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Pharmaceuticals, Volume 6, Issue 1 (January 2013) – 7 articles , Pages 1-123

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241 KiB  
Review
Neurotransmitter CART as a New Therapeutic Candidate for Parkinson’s Disease
by Peizhong Mao, Charles K. Meshul, Philippe Thuillier and P. Hemachandra Reddy
Pharmaceuticals 2013, 6(1), 108-123; https://doi.org/10.3390/ph6010108 - 18 Jan 2013
Cited by 15 | Viewed by 7176
Abstract
Parkinson’s disease (PD) is one of the most common neurodegenerative diseases. To date, there is no effective treatment that halts its progression. Increasing evidence indicates that mitochondria play an important role in the development of PD. Hence mitochondria-targeted approaches or agents may have [...] Read more.
Parkinson’s disease (PD) is one of the most common neurodegenerative diseases. To date, there is no effective treatment that halts its progression. Increasing evidence indicates that mitochondria play an important role in the development of PD. Hence mitochondria-targeted approaches or agents may have therapeutic promise for treatment of the disease. Neuropeptide CART (cocaine-amphetamine-regulated transcript), a hypothalamus and midbrain enriched neurotransmitter with an antioxidant property, can be found in mitochondria, which is the main source of reactive oxygen species. Systemic administration of CART has been found to ameliorate dopaminergic neuronal loss and improve motor functions in a mouse model of PD. In this article, we summarize recent progress in studies investigating the relationship between CART, dopamine, and the pathophysiology of PD, with a focus on mitochondria-related topics. Full article
(This article belongs to the Special Issue Mitochondrial Drugs for Neurodegenerative Diseases)
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222 KiB  
Review
Nanoparticle-Based Delivery of RNAi Therapeutics: Progress and Challenges
by Jiehua Zhou, Ka-To Shum, John C. Burnett and John J. Rossi
Pharmaceuticals 2013, 6(1), 85-107; https://doi.org/10.3390/ph6010085 - 16 Jan 2013
Cited by 166 | Viewed by 17153
Abstract
RNA interference (RNAi) is an evolutionarily conserved, endogenous process for post-transcriptional regulation of gene expression. Although RNAi therapeutics have recently progressed through the pipeline toward clinical trials, the application of these as ideal, clinical therapeutics requires the development of safe and effective delivery [...] Read more.
RNA interference (RNAi) is an evolutionarily conserved, endogenous process for post-transcriptional regulation of gene expression. Although RNAi therapeutics have recently progressed through the pipeline toward clinical trials, the application of these as ideal, clinical therapeutics requires the development of safe and effective delivery systems. Inspired by the immense progress with nanotechnology in drug delivery, efforts have been dedicated to the development of nanoparticle-based RNAi delivery systems. For example, a precisely engineered, multifunctional nanocarrier with combined passive and active targeting capabilities may address the delivery challenges for the widespread use of RNAi as a therapy. Therefore, in this review, we introduce the major hurdles in achieving efficient RNAi delivery and discuss the current advances in applying nanotechnology-based delivery systems to overcome the delivery hurdles of RNAi therapeutics. In particular, some representative examples of nanoparticle-based delivery formulations for targeted RNAi therapeutics are highlighted. Full article
(This article belongs to the Special Issue RNAi-Based Therapeutics)
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184 KiB  
Review
Clevidipine for Perioperative Blood Pressure Control in Infants and Children
by Joseph D. Tobias, David B. Tulman and Sergio D. Bergese
Pharmaceuticals 2013, 6(1), 70-84; https://doi.org/10.3390/ph6010070 - 15 Jan 2013
Cited by 13 | Viewed by 6682
Abstract
Various pharmacologic agents have been used for perioperative BP control in pediatric patients, including sodium nitroprusside, nitroglycerin, β-adrenergic antagonists, fenoldopam, and calcium channel antagonists. Of the calcium antagonists, the majority of the clinical experience remains with the dihydropyridine nicardipine. Clevidipine is a short-acting, [...] Read more.
