Department of Emergency Medicine Faculty Papers Copyright (c) 2013 Thomas Jefferson University All rights reserved. http://jdc.jefferson.edu/emfp Recent documents in Department of Emergency Medicine Faculty Papers en-us Sat, 04 May 2013 01:45:00 PDT 3600 Effect of Iron Chelators on Methemoglobin and Thrombin Preconditioning. http://jdc.jefferson.edu/emfp/17 http://jdc.jefferson.edu/emfp/17 Thu, 02 May 2013 06:47:20 PDT Cell loss immediately adjacent to an intracerebral hemorrhage may be mediated in part by the toxicities of extracellular hemoglobin (Hb) and thrombin. However, at low concentrations, these proteins induce tolerance to hemin and iron that may limit further peri-hematomal injury as erythrocyte lysis progresses. The mechanisms mediating these preconditioning effects have not been completely defined, but increased expression of both heme oxygenase (HO)-1 and iron binding proteins likely contributes. In the present study, we hypothesized that iron chelator therapy would attenuate this protective response. Pretreatment of cortical glial cultures (> 90 % GFAP+) with 3 μM methemoglobin (metHb) or 5 units/ml thrombin for 24 h was nontoxic per se, and increased HO-1 and ferritin expression. When challenged with a toxic concentration of hemin, the increase in cellular redox-active iron was attenuated in preconditioned cultures and cell survival was increased. However, if cultures were pretreated with metHb or thrombin plus deferoxamine or 2,2'-bipyridyl, ferritin induction was prevented and cellular redox-active iron increased with hemin treatment. Preconditioning-mediated cytoprotection was consistently reduced by deferoxamine, while 2,2'-bipyridyl had a variable effect. Neither chelator altered HO-1 expression. A cytoprotective response was preserved when chelator therapy was limited to 11 hours of the 24 h preconditioning interval. These results suggest a potentially deleterious effect of continuous iron chelator therapy after ICH. Intermittent therapy may remove peri-hematomal iron without negating the benefits of exposure to low concentrations of Hb or thrombin.

]]> Jing Chen-Roetling et al. Aortic dissection presenting as gait disturbance: a case report. http://jdc.jefferson.edu/emfp/16 http://jdc.jefferson.edu/emfp/16 Wed, 16 Jan 2013 11:14:31 PST Emergency medicine dogma traditionally teaches that aortic dissection presents as tearing chest pain, radiating to the back. This case report describes a 55 year old woman presenting with a left homonymous hemianopsia and resultant gait disturbance. Initial head CT demonstrated a right parietal infarct, and chest radiograph demonstrated a markedly widened mediastinum. Acute Stanford Type A aortic dissection was subsequently confirmed. This report provides further evidence for atypical, painless presentations of aortic dissection. Given recent literature on the increasing prevalence of painless dissection, the disease entity should be included in the differential diagnosis for stroke, and a simple portable chest x-ray should always be obtained prior to administering thrombolytics.

]]> Michael Estreicher et al. Association of maximum weight with hyperuricemia risk: a retrospective study of 21,414 chinese people. http://jdc.jefferson.edu/emfp/15 http://jdc.jefferson.edu/emfp/15 Thu, 03 Jan 2013 08:13:42 PST BACKGROUND: Obesity has been demonstrated to be associated with increased serum uric acid (SUA); however, little is known regarding the relationship between maximum weight, or maximum weight fluctuation, and uric acid concentration. Through retrospective means, we determined the association of maximum weight with SUA risk.

METHODS: Data of 21,414 participants (8,630 males and 12,784 females) from the 2007-8 China National Diabetes and Metabolic Disorders Study were analyzed for parameters including lifestyle habits, biochemical blood analysis and self-reported maximum weight.

