Cooperation between interleukin-5 and the chemokine eotaxin to induce eosinophil accumulation in vivo.

Experiments were designed to study the effect of systemically administered IL-5 on local eosinophil accumulation induced by the intradermal injection of the chemokine eotaxin in the guinea pig. Intravenous interleukin-5 (IL-5) stimulated a rapid and dramatic increase in the numbers of accumulating eosinophils induced by i.d.-injected eotaxin and, for comparison, leukotriene B4. The numbers of locally accumulating eosinophils correlated directly with a rapid increase in circulating eosinophils: circulating eosinophil numbers were 13-fold higher 1 h after intravenous IL-5 (18.3 pmol/kg). This increase in circulating cells corresponded with a reduction in the number of displaceable eosinophils recovered after flushing out the femur bone marrow cavity. Intradermal IL-5, at the doses tested, did not induce significant eosinophil accumulation. We propose that these experiments simulate important early features of the tissue response to local allergen exposure in a sensitized individual, with eosinophil chemoattractant chemokines having an important local role in eosinophil recruitment from blood microvessels, and IL-5 facilitating this process by acting remotely as a hormone to stimulate the release into the circulation of a rapidly mobilizable pool of bone marrow eosinophils. This action of IL-5 would be complementary to the other established activities of IL-5 that operate over a longer time course

Effect of Laparoscopic-assisted Gastropexy on Gastrointestinal Transit Time in Dogs.

BackgroundProphylactic gastropexy has been promoted as a means of preventing gastric volvulus during gastric dilatation and volvulus (GDV) syndrome. Little is known about the impact of gastropexy on gastrointestinal transit time.HypothesisLaparoscopic-assisted gastropexy (LAG) will not alter gastrointestinal transit times when comparing gastric (GET), small and large bowel (SLBTT), and whole gut transit times (TTT) before and after surgery.Animals10 healthy client-owned large-breed dogs.MethodsProspective clinical trial. Before surgery, all dogs underwent physical examination and diagnostic evaluation to ensure normal health status. Dogs were fed a prescription diet for 6 weeks before determination of gastrointestinal transit with a wireless motility capsule. LAG was then performed, and dogs were fed the diet for 6 additional weeks. Measurement of transit times was repeated 6 weeks after surgery.ResultsTen dogs of various breeds at-risk for GDV were enrolled. No complications were encountered associated with surgery or capsule administration. There were no significant differences in GET 429 [306-1,370] versus 541 [326-1,298] (P = 0.80), SLBTT 1,243 [841-3,070] versus 1,540 [756-2,623] (P = 0.72), or TTT 1,971 [1,205-3,469] versus 1,792 [1,234-3,343] minutes (median, range) (P = 0.65) before and after LAG.Conclusions and clinical importanceAn effect of LAG on gastrointestinal transit time was not identified, and wireless motility capsule can be safely administered in dogs after LAG

Eotaxin: a potent eosinophil chemoattractant cytokine detected in a guinea pig model of allergic airways inflammation.

Eosinophil accumulation is a prominent feature of allergic inflammatory reactions, such as those occurring in the lung of the allergic asthmatic, but the endogenous chemoattractants involved have not been identified. We have investigated this in an established model of allergic inflammation, using in vivo systems both to generate and assay relevant activity. Bronchoalveolar lavage (BAL) fluid was taken from sensitized guinea pigs at intervals after aerosol challenge with ovalbumin. BAL fluid was injected intradermally in unsensitized assay guinea pigs and the accumulation of intravenously injected 111In-eosinophils was measured. Activity was detected at 30 min after allergen challenge, peaking from 3 to 6 h and declining to low levels by 24 h. 3-h BAL fluid was purified using high performance liquid chromatography techniques in conjunction with the skin assay. Microsequencing revealed a novel protein from the C-C branch of the platelet factor 4 superfamily of chemotactic cytokines. The protein, eotaxin, exhibits homology of 53% with human MCP-1, 44% with guinea pig MCP-1, 31% with human MIP-1α, and 26% with human RANTES. Laser desorption time of flight mass analysis gave four different signals (8.15, 8.38, 8.81, and 9.03 kD), probably reflecting differential O-glycosylation. Eotaxin was highly potent, inducing substantial 111In-eosinophil accumulation at a 1-2-pmol dose in the skin, but did not induce significant 111In-neutrophil accumulation. Eotaxin was a potent stimulator of both guinea pig and human eosinophils in vitro. Human recombinant RANTES, MIP-1α, and MCP-1 were all inactive in inducing 111In-eosinophil accumulation in guinea pig skin; however, evidence was obtained that eotaxin shares a binding site with RANTES on guinea pig eosinophils. This is the first description of a potent eosinophil chemoattractant cytokine generated in vivo and suggests the possibility that similar molecules may be important in the human asthmatic lung

