Degeneration of peripheral motor axons is a common feature of several debilitating diseases including complicated forms of hereditary spastic paraplegia. One such form is caused by loss of the mitochondrial energy-dependent protease paraplegin. Paraplegin-deficient mice display a progressive degeneration in several axonal tracts, characterized by the accumulation of morphological abnormal ...

The present invention is directed to a method of transducing mammalian cochlear cells, more preferably, cochlear hair cells and support cells. The method involves the delivery of adeno-associated virus (AAV) to a target mammalian cochlear cell. The AAV co...

Anti-beta-amyloid (A?) immunotherapy is effective in removing brain A?, but has shown to be associated with detrimental effects. We have demonstrated that Adeno-associated virus (AAV)-mediated delivery of an anti-A? single chain antibody (scFv) gene was effective in clearing brain A? without eliciting any inflammatory side effects in old APP(Swe)/PS1dE9 ...

to late-onset obesity, including leptin resistance [29], the role of dopaminergic neurons has not been- cially effective in reducing obesity when other agents have failed such as in the leptin resistant aged injection. Brain Res 1997;747:92�102. [20] Li H, Matheny M, Nicolson M, T�umer N, Scarpace PJ. Leptin gene

Gene therapy is a potential route for the delivery of secreted therapeutic proteins, but pharmacologic control of expression will generally be required for optimal safety and efficacy. Previous attempts to achieve regulated expression in large animal models have been thwarted by transient expression or immune responses to regulatory proteins. We evaluated the ability of the ...

In the present study we demonstrate that adeno-associated virus (AAV)-mediated anti-DR5 (death receptor 5) mouse-human chimeric antibody (shorten as Adximab) expression significantly suppressed tumor cell growth by inducing apoptosis both in vitro and in vivo. The viral-expressed and cell-secreted Adximab efficiently bound DR5 with an affinity of 0.7nM and induced apoptosis of ...

... IM) using needle injection with intra ... compared to IM immunization In ... Descriptors : *INTRAMUSCULAR INJECTIONS, *IMMUNIZATION, *VACCINES ...

Progression in R6/1 Huntington's Disease Transgenic Mice Edgardo Rodriguez-Lebron,1,* Eileen M. Denovan://users.mbi.ufl.edu/mandel/mandel.html. Available online 12 July 2005 Huntington's disease (HD) is a fatal neurodegenerative disorder caused, transcriptional dysregulation, polyglutamine, neuronal intranuclear inclusions INTRODUCTION HuntingtonTs disease

Original reports of adeno-associated virus (AAV) vector-mediated gene transfer to the muscle resulted in high-level ?-galactosidase (?-gal) expression and the promise of a viral vector that was largely nonimmunogenic. Subsequent attempts to utilize these vectors for genetic vaccination, however, demonstrated that it was possible to activate cellular and humoral immunity to AAV-encoded antigens. ...

Adeno-associated virus (AAV)-mediated gene replacement for lysosomal disorders have been spurred by the ability of some serotypes to efficiently transduce neurons in the brain and by the ability of lysosomal enzymes to cross-correct among cells. Here, we explored enzyme replacement therapy in a knock-out mouse model of congenital neuronal ceroid lipofuscinosis (NCL), the most ...

INTRODUCTION: Glycogen storage disease (GSD) type Ia and Ib are disorders of impaired glucose homeostasis affecting the liver and kidney. GSD-Ib also affects neutrophils. Current dietary therapies cannot prevent long-term complications. In animal studies, recombinant adeno-associated virus (rAAV) vector-mediated gene therapy can correct or minimize multiple aspects of the disorders, offering hope ...

Neurotrophic factors such as pituitary adenylate cyclase activating polypeptide (PACAP38) are promising therapeutics for neurodegenerative diseases. However, delivery of trophic factors into brain neurons remains a challenge. The objective of this study is to determine whether adeno-associated virus (AAV) can mediate PACAP38 gene delivery into neurons in ...

The development of a nonhuman primate (NHP) model for vascular delivery of therapeutic transgenes with adeno-associated viral (AAV) vectors is crucial for successfully treating muscular dystrophies. Current animal models for Duchenne muscular dystrophy (DMD) gene therapy have species limitations related to assessing function, immune response, and distribution of the micro- and ...

