20 research outputs found
Exposure and Ritual Prevention, Clomipramine, or Their Combination for Obsessive-Compulsive Disorder
No full textThis chapter provides a summary of a landmark study on the management of obsessive-compulsive disorder (OCD) in adults. Is the combination of exposure and ritual prevention (a cognitive behavior therapy based intervention) along with clomipramine more efficacious than monotherapy with either treatment for OCD? Starting with that question, it describes the basics of the study, including funding, study location, who was studied, how many patients, study design, study interventions, follow-up, endpoints, results, and criticism and limitations. The chapter briefly reviews other relevant studies and information, discusses implications for clinical management, and concludes with an exemplary clinical case applying the evidence.</p
Memantine in Patients with Moderate to Severe Alzheimer’s Disease Already Receiving Donepezil
No full textThis chapter provides a summary of a landmark study on the pharmacological management of cognitive disorders. In patients with moderate to severe Alzheimer disease treated with a cholinesterase inhibitor (donepezil), is the addition of a N-methyl-D-aspartate receptor inhibitor (memantine) a safe and efficacious augmentation strategy? Starting with that question, it describes the basics of the study, including funding, study location, who was studied, how many patients, study design, study intervention, follow-up, endpoints, results, and criticism and limitations. The chapter briefly reviews other relevant studies and controversy within the field, concluding with a discussion of implications, and an exemplary clinical case applying the study evidence.</p
Dealing with Misfolded Proteins: Examining the Neuroprotective Role of Molecular Chaperones in Neurodegeneration
No full textHuman neurodegenerative diseases arise from a wide array of genetic and environmental factors. Despite the diversity in etiology, many of these diseases are considered "conformational" in nature, characterized by the accumulation of pathological, misfolded proteins. These misfolded proteins can induce cellular stress by overloading the proteolytic machinery, ultimately resulting in the accumulation and deposition of aggregated protein species that are cytotoxic. Misfolded proteins may also form aberrant, non-physiological protein-protein interactions leading to the sequestration of other normal proteins essential for cellular functions. The progression of such disease may therefore be viewed as a failure of normal protein homeostasis, a process that involves a network of molecules regulating the synthesis, folding, translocation and clearance of proteins. Molecular chaperones are highly conserved proteins involved in the folding of nascent proteins, and the repair of proteins that have lost their typical conformations. These functions have therefore made molecular chaperones an active area of investigation within the field of conformational diseases. This review will discuss the role of molecular chaperones in neurodegenerative diseases, highlighting their functional classification, regulation, and therapeutic potential for such diseases
Methodological considerations in the analysis of fecal glucocorticoid metabolites in tufted capuchins (Cebus apella)
No full textAnalysis of fecal glucocorticoid (GC) metabolites has recently become the standard method to monitor adrenocortical activity in primates noninvasively. However, given variation in the production, metabolism, and excretion of GCs across species and even between sexes, there are no standard methods that are universally applicable. In particular, it is important to validate assays intended to measure GC production, test extraction and storage procedures, and consider the time course of GC metabolite excretion relative to the production and circulation of the native hormones. This study examines these four methodological aspects of fecal GC metabolite analysis in tufted capuchins (Cebus apella). Specifically, we conducted an adrenocorticotrophic hormone (ACTH) challenge on one male and one female capuchin to test the validity of four GC enzyme immunoassays (EIAs) and document the time course characterizing GC me- tabolite excretion in this species. In addition, we compare a common field-friendly technique for extracting fecal GC metabolites to an established laboratory extraction methodology and test for effects of storing “field extracts” for up to 1 yr. Results suggest that a corticosterone EIA is most sensitive to changes in GC production, provides reliable measures when extracted according to the field method, and measures GC metabolites which remain highly stable after even 12 mo of storage. Further, the time course of GC metabolite excretion is shorter than that described yet for any primate taxa. These results provide guidelines for studies of GCs in tufted capuchins, and underscore the importance of validating methods for fecal hormone analysis for each species of interest
