Acute effects of L-tryptophan on brain extracellular 5-HT and 5-HIAA levels in chronic experimental portal-systemic encephalopathy

Portal-systemic encephalopathy (PSE) is associated with increased brain turnover of serotonin (5-hydroxytryptamine; 5-HT). Despite this metabolic increase, neuronal release of 5-HT is unaltered in neocortex of portacaval shunted (PCS) rats. In the present study, frontal neocortical extracellular 5-HT and 5-hydroxyindole-3-acetic acid (5-HIAA) levels were determined in PCS rats and sham-operated controls prior to, as well as, after acute challenge with L-tryptophan (L-TRP; a bolus dose of 280 mg/kg i.p. followed by 5 consecutive hourly doses of 50 mg/kg). Neither basal 5-HT nor 5-HIAA extracellular levels were significantly altered in PCS rats compared to controls. L-TRP administration resulted in unaltered extracellular 5-HT but elevated 5-HIAA levels in PCS and sham rats. These findings do not suggest that changes in brain neuronal 5-HT release play any major functional role in the pathogenesis of chronic PSE. The present data also emphasize the importance of distinguishing between brain 5-HT metabolism and brain 5-HT release.     

Type A dissection following endovascular thoracic aortic stent-graft repair.

PURPOSE: To describe our experience with endovascular stent-graft repairs in the thoracic aorta focusing on the secondary complication of type A dissection. METHODS: Between January 1996 and April 2004, 73 patients were treated for traumatic thoracic aortic rupture (n=15), type B dissection (n=22), or atherosclerotic descending thoracic aortic aneurysms (TAA, n=36). A retrospective review of the records found 5 (6.8%) patients (3 men; median age 64 years, range 43-87) who experienced a type A dissection at a median 20 days (range 2-124) after thoracic stent-graft repair for 3 type B dissections, 1 TAA, and a late type I endoleak that appeared 28 months after initial stent-graft repair of a traumatic dissection. RESULTS: In 3 patients (2 dissections, 1 endoleak), a tear in the aortic wall at the proximal stent-graft was responsible for a retrograde type A dissection. Underlying disease was the cause of the type A dissection in the 2 other patients (1 dissection, 1 TAA) and was unrelated to the stent-grafts. Three patients underwent open surgery at 3, 26, and 124 days after stent-graft placement; 2 procedures were successful, but the third patient died 3 months later due to multiorgan failure. Two type A dissections were untreated: one patient died from cardiac tamponade 14 days after successful stent-graft exclusion of the type I endoleak; the other patient refused further treatment and survived. The procedure-related mortality following acute retrograde type A dissection was 40%. CONCLUSIONS: Endovascular stent-graft repair of the thoracic aorta is associated with lower morbidity and mortality rates than surgical repair, although potentially lethal complications, acute or delayed, may occur.     

Amount of systemic steroid medication is a strong predictor for the use of complementary and alternative medicine in patients with inflammatory bowel disease: results from a German national survey

OBJECTIVES: Previous studies have suggested that inflammatory bowel disease (IBD) patients rank high among users of complementary and alternative medicine (CAM). To further elucidate this phenomenon, we sent questionnaires to a large sample of IBD patients in Germany to determine the patterns and predictors of their CAM use. METHODS: Pretested 73-item questionnaires were mailed to a randomly selected representative sample of 1000 IBD patients from the approximately 16,000 members and associates of the German Crohn's and Colitis Association. Predictors of CAM use were evaluated by logistic regression models. RESULTS: Completed questionnaires were returned by 684 patients (female patients, 61.4%; Crohn's disease patients, 58.3%; ulcerative colitis patients, 38.2%). Of the 671 adult respondents, 344 (51.3%) had experience with CAM, and significantly more of the ulcerative colitis patients (59.8%) than the Crohn's disease patients (48.3%) had experience with CAM. There was no difference by gender. Homeopathy (52.9%) and herbal medicine (43.6%) were the most commonly used types of CAM. The most frequent personal reasons for CAM use were the search for an "optimum treatment" (78.9%) and the wish to stop taking steroids (63.8%). Using logistic regression, we found that total cortisone intake (P = 0.0077), but not duration of disease, was a strong predictor of CAM use. Other predictors were experience with psychosomatic and psychotherapeutic support (P = 0.0029), relaxation techniques (P = 0.0284), an academic education (P = 0.0173), a diet utilizing whole grains (P = 0.0123), and a normal body weight (P = 0.0215). Although 80% of patients indicated that they were interested in using CAM in the future, only 24.7% felt sufficiently informed about it. CONCLUSIONS: More than 50% of a large group of German IBD patients had used CAM. Prolonged or intensive steroid treatment, an academic education, active ways of coping, and a health-conscious life-style are associated with CAM use. Given the potential side effects and interactions, the treating physician should focus on thorough information about the benefits and limitations of conventional and complementary treatment options, especially for IBD patients who have received prolonged or intensive steroid treatment.     

Insulin-mediated immune dysfunction in the development of preeclampsia

Journal of Molecular Medicine - Epidemiological observations implicate insulin resistance as a predisposing factor in the development of preeclampsia (PE). It is also well established that PE...     

Heart wall myofibers are arranged in minimal surfaces to optimize organ function

Heart wall myofibers wind as helices around the ventricles, strengthening them in a manner analogous to the reinforcement of concrete cylindrical columns by spiral steel cables [Richart FE, et al. (1929) Univ of Illinois, Eng Exp Stn Bull 190]. A multitude of such fibers, arranged smoothly and regularly, contract and relax as an integrated functional unit as the heart beats. To orchestrate this motion, fiber tangling must be avoided and pumping should be efficient. Current models of myofiber orientation across the heart wall suggest groupings into sheets or bands, but the precise geometry of bundles of myofibers is unknown. Here we show that this arrangement takes the form of a special minimal surface, the generalized helicoid [Blair DE, Vanstone JR (1978) Minimal Submanifolds and Geodesics 13-16], closing the gap between individual myofibers and their collective wall structure. The model holds across species, with a smooth variation in its three curvature parameters within the myocardial wall providing tight fits to diffusion magnetic resonance images from the rat, the dog, and the human. Mathematically it explains how myofibers are bundled in the heart wall while economizing fiber length and optimizing ventricular ejection volume as they contract. The generalized helicoid provides a unique foundation for analyzing the fibrous composite of the heart wall and should therefore find applications in heart tissue engineering and in the study of heart muscle diseases.     

Tubular atrophy in the pathogenesis of chronic kidney disease progression

The longstanding focus in chronic kidney disease (CKD) research has been on the glomerulus, which is sensible because this is where glomerular filtration occurs, and a large proportion of progressive CKD is associated with significant glomerular pathology. However, it has been known for decades that tubular atrophy is also a hallmark of CKD and that it is superior to glomerular pathology as a predictor of glomerular filtration rate decline in CKD. Nevertheless, there are vastly fewer studies that investigate the causes of tubular atrophy, and fewer still that identify potential therapeutic targets. The purpose of this review is to discuss plausible mechanisms of tubular atrophy, including tubular epithelial cell apoptosis, cell senescence, peritubular capillary rarefaction and downstream tubule ischemia, oxidative stress, atubular glomeruli, epithelial-to-mesenchymal transition, interstitial inflammation, lipotoxicity and Na⁺/H⁺ exchanger-1 inactivation. Once a a better understanding of tubular atrophy (and interstitial fibrosis) pathophysiology has been obtained, it might then be possible to consider tandem glomerular and tubular therapeutic strategies, in a manner similar to cancer chemotherapy regimens, which employ multiple drugs to simultaneously target different mechanistic pathways.