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Delivery Approaches (delivery + approach)
Selected AbstractsMalonyl-CoA decarboxylase (MCD) is differentially regulated in subcellular compartments by 5,AMP-activated protein kinase (AMPK)FEBS JOURNAL, Issue 13 2004AMPK by adenoviral gene transfer technique, Studies using H9c2 cells overexpressing MCD Malonyl-CoA, a potent inhibitor of carnitine pamitoyl transferase-I (CPT-I), plays a pivotal role in fuel selection in cardiac muscle. Malonyl-CoA decarboxylase (MCD) catalyzes the degradation of malonyl-CoA, removes a potent allosteric inhibition on CPT-I and thereby increases fatty acid oxidation in the heart. Although MCD has several Ser/Thr phosphorylation sites, whether it is regulated by AMP-activated protein kinase (AMPK) has been controversial. We therefore overexpressed MCD (Ad.MCD) and constitutively active AMPK (Ad.CA-AMPK) in H9c2 cells, using an adenoviral gene delivery approach in order to examine if MCD is regulated by AMPK. Cells infected with Ad.CA-AMPK demonstrated a fourfold increase in AMPK activity as compared with control cells expressing green fluorescent protein (Ad.GFP). MCD activity increased 40- to 50-fold in Ad.MCD + Ad.GFP cells when compared with Ad.GFP control. Co-expressing AMPK with MCD further augmented MCD expression and activity in Ad.MCD + Ad.CA-AMPK cells compared with the Ad.MCD + Ad.GFP control. Subcellular fractionation further revealed that 54.7 kDa isoform of MCD expression was significantly higher in cytosolic fractions of Ad.MCD + Ad.CA-AMPK cells than of the Ad.MCD +Ad.GFP control. However, the MCD activities in cytosolic fractions were not different between the two groups. Interestingly, in the mitochondrial fractions, MCD activity significantly increased in Ad.MCD + Ad.CA-AMPK cells when compared with Ad.MCD + Ad.GFP cells. Using phosphoserine and phosphothreonine antibodies, no phosphorylation of MCD by AMPK was observed. The increase in MCD activity in mitochondria-rich fractions of Ad.MCD + Ad.CA-AMPK cells was accompanied by an increase in the level of the 50.7 kDa isoform of MCD protein in the mitochondria. This differential regulation of MCD expression and activity in the mitochondria by AMPK may potentially regulate malonyl-CoA levels at sites nearby CPT-I on the mitochondria. [source] Investigating customer perceptions of refillable packaging and assessing business drivers and barriers to their usePACKAGING TECHNOLOGY AND SCIENCE, Issue 6 2009V. A. Lofthouse Abstract A collaborative UK government-funded research project drawing on the design and sustainability expertise of the Department of Design and Technology at Loughborough University and the sustainability and product bank functions at The Boots Company set out to investigate the potential that refillable packaging systems can offer the consumer and the environment. In the past, refills have generally been categorized under one general heading and often branded as a failure. However, early in the project, the team identified that by taking a creative approach to interpreting refills, there are actually a wide range of different types of refills that can be differentiated with respect to their delivery approach and level of consumer/business interaction. Once these had been identified, collated and categorized, the team set out to investigate the consumer perceptions, and the business barriers and drivers found to influence the adoption and success of a number of different types of refillable packaging. This paper reports on those findings. It concludes that differentiating between refill types holds the key to developing more suitable and more successful refillable packaging systems as positive and negative attributes can be more accurately identified and responded to. Copyright © 2009 John Wiley & Sons, Ltd. [source] Intramuscular SP1017-formulated DNA electrotransfer enhances transgene expression and distributes hHGF to different rat tissuesTHE JOURNAL OF GENE MEDICINE, Issue 1 2004Marta Riera Abstract Background The systemic administration of a therapeutic protein is a common approach for the treatment of multiple disorders. Intramuscular (i.m.) injection of plasmids, followed by electroporation, has been shown to facilitate naked DNA gene transfer in skeletal muscle allowing proteins to be produced and secreted at therapeutically relevant levels. Methods Plasmid DNA, unformulated or formulated with the non-ionic carrier SP1017, was injected at the rat tibialis anterior muscle followed by the application of electric pulses. Follow-up of protein expression was measured. Results In our study we report that the non-ionic carrier SP1017 significantly increases transgene expression in rat muscle after the i.m. injection of a formulated-pCMV, plasmid followed by electroporation. Such increased expression was observed after delivering square-wave unipolar electric pulses at two different field strengths: low (110 V/cm) and high (175 V/cm). Moreover, elevated secreted placental alkaline phosphatase (SEAP) plasma levels were achieved with low-voltage (110 V/cm) electroporation. Our results also show that human hepatocyte growth factor (hHGF) can be produced from rat muscle and delivered to blood circulation at a biologically active level after a single i.m. injection of an SP1017-formulated plasmid (pCMV/hHGF) followed by electroporation. Tissue distribution studies mostly identified hHGF in the liver, but it was also found in the kidneys and lungs suggesting that here too the HGF could be of therapeutic benefit. Conclusions Our results indicate that SP1017 enhances the expression of electrotransferred genes. Such a delivery approach could prove an efficient method for the systemic production of therapeutic proteins. Copyright © 2003 John Wiley & Sons, Ltd. [source] FINDING AUTONOMY IN BIRTHBIOETHICS, Issue 1 2009THE OBSTETRICS AND GYNECOLOGY RISK RESEARCH GROUP: ABSTRACT Over the last several