Inherited retinal disease, which includes conditions such as retinitis pigmentosa (RP), affects about 1/3000 of the population in the Western world. It is characterized by gradual loss of vision and results from mutations in any one of 60 or so different genes. There are currently no effective treatments, but many of the genes have now been identified and their functions elucidated, providing a ...

Adeno-associated virus (AAV) vectors are effective gene delivery vehicles mediating long-lasting transgene expression. Data from a clinical trial of AAV2-mediated hepatic transfer of the Factor IX gene (F9) into hemophilia B subjects suggests that CTL responses against AAV capsid can eliminate transduced hepatocytes and prevent long-term F9 expression. However, the capacity of ...

Stroke is one of the neurological diseases which lead to permanently neuronal damage after temporary or long-term occlusion of vessels or after heart attack. However, there are few efficient strategies to prevent or treat this kind of insult in clinical because the consequence is irreversible and could be long-lasting after the onset of stroke. Gene therapy especially using viral system has long ...

Stroke is one of the neurological diseases which lead to permanently neuronal damage after temporary or long-term occlusion of vessels or after heart attack. However, there are few efficient strategies to prevent or treat this kind of insult in clinical because the consequence is irreversible and could be long-lasting after the onset of stroke. Gene therapy especially using viral system has long ...

A wide range of retinal disorders can potentially be treated using viral vector-mediated gene therapy. The most widely used vectors for ocular gene delivery are based on adeno-associated virus (AAV), because they elicit minimal immune responses and mediate long-term transgene expression in a variety of retinal cell types. Proof-of-concept experiments have demonstrated the ...

The Neuronal PAS domain protein 4 (Npas4) is a neuronal activity-dependent immediate early gene that has recently been identified as a transcription factor which regulates the transcription of genes that control inhibitory synapse development and synaptic plasticity. The role Npas4 in learning and memory, however, is currently unknown. Here, we systematically examine the role of Npas4 in auditory ...

LIGHT is a tumor necrosis factor superfamily ligand that is considered as a promising candidate for cancer therapy. It has a potent antitumor activity through establishing lymphoid-like tissues inside tumor sites and recruiting naive T cells into the tumor. In this study, we examined the possibility of antitumor activity by expressing LIGHT in cervical cancer (CC) model. A recombinant ...

... We have evaluated DNA vectors that express antigen alone or together with the ... An intramuscular approach was compared with gene gun delivery. ...

BackgroundThe current method of delivering gene replacement to the posterior segment of the eye involves a three-port pars plana vitrectomy followed by injection of the agent through a 37-gauge cannula, which is potentially wrought with retinal complications. In this paper we investigate the safety and efficacy of delivering adeno-associated viral (AAV) vector to the suprachoroidal space using an ...

Recombinant adeno-associated virus (rAAV)-mediated gene transfer is an attractive approach to the treatment of Duchenne muscular dystrophy (DMD). We investigated the muscle transduction profiles and immune responses associated with the administration of rAAV2 and rAAV8 in normal and canine X-linked muscular dystrophy in Japan (CXMD_J) dogs. rAAV2 or rAAV8 ...

The ability of transient immunosuppression with a combination of a non-depleting anti-CD4 (NDCD4) antibody and cyclosporine (CyA) to abrogate immune reactivity to both adeno-associated viral vector (AAV) and its transgene product was evaluated. This combination of immunosuppressants resulted in a 20-fold reduction in the resulting anti-AAV8 antibody titres, to levels in na�ve mice, following ...

Phenylketonuria (PKU) caused by phenylalanine hydro-xylase (PAH) deficiency leads to toxic accumulation of phenylalanine (Phe). PAH is predominantly expressed in liver and its activity requires a supply of tetrahydrobiopterin (BH₄) cofactor, but we propose that expression of a complete Phe hydroxylating system (PAH plus BH₄ synthetic enzymes) in ...

We previously reported that intravenous delivery of the human tissue kallikrein (HK) gene reduced blood pressure and plasma insulin levels in fructose-induced hypertensive rats with insulin resistance. In the current study, we evaluated the potential of a recombinant adeno-associated viral vector expressing the HK cDNA (rAAV�HK) as a sole, long term therapy to correct ...

