Haim Shirin

Inhibition of Immune-Mediated Concanavalin A-Induced Liver Damage by Free-Radical Scavengers

Background/Aims The aims of the present study were to elucidate whether oxidative stress has a role in Conxa0A-induced hepatitis and to examine if antioxidants may protect against liver damage in this model. Methods Hepatitis was induced in Balb/c mice by administration of Conxa0A (18xa0mg/kg) to the tail vein. Liver enzymes and histology were determined 24xa0h after Conxa0A injection. Tumor necrosis factor alpha (TNFα) and interleukin-10 (IL-10) levels were assayed 2xa0h after Conxa0A injection. Hepatic malondialdehyde levels were measured at 1, 3, 8, 12, 18, and 24xa0h after Conxa0A injection in order to examine the timing of free-radicals formation. Nuclear factor kappa B (NF-κβ) activation was determined by electrophoresis mobility shift assay (EMSA) 1 and 2xa0h after Conxa0A injection. In separate experiments, mice were pretreated with either dimethylsulfoxide or dimethylthiourea before Conxa0A inoculation. The antioxidant and NF-κβ inhibitor pyrrolidine dithiocarbamate (PDTC) was used as positive control. Results Hepatic malondialdehyde levels increased 12, 18, and 24xa0h after Conxa0A inoculation but not earlier. Serum levels of liver enzymes and TNFα, hepatic malondialdehyde, and protein carbonyls and the histologic necroinflammatory score were significantly reduced in the antioxidants-treated mice, while IL-10 levels were increased. Dimethylsulfoxide, dimethylthiourea, and PDTC inhibited oxidative stress, but only PDTC inhibited Conxa0A-induced NF-κB activation. Conclusions Reactive oxygen species play a role in immune-mediated Conxa0A-induced hepatitis probably secondary to immune-mediated liver damage. Scavenging of reactive oxygen species by antioxidants prevents hepatitis independently of NF-κB inhibition and may be a new therapeutic target in this experimental model.

Age and gender differences in urea breath test results

Eur J Clin Invest 2011; 41 (7): 767–772

Applicability of a short/rapid 13C-urea breath test for Helicobacter pylori: retrospective multicenter chart review study

BackgroundCarbon labeled urea breath tests usually entail a two point sampling with a 20 to 30-minute gap. Our aim was to evaluate the duration of time needed for diagnosing Helicobacter pylori by the BreathID® System.MethodsThis is a retrospective multicenter chart review study. Test location, date, delta over baseline, and duration of the entire test were recorded. Consecutively 13C urea breath tests results were extracted from the files over a nine year period.ResultsOf the 12,791 tests results, 35.1% were positively diagnosed and only 0.1% were inconclusive. A statistically significant difference in prevalence among the countries was found: Germany showing the lowest, 13.3%, and Israel the highest, 44.1%. Significant differences were found in time to diagnosis: a positive diagnosis had the shortest and an inconclusive result had the longest. Overall test duration averaged 15.1 minutes in Germany versus approximately 13 minutes in other countries. Diagnosis was achieved after approximately 9 minutes in Israel, Italy and Switzerland, but after 10 on average in the others. The mean delta over baseline value for a negative diagnosis was 1.03 ± 0.86, (range, 0.9 - 5), versus 20.2 ± 18.9, (range, 5.1 - 159.4) for a positive one.ConclusionsThe BreathID® System used in diagnosing Helicobacter pylori can safely shorten test duration on average of 10-13 minutes without any loss of sensitivity or specificity and with no test lasting more than 21 minutes.