Various pharmacologic agents have been used for perioperative BP control in pediatric patients, including sodium nitroprusside, nitroglycerin, β-adrenergic antagonists, fenoldopam, and calcium channel antagonists. Of the calcium antagonists, the majority of the clinical experience remains with the dihydropyridine nicardipine. Clevidipine is a short-acting, intravenous calcium channel antagonist of the dihydropyridine class. It undergoes rapid metabolism by non-specific blood and tissue esterases with a half-life of less than 1 minute. As a dihydropyridine, its cellular and end-organ effects parallel those of nicardipine. The clevidipine trials in the adult population have demonstrated efficacy in rapidly controlling BP in various clinical scenarios with a favorable adverse effect profile similar to nicardipine. Data from large clinical trials regarding the safety and efficacy of clevidipine in children is lacking. This manuscript aims to review the commonly used pharmacologic agents for perioperative BP control in children, discuss the role of calcium channel antagonists such as nicardipine, and outline the preliminary data regarding clevidipine in the pediatric population. Full article
(This article belongs to the Special Issue Calcium Antagonists)
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Article
A Potent (R)-alpha-bis-lipoyl Derivative Containing 8-Hydroxyquinoline Scaffold: Synthesis and Biological Evaluation of Its Neuroprotective Capabilities in SH-SY5Y Human Neuroblastoma Cells
by Ivana Cacciatore, Erika Fornasari, Leonardo Baldassarre, Catia Cornacchia, Stefania Fulle, Ester Sara Di Filippo, Tiziana Pietrangelo and Francesco Pinnen
Pharmaceuticals 2013, 6(1), 54-69; https://doi.org/10.3390/ph6010054 - 07 Jan 2013
Cited by 95 | Viewed by 8953
Abstract
A novel bis-lipoyl derivative containing 8-hydroxyquinoline scaffold (LA-HQ-LA, 5) was synthesized as a new multifunctional drug candidate with antioxidant, chelant, and neuroprotective properties for the treatment of neurodegenerative diseases. We have investigated the potential effectiveness of LA-HQ-LA against the cytotoxicity induced by [...] Read more.
A novel bis-lipoyl derivative containing 8-hydroxyquinoline scaffold (LA-HQ-LA, 5) was synthesized as a new multifunctional drug candidate with antioxidant, chelant, and neuroprotective properties for the treatment of neurodegenerative diseases. We have investigated the potential effectiveness of LA-HQ-LA against the cytotoxicity induced by 6-OHDA and H2O2 on human neuroblastoma SH-SY5Y cell line. Our outcomes showed that LA-HQ-LA resulted in significant neuroprotective and antioxidant effects against H2O2- and 6-OHDA-induced neurotoxicity in human neuroblastoma SH-SY5Y cells, as assessed by MTT assay. In particular, it showed potent neuroprotective effects against 6-OHDA in RA/PMA differentiated cells at all the tested concentrations. Full article
(This article belongs to the Special Issue CNS-Drugs and Therapy)
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223 KiB  
Concept Paper
The Potential Role of Cell Penetrating Peptides in the Intracellular Delivery of Proteins for Therapy of Erythroid Related Disorders
by Lefkothea C. Papadopoulou and Asterios S. Tsiftsoglou
Pharmaceuticals 2013, 6(1), 32-53; https://doi.org/10.3390/ph6010032 - 07 Jan 2013
Cited by 95 | Viewed by 7564
Abstract
The erythroid related disorders (ERDs) represent a large group of hematological diseases, which in most cases are attributed either to the deficiency or malfunction of biosynthetic enzymes or oxygen transport proteins. Current treatments for these disorders include histo-compatible erythrocyte transfusions or allogeneic hematopoietic [...] Read more.
