Behavioral Self-management in an Inpatient Headache Treatment Unit: Increasing Adherence and Relationship to Changes in Affective Distress

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74935/1/j.1526-4610.2000.00057.x.pd

Erythropoietin (EPO) increases myelin gene expression in CG4 oligodendrocyte cells through the classical EPO receptor

Erythropoietin (EPO) has protective effects in neurodegenerative and neuroinflammatory diseases, including in animal models of multiple sclerosis, where EPO decreases disease severity. EPO also promotes neurogenesis and is protective in models of toxic demyelination. In this study, we asked whether EPO could promote neurorepair by also inducing remyelination. In addition, we investigated whether the effect of EPO could be mediated by the classical erythropoietic EPO receptor (EPOR), since it is still questioned if EPOR is functional in non-hematopoietic cells. Using CG4 cells, a line of rat oligodendrocyte precursor cells, we found that EPO increases the expression of myelin genes (myelin oligodendrocyte glycoprotein (MOG) and myelin basic protein (MBP)). EPO had no effect in wild-type CG4 cells, which do not express EPOR, whereas it increased MOG and MBP expression in cells engineered to overexpress EPOR (CG4-EPOR). This was reflected in a marked increase in MOG protein levels, as detected by western blot. In these cells, EPO induced by 10-fold the early growth response gene 2 (Egr2), which is required for peripheral myelination. However, Egr2 silencing with a siRNA did not reverse the effect of EPO, indicating that EPO acts through other pathways. In conclusion, EPO induces the expression of myelin genes in oligodendrocytes and this effect requires the presence of EPOR. This study demonstrates that EPOR can mediate neuroreparative effects

Land use, residential density, and walking. The multi-ethnic study of atherosclerosis.

BACKGROUND: The neighborhood environment may play a role in encouraging sedentary patterns, especially for middle-aged and older adults. PURPOSE: The aim of this study was to examine the associations between walking and neighborhood population density, retail availability, and land-use distribution using data from a cohort of adults aged 45 to 84 years. METHODS: Data from a multi-ethnic sample of 5529 adult residents of Baltimore MD, Chicago IL, Forsyth County NC, Los Angeles CA, New York NY, and St. Paul MN enrolled in the Multi-Ethnic Study of Atherosclerosis in 2000-2002 were linked to secondary land-use and population data. Participant reports of access to destinations and stores and objective measures of the percentage of land area in parcels devoted to retail land uses, the population divided by land area in parcels, and the mixture of uses for areas within 200 m of each participant's residence were examined. Multinomial logistic regression was used to investigate associations of self-reported and objective neighborhood characteristics with walking. All analyses were conducted in 2008 and 2009. RESULTS: After adjustment for individual-level characteristics and neighborhood connectivity, it was found that higher density, greater land area devoted to retail uses, and self-reported proximity of destinations and ease of walking to places were each related to walking. In models including all land-use measures, population density was positively associated with walking to places and with walking for exercise for more than 90 minutes/week, both relative to no walking. Availability of retail was associated with walking to places relative to not walking, and having a more proportional mix of land uses was associated with walking for exercise for more than 90 minutes/week, while self-reported ease of access to places was related to higher levels of exercise walking, both relative to not walking. CONCLUSIONS: Residential density and the presence of retail uses are related to various walking behaviors. Efforts to increase walking may benefit from attention to the intensity and type of land development.http://deepblue.lib.umich.edu/bitstream/2027.42/78515/1/RodriguezEvenson2009_Am J Prev Med.pd

Erythropoietin Selectively Attenuates Cytokine Production and Inflammation in Cerebral Ischemia by Targeting Neuronal Apoptosis

