Glial cell line-derived neurotrophic factor-induced mice liver defatting: A novel strategy to enable transplantation of steatotic livers.

Moderate macrovesicular steatosis (>30%), which is present in almost 50% of livers considered for transplantation, increases the risk of primary graft dysfunction. Our previously published data showed that glial cell line-derived neurotrophic factor (GDNF) is protective against high-fat diet (HFD)-induced hepatic steatosis in mice. Hence, we hypothesized that perfusion of steatotic livers with GDNF may reduce liver fat content before transplantation. Livers from 8 weeks of regular diet (RD) and of HFD-fed mice were perfused ex vivo for 4 hours with either vehicle, GDNF, or a previously described defatting cocktail. The liver's residual fat was quantified colorimetrically using a triglyceride (TG) assay kit and by Oil Red O (ORO) and Nile red/Hoechst staining. Liver tissue injury was assessed by using a lactate dehydrogenase (LDH) activity assay. In vitro induction of lipolysis in HepG2 cells was assessed by measuring glycerol and free fatty acid release. ORO staining showed significantly more steatosis in livers from HFD-fed mice compared with RD-fed mice (P < 0.001). HFD livers perfused with GDNF had significantly less steatosis than those not perfused (P = 0.001) or perfused with vehicle (P < 0.05). GDNF is equally effective in steatotic liver defatting compared to the defatting cocktail; however, GDNF induces less liver damage than the defatting cocktail. These observations were consistent with data obtained from assessment of liver TG content. Assessment of liver injury revealed significant hepatocyte injury in livers perfused with the control defatting cocktail but no evidence of injury in livers perfused with either GDNF or vehicle. In vitro, GDNF reduced TG accumulation in HepG2 cells and stimulated increased TG lipolysis. In conclusion, GDNF can decrease mice liver fat content to an acceptable range and could be a potential defatting agent before liver transplantation.

Loin pain hematuria syndrome.

Loin pain hematuria syndrome is a rare disease with a prevalence of ∼0.012%. The most prominent clinical features include periods of severe intermittent or persistent unilateral or bilateral loin pain accompanied by either microscopic or gross hematuria. Patients with loin pain hematuria syndrome initially present with hematuria, flank pain, or most often both hematuria and flank pain. Kidney biopsies from patients with loin pain hematuria typically reveal only minor pathologic abnormalities. Further, loin pain hematuria syndrome is not associated with loss of kidney function or urinary tract infections. Loin pain hematuria syndrome-associated hematuria and pain are postulated to be linked to vascular disease of the kidney, coagulopathy, renal vasospasm with microinfarction, hypersensitivity, complement activation on arterioles, venocalyceal fistula, abnormal ureteral peristalsis, and intratubular deposition of calcium or uric acid microcrystals. Many patients with loin pain hematuria syndrome also meet criteria for a somatoform disorder, and analgesic medications, including narcotics, commonly are used to treat loin pain hematuria syndrome-associated pain. Interventional treatments include renal denervation, kidney autotransplantation, and nephrectomy; however, these methods should be used only as a last resort when less invasive measures have been tried unsuccessfully. In this review article, we discuss and critique current clinical practices related to loin pain hematuria syndrome pathophysiology, diagnosis, treatment, and prognosis.

The Relation between Helicobacter pylori Infection and Acute Bacterial Diarrhea in Children.

Background. H. pylori infection leads to chronic gastritis in both children and adults. But recently, there are arising theories of its protective effect in diarrheal diseases. Aim. To explore the prevalence of H. pylori infection in children with bacterial diarrhea and compare it with healthy controls. Patients and Methods. Two matched groups consisted of 122 consecutive children, aged 24-72 months old, with acute bacterial diarrhea, who had Shigellosis (N = 68) and Salmonellosis (N = 54) as patients group and 204 healthy asymptomatic children as control group enrolled in this study. Results. The prevalence of H. pylori infection in healthy control children was significantly higher than in patients group, (odds ratio = 3.6, 95% CI: 1.33-9.5, P = 0.007). In our study, only 2/54 Salmonella infected patients and 3/68 of Shigellosis had evidence of H. pylori infection, while normal control children had 27/204 infected individuals. Conclusion. H. pylori infection may play a protective role against bacterial diarrhea in children. So it is important to consider all of the positive and negative aspects of H. pylori infection before its eradication.