Revealing the Puzzle of Nonadherence in IBD—Assembling the Pieces

BackgroundnAdherence is generally associated with improved treatment outcomes in inflammatory bowel disease (IBD) patients. Different components of the patient profile have an impact on patient adherence. Capturing nonadherent patients by identifying modifiable risk factors in daily practice still remains a challenge. The objective of this study was to identify modifiable and nonmodifiable risk factors for nonadherence in IBD patients.nnnMethodsnPatients filled out questionnaires including demographic, clinical, and socioeconomic information and accessibility to gastrointestinal services. Psychological features were assessed using the Sense of Coherence, Hospital Anxiety and Depression Scale, IBD-Self Efficacy, and Brief Illness Perception (BIPQ) questionnaires. Adherence to treatment was evaluated using the Morisky score.nnnResultsnThe study included 311 patients: 62.4% females, median age 34.78 years, 70.4% Crohns disease (CD). Multivariate analysis was done in 3 sections: demographic and disease characteristics, communication with medical staff, and psychological aspects; all included sex and disease type. Ulcerative colitis (UC) patients were less adherent (odds ratio [OR], 1.792; OR, 1.915; OR, 1.748; respectively). Females were less adherent in 2 sections (OR, 1.841; OR, 1.751; respectively). Employment (OR, 2.449), low score in on the BIPQ-understanding of disease (OR, 0.881), and poor communication with the gastroenterologist (OR, 1.798) were also predictors of low adherence.nnnConclusionsnNonmodifiable characteristics such as female sex and UC are associated with low adherence. Good communication with the treating physician and understanding the disease are modifiable factors associated with high adherence. Early intervention might improve patients adherence.

Expression of Duodenal Iron Transporter Proteins in Diabetic Patients with and without Iron Deficiency Anemia

The role of iron transport proteins in the pathogenesis of anemia in patients with diabetes mellitus (T2DM) is still unclear. We investigated the expression of duodenal transporter proteins in diabetic patients with and without iron deficiency anemia (IDA). Methods. Overall, 39 patients were included: 16 with T2DM and IDA (group A), 11 with T2DM without IDA (group B), and 12 controls (group C). Duodenal mucosal expression of divalent metal transporter 1 (DMT1), ferroportin 1 (FPN), hephaestin (HEPH), and transferrin receptor 1 (TfR) was evaluated by Western blotting. Chronic disease activity markers were measured as well. Results. FPN expression was increased in group A compared to group B and controls: 1.17 (0.72–1.46), 0.76 (0.53–1.04), and 0.71 (0.64–0.86), respectively (p = 0.011). TfR levels were over expressed in groups A and B compared to controls: 0.39 (0.26–0.61), 0.36 (0.24–0.43), and 0.18 (0.16–0.24), respectively, (p = 0.004). The three groups did not differ significantly with regard to cellular HEPH and DMT1 expression. The normal CRP and serum ferritin levels, accompanied with normal FPN among diabetic patients without IDA, do not support the association of IDA with chronic inflammatory state. Conclusion. In patients with T2DM and IDA, duodenal iron transport protein expression might be dependent on body iron stores rather than by chronic inflammation or diabetes per se.

The Relationship between Gender, Severity of Disease, Treatment Type, and Employment Outcome in Patients with Inflammatory Bowel Disease in Israel

Introduction Since individuals with IBD typically experience symptoms during their prime years of employment, it raises the question about IBD impact on employment status. Most studies concentrated on absenteeism from work with varying results in different populations. However, absenteeism reflects only one dimension of the ability to work and does not expose the problem of inability to hold a full-time job. Aims To evaluate the influence of IBD on unemployment and working hours in Israel. Secondary aims were to investigate the correlation between working hours and the type of medical treatment and the impact of severity of disease. Patients and Methods Demographic data, employment status, number of weekly working hours, and disease parameters. The data was compared to that of the general Israeli population extracted from the website of the Central Bureau of Statistics. Results 242 IBD patients were interviewed. Patients median age was 37.04(IQR 30.23-44.68) years and 88 (36.4%) were men and 154 (63.6%) women. Diagnosis of CD was established in 167 (69%) patients and UC in 65 (26.9%). There was no significant reduction in employment rates or working hours among the IBD patients comparing to the general population. Immunosuppressive or biologic treatment did not influence employment status. The unemployed patients had higher disease severity (median 7.33, IQR 5-10.66) compared to employed patients (median 6, IQR 3.66-7.66; p=0.003). Conclusions Although IBD patients in Israel do not have higher unemployment, those with severe disease have lower proportion of employment.

