Hakan Alagozlu

Increased plasma levels of advanced oxidation protein products (AOPP) as a marker for oxidative stress in patients with active ulcerative colitis.

BACKGROUND AND AIMS After NADPH oxidase mediated radical formation, hypochloric acid (HOCl) is formed when Cl is used as a substrate by the myeloperoxidase enzyme. Myeloperoxidase is secreted from H2O2 activated leukocytes with polymorphic nuclei. The generation of HOCl also causes the formation of advanced oxidation protein products (AOPP) through damage to normal tissue and protein oxidation. AOPP has been identified as a marker of inflammation in many diseases. However, AOPP has not been investigated in ulcerative colitis. As a result of mucosal inflammation in ulcerative colitis, oxidative stress can occur. We aimed to determine whether plasma AOPP and oxidative stress markers are detectable in active ulcerative colitis. METHODS The patient group consisted of 59 patients who were diagnosed with ulcerative colitis in the clinic by histology and endoscopy. The patients were hospitalised and treated in the Gastroenterology Department of Gazi University Medical Facility. The 59 patients were separated into active and inactive groups according to the endoscopic activation index (EAI). Group I consisted of 33 active ulcerative colitis patients, Group II consisted of 26 inactive ulcerative colitis patients and Group III consisted of healthy control subjects. The disease activity of these patients were measured using the Rachmilewitz EAI based on rectosigmoidoscopic or colonoscopic findings. Patients with EAI scores greater than 4 were scored as having active disease (Group I). Patients with EAI<4 were scored as being in disease remission (Group II). The control subjects (Group III) were 51 healthy individuals. The plasma AOPP levels were measured using a spectrophotometric method. RESULTS There were no statistically significant differences in gender (P<0.22) and age (P<0.11) between the groups examined. The plasma AOPP level in Group I was 148.72±9.08μmol/L. The plasma AOPP level in Group II was 74.48±7.06μmol/L, and the plasma AOPP level in Group III was 64.93±2.55μmol/L. The AOPP levels in Group I were statistically different than in Group II and III (P<0.05). The AOPP levels were similar between Group II and Group III (P>0.05). The EAI value was 8.84±0.31 in Group I and 2.76±0.08 in Group II. There were statistically significant differences for EAI between groups (P<0.05). The correlation between AOPP and EAI in all patients with ulcerative colitis were statistically significant (P<0.05, r=0.61). The regression model in this correlation was statistically significant (y=49.68+10.75x, P<0.05). DISCUSSION Based on our results, we suggest that AOPP could be used as a non invasive activation marker for ulcerative colitis patients.

Anticardiolipin antibody positivity in diabetic patients with and without diabetic foot

Anticardiolipin (aCL) antibodies may play a role in the enhancement of platelet aggregation and/or progression of the macrovascular diabetic complications. Also, aCL antibodies may cause or promote ischemia and thrombosis. Therefore, we aimed to investigate IgG aCL and IgM aCL antibodies positivity in type 2 diabetic patients with and without ischemic diabetic foot. In this case-control study, we examined 40 diabetic patients without diabetic foot problem and 35 diabetic patients with ischemic diabetic foot. Forty diabetic patients (19 females, 21 males) without diabetic foot served as Group 1 and 35 diabetic patients (17 females, 18 males) who had ischemic diabetic foot served as Group 2. In the control group, 35 nondiabetic healthy subjects (18 females, 17 males) were included in Group 3. The groups were similar in age and sex, which is not statistically significant (P>.05). There was no difference in the IgG aCL antibodies positivity between Groups 1 and 3 (P>.05). However, IgG aCL antibodies positivity in Group 2 was significantly higher than those of the other groups (P<.05). IgG aCL antibodies were found positive in 10% (4/40) of Group 1, 34.3% (12/35) of Group 2 and 8.6% (3/35) of Group 3. When Groups 1 and 2 were compared, the odds ratio adjusted for age, gender, hypertension, coronary artery disease history, cigarette smoking, duration of diabetes mellitus, cholesterol, and haemoglobin A(1C) (HbA1c) was 6.8 [95% confidence interval (CI), 1.41-32.66; P=.016] for aCL positivity. In conclusion, although available evidence does not prove a causal association between positivity of aCL and diabetic foot, we believe that a causal association is supported by the data obtained from this study.

A Case of Budd-Chiari Syndrome Associated with Alveolar Echinococcosis

Although alveolar echinococcosis (AE) can cause a serious disease with high mortality and morbidity similar to malign neoplasms. A 62-year-old woman admitted to a hospital located in Sivas, Turkey, with the complaints of fatigue and right upper abdominal pain. On contrast abdominal CT, a 54×70×45 mm sized cystic lesion was detected in the left lobe of the liver that was seen to extend to the posterior mediastinum and invade the diaphragm, esophagus, and pericardium. The cystic lesion was seen to be occluding the inferior vena cava and left hepatic vein at the level where the hepatic veins poured into the inferior vena cava. Bilateral pleural effusion was also detected. We discussed this secondary Budd-Chiari Syndrome (BCS) case, resulting from the AE occlusion of the left hepatic vein and inferior vena cava, in light of the information in literature.

