Nevin Oruç

Infliximab: a new therapeutic agent in acute pancreatitis?

Purpose Tumor necrosis factor alpha (TNF-alpha) has a central role in the pathogenesis of acute pancreatitis and related systemic complications. The aim of this study is to investigate the therapeutic effectiveness of monoclonal TNF antibody (infliximab) in acute edematous and severe necrotizing pancreatitis models in rats. Methods One hundred rats were randomly divided into 10 groups. Acute edematous pancreatitis (AEP) was induced by injection of cerulein 20 &mgr;g/kg 4 times subcutaneously at hourly intervals. Severe necrotizing pancreatitis (SNP) was induced by retrograde injection of 3% taurocholate into the common biliopancreatic duct. Infliximab 8 mg/kg was given via intravenous infusion. Serum amylase activity, pancreatic histopathology, myeloperoxidase enzyme activity (MPO), and pulmonary changes were assessed. Results Infliximab treatment significantly decreased serum amylase activity (11939 ± 1914 U/L versus 3458 ± 915 U/L, P < 0.001) and histopathologic score (4.1 ± 0.5 versus 1.5 ± 0.3, P < 0.001) in AEP. It also suppressed neutrophil infiltration and MPO activity of the pancreatic tissue. In SNP, infliximab treatment was found to decrease pathologic score (9.4 ± 1.2 versus 3.6 ± 0.8, P < 0.001) and serum amylase activity (20442 ± 2375 versus 8990 ± 1730, P < 0.01). It ameliorated both parenchymal and fatty tissue necrosis of the pancreas. Infliximab also alleviated alveolar edema and acute respiratory distress syndrome like pulmonary complications, but the difference was not significant. Conclusions Chimeric TNF antibody, infliximab, should be evaluated for treatment of acute pancreatitis.

Inhibition of renin-angiotensin system in experimental acute pancreatitis in rats: a new therapeutic target?

OBJECTIVE Pancreatic renin-angiotensin system has been implied to play a role in the regulation of pancreatic functions and could be a new therapeutic target in acute pancreatitis. The aim of this study was to evaluate the therapeutic potential of angiotensin-converting-enzyme inhibition by captopril and angiotensin II type 1 receptor inhibition by L-158809 and losartan experimentally in acute pancreatitis. DESIGN Rats were randomly divided into 15 groups. Acute edematous pancreatitis was induced by injection of cerulein 20microg/kg SC four times at hourly intervals. Severe necrotizing pancreatitis was induced by retrograde injection of 3% taurocholate into the biliary-pancreatic duct. INTERVENTIONS Captopril, L-158809 and losartan were given intraperitoneally. Main outcome features: pancreatic pathology, pancreatic myeloperoxidase activity and serum amylase activity were assessed. RESULTS Captopril decreased serum amylase (10,809+/-1867 vs. 4085+/-1028U/L, p<0.01), myeloperoxidase activity (3.5+/-0.5 vs. 1.5+/-0.1, p<0.05) and histopathological score (5.0+/-0.4 vs. 1.1+/-0.5, p<0.01) in acute edematous pancreatitis. In taurocholate induced severe necrotizing pancreatitis captopril ameliorated histopathological score (10.1+/-1.2 vs. 3.4+/-0.5, p<0.01), pancreatic parenchymal necrosis (4.5+/-0.6 vs. 0.0+/-0.0, p<0.001), fatty necrosis (2.8+/-0.9 vs. 0.1+/-0.1, p<0.01) and edema (2.1+/-0.3 vs. 1.4+/-0.3, p<0.05). However, L-158809 did not have similar beneficial effects on acute pancreatitis in rats while losartan decreased pancreatic parenchymal necrosis and neutrophil infiltration. CONCLUSIONS This study not only demonstrated the differential effects of captopril, losartan and L-158809 in acute pancreatitis but also showed that there is still much to investigate about pancreatic renin-angiotensin system. Inhibition of angiotensin-converting enzyme should be evaluated carefully as a potential new therapeutic target in acute pancreatitis.