Real-world Helicobacter pylori diagnosis in patients referred for esophagoduodenoscopy: The gap between guidelines and clinical practice

Background and aims Histopathology is the most accurate test to detect H. pylori when performed correctly with unknown validity in daily practice clinic settings. We aimed to determine the rate of potentially false-negative H. pylori results that might be due to continued use of proton pump inhibitors (PPIs) in routine endoscopy practice. We also aimed to establish whether gastroenterologists recommend routine cessation of PPIs before esophagogastroduodenoscopy (EGD) and whether they regularly document that biopsies for H. pylori testing have been taken while the patients are on PPI treatment. Methods Detailed information about three known factors (PPIs, antibiotics and prior H. pylori eradication treatment), which may cause histology or rapid urease test (RUT) to be unreliable, had been prospectively collected through interviews using a questionnaire before each test. Gastric biopsies were stained with H&E for histological analysis. Results A total of 409 individuals at three academic gastroenterology institutions were tested 200 times with histology. Fifty-six per cent (68 of 122) of all negative tests fell in the category of continuing PPI use, which had the potential to make the histology and RUT results unreliable. Conclusions These data demonstrate a clear and important gap between current guidelines and real-world practice with regards to the diagnosis of H. pylori during EGD. A negative histology or RUT should be considered false negative until potential protocol violations are excluded. Documentation of PPI use during the EGD should be an integral part of the EGD report. The current practice of taking biopsies for H. pylori testing in patients under PPIs should be reevaluated.

Rare, Life-Threatening Duodenal Bleeding

Question: A 61-year-old male born in Ethiopia with a past medical history of hepatitis B carrier, tuberculosis, arterial hypertension, and aortic valve replacement (on coumadin treatment since 2009), presented with epigastric pain radiating to the right upper quadrant. The pain worsened after meals and was accompanied with a weight loss of 5 kg in the last month. He had recently discharged from the Neurosurgery Department with dexamethasone treatment for subdural hygroma. On physical examination, the patient was afebrile with normal blood pressure and soft abdomen with diffuse mild tenderness. Initially, laboratory examination was remarkable for mild normocytic normochromic anemia 11.6 g/dL, mean corpuscular volume of 84.4, normal white cell count of 7800/mm (normal range, 4500–11,000/mm) with absolute eosinophil count of 300/mm (normal range, 0–700/mm), international normalized ratio of 10.8, albumin 18 g/L, C-reactive protein 111 mg/L (normal, <5), sodium 127 mmol/L, and potassium 3.5 mmol/L. All other biochemical tests, creatinine, liver enzymes, pancreatic enzymes, and HIV screening revealed normal findings. Twenty-four hours after his admission, the patient developed massive hematemesis. An urgent upper gastrointestinal (GI) endoscopy showed severe duodenitis in the bulbus continuing down to the second part of the duodenum accompanied by multiple ulcers covered with exudate (Figure A, B). The mucosa was bleeding to touch and no definite bleeding vessel was identified. Biopsies were taken from the lesions and he began proton pump inhibitor drip. Over the following 8 hours, he developed recurrent hematemesis and hypotension and computed tomography angiography revealed extensive damage to the proximal small bowel (Figure C, D). Because of the high surgical risk, a selective embolization of the gastroduodenal artery was performed (Figure E, F). Despite this approach the patient continued to bleed and required blood transfusions. Correlating these clinical and endoscopic findings with the patient’s history and background.

Different roles of free hydroxyl radicals, nitric oxide and tumor necrosis factor α in thioacetamide induced liver cirrhosis in rats

Reactive oxygen species, proinfiammatory cytokines, and nitric oxide have all been implicated in the pathogenesis of hepatic fibrosis. The aim of the present study was to examine the respective roles of these factors in the pathogenesis of thioacetamide-induced hepatic cirrhosis in rats. Methods: Liver cirrhosis was induced by intraperitoneal injections of thioacetamide (200 mg/kg) twice a week, for 12 weeks. Rats were treated concurrently with one of the following agents: the hydroxyl free radical scavenger, dimethylsulfoxide (DMSO, 4 g/kg, i.p. or p.o., 3 times a week), the anti tumor necrosis factor-~x agent pentoxifylline (PTX, 20, 100 and mg/kg, 3 times a week) or the nitric oxide synthase inhibitor N-mono-methyl arginine ester (L-NAME) (0.1 mg/ml in the drinking water), given either alone or together with pentoxifylline 20 mg/kg. Results: The degree of liver fibrosis, spleen weights and hepatic hydroxyproline levels were determined after 12 weeks in the different treatment groups, and shown in the Table: