Transdermal Pharmacology of Small Molecule Cyclic C5a Antagonists

Overproduction or underregulation of the proinflammatory complement component C5a has been implicated in numerous immune and inflammatory conditions. Therefore, targeting the C5a receptor (C5aR) has become an innovative strategy for antiinflammatory drug development. The novel cyclic peptide C5aR antagonist, AcF-[OP(D-Cha)WR] (PMX53), attenuates injury in numerous animal models of inflammation following intravenous, subcutaneous, intraperitoneal, and oral administration. In the present study the transdermal pharmacology of PMX53 and three analogs designed with increased lipophilicity, hydrocinnamate-[OP(D-Cha)WCit] (PMX200), AcF-[OP(D-Cha)WCit] (PMX201) and hydrocinnamate-[OP(D-Cha)WR] (PMX205), have been examined in order to assess their transdermal permeability and inhibitory effect on C5a-mediated lipopolysaccharide (LPS)-induced systemic responses. In the rat, PMX53, PMX201, and PMX205, were bioavailable following topical dermal administration (10 mg/50 cm(2) site/rat). All analogs functionally antagonized neutropenia and hypotension induced by systemic challenge with LPS (I mg/kg i.v.). Interestingly, PMX200 attenuated LPS-induced neutropenia more effectively than other analogs, despite undetectable (< 5 ng/ml) circulating levels following topical administration. In conclusion, we have demonstrated that cyclic peptide C5aR antagonists can penetrate transdermally sufficiently to have systemic effects. However, increasing lipophilicity in these compounds did not result in increased blood levels. Nonetheless, topical application of C5aR antagonists produced circulating levels of the drugs that antagonized the LPS-induced systemic responses of neutropenia and hypotension. This suggests that these small-molecule C5aR antagonists may be developed for topical administration for the treatment of local and systemic inflammatory conditions in the human and veterinary pharmaceutical markets.

Conservation and economic benefits of wildlife-based marine tourism: Sea turtles and whales as case studies

Tourism development can have positive and/or negative impacts on wildlife. However, if tourism is developed in accordance with the basic tenets of wildlife tourism such an activity can be sustainable and can aid the conservation of species. Based on two case studies in Queensland, Australia, this article outlines the various economic and conservation benefits arising from wildlife-based tourism. Some of the benefits are direct, such as tangible economic benefits, others are less tangible, such as increased visitors’ willingness to pay in principle for the conservation of species. Wildlife-based tourism is shown to foster political support for the conservation of species utilized for such tourism by various mechanisms. Non-consumptive uses of wildlife are not only sustainable, but may provide a viable alternative to consumptive uses.

Ecotourism/Wildlife-based tourism as contributor to nature conservation with reference to Vanni, Sri Lanka

After discussing definitions of ecotourism, outlines possible economic and conservational benefits from developing ecotourism or wildlife-based tourism. Identifies possible economic benefits for local communities but also outlines possible economic costs to such communities. Observations are made on the potential of developing ecotourism in the Giant’s Tank/Mannar area. A sufficient market does not always exist for wildlife-based tourism to make it economically viable. Therefore, market analysis should be undertaken before promoting the development of wildlife-based tourism in a locality. A checklist is provided to give some guidance in market appraisal. It is observed that even non-consumptive wildlife-based tourism can have adverse environmental consequences and these are listed. Care is needed to avoid these negative consequences and to ensure that local communities do in fact obtain adequate economic benefits from the development of wildlife-based tourism.