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Sent on Saturday, 2010 May 01Search kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"
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| PubMed Results |
| 1. | Eur J Med Chem. 2010 Apr 7. [Epub ahead of print]Synthesis and biological activity of 2-(trifluoromethyl)-1H-benzimidazole derivatives against some protozoa and Trichinella spiralis.Hernández-Luis F, Hernández-Campos A, Castillo R, Navarrete-Vázquez G, Soria-Arteche O, Hernández-Hernández M, Yépez-Mulia L.Facultad de Química, Departamento de Farmacia, UNAM, México, DF 04510, Mexico. AbstractA series of 2-(trifluoromethyl)-1H-benzimidazole derivatives (1a-1i) were synthesized via Phillips cyclocondensation of a substituted 1,2-phenylenediamine and trifluoroacetic acid. The synthesized compounds were evaluated in vitro against various protozoan parasites: Giardia intestinalis, Entamoeba histolytica, Trichomonas vaginalis and Leishmania mexicana, and they showed nanomolar activities against the first three protozoa tested. The compounds were also tested in vitro and in vivo against the nematode Trichinella spiralis. Compounds 1b, 1c and 1e had the most desirable in vitro antiparasitic profile against all parasites studied. In the in vivo model against T. spiralis, compounds 1b and 1e showed good activity against the adult phase at 75 mg/Kg. However, against the muscle larvae stage, only compound 1f exhibited in vivo antiparasitic efficacy. Copyright © 2010 Elsevier Masson SAS. All rights reserved. |
| PMID: 20430484 [PubMed - as supplied by publisher] | |
| 2. | Vet Immunol Immunopathol. 2010 Apr 8. [Epub ahead of print]Differential alterations in the activity of matrix metalloproteinases within the nervous tissue of dogs in distinct manifestations of visceral leishmaniasis.Machado GF, Melo GD, Moraes OC, Souza MS, Marcondes M, Perri SH, Vasconcelos RO.Departamento de Clínica, Cirurgia e Reproducão Animal, Universidade Estadual Paulista "Júlio de Mesquita Filho" (UNESP), School of Veterinary Medicine, FO-Araçatuba, São Paulo, Brazil. AbstractCanine visceral leishmaniasis is an important emerging disease with a multitude of clinical symptoms, including neurological alterations. Matrix metalloproteinases (MMP) are proteases implicated with the extracellular matrix remodelling and, within the central nervous system, these enzymes are involved with blood-brain-barrier disruption and inflammation. To establish the involvement of MMP-2 and -9 within the nervous tissue of dogs with spontaneous visceral leishmaniasis, fragments of nervous tissue from oligosymptomatic (n=9), symptomatic (n=8), neurological (n=12) and normal dogs (n=8) were subjected to zymographic and to immunohistochemical analysis. Immunohistochemistry evidenced MMP-2 staining in inflammatory cells inside and outside blood vessels. MMP-9 was found in endothelial cells and in the ependyma. Zymographic evaluation revealed only the latent forms of MMP-2 and -9 within the nervous tissue. ProMMP-9 activity in the infected animals was found higher than the normal dogs, but with no difference among the infected dogs. Oligosymptomatic dogs presented the highest proMMP-2 activity, followed by the symptomatic and then, by the neurological and the normal dogs. In summary, the nervous tissue compartment seems to be preserved in dogs with VL, due to the absence of active MMPs, even though the elevated levels of proMMP-2 and -9 would indicate a pro-inflammatory state in the brain. Copyright © 2010 Elsevier B.V. All rights reserved. |
| PMID: 20430448 [PubMed - as supplied by publisher] | |
| 3. | Infect Genet Evol. 2010 Apr 26. [Epub ahead of print]The -2518bp promoter polymorphism at CCL2/MCP1 influences susceptibility to mucosal but not localized cutaneous leishmaniasis in Brazil.Ramasawmy R, Menezes E, Magalhães A, Oliveira J, Castellucci L, Almeida R, Rosa ME, Guimarães LH, Lessa M, Noronha E, Wilson ME, Jamieson SE, Kalil J, Blackwell JM, Carvalho EM, Jesus AR.Universidade Federal da Bahia, Salvador, Brazil; Laboratorio de Imunologia-InCor-USP, São Paulo, Brazil; Instituto de Investigação em Imunologia, São Paulo, Brazil. AbstractMucosal leishmaniasis (ML) follows localized cutaneous leishmaniasis (CL) caused by Leishmania braziliensis. Proinflammatory responses mediate CL self-healing but are exaggerated in ML. Proinflammatory monocyte chemoattractant protein 1 (MCP-1; encoded by CCL2) is associated with CL. We explore its role in CL/ML through analysis of the