Recombinant Entamoeba histolytica Protein [His]

Diarrhoeal diseases caused by the intestinal parasites Giardia lamblia and Entamoeba histolytica constitute a major global health burden. Nitroimidazoles are first-line drugs for the treatment of giardiasis and amebiasis, with metronidazole 1 being the most commonly used drug worldwide. However, treatment failures in giardiasis occur in up to 20% of cases and development of resistance to metronidazole is of concern. We have re-examined 'old' nitroimidazoles as a foundation for the systematic development of next-generation derivatives. Using this approach, derivatisation of the nitroimidazole carboxamide scaffold provided improved antiparasitic agents. Thirty-three novel nitroimidazole carboxamides were synthesised and evaluated for activity against G. lamblia and E. histolytica. Several of the new compounds exhibited potent activity against G. lamblia strains, including metronidazole-resistant strains of G. lamblia (EC50 = 0.1-2.5 mu M cf. metronidazole EC50 = 6.1-18 mu M). Other compounds showed improved activity against E. histolytica (EC50 = 1.7-5.1 mu M cf. metronidazole EC50 = 5.0 mu M), potent activity against Trichomonas vaginalis (EC50 = 0.6-1.4 mu M cf. metronidazole EC50 = 0.8 mu M) and moderate activity against the intestinal bacterial pathogen Clostridium difficile (0.5-2 mu g/mL, cf. metronidazole = 0.5 mu g/mL). The new compounds had low toxicity against mammalian kidney and liver cells (CC50 > 100 mu M), and selected antiparasitic hits were assessed for human plasma protein binding and metabolic stability in liver microsomes to demonstrate their therapeutic potential. (C) 2016 The Authors. Published by Elsevier Masson SAS.

Myotragus balearicus (Artiodactyla, Caprinae) is an extinct caprine endemic of the Eastern Balearic Islands or Gymnesics (i.e., Mallorca, Menorca and surrounding islets, Western Mediterranean Sea). In spite of its small size, c. 50 cm height at the shoulder, it was the largest mammal inhabiting these islands until the human arrival, and it had peculiar short legs and frontal vision. It disappeared between 2830 and 2210 cal BCE. The coprolites here studied were recovered from Cova Estreta, in Pollenca, Mallorca. The samples were subjected to microscopic examination and enzyme-linked immunosorbent assays (ELISA) for E. histolytica/E. dispar, Giardia intestinalis and Cryptosporidium parvum. This study provides new paleoparasitological data from an extinct animal species of the Holocene period. The microscopy revealed one sample containing uninucleated-cyst of Entamoeba sp., whereas ELISA detected nine positive samples for Cryptosporidium sp. The finding of these protozoans can help in the discussion of its extinction cause and demonstrates the antiquity and the evolutionary history of host-parasite relationships between protozoa and caprines since the Messinian. (C) 2016 Elsevier Ireland Ltd. All rights reserved.