RESULTS: Elevated SUA subjects shared a cluster of demographic features. After adjustment for age, gender, education, smoking, drinking, physical activity, WHR, height, eGFR(evaluate glomerular filtration rate), and diuretic usage, multivariate logistic regression models demonstrated maximum weight was associated with increased risk of elevated SUA level (P

CONCLUSIONS: Maximum weight is a strong risk factor for increased uric acid level in the Chinese population, which might serve as a novel clinical indicator suggesting hyperuricemia. Controlling maximum weight, keeping weight to the appropriate range, and maintaining the stable weight may be conducive for decreasing risk of hyperuricemia.

]]> Bin Gao et al. Decrease in Central Venous Catheter Placement and Complications Due to Utilization of Ultrasound-Guided Peripheral Intravenous Catheters http://jdc.jefferson.edu/emfp/14 http://jdc.jefferson.edu/emfp/14 Fri, 09 Nov 2012 08:01:51 PST Poster presented at: American College of Emergency Physicians (ACEP) conference.

Introduction: -Up to 40% of ED visits include diagnostic blood tests and 26% result in administration of IV fluids necessitating successful peripheral intravenous (IV) catheter placement.1 -There is a subset of patients with difficult IV access (DIVA) in which traditional cannulation methods are unsuccessful resulting in central venous cannulation (CVC). -CVCs have a 5-15 percent complication rate2 and attributable costs per CVC related infection have been estimated at $34,508-$56,000.3 -Ultrasound-guided peripheral IV catheters (USGPIVs) provide a method of potentially decreasing the need for CVC placement, however due to poor durability of USGPIVs the actual reduction in CVCs is unclear. -This study set out to quantify the reduction in CVCs in patients with DIVA by utilization of USGPIVs. Paper will be be published in: American Journal of Emergency Medicine

]]> Arthur K Au et al. The effect of vessel depth, diameter, and location on ultrasound-guided peripheral intravenous catheter longevity. http://jdc.jefferson.edu/emfp/13 http://jdc.jefferson.edu/emfp/13 Mon, 22 Oct 2012 07:40:40 PDT INTRODUCTION: Ultrasound-guided peripheral intravenous catheters (USGPIVs) have been observed to have poor durability. The current study sets out to determine whether vessel characteristics (depth, diameter, and location) predict USGPIV longevity.

METHODS: A secondary analysis was performed on a prospectively gathered database of patients who underwent USGPIV placement in an urban, tertiary care emergency department. All patients in the database had a 20-gauge, 48-mm-long catheter placed under ultrasound guidance. The time and reason for USGPIV removal were extracted by retrospective chart review. A Kaplan-Meier survival analysis was performed.

RESULTS: After 48 hours from USGPIV placement, 32% (48/151) had failed prematurely, 24% (36/151) had been removed for routine reasons, and 44% (67/151) remained in working condition yielding a survival probability of 0.63 (95% confidence interval [CI], 0.53-0.70). Survival probability was perfect (1.00) when placed in shallow vessels (

CONCLUSION: Cannulation of deep and proximal vessels is associated with poor USGPIV survival. Careful selection of target vessels may help improve success of USGPIV placement and durability.

]]> J Matthew Fields et al. Essential role of caveolin-3 in adiponectin signalsome formation and adiponectin cardioprotection. http://jdc.jefferson.edu/emfp/12 http://jdc.jefferson.edu/emfp/12 Fri, 03 Aug 2012 09:05:49 PDT OBJECTIVE: Adiponectin (APN) system malfunction is causatively related to increased cardiovascular morbidity/mortality in diabetic patients. The aim of the current study was to investigate molecular mechanisms responsible for APN transmembrane signaling and cardioprotection.

METHODS AND RESULTS: Compared with wild-type mice, caveolin-3 knockout (Cav-3KO) mice exhibited modestly increased myocardial ischemia/reperfusion injury (increased infarct size, apoptosis, and poorer cardiac function recovery; P

CONCLUSIONS: Taken together, these results demonstrated for the first time that Cav-3 plays an essential role in APN transmembrane signaling and APN anti-ischemic/cardioprotective actions.

