What's new for 'Trypanosomatids' in PubMed

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Sent on Thursday, 2009 Dec 10
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 -6 of 6

1.	Amino Acids. 2009 Dec 8. [Epub ahead of print] Novel convenient synthesis of biologically active esters of hydroxylamine. Khomutov MA, Mandal S, Weisell J, Saxena N, Simonian AR, Vepsalainen J, Madhubala R, Kochetkov SN. Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia, hommaximus@mail.ru. Alkylation of ethyl N-hydroxyacetimidate with readily available methanesulfonates of functionally substituted alcohols and subsequent deprotection of aminooxy group is a novel and convenient method to prepare functionally substituted esters of hydroxylamine with high overall yield. This approach is a good alternative to well-known reaction of N-hydroxyphthalimide with alcohols under the Mitsunobu conditions. The properties of ethoxyethylidene protection of aminooxy group on the contrary to that of N-alkoxyphthalimide group allow to perform a wide spectra of the transformations in the radical of N-protected hydroxylamine derivatives. This is essential for synthetic strategies consisting in the introduction of N-protected aminooxy group at one of the first steps of synthesis and subsequent transformations of the radical.The inhibitory effect of one of the newly synthesized compound, 1-guanidinooxy-3-aminopropane (GAPA), was compared with that of well-known inhibitors of ornithine decarboxylase namely, alpha-difluoromethylornithine (DFMO) and 1-aminooxy-3-aminopropane (APA) on Leishmania donovani, a protozoan parasite that causes visceral leishmaniasis. GAPA, on the contrary with APA and DFMO, in micromolar concentrations, inhibited the growth of both amastigotes and promastigotes of sodium antimony gluconate-resistant forms of L. donovani.
	PMID: 19997759 [PubMed - as supplied by publisher]

2.	PLoS Pathog. 2009 Dec;5(12):e1000685. Epub 2009 Dec 4. C-Terminal Mutants of Apolipoprotein L-I Efficiently Kill Both Trypanosoma brucei brucei and Trypanosoma brucei rhodesiense. Lecordier L, Vanhollebeke B, Poelvoorde P, Tebabi P, Paturiaux-Hanocq F, Andris F, Lins L, Pays E. Laboratory of Molecular Parasitology, IBMM, Université Libre de Bruxelles, Gosselies, Belgium. Apolipoprotein L-I (apoL1) is a human-specific serum protein that kills Trypanosoma brucei through ionic pore formation in endosomal membranes of the parasite. The T. brucei subspecies rhodesiense and gambiense resist this lytic activity and can infect humans, causing sleeping sickness. In the case of T. b. rhodesiense, resistance to lysis involves interaction of the Serum Resistance-Associated (SRA) protein with the C-terminal helix of apoL1. We undertook a mutational and deletional analysis of the C-terminal helix of apoL1 to investigate the linkage between interaction with SRA and lytic potential for different T. brucei subspecies. We confirm that the C-terminal helix is the SRA-interacting domain. Although in E. coli this domain was dispensable for ionic pore-forming activity, its interaction with SRA resulted in inhibition of this activity. Different mutations affecting the C-terminal helix reduced the interaction of apoL1 with SRA. However, mutants in the L370-L392 leucine zipper also lost in vitro trypanolytic activity. Truncating and/or mutating the C-terminal sequence of human apoL1 like that of apoL1-like sequences of Papio anubis resulted in both loss of interaction with SRA and acquired ability to efficiently kill human serum-resistant T. b. rhodesiense parasites, in vitro as well as in transgenic mice. These findings demonstrate that SRA interaction with the C-terminal helix of apoL1 inhibits its pore-forming activity and determines resistance of T. b. rhodesiense to human serum. In addition, they provide a possible explanation for the ability of Papio serum to kill T. b. rhodesiense, and offer a perspective to generate transgenic cattle resistant to both T. b. brucei and T. b. rhodesiense.
	PMID: 19997494 [PubMed - in process]

3.	Am J Trop Med Hyg. 2009 Dec;81(6):1004-6. Short report: Contribution of quantitative real-time polymerase chain reaction to follow-up of visceral leishmaniasis patients treated with meglumine antimoniate. Aoun K, Chouihi E, Amri F, Ben Alaya N, Raies A, Mary C, Bouratbine A. Research Laboratory of Emerging Parasitic Diseases, Tunis, Tunisia. karim.aoun@fmt.rnu.tn Forty-two patients with visceral leishmaniasis in Tunisia were treated with meglumine antimoniate and followed-up for clinical improvement and blood parasite load determined by quantitative real-time polymerase chain reaction (PCR). Parasite loads before treatment ranged from 27 to 5.3 x 10(7) parasites/mL. At the end of treatment, parasite load decreased significantly in 39 cured patients (P < 0.001). The decrease in parasite load after treatment was greater than 99% for 34 patients and PCR results became negative in 23 of them. Two patients without clinical improvement showed no or slight decreases in parasite load (209 versus 202 parasites/mL and 1,765 versus 146 parasites/mL). One patient showed had a relapse seven months after showing a good response to treatment. His parasitemia remained high despite a sharp decrease (5.2 x 10(5) versus 5.9 x 10(3) parasites/mL).
	PMID: 19996428 [PubMed - in process]
	Publication Types: Research Support, Non-U.S. Gov't