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662. The Tracking of Exogenous Cells in the Injured Central Nervous System: Viral Vector Labeling Versus an Intrinsic Genetic Marker
No full textTransplantation of exogenous cells into the injured central nervous system and subsequent examination of how these cells survive, integrate and perform physiological functions within the host environment requires that the cells be clearly identifiable from host cells. As many of the cells used for transplantation studies are derived from cultures of cells indistinguishable from the host using immunochemical approaches, numerous dyes or genetic markers have been devised and used for this purpose. These markers used to label and track these transplanted cells need to be specific, reliable, resistant to leakage or cellular transfer, and remain chemically stable once inside the host to allow long-term tracking. In the current study we compared two labeling methods for long-term tracking of cells following transplantation into the injured rat spinal cord; lentiviral vector transduction with green fluorescent protein (GFP) and DNA in situ hybridization for the Y chromosome after male cell transplantation in female rats. Examination of labeled cells at 12 wk post-injury demonstrated that both labels did not exhibit significant fading or loss of the signal due to instability over time. The visualization procedure for the DNA in situ reaction product was significantly more labor intensive than simple identification of GFP by fluorescent microscopy. Y chromosome positive cells were, however, easier to definitely count for assessment of cell survival than GFP labeled cells, due to the presence of the label as a single point within the nucleus rather than diffuse labeling throughout the entirety of the cell. The limited presence of the signal in Y chromosome positive cells though, made examination of their ability to integrate within the injured spinal cord, migrate and associate with axons impossible without additional immunochemical methods for labeling the entire cell. The combination of immunochemistry with DNA in situ however proved to be unsuccessful with the many antibody combinations tested. In conclusion GFP delivery by lentiviral vectors was far superior to DNA in situ detection of the Y chromosome for labeling of transplanted cells due to its rapid visualization and its applicability to a wide range of assessment techniques
When the working day is through: The end of work as identity?
No full textThis article seeks to present a counter-case to the ‘end of work thesis’ advocated by writers such as Beck, Sennett and Bauman. It argues that work remains a significant locus of personal identity and that the depiction by these writers of endemic insecurity in the workplace is inaccurate and lacks empirical basis. The article draws upon case study data to illustrate how, across a range of workplaces, work remains an importance source of identity, meaning and social affiliation
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518. Long-term lentiviral vector-mediated transgene expression in neural progenitor cells following implantation into the injured rat spinal cord
No full textDue to their self-renewal and multi-potency, stem cells represent an attractive source for cell replacement therapy in neurological disorders. Genetic manipulation of these cells may allow controlled release of therapeutic proteins, suppress immune rejection, or produce essential neurotransmitters. Furthermore, when the expression cassette is incorporated into the host genome ex vivo, this technique also may be used as a method to trace cells following implantation into tissues of interest. We explored the possibility of transducing pluripotent fetal rat cortical neural progenitor cells using lentiviral vectors encoding either the green fluorescent protein (GFP) or neurotrophic factors (NT-3, BDNF, GDNF and CNTF) under control of the CMV promoter and the Woodchuck post-transcriptional regulatory element. Following isolation and expansion of the cells at clonal density on poly-ornithine-fibronectin-coated dishes in the presence of bFGF, cells were collected, infected and replated on the dishes. Staining of these cells for neural markers (such as nestin, GFAP, Tuj-1 and RIP) after transduction did not reveal any significant difference from non-transduced cells. However, when they were transduced with a vector encoding CNTF, cells started expressing GFAP. Cells continued to express the transgene, including when bFGF was withdrawn and when cells started to differentiate into GFAP positive cells. Following delayed (1 week) implantation into the lesion site of the moderately contused spinal cord, transduced cells survived well up to 4 weeks post-implantation (the longest time point currently examined). Migration of the cells was mainly restricted to white matter on either side of the lesion. Currently, the therapeutic and axonal growth stimulating properties of the implanted cells are being investigated in injured rats