]]> Yajing Wang et al. AMP-Activated Protein Kinases Adaptor Proteins, Signal Transducing Adenylate Cyclase Adiponectin Animals Apoptosis Cadherins Caveolin 3 Cyclic AMP Disease Models, Animal Enzyme Activation Enzyme Activators HEK293 Cells Humans Male Mice Mice, Knockout Myocardial Infarction Myocardial Reperfusion Injury Myocardium Protein Interaction Domains and Motifs Receptors, Adiponectin Signal Transduction Time Factors Transfection Ventricular Function, Left Increased susceptibility to metabolic syndrome in adult offspring of Angiotensin type 1 receptor autoantibody-positive rats. http://jdc.jefferson.edu/emfp/11 http://jdc.jefferson.edu/emfp/11 Fri, 03 Aug 2012 08:53:45 PDT Abstract Aims: Abnormal fetal and early postnatal growth is closely associated with adult-onset metabolic syndrome (MetS). However, the underlying etiological factors remain complex. The presence of the autoantibody against the angiotensin II type 1 receptor (AT1-Ab), a known risk factor for pre-eclampsia, may create a suboptimal intrauterine fetal environment. The current study investigated whether middle-aged offspring of AT1-Ab-positive mothers were prone to metabolic disorder development. Results: The AT1-Abs was detected in placental trophoblastic cells, capillary endothelium, and milk of pregnant rats actively immunized with the second extracellular loop of the AT1 receptor. AT1-Abs in newborn rats induced vasoconstriction, increased intracellular-free Ca(2+) in vitro, and was undetectable 7 weeks later. Immunized group offspring exhibited increased weight variability and insulin resistance at 40 weeks of age under a normal diet, evidenced by elevated fasting serum insulin and homeostasis model assessment score compared with the vehicle control. To further observe metabolic alterations, the offspring were given a high-sugar diet (containing 20% sucrose) 40-48 weeks postnatally. The fasting plasma glucose in immunized group offspring was markedly increased. Concomitantly, these offspring manifested increased visceral adipose tissue, increased fatty liver, increased triglycerides, decreased high-density lipoprotein cholesterol, and decreased adiponectin levels, indicative of MetS. Innovation: AT1-Abs could be transferred from mother to offspring via the placenta and milk. Moreover, offspring of an AT1-Ab-positive mother were more vulnerable to MetS development in middle age. Conclusion: AT1-Ab-positivity of mothers during pregnancy is a previously unrecognized "silent" risk factor for MetS development in their offspring. Antioxid. Redox Signal. 17, 733-743.

]]> Suli Zhang et al. Advanced glycation end products accelerate ischemia/reperfusion injury through receptor of advanced end product/nitrative thioredoxin inactivation in cardiac microvascular endothelial cells. http://jdc.jefferson.edu/emfp/10 http://jdc.jefferson.edu/emfp/10 Thu, 22 Mar 2012 11:39:59 PDT The advanced glycation end products (AGEs) are associated with increased cardiac endothelial injury. However, no causative link has been established between increased AGEs and enhanced endothelial injury after ischemia/reperfusion. More importantly, the molecular mechanisms by which AGEs may increase endothelial injury remain unknown. Adult rat cardiac microvascular endothelial cells (CMECs) were isolated and incubated with AGE-modified bovine serum albumin (BSA) or BSA. After AGE-BSA or BSA preculture, CMECs were subjected to simulated ischemia (SI)/reperfusion (R). AGE-BSA increased SI/R injury as evidenced by enhanced lactate dehydrogenase release and caspase-3 activity. Moreover, AGE-BSA significantly increased SI/R-induced oxidative/nitrative stress in CMECs (as measured by increased inducible nitric oxide synthase expression, total nitric oxide production, superoxide generation, and peroxynitrite formation) and increased SI/R-induced nitrative inactivation of thioredoxin-1 (Trx-1), an essential cytoprotective molecule. Supplementation of EUK134 (peroxynitrite decomposition catalyst), human Trx-1, or soluble receptor of advanced end product (sRAGE) (a RAGE decoy) in AGE-BSA precultured cells attenuated SI/R-induced oxidative/nitrative stress, reduced SI/R-induced Trx-1 nitration, preserved Trx-1 activity, and reduced SI/R injury. Our results demonstrated that AGEs may increase SI/R-induced endothelial injury by increasing oxidative/nitrative injury and subsequent nitrative inactivation of Trx-1. Interventions blocking RAGE signaling or restoring Trx activity may be novel therapies to mitigate endothelial ischemia/reperfusion injury in the diabetic population.