Ischemic brain injury resulting from stroke arises from primary neuronal losses and by inflammatory responses. Previous studies suggest that erythropoietin (EPO) attenuates both processes. Although EPO is clearly antiapoptotic for neurons after experimental stroke, it is unknown whether EPO also directly modulates EPO receptor (EPO-R)–expressing glia, microglia, and other inflammatory cells. In these experiments, we show that recombinant human EPO (rhEPO; 5,000 U/kg body weight, i.p.) markedly reduces astrocyte activation and the recruitment of leukocytes and microglia into an infarction produced by middle cerebral artery occlusion in rats. In addition, ischemia-induced production of the proinflammatory cytokines tumor necrosis factor, interleukin 6, and monocyte chemoattractant protein 1 concentration is reduced by >50% after rhEPO administration. Similar results were also observed in mixed neuronal-glial cocultures exposed to the neuronal-selective toxin trimethyl tin. In contrast, rhEPO did not inhibit cytokine production by astrocyte cultures exposed to neuronal homogenates or modulate the response of human peripheral blood mononuclear cells, rat glial cells, or the brain to lipopolysaccharide. These findings suggest that rhEPO attenuates ischemia-induced inflammation by reducing neuronal death rather than by direct effects upon EPO-R–expressing inflammatory cells

Erythropoietin Ameliorates Rat Experimental Autoimmune Neuritis by Inducing Transforming Growth Factor-Beta in Macrophages

Erythropoietin (EPO) is a pleiotropic cytokine originally identified for its role in erythropoiesis. In addition, in various preclinical models EPO exhibited protective activity against tissue injury. There is an urgent need for potent treatments of autoimmune driven disorders of the peripheral nervous system (PNS), such as the Guillain-Barré syndrome (GBS), a disabling autoimmune disease associated with relevant morbidity and mortality. To test the therapeutic potential of EPO in experimental autoimmune neuritis (EAN) - an animal model of human GBS – immunological and clinical effects were investigated in a preventive and a therapeutic paradigm. Treatment with EPO reduced clinical disease severity and if given therapeutically also shortened the recovery phase of EAN. Clinical findings were mirrored by decreased inflammation within the peripheral nerve, and myelin was well maintained in treated animals. In contrast, EPO increased the number of macrophages especially in later stages of the experimental disease phase. Furthermore, the anti-inflammatory cytokine transforming growth factor (TGF)-beta was upregulated in the treated cohorts. In vitro experiments revealed less proliferation of T cells in the presence of EPO and TGF-beta was moderately induced, while the secretion of other cytokines was almost not altered by EPO. Our data suggest that EPO revealed its beneficial properties by the induction of beneficial macrophages and the modulation of the immune system towards anti-inflammatory responses in the PNS. Further studies are warranted to elaborate the clinical usefulness of EPO for treating immune-mediated neuropathies in affected patients

A spatial analysis of health-related resources in three diverse metropolitan areas

Few studies have investigated the spatial clustering of multiple health-related resources. We constructed 0.5 mile kernel densities of resources for census areas in New York City, NY (n=819 block groups), Baltimore, MD (n=737), and Winston-Salem, NC (n=169). Three of the four resource densities (supermarkets/produce stores, retail areas, and recreational facilities) tended to be correlated with each other, whereas park density was less consistently and sometimes negatively correlated with others. Blacks were more likely to live in block groups with multiple low resource densities. Spatial regression models showed that block groups with higher proportions of black residents tended to have lower supermarket/produce, retail, and recreational facility densities, although these associations did not always achieve statistical significance. A measure that combined local and neighboring block group racial composition was often a stronger predictor of resources than the local measure alone. Overall, our results from three diverse U.S. cities show that health-related resources are not randomly distributed across space and that disadvantage in multiple domains often clusters with residential racial patterning.http://deepblue.lib.umich.edu/bitstream/2027.42/78330/1/SmileyDiezRoux2010_HealthPlace.pd

Availability of Recreational Resources in Minority and Low Socioeconomic Status Areas

Differences in availability of recreational resources may contribute to racial and SES disparities in physical activity. Variations in the location and density of recreational resources were examined by SES and racial composition of neighborhoods

Haemoglobin mass and running time trial performance after recombinant human erythropoietin administration in trained men

