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Pharmaceuticals, Volume 4, Issue 10 (October 2011) – 7 articles , Pages 1281-1399

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518 KiB  
Review
Lipothioureas as Lipids for Gene Transfection: A Review
by Marie Breton, Jeanne Leblond, Isabelle Tranchant, Daniel Scherman, Michel Bessodes, Jean Herscovici and Nathalie Mignet
Pharmaceuticals 2011, 4(10), 1381-1399; https://doi.org/10.3390/ph4101381 - 24 Oct 2011
Cited by 8 | Viewed by 7675
Abstract
Non-viral gene therapy requires innovative strategies to achieve higher transfection efficacy. A few years ago, our group proposed bioinspired lipids whoseinteraction with DNA was not based on ionic interactions, but on hydrogen bonds. We thusdeveloped lipids bearing a thiourea head which allowed an [...] Read more.
Non-viral gene therapy requires innovative strategies to achieve higher transfection efficacy. A few years ago, our group proposed bioinspired lipids whoseinteraction with DNA was not based on ionic interactions, but on hydrogen bonds. We thusdeveloped lipids bearing a thiourea head which allowed an interaction with DNAphosphates through hydrogen bonds. After a proof of concept with a lipid bearing threethiourea functions, a molecular and cellular screening was performed by varying all partsof the lipids: the hydrophobic anchor, the spacer, the linker, and the thiourea head. Twolipothiourea-based structures were identified as highly efficient in vitro transfecting agents.The lipothioureas were shown to reduce non specific interactions with cell membranes anddeliver their DNA content intracellularly more efficiently, as compared to cationiclipoplexes. These lipids could deliver siRNA efficiently and allowed specific cell targetingin vitro. In vivo, thiourea lipoplexes presented a longer retention time in the blood and lessaccumulation in the lungs after an intravenous injection in mice. They also inducedluciferase gene expression in muscle and tumor after local administration in mice.Therefore, these novel lipoplexes represent an excellent alternative to cationic lipoplexes astransfecting agents. In this review we will focus on the structure activity studies thatpermitted the identification of the two most efficient thiourea lipids. Full article
(This article belongs to the Special Issue Gene Therapy)
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543 KiB  
Review
Stem Cell Therapy: A New Treatment for Burns?
by Anna Arno, Alexandra H. Smith, Patrick H. Blit, Mohammed Al Shehab, Gerd G. Gauglitz and Marc G. Jeschke
Pharmaceuticals 2011, 4(10), 1355-1380; https://doi.org/10.3390/ph4101355 - 21 Oct 2011
Cited by 55 | Viewed by 13765
Abstract
Stem cell therapy has emerged as a promising new approach in almost every medicine specialty. This vast, heterogeneous family of cells are now both naturally (embryonic and adult stem cells) or artificially obtained (induced pluripotent stem cells or iPSCs) and their fates have [...] Read more.
Stem cell therapy has emerged as a promising new approach in almost every medicine specialty. This vast, heterogeneous family of cells are now both naturally (embryonic and adult stem cells) or artificially obtained (induced pluripotent stem cells or iPSCs) and their fates have become increasingly controllable, thanks to ongoing research in this passionate new field. We are at the beginning of a new era in medicine, with multiple applications for stem cell therapy, not only as a monotherapy, but also as an adjunct to other strategies, such as organ transplantation or standard drug treatment. Regrettably, serious preclinical concerns remain and differentiation, cell fusion, senescence and signalling crosstalk with growth factors and biomaterials are still challenges for this promising multidisciplinary therapeutic modality. Severe burns have several indications for stem cell therapy, including enhancement of wound healing, replacement of damaged skin and perfect skin regeneration – incorporating skin appendages and reduced fibrosis –, as well as systemic effects, such as inflammation, hypermetabolism and immunosuppression. The aim of this review is to describe well established characteristics of stem cells and to delineate new advances in the stem cell field, in the context of burn injury and wound healing. Full article
(This article belongs to the Special Issue Stem Cell Therapy)
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1239 KiB  
Review
Targeting the Large Subunit of Human Ribonucleotide Reductase for Cancer Chemotherapy
by Sanath R. Wijerathna, Md. Faiz Ahmad, Hai Xu, James W. Fairman, Andrew Zhang, Prem Singh Kaushal, Qun Wan, Jianying Kiser and Chris G. Dealwis
Pharmaceuticals 2011, 4(10), 1328-1354; https://doi.org/10.3390/ph4101328 - 13 Oct 2011
Cited by 13 | Viewed by 10078
Abstract
Ribonucleotide reductase (RR) is a crucial enzyme in de novo DNA synthesis, where it catalyses the rate determining step of dNTP synthesis. RRs consist of a large subunit called RR1 (α), that contains two allosteric sites and one catalytic site, and a small [...] Read more.
