Annals of the New York Academy of Sciences
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Ann. N. Y. Acad. Sci. · Dec 2007
Review Historical ArticleNeuro- and cardioprotective effects of blockade of nitric oxide action by administration of methylene blue.
Methylene blue (MB), generic name methylthioninium (C(16)H(18)ClN(3) S . 3H(2)O), is a blue dye synthesized in 1876 by Heinrich Caro for use as a textile dye and used in the laboratory and clinically since the 1890s, with well-known toxicity and pharmacokinetics. It has experimentally proven neuroprotective and cardioprotective effects in a porcine model of global ischemia-reperfusion in experimental cardiac arrest. ⋯ The physiological effects during reperfusion include stabilization of the systemic circulation without significantly increased total peripheral resistance, moderately increased cerebral cortical blood flow, a decrease of lipid peroxidation and inflammation, and less anoxic tissue injury in the brain and the heart. The last two effects are recorded as less increase in plasma concentrations of astroglial protein S-100beta, as well as troponin I and creatine kinase isoenzyme MB, respectively.
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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.
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Ann. N. Y. Acad. Sci. · Jun 2007
ReviewGlomerular targets for autoantibodies in lupus nephritis--an apoptotic origin.
Systemic lupus erythematosus (SLE) is an autoimmune syndrome where different organs may individually or simultaneously be affected. Whether SLE is one disease entity or represents a variety of intrinsically unrelated organ manifestations is unknown. Variability of clinical presentations of SLE argues against the former. ⋯ It is believed that in situ binding of anti-dsDNA antibodies by nucleosomes is involved in organ manifestations in SLE. This review will focus on nature and origin of target structures for anti-dsDNA and antinucleosome antibodies in glomerular capillary and mesangial matrix membranes. We will particularly discuss the potential role of apoptosis and release of apoptotic chromatin in terms of their putative impact in SLE.