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Sent on Thursday, 2010 Sep 23Search kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"
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| PubMed Results |
| 1. | Lancet. 2010 Sep 4;376(9743):768; author reply 768-9.Antitrypanosomal agents: treatment or threat?Issa VS, Bocchi EA.Comment on: |
| PMID: 20816538 [PubMed - indexed for MEDLINE] | |
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| 2. | Antimicrob Agents Chemother. 2010 Jul;54(7):2940-52. Epub 2010 May 10.Arylimidamide DB766, a potential chemotherapeutic candidate for Chagas' disease treatment.Batista Dda G, Batista MM, de Oliveira GM, do Amaral PB, Lannes-Vieira J, Britto CC, Junqueira A, Lima MM, Romanha AJ, Sales Junior PA, Stephens CE, Boykin DW, Soeiro Mde N.Laboratório de Biologia Celular, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brazil. AbstractChagas' disease, a neglected tropical illness for which current therapy is unsatisfactory, is caused by the intracellular parasite Trypanosoma cruzi. The goal of this work is to investigate the in vitro and in vivo effects of the arylimidamide (AIA) DB766 against T. cruzi. This arylimidamide exhibits strong trypanocidal activity and excellent selectivity for bloodstream trypomastigotes and intracellular amastigotes (Y strain), giving IC(50)s (drug concentrations that reduce 50% of the number of the treated parasites) of 60 and 25 nM, respectively. DB766 also exerts striking effects upon different parasite stocks, including those naturally resistant to benznidazole, and displays higher activity in vitro than the reference drugs. By fluorescent and transmission electron microscopy analyses, we found that this AIA localizes in DNA-enriched compartments and induces considerable damage to the mitochondria. DB766 effectively reduces the parasite load in the blood and cardiac tissue and presents efficacy similar to that of benznidazole in mouse models of T. cruzi infection employing the Y and Colombian strains, using oral and intraperitoneal doses of up to 100 mg/kg/day that were given after the establishment of parasite infection. This AIA ameliorates electrocardiographic alterations, reduces hepatic and heart lesions induced by the infection, and provides 90 to 100% protection against mortality, which is similar to that provided by benznidazole. Our data clearly show the trypanocidal efficacy of DB766, suggesting that this AIA may represent a new lead compound candidate to Chagas' disease treatment. |
| PMID: 20457822 [PubMed - indexed for MEDLINE] | |
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| 3. | Antimicrob Agents Chemother. 2010 Jul;54(7):2979-86. Epub 2010 Apr 19.Effects of ravuconazole treatment on parasite load and immune response in dogs experimentally infected with Trypanosoma cruzi.Diniz Lde F, Caldas IS, Guedes PM, Crepalde G, de Lana M, Carneiro CM, Talvani A, Urbina JA, Bahia MT.Departamento de Ciências Biológicas, Universidade Federal de Ouro Preto, Ouro Preto, MG, Brazil. AbstractIn this work, we investigated the in vivo activity of ravuconazole against the Y and Berenice-78 Trypanosoma cruzi strains using acutely infected dogs as hosts. Ravuconazole was well tolerated, as no significant side effects were observed during the treatment using 6.0 mg/kg twice a day (12 mg/kg/day) for up to 90 days. In all treated animals, parasitemia was permanently suppressed by the first day of treatment, independently of the parasite strain. Cultures of blood obtained posttreatment were negative for 90% of the animals, confirming that the drug induced a marked reduction in the parasite load. The results of PCR tests for T. cruzi in blood performed 1 month posttreatment were consistently negative for three of five and two of five animals infected with the Y and Berenice-78 strains, respectively. All ravuconazole-treated dogs consistently had negative serological test results during and until 30 days after treatment, regardless of the therapeutic scheme used. However, after the end of treatment, an increase in specific antibody levels was observed in all treated animals, although the antibody levels were always significantly lower than those of the nontreated control dogs. Despite being unable to induce a parasitological cure, ravuconazole treatment led to significant reductions in the levels of gamma interferon expression and lesions in cardiac tissues in animals infected with the Y strain, while the level of interleukin-10 mRNA expression increased. We conclude that ravuconazole has potent suppressive but not curative activity in the canine model of acute Chagas' disease, probably due to its unfavorable pharmacokinetic properties (half-life, 8.8 h). The longer half-life of ravuconazole in humans (4 to 8 days) makes it a promising drug for assessment for use as chemotherapy in human Chagas' disease. |
| PMID: 20404124 [PubMed - indexed for MEDLINE] | |
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| 4. | Afr J Tradit Complement Altern Med. 2009 Jul 3;6(4):585-91.The effect of aqueous extracts of Hibiscus sabdariffa (So rrel) calyces on heamatological profile and organ pathological changes in Trypanasoma congolense - infected rats.Umar IA, Maryoms NG, Daikwo E, Gidado A, Buratai LB, Igbokwe IO, Ibrahim MA.Department of Biochemistry, Faculty of sciences, Ahmadu Bello University, Zaria, Nigeria. smaumar@yahoo.com AbstractThe effects of aqueous extract of Hibiscus sabdariffa calyces on haematology and pathological changes in some selected organs during experimental Trypanosoma congolense infection of rats were investigated. Three groups of rats were intraperitoneally infected with T. congolense (Karu stock). One group was administered with the aqueous extract and another given a solution of vitamin C in drinking water; the remaining infected group was left untreated. Data from these groups were compared with those of two groups of healthy rats, one of which was similarly treated with the aqueous extract. The experiment was terminated three weeks, post-infection (pi). The uninfected and infected rats administered the extract consumed the equivalent of 9.94 mg - and 9.61 mg ascorbic acid / 100g / day during the experiment. Consumption of the extract significantly (p<0.01) retarded the rate of weight gain in both healthy and infected rats; even though the feed-intake was not significantly affected. After two weeks of infection the extract and vitamin C kept the parasitaemia significantly (p<0.01) lower than the untreated infected group. The anaemia in the untreated infected group was significantly (p<0.01) more severe than that of the corresponding extract- or vitamin-treated groups. Trypanosoma congolense infection caused significant (p<0.01) decreases in serum total proteins and albumin; serum and organ ascorbic acid as well as significant (p<0.01) elevation of serum alanine amino transferase levels in untreated rats. Consumption of the extract or vitamin C, however, prevented these disease-induced anomalies in the treated infected rats. Serum creatinine and urea levels were not affected by infection but the extract elevated these parameters significantly (p<0.01) above infection levels. It was concluded that consumption of the extract ameliorated the pathological changes in blood and organs of T. congolense-infected rats. |
| PMID: 20606781 [PubMed - indexed for MEDLINE] | |
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