4.	Am J Trop Med Hyg. 2009 Dec;81(6):994-1003. Clinical, parasitologic, and immunologic evolution in dogs experimentally infected with sand fly-derived Leishmania chagasi promastigotes. Travi BL, Osorio EY, Saldarriaga OA, Cadena H, Tabares CJ, Peniche A, Lee S, Melby PC. University of Texas Health Science Center, San Antonio, TX 78229-3900, USA. travi@uthscsa.edu Experimental infection of dogs with Leishmania infantum has yielded heterogeneous clinical, parasitologic, and immunologic results. We studied dogs infected with 10(5) or 10(4) sand fly-derived promastigotes delivered by the intradermal (ID) or intravenous (IV) routes. Total mortality over 1 year post-infection reached 23.8%. The mortality and proportion of sustained polysymptomatic dogs was highest in the IV-10(5) group. The early appearance of polysymptoms was associated with an increased risk of progression to death. Dissemination of the parasite to lymph nodes was faster, and the subsequent infectivity to sand flies higher, in the IV compared with ID-infected dogs. Parasite-specific IgG1 or IgG2 production was similar among the groups, but higher interferon-gamma (IFN-gamma) and interleukin-10 (IL-10) expression was associated with polysymptomatic dogs. On the basis of the data obtained from this study, a sample size analysis using different endpoints for future vaccine trials is described.
	PMID: 19996427 [PubMed - in process]
	Publication Types: Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Grant Support: AI48823/AI/NIAID NIH HHS/United States

5.	Antimicrob Agents Chemother. 2009 Dec 7. [Epub ahead of print] Miltefosine efficiently eliminates L. major amastigotes from murine infected dendritic cells without altering their immune functions. Griewank K, Gazeau C, Eichhorn A, von Stebut E. Department of Dermatology, Johannes Gutenberg-University Mainz, Germany. As treatment for leishmaniasis, miltefosine exerts direct toxic effects on the parasites. Miltefosine also modulates immune cells such as macrophages (MPhi) leading to parasite elimination via oxidative radicals. Dendritic cells (DC) are critical for initiation of protective immunity against Leishmania through induction of Th1 immunity via IL-12. We now investigated the effects of miltefosine on DC in L. major infections. When co-cultured with miltefosine for 4 days, the majority of in vitro infected DC were free of parasites. Miltefosine treatment did not influence DC maturation (upregulation of MHC II or costimulatory molecules, e.g. CD40, CD54, CD86) or significantly alter cytokine release (IL-12, TNFalpha, IL-10). Further, miltefosine DC treatment did not alter antigen presentation, since unrestricted antigen-specific proliferation of CD4(+) and CD8(+) T cells was observed upon stimulation with miltefosine-treated, infected DC. In addition, miltefosine application in vivo did not lead to maturation/emigration of skin DC. DC NO(-) production, a mechanism used by phagocytes to rid themselves of intracellular parasites, was also unaltered upon miltefosine treatment. Our data confirm prior studies indicating that - in contrast to e.g. pentavalent antimones - miltefosine functions independent of the immune system, mostly through direct toxicity against the Leishmania parasite.
	PMID: 19995922 [PubMed - as supplied by publisher]

6.	Prog Neurobiol. 2009 Dec 5. [Epub ahead of print] African trypanosome infections of the nervous system: parasite entry and effects on sleep and synaptic functions By. Kristensson K, Nygård M, Bertini G, Bentivoglio M. Department of Neuroscience, Karolinska Institutet, Stockholm, Retzius väg 8 SE-171 77 Sweden. The extracellular parasite Trypanosoma brucei causes human African trypanosomiasis (HAT), also known as sleeping sickness. Trypanosomes are transmitted by tsetse flies and HAT occurs in foci in sub-Saharan Africa. The disease, which is invariably lethal if untreated, evolves in a first hemo-lymphatic stage, progressing to a second meningo-encephalitic stage when the parasites cross the blood-brain barrier.At first, trypanosomes are restricted to circumventricular organs and choroid plexus in the brain outside the blood-brain barrier, and to dorsal root ganglia. Later, parasites cross the blood-brain barrier at post-capillary venules, through a multistep process similar to that of lymphocytes. Accumulation of parasites in the brain is regulated by cytokines and chemokines.Trypanosomes can alter neuronal function and the most prominent manifestation is represented by sleep alterations. These are characterized, in HAT and experimental rodent infections, by disruption of the sleep-wake 24h cycle and internal sleep structure. Trypanosome infections alter also some, but not all, other endogenous biological rhythms. A number of neural pathways and molecules may be involved in such effects. Trypanosomes secrete prostaglandins including the somnogenic PGD2, and they interact with the host's immune system to cause release of pro-inflammatory cytokines. From the sites of early localization of parasites in the brain and meninges, such molecules could affect adjacent brain areas implicated in sleep-wakefulness regulation, including the suprachiasmatic nucleus and its downstream targets, to cause the changes characteristic of the disease. This raises challenging issues on the effects of cytokines on synaptic functions potentially involved in sleep-wakefulness alterations.
	PMID: 19995590 [PubMed - as supplied by publisher]