Farzad Alemi

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Patients with cholestatic disease exhibit pruritus and analgesia, but the mechanisms underlying these symptoms are unknown. We report that bile acids, which are elevated in the circulation and tissues during cholestasis, cause itch and analgesia by activating the GPCR TGR5. TGR5 was detected in peptidergic neurons of mouse dorsal root ganglia and spinal(More)
BACKGROUND & AIMS Abnormal delivery of bile acids (BAs) to the colon as a result of disease or therapy causes constipation or diarrhea by unknown mechanisms. The G protein-coupled BA receptor TGR5 (or GPBAR1) is expressed by enteric neurons and endocrine cells, which regulate motility and secretion. METHODS We analyzed gastrointestinal and colon transit,(More)
TGR5 is a G protein-coupled receptor that mediates bile acid (BA) effects on energy balance, inflammation, digestion, and sensation. The mechanisms and spatiotemporal control of TGR5 signaling are poorly understood. We investigated TGR5 signaling and trafficking in transfected HEK293 cells and colonocytes (NCM460) that endogenously express TGR5. BAs(More)
Calcitonin gene-related peptide (CGRP) exerts its diverse effects on vasodilation, nociception, secretion, and motor function through a heterodimeric receptor comprising of calcitonin receptor-like receptor (CLR) and receptor activity-modifying protein 1 (RAMP1). Despite the importance of CLR·RAMP1 in human disease, little is known about its distribution in(More)
Hepatic steatosis is generally thought to develop via peripheral mechanisms associated with obesity. We show that chronic central infusion of leptin suppresses hepatic lipogenic gene expression and reduces triglyceride content via stimulation of hepatic sympathetic activity. This leptin function is independent of feeding and body weight but requires(More)
BACKGROUND The development of a hepatic surgery center within a US Department of Veterans Affairs hospital is dependent on proper training and institutional support, which can translate into low operative morbidity and mortality rates. METHODS Patients who underwent hepatic procedures between 2003 and 2009 were retrospectively reviewed. A subset analysis(More)
BACKGROUND Many hepatobiliary centres are increasingly utilizing thermocoagulative devices such as bipolar-radiofrequency ablation (B-RFA). Compared with monopolar-radiofrequency ablation (M-RFA), B-RFA does not require grounding pads, thereby avoiding dermal burn injuries, and does not position probes directly into the tumour but rather on the perimeter.(More)
BACKGROUND Surgical resection is the only cure for hepato-pancreato-biliary (HPB) malignancy. In the era of multidisciplinary approaches and neoadjuvant therapies for locally advanced, borderline resectable tumors, the feasibility and efficacy of en bloc vascular resection has been validated across multiple studies. However, the variability of venous(More)
Sonic hedgehog pathway is highly activated in pancreatic cancer stem cells (CSC) which play crucial roles in cancer initiation, progression and metastasis. However, the molecular mechanisms by which sanguinarine regulates pancreatic CSC characteristics is not well understood. The objectives of this study were to examine the molecular mechanisms by which(More)