REMOVING THE THREAT OF DICLOFENAC TO CRITICALLY ENDANGERED ASIAN VULTURES

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The Vulture Crisis

At least three species of vulture, endemic to South Asia, are in grave danger of extinction across the Indian subcontinent54,106,122. Populations of Oriental white-backed vulture (Gyps bengalensis), long-billed vulture (G. indicus) and slender-billed vulture (G. tenuirostris) have declined by more than 97% in India and Pakistan with the annual rates of decline, appearing to be on the increase54,106,122. Due to these declines, all three species were listed by IUCN, The World Conservation Union, as Critically Endangered15.
Research by Oaks et al., 2004, first indicated diclofenac, a non-steroidal anti-inflammatory drug (NSAID), as the only cause of the observed rapid population decline across the Indian subcontinent in 2003100. This indicated that the catastrophe was purely secondary, following exposure to diclofenac residues in the food source. This problem has since been reproduced under controlled experimental conditions in captive Asian white-backed vultures100.
From the current literature published for mammalian species, diclofenac is a typical NSAID which works by suppressing inflammation, pain and fever112. Diclofenac, as with other first generation NSAIDs, inhibits the activity of both the cyclo-oxygenase-1 and cyclo-oxygenase-2 enzymes to produce their beneficial effects. This mechanism is unfortunately also related to their toxicophoric effects such as gastric ulceration, renal toxicity and impaired liver function20. In addition to the typical use of the NSAIDs diclofenac is an important component in the control of gout in people. This effect is directly opposite to that seen in vultures i.e. the drug treats gout in people and yet is the major cause of gout in vultures112.
Although the use of diclofenac has been conclusively shown to be the cause of the vulture population decline, the mechanism of toxicity has not been adequately explained. At present the only consistent change present at all post mortem examinations was severe Picture of a golden vulture 89; Picture of vulture with outspread wing4 Diclofenac in Gyps vultures:
A molecular mechanism of toxicity diffuse visceral gout, which tends to suggest the kidneys or its supportive circulatory system are the target for drug toxicity90,100. More importantly the decline in the vulture numbers needs to be stemmed. At present the Royal Society for the protection of birds, has set up numerous breeding colonies in India to achieve this goal. Unfortunately with vulture pairs producing only one egg a year, these breeding centres will never re-populate the species. This has therefore made it very important to prevent further losses in the current vulture population. A major obstacle to achieving this has been the Indian Governments refusal to ban the sale and manufacture of diclofenac, due to its importance in a holy animal. They, however, made the proviso that their stance may be re-considered if an alternate vulture-safe NSAID were to be described.

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CHAPTER 1: INTRODUCTION 
1.1 The Vulture Crisis
1.2 Hypotheses.
1.3 Objectives
CHAPTER 2: LITERATURE REVIEW.
2.1 Vultures: Twenty-first century outcasts
2.2 A crash in the Indian Vulture Population.
2.3 Impact of a Declining Vulture Population
2.4 NSAIDs: An Overview .
2.5 Diclofenac .
2.6 Towards the protection of a disappearing species
2.7 Conclusion
2.8 References
CHAPTER 3: REMOVING THE THREAT OF DICLOFENAC TO CRITICALLY
ENDANGERED ASIAN VULTURES .
3.1 Abstract
3.2 Introduction
3.3 Results and Discussion
3.4 Conclusions
3.5 Materials and Methods .
3.6 Acknowledgements
3.7 References.
CHAPTER 4: THE PHARMACOKINETICS OF MELOXICAM IN VULTURES 
4.1 Abstract
4.2 Introduction
4.3 Material and Methods.
4.4 Results.
4.5 Discussion
4.6 Conclusion .
4.7 Acknowledgements .
4.8 References.
CHAPTER 5: VALIDATING THE DOMESTIC FOWL AS A MODEL TO
INVESTIGATE THE PATHOPHYSIOLOGY OF DICLOFENAC IN GYPS
VULTURES.
CHAPTER 6: ESTABLISHMENT OF SELECTED BASELINE BLOOD CHEMISTRY AND HEMATOLOGICAL PARAMETERS IN CAPTIVE AND WILDCAUGHT AFRICAN WHITE-BACKED VULTURES (GYPS AFRICANUS)
CHAPTER 7: DICLOFENAC IN GYPS VULTURES: A MOLECULAR MECHANISM OF TOXICITY.
CHAPTER 8: GENERAL DISCUSSION 

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