Despite the well-documented advantages of the recombinant adeno-associated virus (rAAV) as a gene delivery vehicle, including its non-pathogenic and long-term therapeutic gene expression, there have been very limited studies on its potential for producing persistent anti-tumor effects, particularly in vivo. To address this issue, we constructed rAAV vectors encoding herpes ...

Purpose. To evaluate the suitability of gene delivery-based approaches as potential treatment of Leber congenital amaurosis 4 (LCA4) due to AIPL1 mutations. Methods. Genomic DNA from patients was analyzed using a microarray chip and direct sequencing. A detailed clinical evaluation including fundus autofluorescence (FAF) and optical coherence tomography (OCT) was performed in ...

BackgroundGM1-gangliosidosis is a glycosphingolipid (GSL) lysosomal storage disease caused by a genetic deficiency of acid ?-galactosidase (?gal), which results in the accumulation of GM1-ganglioside and its asialo-form (GA1) primarily in the CNS. Age of onset ranges from infancy to adulthood, and excessive ganglioside accumulation produces progressive neurodegeneration and psychomotor retardation ...

This study aimed to compare the effects of intra-muscular immunization (IM) using needle injection with intra-dermal (ID) immunization using a ballistic gene gun. Serum levels of antigen specific IgG were assessed by ELISA, following immunization with pla...

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Cataplexy, a sudden unexpected muscle paralysis, is a debilitating symptom of the neurodegenerative sleep disorder, narcolepsy. During these attacks, the person is paralyzed, but fully conscious and aware of their surroundings. To identify potential neurons that might serve as surrogate orexin neurons to suppress such attacks, the gene for orexin (hypocretin), a peptide lost in most human ...

GM1-gangliosidosis is a lysosomal storage disease (LSD) caused by an autosomal recessive deficiency of lysosomal acid beta-galactosidase (betagal). This leads to accumulation of GM1-ganglioside and its asialo derivative GA1 in the central nervous system (CNS), and progressive neurodegeneration. Therapeutic AAV-mediated gene delivery to the brain for LSDs ...

The tissue kallikrein�kinin system is important in regulating cardiovascular and renal function, and dysregulation of the system has been implicated in heart and kidney pathologies. These findings suggest that if balance can be restored to the kallikrein-kinin axis, then associated disease progression may be attenuated. To test this hypothesis, recombinant adeno-associated virus ...

We used recombinant adeno-associated virus (rAAV)-mediated gene delivery to overexpress a mutant of rat leptin yielding a protein that acts as a neutral leptin receptor antagonist. The long-term consequences of this overexpression on body weight homeostasis and physical activity, as assessed by voluntary wheel running (WR), were determined in F344 x Brown ...

We used recombinant adeno-associated virus (rAAV)-mediated gene delivery to overexpress a mutant of rat leptin yielding a protein that acts as a neutral leptin receptor antagonist. The long-term consequences of this overexpression on body weight homeostasis and physical activity, as assessed by voluntary wheel running (WR), were determined in F344 � ...

Non-human primates (NHPs) are considered to be among the most relevant animal models for pre-clinical testing of human therapies, on the basis of their close evolutionary relatedness to humans in terms of organ cell biology and physiology. In this study, we sought to investigate whether NHP models accurately reflect the effectiveness of recombinant adeno-associated virus ...

Despite evidence that hyperactivity of the vasodeleterious axis (ACE/angiotensin II (Ang II)/AT1 receptor) of the renin-angiotensin system (RAS) is associated with the pathogenesis of diabetic retinopathy (DR) use of the inhibitors of this axis has met with limited success in the control of this pathophysiology. We investigated the hypothesis that enhancing the local activity of the recently ...

Vascular endothelial growth factor (VEGF) produced by tumor cells has a central role in stimulating angiogenesis required for tumor growth. Humanized monoclonal anti-VEGF antibody (bevacizumab, Avastin), approved as a treatment for non-squamous, non-small cell lung cancer, requires administration every 3 weeks. We hypothesized that an intrapleural administration of an adeno-associated virus (AAV) ...

