Effectiveness of interleukin-1 receptor antagonist (Anakinra) on cerulein-induced experimental acute pancreatitis in rats.

AIM: Acute pancreatitis (AP) is defined as an inflammatory disease of the pancreas. The purpose of this study was to examine the effectiveness of Anakinra on cerulein-induced experimental pancreatitis rat model by using the results of biochemical and histopathological findings. MATERIALS AND METHODS: Cerulein was administered to induce AP in rats. Group 1 was the sham group. Subcutancerulein was injected to the rats in group 2 for experimental pancreatitis group. In groups 3 and 4, 100 and 50 mg/kg intraperitoneal Anakinra were injected after the induction of experimental pancreatitis by subcutaneous cerulein in rats, respectively. Lastly, in group 5, rats were injected with intraperitoneal saline and subcutan cerulean for placebo group. The following parameters were evaluated: histopathological score of pancreatitis, apoptotic index, amylase, lipase, TNF-α levels, IL-1ß and the leukocyte count. RESULTS: When the results of serum amylase, lipase, TNF-α and IL-1ß levels, the leukocyte count, histopathologic scores and apoptotic indices of control group compared to the results of other groups, the differences exhibited statistical significance (all p < 0.05). On the other hand, when the results of fourth group compared with the results of third group, the data demonstrated statistical insignificance (p > 0.05). However, no any significant differences were found between the results of fourth and fifth groups (p > 0.05). CONCLUSION: In the light of these results, cerulein is an appropriate agent for experimental AP rat model and Anakinra has a favorable therapeutic effect on acute experimental pancreatitis model. Moreover, Anakinra significantly decreases cerulein-related pancreatic tissue injury and pancreatic apoptosis.

Can serum fetuin-A be regarded as an inflammatory marker among patients with familial Mediterranean fever?

BACKGROUND/AIM: Familial Mediterranean fever (FMF), the most frequent periodic fever syndrome, is an autosomal recessive inherited disease that predominantly affects eastern Mediterranean populations. Fetuin-A is a well known negative acute-phase protein. Studies of this glycoprotein as a marker of inflammation in FMF are limited. We have investigated the relationship between serum levels of fetuin-A and inflammatory markers in patients with FMF before, during, and after FMF attacks. METHODS: Sixty-seven patients with FMF were enrolled in this study. Serum fetuin-A, seruloplasmin, fibrinogen, C reactive protein (CRP), white blood cell count (WBC), calcium, and erythrocyte sedimentation rate (ESR) were measured three times: during the attack-free period, 12 h after FMF attacks, and 7 days after FMF attacks. Plasma fetuin-A concentration was measured by use of an enzyme-linked immunoassay (ELISA) kit. Correlations and differentiation between the serum fetuin-A and other inflammatory markers in patients with FMF were investigated by use of the paired-samples T test and the Pearson correlation test (p < 0.01). RESULTS: Serum fetuin-A levels of all FMF patients in the attack period were significantly lower than in the attack-free period (p < 0.001). In contrast, serum seruloplasmin (p < 0.05), fibrinogen (p < 0.001), CRP (p < 0.05), WBC (p < 0.05), and ESR (p < 0.05) were all significantly higher than in the attack-free period. Plasma fetuin-A is significantly and inversely highly correlated with the other inflammatory markers. CONCLUSION: Fetuin-A might be a novel indicator of disease activity in patients with FMF and could be used as an adjunctive marker for differentiation of FMF attacks. The negative correlation between serum fetuin-A and other inflammatory markers may also be indicative of inflammation-dependent downregulation of fetuin-A expression in FMF patients.

Malignant biliary obstruction significantly increases serum lipid levels: a novel biochemical tumor marker?

BACKGROUND/AIMS: We aimed to investigate the alterations in serum lipid levels due to biliary obstruction associated with benign and malignant cases. Also, we aimed to examine the possibility of the theory that extremely high serum lipid levels can predict the malignant biliary obstruction in the differantial diagnosis. METHODOLOGY: Three hundred twenty two patients who were performed endoscopic retrograde cholangiopancreatography with the intrahepatic and extrahepatic cholestasis were reviewed in the period from September 2007 to October 2010. RESULTS: In the malignant obstruction group, meaningfully higher total cholesterol (p<0,001), low-density lipoprotein (p>0.05) and triglycerides (p<0.05) were observed but high-density lipoprotein (p<0.05) levels were lower. The receiver operating characteristic analysis showed that total cholesterol (246.74 mg/dL or less, sensitivity: 84.3%, specificity: 83.3%, area under the curve: 0.705 (0.620-0.790) (p<0.001)) and high-density lipoprotein cholesterol (area under the curve: 0.577 (0.444-0.710)) were predictors of malignant biliary obstruction. CONCLUSIONS: Serum lipid profile may be used as an applicant marker to identify malignant reasons of the obstructive jaundice.