years, as cesarean deliveries have grown increasingly common, there has been a great deal of public and professional interest in the phenomenon of women ,choosing' to deliver by cesarean section in the absence of any specific medical indication. The issue has sparked intense conversation, as it raises questions about the nature of autonomy in birth. Whereas mainstream bioethical discourse is used to associating autonomy with having a large array of choices, this conception of autonomy does not seem adequate to capture concerns and intuitions that have a strong grip outside this discourse. An empirical and conceptual exploration of how delivery decisions ought to be negotiated must be guided by a rich understanding of women's agency and its placement within a complicated set of cultural meanings and pressures surrounding birth. It is too early to be ,for' or ,against' women's access to cesarean delivery in the absence of traditional medical indications , and indeed, a simple pro- or con- position is never going to do justice to the subtlety of the issue. The right question is not whether women ought to be allowed to choose their delivery approach but, rather, taking the value of women's autonomy in decision-making around birth as a given, what sorts of guidelines, practices, and social conditions will best promote and protect women's full inclusion in a safe and positive birth process. [source] PEI,PEG,Chitosan-Copolymer-Coated Iron Oxide Nanoparticles for Safe Gene Delivery: Synthesis, Complexation, and TransfectionADVANCED FUNCTIONAL MATERIALS, Issue 14 2009Forrest M. Kievit Abstract Gene therapy offers the potential of mediating disease through modification of specific cellular functions of target cells. However, effective transport of nucleic acids to target cells with minimal side effects remains a challenge despite the use of unique viral and non-viral delivery approaches. Here, a non-viral nanoparticle gene carrier that demonstrates effective gene delivery and transfection both in vitro and in vivo is presented. The nanoparticle system (NP,CP,PEI) is made of a superparamagnetic iron oxide nanoparticle (NP), which enables magnetic resonance imaging, coated with a novel copolymer (CP,PEI) comprised of short chain polyethylenimine (PEI) and poly(ethylene glycol) (PEG) grafted to the natural polysaccharide, chitosan (CP), which allows efficient loading and protection of the nucleic acids. The function of each component material in this nanoparticle system is illustrated by comparative studies of three nanoparticle systems of different surface chemistries, through material property characterization, DNA loading and transfection analyses, and toxicity assessment. Significantly, NP,CP,PEI demonstrates an innocuous toxic profile and a high level of expression of the delivered plasmid DNA in a C6 xenograft mouse model, making it a potential candidate for safe in vivo delivery of DNA for gene therapy. [source] Applications of Sleeping Beauty transposons for nonviral gene therapyIUBMB LIFE, Issue 6 2007Hanzhong Liu Abstract Virus-based gene therapy has advanced to clinical trials; however, this approach may result in serious adverse events including oncogenesis and the possibility of triggering fatal immune responses. Nonviral gene delivery approaches have a better safety profile, but their in vivo application has been largely limited in the past due to their inefficient delivery into cells and lack of stable chromosomal integration that is necessary for long-term therapeutic benefit. However, recent advances suggest that the use of Sleeping Beauty transposons, a novel integrating nonviral vector system, are capable of achieving long-lasting therapeutic levels of transgene expression in preclinical settings. These observations and other ongoing relevant studies may unlock the therapeutic potential of nonviral gene therapy for human diseases. iubmb Life, 59: 1 - 6, 2007 [source] Spatiotemporal Delivery Strategies for Promoting Musculoskeletal Tissue Regeneration,,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 9 2009Robert E Guldberg PhD Abstract A primary regenerative medicine strategy is to stimulate or augment endogenous repair mechanisms that promote functional restoration of damaged or degenerated tissues. There is increasing evidence that maximizing the potency of tissue regenerative therapies will require design and development of delivery approaches that provide controlled spatiotemporal release of key signaling molecules. Guidance on which factors to deliver and the timing of delivery is emerging from advances in understanding of critical pathways involved in the development of integrated musculoskeletal tissues. A broad range of biomaterials-based deployment technologies are becoming available that allow controlled spatial presentation and release kinetics of biological cues. The purpose of this perspective article is to review promising spatiotemporal delivery strategies designed to promote functional tissue regeneration with an emphasis on vascularized bone repair. [source] The manager's role in mobilizing and nurturing development: entrenched and engaged approaches to changeJOURNAL OF NURSING MANAGEMENT, Issue 3 2010BA RGN RHV HVL RNT PGCE, SUSAN M. CARR PhD carr s.m. & clarke c.l. (2010) Journal of Nursing Management 18, 332,338 The manager's role in mobilizing and nurturing development: entrenched and engaged approaches to change Aims, Drawing on findings from the evaluation of a Health Action Zone (HAZ), this paper explores the manager's role in promoting and nurturing learning. Background, Initiating practice development is a core function of the manager's role. Learning must be nurtured to reach beyond individual to organizational learning and address knowledge exchange as well as creation. In the United Kingdom, HAZs were established to reduce health inequalities. They embraced a variety of service delivery approaches, all with