In vivo gene introduction into keratinocytes using jet injection.
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Successful keratinocyte gene therapy requires the development of efficient methods of gene transfer to keratinocytes. Jet injection of a solution containing DNA can be used to transfer genes to several tissues in vivo. In this article, we tried to introduce DNA into rat and human keratinocytes using this method. First, we fired a beta-gal expression vector into rat skin at several distances using a jet injector and examined beta-gal activity in the epidermal keratinocytes. The highest activity in keratinocytes was found when the plasmid was fired at 10 cm from the skin surface; the activity lessened as the firing distance became shorter than 10 cm. Next, we transplanted human skin on to a nude rat, fired the vector into the human skin from a distance of 10 cm and examined the beta-gal activity. We also injected the same amount of plasmid with a needle to compare jet with needle injections. The results showed that jet injection of the naked DNA could introduce and express DNA in human keratinocytes in vivo and that jet injection exhibited much higher activity than needle injection. Jet injection of the naked DNA will provide a method for keratinocyte gene therapy in the future. (+info)
Local tolerance, pharmacokinetics, and dynamics of ganirelix (Orgalutran) administration by Medi-Jector compared to conventional needle injections.
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The feasibility of administering a relatively high dose of the gonadotrophin-releasing hormone (GnRH) antagonist ganirelix by means of a needle-free injection device, which could be useful in the long-term treatment of sex-steroid-dependent disorders, was evaluated in a randomized, crossover study in 16 healthy females. Local tolerance and pharmacokinetics of ganirelix administered by MediJector versus conventional needle injections were compared. Additionally, the pharmacodynamic effect was evaluated. Two milligrams of ganirelix was administered s.c. once daily for 7 days by Medi-Jector or conventional needle in a randomized sequence, without a washout period. No apparent differences in local tolerance were observed. Most injections (87.5%) gave either no or only a mild reaction. Of the moderate reactions, swelling and redness were reported most frequently (overall 4.9 and 8.5% per injection, respectively). Administration by Medi-Jector was bioequivalent to conventional needle injection with respect to the peak concentration and area under the curve. A profound suppression of luteinizing hormone and follicle stimulating hormone was observed. Serum oestradiol and progesterone concentrations were relatively low prior to treatment and remained low during the entire study period. In conclusion, administration of a relatively high dose of ganirelix by Medi-Jector might be useful for long-term treatment of sex-steroid dependent disorders. (+info)
Delivery of low molecular weight heparin for prophylaxis against deep vein thrombosis using a novel, needle-less injection device (J-Tip).
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Given daily, low molecular weight (LMW) heparins are established for prophylaxis against deep vein thrombosis (DVT). We describe delivery by a novel, needle-less device that is virtually painless in action. Its use could provide benefits for patients in terms of comfort both psychologically and physically, and for healthcare workers in terms of safety from needle-stick injury. Patients undergoing elective surgery received LMW heparin delivered subcutaneously by either a standard needle and syringe or by the needle-less injection device, J-Tip. Pain was scored at the time of injection and plasma anti-factor Xa levels compared between the two methods of drug delivery 4 h later: 29 patients received LMW heparin delivered by the J-Tip and 31 patients by standard needle and syringe. The J-Tip was significantly more comfortable for the patient as the method of drug delivery (P < 0.001). When delivered by the J-Tip, LMW heparin was equally as efficacious, as plasma anti-factor Xa levels were similar for both methods of delivery (P < 0.42). In summary, delivery of LMW heparin by the J-Tip device was both comfortable and effective. These findings, taken in conjunction with its ease of use and complete freedom from risk of needle-stick injury might encourage further examination and use of this type of product. (+info)
Nonviral in vivo gene delivery into tumors using a novel low volume jet-injection technology.
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The jet-injection technology has developed as an applicable alternative to viral or liposomal gene delivery systems. In this study a novel, low-volume, 'high-speed jet injector' hand-held system was used for the direct gene transfer of naked DNA into tumors. Lewis-lung carcinoma bearing mice were jet-injected with the beta-galactosidase (LacZ), the green fluorescence (GFP) or the human tumor necrosis factor alpha (TNF-alpha) gene carrying vector plasmids. The animals received five jet injections into the tumor at a pressure of 3.0 bar, delivering 3--5 microl plasmid DNA (1 microg DNA/microl in water) per single jet injection. The jet injection of DNA leads to a widespread expression pattern within tumor tissues with penetration depths of 5--10 mm. Analysis of tumor cryosections revealed moderate LacZ or GFP expression at 48 h and strong reporter gene expression 72 h and 96 h after jet injection. The simultaneous jet injection of the TNF-alpha and LacZ carrying vectors demonstrated efficient expression and secretion of both the cytokine, as well as LacZ expression within the tumor 24 h, 48 h, 72 h, 96 h and 120 h after jet injection. These studies demonstrate the applicability of jet injection for the efficient in vivo gene transfer into tumors for nonviral gene therapy of cancer using minimal amounts of naked DNA. (+info)
Adjuncts to local anesthesia: separating fact from fiction.
