Induction of anti-chlamydial mucosal immunity by transcutaneous immunization is enhanced by topical application of GM-CSF

Transcutaneous immunization (TCI) involves the direct application of antigen plus adjuvant to skin, taking advantage of the large numbers of Langerhans cells and other resident skin dendritic cells, that process antigen then migrate to draining lymph nodes where immune responses are initiated. We have used this form of immunization to protect mice against genital tract and respiratory tract chlamydial infection. Protection was associated with local antibody responses in the vagina, uterus and lung as well as strong Th1 responses in the lymph nodes draining the reproductive tract and lungs respectively. In this study we show that topical application of GM-CSF to skin enhances the numbers and activation status of epidermal dendritic cells. Topical application of GM-CSF also increased the immune responses elicited by TCI. GM-CSF supplementation greatly increased cytokine (IFNgamma and IL-4) gene expression in lymph node and splenic cells compared to cells from animals immunized without GM-CSF. IgG responses in serum, uterine lavage and bronchoalveolar lavage and IgA responses in vaginal lavage were also increased by topical application of GM-CSF. The studies show that TCI induces protection against genital and respiratory tract chlamydial infections and that topical application of cytokines such as GM-CSF can enhance TCI-induced antibody and cell-mediated immunity.

Challenging the distal-to-proximal cannulation technique for administration of anti-cancer therapies : a prospective cohort study

Background: Distal-to-proximal technique has been recommended for anti-cancer therapy administration. There is no evidence to suggest that a 24-hour delay of treatment is necessary for patients with a previous uncomplicated venous puncture proximal to the administration site. Objectives: This study aims to identify if the practice of 24-hour delay between a venous puncture and subsequent cannulation for anti-cancer therapies at a distal site is necessary for preventing extravasation. Methods: A prospective cohort study was conducted with 72 outpatients receiving anti-cancer therapy via an administration site distal to at least one previous uncomplicated venous puncture on the same arm in a tertiary cancer centre in Australia. Participants were interviewed and assessed at baseline data before treatment and on day 7 for incidence of extravasation/phlebitis. Results: Of 72 participants with 99 occasions of treatment, there was one incident of infiltration (possible extravasation) at the venous puncture site proximal to the administration site and two incidents of phlebitis at the administration site. Conclusions: A 24 hour delay is unnecessary if an alternative vein can be accessed for anti-cancer therapy after a proximal venous puncture. Implications for practice: Extravasation can occur at a venous puncture site proximal to an administration site in the same vein. However, the nurse can administer anti-cancer therapy at a distal site if the nurse can confidently determine the vein of choice is not in any way connected to the previous puncture site through visual inspection and palpation.

Attitudes of employees and employers towards older workers in a climate of anti-discrimination

Attitudes and practices towards older workers were surveyed in Brisbane with 525 employees randomly sampled from the electoral roll and executives of 104 companies obtained by stratified random sampling from the Register of Workplaces (response rates, 60% and 80% respectively). The results indicated that “older workers” are young in terms of contemporary life expectancy, and younger for employers than employees; they have some desirable personal qualities (eg. loyalty), but are not perceived as adaptable; workers aged 25–39 were preferred on qualities held to be important in the workplace and there was minimal interest in recruiting anyone over 45 years.

Innate Immunity in Lobsters: Partial Purification and Characterization of a Panulirus cygnus Anti-A Lectin

A lectin detected in haemolymph from the Australian spiny lobster Panulirus cygnus agglutinated human ABO Group A cells to a higher titre than Group O or B. The lectin also agglutinated rat and sheep erythrocytes, with reactivity with rat erythrocytes strongly enhanced by treatment with the proteolytic enzyme papain, an observation consistent with reactivity via a glycolipid. The lectin, purified by affinity chromatography on fixed rat-erythrocyte stroma, was inhibited equally by N-acetylglucosamine and N-acetylgalactosamine. Comparison of data from gel filtration of haemolymph (behaving as a 1,800,000 Da macromolecule), and polyacrylamide gel electrophoresis of purified lectin (a single 67,000 Da band), suggested that in haemolymph the lecin was a multimer. The purified anti-A lectin autoprecipitated unless the storage solution contained chaotropic inhibitors (125 mmol/L sucrose: 500 mmol/L urea). The properties of this anti-A lectin and other similar lectins are consistent with a role in innate immunity in these invertebrates.

