How Can You Mend a Broken Heart?

Being a resident is hard. Being a resident dealing with a recent breakup is even harder. I wrote this piece after a serendipitous encounter on Valentine's Day with an elderly woman who embraced her messy journey to finding love, no matter her age or circumstance. We learn a lot from our patients: from their bodies, physiologies, and illnesses, we learn to become stronger clinicians; from their stories, traumas, and emotions, we learn to become more full, well-rounded humans. Looking back, I think about how easily I almost missed this heartfelt connection by being absorbed in my usual checklist of tasks for a new hospital admission. My patient's keen insight into her own romantic life taught me a vital skill in both medicine and personal relationships: the importance of being open to the unexpected.Annals "Online First" article.

The Yin and Yang of bile acid action on tight junctions in a model colonic epithelium.

Gastrointestinal epithelial barrier loss due to tight junction (TJ) dysfunction and bile acid-induced diarrhea are common in patients with inflammatory diseases. Although excess colonic bile acids are known to alter mucosal permeability, few studies have compared the effects of specific bile acids on TJ function. We report that the primary bile acid, chenodeoxycholic acid (CDCA), and its 7α-dehydroxylated derivative, lithocholic acid (LCA) have opposite effects on epithelial integrity in human colonic T84 cells. CDCA decreased transepithelial barrier resistance (pore) and increased paracellular 10 kDa dextran permeability (leak), effects that were enhanced by proinflammatory cytokines (PiC [ng/mL]: TNFα[10] + IL-1ß[10] + IFNγ[30]). CDCA reversed the cation selectivity of the monolayer and decreased intercellular adhesion. In contrast, LCA alone did not alter any of these parameters, but attenuated the effects of CDCA ± PiC on paracellular permeability. CDCA, but not PiC, decreased occludin and not claudin-2 protein expression; CDCA also decreased occludin localization. LCA ± CDCA had no effects on occludin or claudin expression/localization. While PiC and CDCA increased IL-8 production, LCA reduced both basal and PiC ± CDCA-induced IL-8 production. TNFα + IL1ß increased IFNγ, which was enhanced by CDCA and attenuated by LCA CDCA±PiC increased production of reactive oxygen species (ROS) that was attenuated by LCA Finally, scavenging ROS attenuated CDCA's leak, but not pore actions, and LCA enhanced this effect. Thus, in T84 cells, CDCA plays a role in the inflammatory response causing barrier dysfunction, while LCA restores barrier integrity. Understanding the interplay of LCA, CDCA, and PiC could lead to innovative therapeutic strategies for inflammatory and diarrheal diseases.