]]> Yi Liu et al. Animals Cell Hypoxia Cells, Cultured Endothelial Cells Glycosylation End Products, Advanced L-Lactate Dehydrogenase Male Microvessels Myocardial Ischemia Myocardial Reperfusion Injury Nitrates Nitric Oxide Oxidative Stress Primary Cell Culture Rats Rats, Wistar Receptors, Immunologic Serum Albumin, Bovine Superoxides Thioredoxins Systemic adiponectin malfunction as a risk factor for cardiovascular disease. http://jdc.jefferson.edu/emfp/9 http://jdc.jefferson.edu/emfp/9 Thu, 22 Mar 2012 11:35:28 PDT Adiponectin (Ad) is an abundant protein hormone regulatory of numerous metabolic processes. The 30 kDa protein originates from adipose tissue, with full-length and globular domain circulatory forms. A collagenous domain within Ad leads to spontaneous self-assemblage into various oligomeric isoforms, including trimers, hexamers, and high-molecular-weight multimers. Two membrane-spanning receptors for Ad have been identified, with differing concentration distribution in various body tissues. The major intracellular pathway activated by Ad includes phosphorylation of AMP-activated protein kinase, which is responsible for many of Ad's metabolic regulatory, anti-inflammatory, vascular protective, and anti-ischemic properties. Additionally, several AMP-activated protein kinase-independent mechanisms responsible for Ad's anti-inflammatory and anti-ischemic (resulting in cardioprotective) effects have also been discovered. Since its 1995 discovery, Ad has garnered considerable attention for its role in diabetic and cardiovascular pathology. Clinical observations have demonstrated the association of hypoadiponectinemia in patients with obesity, cardiovascular disease, and insulin resistance. In this review, we elaborate currently known information about Ad malfunction and deficiency pertaining to cardiovascular disease risk (including atherosclerosis, endothelial dysfunction, and cardiac injury), as well as review evidence supporting Ad resistance as a novel risk factor for cardiovascular injury, providing insight about the future of Ad research and the protein's potential therapeutic benefits.

]]> Wayne Bond Lau et al. Adenylate Kinase Adiponectin Animals Antioxidants Cardiovascular Diseases Drug Resistance Endothelium Humans Protein Structure, Tertiary Receptors, Adiponectin Risk Factors Signal Transduction Reduced cardioprotective action of adiponectin in high-fat diet-induced type II diabetic mice and its underlying mechanisms. http://jdc.jefferson.edu/emfp/8 http://jdc.jefferson.edu/emfp/8 Thu, 22 Mar 2012 09:37:51 PDT Diabetes exacerbates ischemic heart disease morbidity and mortality via incompletely understood mechanisms. Although adiponectin (APN) reduces myocardial ischemia/reperfusion (MI/R) injury in nondiabetic animals, whether APN's cardioprotective actions are altered in diabetes, a pathologic condition with endogenously reduced APN, has never been investigated. High-fat diet (HD)-induced diabetic mice and normal diet (ND) controls were subjected to MI via coronary artery ligation, and given vehicle or APN globular domain (gAPN, 2 μg/g) 10 min before reperfusion. Compared to ND mice (where gAPN exerted pronounced cardioprotection), HD mice manifested greater MI/R injury, and a tripled gAPN dose was requisite to achieve cardioprotective extent seen in ND mice (i.e., infarct size, apoptosis, and cardiac function). APN reduces MI/R injury via AMP-activated protein kinase (AMPK)-dependent metabolic regulation and AMPK-independent antioxidative/antinitrative pathways. Compared to ND, HD mice manifested significantly blunted gAPN-induced AMPK activation, basally and after MI/R (p<0.05). Although both low- and high-dose gAPN equally attenuated MI/R-induced oxidative stress (i.e., NADPH oxidase expression and superoxide production) and nitrative stress (i.e., inducible nitric oxide synthase expression, nitric oxide production, and peroxynitrite formation) in ND mice, only high-dose gAPN efficaciously did so in HD mice. We demonstrate for the first time that HD-induced diabetes diminished both AMPK-dependent and AMPK-independent APN cardioprotection, suggesting an unreported diabetic heart APN resistance.