rac-3-exo-Ammonio-7-anti-carboxytricyclo-[2.2.10.2,6]heptane-3-endo-carboxylate

The racemic title compound, C9H11NO4 . H2O, a tricyclic rearranged aminonorbornane dicarboxylic acid is a conformationally rigid analogue of glutamic acid and exists as an ammonium-carboxylate zwitterion, with the bridghead carboxylic acid group anti-related. In the crystal, intermolecular N-H...O and O-H...O hydrogen-bonding interactions involving the ammonium, carboxylic acid and water donor groups with both water and carboxyl O-atom acceptors give a three-dimensional framework structure.

Do anti-inflammatory agents promote linear ablation lesion discontinuities? : an electrophysiological examination

Background: Catheter ablation for atrial fibrillation (AF) is more efficacious than antiarrhythmic therapy. Post ablation recurrences reduce ablation effectiveness and are contributed by lesion discontinuity in the fibrotic linear ablation lesions. The anti-fibrotic role of statins in reducing AF is being assessed in current trials. By reducing the chronic pathological fibrosis that occurs in AF they may reduce AF. However if statins also have an effect on the acute therapeutic fibrosis of an ablation, this could exacerbate lesion discontinuity and AF recurrence. We tested the hypothesis that statins attenuate ablation lesion continuity in a recognised pig atrial linear ablation model. Aims: To assess whether Atorvastatin diminishes the bi-directional conduction block produced by a linear atrial ablation lesion. Methods: Sixteen pigs were randomised to statin (n=8) or placebo (n=8) with drug pre-treatment for 3 days and a further 4 weeks. At initial electrophysiological study (EPS1) 3D right atrium (RA) mapping and a vertical ablation linear lesion in the posterior RA with bidirectional conduction block were completed (Gepstein Circ 1999). Follow-up electrophysiological assessment (EPS2) at 28 days assessed bidirectional conduction block maintenance. Results: Data of 15/16 (statin=7) pigs were analysed. Mean lesion length was 3.7 ± 0.8cm with a mean of 17.9 ± 5.7 lesion applications. Bi-directional conduction block was confirmed in 15/15 pigs (100%) at EPS1 and EPS2. Conclusions: Atorvastatin did not affect ablation lesion continuity in this pig atrial linear ablation model. If patients are on long-term statins for AF reduction, periablation cessation is probably not necessary.

Proteasome inhibitors as anti-cancer agents

The ubiquitin (Ub)-proteasome pathway is the major nonlysosomal pathway of proteolysis in human cells and accounts for the degradation of most short-lived, misfolded or damaged proteins. This pathway is important in the regulation of a number of key biological regulatory mechanisms. Proteins are usually targeted for proteasome-mediated degradation by polyubiquitinylation, the covalent addition of multiple units of the 76 amino acid protein Ub, which are ligated to 1-amino groups of lysine residues in the substrate. Polyubiquitinylated proteins are degraded by the 26S proteasome, a large, ATP-dependent multicatalytic protease complex, which also regenerates monomeric Ub. The targets of this pathway include key regulators of cell proliferation and cell death. An alternative form of the proteasome, termed the immunoproteasome, also has important functions in the generation of peptides for presentation by MHC class I molecules. In recent years there has been a great deal of interest in the possibility that proteasome inhibitors, through elevation of the levels of proteasome targets, might prove useful as a novel class of anti-cancer drugs. Here we review the progress made to date in this area and highlight the potential advantages and weaknesses of this approach.