Synthesis of Various Classes of Cyanine Fluorophores and Their Application In In Vivo Tissue Imaging

A novel series of near-infrared fluorescent contrast agents was developed and characterized. Their physicochemical and optical properties were measured. By altering functional groups of cyanine fluorophores, the selective targeting of endocrine glands, exocrine glands, cartilage and bone using NIR fluorescence to visualize the targeted tissue has been reported. These agents have high specificity for tissue targeting inherent to the chemical structure of the fluorophore. After a single low-dose intravenous injection these agents have high specificity for tissue targeting inherent to the chemical structure of the fluorophore. The results lay the foundation for future improvements in optical imaging in endocrine surgery, tissue engineering, joint surgery, and cartilage-specific drug development

Unsymmetrical Trimethine Cyanine Dyes: Synthesis, Optical Properties, and Evaluations as Inhibitors of Protein Arginine Methyl Transferases

Carbocyanine dyes are a class of organic compounds that possess two nitrogen containing heterocycles that act as electron donors and acceptors connected by a conjugated methine bridge. This thesis will present the synthetic methodology of symmetrical and unsymmetrical trimethine cyanine dyes in three chapters. The first chapter is a review on the synthesis and application of unsymmetric cyanine dyes. The second will describe the synthesis of unsymmetrical trimethine cyanine dyes and how their optical properties differ from symmetrical dyes. The third chapter will not only discuss the synthetic procedure for synthesis of symmetrical trimethine cyanine dyes, but also will show how varying the N-alkyl substituents and hydrophobicity of the heterocycles affects the dyes interaction with and ability to be used as inhibitors for protein arginine methyltransferases (PRMTs). Several synthesized compounds have displayed lower IC50 values for the inhibition of PRMT1 and PRMT5 comparable to that of current inhibitors

Benz[c,d]indolium-containing Monomethine Cyanine Dyes: Synthesis and Photophysical Properties

Asymmetric monomethine cyanines have been extensively used as probes for nucleic acids among other biological systems. Herein we report the synthesis of seven monomethine cyanine dyes that have been successfully prepared with various heterocyclic moieties such as quinoline, benzoxazole, benzothiazole, dimethyl indole, and benz[e]indole adjoining benz[c,d]indol-1-ium, which was found to directly influence their optical and energy profiles. In this study the optical properties vs. structural changes were investigated using nuclear magnetic resonance and computational approaches. The twisted conformation unique to monomethine cyanines was exploited in DNA binding studies where the newly designed sensor displayed an increase in fluorescence when bound in the DNA grooves compared to the unbound form

Multi-spectral Vascular Oximetry of Rat Dorsal Spinal Cord

No abstract available

AIDS-related mycoses: the way forward.

The contribution of fungal infections to the morbidity and mortality of HIV-infected individuals is largely unrecognized. A recent meeting highlighted several priorities that need to be urgently addressed, including improved epidemiological surveillance, increased availability of existing diagnostics and drugs, more training in the field of medical mycology, and better funding for research and provision of treatment, particularly in developing countries

Paradoxical Immune Responses in Non-HIV Cryptococcal Meningitis

<div><p>The fungus <i>Cryptococcus</i> is a major cause of meningoencephalitis in HIV-infected as well as HIV-uninfected individuals with mortalities in developed countries of 20% and 30%, respectively. In HIV-related disease, defects in T-cell immunity are paramount, whereas there is little understanding of mechanisms of susceptibility in non-HIV related disease, especially that occurring in previously healthy adults. The present description is the first detailed immunological study of non-HIV-infected patients including those with severe central nervous system (s-CNS) disease to 1) identify mechanisms of susceptibility as well as 2) understand mechanisms underlying severe disease. Despite the expectation that, as in HIV, T-cell immunity would be deficient in such patients, cerebrospinal fluid (CSF) immunophenotyping, T-cell activation studies, soluble cytokine mapping and tissue cellular phenotyping demonstrated that patients with s-CNS disease had effective microbiological control, but displayed strong intrathecal expansion and activation of cells of both the innate and adaptive immunity including HLA-DR+ CD4+ and CD8+ cells and NK cells. These expanded CSF T cells were enriched for cryptococcal-antigen specific CD4+ cells and expressed high levels of IFN-γ as well as a lack of elevated CSF levels of typical T-cell specific Th2 cytokines -- IL-4 and IL-13. This inflammatory response was accompanied by elevated levels of CSF NFL, a marker of axonal damage, consistent with ongoing neurological damage. However, while tissue macrophage recruitment to the site of infection was intact, polarization studies of brain biopsy and autopsy specimens demonstrated an M2 macrophage polarization and poor phagocytosis of fungal cells. These studies thus expand the paradigm for cryptococcal disease susceptibility to include a prominent role for macrophage activation defects and suggest a spectrum of disease whereby severe neurological disease is characterized by immune-mediated host cell damage.</p></div

Immunophenotyping demonstrates increased absolute counts of CSF circulating activated HLA-DR+ CD4+ and CD8+ as well as—B-cells in s-CNS patients.

<p>Absolute numbers and proportions of activated CD4+ and CD8+ T lymphocytes (HLA-DR+),—and B lymphocytes were assessed in fresh CSF or blood by flow cytometry as described in Materials and Methods in patients with s-CNS disease (N = 17), non-CNS disease (N = 6), and healthy donors (HD; N = 11). Proportions are calculated from the total CD45+ cells. *0.01≤p<0.05; **0.001≤p<0.01; ***0.0001≤p<0.001.</p