An algorithm for glaucoma screening in clinical settings and its preliminary performance profile.

PURPOSE: To devise and evaluate a screening algorithm for glaucoma in clinical settings. METHODS: Screening included examination of the optic disc for vertical cupping (≥0.4) and asymmetry (≥0.15), Goldmann applanation tonometry (≥21 mmHg, adjusted or unadjusted for central corneal thickness), and automated perimetry. In the diagnostic step, retinal nerve fiber layer imaging was performed using scanning laser polarimetry. Performance of the screening protocol was assessed in an eye hospital-based program in which 124 non-physician personnel aged 40 years or above were examined. A single ophthalmologist carried out the examinations and in equivocal cases, a glaucoma subspecialist's opinion was sought. RESULTS: Glaucoma was diagnosed in six cases (prevalence 4.8%; 95% confidence interval, 0.01-0.09) of whom five were new. The likelihood of making a definite diagnosis of glaucoma for those who were screened positively was 8.5 times higher than the estimated baseline risk for the reference population; the positive predictive value of the screening protocol was 30%. Screening excluded 80% of the initial population. CONCLUSION: Application of a formal screening protocol (such as our algorithm or its equivalent) in clinical settings can be helpful in detecting new cases of glaucoma. Preliminary performance assessment of the algorithm showed its applicability and effectiveness in detecting glaucoma among subjects without any visual complaint.

Update on the management of ulcerative colitis.

The present treatment goals for inflammatory bowel diseases (IBD) especially ulcerative colitis (UC) include rapid induction of clinical remission, steroid-free maintenance of clinical remission, mucosal healing and improvement of quality of life in UC patients. Immunomodulators have been reserved for steroid- dependent or steroid- refractory UC patients. Among these agents, azathioprine/6-mercaptopurine should be used for maintenance of remission in quiescent UC. Calcineurin inhibitors can be prescribed as a short-term rescue therapy in steroid- refractory UC patients, but the long term efficacy of these agents remains unclear. According to retrospective studies, methotraxate is not recommended for inducing and maintaining remission in UC. Novel biological therapies targeting different specific immunological pathways continue to be developed and introduced for a variety of clinical scenarios in IBD. Infliximab is currently used for induction and maintenance therapy in patients who have moderately to severely active UC with an inadequate response to conventional agents such as aminosalicylates, corticosteroids, or immunomodulators. Other anti-TNF agents and biologic therapies are undergoing evaluation in clinical trials for their efficacy in IBD. Most patients who start biologics should continue treatment for the foreseeable future and potential consequences of discontinuation should be discussed with individual patients. Currently, data do not exist to administer biologics as first-line therapy in UC. Emerging data suggest that biologics may have the potential to prevent complications and limit disease progression. If such benefits are proven, biologics may be used in the future to modulate subclinical inflammation and to prevent the development of clinical disease.

Association between irritable bowel syndrome and restless legs syndrome: a comparative study with control group.

