In recent years, there has been a prodigious expansion of knowledge about cyclic nucleotide phosphodiesterases (PDEs). This isozyme superfamily has now become a major focus of drug discovery efforts owing to its diversity, molecular nature, differential regulation and expression in different cell types, and the range of biological functions. Inhibition of these isozymes can lead to an increase in cAMP and cGMP levels, which can affect a variety of physiological responses. Selective inhibitors for each of the multiple forms of PDE can offer an opportunity for desired therapeutic intervention and would be an extremely useful tool in drug discovery efforts for a medicinal chemist. This review details many key aspects of multiple forms of PDEs and their inhibitors with diversified chemical structures, which can act as leads for synthesis of novel drugs.
Plasmablastic lymphoma (PBL) is a rare and aggressive variant of diffuse large B cell lymphoma. The prognosis of PBL patients is poor. The majority of patients succumb to a fulminant disease course, with most dying in the first year after diagnosis. The small number of HIV-negative PBL cases reported in the literature to date is composed of single case reports and small case series. Consequently, the natural history of the disease in HIV-negative individuals and the optimum treatment are not well characterized. Intensive induction chemotherapy has been associated with marked improved overall survival. However the optimal regimen has not been defined. We describe the third case of PBL of the maxillary sinus which occurred in a 24-year old HIV-negative man. We outline the clinicopathological features and report success using a hyper-CVAD regimen with 6 cycles and consolidation radiation therapy yielding a complete remission of four years.
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