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Serum and colostrum antibody responses induced by jet-injection of sheep with DNA encoding a Cryptosporidium parvum antigen.

In an effort to generate high titer colostrum for immunotherapy of cryptosporidiosis, a study was conducted to test the efficacy of immunizing sheep with recombinant plasmid DNA (pCMV-CP15/60) encoding epitopes of 15 and 60 kDa surface antigens of Cryptosporidium parvum sporozoites. The plasmid DNA was used to immunize preparturient ewes at three dose levels by jet-injection into either hind limb muscle (IM) or mammary tissue (IMAM). Regardless of route of injection, a dose-dependent anti-CP15/60 immunoglobulin response was observed in sera and colostrum from sheep immunized with pCMV-CP15/60 plasmid DNA. High titer antibody responses were observed in one of three animals per group receiving an IM injection of 100 or 1000 micrograms pCMV-CP15/60. IMAM immunization with 100 or 1000 micrograms pCMV-CP15/60 plasmid DNA elicited higher titer colostrum responses and more consistent serum responses compared to IM injections. A negligible serum and colostrum anti-CP15/60 response was observed in ewes injected IM with 10 micrograms pCMV-CP15/60 or 1000 micrograms control plasmid DNA. Immunoblotting of native C. parvum sporozoite/oocyst protein with hyperimmune serum and colostrum corroborated the increased titers against CP15/60 antigen. Serum and colostrum antibodies from pCMV-CP15/60-immunized sheep were eluted from native CP15 protein and bound a surface antigen of C. parvum sporozoites as indicated by indirect immunofluorescence staining.

Animals↗

A new route, jet-injection for anesthetic induction in children - II. ketamine dose-range finding studies.

Ketamine (K) i.m. has been widely used for anesthetic induction in small children in the last decades, if mask induction has failed. In many instances, however, physical restraint was required. In order to eliminate the pain of i.m. injection and to prevent the psychological and physical trauma associated with restraint, we evaluated the utility of jet-injection (j.i.) of K for anesthetic induction in a dose-range finding study. Thirty children (age 1-6 years), whose parents gave a valid consent approved by the IRB and were scheduled for minor surgeries, were randomized into 3 equal groups: A/ketamine 6.0 mg/kg j.i., B/ketamine 3.5 mg/kg j.i., C/ketamine 2.5 mg/kg j.i. As a drying agent atropine 20 microg/kg was also given i.v. The onset of full amnesic/sedative effect of K, the scoring of sedation and emotional state, the ease of placement of the i.v. catheter, the speed of recovery by Aldrete scores, and the time for safe discharge were evaluated. Although no demographic differences were observed among the groups the duration of surgery and anesthesia were longer in the B group (41 and 49 min) than in the A or C groups. The onset of sedation was significantly (p < 0.05) faster in group A (174 sec) than in group B (312 sec) or C (303 sec). However, no significant difference was observed in the onset of complete sedation among the groups. The sedation index was the lowest representing the best sedation in group A (4.2) while in group B and C were somewhat higher (4.6 and 4.4). There were no differences in the ease of i.v. cannulation among the groups. Recovery from anesthesia was the slowest in group A, although the differences among the 3 groups did not reach statistical significance. The mean discharge times ranged from 10-13 min with no differences among the groups. Laryngospasm occurred in 4:10 in group A and 1:10 in groups B and C. Evidently the high dose of K, 6.0 mg/kg caused a proneness to laryngospasm. Since no additional benefit was derived from this high dose, the lower doses (3.0 mg/kg) of K may be sufficient for routine use. None of the children experienced unpleasant recall or pain for the injection or the whole procedure. This new route of anesthetic induction with the jet-injector utilizing K may provide pain-free and stress-free induction as compared to its i.m. injection. This technique also prevents transmission of infection and is [correction of and cost] cost effective since simultaneous and/or sequential injection can be given from a single vial of K.

Anesthesia↗

Genetic immunization by jet injection of targeted pDNA-coated nanoparticles.