regulatory CCL2 -2518bp promoter polymorphism in CL/ML population samples and families from Brazil. Genotype frequencies were compared among ML/CL cases and control groups using logistic regression and the family-based association test (FBAT). MCP-1 was measured in plasma and macrophages. The GG recessive genotype at CCL2 -2518bp was more common in patients with ML (N=67) than in neighborhood control (NC; N=60) subjects (OR 1.78; 95% CI 1.01-3.14; P=0.045), than in NC combined with leishmanin skin-test positive (N=60) controls (OR 4.40; 95% CI 1.42-13.65; P=0.010), and than in controls combined with CL (N=60) patients (OR 2.78; 95% CI 1.13-6.85; P=0.045). No associations were observed for CL compared to any groups. FBAT (91 ML and 223 CL cases in families) confirmed recessive association of ML with allele G (Z=2.679; P=0.007). Higher levels of MCP-1 occurred in plasma (P=0.03) and macrophages (P<0.0001) from GG compared to AA individuals. These results suggest that high MCP-1 increases risk of ML. Copyright © 2010. Published by Elsevier B.V. |
| PMID: 20430117 [PubMed - as supplied by publisher] | |
| 4. | Infect Disord Drug Targets. 2010 Apr 29. [Epub ahead of print]The Human Trypanolytic Factor: A Drug Shaped Naturally.Vanhamme L.Laboratory of Molecular Parasitology and Laboratory of Molecular Biology of Ectoparasites, IBMM (Institute for Molecular Biology and Medicine), Université Libre de Bruxelles, 12 rue des Professeurs Jeener et Brachet,6041 Gosselies, Belgium luvhamme@ulb.ac.be. AbstractAfrican trypanosomes are responsible for sleeping sickness in man and nagana in cattle, which are both tremendous health burdens in Africa. Most African trypanosome species are killed by human serum. This is due to a serum trypanolytic particle specific of some old world monkeys and great apes, an HDL subclass containing two proteins which appeared recently in mammalian evolution, apolipoprotein L1 and haptoglobin related protein. Nevertheless, two African trypanosome species, Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense are able to infect humans, because they developed resistance to trypanolysis. Resistance to human serum in Trypanosoma brucei rhodesiense is due to a single gene called SRA. This mechanism of lysis-resistance is therefore an example of a natural drug-antidote system which evolved during a pathogen-host arms race. The lysis and resistance mechanisms, their molecular components as well as their mode of action are reviewed. I also discuss how components of the system would be suitable drug targets and how the system could be engineered to generate an effective synthetic drug. |
| PMID: 20429865 [PubMed - as supplied by publisher] | |
| 5. | Berl Munch Tierarztl Wochenschr. 2010 Mar-Apr;123(3-4):96-102.[Euthanasia of cattle: a clinical comparison of T 61 and pentobarbital (Eutha 77)][Article in German] Blank C, Metzner M, Lorch A, Klee W.Klinik für Wiederkäuer mit Ambulanz und Bestandsbetreuung, Ludwig-Maximilians-Universität München. AbstractThe objective of this study was a comparison of pentobarbital and T 61 in the euthanasia of cattle. 397 cattle of different ages and breeds which had to be euthanised in the Clinic for Ruminants were enrolled. Following clinical examination, euthanasia was performed by intravenous injection of either 40 mg pentobarbital per kg body weight (BW) (0.1 ml Eutha 77) or 0.1 ml T 61/kg BW. The intervals between the beginning of injection and the following events were noted: collapse of the animal, cessation of respiration, cessation of cardiac action, disappearance of the palpebral and corneal reflexes, and maximum dilatation of the pupils. These post-injection events occurred significantly earlier with Eutha 77. In addition, events like excitations and vocalisations were recorded. Excitations occurred twice as often with T 61 (in 34% of cases) than with Eutha 77 (17%), and strong excitations (grade 3 of 3) were also more frequent with T 61 (9.8%) than with Eutha 77 (3%). Vocalisations were less frequent (30%) with T 61 than with pentobarbital (39%), but this difference was not significant. Severe vocalisations occurred very rarely. With both drugs, intervals between the beginning of injection until cessation of reflexes were longer in older animals. Following injection of Eutha 77, cessation of the corneal reflex and maximal dilatation of the pupils occurred earlier in cattle with severe disturbance of the general condition than in cattle with lesser disturbance; in the T 61-group this difference was only significant for the interval until cessation of the corneal reflex. In anaesthetized patients euthanized with T 61 cessation of cardiac action and respiration occurred earlier than in patients that were not under general anaesthesia when euthanized; in the Eutha 77 group, the difference was significant only for the interval until cessation of cardiac action. |
