Allogeneic bone marrow stromal cells promote glial–axonal remodeling without immunologic sensitization after stroke in rats

We evaluated the effects of allogeneic bone marrow stromal cell treatment of stroke on functional outcome, glial–axonal architecture, and immune reaction. Female Wistar rats were subjected to 2 h of middle cerebral artery occlusion. Rats were injected intravenously with PBS, male allogeneic ACI – or syngeneic Wistar –bone marrow stromal cells at 24 h after ischemia and sacrificed at 28 days. Significant functional recovery was found in both cell-treated groups compared to stroke rats that did not receive BMSCs, but no difference was detected between allogeneic and syngeneic cell-treated rats. No evidence of T cell priming or humoral antibody production to marrow stromal cells was found in recipient rats after treatment with allogeneic cells. Similar numbers of Y-chromosome⁺ cells were detected in the female rat brains in both groups. Significantly increased thickness of individual axons and myelin, and areas of the corpus callosum and the numbers of white matter bundles in the striatum were detected in the ischemic boundary zone of cell-treated rats compared to stroked rats. The areas of the contralateral corpus callosum significantly increased after cell treatment compared to normal rats. Processes of astrocytes remodeled from hypertrophic star-like to tadpole-like shape and oriented parallel to the ischemic regions after cell treatment. Axonal projections emanating from individual parenchymal neurons exhibited an overall orientation parallel to elongated radial processes of reactive astrocytes of the cell-treated rats. Allogeneic and syngeneic bone marrow stromal cell treatment after stroke in rats improved neurological recovery and enhanced reactive oligodendrocyte and astrocyte related axonal remodeling with no indication of immunologic sensitization in adult rat brain.     

Update on the Interaction of Rifampin and Warfarin

A 79-year-old man with a history of deep vein thrombosis and pulmonary embolism received anticoagulation therapy with warfarin 5 mg daily for 8 months. He was diagnosed with osteomyelitis and underwent partial metatarsal resection of his right foot. After surgery, antibiotics were initiated including ertapenem sodium 1 g intravenously every 24 hours, vancomycin 1400 mg intravenously every 24 hours, and rifampin 300 mg by mouth twice daily. Achieving a therapeutic level of anticoagulation was difficult despite escalating doses of warfarin, because of the interaction with rifampin. A 5- to 6-fold increase in warfarin dose was prescribed to reach therapeutic international normalized ratios (INRs), but even these increases were insufficient to maintain his INR in the therapeutic range. After rifampin was discontinued, warfarin doses were gradually reduced over the next 2 months. When concurrent warfarin-rifampin therapy is necessary, vigilant monitoring is imperative and significant increases in warfarin doses are likely.     

Bamboo joint-like appearance of stomach in Korean patients with Crohn's disease]

BACKGROUND/AIMS: Bamboo joint-like (BJL) appearance is an endoscopic finding characterized by swollen longitudinal folds transversed by erosive fissures or linear furrows on the lesser curvature side of gastric body and cardia. It has been reported to be associated with Crohn's disease (CD). This study was aimed to evaluate the incidence of BJL appearance in Korean patients with CD. METHODS: From January to December in 2005, we performed esophagogastroduodenoscopy (EGD) in patients diagnosed as CD and ulcerative colitis (UC) in our hospital. Non-inflammatory bowel disease (IBD) subjects with upper gastrointestinal symptoms who underwent EGD were consecutively enrolled during the same period. One endoscopist performed all the endoscopic examinations to avoid inter-observer variation. A dye-spraying technique with 0.4% indigocarmine was used to allow the detection of subtle changes during the endoscopic examination. RESULTS: A total of 21 patients with CD (mean age+/-SD, 40+/-15 yr; M/F, 13/8), 28 patients with UC (42+/-15 yr; 21/7), and 685 non-IBD subjects (49+/-14 yr; 354/331) were enrolled. EGD findings in CD patients were gastric erosions (11/21), chronic superficial gastritis (5/21), chronic atrophic gastritis (1/21), duodenal erosions or ulcers (2/21), and normal (2/21). Incidence of BJL appearance was significantly higher in patients with CD (47.6%, 10/21) than others (UC, 3.6%, 1/28; non-IBD, 0.1%, 1/685) (p< 0.0001). Among patients with CD, incidence of BJL appearance was not significantly different according to the sex, status of H. pylori infection, Vienna classification for phenotype, medications or EGD findings. CONCLUSIONS: BJL appearance on the gastric body and cardia can be a diagnostic clue to CD.     

A case of Non-Hodgkin's lymphoma in a patient with Crohn's disease]

Although adenocarcinoma is a well known complication of chronic inflammatory bowel disease, primary gastrointestinal lymphoma occurring in Crohn's disease is rare. A 40-year-old man with 10 year-history of Crohn's disease had multiple longitudinal ulcerative lesions on descending colon in follow-up colonoscopic examination. Microscopic examination of proximal descending colon revealed peripheral T cell lymphoma and other site of the descending colon was consistent with Crohn's disease. The patient reached complete remission of malignant lymphoma after three cycles of combined chemotherapy. He has been well for 10 months with sulfasalazine maintenance therapy but was admitted to the hospital due to spontaneous bowel perforation of ascending colon. Right hemicolectomy was done, but the patient died of post-surgical recurrent mesenteric abscess and sepsis. To the best of our knowledge, this is the first case of Non-Hodgkin's lymphoma complicating Crohn's disease in Korea which was confirmed by immunohistochemical studies.     

Importance of spatiotemporal heterogeneity of cellular restitution in mechanism of arrhythmogenic discordant alternans

BACKGROUND: Spatially discordant cellular alternans form a substrate for development of unidirectional block and ventricular fibrillation. However, the mechanisms responsible for discordant alternans remain poorly understood. Previous work suggests electrical restitution is critical to the development of alternans in single cells. OBJECTIVES: The purpose of this study was to investigate the hypothesis that spatial and temporal heterogeneities of restitution underlie the mechanism eliciting discordant alternans. METHODS: Steady-state pacing was used to elicit concordant cellular alternans in nine Langendorff-perfused guinea pig hearts. A single extrastimulus (S2) was applied every 51st beat following either the even or the odd beat of alternans. The cellular response to S2 was determined using optical mapping to generate action potential duration (APD) restitution curves from 256 ventricular sites for both the even and the odd beats. RESULTS: Restitution kinetics were temporally heterogeneous during alternans, as restitution curves between the even and the odd beats differed significantly. Temporal heterogeneity was quantified by the average separation of restitution between the two curves, or Delta-restitution. Delta-Restitution was spatially heterogeneous and proportional to the amount of alternans at a given ventricular site. A computer simulation based on the experimental results showed the mechanism of discordant alternans was dependent on both spatial and temporal heterogeneities of restitution. CONCLUSION: Both temporal and spatial heterogeneities of restitution exist during cellular alternans in the intact heart. Temporal heterogeneities of restitution, quantified by Delta-restitution, are proportional to the magnitude of cellular alternans. The combination of spatial and temporal heterogeneities of restitution may underlie the genesis of discordant alternans.