]]> Wei Yi et al. Acetyl-CoA Carboxylase Adenylate Kinase Adiponectin Animals Antioxidants Blood Pressure Cardiotonic Agents Diabetes Mellitus, Type 2 Diet, High-Fat Enzyme Activation Male Mice Mice, Inbred C57BL Myocardial Ischemia Myocardial Reperfusion Injury Myocardium Nitric Oxide Nitric Oxide Synthase Type II Peroxynitrous Acid Superoxides Ventricular Dysfunction, Left Apotransferrin Protects Cortical Neurons from Hemoglobin Toxicity http://jdc.jefferson.edu/emfp/7 http://jdc.jefferson.edu/emfp/7 Tue, 01 Mar 2011 07:24:35 PST The protective effect of iron chelators in experimental models of intracerebral hemorrhage suggests that nonheme iron may contribute to injury to perihematomal cells. Therapy with high affinity iron chelators is limited by their toxicity, which may be due in part to sequestration of metals in an inaccessible complex. Transferrin is unique in chelating iron with very high affinity while delivering it to cells as needed via receptor-mediated endocytosis. However, its efficacy against iron-mediated neuronal injury has never been described, and was therefore evaluated in this study using an established cell culture model of hemoglobin neurotoxicity. At concentrations similar to that of CSF transferrin (50-100 micrograms/ml), both iron-saturated holotransferrin and apotransferrin were nontoxic per se. Overnight exposure to 3 μM purified human hemoglobin in serum-free culture medium resulted in death, as measured by lactate dehydrogenase release assay, of about three-quarters of neurons. Significant increases in culture iron, malondialdehyde, protein carbonyls, ferritin and heme oxygenase-1 were also observed. Holotransferrin had no effect on these parameters, but all were attenuated by 50-100 micrograms/ml apotransferrin. The effect of apotransferrin was very similar to that of deferoxamine at a concentration that provided equivalent iron binding capacity, and was not antagonized by concomitant treatment with holotransferrin. Transferrin receptor-1 expression was localized to neurons and was not altered by hemoglobin or transferrin treatment. These results suggest that apotransferrin may mitigate the neurotoxicity of hemoglobin after intracerebral hemorrhage. Increasing its concentration in perihematomal tissue may be beneficial.

]]> Jing Chen-Roetling et al. Identifying inaccuracies on emergency medicine residency applications. http://jdc.jefferson.edu/emfp/6 http://jdc.jefferson.edu/emfp/6 Sun, 16 May 2010 17:22:24 PDT BACKGROUND: Previous trials have showed a 10-30% rate of inaccuracies on applications to individual residency programs. No studies have attempted to corroborate this on a national level. Attempts by residency programs to diminish the frequency of inaccuracies on applications have not been reported. We seek to clarify the national incidence of inaccuracies on applications to emergency medicine residency programs. METHODS: This is a multi-center, single-blinded, randomized, cohort study of all applicants from LCME accredited schools to involved EM residency programs. Applications were randomly selected to investigate claims of AOA election, advanced degrees and publications. Errors were reported to applicants' deans and the NRMP. RESULTS: Nine residencies reviewed 493 applications (28.6% of all applicants who applied to any EM program). 56 applications (11.4%, 95%CI 8.6-14.2%) contained at least one error. Excluding "benign" errors, 9.8% (95% CI 7.2-12.4%), contained at least one error. 41% (95% CI 35.0-47.0%) of all publications contained an error. All AOA membership claims were verified, but 13.7% (95%CI 4.4-23.1%) of claimed advanced degrees were inaccurate. Inter-rater reliability of evaluations was good. Investigators were reluctant to notify applicants' dean's offices and the NRMP. CONCLUSION: This is the largest study to date of accuracy on application for residency and the first such multi-centered trial. High rates of incorrect data were found on applications. This data will serve as a baseline for future years of the project, with emphasis on reporting inaccuracies and warning applicants of the project's goals.

