Human Enterocytes as an In Vitro Model for the Evaluation of Intestinal Drug Metabolism: Characterization of Drug-Metabolizing Enzyme Activities of Cryopreserved Human Enterocytes from Twenty-Four Donors.

We report in this work successful isolation and cryopreservation of enterocytes from human small intestine. The enterocytes were isolated by enzyme digestion of the intestinal lumen, followed by partial purification via differential centrifugation. The enterocytes were cryopreserved directly after isolation without culturing to maximize retention of in vivo drug-metabolizing enzyme activities. Post-thaw viability of the cryopreserved enterocytes was consistently over 80% based on trypan blue exclusion. Cryopreserved enterocytes pooled from eight donors (four male and four female) were evaluated for their metabolism of 14 pathway-selective substrates: CYP1A2 (phenacetin hydroxylation), CYP2A6 (coumarin 7-hydroxylation), CYP2B6 (bupropion hydroxylation), CYP2C8 (paclitaxel 6α-hydroxylation), CYP2C9 (diclofenac 4-hydroxylation), CYP2C19 (S-mephenytoin 4-hydroxylation), CYP2D6 (dextromethorphan hydroxylation), CYP2E1 (chlorzoxazone 6-hydroxylation), CYP3A4 (midazolam 1'-hydroxylation and testosterone 6ß-hydroxylation), CYP2J2 (astemizole O-demethylation), UDP-glucuronosyltransferase (UGT; 7-hydroxycoumarin glucuronidation), sulfotransferase (SULT; 7-hydroxycoumarin sulfation), and carboxylesterase 2 (CES2; irinotecan hydrolysis) activities. Quantifiable activities were observed for CYP2C8, CYP2C9, CYP2C19, CYP2E1, CYP3A4, CYPJ2, CES2, UGT, and SULT, but not for CYP1A2, CYP2A6, CYP2B6, and CYP2D6. Enterocytes from all 24 donors were then individually evaluated for the quantifiable drug metabolism pathways. All demonstrated quantifiable activities with the expected individual variations. Our results suggest that cryopreserved human enterocytes represent a physiologically relevant and convenient in vitro experimental system for the evaluation of intestinal metabolism, akin to cryopreserved human hepatocytes for hepatic metabolism.

Systemic septic embolisation secondary to an atrial myxoma in a young woman.

We present a case of a left atrial myxoma infected with Staphylococcus aureus in a 35-year-old woman who was found to have a retained tampon. Multiple systemic septic emboli were seen on computed tomography imaging of the brain, spleen and kidneys. She was successfully treated by surgical excision of the myxoma and 4 weeks of antibiotic therapy. We postulate that the source of this patient's S. aureus infection was tampon use, leading to a toxic shock syndrome and causing infection of an undiagnosed left atrial myxoma, which led to the embolisation. As far as the authors are aware, this is the first reported case of such an entity. In those with an underlying cardiac predisposition, tampon use may represent a risk of infection with S. aureus, and we intend to heighten clinical awareness of this potentially life-threatening association. We also discuss the diagnosis, complications and treatment of infected atrial myxoma and illustrate the imaging findings.

Constrictive pericarditis: lessons from the past five years' experience in the South West Cardiothoracic Centre.

There are still patients who develop constrictive pericarditis. The aetiology has changed from times when it usually resulted from tuberculosis or purulent infection. The symptoms and signs may be misinterpreted and lead to the wrong diagnosis of congestive cardiac failure, lung disease, or liver disease. Patients with constrictive pericarditis present to specialists in different disciplines. We describe our experience, over five years, in one tertiary referral centre. We highlight the presentation, aetiology, investigation, and treatment and hope to remind all physicians of an uncommon but treatable condition.