Mycobacterium ulcerans DNA Not Detected in Faecal Samples from Buruli Ulcer Patients: Results of a Pilot Study

It has recently been shown that in a Buruli ulcer (BU) endemic region of southeastern Australia, significant numbers of possums (native tree-dwelling marsupials) have clinical BU disease. Furthermore, based on quantitative PCR (qPCR) analysis, animals with BU lesions (and some without) shed M. ulcerans DNA in their faeces, indicative of bacterial loads of up to 108 organisms/gram. These findings led us to propose that humans might also harbour M. ulcerans in their gastrointestinal tract and shed the bacterium in their faeces. We conducted a pilot study and collected faecal swabs from 26 patients with confirmed BU and 31 healthy household controls. Faecal samples were also collected from 10 healthy controls from non-endemic regions in Ghana. All 67 specimens were negative when tested by IS2404 PCR. The detection sensitivity of this method was ≥104 bacteria per gram (wet-weight) of human faecal material. We conclude that the human gastrointestinal tract is unlikely to be a significant reservoir of M. ulcerans

The effect of fungal pathogens on the water and carbon economy of trees: implications for drought-induced mortality

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The discovery of a novel antibiotic for the treatment of Clostridium difficile infections: a story of an effective academic-industrial partnership

Academic drug discovery is playing an increasingly important role in the identification of new therapies for a wide range of diseases. There is no one model that guarantees success. We describe here a drug discovery story where chance, the ability to capitalise on chance, and the assembling of a range of expertise, have all played important roles in the discovery and subsequent development of an antibiotic chemotype based on the bis-benzimidazole scaffold, with potency against a number of current therapeutically challenging diseases. One compound in this class, SMT19969, has recently entered Phase 2 human clinical trials for the treatment of Clostridium difficile infections

Kelp forest restoration in Australia

Kelp forests dominate the rocky coasts of temperate Australia and are the foundation of the Great Southern Reef. Much like terrestrial forests, these marine forests create complex habitat for diverse communities of flora and fauna. Kelp forests also support coastal food-webs and valuable fisheries and provide a suite of additional ecosystem services. In many regions of Australia and around the world, kelp forests are in decline due to ocean warming, overgrazing, and pollution. One potential tool in the conservation and management of these important ecosystems is habitat restoration, the science and practice of which is currently undergoing substantial expansion. We summarize the present state of Australian kelp forests and emphasize that consideration of the initial drivers of kelp decline is a critical first step in restoration. With a focus on Australian examples, we review methods, implementation and outcomes of kelp forest restoration, and discuss suitable measures of success and the estimated costs of restoration activities. We propose a workflow and decision system for kelp forest restoration that identifies alternative pathways for implementation and acknowledges that under some circumstances restoration at scale is not possible or feasible. As a case study, we then apply the Society for Ecological Restoration’s 5-star evaluation to Operation Crayweed, Australia’s primary example of kelp forest restoration. Overall, no single method of kelp forest restoration is suitable for all situations, but outcomes can be optimized by ameliorating the driver(s) of kelp decline and achieving ongoing natural recruitment of kelp. Whilst scalability of kelp forest restoration to the seascape-scale remains a considerable challenge, the present review should provide a platform for future restoration efforts. However, it is also crucial to emphasize that the challenges of restoration place a high value on preventative conservation and protection of existing kelp forest ecosystems – prevention is invariably better than cure