Ribonucleotide reductase (RR) is a crucial enzyme in de novo DNA synthesis, where it catalyses the rate determining step of dNTP synthesis. RRs consist of a large subunit called RR1 (α), that contains two allosteric sites and one catalytic site, and a small subunit called RR2 (β), which houses a tyrosyl free radical essential for initiating catalysis. The active form of mammalian RR is an anbm hetero oligomer. RR inhibitors are cytotoxic to proliferating cancer cells. In this brief review we will discuss the three classes of RR, the catalytic mechanism of RR, the regulation of the dNTP pool, the substrate selection, the allosteric activation, inactivation by ATP and dATP, and the nucleoside drugs that target RR. We will also discuss possible strategies for developing a new class of drugs that disrupts the RR assembly. Full article
(This article belongs to the Special Issue Advances in Drug Design)
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300 KiB  
Review
Neural Changes Developed during the Extinction of Cocaine Self-Administration Behavior
by Alejandro Higuera-Matas, Miguel Miguens, Nuria del Olmo, Carmen García-Lecumberri and Emilio Ambrosio
Pharmaceuticals 2011, 4(10), 1315-1327; https://doi.org/10.3390/ph4101315 - 13 Oct 2011
Cited by 2 | Viewed by 5629
Abstract
The high rate of recidivism in cocaine addiction after prolonged periods of abstinence poses a significant problem for the effective treatment of this condition. Moreover, the neurobiological basis of this relapse phenomenon remains poorly understood. In this review, we will discuss the evidence [...] Read more.
The high rate of recidivism in cocaine addiction after prolonged periods of abstinence poses a significant problem for the effective treatment of this condition. Moreover, the neurobiological basis of this relapse phenomenon remains poorly understood. In this review, we will discuss the evidence currently available regarding the neurobiological changes during the extinction of cocaine self-administration. Specifically, we will focus on alterations in the dopaminergic, opioidergic, glutamatergic, cholinergic, serotoninergic and CRF systems described in self-administration experiments and extinction studies after chronic cocaine administration. We will also discuss the differences related to contingent versus non-contingent cocaine administration, which highlights the importance of environmental cues on drug effects and extinction. The findings discussed in this review may aid the development of more effective therapeutic approaches to treat cocaine relapse. Full article
(This article belongs to the Special Issue Drug Abuse Targets)
416 KiB  
Review
Antimicrobial, Antiviral and Immunomodulatory Activity Studies of Pelargonium sidoides (EPs® 7630) in the Context of Health Promotion
by Herbert Kolodziej
Pharmaceuticals 2011, 4(10), 1295-1314; https://doi.org/10.3390/ph4101295 - 10 Oct 2011
Cited by 48 | Viewed by 14066
Abstract
Pelargonium species contribute significantly to the health care of a large population in the Southern African region, as part of a long-standing medical system intimately linked to traditional healing practices. Most notably, extracts of the roots of P. sidoides have commonly been applied [...] Read more.