<p>Recombinant human erythropoietin (rHuEpo) increases haemoglobin mass (Hbmass) and maximal oxygen uptake (v˙ O2 max).</p> <p>Purpose: This study defined the time course of changes in Hbmass, v˙ O2 max as well as running time trial performance following 4 weeks of rHuEpo administration to determine whether the laboratory observations would translate into actual improvements in running performance in the field.</p> <p>Methods: 19 trained men received rHuEpo injections of 50 IUNkg21 body mass every two days for 4 weeks. Hbmass was determined weekly using the optimized carbon monoxide rebreathing method until 4 weeks after administration. v˙ O2 max and 3,000 m time trial performance were measured pre, post administration and at the end of the study.</p> <p>Results: Relative to baseline, running performance significantly improved by ,6% after administration (10:3061:07 min:sec vs. 11:0861:15 min:sec, p,0.001) and remained significantly enhanced by ,3% 4 weeks after administration (10:4661:13 min:sec, p,0.001), while v˙ O2 max was also significantly increased post administration (60.765.8 mLNmin21Nkg21 vs. 56.066.2 mLNmin21Nkg21, p,0.001) and remained significantly increased 4 weeks after rHuEpo (58.065.6 mLNmin21Nkg21, p = 0.021). Hbmass was significantly increased at the end of administration compared to baseline (15.261.5 gNkg21 vs. 12.761.2 gNkg21, p,0.001). The rate of decrease in Hbmass toward baseline values post rHuEpo was similar to that of the increase during administration (20.53 gNkg21Nwk21, 95% confidence interval (CI) (20.68, 20.38) vs. 0.54 gNkg21Nwk21, CI (0.46, 0.63)) but Hbmass was still significantly elevated 4 weeks after administration compared to baseline (13.761.1 gNkg21, p<0.001).</p> <p>Conclusion: Running performance was improved following 4 weeks of rHuEpo and remained elevated 4 weeks after administration compared to baseline. These field performance effects coincided with rHuEpo-induced elevated v˙ O2 max and Hbmass.</p&gt

Availability of recreational resources and physical activity in adults

OBJECTIVES: Using data from a large cohort of adults aged 45 to 84 years-old, we investigated whether availability of recreational resources is related to physical activity levels. METHODS: Data from a multiethnic sample of 2723 adult residents of New York City, NY; Baltimore, Md; and Forsyth County, NC, were linked to data on locations of recreational resources. We measured the availability (density) of resources within 0.5 (0.8 km), 1, 2, and 5 miles of each participant's residence and used binomial regression to investigate associations of density with physical activity. RESULTS: After adjustment for potential confounders, individuals in the tertile of participants residing in areas with the highest density of resources were more likely to report physical activity during a typical week than were individuals in the lowest tertile. Associations between availability of recreational resources and physical activity levels were not present for the smallest area assessed (0.5 miles) but were present for areas ranging from 1 to 5 miles. These associations were slightly stronger among minority and low-income residents. CONCLUSIONS: Availability of resources may be 1 of several environmental factors that influence individuals' physical activity behaviors.http://deepblue.lib.umich.edu/bitstream/2027.42/78573/1/DiezRouxEvenson2007_AJPH.pd

ERYTHROPOIETIN FOR THE TREATMENT OF SUBARACHNOID HEMORRAGE: A FEASIBLE INGREDIENT FOR A SUCCESS MEDICAL RECIPE

Subaracnhoid hemorrage (SAH) following aneurysm bleeding accounts for 6% to 8% of all cerebrovascular accidents. Althoug an aneurysm can be effectively managed by surgery or endovascular therapy, delayed cerebral ischemia is diagnosed in a high percentage of patients resulting in significant morbility and mortality. Cerebral vasospasm occurs in more than half of all patients after aneurysm rupture and is recognized as the leading cause of delayed cerebral ischemia after SAH. Hemodynamic strategies and endovascular procedures may be considered fo the treatment of cerebral vasospasm. In recent years, the mechanism contributing to the development of vasospasm, abnormal reactivity of cerebral arteries and cerebral ischemia following SAH, have been intensively investigated. A number of pathological processes have been identified in the pathogenesis of vasospasm including endothelial injury, smooth muscle cell contraction from spasmogenic substances produced by the subarachnoid blood clots, changes in vascular responsiveness and inflammatory response of the vascular endothelium. to date, the current therapeutic interventions remain ineffective being limited to the manipulation os systemic blood pressure, variation of blood volume and viscosity, and control of arterial carbon dioxide tension. In this scenario, the hormone erythropoietin (EPO), has been found to exert neuroprotective action during experimental SAH when its recombinant form (rHuEPO) is systematically administered. However, recent translation of experimental data into clinical trials has suggested an unclear role of recombinant human EPO in the setting of SAH. In this context, the aim of the recurrent review is to present current evidence on the potential role of EPO in cerebrovascular dysfunction following aneurysmal subarachnoid hemorrage