The erythroid related disorders (ERDs) represent a large group of hematological diseases, which in most cases are attributed either to the deficiency or malfunction of biosynthetic enzymes or oxygen transport proteins. Current treatments for these disorders include histo-compatible erythrocyte transfusions or allogeneic hematopoietic stem cell (HSC) transplantation. Gene therapy delivered via suitable viral vectors or genetically modified HSCs have been under way. Protein Transduction Domain (PTD) technology has allowed the production and intracellular delivery of recombinant therapeutic proteins, bearing Cell Penetrating Peptides (CPPs), into a variety of mammalian cells. Remarkable progress in the field of protein transduction leads to the development of novel protein therapeutics (CPP-mediated PTs) for the treatment of monogenetic and/or metabolic disorders. The “concept” developed in this paper is the intracellular protein delivery made possible via the PTD technology as a novel therapeutic intervention for treatment of ERDs. This can be achieved via four stages including: (i) the production of genetically engineered human CPP-mediated PT of interest, since the corresponding native protein either is missing or is mutated in the erythroid progenitor cell (ErPCs) or mature erythrocytes of patients; (ii) isolation of target cells from the peripheral blood of the selected patients; (iii) ex vivo transduction of cells with the CPP-mediated PT of interest; and (iv) re-administration of the successfully transduced cells back into the same patients. Full article
(This article belongs to the Special Issue Cell-penetrating Peptides 2012)
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Article
Stability of Recombinant Tissue Plasminogen Activator at −30 °C over One Year
by Abdulmalik Alkatheri
Pharmaceuticals 2013, 6(1), 25-31; https://doi.org/10.3390/ph6010025 - 02 Jan 2013
Cited by 33 | Viewed by 5695
Abstract
Recombinant tissue plasminogen activator (rt-PA) is used to restore patency and avoid inadvertent removal of peripheral and central venous catheters. rt-PA was reconstituted (1 mg/mL) then cryopreserved at −30 °C for 1, 2, 3, 6, 8, and 12 months and, then its stability [...] Read more.
Recombinant tissue plasminogen activator (rt-PA) is used to restore patency and avoid inadvertent removal of peripheral and central venous catheters. rt-PA was reconstituted (1 mg/mL) then cryopreserved at −30 °C for 1, 2, 3, 6, 8, and 12 months and, then its stability was determined. After cryopreservation for one and two months, rt-PA kept more than 95% of its activity compared to standard samples, while cryopreservation for three months caused 8% loss of activity. However, after cryopreservation for six months or more, rt-PA retained only 87.5% or less activity compared to standard samples. Therefore, it is recommended that reconstituted rt-PA be cryopreserved at −30 °C for a maximum period of three months. Full article
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Review
Strategies To Modulate Heritable Epigenetic Defects in Cellular Machinery: Lessons from Nature
by Ganesh N. Pandian and Hiroshi Sugiyama
Pharmaceuticals 2013, 6(1), 1-24; https://doi.org/10.3390/ph6010001 - 27 Dec 2012
Cited by 17 | Viewed by 9214
Abstract
Natural epigenetic processes precisely orchestrate the intricate gene network by expressing and suppressing genes at the right place and time, thereby playing an essential role in maintaining the cellular homeostasis. Environment-mediated alteration of this natural epigenomic pattern causes abnormal cell behavior and shifts [...] Read more.
Natural epigenetic processes precisely orchestrate the intricate gene network by expressing and suppressing genes at the right place and time, thereby playing an essential role in maintaining the cellular homeostasis. Environment-mediated alteration of this natural epigenomic pattern causes abnormal cell behavior and shifts the cell from the normal to a diseased state, leading to certain cancers and neurodegenerative disorders. Unlike heritable diseases that are caused by the irreversible mutations in DNA, epigenetic errors can be reversed. Inheritance of epigenetic memory is also a major concern in the clinical translation of the Nobel Prize-winning discovery of induced pluripotent stem cell technology. Consequently, there is an increasing interest in the development of novel epigenetic switch-based therapeutic strategies that could potentially restore the heritable changes in epigenetically inherited disorders. Here we give a comprehensive overview of epigenetic inheritance and suggest the prospects of therapeutic gene modulation using epigenetic-based drugs, in particular histone deacetylase inhibitors. This review suggests that there is a need to develop therapeutic strategies that effectively mimic the natural environment and include the ways to modulate the gene expression at both the genetic and epigenetic levels. The development of tailor-made small molecules that could epigenetically alter DNA in a sequence-specific manner is a promising approach for restoring defects in an altered epigenome and may offer a sustainable solution to some unresolved clinical issues. Full article
(This article belongs to the Special Issue Epigenetic Therapies and Biomarkers)
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