]]> Eric D Katz et al. The interaction of HAb18G/CD147 with integrin alpha6beta1 and its implications for the invasion potential of human hepatoma cells. http://jdc.jefferson.edu/emfp/5 http://jdc.jefferson.edu/emfp/5 Sun, 09 May 2010 17:08:49 PDT BACKGROUND: HAb18G/CD147 plays pivotal roles in invasion by hepatoma cells, but the underlying mechanism remains unclear. Our previous study demonstrated that overexpression of HAb18G/CD147 promotes invasion by interacting with integrin alpha3beta1. However, it has never been investigated whether alpha3beta1 is solely responsible for this process or if other integrin family members also interact with HAb18G/CD147 in human hepatoma cells. METHODS: Human SMMC-7721 and FHCC98 cells were cultured and transfected with siRNA fragments against HAb18G/CD147. The expression levels of HAb18G/CD147 and integrin alpha6beta1 were determined by immunofluorescent double-staining and confocal imaging analysis. Co-immunoprecipitation and Western blot analyses were performed to examine the native conformations of HAb18G/CD147 and integrin alpha6beta1. Invasion potential was evaluated with an invasion assay and gelatin zymography. RESULTS: We found that integrin alpha6beta1 co-localizes and interacts with HAb18G/CD147 in human hepatoma cells. The enhancing effects of HAb18G/CD147 on invasion capacity and secretion of matrix metalloproteinases (MMPs) were partially blocked by integrin alpha6beta1 antibodies (P < 0.01). Wortmannin, a specific phosphatidylinositol kinase (PI3K) inhibitor that reverses the effect of HAb18G/CD147 on the regulation of intracellular Ca2+ mobilization, significantly reduced cell invasion potential and secretion of MMPs in human hepatoma cells (P < 0.05). Importantly, no additive effect between Wortmannin and alpha6beta1 antibodies was observed, indicating that alpha6beta1 and PI3K transmit the signal in an upstream-downstream relationship. CONCLUSION: These results suggest that alpha6beta1 interacts with HAb18G/CD147 to mediate tumor invasion and metastatic processes through the PI3K pathway.

