Current drug targets
-
Approximately seventy patients undergo solid organ transplantation (SOT) every day in the United States. Sepsis remains the first or second most common cause of death in transplant recipients, depending on the allograft type. The rapid diagnosis and treatment of sepsis is critical to ensure improved survival outcome in this special patient population. ⋯ This correlation can further advance the diagnosis and treatment of sepsis. In conclusion, precocious diagnosis, rapid initiation of antibiotics, surgical correction when necessary, and reduction of immunosuppression, are the mainstream approach to sepsis in the SOT patient. The recent developments in severe sepsis are discussed in the context of the transplant recipient.
-
Current drug targets · Jan 2007
ReviewNociceptin/orphanin FQ peptide receptors: pharmacology and clinical implications.
The advance of functional genomics revealed the superfamily of G-protein coupled receptors (GPCRs). Hundreds of GPCRs have been cloned but many of them are orphan GPCRs with unidentified ligands. The first identified orphan GPCR is the opioid receptor like orphan receptor, ORL1. ⋯ N/OFQ is also involved in cardiovascular, gastrointestinal and immune regulation. Altered plasma levels of N/OFQ have been reported in patients with various pain states, depression and liver diseases. This review summarizes the pharmacological characteristics of, and studies with, the available NOP receptor ligands and their possible clinical implications.
-
Current drug targets · Dec 2006
ReviewPharmacogenomics in the Americas: the impact of genetic admixture.
In this review we focus on the impact of genetic admixture on pharmacogenomics in the American continent, where five centuries of intermarriage between Amerindians, European and Africans, resulted in the extensive population heterogeneity observed nowadays. We compare two alternative views of human genomic variation, one stressing populations and the other stressing individuals, and discuss their important and far-reaching consequences to implementation of pharmacogenetics/genomics in practice, especially when dealing with admixed populations. We conclude that a variable mosaic genome paradigm, which envisages the genome of any particular individual as a unique mosaic of variable haplotype blocks--has considerably higher explanation and predictive power for the populations of the Americas. ⋯ Intra-ethnic diversity adds complexity to the scientific appraisal, regulatory decisions and, eventually, prescribing of drugs purportedly targeted to a given "race" or ethnicity. Pharmacogenetics/genomics has the potential to benefit people worldwide and to reduce the health disparities between developing and developed nations. This goal is unlikely to be achieved by relinquishing the notion of personalized drug therapy tailored to individual genetic characteristics--the original promise of pharmacogenetics--in favor of a model (pharmacogenomic?) of population-based drug development and prescription, with all its potential pitfalls, especially when extended to admixed populations in developing or developed nations.
-
Current drug targets · Sep 2006
ReviewThe guanylyl cyclase inhibition by MB as vasoplegic circulatory shock therapeutical target.
There were strong evidences that NO has capital importance in the progressive vasodilatation that associates to the varied circulatory shock forms. The decreased systemic vascular resistance observed in irreversible hemorrhagic (hypovolemic) and septic shock may be due to the excess production of nitric oxide. Other forms of shock associated to anaphylaxis (anaphylactic shock, SIRS) and ischemia reperfusion injury (cardiogenic shock, organ transplants), may involve nitric oxide overproduction. ⋯ As NO vasodilatation is cyclic GMP-mediated, there were two therapeutical options: a) The unspecific NO synthesis inhibition by L-arginine analogs, iNOS-specific inhibition by corticoids and/or aminoguanidine and; b) Guanylyl cyclase inhibition by MB. As the NO synthesis inhibition is associated to tissue necrosis and adverse hemodynamic effects and its clinical use was associated with high mortality, the second option using MB is safer and more rational. The elaboration of this text was motivated to suggest the guanylyl cyclase inhibition by MB as vasoplegic circulatory shock therapeutical target.