an emphasis on developing new ways of working and innovation. Methods, Qualitative interviews of the HAZ coordinators, performance manager and staff delivering services. Results, Two alternative ways of engagement and entrenchment to practice were identified to developing new ways of working and learning from experience. Conclusions, Development of sustainable and enduring structures which facilitate learning at both individual and organizational levels are key to utilization of knowledge and accumulation of learning. Implications for nursing management, When entrenched and engaged experiential learning in practice are pursued, the role of the manager as a catalyst needs to be highlighted. A tool is proposed to facilitate reflection and promote action plan development. This tool has potential general application, but our experience is that it makes a specific contribution to public health and primary care. [source] Alternative drug delivery approaches for the therapy of inflammatory bowel diseaseJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 8 2008Yvette Meissner Abstract This article shall give an overview on drug delivery systems for new therapeutic strategies in the treatment of inflammatory bowel disease. The various features of the different approaches allowing locally restricted drug delivery to the inflamed colon are discussed including the main physiological and pathophysiological limitations for the different systems. Conventional drug delivery systems are tightly adapted from developments for colonic delivery by oral administration triggered by release mechanisms owing to the physiological environment that these systems encounter in the colonic region. The newer developments in this context aim for an increased selectivity of drug delivery by targeting mechanisms which have a closer relation to pathophysiological particularities of the disease. Therefore, we were focused especially on new strategies for such treatment including liposomal formulations, cyclodextrins, micro- or nanoparticles, viral gene therapy approaches, and others. Effective and selective delivery even of an otherwise nonspecifically acting drug could provide new therapeutic pathways in the treatment of inflammatory bowel disease. © 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 97: 2878,2891, 2008 [source] Design of anticancer prodrugs for reductive activationMEDICINAL RESEARCH REVIEWS, Issue 1 2009Yu Chen Abstract Anticancer prodrugs designed to target specifically tumor cells should increase therapeutic effectiveness and decrease systemic side effects in the treatment of cancer. Over the last 20 years, significant advances have been made in the development of anticancer prodrugs through the incorporation of triggers for reductive activation. Reductively activated prodrugs have been designed to target hypoxic tumor tissues, which are known to overexpress several endogenous reductive enzymes. In addition, exogenous reductive enzymes can be delivered to tumor cells through fusion with tumor-specific antibodies or overexpressed in tumor cells through gene delivery approaches. Many anticancer prodrugs have been designed to use both the endogenous and exogenous reductive enzymes for target-specific activation and these prodrugs often contain functional groups such as quinones, nitroaromatics, N-oxides, and metal complexes. Although no new agents have been approved for clinical use, several reductively activated prodrugs are in various stages of clinical trial. This review mainly focuses on the medicinal chemistry aspects of various classes of reductively activated prodrugs including design principles, structure-activity relationships, and mechanisms of activation and release of active drug molecules. © 2008 Wiley Periodicals, Inc. Med Res Rev, 29, No. 1, 29,64, 2009 [source] Restoration of central nervous system ,- N -acetylglucosaminidase activity and therapeutic benefits in mucopolysaccharidosis IIIB mice by a single intracisternal recombinant adeno-associated viral type 2 vector deliveryTHE JOURNAL OF GENE MEDICINE, Issue 7 2010Haiyan Fu Abstract Background Finding efficient central nervous system (CNS) delivery approaches has been the major challenge facing therapeutic development for treating diseases with global neurological manifestation, such as mucopolysaccharidosis (MPS) IIIB, a lysosomal storage disease, caused by autosomal recessive defect of ,- N -acetylglucosaminidase (NaGlu). Previously, we developed an approach, intracisternal (i.c.) injection, to deliver recombinant adeno-associated viral (rAAV) vector to the CNS of mice, leading to a widespread periventricular distribution of transduction. Methods In the present study, we delivered rAAV2 vector expressing human NaGlu into the CNS of MPS IIIB mice by an i.c. injection approach, to test its therapeutic efficacy and feasibility for treating the neurological manifestation of the disease. Results We demonstrated significant functional neurological benefits of a single i.c. vector infusion in adult MPS IIIB mice. The treatment slowed the disease progression by mediating widespread recombinant NaGlu expression in the CNS, resulting in the reduction of brain lysosomal storage pathology, significantly improved cognitive function and prolonged survival. However, persisting motor function deficits suggested that pathology in areas outside the CNS contributes to the MPS IIIB behavioral phenotype. The therapeutic benefit of i.c. rAAV2 delivery was dose-dependent and could be attribute solely to the CNS transduction because the procedure did not lead to detectable transduction in somatic tissues. Conclusions A single IC rAAV2 gene delivery is functionally beneficial for treating the CNS disease of MPS IIIB in mice. It is immediately clinically translatable, with the potential of improving the quality of life for patients with MPS IIIB. Copyright © 2010 John Wiley & Sons, Ltd. [source] | ||||||||||||||||