BACKGROUND/AIMS: As a common gastrointestinal (GI) disorder, irritable bowel syndrome (IBS) has been reported to be associated with some psychological and neurological factors. This study aimed to evaluate the prevalence rate of restless legs syndrome (RLS) in a sample of IBS patients and to compare this prevalence with that of matched healthy controls. METHODS: This prospective comparative study was conducted in Tehran, Iran during 2010-2011. Based on the Rome III criteria, a total number of 225 definite IBS patients and 262 age- and sex-matched healthy controls were recruited in the final assessment to compare the prevalence rate of RLS between the 2 groups. RESULTS: RLS was significantly more frequent in IBS group (25.3% vs 6.5%, P < 0.001) which led to an odds ratio (OR) of 4.89 (95% CI, 2.75-8.70). IBS patients with co-morbid RLS significantly suffered more from stomach pain (96.5% vs 86.3%, OR = 4.36 [95% CI, 1.00-19.12]), nausea (40.4% vs 21.4%, OR = 2.48 [95% CI, 1.30-4.73]) and vomiting (10.5% vs 2.4%, OR = 4.82 [95% CI, 1.31-17.76]). CONCLUSIONS: By enrolling a considerable number of IBS patients and healthy controls, our study showed a significantly higher prevalence of RLS in IBS patients. Surprisingly, a higher prevalence rate of RLS was also accompanied with a more severe discomfort and stomach pain in IBS patients. It seems that screening patients with IBS for RLS may lead to greater identification of RLS and improved treatment for both conditions.

Gender Role in Irritable Bowel Syndrome: A Comparison of Irritable Bowel Syndrome Module (ROME III) Between Male and Female Patients.

BACKGROUND/AIMS: Irritable bowel syndrome (IBS) is a widespread chronic health condition which is significantly more prevalent in women. We conducted a gender difference analysis by comparing findings of men and women to determine whether any significant differences exist or not. METHODS: This single-center study was conducted in Tehran, Iran during 2009-2010. IBS was diagnosed on the basis of Rome III criteria. A simple "10 point" objective questionnaire was used. RESULTS: A total number of 144 IBS patients including 44 (30.6%) males and 100 (69.4%) females with the mean age of 37.50 ± 11.50 years, were assessed. The only differently observed symptom was nausea which was significantly more prevalent in females (49% vs 18.2%, P < 0.001). The commonest subtype of IBS in male patients was diarrhea predominant IBS (38.6%); while, constipation predominant IBS was the most frequent type among females (38%). Moreover, the frequency of loose, mushy or watery stools within the last 3 months was significantly higher among males (2.11 ± 1.67 vs 1.37 ± 1.50, P = 0.009). CONCLUSIONS: We report that gender is important in IBS. Although qualitative comparison of different subtypes of IBS between male and female failed to meet the statistically significant level, the answers to the corresponding questions of ROME III IBS module suggest the higher prevalence of bowel movements and looser stool in males. Moreover, nausea was reported more often by females.

Non-alcoholic fatty liver disease and correlation of serum alanin aminotransferase level with histopathologic findings.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) has been recognized as the most common cause of chronic liver disease worldwide. It occurs in patients who do not consume alcohol in large amounts. Alanine aminotranferase (ALT) and aspartate aminotransferase (AST) are indicators of hepatocellular injury. OBJECTIVES: To determine correlation between histopathologic specifications of NAFLD in patients with little or no history of alcohol consumption and the serum level of ALT. PATIENTS AND METHODS: In a cross-sectional study carried out in two gastroenterology and hepatology clinics in Tehran, Iran, the medical records of those who had undergone liver biopsies between years 2005 and 2009 were reviewed. Clinical and laboratory information of biopsy-proven cases of NAFLD were obtained from 147 eligible medical records. The histopathologic, demographic, and laboratory data of the participants were also collected. Two groups of patients according to their serum ALT level (cut-point of 35 U/L) were defined. The quantitative pathologic grade of the biopsy specimens was determined based on Brunt scoring system. RESULTS: We studied 147 NAFLD patients including 127 men (86.4%) and 20 women (13.6%) with a mean ± SD age of 41.4 ± 11.2 years. Considering serum ALT, the mean ± SD quantitative grade of hepatosteatosis was 1.50 ± 0.67 and 1.74 ± 0.73 (p=0.136); advanced fibrosis (consisted of grade III and cirrhosis) was found in 4.5% (1/22) and 5.6% (7/125) of patients (p=0.327). CONCLUSIONS: We found that using the cut-off value of 35 U/L for serum ALT level, it has little contribution to predict NAFLD severity.