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2.
Antimicrob Agents Chemother ; 58(7): 3720-6, 2014 Jul.
Article in English | MEDLINE | ID: mdl-24752263

ABSTRACT

Chagas disease (CD), a neglected tropical disease caused by Trypanosoma cruzi, remains a serious public health problem in several Latin American countries. The available chemotherapies for CD have limited efficacy and exhibit undesirable side effects. Aromatic diamidines and arylimidamides (AIAs) have shown broad-spectrum activity against intracellular parasites, including T. cruzi. Therefore, our aim was to evaluate the biological activity of eight novel AIAs (16DAP002, 16SAB079, 18SAB075, 23SMB022, 23SMB026, 23SMB054, 26SMB070, and 27SMB009) against experimental models of T. cruzi infection in vitro and in vivo. Our data show that none of the compounds induced a loss of cellular viability up to 32 µM. Two AIAs, 18SAB075 and 16DAP002, exhibited good in vitro activity against different parasite strains (Y and Tulahuen) and against the two relevant forms of the parasite for mammalian hosts. Due to the excellent selective indexes of 18SAB075, this AIA was moved to in vivo tests for acute toxicity and parasite efficacy; nontoxic doses (no-observed-adverse-effect level [NOAEL], 50 mg/kg) were employed in the tests for parasite efficacy. In experimental models of acute T. cruzi infection, 18SAB075 reduced parasitemia levels only up to 50% and led to 40% protection against mortality (at 5 mg/kg of body weight), being less effective than the reference drug, benznidazole.


Subject(s)
Amidines/pharmacology , Trypanocidal Agents/pharmacology , Trypanosoma cruzi/drug effects , Amidines/therapeutic use , Amidines/toxicity , Animals , Cell Survival , Chagas Disease/drug therapy , Chagas Disease/parasitology , Galactosidases/metabolism , Male , Mice , Nitroimidazoles/pharmacology , No-Observed-Adverse-Effect Level , Parasitemia/drug therapy , Parasitemia/parasitology , Primary Cell Culture , Trypanocidal Agents/therapeutic use , Trypanocidal Agents/toxicity
3.
Conserv Physiol ; 2(1): cou013, 2014.
Article in English | MEDLINE | ID: mdl-27293634

ABSTRACT

Identification of the importance of habitats that are frequently used by any species is essential to a complete understanding of the species' biology and to incorporate their ecological role into conservation and management programmes. In this context, the present study investigated whether Tasmanian coastal waters have any reproductive relevance for the broadnose sevengill shark (Notorynchus cepedianus). Although this species is a large coast-associated apex predator in these areas, there is a complete gap in understanding the role that these coastal systems could play in its reproduction. Reproductive hormones were used as a non-lethal method to address the reproductive biology of this species. Females seemed to have at least a bi-annual reproductive cycle, being pregnant for ∼1 year and spending at least 1 year non-pregnant, with the ovulatory cycle separated from gestation. Mature females were found to be ovulating, in the initial stages of pregnancy, resting or starting a new vitellogenic cycle. Notorynchus cepedianus did not use these coastal habitats for mating or as a pupping ground. Although the mating season was distinguished between September to April, only 22% of males showed mating scars during the peak of the mating period and no near-term pregnant females were observed. Thus, despite these coastal waters being an important foraging ground for this species, these areas did not have any reproductive relevance. In consequence, future management and conservation planning programmes need to identify whether there are other areas in Tasmania that play a critical role for reproductive purposes in this species. Finally, although previous studies have linked reproductive hormones with external examination of the gonads to validate the use of steroids as a non-lethal tool to address reproduction, the present study used this methodology without killing any animals. This has important implications for conservation programmes of threatened and endangered species worldwide where the methodology cannot be validated.

4.
Mol Phylogenet Evol ; 42(3): 612-21, 2007 Mar.
Article in English | MEDLINE | ID: mdl-17254806

ABSTRACT

Coptotermes gestroi, the Asian subterranean termite (AST), is an economically important structural and agricultural pest that has become established in many areas of the world. For the first time, phylogeography was used to illuminate the origins of new found C. gestroi in the US Commonwealth of Puerto Rico; Ohio, USA; Florida, USA; and Brisbane, Australia. Phylogenetic relationships of C. gestroi collected in indigenous locations within Malaysia, Thailand, and Singapore as well as from the four areas of introduction were investigated using three genes (16S rRNA, COII, and ITS) under three optimality criteria encompassing phenetic and cladistic assumptions (maximum parsimony, maximum likelihood, and neighbor-joining). All three genes showed consistent support for a close genetic relationship between C. gestroi samples from Singapore and Ohio, whereas termite samples from Australia, Puerto Rico, and Key West, FL were more closely related to those from Malaysia. Shipping records further substantiated that Singapore and Malaysia were the likely origin of the Ohio and Australia C. gestroi, respectively. These data provide support for using phylogeography to understand the dispersal history of exotic termites. Serendipitously, we also gained insights into concerted evolution in an ITS cluster from rhinotermitid species in two genera.


Subject(s)
Animal Migration/physiology , Genes, Mitochondrial , Geography , Isoptera/genetics , Phylogeny , Algorithms , Animals , Australia , DNA, Ribosomal Spacer/genetics , Florida , Ohio , Puerto Rico , RNA, Ribosomal, 16S/analysis , RNA, Ribosomal, 16S/genetics
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