What's new for 'Trypanosomatids' in PubMed

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Sent on Saturday, 2010 Nov 20
Search kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"
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PubMed Results

Items 1 - 5 of 5

1.	Naunyn Schmiedebergs Arch Pharmacol. 2010 Nov 19. [Epub ahead of print] Δ(2,3) -Ivermectin ethyl secoester, a conjugated ivermectin derivative with leishmanicidal activity but without inhibitory effect on mammalian P-type ATPases. Noël F, Pimenta PH, Dos Santos AR, Tomaz EC, Quintas LE, Kaiser CR, Silva CL, Férézou JP. Laboratório de Farmacologia Bioquímica e Molecular, Instituto de Ciências Biomédicas, Centro de Ciências da Saúde, Bloco J - sala 17, Universidade Federal do Rio de Janeiro, Ilha do Fundão, Av. Carlos Chagas Filho, 373, CEP: 21941-902, Rio de Janeiro, RJ, Brazil, fnoel@pharma.ufrj.br. Abstract Looking at a new putative target for the large spectrum antiparasitic drug ivermectin, we recently showed that avermectin-derived drugs are active against promastigote and amastigote forms of Leishmania amazonensis at low micromolar concentrations. However, we then reported that at this concentration range ivermectin is also able to inhibit three important mammalian P-type ATPases so that unacceptable adverse effects could occur if this drug were used at such high doses therapeutically. The present work aimed to test the activity of ten ivermectin analogs on these rat ATPases in search of a compound with similar leishmanicidal activity but with no effect on the mammalian (host) ATPases at effective concentrations. We synthesized three new ivermectin analogs for testing on rat SERCA (1a and 1b), Na(+), K(+)-ATPase (α(1) and α(2)/α(3) isoforms) and H(+)/K(+)-ATPase activity, along with seven analogs already characterized for their leishmanicidal activity. Our main finding is that one of the prepared derivatives, Δ(2,3) -ivermectin ethyl secoester 8, is equipotent to ivermectin 1 for the in vitro leishmanicidal effects but is nearly without effect on the rat ATPases, indicating that it could have a better therapeutic index in vivo and could serve as a candidate for hit-to-lead progression. This conclusion is further supported by the fact that compound 8 produced only 6% (vs 77% for ivermectin) inhibition of the human kidney enzyme at 5 μM, a concentration corresponding to the IC(50) for the activity against L. amazonensis amastigotes.
	PMID: 21088826 [PubMed - as supplied by publisher]

2.	Braz J Med Biol Res. 2010 Nov;43(11):1054-1061. Epub 2010 Oct 14. In vitro activity of hypnophilin from Lentinus strigosus: a potential prototype for Chagas disease and leishmaniasis chemotherapy. Souza-Fagundes EM, Cota BB, Rosa LH, Romanha AJ, Corrêa-Oliveira R, Rosa CA, Zani CL, Teixeira-Carvalho A, Martins-Filho OA. Departamento de Fisiologia e Biofísica, Universidade Federal de Minas Gerais. Abstract Hypnophilin and panepoxydone, terpenoids isolated from Lentinus strigosus, have significant inhibitory activity onTrypanosoma cruzi trypanothione reductase (TR). Although they have similar TR inhibitory activity at 10 μg/mL (40.3 μM and 47.6 μM for hypnophilin and panepoxydone, respectively; ~100%), hypnophilin has a slightly greater inhibitory activity (~71%) on T. cruzi amastigote (AMA) growth in vitro as well as on in vitro phytohemagglutinin (PHA)-induced peripheral blood mononuclear (PBMC) proliferation (~70%) compared to panepoxydone (69% AMA inhibition and 91% PBMC inhibition). Hypnophilin and panepoxydone at 1.25 μg/mL had 67% inhibitory activity onLeishmania (Leishmania) amazonensis amastigote-like (AMA-like) growth in vitro. The panepoxydone activity was accompanied by a significant inhibitory effect on PHA-induced PBMC proliferation, suggesting a cytotoxic action. Moreover, incubation of human PBMC with panepoxydone reduced the percentage of CD16+ and CD14+ cells and down-regulated CD19+, CD4+ and CD8+ cells, while hypnophilin did not alter any of the phenotypes analyzed. These data indicate that hypnophilin may be considered to be a prototype for the design of drugs for the chemotherapy of diseases caused by Trypanosomatidae.
	PMID: 21088803 [PubMed - as supplied by publisher]

3.	Parasitology. 2010 Dec;137(14):2051-2063. Modulation of innate immunity by African Trypanosomes. Paulnock DM, Freeman BE, Mansfield JM. Department of Bacteriology, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA. Abstract SUMMARYThe experimental studies of Brucei group trypanosomes presented here demonstrate that the balance of host and parasite factors, especially IFN-γ GPI-sVSG respectively, and the timing of cellular exposure to them, dictate the predominant MP and DC activation profiles present at any given time during infection and within specific tissues. The timing of changes in innate immune cell functions following infection consistently support the conclusion that the key events controlling host resistance occur within a short time following initial exposure to the parasite GPI substituents. Once the changes in MP and DC activities are initiated, there appears little that the host can do to reverse these changes and alter the final outcome of these regulatory events. Instead, despite the availability of multiple innate and adaptive immune mechanisms that can control parasites, there is an inability to control trypanosome numbers sufficiently to prevent the emergence and establishment of virulent trypanosomes that eventually kill the host. Overall it appears that trypanosomes have carefully orchestrated the host innate and adaptive immune response so that parasite survival and transmission, and alterations of host immunity, are to its ultimate benefit.
	PMID: 21087532 [PubMed - as supplied by publisher]

4.	Parasitology. 2010 Dec;137(14):1975. African trypanosomiasis: New insights for disease control. Sternberg JM, Black SJ, Magez S.
	PMID: 21087531 [PubMed - as supplied by publisher]

5.	Parasite Immunol. 2010 Nov-Dec;32(11-12):769-72. The expression of TLR9 in human cutaneous leishmaniasis is associated with granuloma. Tuon FF, Fernandes ER, Pagliari C, Duarte MI, Amato VS. Department of Infectious Diseases, University of Sao Paulo, Medical School, São Paulo, Brasil. flptuon@gmail.com Abstract The Toll-like receptor (TLR) signalling pathway is the first system that defends against Leishmania. After recognising Leishmania as nonself, TLRs trigger NF-κB expression.NF-κB proceeds to the nucleus and promotes the transcription of pro-inflammatory cytokines. TLR9 is thus an important factor in the induction of an effective immune response against Leishmania. We examined the pattern of TLR9 expression in 12 patients with cutaneous leishmaniasis caused by Leishmania braziliensis detected by polymerase chain reaction. Normal skin was analysed as a negative control. TLR9 expression was examined in the dermis and epidermis by immunohistochemical analysis of paraffin-embedded biopsy tissue. TLR9 expression was primarily observed in the granuloma. The protein was detected in a few cells in the dermis. A lower expression level was detected in the epidermis of patients with leishmaniasis when compared with normal skin. The presence of TLR9 in the skin of patients with cutaneous leishmaniasis is associated with granuloma and expressed by macrophages.
	PMID: 21086718 [PubMed - in process]