Association Between ABCB1 (MDR1) Gene Polymorphism and Unresponsiveness Combined Therapy in Chronic Hepatitis C virus

Background To treat viral infection of chronic hepatitis C (CHC) is a main strategy to prevent progression of liver disease, and cancer. Some patients with CHC have failed to respond to the common antiviral therapy in different populations. Objectives In the current study it was aimed to find out the possible role of multiple drug resistance gene1 (MDR1) in non-responder patients with CHC infection in Turkish population. Patients and Methods Peripheral blood-EDTA samples were used for total genomic DNA isolation. In total of 55 patients with chronic hepatitis C and positive results for genotype 1 [31 male (56.4%), 24 female (43.6%) and mean age-min-max; 56.9 ± 9.66 (39-71)]; 19 responder (34.5%), 21 non responder (38.2%), and 15 recurrence (27.3%) were included in the presented results. Functional MDR1 gene was genotyped by multiplex PCR-based reverse-hybridization Strip Assay method, and some samples were confirmed by direct sequencing. Results Our results indicate that MDR1 gene polymorphism is strongly associated with non-responder patients and those with recurrent chronic hepatitis C during conventional drug therapy when compared to the responder patients. Homozygous of the TT genotype for MDR1 exon 26 polymorphism was at 2.0-fold higher risk of non-responder than patients with CC and CT. Conclusions The homozygous MDR1 3435TT genotype which encodes the xenobiotic transporter P-glycoprotein may be associated with a poor antiviral response in HCV chronicity during conventional therapy, and large-scale studies are needed to validate this association.

Steatohepatitis and liver cirrhosis in Chanarin-Dorfman syndrome with a new ABDH5 mutation.

Chanarin-Dorfman syndrome (CDS) is an autosomal recessive neutral lipid storage disease. It is very rare and characterized by ichtiosis, intracellular fat droplets in leucocytes (Jordan anomaly) and involvement of multiple tissues (skeletal muscle, central nervous system, bone marrow, eye and ear) mainly the liver. Our patients were diagnosed as CDS because they had ichtiosis, Jordon anomaly of leucocytes in peripheral blood smear, liver involvement and presence of homozygous 88 insertion C frame shift mutation on exon 4 of ABHD5/CGI-58 gene in genetic analysis. Our cases were two sisters. One of them developed severe steatohepatitis on age 19 and the other one was diagnosed as decompensated cirrhosis when she was 26 years old. We report here a new mutation in comparative gene identification-58 (CGI-58) gene causing syndactyly and steatohepatitis induced early cirrhosis.

Prevelance of Common YMDD Motif Mutations in Long Term Treated Chronic HBV Infections in a Turkish Population

In the current study we aimed to show the common YMDD motif mutations in viral polymerase gene in chronic hepatitis B patients during lamivudine and adefovir therapy. Forty-one serum samples obtained from chronic hepatitis B patients (24 male, 17 female; age range: 34-68 years) were included in the study. HBV-DNA was extracted from the peripheral blood of the patients using an extraction kit (Invisorb, Instant Spin DNA/ RNA Virus Mini Kit, Germany). A line probe assay and direct sequencing analyses (INNO-LIPA HBV DR v2; INNOGENETICS N.V, Ghent, Belgium) were applied to determine target mutations of the viral polymerase gene in positive HBV-DNA samples. A total of 41 mutations located in 21 different codons were detected in the current results. In 17 (41.5%) patients various point mutations were detected leading to lamivudin, adefovir and/ or combined drug resistance. Wild polymerase gene profiles were detected in 24 (58.5%) HBV positive patients of the current cohort. Eight of the 17 samples (19.5%) having rtM204V/I/A missense transition and/or transversion point mutations and resistance to lamivudin. Six of the the mutated samples (14.6%) having rtL180M missense transversion mutation and resistance to combined adefovir and lamivudin. Three of the mutated samples (7.5%) having rtG215H by the double base substituation and resistance to adefovir. Three of the mutated samples (7.5%) having codon rtL181W due to the missense transversion point mutations and showed resistance to combined adefovir and lamivudin. Unreported novel point mutations were detected in the different codons of polymerase gene region in the current HBV positive cohort fromTurkish population. The current results provide evidence that rtL180M and rtM204V/I/A mutations of HBV-DNA may be associated with a poor antiviral response and HBV chronicity during conventional therapy in Turkish patients.

Effects of the Chemokine Receptor 5 (CCR5)-Delta32 Mutation on Hepatitis C Virus-Specific Immune Responses and Liver Tissue Pathology in HCV Infected Patients.

