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At least 523 records · Page 29Linked to original sources
PubMed2003

Retrograde transport of sodium selenite and intracellular injection of micro-ruby: a combined method to describe the morphology of zinc-rich neurones.

Zinc is found in synaptic vesicles in a large number of glutamatergic systems. Its involvement in neurotransmission and neurological disorders has been suggested. There are methods for tracing these circuits, but they do not fill the dendritic tree. In this study, extracellular selenite injections in vivo were combined with intracellular injection of fluorochromes in fixed tissue to reveal the morphology of these zinc-rich neurones. Intraperitoneal and intracerebral injections of sodium selenite alone or intracerebral injections of selenite combined with bisbenzimide were made in the visual cortex of the rat in order to locate the somata of zinc-rich neurones. After 24 h of retrograde transport, animals were killed and fluorescent markers were injected intracellularly into fixed slices to show neuronal morphology: (a) Lucifer Yellow (LY) followed by biocytin, (b) LY coupled to biocytin or (c) micro-ruby (MR) (dextranamines bound to rhodamine and biotin). Double-labelled somata (selenite+fluorochrome) were plotted. Details of the dendritic morphology were then revealed by incubation in avidin-biotin complex and development in 3,3'-diaminobenzidine and H(2)O(2). Camera lucida drawings showed that zinc-rich neurones in layers II-III involved in cortico-cortical visual projections were typical pyramidal neurones. This technique is noteworthy for its analysis of the morphology (and connections) of zinc-rich neurones.

Animals↗
PubMed1994

[Primary antiphospholipid syndrome of fatal course and osteoarticular cytosteatonecrosis].

The antiphospholipid syndrome produces acute occlusions of arteries and veins. This syndrome can cause a multiple organ systems failure whose outcome is often fatal. The authors report a case of the primary, antiphospholipid syndrome characterized by this fatal outcome, a so-called "devastating" syndrome following pulse steroids. In this patient, the antiphospholipid antibodies had been found after presenting bone-marrow fat necrosis, which led to extensive lesions of knees, hips and shoulders. Damage to the cell membranes in necrotic lesions might have promoted the immune response against phospholipids. The potential risks of pulse doses of steroids in the antiphospholipid syndrome are documented by the present observation, which also suggests that antiphospholipid antibodies should be determined in cases of fat necrosis of all origins.

Antiphospholipid Syndrome↗
PubMed1998

Nicotine-evoked nitric oxide release in the rat hippocampal slice.

The effects of cholinergic agonists on nitric oxide (NO) release in hippocampal slices from male Sprague-Dawley rats were investigated using electrochemical recording procedures using Nafion and O-phenylenediamine-treated carbon fiber microelectrodes. These microelectrodes are highly selective for NO versus other interferents. Acetylcholine (Ach) with neostigmine, or nicotine was delivered by pressure ejection from pipettes placed within 300 microm of the NO sensors. Both Ach and nicotine produced NO signals ranging from 0.04 to 2.14 microM in the CA1, CA3, and dentate gyrus of the rat hippocampus that lasted for 2-5 min. The Ach responses were not antagonized by the muscarinic antagonist atropine. However, nicotine-evoked responses were partially antagonized by alpha-bungarotoxin, a finding consistent with alpha7-nicotinic cholinergic receptors being involved with the effects of nicotine. These data support the hypothesis that nicotine is capable of evoking long lasting NO release in the hippocampus.

Acetylcholine↗
PubMed1997

An easily constructed pipette for pressure microinjections into the brain.

A simple device for making pressure microinjections into the brain, its application for delivery of a tracer substance, biotin dextran amine, and an example of the resulting axonal transport are described. The device is based on the use of a Luer Up Hamilton microliter syringe mated directly to the plastic hub of an injection needle assembly in which the metal needle has been replaced by a glass pipette. In model experiments, the injection sites were measured in brain sections of rats, which were perfused with fixative immediately after administration of the tracer, and the relationship between the injected volume and the area of the injection site was evaluated. The results showed that the device provided accurate and reproducible delivery of the fluid.

Animals↗
PubMed2003

Non-viral and hybrid vectors in human gene therapy: an update.

Non-viral DNA vectors have several advantages over viral vectors. For example, virus production is expensive and there are safety concerns regarding viral manipulations. In addition, the size of the delivered plasmid is limited by the size of the viral capsid, whereas this is not a problem with non-viral vectors. The major disadvantage of using non-viral DNA delivery vectors, compared with their viral counterparts, is the low transfection efficiency. This has resulted in low levels of usage in clinical trials. Consequently, the majority of research into non-viral gene therapy has been focused on developing more efficient vectors.

Biolistics↗
PubMed1999

Synergistic effect of formulated plasmid and needle-free injection for genetic vaccines.

