroesophageal reflux (GER).Forty-one patients and 16 controls between 5 and 18 years of age were enrolled. H. pylori was investigated on polymerase chain reaction and culture in gastric juice (GJ) and bronchoalveolar lavage fluid (BALF). Urea breath test (UBT) was also used for defining H. pylori infection. GER was detected on 24 h pH monitoring or scintigraphy. Computed tomography (CT) scoring was used to quantify the severity and extent of bronchiectasis.Nine patients (22%) in the bronchiectasis group (BG) and three patients (18.8%) in the control group (CG) had H. pylori-positive BALF. Sixteen BG patients (39%) and seven CG patients (43.8%) had H. pylori-positive GJ. UBT was positive in 11 BG patients (26.8%) and in three CG patients (18.8%). H. pylori positivity in BALF, GJ and UBT was not significantly different between the two groups (P0.05). Six patients with GER and five patients without GER in BG had H. pylori-positive BALF and GJ (P = 0.827). No association was found between BALF H. pylori positivity and forced expiratory volume in 1 s (FEV1 ) in BG. CT score was significantly higher in BG patients with H. pylori-positive compared with H. pylori-negative BALF (P0.05).Helicobacter pylori is not associated with the pathogenesis of bronchiectasis but it may be responsible for the severity of the disease.

Celiac disease was previously reported to be frequent among individuals with Williams-Beuren syndrome; however, this suggestion was not investigated further. The present study was conducted to estimate the prevalence of celiac disease in a group of Turkish individuals with Williams-Beuren syndrome (n=33, age range: 1-24 years) by using anti-tissue transglutaminase immunoglobulin (Ig)A and IgG, anti-endomysium IgA, and intestinal biopsy in individuals with positive serology. The prevalence of celiac disease in this population was compared to its prevalence among healthy Turkish schoolchildren. Of all participants, celiac disease was diagnosed in one patient. Although statistically insignificant (p=0.145), the prevalence of celiac disease was higher among individuals with Williams-Beuren syndrome (3%) than among healthy Turkish schoolchildren (0.47%). We recommend questioning individuals with Williams-Beuren syndrome during routine visits regarding celiac disease symptoms and performing serological screening when consistent symptoms are present. Anti-tissue transglutaminase and anti-endomysial antibodies may help to identify those individuals in whom intestinal biopsy is indicated for the diagnosis of celiac disease.

Amac: Bu cal›flman›n amac› yeni tan› ve diet alt›ndaki colyak hastalar› ile sal›kl› cocuklardaki fekal kalprotektin miktar›n› kar- fl›laflt›rmakt›r. Ayr›ca histopatolojik evre (Marsh evresi) ve notrofilik infiltrasyon derecesi ile de fekal kalprotektin oran› karfl›laflt›- r›ld›. Gerec ve Yontem: Cal›flma, yeni tan›, glutensiz diet alt›ndaki hastalar ve sal›kl› kontrol grubu olmak uzeri 3 grubu icer- mektedir. Ayr›ca cal›flma boyunca glutensiz diet ile serolojisi negatifleflen 9 hastada fekal kalprotektin miktar› tekrar cal›fl›ld›. Bulgular: Fekal kalprotektin oran› yeni tan› colyak hastalar›nda (n=31), diet alt›ndaki hastalara (n=33) ve sal›kl› kontrol gru- buna (n=34) gore yuksek saptand› (s›ras›yla 117,2 μg/g (3.2-306), 3.7 μg/g (0.5-58.2) ve 9.6 μg/g (1-70), p

Helicobacter pylori is a gram-negative, microaerophilic bacterium that colonizes human gastric mucosa and affects approximately 50% of the whole world population. It has put the blame on gastric ulcer, duodenal ulcer, chronic atrophic gastritis, mucosa-associated lymphoid tissue lymphoma and stomach adenocarcinoma, as the etiological agent. The cagA (cytotoxin-associated gene A) gene which is one of the most important virulence factors of H.pylori, encodes a 120-145 kDa protein called CagA antigen that may cause cell transformation. The prevalence of cagA positive H.pylori infections varies according to geographical area and age of the patients. Recent studies have suggested that cagA positive H.pylori strains play a role in the development of gastric carcinoma. The aim of this study was to evaluate the prevalence of cagA positive H.pylori isolates in adult and pediatric patient groups in Hacettepe University, Faculty of Medicine. The study was performed on 198 H.pylori stocked strains which have been isolated between 1997-2003 period from biopsy specimens of 107 adult and 91 pediatric patients with gastrointestinal pathology. Chromosomal DNA was extracted by the cetyltrimethyl-ammonium bromide (CTAB) method, and a 348 bp region of the cagA gene was amplified by an "in-house" polymerase chain reaction (PCR) using F1 and B1 primers (Gene Bank number: L11714 position 1231 and 1578R). The evaluation of PCR products revealed that 58.6% (116/198) of the isolates were cagA positive. The rates of cagA positive H.pylori among the adult and pediatric isolates were 62% and 55%, respectively. The present study demonstrates the prevalence of cagA in clinical isolates of H.pylori in our university hospital, and our data was found concordant with the results of studies reported from developed countries.