Benign recurrent intrahepatic cholestasis: late initial diagnosis in adulthood.

Benign recurrent intrahepatic cholestasis (BRIC) is a rare autosomal recessive or sporadic disorder, characterized by recurrent episodes of intense pruritus and jaundice that resolve spontaneously without leaving considerable liver damage. The attacks can start at any age, but the first attack is usually seen before the second decade of life. We report the case of a young adult male patient with BRIC who presented with recurrent cholestatic jaundice and pruritus with negative work up for all possible etiologies and a liver biopsy consistent with intrahepatic cholestasis. He improved on treatment with rifampicin and has not suffered another attack on follow up. Although in adulthood, BRIC diagnosis should be kept in mind in patients with recurrent cholestatic attacks with symptom free intervals after main bile duct obstruction and other congenital or acquired causes of intrahepatic cholestasis excluded.

Landmark reading alterations in patients with gastro-oesophageal reflux symptoms undergoing diagnostic gastroscopy.

BACKGROUND AND STUDY AIMS: There is still a debate about the exact measurement of the oesophagogastric junction and the diaphragmatic hiatus among clinicians. The aim of this study was to investigate the differences between landmark readings of gastroscopy on intubation and extubation, and to correlate these readings with a gastro-oesophageal reflux questionnaire. PATIENTS AND METHODS: 116 cases who underwent diagnostic gastroscopy between January 2013 and June 2013 were included in this study. Landmark measurements were noted while withdrawing the endoscope and were also evaluated after the gastric air was fully emptied. We first used a frequency scale for the gastro-oesophageal reflux disease symptoms (FSSG) questionnaire in order to investigate dysmotility and acid reflux symptoms in the study population and correlated the FSSG questionnaire with intubation and extubation measurements at endoscopic examination. RESULTS: Mean age of included subjects was 49.41±17.7 (19-82) years. Males and females were equally represented. On FSSG scores, the total dysmotility score was 7.99±5.06 and the total score was 15.18±10.11. The difference between intubation and extubation measurements ranged from -3cm to +2cm (mean: -0.4). When an FSSG score of 30 was accepted as a cut-off value, we detected a significant difference between the measurements (p<0.05; t: 0.048). CONCLUSION: Accuracy of landmark measurements during gastroscopy is clearly affected from insertion or withdrawal of the endoscope. When differences in measurements between insertion and withdrawal were evident, comparable with the FSSG scores, the results became significantly different. In conclusion, according to FSSG scores, these measurements should be performed at the end of the endoscopy.

Immunohistochemical activity of Prohibitin-2 and Stomatin-Like Protein-2 in patients with ulcerative colitis.

BACKGROUND/AIMS: We aimed to semi-quantitatively investigate prohibitin-2 (Phb-2) and stomatin-like protein-2 (Slp-2) expressions in patients with ulcerative colitis (UC) and healthy controls using the immunohistochemical (IHC) method. We also aimed to evaluate the correlations between the activity of UC and the expressions of these two proteins. MATERIALS AND METHODS: Ninety-five patients with UC (82 males and 13 females) and 38 healthy controls (35 males and 3 females) were included. Clinical and endoscopic activities of UC were assessed. Conventional laboratory activation parameters and severity of inflammation measures were used for the evaluation of histological activity. IHC staining of biopsy samples for the two proteins were semi-quantitatively applied, similar to previously described methods for colon adenocarcinomas. RESULTS: IHC scores of Phb-2 were lower but Slp-2 scores were higher in the UC group than in the healthy controls (p<0.05 and p=0.003, respectively). Phb-2 scores were positively correlated with clinical and histological activities (r=0.364, p<0.05 and r=0.220, p<0.032, respectively). In the UC group, endoscopic activity scores, C-reactive protein levels, and sedimentation rates were also positively correlated with Phb-2 scores (r=0.279, p<0.05, r=0.216, p<0.05, and r=0.216, p<0.05, respectively). IHC scores of Slp-2 were not significantly correlated with the activity parameters of UC. However, there was a significant positive correlation between the expressions of Phb-2 and Slp-2 proteins (p<0.001). CONCLUSION: Phb-2 may serve as a valuable new biomarker for predicting the severity of all UC activity parameters. The therapeutic effectiveness of both Phb-2 and Slp-2 should be taken into consideration.

Serum matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 expression in patients with familial Mediterranean fever.