| PMID: 20329641 [PubMed - indexed for MEDLINE] | |
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| 6. | Int J Parasitol. 2010 Mar 1;40(3):345-55. Epub 2009 Sep 18.Phylogeographical, ecological and biological patterns shown by nuclear (ssrRNA and gGAPDH) and mitochondrial (Cyt b) genes of trypanosomes of the subgenus Schizotrypanum parasitic in Brazilian bats.Cavazzana M Jr, Marcili A, Lima L, da Silva FM, Junqueira AC, Veludo HH, Viola LB, Campaner M, Nunes VL, Paiva F, Coura JR, Camargo EP, Teixeira MM.Departamento de Parasitologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, SP 05508-900, Brazil. AbstractThe genetic diversity and phylogeographical patterns of Trypanosoma species that infect Brazilian bats were evaluated by examining 1043 bats from 63 species of seven families captured in Amazonia, the Pantanal, Cerrado and the Atlantic Forest biomes of Brazil. The prevalence of trypanosome-infected bats, as estimated by haemoculture, was 12.9%, resulting in 77 cultures of isolates, most morphologically identified as Trypanosoma cf. cruzi, classified by barcoding using partial sequences from ssrRNA gene into the subgenus Schizotrypanum and identified as T. cruzi (15), T. cruzi marinkellei (37) or T. cf. dionisii (25). Phylogenetic analyses using nuclear ssrRNA, glycosomal glyceraldehyde 3-phosphate dehydrogenase (gGAPDH) and mitochondrial cytochrome b (Cyt b) gene sequences generated three clades, which clustered together forming the subgenus Schizotrypanum. In addition to vector association, bat trypanosomes were related by the evolutionary history, ecology and phylogeography of the bats. Trypanosoma cf. dionisii trypanosomes (32.4%) infected 12 species from four bat families captured in all biomes, from North to South Brazil, and clustered with T. dionisii from Europe despite being separated by some genetic distance. Trypanosoma cruzi marinkellei (49.3%) was restricted to phyllostomid bats from Amazonia to the Pantanal (North to Central). Trypanosoma cruzi (18.2%) was found mainly in vespertilionid and phyllostomid bats from the Pantanal/Cerrado and the Atlantic Forest (Central to Southeast), with a few isolates from Amazonia. 2009 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved. |
| PMID: 19766649 [PubMed - indexed for MEDLINE] | |
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| 7. | Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2008 Jan;24(1):16-9.[The molecular mechanism of survivin expression in activated human peripheral lymphocytes][Article in Chinese] Dong Y, Mei ZZ, Qian JJ, Song Y, Tian BL, Liu B, Sun ZX.Institute of Radiation Medicine, Beijing 100850, China. AbstractAIM: Investigate the molecular mechanism of regulating survivin expression and related signal transduction pathway, molecular cascade reaction and biological effects in activated PBMC. METHODS: The expression of survivin and related proteins were detected by Western blot in PBMC stimulated by PHA and rhIL-2 with or without JAK inhibitor-AG490 treatment, and FCM was performed to analyze cell cycle and cell division. RESULTS: Our results indicated that molecular and cellular reactions in PBMC activated by PHA and rhIL-2 were dependent on time series. At first, the phosphorylation of Stat3 and Stat5 were observed, then, protein levels of CyclinD3 and CyclinE increased, and the stimulated PBMC began to enter to S phage with survivin protein expression was initiated, which at last resulted in cell division with dramatically increasing expression of survivin protein. AG490 could significantly inhibit all these reactions but had no effect on the expressions of the cell cycle inhibitor-P21 and anti-apoptosis protein-Bcl-2. CONCLUSION: The expression of survivin in stimulated PBMC was dependent on the primarily activated JAK-STAT pathway, which upregulated CyclinD3 and CyclinE protein levels, initiated the cell cycle progression, and induced cell cycle-dependent survivin expression, and so survivin was involved in cell division and cell proliferation. |
| PMID: 18177610 [PubMed - indexed for MEDLINE] | |
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