Serum procalcitonin and CRP levels in non-alcoholic fatty liver disease: a case control study

BackgroundBoth C reactive protein (CRP) and procalcitonin (PCT) are well known acute phase reactant proteins. CRP was reported to increase in metabolic syndrome and type-2 diabetes. Similarly altered level of serum PCT was found in chronic liver diseases and cirrhosis. The liver is considered the main source of CRP and a source of PCT, however, the serum PCT and CRP levels in non-alcoholic fatty liver disease (NAFLD) were not compared previously. Therefore we aimed to study the diagnostic and discriminative role of serum PCT and CRP in NAFLD.MethodsFifty NAFLD cases and 50 healthy controls were included to the study. Liver function tests were measured, body mass index was calculated, and insulin resistance was determined by using a homeostasis model assessment (HOMA-IR). Ultrasound evaluation was performed for each subject. Serum CRP was measured with nephalometric method. Serum PCT was measured with Kryptor based system.ResultsSerum PCT levels were similar in steatohepatitis (n 20) and simple steatosis (n 27) patients, and were not different than the control group (0.06 ± 0.01, 0.04 ± 0.01 versus 0.06 ± 0.01 ng/ml respectively). Serum CRP levels were significantly higher in simple steatosis, and steatohepatitis groups compared to healthy controls (7.5 ± 1.6 and 5.2 ± 2.5 versus 2.9 ± 0.5 mg/dl respectively p < 0.01). CRP could not differentiate steatohepatitis from simple steatosis. Beside, three patients with focal fatty liver disease had normal serum CRP levels.ConclusionSerum PCT was within normal ranges in patients with simple steatosis or steatohepatitis and has no diagnostic value. Serum CRP level was increased in NAFLD compared to controls. CRP can be used as an additional marker for diagnosis of NAFLD but it has no value in discrimination of steatohepatitis from simple steatosis.

Effects of mast-cell stabilization in cerulein-induced acute pancreatitis in rats

SummaryAim. In this study we aimed to clarify the role of mast cells in the development and progression of inflammation in cerulein-induced acute pancreatitis (AP) in rats. We have also examined the effects of ketotifen; a mast-cell stabilizing agent in the treatment of acute pancreatitis and its relation with nitric oxide (NO) synthesis.Methods. In the first part of the study we planned to examine the effects mast cell stabilization in acute pancreatitis, while the second part was focused on examining the relation between NO synthesis and the potential effects of ketotifen in AP. Wistar albino rats were randomly divided into 6 groups (n: 10). In the first part of the study, AP was induced by four subcutaneous (sc) injections of 20 µg/kg body weight of cerulein at hourly intervals in Groups A and B while Group C was treated with saline as the control group. Group B was pretreated with ketotifen 1 mg/kg (ip). In the second part, the study design was similar except for the inhibition of nitric oxide synthesis by N-nitro L-arginine methyl ester (L-NAME) 30 mg/kg (ip) in Groups D, E and F. Group D was treated with L-NAME and cerulein and Group E was treated with ketotifen, L-NAME and cerulein. Group F was treated with L-NAME and saline as the control group. Serum amylase activity and pancreatic myeloperoxidase activity (MPO) were measured. Pancreatic histology and mast-cell count in pancreatic tissue were evaluated.Results. Mast cell count was found to be increased in the pancreatic tissue in cerulein-induced AP. (2.93±0.26 vs 1.98±0.26; p<0.001). Ketotifen treatment significantly reduced cerulein induced edema (1.30±0.21 vs 0.70±0.15; p<0.001), neutrophil infiltration (1.50±0.16 vs 0.60±0.16; p<0.001) and attenuated the increase in amylase (4394.0±149.5 U/L vs 3350.5±216.9 U/L; p<0.05) and MPO activity (1.14±0.13 U/gr tissue vs 0.54±0.08 U/gr tissue; p<0.001). Mast-cell count in pancreatic tissue was also decreased significantly with ketotifen pretreatment (2.93±0.26 vs 1.70±0.21; p<0.05). Inhibition of NO synthesis with L-NAME treatment decreased the beneficial effects of ketotifen.Conclusion. It seems likely that mast cell activity may play an important role in the initiation and progression of acute pancreatitis. Ketotifen treatment may reduce the severity of AP in rats. The protective action of ketotifen in cerulein-induced acute pancreatitis is most probably owing to mast cell stabilization and stimulation of NO synthesis.