Heterotopic pancreatic tissue consists of normally differentiated pancreatic tissue without a real anatomic and vascular connection to the pancreas, whereas Meckel's diverticulum is one of the most important cause of lower gastrointestinal bleeding in children. Although heterotopic pancreatic tissue is related to various gastrointestinal diseases/malformations in both humans and animals, it is rarely associated with Meckel's diverticulum. Herein, we report a five-year old boy who presented with melena and hematochezia, which were discovered to be the result of Meckel's diverticulum. He also had multiple heterotopic pancreatic tissues in various parts of the gastrointestinal tract. The reason for this association is not known, but might involve some abnormalities of signaling molecules expressed in the development of the gastrointestinal tract and associated organs. In clinical practice, it is important to remember that Meckel's diverticulum and heterotopic pancreatic tissue might occur together or accompany various other gastrointestinal anomalies.

The aim of this study was to investigate the presentation pattern of newly diagnosed celiac disease (CD) in Turkish children in the last eight years. Two hundred twenty patients with newly diagnosed CD were included. The medical records of all the patients between January 2000 and October 2008 were reviewed. The clinical spectrum was divided into three categories according to the main symptoms that led to the diagnosis: gastrointestinal presentation, non-gastrointestinal presentation, and silent cases. The mean age of the patients was 7.2 +/- 4.3 years at diagnosis. According to the presenting signs, the patients were defined as gastrointestinal presentation (129 patients, 58.6%), non-gastrointestinal presentation (76 patients, 34.6%) and silent cases (15 patients, 6.8%). This study showed that the number/percentage of CD cases who presented with non-gastrointestinal symptoms/conditions, so-called "non-gastrointestinal presentation", have been increasing in the last eight years.

Histomoniasis was detected and described in naturally affected 35 turkeys. A polymerase chain reaction, which amplified a 209 bp region from the small subunit ribosomal RNA gene of H. meleagridis, was used and compared to the detection by histopathological observation of the histomonad trophozoits. In gross examination, typical histomoniasis lesions of hyperaemia and thickening of the cecal wall with grayish-yellow cecal cores were seen. In livers and kidneys, variably sized multiple foci of circumscribed necrotic areas were observed. Microscopically, varying amounts of histomonad trophozoits were detected in cecum (100%), liver (91.4%), kidney (17.1%), spleen (11.4%), proventriculus (5.7%) and bursa of Fabricius (2.8%). Mononuclear cell infiltration often containing giant cells in ceca, livers, kidneys and a proventriculus was observed. Lymphoid depletion was present in spleen and bursa of Fabricius. PCR assay detected the agent in cecum (100%), liver (100%), kidney (31.4%), spleen (25.7%), proventriculus (11.4%), bursa of Fabricius (11.4%) and lung (17.1%). This study describes histomoniasis lesions especially in several unusual locations such as kidney, spleen, bursa of Fabricius and proventriculus and could provide a help in the diagnosis of the natural histomoniasis in turkeys. It was also shown that PCR based detection was a more sensitive technique than detection based on histopathological observation.

Bone demineralization is a significant problem in pediatric inflammatory bowel disease. Contributing factors include inadequate nutrition, corticosteroid therapy and decreased physical activity. Although zinc is needed for osteoblastic activity and collagen synthesis, its role in bone development is uncertain. The aim of this study was to investigate the relation between the serum zinc level and bone mineral indexes of 28 children with inflammatory bowel disease.Bone mineral content and bone mineral density at lumbar 1-4 vertebrae were measured by dual energy X-ray absorptiometry in all patients and 56 controls. Serum zinc levels of patients and 31 controls were determined by spectrophotometric method.The mean bone mineral density values of patients and controls were 0.661+/-0.201 g/cm2 and 0.751+/-0.175 g/cm2, the mean bone mineral content values were 33.357+/-17.104 g and 38.968+/-14.663 g, and the mean serum zinc levels were 101.2+/-28.8 microg/dl and 108.9+/-15.9 microg/dl, respectively. All controls had normal serum zinc level; however, 11 (39.3%) patients had low serum zinc level (p=0.000). The ratio of patients with Z-score below the -2SD was higher in patients with low zinc level than in patients with normal zinc level (70% vs. 42.8%).Although insignificant, some of the children with IBD had low levels of serum zinc and these patients had lower Z-scores than the others. Further studies including large numbers of patients may reveal a certain effect of zinc on bone development in patients with inflammatory bowel disease.