Genetic immunization strategies have largely focused on the use of "naked" plasmid DNA or the gene gun. However, there remains a clear need to further improve the efficiency and/or cost of potential DNA vaccines. The theoretical basis of our research is to rationally design genetic immunization methodologies for nanoparticle-based delivery systems of plasmid DNA, perhaps in combination with already commercially available needle-free devices, such as the Biojector 2000. These methodologies may both reduce the dose of pDNA required and enhance the breadth and depth of protective immune responses (i.e., humoral and cellular). The purpose of this article is to provide detailed experimental methods to (1) engineer and characterize pDNA-coated cationic nanoparticles (<100nm) directly from oil-in-water microemulsion precursors and (2) enhance both the breadth and depth of immune responses after immunization of mice with pDNA-coated nanoparticles by different routes of administration, including intradermal, using a needle-free jet injection device.

Animals↗

Use of the nuclease inhibitor aurintricarboxylic acid (ATA) for improved non-viral intratumoral in vivo gene transfer by jet-injection.

BACKGROUND: Stability, integrity and retention of the DNA within the targeted tissue is decisive for efficient gene transfer using naked DNA. Pre-clinical and clinical studies require reproducible transfection rates by preventing rapid degradation of naked DNA in the transduced tissue. Tumor tissues contain nuclease activity, which can affect DNA stability if naked DNA is used. Therefore, inhibition of nuclease-mediated DNA degradation by the nuclease inhibitor aurintricarboxylic acid (ATA) might lead to improved gene transfer efficiency in tumor tissues. METHODS: For both, DNA-degradation analysis and in vivo gene transfer experiments, the beta-galactosidase (LacZ)-expressing pCMVbeta and the cytosine deaminase (CD)-expressing pCMV-CD plasmid were used. Influence of the nuclease inhibitor ATA was determined in tumors, in which naked pCMVbeta or pCMV-CD DNA and ATA was co-administered by jet-injection. The nuclease activity and inhibition by ATA was analyzed using the DNase Alert detection system. The influence of ATA on LacZ expression was determined by specific ELISA and its effect on the therapeutic efficacy of CD gene transfer on tumor growth was determined in vivo. RESULTS: The screening of different human mammary and colon carcinoma models revealed strong nuclease activity rapidly degrading naked plasmid DNA. Co-administration of ATA with pCMVbeta or pCMV-CD for in vivo jet-injection of tumors prevented DNA from nuclease degradation associated with either increased LacZ gene expression or improved reduction in tumor growth. CONCLUSIONS: Tumor-associated nuclease activity is a notable hurdle in gene transfer of naked DNA and therefore inhibition of nucleolytic degradation of plasmid DNA facilitates intratumoral gene expression.

Aurintricarboxylic Acid↗

[Determination of the take efficiency of lyophilized smallpox vaccine as a function of the vaccination technic (double scarification, multi-puncture and jet injection)].

Revaccination against smallpox was performed by three techniques: double scarification, multiple puncture and jet injection in 352 youths aged 16 and 17 years. The results were assessed by the number of takes, the quality of the cutaneous and humoral response. The highest proportion of major skin reactions was obtained by multiple puncture vaccination (62.4%) and the best humoral response, tested by passive haemagglutination, by jet revaccination. Multiple puncture is recommended as a method of election both in restricted and mass vaccination in view of the high proportion of major skin rections accompanied by a corresponding humoral response, the rapid and readily performed technique and small amount of vaccine needed.

Adolescent↗

Delivery of insulin by jet injection: recent observations.