SummaryVascular endothelial growth factor (VEGF) produced by tumor cells plays a central role in stimulating angiogenesis required for tumor growth. Humanized monoclonal anti-VEGF antibody (bevacizumab, Avastin^�), approved as a treatment for non-squamous, non-small cell lung cancer, requires administration every 3 wk. We hypothesized that an intrapleural administration of ...

RNA interference (RNAi) has been successfully employed for specific inhibition of gene expression; however, safety and delivery of RNAi remain critical issues. We investigated the combinatorial use of RNAi and U1 interference (U1i). U1i is a gene-silencing technique that acts on the pre-mRNA by preventing polyadenylation. RNAi and U1i have distinct mechanisms of action in ...

Purpose. Mutations in the PDE6B gene cause recessive, severe retinitis pigmentosa (RP). PDE6B encodes the ? subunit of the rod-specific phosphodiesterase (?PDE), which, when absent, results in toxic levels of intracellular Ca(2+) and photoreceptor cell death. Ca(2+) blockers, such as nilvadipine, as well as light restriction, slow photoreceptor degeneration in animal models of ?PDE deficiencies. ...

Tattooing is one of a number of DNA delivery methods which results in an efficient expression of an introduced gene in the epidermal and dermal layers of the skin. The tattoo procedure causes many minor mechanical injuries followed by hemorrhage, necrosis, inflammation and regeneration of the skin and thus non-specifically stimulates the immune system. DNA vaccines delivered ...

Recombinant adeno-associated viral (rAAV) vectors expressing neurotrophic genes reduce neuronal death and promote axonal regeneration in CNS injury models. Currently however, use of rAAV to treat clinical neurotrauma is problematic because there is a delay in the onset of transgene expression. Using the adult rat retina and optic nerve (ON), we have tested whether rAAV gene therapy administered at ...

The potential use of Yersinia pestis as a bioterror agent is a great concern. Development of a stable powder vaccine against Y. pestis and administration of the vaccine by minimally invasive methods could provide an alternative to the traditional liquid formulation and intramuscular injection. We evaluated a spray-freeze-dried powder vaccine containing a recombinant F1-V ...

The potential use of Yersinia pestis as a bioterror agent is a great concern. Development of a stable powder vaccine against Y. pestis and administration of the vaccine by minimally invasive methods could provide an alternative to the traditional liquid formulation and intramuscular injection. We evaluated a spray-freeze-dried powder vaccine containing a recombinant F1-V ...

DNA vaccines are an attractive approach to eliciting antigen-specific immunity. Intracellular targeting of tumor antigens through its linkage to immunostimulatory molecules such as calreticulin (CRT) can improve antigen processing and presentation through the MHC class I pathway and increase cytotoxic CD8+ T cell production. However, even with these enhancements, the efficacy of such ...

DNA vaccines are an attractive approach to eliciting antigen-specific immunity. Intracellular targeting of tumor antigens through its linkage to immunostimulatory molecules such as calreticulin (CRT) can improve antigen processing and presentation through the MHC Class I pathway and increase cytotoxic CD8+ T cell production. However, even with these enhancements, the efficacy of such ...

OBJECTIVE--To assess unexpected associations between childhood cancer and pethidine given in labour and the neonatal administration of vitamin K that had emerged in a study performed in the 1970 national birth cohort. DESIGN AND SETTING--195 children with cancer diagnosed in 1971-March 1991 and born in the two major Bristol maternity hospitals in 1965-87 were compared with 558 controls identified ...

Vaccination is one of the major achievements of modern medicine. As a result of vaccination, diseases such as polio and measles have been controlled and small pox has been eradicated. However, despite these successes there are still many microbial diseases that cause tremendous suffering because there is no vaccine or the vaccines available are inadequate. In addition, even if vaccines were ...

