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p. 323-344
Received: 1 December 2009; in revised form: 20 January 2010 / Accepted: 25 January 2010 / Published: 28 January 2010
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Abstract: The prevailing dogma is that, to be systemically effective, interferon-alpha (IFNα) must be administered in sufficiently high doses to yield functional blood concentrations. Such an approach to IFNa therapy has proven effective in some instances, but high-dose parenteral IFNα therapy has the disadvantage of causing significant adverse events. Mounting evidence suggests that IFNα delivered into the oral cavity in low doses interacts with the oral mucosa in a unique manner to induce systemic host defense mechanisms without IFNα actually entering the circulation, thus reducing the potential for toxic side effects. A better understanding of the applications and potential benefits of this treatment modality are under active investigation. This paper provides a review of the relevant literature on the clinical use of the oromucosal route of administration of interferon, with an emphasis on the treatment of influenza.
(This article belongs to the Special Issue
Interferons )
p. 345-368
Received: 23 December 2009; in revised form: 20 January 2010 / Accepted: 25 January 2010 / Published: 28 January 2010
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Abstract: Olesoxime (TRO19622) is a novel mitochondrial-targeted neuroprotective compound undergoing a pivotal clinical efficacy study in Amyotrophic Lateral Sclerosis (ALS) and also in development for Spinal Muscular Atrophy (SMA). It belongs to a new family of cholesterol-oximes identified for its survival-promoting activity on purified motor neurons deprived of neurotrophic factors. Olesoxime targets proteins of the outer mitochondrial membrane, concentrates at the mitochondria and prevents permeability transition pore opening mediated by, among other things, oxidative stress. Olesoxime has been shown to exert a potent neuroprotective effect in various in vitro and in vivo models. In particular olesoxime provided significant protection in experimental animal models of motor neuron disorders and more particularly ALS. Olesoxime is orally active, crosses the blood brain barrier, and is well tolerated. Collectively, its pharmacological properties designate olesoxime as a promising drug candidate for motor neuron diseases.
p. 369-378
Received: 14 December 2009; in revised form: 12 January 2010 / Accepted: 21 January 2010 / Published: 1 February 2010
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Abstract: In the attempt to discover a new polymorph of rofecoxib (Vioxx®), an unexpected product resulted. The product was characterised by chemical composition, thermal behaviour and structure and found to be 6-methylsulphonylphenanthro-[9,10-C] furan-1(3H )-one, a photo-cyclization degradation product of rofecoxib. This is a significant finding because it indicates that without appropriate control of the recrystallisation procedures, the structural integrity of rofecoxib may be seriously compromised.
p. 379-392
Received: 18 December 2008; in revised form: 20 January 2010 / Accepted: 28 January 2010 / Published: 3 February 2010
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Abstract: The inability of most drugs to cross the blood-brain barrier and/or plasma membrane limits their use for biomedical applications in the brain. Cell Permeable Peptides (CPPs) overcome this problem and are effective in vivo , crossing the plasma membrane and the blood-brain barrier. CPPs deliver a wide variety of compounds intracellularly in an active form. In fact, many bioactive cargoes have neuroprotective properties, and due to their ability to block protein-protein interactions, offer exciting perspectives in the clinical setting. In this review we give an overview of the Cell Permeable Peptides strategy to deliver neuroprotectants against neurodegeneration in the CNS.
p. 393-405
Received: 24 November 2009; in revised form: 15 January 2010 / Accepted: 21 January 2010 / Published: 3 February 2010
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Abstract: Non-steroidal anti-inflammatory drugs like ibuprofen or indomethacin are commonly prescribed drugs to induce pharmacologic closure of a patent ductus arteriosus in preterm neonates. Based on a recently published Cochrane meta-analysis, both drugs are equally effective to induce closure. Drug choice can therefore be based on differences in side effects or pharmaco-economic arguments. The current review quantifies the negative impact of either ibuprofen or indomethacin on renal function, including diuresis, glomerular filtration rate and renal tubular function. Both ibuprofen and indomethacin have a quantifiable impact on renal function. However, compared to ibuprofen, the negative impact of indomethacin is more pronounced.
p. 406-418
Received: 10 December 2009; in revised form: 28 January 2010 / Accepted: 1 February 2010 / Published: 4 February 2010
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Abstract: Interferons (IFNs) are a family of cytokines with potent antiproliferative, antiviral, and immunomodulatory properties. Much has been learned about IFNs and IFN-activated signaling cascades over the last 50 years. Due to their potent antitumor effects in vitro and in vivo , recombinant IFNs have been used extensively over the years, alone or in combination with other drugs, for the treatment of various malignancies. This review summarizes the current knowledge on IFN signaling components and pathways that are deregulated in human malignancies. The relevance of deregulation of IFN signaling pathways in defective innate immune surveillance and tumorigenesis are discussed.
(This article belongs to the Special Issue
Interferons )
p. 419-432
Received: 14 December 2009; in revised form: 29 January 2010 / Accepted: 2 February 2010 / Published: 4 February 2010
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Abstract: Appropriate control of blood pressure (BP) is essential for prevention of future cardiovascular events. However, BP control among treated hypertensive patients has been insufficient. Recently, the usefulness of self-measured BP at home (home BP measurement) for the management of hypertension has been reported in many studies. We evaluated BP control both at home and in the office among treated hypertensive patients in primary care settings in Japan (the J-HOME study). We found poor control of home and office BPs and clarified some factors affecting control. We also examined factors associated with the magnitude of the white-coat effect, the morning–evening BP difference, and home heart rate in this J-HOME study.
p. 433-440
Received: 13 January 2010; in revised form: 23 January 2010 / Accepted: 3 February 2010 / Published: 5 February 2010
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Abstract: Angiogenesis is regulated by the local balance between angiogenesis stimulators and inhibitors. A number of endogenous angiogenesis inhibitors have been found in the body. The origin of these inhibitors is mostly extrinsic to the vasculature. Recently, however, vascular endothelial cells themselves have been found to produce angiogenesis inhibitors including vasohibin-1. These intrinsic inhibitors are thought to regulate angiogenesis by an auto-regulatory or negative-feedback mechanism. This review will focus on vasohibin-1 produced by vascular endothelial cells and on its homologue, vasohibin-2.
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