Medi-Ject Corporation (now Antares Pharma, Inc.) has been providing delivery devices for the needle-free administration of insulin for over 25 years. This study was one of the final steps in the development and premarket evaluation of Medi-Ject's newest needle-free system, the Medi-Jector Vision. This study was conducted to evaluate the performance of this device in the hands of experienced jet injection users in a home environment. Diabetic subjects currently using a needle-free device for the administration of their insulin were studied. Subjects used the new Medi-Jector Vision for all of their insulin administration during the course of the study. Insulin was injected on schedule and at doses consistent with their standard of practice as directed by their health care provider. All subjects were required to document each injection in a daily diary. Study subjects utilized all common insulin types (rapid, regular, intermediate, and long acting), and injections were administered in all of the common injection sites (arms, thighs, abdomen, and buttocks). Once subjects optimized the system to the most appropriate orifice size based on completeness of injection, average completeness percentages were greater than 94% for all orifice sizes. Most patients using the new Medi-Jector Vision in the home were able to manage their insulin therapy without significant complication. We conclude that the jet delivery of insulin with the new Medi-Jector Vision is well accepted by people with diabetes and offers a reliable alternative to the use of needles.

Data Collection↗

Peyronie's disease: results with dermo-jet injection of dexamethasone.

The results in 21 patients with Peyronie's disease who were managed with a course of dermo-jet percutaneous injections of dexamethasone into the plaques are described herein. These patients had 6 to 10 injections at intervals of 1 month for 6 months. In a high percentage of the cases there occurred a disappearance or decrease in the size of the plaques, pain on erection and discomfort during sexual relations. Also, there was a high rate of improvement in the chordee. Because of the natural history of resolution of the plaques and the small number of patients, statistical significance is not believed applicable, although 71 per cent of the patients had experienced prior failure with other modes of therapy. Eight patients experienced urinary or prostato-epididymal infections at some time in their medical history, correlating well with the inflammatory theory as the cause of the disorder.

Adult↗

Painfulness of needle and jet injection in children with diabetes mellitus.

The aim of this study was to investigate whether insulin application by jet injector is less painful than by needle. Pain was scored by 41 diabetic and seven healthy volunteers after injections with both methods. Injections by jet were no less painful than those by needle but produced several local side-effects.

Adolescent↗

[Experimental basis for associated subcutaneous jet injection immunization against plague and smallpox].

Experiments in guinea-pigs have indicated that combined immunization with the mixture of live plague and smallpox vaccines introduced subcutaneously by means of a jet injector are safe and faintly reactogenic. Highly intense immunity, as revealed by serological shifts and by the degree of protection of the vaccinated animals challenge with the virulent cultures of the corresponding infective agents, allows the recommendation that combined subcutaneous immunization against plague and smallpox by means of a jet injector be further studied on humans.

Animals↗

Human insulin-induced lipoatrophy. Successful treatment using a jet-injection device.

OBJECTIVE: To evaluate the efficacy of the administration of insulin by a jet-injector device in stopping and reversing severe human insulin-induced lipoatrophy. CASE: We report a case of a woman with severe human insulin-induced lipoatrophy who has been treated exclusively with recombinant DNA human insulin since the onset of IDDM. RESULTS: The loss of subcutaneous tissue in the injection areas was demonstrated and measured by high-frequency ultrasound. Dermatologic exam demonstrated a severe reduction of fat tissue. After 8 months of administration of human insulin by a jet injector, there were no more new lesions of lipoatrophy and those affected areas were substantially ameliorated. CONCLUSIONS: Jet-injection devices might constitute a helpful method to treat those patients affected by severe human insulin-induced lipoatrophy.

Adult↗

An outbreak of hepatitis B associated with jet injections in a weight reduction clinic.

From January 1984 through November 1985, 31 clinical cases of hepatitis B occurred among attendees of a weight reduction clinic (clinic 1). Before the onset of illness, each case-patient had received a series of injections of human chorionic gonadotropin administered by jet injectors at clinic 1. Clinical history, risk factor assessment, serologic evaluation, and review of clinic injection records were obtained on 287 (84%) of 341 persons who had attended clinic 1 in the first 6 months of 1985. Of this cohort, 21% (60/287) had evidence of acute infection with hepatitis B virus (either documented clinical cases or antibody to hepatitis B core antigen, IgM positive). Of persons who had been given human chorionic gonadotropin at the clinic during the period studied, 24% (57/239) of those receiving human chorionic gonadotropin only by jet injector experienced acute hepatitis B virus infection. None of the 22 persons who had received injections only by syringe experienced hepatitis B virus infection. Stopping the use of the jet injectors on July 2, 1985, at clinic 1, was associated with the termination of this outbreak. This investigation demonstrated that jet injectors can become contaminated with hepatitis B virus and then may be vehicles for its transmission.