Purpose. We previously showed that subretinal delivery of AAV5 vectors containing murine GC1 cDNA driven by either photoreceptor-specific, (hGRK1) or ubiquitous (smCBA) promoters were capable of restoring cone-mediated function and visual behavior and preserving cone photoreceptors in the guanylatecylase 1 knockout (GC1KO) mouse for three months. Here, we compare therapy ...

of Medicine, The University of Iowa, Iowa City, IA, USA and 4 Center for Gene Therapy of Cystic Fibrosis- associated virus (rAAV)-mediated gene therapies to the lung for cystic fibrosis (CF). As new ferret and pig Keywords: AAV; species; tropism; sialic acid; lung; cystic fibrosis Recombinant adeno-associated virus (r

Apart from its role in axon guidance, netrin-1 is also known to be pro-angiogenic. The aim of this study is to determine whether adeno-associated viral (AAV) mediated overexpression of netrin-1 improves post-stroke neurovascular structure and recovery of function. AAV-Netrin-1 or AAV-LacZ of 1�10(10) genome copies each was injected medial and posterior ...

The improved efficacy of cutaneous vaccination at lower doses can address the poor immunogenicity of intramuscular DNA vaccines. However, a simple and inexpensive cutaneous vaccination method is lacking. This study assessed use of micron-scale needles coated with DNA as a simple, inexpensive device for delivery targeted to skin. ...

Protein-based vaccines have emerged as a potentially promising approach for the generation of antigen-specific immune responses. However, due to their low immunogenicity, there is a need for innovative approaches to enhance protein-based vaccine potency. One approach to enhance protein-based vaccine potency is the employment of toll-like receptor ligands, such as CpG oligonucleotides, to activate ...

Plasmid-loaded microspheres can provide localized and sustained release into the target tissue, and thus have the potential to enhance the efficiency of naked DNA at promoting transgene expression. In this report, microsphere design parameters are investigated by correlating the extent and duration of transgene expression intramuscularly to the polymer molecular weight and the ...

As local drug delivery continues to emerge as a clinical force, so does understanding of its potentially narrow therapeutic window. Classic molecular transport studies are of value but do not typically account for the local nature of drug transport or the regional dynamic function in target tissues like muscle that may undergo cyclical and variable mechanical motion and ...

BackgroundIntramuscular pethidine is routinely used throughout the UK for labour analgesia. Studies have suggested that pethidine provides little pain relief in labour and has a number of side effects affecting mother and neonate. It can cause nausea, vomiting and dysphoria in mothers and can cause reduced fetal heart rate variability and accelerations. Neonatal effects ...

Electroporation (EP) of either muscle or skin has proven to be an efficient method for increasing DNA-based vaccine delivery and immunogenicity in small and large animals. Previous comparative studies in large animals suggest that intramuscular (i.m.) DNA EP delivery appears to favor cellular immunity, while intradermal (i.d.) EP ...

... Title : Use of Physostigmine by the Intravenous, Intramuscular, and Oral Routes in the Therapy of Anticholinergic Drug Intoxication. ...

... Title : THE EFFECT OF HIGH INTRAMUSCULAR DOSES OF ATROPINE SULFATE ON THE HUMAN ELECTROCARDIOGRAM. ...

... planning, national and international politics, and ... Intramuscular Kanamycin Treatment of Respiratory ... OF INFECTIOUS DISEASES FREDERICK MD. ...

... Title : Aerosol and Intramuscular Prophylaxis of Respiratory 'Klebsiella pneumoniae' Infection in Mice and Squirrel Monkeys. ...

BackgroundMore than 90% of Duchenne muscular dystrophy (DMD) patients develop cardiomyopathy, and many die of cardiac failure. Despite tremendous progress in skeletal muscle gene therapy, few attempts have been made to treat cardiomyopathy. Microdystrophin genes are shown to correct skeletal muscle pathological lesions in the mdx mouse model for DMD. Here, we tested the therapeutic potential of ...

Recent success in clinical trials supports the use of adeno-associated viral (AAV) vectors for gene therapy of retinal diseases caused by defects in the retinal pigment epithelium (RPE). In contrast, evidence of the efficacy of AAV-mediated gene transfer to retinal photoreceptors, the major site of inherited retinal diseases, is less robust. In addition, although AAV-mediated ...

Recent success in clinical trials supports the use of adeno-associated viral (AAV) vectors for gene therapy of retinal diseases caused by defects in the retinal pigment epithelium (RPE). In contrast, evidence of the efficacy of AAV-mediated gene transfer to retinal photoreceptors, the major site of inherited retinal diseases, is less robust. In addition, although AAV-mediated ...

