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Significant Impediment (significant + impediment)
Selected AbstractsSite-specific opening of the blood-brain barrierJOURNAL OF BIOPHOTONICS, Issue 5-6 2010Steen J. Madsen Abstract The blood-brain barrier (BBB) poses a significant impediment for the delivery of therapeutic drugs into the brain. This is particularly problematic for the treatment of malignant gliomas which are characterized by diffuse infiltration of tumor cells into normal brain where they are protected by a patent BBB. Selective disruption of the BBB, followed by administration of anti-cancer agents, represents a promising approach for the elimination of infiltrating glioma cells. A summary of the techniques (focused ultrasound, photodynamic therapy and photochemical internalization) for site-specific opening of the BBB will be discussed in this review. Each approach is capable of causing localized and transient opening of the BBB with minimal damage to surrounding normal brain as evidenced from magnetic resonance images and histology. (© 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [source] Differential pharmacological regulation of drug efflux and pharmacoresistant schizophreniaBIOESSAYS, Issue 2 2008Mary Bebawy Pharmacoresistant schizophrenia is a significant impediment to the successful management of the disease. The expression and function of P-glycoprotein (P-gp) has recently been implicated in this phenomenon. P-gp is a multidrug efflux transporter that prevents drug substrates from crossing the blood,brain barrier (BBB). Although the direct interaction between individual antipsychotic agents and P-gp has been demonstrated, the effect of antipsychotic drug combinations used in disease management on P-gp transport function remains to be elucidated. This could have important clinical implications in some individuals as dosage adjustments based on plasma drug concentration changes may not always be appropriate if drug,drug interactions and the resulting changes in drug concentration in the brain are not considered. This paper introduces the potential impact that combination antipsychotic therapy may have on P-gp function at the BBB and discusses the consequences of this in the prevention and circumvention of unfavourable therapeutic response in schizophrenic disorders. BioEssays 30:183,188, 2008. © 2008 Wiley Periodicals, Inc. [source] A simple and highly successful C-terminal sequence analysis of proteins by mass spectrometryPROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 8 2008Hiroki Kuyama Dr. Abstract A simple and efficient method for C-terminal sequencing of proteins has long been pursued because it would provide substantial information for identifying the covalent structure, including post-translational modifications. However, there are still significant impediments to both direct sequencing from C termini of proteins and specific isolation of C-terminal peptides from proteins. We describe here a highly successful, de novo C-terminal sequencing method of proteins by employing succinimidyloxycarbonylmethyl tris (2,4,6-trimethoxyphenyl) phosphonium bromide and mass spectrometry. [source] Cultural Perspectives Concerning Adolescent Use of Tobacco and Alcohol in the Appalachian Mountain RegionTHE JOURNAL OF RURAL HEALTH, Issue 1 2008Michael G. Meyer MA ABSTRACT:,Context:Appalachia has high rates of tobacco use and related health problems, and despite significant impediments to alcohol use, alcohol abuse is common. Adolescents are exposed to sophisticated tobacco and alcohol advertising. Prevention messages, therefore, should reflect research concerning culturally influenced attitudes toward tobacco and alcohol use. Methods: With 4 grants from the National Institutes of Health, 34 focus groups occurred between 1999 and 2003 in 17 rural Appalachian jurisdictions in 7 states. These jurisdictions ranged between 4 and 8 on the Rural-Urban Continuum Codes of the Economic Research Service of the US Department of Agriculture. Of the focus groups, 25 sought the perspectives of women in Appalachia, and 9, opinions of adolescents. Findings: The family represented the key context where residents of Appalachia learn about tobacco and alcohol use. Experimentation with tobacco and alcohol frequently commenced by early adolescence and initially occurred in the context of the family home. Reasons to abstain from tobacco and alcohol included a variety of reasons related to family circumstances. Adults generally displayed a greater degree of tolerance for adolescent alcohol use than tobacco use. Tobacco growing represents an economic mainstay in many communities, a fact that contributes to the acceptance of its use, and many coal miners use smokeless tobacco since they cannot light up in the mines. The production and distribution of homemade alcohol was not a significant issue in alcohol use in the mountains even though it appeared not to have entirely disappeared. Conclusions: Though cultural factors support tobacco and alcohol use in Appalachia, risk awareness is common. Messages tailored to cultural themes may decrease prevalence. [source] | ||||||||||