PURPOSE: A plasmid-based gene expression system was complexed with protective, interactive, and non-condensing (PINC) polymer system and administered with Medi-Jector, a needle-free injection device (NFID), to achieve high and sustained levels of antigen-specific antibodies in blood circulation. METHODS: Human growth hormone (hGH) or bacterial beta-galactosidase gene expression plasmids driven by a cytomegalovirus (CMV) promoter were formulated in saline or complexed with a PINC polymer, polyvinylpyrrolidone (PVP), and intramuscularly or subcutaneously administered into dogs and pigs using a 22-gauge needle or a NFID. The hGH-specific IgG titers in serum were measured by an ELISA. Beta-galactosidase expression was measured in injected muscles by an enzymatic assay or immunohistochemistry. The effect of NFID on DNA stability and topology was assessed by gel electrophoresis. RESULTS: Intramuscular (i.m.) or subcutaneous (s.c.) injection of a hGH expression plasmid pCMV-hGH (0.05-0.5 mg/kg) in dogs and pigs elicited antigen-specific IgG antibody titers to expressed hGH. With both routes of injection, pDNA delivery by a NFID was superior to pDNA injection by needle. The magnitude of hGH-specific IgG titers with NFID was 15-20-fold higher than needle injection when pDNA was complexed with PVP, and only 3-4-fold higher with pDNA in saline. The transfection efficiency in the injected muscle, as measured by beta-galactosidase expression, following i.m. injection of pCMV-betagalactosidase/PVP, was not significantly different between needle and NFID-injected groups. CONCLUSIONS: These data demonstrate that the combination of pDNA/ PVP complexes and a NFID act synergistically to achieve high and sustained levels of antigen-specific IgG response to expressed antigen. This gene delivery approach may offer advantage over needle injection of naked DNA for the development of genetic vaccines.

Animals↗
PubMed2004

Novel approaches to vaccine delivery.

Although the currently available vaccines represent an outstanding success story in modern medicine and have had a dramatic effect on morbidity and mortality worldwide, it is clear that improvements are required in the current vaccine delivery technologies. Improvements are required to enable the successful development of vaccines against infectious diseases that have so far proven difficult to control with conventional approaches. Improvements may include the addition of novel injectable adjuvants or the use of novel routes of delivery, including mucosal immunization. Mucosal delivery may be required to provide protection against pathogens that infect at mucosal sites, including sexually transmitted diseases. Alternatively, novel approaches to delivery, including mucosal administration, may be used to improve compliance for existing vaccines. Of particular interest for safer mass immunization campaigns are needle-free delivery devices, which would avoid problems due to needle re-use in many parts of the world and would avoid needle-stick injuries.

Adjuvants, Immunologic↗
PubMed1997

Gene gun-based nucleic acid immunization alone or in combination with recombinant vaccinia vectors suppresses virus burden in rhesus macaques challenged with a heterologous SIV.

Gene gun-based DNA immunization alone or in combination with recombinant vaccinia vectors was evaluated for the ability to elicit protective immune responses in rhesus macaques challenged with a pathogenic, heterologous simian immunodeficiency virus (SIV). Six monkeys primed with seven consecutive doses of DNA encoding SIVmac239 gp120 and gp160 (DNA + DNA) were divided into two groups. Three of these animals received another DNA booster immunization and the remaining three received a booster immunization containing a homologous, live recombinant vaccinia virus expressing SIVmac251 gp160 (DNA + VAC). In addition, a group of 15 animals primed with recombinant vaccinia vectors were divided into two groups. One group of six monkeys received another immunization of vaccinia (VAC + VAC) and the other nine animals received a DNA (mac239) booster immunization (VAC + DNA). Geometric mean end-point IgG titres in the DNA + VAC and VAC + DNA groups were substantially higher than the responses seen in the VAC + VAC and DNA + DNA groups, demonstrating a synergistic relationship between DNA-based vaccines and recombinant vaccinia virus-based vaccines. All vaccinates and five naive controls were challenged 19 weeks after the final booster immunization with 10 animal infectious doses of SIVDelta/B670. The vaccines did not prevent infection. However, all vaccine groups showed significant virus load reductions from seven to 56 days post challenge when compared to controls. Although the DNA + DNA group developed the lowest prechallenge antibody responses, the most significant reduction (200-fold) in virus load was associated with this group. In addition, a significant delay in CD4+ T cell loss relative to controls was observed in the DNA + DNA group. These results demonstrate that a gene gun-based DNA vaccine provided some attenuation of infection and CD4+ T cell loss after a heterologous challenge.

Animals↗
PubMed2002

Comparison of a needle-free high-pressure injection system with needle-tipped injection of intracavernosal alprostadil for erectile dysfunction.

Patients identified from hospital records as using alprostadil injections for erectile dysfunction were invited to take part in this open crossover study. On alternate weeks eight patients were given intracavernosal needle injections and transdermal needle-free injection of alprostadil in a randomized order. Efficacy of injection and associated pain were assessed and compared for the two methods. Pain produced during injection was significantly greater with the needle-free system than with the needle-tipped injection whilst efficacy was significantly less. Bruising was reported in all except one patient following needle-free injection only. Patient ratings of the needle-free injector were significantly lower than ratings for needle-tipped alprostadil delivery and when asked to express a preference, every patient chose the needle-tipped injection over the needle-free device.

Adult↗
PubMed2000

Evaluation of a needle-free injection system for local anaesthesia prior to venous cannulation.

We evaluated a single-use, disposable, carbon-dioxide-powered, needleless injector (J-Tip, National Medical Products Inc., CA, USA), which is claimed to deliver a virtually painless, subcutaneous injection. Seventy-two patients undergoing various types of surgery had a large-bore intravenous cannula inserted prior to induction of general anaesthesia. Three minutes beforehand, a subcutaneous injection of 0.3 ml of 1% plain lidocaine was administered. Subjects were randomly allocated to receive the lidocaine either by the needleless injector or from a conventional syringe and a 25 G needle. Pain scores were recorded on injection of the lidocaine and on insertion of the cannula. There was significantly less pain on injection with the needleless injector than with the 25 G needle (p < 0.001) but, surprisingly, there was more pain on cannulation (p < 0. 001). We conclude that the device certainly delivers a less painful subcutaneous injection than a 25 G needle, but perhaps provides less effective skin anaesthesia for venous cannulation at sites where the subcutaneous space is small; its use might be better suited to areas where the subcutaneous space is deeper.

Anesthesia, Local↗