The Extended N-Terminal Domain Confers Atypical Chemokine Receptor Properties to CXCR3-B.

peer reviewedThe chemokine receptor CXCR3 plays a critical role in immune cell recruitment and activation. CXCR3 exists as two main isoforms, CXCR3-A and CXCR3-B, resulting from alternative splicing. Although the two isoforms differ only by the presence of an N-terminal extension in CXCR3-B, they have been attributed divergent functional effects on cell migration and proliferation. CXCR3-B is the more enigmatic isoform and the mechanisms underlying its function and signaling remain elusive. We therefore undertook an in-depth cellular and molecular comparative study of CXCR3-A and CXCR3-B, investigating their activation at different levels of the signaling cascades, including G protein coupling, β-arrestin recruitment and modulation of secondary messengers as well as their downstream gene response elements. We also compared the subcellular localization of the two isoforms and their trafficking under resting and stimulated conditions along with their ability to internalize CXCR3-related chemokines. Here, we show that the N-terminal extension of CXCR3-B drastically affects receptor features, modifying its cellular localization and preventing G protein coupling, while preserving β-arrestin recruitment and chemokine uptake capacities. Moreover, we demonstrate that gradual truncation of the N terminus leads to progressive recovery of surface expression and G protein coupling. Our study clarifies the molecular basis underlying the divergent effects of CXCR3 isoforms, and emphasizes the β-arrestin-bias and the atypical nature of CXCR3-B

Occult sporadic insulinoma: Localization and surgical strategy

Insulinomas continue to pose a diagnostic challenge to physicians, surgeons and radiologists alike. Most are intrapancreatic, benign and solitary. Biochemical diagnosis is obtained and imaging techniques to localize lesions continue to evolve. Surgical resection is the treatment of choice. Despite all efforts, an occult insulinoma (occult insulinoma refers to a biochemically proven tumor with indeterminate anatomical site before operation) may still be encountered. New localization preoperative techniques decreases occult cases and the knowledge of the site of the mass before surgery allows to determine whether enucleation of the tumor or pancreatic resection is likely to be required and whether the tumor is amenable to removal via a laparoscopic approach. In absence of preoperative localization and intraoperative detection of an insulinoma, blind pancreatic resection is not recommended

© 2009 The WJG Press and Baishideng. All rights reserved. LETTERS TO THE EDITOR An exceptional cause of left lower quadrant abdominal pain

Acute appendicitis is an exceptional cause of left lower quadrant abdominal pain. Computed tomography scan is the key to its diagnosis and helps to establish its early treatment. We present a case of a 35-year-old male patient who presented acute appendicitis with redundant and loosely attached cecum which was diagnosed based on his left lower quadrant abdominal pain. © 2009 The WJG Press and Baishideng. All rights reserved

An exceptional cause of left lower quadrant abdominal pain

Acute appendicitis is an exceptional cause of left lower quadrant abdominal pain. Computed tomography scan is the key to its diagnosis and helps to establish its early treatment. We present a case of a 35-year-old male patient who presented acute appendicitis with redundant and loosely attached cecum which was diagnosed based on his left lower quadrant abdominal pain

Idiopathic sclerosing encapsulating peritonitis: Abdominal cocoon

Abdominal cocoon, the idiopathic form of sclerosing encapsulating peritonitis, is a rare condition of unknown etiology that results in an intestinal obstruction due to total or partial encapsulation of the small bowel by a fibrocollagenous membrane. Preoperative diagnosis requires a high index of clinical suspicion. The early clinical features are nonspecific, are often not recognized and it is difficult to make a definite pre-operative diagnosis. Clinical suspicion may be generated by the recurrent episodes of small intestinal obstruction combined with relevant imaging findings and lack of other plausible etiologies. The radiological diagnosis of abdominal cocoon may now be confidently made on computed tomography scan. Surgery is important in the management of this disease. Careful dissection and excision of the thick sac with the release of the small intestine leads to complete recovery in the vast majority of cases

Acute mesenteric ischemia after cardio-pulmonary bypass surgery

Acute mesenteric ischemia (AMI) is a highly-lethal surgical emergency. Several pathophysiologic events (arterial obstruction, venous thrombosis and diffuse vasospasm) lead to a sudden decrease in mesenteric blood flow. Ischemia/reperfusion syndrome of the intestine is responsible for systemic abnormalities, leading to multi-organ failure and death. Early diagnosis is difficult because the clinical presentation is subtle, and the biological and radiological diagnostic tools lack sensitivity and specificity. Therapeutic options vary from conservative resuscitation, medical treatment, endovascular techniques and surgical resection and revascularization. A high index of suspicion is required for diagnosis, and prompt treatment is the only hope of reducing the mortality rate. Studies are in progress to provide more accurate diagnostic tools for early diagnosis. AMI can complicate the post-operative course of patients following cardio-pulmonary bypass (CPB). Several factors contribute to the systemic hypo-perfusion state, which is the most frequent pathophysiologic event. In this particular setting, the clinical presentation of AMI can be misleading, while the laboratory and radiological diagnostic tests often produce inconclusive results. The management strategies are controversial, but early treatment is critical for saving lives. Based on the experience of our team, we consider prompt exploratory laparotomy, irrespective of the results of the diagnostic tests, is the only way to provide objective assessment and adequate treatment, leading to dramatic reduction in the mortality rate