This study was designed so that three sensitive and widely-used polymerase chain reaction (PCR) methods for the detection of TT virus or Torque Teno virus (TTV) would be simultaneously applied to a large number of subjects to evaluate performances of the various PCR protocols with different genotype sensitivities. Sera were collected from 92 children admitted to Hacettepe University Ihsan Doğramaci Children's Hospital Pediatric Gastroenterology Unit (17 cryptogenic chronic hepatitis, 17 asymptomatic HBs carriers, 18 chronic HBV patients and 40 healthy children). TTV DNA was detected via nested N22, nested 3'-UTR and 5'-UTR PCRs for all samples. Differences in TTV D N A detection prevalences were n o t statistically significantbetween the study groups with all TTV DNA and liver enzyme levels. A significant agreement between PCR methods that target UTR was observed. TTV detection rate increased with age, suggesting a non-parenteral, environmental exposure to the virus for the study population.

Ganciclovir treatment in children with cytomegalovirus (CMV) infection is still controversial and only indicated in selected cases. The aim of thi study was to evaluate clinical and demographic features of CMV hepatitis in immunocompetent children and to determine the effect of ganciclovir treatment in these patients retrospectively. The study was carried out in a group o 29 children with CMV hepatitis. All the patients were investigated for signs of infection, inborn errors of metabolism, genetic diseases, extrahepatic biliary atresia and other causes of hepatitis. Two patients with congenital CMV infection and two patients with biliary atresia were excluded from the study group. The patients included in the study were divided into two groups: non-cholestatic hepatitis (n=16) as Group I and cholestatic hepatitis (n=9) as Group II. Four (25%) patients in the non-cholestatic group and four (44.4 in the cholestatic group were treated with ganciclovir for a median of 21 days. The mean age was 9.6+/- 10.9 months (median age 6 months) in Group I, while cholestatic hepatitis patients in Group II were significantly younger, with a mean age of 2.7+/-0.9 months (p0.01). The most prominent symptoms at admission were diarrhea and vomiting (25%) in Group I. In Group I, all cases (100%) and in Group II, three of four cases (75%) treated with ganciclovir had recovery from acute CMV hepatitis. In the non-cholestatic group, no relapses were observed while one patient in the cholestatic group relapsed and progressed into chronic liver disease. Patients who received supportive treatment showed a marked decrease in GGT, ALT, AST and bilirubin levels spontaneously and no relapses of hepatitis were observed in at least one year of follow-up. Although ganciclovir therapy is not indicated particularly in immunocompetent cases, since most were self-limited infections, in case of progressive and persistent hepatitis, such as in our cases, ganciclovir was a treatment option; no side effect due to ganciclovir therapy was observed in our cases. Although ganciclovir seems to be effective in progressive CMV hepatitis, multicenter randomized studies in a large study group are necessar to determine the efficacy and indications for ganciclovir treatment.

A seven-year-old patient was admitted to our hospital with the complaints of fever, malaise, and abdominal distention. In the bone marrow aspiration smears, leishmania amastigotes were observed. The patient was diagnosed as having visceral leishmaniasis (VL) and treated with liposomal amphotericin B (L-AMB). The authors report their observation of foamy histiocytes seen in the bone marrow aspiration smears of the patient with VL after L-AMB treatment. This effect of L-AMB needs to be recognized, since L-AMB may represent a further condition in addition to the other diseases that are associated with foamy histiocytes in the bone marrow.

Whereas anorexia is a common behavioral response to infectious diseases, the reasons for and mechanisms behind this observation are still unknown. When it is considered on an evolutionary basis, the organism must have net benefits from anorexia. The first response to infection is the development of acute phase response (APR). The APR is triggered by microbial products and characterized by production of several cytokines known to induce anorexia. Several microbial products and cytokines reduce food intake after parenteral administration, suggesting a role of these substances in the anorexia during infection. Locally released cytokines may inhibit feeding by activating peripheral sensory fibers directly or indirectly, and without a concomitant increase in circulating cytokines. However, the final center for appetite or eating is the central nervous system (CNS). Thus, these peripheral signals must reach and interact with brain regions that control appetite. In addition, a direct action of cytokines and microbial products on the CNS is presumably involved in the anorexia during infection.