In the midst of new investigations into the mechanisms of both delivery and protection of new vaccines and vaccine carriers, it has become clear that immunization with delivery mechanisms that do not involve living, replicating organisms are vastly preferred. In this report, non-replicating bacterial minicells simultaneously co-delivering the nucleoprotein ...

BackgroundGene transduction has been considered advantageous for the sustained delivery of proteins to specific target tissues. However, in the case of hard tissues, such as bone, local gene delivery remains problematic owing to anatomical accessibility limitations of the target sites.Methodology/Principal FindingsHere, we evaluated the feasibility of ...

Herpes simplex virus type 2 is the most common infectious agent in humans that causes genital herpes disease and vaccination is a desirable method to prevent herpes infections. An effective therapeutic vaccine will need to elicit virus-specific immune responses. The route of immunization has important role in immune responses. In this study, DNA vaccine encoding glycoprotein D of herpes simplex ...

A growing number of medications must be administered through parenteral delivery, i.e., intravenous, intramuscular, or subcutaneous injection, to ensure effectiveness of the therapeutic. For some therapeutics, the use of delivery vehicles in conjunction with this delivery mechanism can improve drug efficacy and ...

We use a novel technique that allows for closed recirculation of vector genomes in the cardiac circulation using cardiopulmonary bypass, referred to here as molecular cardiac surgery with recirculating delivery (MCARD). We demonstrate that this platform technology is highly efficient in isolating the heart from the systemic circulation in vivo. Using MCARD, we compare the ...

A retrospective cross-sectional survey was conducted to assess key practices and costs relating to home- and institutional delivery care in rural Rajasthan, India. One block from each of two sample districts was covered (estimated population�279,132). Field investigators listed women who had delivered in the past three months and contacted them for structured case interview. ...

BackgroundSimple and effective vaccine administration is particularly important for annually recommended influenza vaccination. We hypothesized that vaccine delivery to the skin using a patch containing vaccine-coated microneedles could be an attractive approach to improve influenza vaccination compliance and efficacy.Methodology/Principal FindingsSolid microneedle arrays ...

Antisense oligonucleotides (AOs) have the capacity to alter the processing of pre-mRNA transcripts in order to correct the function of aberrant disease-related genes. Duchenne muscular dystrophy (DMD) is a fatal X-linked muscle degenerative disease that arises from mutations in the DMD gene leading to an absence of dystrophin protein. AOs have been shown to restore the expression of functional ...

Antisense oligonucleotides (AOs) have the capacity to alter the processing of pre-mRNA transcripts in order to correct the function of aberrant disease-related genes. Duchenne muscular dystrophy (DMD) is a fatal X-linked muscle degenerative disease that arises from mutations in the DMD gene leading to an absence of dystrophin protein. AOs have been shown to restore the expression of functional ...

BackgroundThe greatest challenges in vaccine development include optimization of DNA vaccines for use in humans, creation of effective single-dose vaccines, development of delivery systems that do not involve live viruses, and the identification of effective new adjuvants. Herein, we describe a novel, simple technique for efficiently vaccinating mice against tuberculosis (TB). ...

Plague is a zoonotic disease caused by Yersinia pestis, an etiological agent of pneumonic and bubonic plague. There is a need for an improved plague vaccine that may overcome the limitation of presently available whole cell vaccine. An alternative approach described here, is the use of protective epitopes from immunodominant antigen of Y. pestis. One such antigen is the F1 antigen, a major ...

Anaphylaxis is a systemic allergic reaction that often involves respiratory symptoms and cardiovascular collapse, which are potentially life-threatening if not treated promptly with intramuscular adrenaline. Owing to the unpredictable nature of anaphylaxis and accidental exposure to allergens (such as peanuts and shellfish), patients should be prescribed ...

In this study pulmonary vaccination with a new influenza subunit vaccine powder was evaluated. Vaccine powder was produced by spray-freeze drying (SFD) using the oligosaccharide inulin as stabilizer. Immune responses after pulmonary vaccination of BALB/c mice with vaccine powder were determined and compared to those induced by intramuscular and pulmonary vaccination with a ...