]]> Jing-yao Dai et al. Heme oxygenase-2 gene deletion attenuates oxidative stress in neurons exposed to extracellular hemin. http://jdc.jefferson.edu/emfp/4 http://jdc.jefferson.edu/emfp/4 Tue, 04 May 2010 15:43:40 PDT BACKGROUND: Hemin, the oxidized form of heme, accumulates in intracranial hematomas and is a potent oxidant. Growing evidence suggests that it contributes to delayed injury to surrounding tissue, and that this process is affected by the heme oxygenase enzymes. In a prior study, heme oxygenase-2 gene deletion increased the vulnerability of cultured cortical astrocytes to hemin. The present study tested the effect of HO-2 gene deletion on protein oxidation, reactive oxygen species formation, and cell viability after mixed cortical neuron/astrocyte cultures were incubated with neurotoxic concentrations of hemin. RESULTS: Continuous exposure of wild-type cultures to 1-10 microM hemin for 14 h produced concentration-dependent neuronal death, as detected by both LDH release and fluorescence intensity after propidium iodide staining, with an EC50 of 1-2 microM; astrocytes were not injured by these low hemin concentrations. Cell death was consistently reduced by at least 60% in knockout cultures. Exposure to hemin for 4 hours, a time point that preceded cell lysis, increased protein oxidation in wild-type cultures, as detected by staining of immunoblots for protein carbonyl groups. At 10 microM hemin, carbonylation was increased 2.3-fold compared with control sister cultures subjected to medium exchanges only; this effect was reduced by about two-thirds in knockout cultures. Cellular reactive oxygen species, detected by fluorescence intensity after dihydrorhodamine 123 (DHR) staining, was markedly increased by hemin in wild-type cultures and was localized to neuronal cell bodies and processes. In contrast, DHR fluorescence intensity in knockout cultures did not differ from that of sham-washed controls. Neuronal death in wild-type cultures was almost completely prevented by the lipid-soluble iron chelator phenanthroline; deferoxamine had a weaker but significant effect. CONCLUSIONS: These results suggest that HO-2 gene deletion protects neurons in mixed neuron-astrocyte cultures from heme-mediated oxidative injury. Selective inhibition of neuronal HO-2 may have a beneficial effect after CNS hemorrhage.

]]> Raymond F Regan et al. Heme oxygenase activity and hemoglobin neurotoxicity are attenuated by inhibitors of the MEK/ERK pathway. http://jdc.jefferson.edu/emfp/2 http://jdc.jefferson.edu/emfp/2 Mon, 11 May 2009 08:23:58 PDT Hemoglobin breakdown produces an iron-dependent neuronal injury after experimental CNS hemorrhage that may be attenuated by heme oxygenase (HO) inhibitors. The HO enzymes are phosphoproteins that are activated by phosphorylation in vitro. While testing the effect of kinase inhibitors in cortical cell cultures, we observed that HO activity was consistently decreased by the MEK inhibitor U0126. The present study tested the hypothesis that MEK/ERK pathway inhibitors reduce HO activity and neuronal vulnerability to hemoglobin. The MEK inhibitors U0126 and SL327 and the ERK inhibitor FR180204 reduced baseline culture HO activity by 35-50%, without altering the activity of recombinant HO-1 or HO-2; negative control compounds U0124 and FR180289 had no effect. Hemoglobin exposure for 16h produced widespread neuronal injury, manifested by release of 59.2+/-7.8% of neuronal lactate dehydrogenase and a twelve-fold increase in malondialdehyde; kinase inhibitors were highly protective. HO-1 induction after hemoglobin treatment was also decreased by U0126, SL327, and FR180204. These results suggest that reduction in HO activity may contribute to the protective effect of MEK and ERK inhibitors against heme-mediated neuronal injury.

]]> Jing Chen-Roetling et al. Anthroposophic perspectives in primary care http://jdc.jefferson.edu/emfp/1 http://jdc.jefferson.edu/emfp/1 Thu, 13 Apr 2006 11:35:19 PDT A core challenge of contemporary medicine is to integrate the technological successes of biomedical science with a comprehensive under-standing of the physical, psychosocial, ecological, and spiritual dimensions of health and illness. Toward this end, bridges are being created between conventional medicine and alternative systems of healing which reflect a holistic model of the human being.

Even when both conventional and complementary approaches are used side-by-side in the same patient, they remain separate in their basic assumptions and goals. Today's mechanistic disease model is cut off from such notions as life-energy, consciousness, and spirituality, so integral to many alternative paradigms.

Anthroposophically Extended Medicine (AEM) is a comprehensive healing system that successfully integrates biomedicine with a more complete understanding of human reality. Originating in Europe at the beginning of the 20th century, AEM has its roots in the Western, scientific worldview. By expanding this worldview, anthroposophy offers the clinician new possibilities for scientific investigation; it also creates bridges to the wisdom of older healing traditions of both East and West.

]]> Ira S. Cantor MD et al.