Adult↗

[Jet injection, a new method for the induction of anesthesia in children].

In order to shorten anaesthesia induction and to avoid pain of the intramuscular injection, we evaluated the efficacy and safety of midazolam given by a jet-injector, utilized solely for mass inoculations until now. Premedication with midazolam with the jet-injector, indeed, proved to be effective, rapid and safe in children. The best results were found in two groups receiving 150-200 microgram/kg midazolam. Within 5 minutes, it was easy to cannulate a vein in children injected by the jet-injector, whereas the effect of intramuscular injection developed slowly, within 7 minutes. In the latter group, cannulation of the vein was more difficult than in the other groups. The separation from the parents and anaesthetic induction were greatly facilitated by midazolam given by the jet-injector. Amnesia was present not only for anaesthetic induction but also for the injection. Recovery was not more prolonged in those premedicated with midazolam with the jet-injector than with midazolam administered by other routes: oral, rectal or nasal. The children induced with the aid of jet-injector had no unpleasant recall based on interviews with the patients and parents.

Adjuvants, Anesthesia↗

[Ampicillin concentration in the blood when administered by jet injection and needle-syringe methods].

The studies were carried out on 50 persons. Ampicillin was administered with the help of a jet injector B1-2 and needle syringe in doses of 250 or 500 and 500 mg respectively. When the drug was administered by infusion, its maximum blood levels were achieved earlier than after needle-syringe administration of the drug and were higher (22.83+/-4.10 and 6.3+/-0.09 gamma/ml respectively). Even when ampicillin was administered with the help of the injector in a dose of 250 mg its blood levels were much higher than those after needle-syringe administration in a dose of 500 mg. After jet infusion the prolongation of the drug retention time in the blood at therapeutical levels was observed as compared to the needle-syringe administration.

Adult↗

A needle-free jet-injection system with lidocaine for peripheral intravenous cannula insertion: a randomized controlled trial with cost-effectiveness analysis.

UNLABELLED: Insertion of a peripheral IV cannula is a common, although painful, procedure. We tested the analgesic efficacy, adverse effects, and cost-effectiveness of a needle-free intradermal drug delivery system (Jet) with lidocaine for the insertion of an IV cannula (18-gauge; dorsum of hand). Four-hundred patients were randomly allocated to one of four groups: (a) no treatment, (b) Jet (J-Tip), National Medical Products Inc, CA; $3.0 per device) with 0.5 mL of saline, (3) Jet with 0.5 mL of lidocaine 1%, and (4) Jet with 0.5 mL of lidocaine 2%. Pain was evaluated using a numerical verbal scale (NVS 0-10). A NVS < or =3 was considered as acceptable in this context. Incremental cost-effectiveness ratios were calculated. Without treatment, 42.4% of patients had a NVS < or = 3, 39.3% with saline, 60.7% with 1% lidocaine (relative risk [RR] compared with no treatment, 0.70; 95% confidence interval [CI], 0.53-0.93), and 86.7% with 2% lidocaine (RR, 0.49; 95% CI, 0.38-0.62). Nineteen and one-half percent of patients had a NVS >3 because of Jet treatment, 13.5% had local hyperemia, and 16.9% had minor local bleeding. Of all Jet treatments, 10.5% were technical failures, and there were 17.6% cannula insertion failures (10.1% without treatment [RR, 1.74; 95% CI, 0.92-3.32]). Compared with no treatment, costs to generate one additional patient with a NVS < or =3 were $23 with lidocaine 1% and $10 with lidocaine 2%. On insertion of an IV cannula on the back of the hand, 58% of patients report at least moderate pain. Lidocaine-Jet is analgesic; there is dose-responsiveness. However, Jet treatment is not painless, and costs incurred to achieve one success compared with doing nothing are not negligible. IMPLICATIONS: Insertion of an IV cannula is painful. Four-hundred patients were randomly allocated to test the analgesic efficacy, adverse effects, and cost-effectiveness of the needle-free intradermal drug delivery system (J-Tip); Jet). Jet with lidocaine is effective, but its application is not painless. Costs to achieve one patient with no more than moderate pain (numerical verbal scale < or =3 of 10) on insertion of an IV cannula are $10.

