Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan
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Review
[Development of the MITO-porter, a nano device for mitochondrial drug delivery via membrane fusion].
Many human diseases have been reported to be associated with mitochondrial dysfunction. Therefore, mitochondrial therapy would be expected to be useful and productive in the treatment of various diseases. To achieve such an innovative therapy, it will be necessary to deliver therapeutic agents into mitochondria. ⋯ Furthermore, when biomacromolecules were delivered using the DF-MITO-Porter to estimate the mitochondrial gene targeting of the carrier, the results confirmed that the MITO-Porter system has the potential for use in therapies aimed at mitochondrial DNA. This paper sumarizes our findings on mitochondrial drug delivery systems that are directed toward mitochondrial medicine development and mitochondrial gene therapy. It is expected that the MITO-Porter system will open new research areas in mitochondrial drug delivery systems and have a significant impact on the medical and life sciences.
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Fatty acids, one class of essential nutrients for humans, are an important source of energy and an essential component of cell membranes. They also function as signal transduction molecules in a variety of biological phenomena. The important functional role of fatty acids in both onset and suppression of pain has become increasingly apparent in recent years. ⋯ In the peripheral area, GPR40 is preferentially expressed in pancreatic β-cells and is known to relate to the secretion of hormone and peptides. On the other hand, even though this receptor is widely distributed in the central nervous system, reports studying the role and functions of GPR40 in the brain have not been found. In this review, we summarize the findings of our recent study about the long-chain fatty acid receptor GPR40 as a novel pain regulatory system.
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Pain control is very important since, even today, 20 million people suffer from neuropathic pain. Although many basic science and clinical researchers have made efforts to control pain, the mechanism of neuropathic pain is unfortunately still not fully understood. Morphine, a prototypical opioid, is a useful medicine to relieve severe pain. ⋯ In addition, morphine is not always effective in neuropathic pain. In this review we focus on: (1) the role of muscarinic receptors in the spinal cord and anterior cingulate cortex (ACC) in neuropathic pain, (2) how chemokine (C-C motif) ligand 1 (CCL-1) is involved in neuropathic pain, and (3) the novel mechanism of morphine tolerance. The findings in this study may cast new light on novel mechanism of neuropathic pain and development of novel clinical medicines in the future.
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The Guidelines for Management of Deep-seated Mycoses 2007 recommend the use of micafungin as a first-line agent for the treatment of candidemia. On the package insert, the recommended dose of micafungin is 50 mg/d. However, the Guidelines recommend a micafungin dose of 100-150 mg/d. ⋯ Among all patients, the efficacy rate of micafungin was found to be lower in patients infected by Candida parapsilosis as compared to those infected by other Candida species. However, among the patients who received ≥100 mg/d of micafungin, the efficacy rate in patients infected by Candida parapsilosis was equivalent to that of patients who were infected by other Candida species. Thus, based on the results of the present study, the optimal micafungin dose for the treatment of candidemia appears to range from 100 to 150 mg/d, as recommended by the Guidelines.
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Recently companion diagnostics (CoDx) have been getting more importance to promote personalized medicine which can improve not only the efficacy and safety of treatments but also increase the cost-effectiveness of medication. In July 2011, the U. S. ⋯ The Ministry of Health, Labour and Welfare in Japan also issued on July 1, 2013, their official notification regarding considerable items on co-development of CoDx if the drug needs its dedicate diagnostics test or medical device to predict the efficacy or adverse reaction to the drug. However, since many useful and predictive biomarkers may be discovered after commercial launch of the drug, the validātion process and regulatory criteria of CoDx including Laboratory Developed Test (LDT) should be changed in order to avoid biomarker test lag. The reimbursement system, moreover, is not always suitable to assess the clinical and technological values of CoDx and those systems need to be reformed for encouraging personalized medicine with co-developed CoDx.