BACKGROUND/AIMS: Serum matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) are well-known inflammatory biomarkers, with a diagnostic potential for various diseases. The aim of the present study was to determine the potential diagnostic applications of serum MMP-9 and TIMP-1 concentrations in patients with familial Mediterranean fever (FMF). MATERIALS AND METHODS: A total of 66 male FMF patients and 40 age-matched healthy subjects were included in this research. TIMP-1 and MMP-9 levels with conventional inflammation markers were determined. Pearson correlation analysis was used to determine the correlation between the characteristics of patients and the laboratory data. RESULTS: In patients with FMF, serum MMP-9 levels and MMP-9/TIMP-1 ratios were found to be significantly elevated in both acute episode and asymptomatic periods (p=0.0001 and p=0.0001, respectively). There was no significant difference between TIMP-1 levels. A significant negative correlation between patients' current age and TIMP-1 level in patients with acute episodes was detected (p=0.0008, r=-0.52). Moreover, a moderate negative correlation was noticed between erythrocyte sedimentation rate and TIMP-1 level in patients with acute episodes (p=0.01, r=-0.39). Additionally, a moderate negative correlation was found between the duration of colchicine use and MMP-9 and TIMP-1 levels during the attack period (p=0.04, r=-0.36 and p=0.02, r=-0.39, respectively). CONCLUSION: Our findings demonstrate that a significant MMP-9/TIMP-1 imbalance exists in patients with FMF, which reflects an ongoing inflammation in both FMF periods. Thus, the increased MMP-9 levels observed in FMF patients could rationalize therapeutic targeting to MMPs.

The effect of taurine treatment on oxidative stress in experimental liver fibrosis.

Oxidative stress is important in pathogenesis of liver fibrosis, which is the result of deposition of excessive ECM proteins produced by activated hepatic stellate cells (HSCs). Reducing reactive oxygen species (ROS) production decreases collagen accumulation in liver. We investigated the benefits of antioxidant therapy in liver fibrosis and its association with HSC apoptosis. Forty-five male Spraque-Dawley rats were subdivided into three groups. Group I was treated with CCl(4) plus taurine, Group II with CCl(4) plus saline, and Group III with saline for 12 weeks. Erythrocyte and liver malondialdehyde (MDA) levels, superoxide dismutase (SOD) activities, Glutathione peroxidase (GSHpx) activities, and serum and liver TIMP-1 and MMP-13 levels were measured. Histopathological examinations were performed. Activated and total HSCs were quantified immunohistochemically. Apoptotic HSCs were detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) staining. Taurine decreased histopathological injury scores and oxidative stress parameters significantly. The number of activated HSCs was significantly higher in taurine untreated group ( [Formula: see text] ). Serum and tissue MMP-13 levels were significantly higher and TIMP-1 levels were significantly lower in taurine-treated group ( [Formula: see text] and [Formula: see text], respectively). The number of apoptotic activated hepatic stellate cells was significantly higher with taurine treatment ( [Formula: see text] ). Preventing the production of reactive oxygen species is effective in inhibiting fibrogenesis in experimental rat model. Inhibitory activity of this agent on HSCs' activation, apoptosis, and further fibrogenic events should be clearly identified.

Indications, complications and long-term follow-up of patients undergoing percutaneous endoscopic gastrostomy: A retrospective study.

INTRODUCTION: Gastroenterology units have faced a major increase in referrals for PEG insertion over the last decade. For this reason we decided to review our PEG insertion procedures with regard to indications, complications and follow-up. MATERIALS AND METHODS: The indications, success of procedure, complications, long-term results of PEG in patients of Gulhane Military Medical Academy, Haydarpasa Training Hospital between October 2002 and April 2009 were retrospectively evaluated. RESULTS: 81 patients had undergone PEG insertion and follow-up information has been available for 77 patients. 40 were men with the mean age of all patients 70.74 ± 20.82 (range 20 to 104 years). PEG was successfully placed in all patients except in one patient who had gastric bleeding during the procedure. There was only one mortality related with the placement procedure. The most common indication for PEG was neurologic disorders in 71 (92%) patients. Other indications were head and neck cancers in 6 (8%) patients. Median follow-up period was 12 months (range, 3 days to 78 months). PEG related complications were seen in only 14 patients (18.2%) in 16 events with a total complication rate as 21%. CONCLUSIONS: PEG placement is a safe procedure and well-tolerated with a low mortality and complication rate even in older patients who have multiple co-morbidities under adequate precautions.

An extremely uncommon case of parasitic infection presenting as eosinophilic ascites in a young patient.