Association Between Pancreatic Intraductal Papillary Mucinous Neoplasms and Extrapancreatic Malignancies

BACKGROUND & AIMS The association between pancreatic intraductal papillary mucinous neoplasms (IPMNs) and extrapancreatic neoplasms (EPNs) is controversial. We performed a multicenter observational study to assess the incidence of EPNs after an IPMN diagnosis. METHODS 1340 patients with IPMNs were evaluated from 2000 through 2013 at 4 academic institutions in Europe for development of EPN. To estimate the actual incidence of EPN, we excluded patients with an EPN previous or synchronous to the IPMN, and patients who had been followed for less than 12 months, resulting in a study population of 816 patients. The incidence of EPN was compared with sex-specific, age-adjusted European cancer statistics; the standardized incidence ratio (SIR), and the 5- and 10-year cumulative incidence rates were calculated. RESULTS A total of 290/1340 patients had a history of EPN (prevalence of 21.6%). In this subgroup of patients, the IPMN was discovered incidentally in 241. Among the 816 patients included in the incidence analysis, 50 developed an EPN after a median time of 46 months from study enrollment. The incidence of any EPN was not greater in patients with than without IPMN with a SIR of 1.48 (95% confidence interval, 0.94-2.22) in males and of 1.39 (95% CI 0.90-2.05) in females. The 5- and 10-year cumulative incidence rates for development of EPN in patients with IPMN were 7.9% and 16.6% in men, and 3.4% and 23.1% in women. CONCLUSIONS Patients with IPMN do not have a significantly higher incidence of EPNs than the general European population. It might not be necessary to screen patients with IPMN for EPN.

The modified sequential treatment regimen containing levofloxacin for Helicobacter pylori eradication in Turkey.

Background:  Eradication rates of Helicobacter pylori have declined to unacceptable levels in recent years. New and effective treatment options are warranted both as a first and second line treatment.

Budd-Chiari syndrome in an afibrinogenemic patient : A paradoxical complication

Qualitative and quantitative abnormalities of fibrinogen can result in hemostatic disorders (1). Congenital afibrinogenemia is a rare coagulation disorder transmitted as an autosomal recessive trait (2). The incidence of afibrinogenemia is 1–2 cases per million population (3). It is more common in populations with a high rate of consanguinity (3). Symptoms of afibrinogenemia vary from mild hemorrhagic events to severe bleeding episodes, though thrombotic events are very rare. We report an afibrinogenemic patient who presented with hepatic venous thrombosis at 16 years old. Evaluation of all hemostatic parameters and coagulation factors revealed no other pathology except afibrinogenemia. Paradoxically, afibrinogenemia may be a risk factor for vascular thrombotic events like Budd–Chiari Syndrome (BCS).

Is procalcitonin a reliable marker for the diagnosis of infected pancreatic necrosis

Background:  Infected necrosis in acute pancreatitis is the main factor in determining the prognosis of the disease. Early and accurate diagnosis of infected pancreatic necrosis might decrease mortality. The aim of the present study is to identify a reliable marker for the onset infection in three different experimentally induced pancreatitis models.

Hyperhomocysteinaemia and factor V Leiden mutation are associated with Budd-Chiari syndrome.

Objectives Budd–Chiari syndrome (BCS) is characterized by hepatic venous outflow obstruction and may be caused by various prothrombotic disorders. We aimed to study the role of hyperhomocysteinaemia, factor V Leiden mutation and G20210A prothrombin gene mutation in the pathogenesis of the syndrome. Methods Thirty-two patients (16 male, 16 female, aged 19–45 years) with angiographically verified BCS and 33 age-matched and sex-matched voluntary healthy controls (15 male, 18 female, aged 19–45 years) were included into the study. Factor V Leiden and prothrombin gene mutations were determined in extracted DNA from peripheric mononuclear cells, using a light cycler amplification system. Plasma homocysteine levels were measured by fluorescence polarization immunoassay. Results The homozygote factor V Leiden mutation was diagnosed in four BCS patients and the heterozygote mutation was diagnosed in five. The frequency of the mutant allele was 20.3% in BCS patients and 7.6% in the controls (P<0.05). There was no significant difference in prothrombin gene mutation frequency between the two groups. Serum homocysteine levels were significantly higher in the BCS group than in the controls (16.4±8.8 vs 11.0±2.7 μmol/l; P<0.01). BCS patients with the mutant factor V Leiden allele have significantly higher levels of serum homocysteine (22.1±13.3 vs 14.4±5.9 μmol/l; P<0.05). Conclusions Hyperhomocysteinaemia, especially when associated with the factor V Leiden mutation, is an important risk factor for the development of BCS.

Acute presentation of autoimmune hepatitis in a patient with myasthenia gravis, thymoma, Hashimoto thyroiditis and connective tissue disorder

Myasthenia gravis is an antibody‐mediated autoimmune disease at the neuromuscular junctions. It can be associated with many other autoimmune diseases. We report a case of acute presentation of autoimmune hepatitis with myasthenia gravis, thymoma, Hashimoto thyroiditis and connective tissue disorder.