The duration of gastric acidity may affect the interpretation of esophageal pH monitoring study. The aim of this study was to increase the sensitivity of pH monitoring by simultaneous gastric and esophageal pH recording. Fifty-seven patients were enrolled in the study. After the first analysis, the recording periods in which gastric pH was4 were excluded and after this exclusion parameters were recalculated. Of the 57 patients, 14 (24.6%) (mean age, 70+/-4.6 years) were diagnosed as having gastroesophageal reflux disease with the use of conventional method. After correction, gastroesophageal reflux disease diagnosis was made in 6 additional patients (mean age, 2.4+/-2.4 years) and total number of patients with reflux increased to 20 (35.1%) (p=0.031). The mean percentage time of gastric pH4 was significantly greater in children younger than 2 years of age than that in those older than 2 years of age (50.6%+/-15.2% vs 33.7%+/-18.1%) (p=0.001). Exclusion of periods in which gastric pH4 affected the results more obviously in patients younger than 2 years. Simultaneous gastric and esophageal pH monitoring is useful for the diagnosis of gastroesophageal reflux disease, particularly in children younger than 2 years of age.

TTV DNA has been reported in patients with a broad spectrum of hepatic disorders as well as in healthy people.To clarify the role of TTV in children with liver disease and in healthy children.Degenerate primers designed to amplify a target sequence from the ORF 1 region of TTV genome were used for nested PCR, to detect TTV DNA in sera.TTV was detected in 3 of 18 children with chronic hepatitis B (16.7%), 2 of 17 hepatitis B carriers (11.8%), 2 of 17 children with cryptogenic chronic liver disease (11.8%), and 1 of 40 (2.5%) children without liver disease. The infection rate was similar among the various study groups and in the various age groups. There was no difference between TTV positive and negative children in respect to gender, history of surgery, parenteral treatment, transfusion of blood and blood products, presence of hepatomegaly, splenomegaly, jaundice, and transaminase values.TTV does not seem to have an etiologic role in cryptogenic liver disease in children and does not seem to influence the clinical course of liver disease.

Wilson's disease (WD) is an autosomal recessive disorder with variable clinical presentation. Its diagnosis depends on a combination of clinical and laboratory findings. We evaluated the sensitivity of various diagnostic tests in children with WD and high liver copper concentrations.Thirty-three children (6-15 years old, 19 male) with confirmed WD (hepatic copper250 mcirog/g dry weight) were evaluated retrospectively. Eyes were examined with biomicroscope for Kayser-Fleischer rings and urinary copper content was determined in 30 patients. Serum ceruloplasmin levels were measured and liver tissue samples were stained with orcein in all.All patients presented with hepatic disease. Four patients also had neurological involvement. Hepatic copper concentration was between 250 and 1200 microg/g. Eighteen patients had liver cirrhosis, 9 chronic hepatitis, and 6 had massive hepatic necrosis on liver biopsy or necropsy. The sensitivity of various tests evaluated was: 100% (30/30) for urinary copper excretion, 88% (29/33) for orcein staining on liver tissues, 82% (27/33) for ceruloplasmin levels, and 63% (19/30) for presence of Kayser-Fleischer ring. Kayser-Fleischer ring was present in all patients with neurological manifestations and in 58% of patients with only hepatic presentation.24-hour urinary copper excretion seems to be the most sensitive test for diagnosis of WD, particularly when liver biopsy cannot be performed due to coagulation abnormalities.

Congenital chloride diarrhea (CLD) (OMIM #214700) is a rare, autosomal recessive disease that is characterized by increased chloride loss in stool. As a result of electrolyte loss, surviving patients might have some complications, one of them being mental retardation. Here, we present three new Turkish patients with new mutations in the SLC26A3 gene. Although the clinical picture of the patients might be similar, consequences of the disease and complications might differ greatly among patients. Pediatricians should be aware of CLD as a potentially fatal or disabling disease if untreated. History of polyhydramnios, watery diarrhea, failure to thrive, poor growth, soiling, metabolic alkalosis and hypokalemia/hypochloremia should be an alarming set of findings for the diagnosis. Salt substitution therapy started early in life prevents early complications, allows normal growth and development, and favors good long-term prognosis.