We report the case of a 24-year-old male patient admitted for recent ascites and splenomegaly of unknown origin. The patient was referred to our institution with complaints of diarrhea, epigastric pain, abdominal cramping and weight loss over the past three weeks. The acute onset presented with colicky abdominal pain and peritoneal effusion. History revealed reduced appetite and weight gain of 7 kg over the last one month. His past medical history and family history was negative. He had no history of alcohol abuse or viral hepatitis infection. Laboratory data revealed normal transaminases and bilirubin levels, and alkaline phosphatase and gammaglutamyltransferase were within normal range. A diagnostic laparoscopy was performed which showed free peritoneal fluid and normal abdominal viscera. Upper gastrointestinal system endoscopy performed a few days later revealed diffuse severe erythematous pangastritis and gastroduodenal gastric reflux. Duodenal biopsies showed chronic nonspecific duodenitis. Antrum and corpus biopsies showed chronic gastritis. The ascitic fluid was straw-colored and sterile with 80% eosinophils. Stool exam was negative for parasitic infection. Treatment with albendazole 400 mg twice daily for 5 days led to the disappearance of ascites and other signs and symptoms. Three months after albendazole treatment the eosinophilic cell count was normal. The final diagnosis was consistent with parasitic infection while the clinical, sonographic and histological findings suggested an eosinophilic ascites. We emphasize the importance of excluding parasitic infection in all patients with eosinophilic ascites. We chose an alternative way (albendazole treatment) to resolve this clinical picture. With our alternative way for excluding this parasitic infection, we treated the patient and then found the cause.

Determination of the frequency of dyssynergic defecation and patient characteristics in patients with functional constipation.

BACKGROUND/AIMS: Dyssynergic defecation, a subgroup of functional constipation, is a relatively new definition, diagnostic criteria of which have recently been described. Distribution of subgroups of functional constipation in our population is scarcely known. We aimed to evaluate the demographic characteristics and defecation features of patients as we determined the frequency of dyssynergic defecation in patients with functional constipation in our community. METHODS: Eighty-two patients, 52 women and 30 men, with functional constipation were included in the study by using a questionnaire after secondary causes were excluded. Colonic transit time and balloon expulsion tests were performed to determine sub-groups of functional constipation. Colonoscopy and/or sigmoidoscopy in all patients and double contrast colonography in some patients were obtained at the beginning of the study to exclude anatomic and organic causes and patients with constipation predominant irritable bowel syndrome were also excluded from the study. RESULTS: The results of the study revealed that functional constipation in our community occurs more frequently in women and at relatively older (middle to old) age. Patients with normal transit constipation pattern are the largest portion (52.4%) of patients with functional constipation, whereas dyssynergic defecation is the second most frequent (25.6%) reason among this population. CONCLUSION: The frequency of dyssynergic constipation is lower in our population compared to western communities, but the symptoms are similar. We believe that the questionnaire we used is helpful in revealing defecation characteristics and when combined with balloon expulsion test and colonic transit time measurements it can be a valuable tool in the diagnosis of dyssynergic defecation.

Comparison of the effects of intravenous midazolam alone and in combination with meperidine on hemodynamic and respiratory responses and on patient compliance during upper gastrointestinal endoscopy: a randomized, double-blind trial.

BACKGROUND/AIMS: We examined hemodynamic responses during gastroscopy in healthy subjects and compared the changes with midazolam alone versus in combination with meperidine. The aim of this study was to evaluate if either method had any advantages or disadvantages with respect to patient compliance and the commonly seen side effects. METHODS: Thirty patients who were otherwise healthy were included in each group. Either midazolam 0.05 mg/kg IV (Group I) or meperidine 0.3 mg/kg IV followed by midazolam 0.05 mg/kg (Group II) IV were used for sedation. Data of noninvasive hemodynamic and cardiac parameters were recorded before and at the 1st minute after medication, and at the 1st minute and 2-min intervals during the procedure. Endoscopists assessed the comfort of patients according to pre-determined criteria. Statistical analysis was performed for both inter-group and in-group comparisons of parameters. RESULTS: Heart rate increased significantly in Group I (p<0.05). Blood pressures and oxygen saturation decreased significantly with sedation in both groups during endoscopy (p<0.05), without significant difference between the groups for the changes in these parameters (p>0.05). Patient compliance was significantly better in Group II than in Group I, for all measured criteria. CONCLUSIONS: We observed that heart rate increases significantly whereas SAP, DAP and SpO2 decrease significantly with both sedation methods. Groups did not differ except for the significantly higher increase in heart rate in Group I. Patient compliance was significantly better with combined sedation. We believe that combined sedation in selected patients provides a safe sedation with a mild to moderate increase in heart rate and a better patient compliance during gastroscopy.