Table of Contents

August 2006; 6 (4)

Speaking of Pharmacology

    • Benedict R. Lucchesi and
    • Darrell R. Abernethy

    Speaking of Pharmacology

    Mol Interv August 2006 6:185

Reflections

    • Stanley Scheindlin

    Rare Diseases, Orphan Drugs, and Orphaned Patients

    Mol Interv August 2006 6:186-191; doi:10.1124/mi.6.4.2

Nascent Transcripts

  • Emerging concepts from the recent literature

    Mol Interv August 2006 6:192; doi:10.1124/mi.6.4.3

Viewpoints

    • Paula H. Stern

    The Calcineurin-NFAT Pathway and Bone: Intriguing New Findings

    Mol Interv August 2006 6:193-196; doi:10.1124/mi.6.4.4

    New findings reveal that the calcineurin-NFAT signaling pathway helps to promote osteoblast differentiation. Three recent papers reveal somewhat different mechanisms by which this could occur. In one study, transduction of calcineurin Aα increased expression of osteoblast differentiation markers, including Runx-2. In another study, NFATc1 cooperatively enhanced Osterix activation of the collagen 1a1 promoter, but did not enhance Runx-2 activity; evidence was provided for the formation of a novel NFATc1-Osterix complex. In a third study, expression of nuclear NFATc1 enhanced Wnt signaling. The observation that the Wnt pathway promotes bone formation is intriguing, because NFATc1 also is critical for osteoclastogenesis. The current findings could be relevant for the osteoporosis seen in patients given the calcineurin inhibitor cyclosporine to prevent transplant rejection, although the results need to be reconciled with aspects of the clinical picture.

    • Wolfgang Sadée and
    • Laura Bohn

    How Specific Are “Target-Specific” Drugs? Celecoxib as a Case in Point

    Mol Interv August 2006 6:196-198; doi:10.1124/mi.6.4.5

    With the push to develop the next blockbuster drugs, continued surveillance of current bestsellers may not be given the full attention due. Upon wide-spread use, unexpected adverse effects begin to emerge. Although touted as highly specific, many of the newly developed drugs are likely to have secondary molecular targets—a potential cause of adverse effects. A molecular pharmacology approach that screens for multiple drug targets may shed light on the mechanisms that underlie both desired and adverse side-effects.

Reviews

    • Ravindra Rajakariar,
    • Muhammad M. Yaqoob,
    • and Derek W. Gilroy

    COX-2 in Inflammation and Resolution

    Mol Interv August 2006 6:199-207; doi:10.1124/mi.6.4.6

    In view of the widespread and effective use of the nonsteroidal anti-inflammatory drugs (NSAIDs), the importance of limiting the side effects of these agents is self-evident. A major goal for both clinicians and drug developers has thus been to improve the specificity with which novel NSAIDs would inhibit their canonical targets, the cyclooxygenase (COX) enzymes. A number of lessons, in a variety of arenas, have been learned in the pursuit of this goal. Some of these lessons have unearthed new challenges in understanding the biology and pharmacology of the COX enzymes. Particularly important is the growing recognition that the inhibition of the COX enzymes, even with the attainment of absolute specificity for one or both of the major COX isoforms, may itself undermine anti-inflammatory therapy or even exacerbate inflammatory disease.

    • Elizabeth Jonas

    BCL-xL Regulates Synaptic Plasticity

    Mol Interv August 2006 6:208-222; doi:10.1124/mi.6.4.7

    Mitochondria produce energy in the form of ATP for highly energy-dependent processes of synaptic vesicle recycling and the operation of ion pumps. Mitochondrial localization to presynaptic sites alters the kinetics of transmitter release by the localized production of ATP and by calcium buffering. BCL-xL changes the conductance of mitochondrial membranes and alters mitochondrial bioenergetics to enhance the life of the synapse. Therapeutic attempts to modulate neuroplasticity and other synaptic activities may thus rest on a more thorough understanding of the organellar trafficking and constitution of neurons.

    • Allan E. Rettie and
    • Guoying Tai

    The Pharmocogenomics of Warfarin: Closing in on Personalized Medicine

    Mol Interv August 2006 6:223-227; doi:10.1124/mi.6.4.8

    As with most drugs, the prescription of warfarin is a balancing act. In this case, the patient who receives too much is at risk for hemorrhagic complications, whereas the patient who receives too little may not be adequately protected against thromboembolism. Dose-response curves for warfarin are especially complex, and the basis of this complexity lies in part in the interindividual variability among patient genomes. Research into the pharmacogenomics of warfarin responsiveness, based on an appreciation of the multiple gene products that metabolize or mediate the efficacy of the drug, has arisen as a model for the considerations that must me addressed in bringing personalized medicine into practice.

Beyond the Bench

    • Christie Carrico

    Breaking the Mold: A Lesson in Perseverance

    Mol Interv August 2006 6:228-229; doi:10.1124/mi.6.4.9

Net Results

  • Sites of interest on the World Wide Web—edited by David Roman

    Mol Interv August 2006 6:230

Outliers

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This Issue

August 2006; 6 (4)
Cover
  1. Speaking of Pharmacology
  2. Reflections
  3. Nascent Transcripts
  4. Viewpoints
  5. Reviews
  6. Beyond the Bench
  7. Net Results
  8. Outliers

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