Teaching immediate cardiac care to general practitioners: a faculty-based approach.

This paper describes the development, piloting and delivery of an immediate care cardiac course (ICCC) to Irish general practitioners. The course utilizes the continuing medical education network of the Irish College of General Practitioners. This has made the course locally accessible even for remote practitioners and has facilitated rapid dissemination. In its first year, 167 GPs (8% of the total number of Irish GPs) have completed the course. Participant feedback has been positive, especially regarding the small group- and skills-based components. The introduction of more formal assessment procedures is now being undertaken. We believe this model to be a possible template for the introduction of other skills courses both in Ireland and abroad.

Assessment of a human recombinant manganese superoxide dismutase in models of inflammation.

We evaluated a novel human recombinant preparation of manganese superoxide dismutase (MnSOD) for anti-inflammatory and anti-oxidant activity compared with a copper zinc (CuZn) SOD preparation. The results showed that administration of MnSOD (50, 100 and 200 micrograms kg-1) in the Freund's Complete Adjuvant (FCA) mediated paw oedema model suppressed the inflammation at 4 hours by 43, 25 and 43% (P < 0.001, P < 0.01 and P < 0.001 at respective doses). However, 24 hours post-challenge, MnSOD (50 and 100 micrograms kg-1), suppressed the inflammation by 19% (P < 0.001). In contrast, Mn SOD at higher doses (400-800 micrograms kg-1; 2 mgkg-1) exacerbated the inflammatory response at 4 hours. This pro-inflammatory response declined progressively by 24 hours. Furthermore, CuZn SOD produced no significant effects on the inflammatory response. In the carrageenan-induced synovitis model, Mn SOD (25 and 50 micrograms; intra-articular administration) exacerbated the inflammation at 48 hours. In contrast, Mn SOD at 5 micrograms produced a significant suppression (44%, P < 0.05) in knee joint swelling at 24 hours. The CuZn SOD preparation produced marked pro-inflammatory effects in the joints whilst it lacked activity in the FCA-mediated paw oedema model. These findings support a therapeutic potential of MnSOD in inflammatory disorders, however the compound has a complex pharmaco-dynamic profile.

The selective protection afforded by ebselen against lipid peroxidation in an ROS-dependent model of inflammation.

The effects of an experimental model of hydrogen-peroxide-induced foot pad oedema on indices of oxidative damage to biomolecules have been investigated. We have demonstrated increased levels of fluorescent protein and lipid peroxides occurring in plasma at 24 and 48 h post-injection. In addition, a decrease in the degree of galactosylation of IgG was observed which kinetically related the degree of inflammation and to the increase in protein autofluorescence (a specific index of oxidative damage). The effects of ebselen, a novel organoselenium compound which protects against oxidative tissue injury in a glutathione-peroxidase-like manner, have also been examined in this model. Pretreatment of animals with a dose of 50 mg/kg ebselen afforded significant and selective protection against lipid peroxidation only. This effect may contribute to the anti-inflammatory effect of this agent in hydroperoxide-linked tissue damage.

Oxidants, joint inflammation and anti-inflammatory strategies.

In summary, we support the hypothesis that the rheumatoid knee is subjected to repeated hypoxic reperfusion injury. Moreover, we speculate that oxidative damage induced as a consequence of hypoxic reperfusion injury leads to the synthesis of intracellular stress proteins. In certain individuals this triggers an autoimmune response which might explain the persistance of the rheumatoid disease process. This gives scope for novel therapeutic approaches in the future development of anti-inflammatory agents.

The ex vivo measurement of malondialdehyde and chemiluminescence as possible indices for anti-inflammatory drug evaluation.

A well-established model of foot-pad oedema in the rat, an example of a cell-mediated hypersensitivity reaction, was used in this study. Male rats were immunized on day 0 with Freund's complete adjuvant (FCA) and then challenged 6 days later with FCA in one hind paw. Within 4 h of the initiation of this acute inflammatory reaction, the presence of free radicals was detected as luminol-amplified chemiluminescence (LAC) directly from the inflamed paws. In addition, an increase in malondialdehyde (MDA), an end product of lipid peroxidation, was measured in both inflamed tissue and plasma. Groups of animals were treated with either diclofenac sodium, indomethacin, piroxicam or prednisolone either 1 h before or 6 h after challenge, oedema, LAC and MDA being measured at various times after challenge. The three non-steroidal anti-inflammatory drugs (NSAIDs) and prednisolone, given 1 h before challenge, significantly inhibited LAC and plasma MDA levels at 4 h post challenge. When given 6 h after challenge all drugs significantly inhibited oedema at 24 h. Furthermore, all the drugs inhibited tissue MDA and LAC but only indomethacin and piroxicam reached significance. The data suggest a role for lipid peroxidation and free-radical generation in inflammation and provide possible indices for in vivo drug activity and evaluation.

Free radical production at the site of an acute inflammatory reaction as measured by chemiluminescence.

A foot-pad oedema model was used to investigate the presence of free radicals using a chemiluminescence method. This model is an example of a cell mediated hypersensitivity reaction. Male rats were inoculated in the scruff with Freund's Complete Adjuvant (FCA) on Day 0 and then challenged 6 days later with FCA in one hind paw. An acute inflammatory reaction was initiated over the following 96 hours and within 4 hours of induction, reactive oxygen species were detected in the inflamed tissue. A peak of chemiluminescence activity was seen 8 hours after the induction of the inflammatory reaction, well before maximum oedema was observed. Using mannitol, catalase and DABCO to elucidate the nature of the reactive oxygen species it was found that hydroxyl radicals, hydrogen peroxide and singlet oxygen all contributed to this burst of oxidative activity and are therefore probably involved with the process of lipid peroxidation and the severity of an inflammatory reaction.