Background: The specific antiviral T cells provide CC chemokine receptor 5 (CCR5) for the immune response during the hepatitis C virus (HCV) infection. Heterogenous and/or homozygous 32 base pair deletion in CCR5 gene (CCR5Δ32 bpdel) leads to reduced protein expression. Objectives: In the current case control study, we aimed to compare the histopathological findings of liver to the CCR5Δ32 bpdel mutation profiles, expression and some other clinical findings in patients with chronic HCV infection. Materials and Methods: Multiple Strip Assay reverse hybridisation and Real Time PCR techniques were used to determine the germline CCR5 mutations and immunohistochemical technique was used to evaluate the gene expression in targer tissue biopsies. Results: Target CCR5 WT/WT, WT/Δ32, and Δ32/Δ32 genotypes were observed in 91.4%, 8.6% and 0.0% for HCV positive patients and 98.3%, 1.7% and 0.0% for control group respectively. The histologic activity index (HAI) was significantly lower (4.0 ± 1.0) in the mutated group than the non-mutated group (5.7 ± 1.0). Decreased fibrosis levels were detected in HCV positive mutated group. Conclusions: Results showed that CCR5 polymorphism was more frequent in HCV positive patients than in healthy population in Turkish population. Current results also showed that mutated CCR5 signalling pathway due to CCR5-Delta32 may potentially result in subtle reduction of HCV specifity to the drug responses due to the positive impact on liver inflammation, fibrosis levels and liver destruction in HCV infection.

Probiotics Are Sensitive Microorganisms: Lactobacillus Can Be Affected by Stomach Acid, Antibiotic, and Bowel Cleansing

We read with great interest the article by Mangell et al. entitled ‘‘Lactobacillus plantarum 299v does not reduce enteric bacteria or bacterial translocation in patients undergoing colon resection’’ [1]. The authors show that Lactobacillus plantarum 299v did not reduce enteric bacteria or bacterial translocation in patients undergoing colon resection. Although the study was well presented, there are some limitations and a few points on the affects of probiotics in the study protocol that we would like to address. Bowel cleansing before surgery can change the concentration of gut microbiota. Also, the patients had consumed food with L. plantarum 299v for 8 days in the preoperative period; however in the postoperative period, the patients had consumed L. plantarum 299v without food for 5 days. Foods typically contain fermentable substrates that can help nourish probiotic organisms as they transit through the gastrointestinal tract. Gastric pH following food intake is usually in the range of 4–7. Many lactobacilli and bifidobacteria secrete hydrolytic enzymes that can aid in the digestion of foods. Gastric pH is below 2 in the fasting state, which rapidly kills probiotics [2]. The main factors affecting the viability of probiotics in the gastrointestinal tract are the acidic environment of the stomach and the presence of bile in the duodenum. Significant numbers of probiotic bacteria can be destroyed unless they have some acid protection. Low pH is one of the most important factors that restricts the growth and stability of probiotic bacteria [3, 4]. Recent evidence shows that the dual-coating technology of probiotic bacteria enhances the survival and the amount of bacteria reaching the distal gut [5]. If there is an encapsulation technique of acid protection against L. plantarum 299v, it should be mentioned in this article. Preoperative and postoperative food intake might influence the transit of L. plantarum 299v to the distal gastrointestinal tractus. On the other hand, preoperative antibiotic prophylaxis may alter gut microbiota as well. The detection of bacterial genome in the lymph node does not reliably indicate recent bacterial translocation. Some bacteria might have already translocated in the preprobiotic phase, and scant amounts of these translocated bacteria might not be clinically important. Supporting this hypothesis, the authors did not mention any correlation with bacterial translocation and postoperative septic complications. And finally, two of these patients had translocation of lactobacilli, which is not a pathogenic bacterium. The rate of postoperative complications, although not significant between groups, is markedly decreased in the probiotic group. The overall complication rate, 16 versus 31 % (nearly twice as much in the control group), needs further comment. As a conclusion, probiotics are sensitive microbial agents to various noxious stimuli. Viability of probiotics in gastrointestinal tractus depends on some factors such as gastric acidity, bile acids, enzymes in intestine, antibiotics and bowel cleansing.

Significance of proton pump inhibitor types for Clostridium difficile infection.

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Usefulness of measuring the gastric emptying time in a case of brittle diabetes

Gastric emptying time measurement by radionuclide study, although quite informative, is rarely remembered in clinical practice. We presented a patient with brittle diabetes who had multiple emergency admissions due to hypoglycemia under routinely prescribed insulin therapy. She had severe gastroparesis, which was determined by scintigraphic gastric emptying study (gastric half-emptying time = 260 min for a mixed meal). She had not presented to the emergency service for two years because of only a slight change the timing of her insulin administration time (after meal instead of before meal) in the light of gastric-emptying study.