Annals of the New York Academy of Sciences
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Ann. N. Y. Acad. Sci. · Dec 2007
Drug delivery to the spinal cord tagged with nanowire enhances neuroprotective efficacy and functional recovery following trauma to the rat spinal cord.
The possibility that drugs attached to innocuous nanowires enhance their delivery within the central nervous system (CNS) and thereby increase their therapeutic efficacy was examined in a rat model of spinal cord injury (SCI). Three compounds--AP173 (SCI-1), AP713 (SCI-2), and AP364 (SCI-5) (Acure Pharma, Uppsala, Sweden)--were tagged with TiO(2)-based nanowires using standard procedure. Normal compounds were used for comparison. ⋯ Interestingly, when these compounds were administered in identical conditions after tagging with nanowires, their beneficial effects on functional recovery and spinal cord pathology were further enhanced. However, topical administration of nanowires alone did not influence trauma-induced spinal cord pathology or motor functions. Taken together, our results, probably for the first time, indicate that drug delivery and therapeutic efficacy are enhanced when the compounds are administered with nanowires.
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Our goal globally is to better identify individuals at risk for osteoporotic fracture so that those at high risk can be treated and unnecessary treatment for those at low risk can be avoided. Bone mineral density (BMD) information is not sufficient to identify all patients at high risk. Approximately half of patients in the community with fractures do not have osteoporosis by the 1994 World Health Organization BMD criteria. ⋯ The use of clinical risk factors with or without BMD information will improve gradient of risk and help us better identify patients at high risk for fracture. The clinical risk factors identified can be integrated to predict a 10-year absolute risk or probability of fracture. Intervention thresholds based on absolute risk will be defined regionally based on each nation's ability and willingness to pay.
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Ann. N. Y. Acad. Sci. · Oct 2007
ReviewEvidence-based practice: limitations and successful implementation.
Evidence-based practice (EBP) has been heralded as the most appropriate way of ensuring that patients receive the most effective care possible. It does, however, have several limitations. It is also not enough just to locate and evaluate the evidence without implementing it. This paper discusses EBP and its limitations and potential barriers; it also suggests strategies for changing current practices to more evidence-based ones according to an accurate understanding of the concept of EBP.
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Ann. N. Y. Acad. Sci. · Oct 2007
ReviewDrugging the cancer chaperone HSP90: combinatorial therapeutic exploitation of oncogene addiction and tumor stress.
The molecular chaperone HSP90 has emerged as an exciting target for cancer treatment. We review the potential advantages of HSP90 inhibitors, particularly the simultaneous combinatorial depletion of multiple oncogenic "client" proteins, leading to blockade of many cancer-causing pathways and the antagonism of all of the hallmark pathological traits of malignancy. Cancer selectivity is achieved by exploiting cancer "dependencies," including oncogene addiction and the stressed state of malignant cells. ⋯ Potential new approaches are discussed, for example, interference with cochaperone binding and function in the superchaperone complex. Biomarkers for use with HSP90 inhibitors are described. We stress how basic and translational research has been mutually beneficial and indicate future directions to enhance our understanding of molecular chaperones and their exploitation in cancer and other diseases.
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Ann. N. Y. Acad. Sci. · Sep 2007
ReviewState-of-the-art treatment of coccidioidomycosis: skin and soft-tissue infections.
Coccidioidomycosis is a fungal infection common in the southwestern United States that is caused by the endemic Coccidioides species of fungus. Coccidioidal infections are generally manifested as self-limited respiratory illnesses, but affected patients rarely present with coccidioidomycosis in extrapulmonary locations. Skin and soft-tissue coccidioidomycosis may occur in 15% to 67% of patients with disseminated infection. ⋯ A biopsy of the abnormal area is the most direct way to diagnose skin and soft-tissue lesions. Fluconazole and itraconazole are preferred therapeutic agents, and surgical intervention may be required as an adjunctive measure. This article reviews the types and locations of disseminated infections, as well as diagnostic studies and treatment of this difficult-to-treat manifestation of coccidioidomycosis.