Pelargonium species contribute significantly to the health care of a large population in the Southern African region, as part of a long-standing medical system intimately linked to traditional healing practices. Most notably, extracts of the roots of P. sidoides have commonly been applied for the treatment of dysentery and diarrhoea but only occasionally for respiratory complaints. Clinical trials have shown that a modern aqueous-ethanolic formulation of P. sidoides extracts (EPs® 7630) is an efficacious treatment for disorders of the respiratory tract, for example bronchitis and sinusitis. It should be noted that EPs® 7630 is the most widely investigated extract and therefore is the focus of this review. In order to provide a rationale for its therapeutic activity extracts have been evaluated for antibacterial activity and for their effects on non-specific immune functions. Only moderate direct antibacterial capabilities against a spectrum of bacteria, including Mycobacteria strains, have been noted. In contrast, a large body of in vitro studies has provided convincing evidence for an anti-infective principle associated with activation of the non-specific immune system. Interestingly, significant inhibition of interaction between bacteria and host cells, a key to the pathogenesis of respiratory tract infections, has emerged from recent studies. In addition, antiviral effects have been demonstrated, including inhibition of the replication of respiratory viruses and the enzymes haemagglutinin and neuraminidase. Besides, an increase of cilliary beat frequency of respiratory cells may contribute to the beneficial effects of P. sidoides extracts. This example provides a compelling argument for continuing the exploration of Nature and traditional medical systems as a source of therapeutically useful herbal medicines. Full article
(This article belongs to the Special Issue Phytomedicine)
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123 KiB  
Correction
Novo, S. et al. Aliskiren: Just a New Drug for Few Selected Patients or an Innovative Molecule Predestinated to Replace Arbs and Ace-Inhibitors? Pharmaceuticals 2009, 2, 118-124
by Salvatore Novo, Giovanni Fazio, Elena Raccuglia, Antonino Mignano and Giuseppina Novo
Pharmaceuticals 2011, 4(10), 1293-1294; https://doi.org/10.3390/ph4101293 - 30 Sep 2011
Viewed by 4853
Abstract
In the published version “Paladini et al. reported that aliskiren 300 mg provided a sustained BP-lowering effect beyond the 24-h dosing interval, with a significantly smaller loss of BP-lowering effect in the 24-48 h period after dose than irbesartan 300 mg or [...] Read more.
In the published version “Paladini et al. reported that aliskiren 300 mg provided a sustained BP-lowering effect beyond the 24-h dosing interval, with a significantly smaller loss of BP-lowering effect in the 24-48 h period after dose than irbesartan 300 mg or ramipril 10 mg [25]”. Paladini et al. should be Palatini et al., and the cited reference number should be [10], not [25].. In the sentence, “Early data suggest a role for aliskiren in preventing end-organ damage but, considering the ONTARGET results with an ACE-I-ARB combination, outcome studies are needed before the use of aliskiren can be recommended in combination with other RAS inhibitors [18–30]” one more citation number was added [5], so the revised sentence is “Early data suggest a role for aliskiren in preventing end-organ damage but, considering the ONTARGET results with an ACE-I-ARB combination, outcome studies are needed before the use of aliskiren can be recommended in combination with other RAS inhibitors [5,18–30]”. [...] Full article
610 KiB  
Article
Degradable Cross-Linked Nanoassemblies as Drug Carriers for Heat Shock Protein 90 Inhibitor 17-N-Allylamino-17-demethoxy-geldanamycin
by Andrei Ponta, Shanjida Akter and Younsoo Bae
Pharmaceuticals 2011, 4(10), 1281-1292; https://doi.org/10.3390/ph4101281 - 26 Sep 2011
Cited by 6 | Viewed by 6498
Abstract
Cross-linked nanoassemblies (CNAs) with a degradable core were prepared for sustained release of 17-N-allylamino-17-demethoxygeldanamycin (17-AAG), a potent inhibitor of heat shock protein 90 (HSP90). The particle size of CNAs ranged between 100 and 250 nm, which changed depending on the cross-linking yields and [...] Read more.
Cross-linked nanoassemblies (CNAs) with a degradable core were prepared for sustained release of 17-N-allylamino-17-demethoxygeldanamycin (17-AAG), a potent inhibitor of heat shock protein 90 (HSP90). The particle size of CNAs ranged between 100 and 250 nm, which changed depending on the cross-linking yields and drug entrapment method. CNAs with a 1% cross-linking yield entrapped 17-AAG in aqueous solutions, yet degraded in 3 hrs. CNAs entrapped 5.2 weight% of 17-AAG as the cross-linking yield increased to 10%, retaining more than 80% of particles for 24 hrs. CNAs with drugs entrapped after the cross-linking reactions were 100 nm and remained stable in both pH 7.4 and 5.0, corresponding to the physiological, tumoral, and intracellular environments. Drug was completely released from CNAs in 48 hrs, which would potentially maximize drug delivery and release efficiency within tumor tissues. Drug release patterns were not negatively affected by changing the cross-linking yields of CNAs. CNAs entrapping 17-AAG suppressed the growth of human non-small cell lung cancer A549 cells as equally effective as free drugs. The results demonstrated that CNAs would be a promising formulation that can be used in aqueous solutions for controlled delivery and release of 17-AAG. Full article
(This article belongs to the Special Issue Hsp90 Inhibitors)
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