The major disadvantage of several currently available vaccines is the need for repeated administrations. The aim of the study was to develop long-acting microspheres based on poly(-?-caprolactone) (PCL) for delivery of recombinant hepatitis B surface antigen (rHBsAg). PCL microspheres were prepared for induction of humoral and cellular immunity by ...

OBJECTIVE: To evaluate the effect of a single 250-mg dose of 17 alpha-hydroxyprogesterone caproate (17-OHPC) intramuscularly as adjunct to nifedipine tocolysis in preterm labor. METHOD: Women diagnosed with threatened preterm labor between 22 and 35�weeks' gestation scheduled to receive nifedipine tocolysis and prophylactic antenatal corticosteroid were randomized to a ...

The biological effects of fullerenes and, in particular, of C60 have been recognized since long time. One of the problems which hindered the application of fullerenes in medicinal chemistry regards their insolubility in water and water-based fluids. In the present chapter it is reported that C60 and C70 fullerenes are soluble in vegetable oils, in general, in esters of fatty acids and in free ...

The key triggers and regulators of immune responses are antigens and their appearance in immune-privileged secondary lymphatic organs. Currently, the majority of vaccines are administered intramuscularly or subcutaneously, although neither the muscular tissue nor the subcutis is particularly rich in immuno-competent cells. Thus, introducing antigens at sites with a higher ...

DNA vaccination is a promising immunization strategy that could be applied in the development of vaccines for a variety of prophylactic and therapeutic indications. Utilizing anthrax protective antigen as a model antigen, we demonstrate that electroporation mediated delivery enhanced the immunogenicity of DNA vaccines in nonhuman primates over 100-fold as compared to ...

Duchenne muscular dystrophy (DMD) is a common X-linked disease resulting from the absence of dystrophin in muscle. Affected boys suffer from incurable progressive muscle weakness, leading to premature death. Stem cell transplantation may be curative, but is hampered by the need for systemic delivery and immune rejection. To address these barriers to stem cell therapy in DMD, ...

Animal models for Duchenne muscular dystrophy (DMD) have species limitations related to assessing function, immune response, and distribution of micro- or mini-dystrophins. Nonhuman primates (NHPs) provide the ideal model to optimize vector delivery across a vascular barrier and provide accurate dose estimates for widespread transduction. To address vascular ...

Information regarding the distribution and persistence of DNA encapsulated in poly-(lactide co-glycolide) microspheres was collected to provide additional information regarding the safety of DNA vaccines and to support the clinical testing of this new delivery system for DNA. Plasmid DNA was encapsulated in poly(lactide co-glycolide) microspheres and the distribution and ...

Postpartum hemorrhage is a significant cause of maternal morbidity and mortality. Most postpartum hemorrhages are caused by uterine atony and occur in the immediate postpartum period. Expectant or physiologic management of the third stage of labor has been compared with active management in several studies. Active management involves administration of uterotonic medication after the ...

siRNA and antisense oligonucleotides, AON, have similar size and negative charge and are often packaged for in vitro delivery with cationic lipids or polymers-but exposed positive charge is problematic in vivo. Here we demonstrate loading and functional delivery of RNAi and AON with non-ionic, nano-transforming polymersomes. These degradable carriers are ...

siRNA and antisense oligonucleotides, AON, have similar size and negative charge and are often packaged for in vitro delivery with cationic lipids or polymers�but exposed positive charge is problematic in vivo. Here we demonstrate loading and functional delivery of RNAi and AON with non-ionic, nano-transforming polymersomes. These degradable carriers are ...

AbstractVector-mediated cardiac gene therapy holds tremendous promise as a translatable platform technology for treating many cardiovascular diseases. The ideal technique is one that is efficient and practical, allowing for global cardiac gene expression, while minimizing collateral expression in other organs. Here we survey the available in vivo vector-mediated cardiac gene ...

The objective of this work was to conduct an in vivo comparison of nanoparticles and microparticles as vaccine delivery systems. Poly (lactide-co-glycolide) (PLG) polymers were used to create nanoparticles size 110 nm and microparticles of size 800-900 nm. Protein antigens were then adsorbed to these particles. The efficacy of these delivery systems was ...