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Adjunctive local anesthetic techniques and their armamentaria, such as intraosseous injection, computer-controlled delivery systems, periodontal ligament injection and needleless jet injection, have been proposed to hold particular advantages over conventional means of achieving local anesthesia. This article describes the use of each technique and proprietary armamentarium and reviews the literature appraising their use. (+info)
Low-volume jet injection for intradermal immunization in rabbits.
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BACKGROUND: This study tested a low-volume (20-30 microl/20-30 microg DNA) jet injection method for intradermal delivery of a DNA vaccine. Jet injection offers the advantages of a needle-less system, low-cost, rapid preparation of the injected DNA solution, and a simple delivery system. More than one construct can be injected simultaneously and the method may be combined with adjuvants. RESULTS: Low-volume jet injection targeted delivery of a DNA solution exclusively to the dermis and epidermis of rabbits. A three injection series of plasmid DNA, encoding the Hepatitis B Surface Antigen stimulated a humoral immune response in 2/5 rabbits. One rabbit developed a significant rise in antibody titer after 1 injection and one following 2 injections. There were no significant differences between jet injection and particle bombardment in the maximal antibody titers or number of injections before response. A three injection series of the same plasmid DNA by particle bombardment elicited a significant rise in antibody titer in 3/5 rabbits. One rabbit developed antibody after 1 injection and two after 3 injections. In contrast, 0/5 rabbits receiving DNA by needle and syringe injection responded. In the jet injection and particle bombardment groups, gene expression levels in the skin did not predict response. While immune responses were similar, luciferase gene expression levels in the skin following particle bombardment were 10-100 times higher than jet injection. CONCLUSION: Low-volume jet injection is a simple, effective methodology for intradermal DNA immunization. (+info)
Jet anesthesia and jet local anesthesia for the 21st century.
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The introduction of the hollow needle and glass syringe in the middle of the 19th century was one gigantic step in the progress of medicine to the current state of art. However, the needle with the pain it causes, become the source of fear for many patients. Indeed, immunization of millions of people who feared the needle, against the deadly contagious diseases, would not have been possible without the introduction of a jet-injector, the Med-E-Jet (Peace Gun), a pain-free way of delivering immunizing medication. (+info)
Model-based estimates of risks of disease transmission and economic costs of seven injection devices in sub-Saharan Africa.
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OBJECTIVE: To investigate and compare seven types of injection devices for their risks of iatrogenic transmission of bloodborne pathogens and their economic costs in sub-Saharan Africa. METHODS: Risk assumptions for each device and cost models were constructed to estimate the number of new hepatitis B virus (HBV) and human immunodeficiency virus (HIV) infections resulting from patient-to-patient, patient-to-health care worker, and patient-to-community transmission. Costs of device purchase and usage were derived from the literature, while costs of direct medical care and lost productivity from HBV and HIV disease were based on data collected in 1999 in Cote d'Ivoire, Ghana, and Uganda. Multivariate sensitivity analyses using Monte Carlo simulation characterized uncertainties in model parameters. Costs were summed from both the societal and health care system payer's perspectives. FINDINGS: Resterilizable and disposable needles and syringes had the highest overall costs for device purchase, usage, and iatrogenic disease: median US dollars 26.77 and US dollars 25.29, respectively, per injection from the societal perspective. Disposable-cartridge jet injectors and automatic needle-shielding syringes had the lowest costs, US dollars 0.36 and US dollars 0.80, respectively. Reusable-nozzle jet injectors and auto-disable needle and syringes were intermediate, at US dollars 0.80 and US dollars 0.91, respectively, per injection. CONCLUSION: Despite their nominal purchase and usage costs, conventional needles and syringes carry a hidden but huge burden of iatrogenic disease. Alternative injection devices for the millions of injections administered annually in sub-Saharan Africa would be of value and should be considered by policy-makers in procurement decisions. (+info)