Adolescent↗

Needle-free jet injection of a mixture of Japanese encephalitis DNA and protein vaccines: a strategy to effectively enhance immunogenicity of the DNA vaccine in a murine model.

Combined immunization with gene-based and protein-based vaccines can increase vaccine effectiveness. We previously demonstrated, using a murine model for Japanese encephalitis (JE), that simultaneous immunization with a DNA vaccine (pcJEME) by the intramuscular route and a protein vaccine consisting of subviral extracellular particles (EPs) by the subcutaneous route provided a synergistic increase in immunogenicities of these vaccines. Here, we investigated a novel immunization protocol consisting of a single inoculation with a mixture of DNA and protein vaccines using a needle-free jet injector. Immunization of ddY mice with 1 microg of pcJEME mixed with 1 microg of EPs or a 1/100 dose of commercial inactivated JE vaccine (JEVAX) induced neutralizing antibody titers of 1:40 to 1:80 (90% plaque reduction) 6 weeks after immunization, whereas immunization with DNA or protein alone only induced low titers (< or =1:10). Co-immunization with pcDNA3, a CpGcontaining vector of the vaccine plasmid, increased immunogenicity of JEVAX to some extent. IgG1/IgG2a isotype profiles supported increased production of EPs in pcJEME-inoculated mice by needle-free injection and an adjuvant effect of the vector on immunogenicity of JEVAX.

Adjuvants, Immunologic↗

Characteristics of various film cooling jets injected in a conduit.

In the present study, film cooling characteristics by the jets through various easy-to-make straight holes and slots have been investigated. In this experiment, seven kinds of injection geometries were used. They were circular, rectangular, elliptic and oval holes and slots, respectively.

Journal Article↗

A needleless liquid jet injection delivery method for cardiac gene therapy: a comparative evaluation versus standard routes of delivery reveals enhanced therapeutic retention and cardiac specific gene expression.

This study evaluates needleless liquid jet method and compares it with three common experimental methods: (1) intramuscular injection (IM), (2) left ventricular intracavitary infusion (LVIC), and (3) LV intracavitary infusion with aortic and pulmonary occlusion (LVIC-OCCL). Two protocols were executed. First (n&#x2009;=&#x2009;24 rats), retention of dye was evaluated 10&#xa0;min after delivery in an acute model. The acute study revealed the following: significantly higher dye retention (expressed as % myocardial cross-section area) in the left ventricle in both the liquid jet [52&#x2009;&#xb1;&#x2009;4] % and LVIC-OCCL [58&#x2009;&#xb1;&#x2009;3] % groups p&#x2009;<&#x2009;0.05 compared with IM [31&#x2009;&#xb1;&#x2009;8] % and LVIC [35&#x2009;&#xb1;&#x2009;4] %. In the second (n&#x2009;=&#x2009;16 rats), each animal received adeno-associated virus encoding green fluorescent protein (AAV.EGFP) at a single dose with terminal 6-week endpoint. In the second phase with AAV.EGFP at 6&#xa0;weeks post-delivery, a similar trend was found with liquid jet [54&#x2009;&#xb1;&#x2009;5] % and LVIC-OCCL [60&#x2009;&#xb1;&#x2009;8] % featuring more LV expression as compared with IM [30&#x2009;&#xb1;&#x2009;9] % and LVIC [23&#x2009;&#xb1;&#x2009;9] %. The IM and LVIC-OCCL cross sections revealed myocardial fibrosis. With more detailed development in future model studies, needleless liquid jet delivery offers a promising strategy to improve direct myocardial delivery.

Animals↗