Kassem Faraj is a third year medical student at Oakland University William Beaumont School of Medicine. He has BS in Chemistry from Wayne State University. He has been involved in research projects in the fields of urology, general surgery and internal medicine.
Acute cholangitis (AC) is an infection of the biliary tract caused by biliary obstruction and stasis. The most common symptoms are fever and abdominal pain, which are seen in 80% of patients. A 47-year-old male presented with a three-week history of scleral icterus, dark urine, and pale stools, consistent with jaundice. He complained of fatigue, but denied any abdominal pain, fever, chills, nausea or vomiting. Laboratory results were significant for AST 959 IU/L, ALT 1563 IU/L, alkaline phosphatase 199 IU/L, total bilirubin 24.0 IU/L, direct bilirubin 19.9 IU/L, total iron 246 mcg/dL, ferritin 5008ng/mL, and transferrin saturation 85%. An acute hepatitis panel was negative, and an abdominal ultrasound and CT scan were unremarkable. Serology results for EBV included: IgG 279, EB-EA (early antigen) >150, EB-NA (nuclear antigen) 544 and a normal IgM. Reactivation of EBV was suspected and a diagnosis of EBV hepatitis was made. The patient did not improve with supportive measures, prompting a liver biopsy, which showed acute inflammation, periportal fibrosis, and neutrophillic infiltration and cholestasis of the biliary tree, which was consistent with AC. MRCP was unremarkable for biliary dilatation. The patient was managed supportively and gradually improved. This case presented major challenges to clinicians including the lack of classic symptoms and biliary dilatation on imaging, the apparent iron overload and the presence of a recent EBV infection. Biliary dilatation is very common, but is not necessary for the diagnosis of AC. Mild cases can be managed with close observation.
Md Kamrul Hasan Chowdhury has completed his Bachelor of Pharmacy from the University of Development Alternative (UODA), Bangladesh. Following his Bachelor’s degree, he has received a scholarship for studying Master of Science (MSc) in Pharmacogenomics at Inje University, College of Medicine, South Korea. After graduating from Inje University, he successfully obtained a competitive PhD Scholarship UIPA (University International Postgraduate Award) from the University of New South Wales Australia, Australia.
Recently it has been found that glucagon is able to activate the β-catenin signaling pathway leading to increased cyclin D1 and c-Myc expression in liver. Therefore, the main aim of this study is to determine if the effect of glucagon activating β-catenin signaling leading to increased target gene expression is mediated through cAMP activation of protein kinase A. Primary rat hepatocytes were incubated with insulin, glucagon or epinephrine and a range of inhibitors of PI 3-kinase, Wnt, mitochondrial uncoupler (niclosamide) or PKA inhibitors to dissection out the pathway leading to increased serine 552 phosphorylation of β-catenin following glucagon exposure. Western blot and real-time PCR were used. In primary rat liver cells, we found that short exposure of glucagon or epinephrine caused a rapid increase in serine-552 phosphorylation on β-catenin that leads to increased cyclin D1 and c-Myc expression. Both glucose and insulin had no effect on this pathway. A range of PI 3-kinase and Wnt inhibitors were unable to block the effect of glucagon phosphorylating β-catenin. Interestingly, both niclosamide and the PKA inhibitor H89 blocked the glucagon effect on β-catenin signaling leading to a reduction in the target genes expression. We have identified a new pathway via glucagon signaling that leads to increased β-catenin activity that can be reversed with the antihelminthic drug niclosamide which has recently shown promise as a potential treatment of type-2 diabetes (T2D). This novel finding could be useful in liver cancer treatment particularly in the context of T2D with increased β-catenin activity.