Saturday, April 4, 2009

What's new for 'Trypanosomatids' in PubMed

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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 -8 of 8

1: Proteins. 2009 Feb 24. [Epub ahead of print]

Solution structure of SUMO from Trypanosoma brucei and its interaction with Ubc9.

Shang Q, Xu C, Zhang J, Zhang X, Tu X.

Hefei National Laboratory for Physical Science at Microscale and School of Life Science, University of Science and Technology of China, Hefei, Anhui 230026, People's Republic of China.

PMID: 19343802 [PubMed - as supplied by publisher]

2: J Immunol. 2009 Apr 15;182(8):4910-6.

The NF-kappaB RelA subunit confers resistance to Leishmania major by inducing nitric oxide synthase 2 and Fas expression but not Th1 differentiation.

Mise-Omata S, Kuroda E, Sugiura T, Yamashita U, Obata Y, Doi TS.

Technology and Development Team for BioSignal Program, Subteam for BioSignal Integration, RIKEN BioResource Center, RIKEN Tsukuba Institute, Tsukuba, Japan.

Although the NF-kappaB transcription factors participate in both innate and adaptive immune responses, little is known about the role of the RelA subunit because mice lacking the rela gene die at embryonic day 14. To elucidate the role of RelA in Leishmania major infection, we prepared fetal liver chimeric mice by adoptively transferring embryonic day 13.5 rela(-/-) or rela(+/+) fetal liver into lethally irradiated host mice. About 90% of the peripheral lymphocytes of the chimeric mice had differentiated from rela fetal liver cells. The rela(-/-) fetal liver chimeric mice were highly sensitive to infection with L. major and died within 11 wk after infection. Despite the severity of the disease, parasite Ag-reactive Th1 cells developed normally. The rela(-/-) macrophages were less able to control intracellular parasite replication than rela(+/+) macrophages, despite showing equally efficient phagocytosis. Both in vitro NO production of macrophages and in vivo expression of NO synthase 2 in the lesions and draining lymph nodes was reduced in rela(-/-) fetal liver chimeric mice. Moreover, up-regulation of Fas in rela(-/-) macrophages was impaired both after in vitro stimulation with LPS and after in vivo infection with L. major, implying a defect in their ability to eliminate infected cells. Thus, RelA is necessary for macrophages to be resistant to intracellular parasite infection.

PMID: 19342670 [PubMed - in process]

3: J Immunol. 2009 Apr 15;182(8):4882-90.

Protective response to Leishmania major in BALB/c mice requires antigen processing in the absence of DM.

Kamala T, Nanda NK.

Laboratory of Cellular and Molecular Immunology, T-Cell Tolerance and Memory Section, National Institutes of Health, Bethesda, MD 20892, USA.

Protection from the parasite Leishmania major is mediated by CD4 T cells. BALB/c mice are susceptible to L. major and show a nonprotective immunodominant CD4 T cell response to Leishmania homolog of activated receptor for c-kinase (LACK) 158-173. Host genes that underlie BALB/c susceptibility to L. major infections are poorly defined. DM, a nonclassical MHC class II molecule, due to its peptide editing properties has been shown to 1) edit the repertoire of peptides displayed by APC, and 2) focus the display of epitopes by APC to the immunodominant ones. We tested the hypothesis that deficiency of DM, by causing presentation of a different array of epitopes by infected APC than that presented by DM-sufficient APC, may change the course of L. major infection in the susceptible BALB/c mice. We show herein that unlike their susceptible wild-type counterparts, BALB/c mice deficient in DM are protected from infections with L. major. Furthermore, DM-deficient mice fail to display the immunodominant LACK 158-173 on infected APC. In its place, infected DM(-/-) hosts show elicitation of CD4 T cells specific for newer epitopes not presented by wild-type L. major-infected APC. Protection of BALB/c DM(-/-) mice is dependent on IFN-gamma. DM is thus a host susceptibility gene in BALB/c mice, and Ag processing in the absence of DM results in elicitation of a protective T cell response against L. major infections. This report suggests a novel mechanism to trigger host resistance against pathogens.

PMID: 19342667 [PubMed - in process]

4: Ann Trop Med Parasitol. 2009 Apr;103(3):275-7.

Seroprevalence of feline leishmaniasis in areas of Iran where Leishmania infantum is endemic.

Sarkari B, Hatam GR, Adnani SJ, Asgari Q.

Department of Parasitology and Mycology, School of Medicine, University of Medical Sciences, Shiraz, Iran.

PMID: 19341541 [PubMed - in process]

5: Ann Trop Med Parasitol. 2009 Apr;103(3):221-34.

Climate and recruitment limitation of hosts: the dynamics of American cutaneous leishmaniasis seen through semi-mechanistic seasonal models.

Chaves LF.

Department of Ecology and Evolutionary Biology, The University of Michigan, Ann Arbor, MI 48109, USA.

Diseases cycle as a response to endogenous and exogenous factors. For infectious diseases caused by vector-transmitted pathogens, the exogenous factors are commonly equated to climatic forces and the endogenous factors to the recruitment of new susceptible individuals. Mathematical models that explicitly (parametrically) consider both types of factor are, however, very rare. An approach is presented to model the effects of endogenous and exogenous factors parametrically, using a time series for American cutaneous leishmaniasis (ACL) from Costa Rica. The seasonality of the disease is modelled using a seasonal autoregressive approach. The latter has the advantage of allowing the use of semi-mechanistic frameworks that consider infection clearance, while explicitly introducing the feedbacks produced by the transition between immune classes, as well as climatic forcing. It also uses a relatively small number of degrees of freedom (compared with the numbers involved in semi-parametric approaches), making it useful for relatively short time series and series with abrupt changes. Compared with non-mechanistic models built for prediction purposes, this way of modelling seems to increase the likelihood of the data being explained by a plausible mechanism. The approach used in this study of ACL could be useful in investigating the changes that occur in other diseases that show non-stationary seasonal dynamics, and can be easily adapted to model the dynamics of other infectious diseases that show trends or breakpoints. The present results support the view that humans affected by ACL are mostly incidental hosts, and indicate that, at the population level, there is a delay of about 5 months between human infection with the causative parasites and the onset of clinical symptoms. They encourage the development of surveillance systems, for monitoring the prevalence of infection in the sandflies that act as vectors, and the use of sentinel hosts, so that control measures can be rapidly applied or strengthened before a serious outbreak occurs. The development of more accurate mathematical models of ACL will depend largely on advances in the ecology of the disease and of all the hosts of the causative parasites.

PMID: 19341537 [PubMed - in process]

6: Ann Trop Med Parasitol. 2009 Apr;103(3):211-20.

The treatment pathways followed by cases of human African trypanosomiasis in western Kenya and eastern Uganda.

Bukachi SA, Wandibba S, Nyamongo IK.

Institute of Anthropology, Gender and African Studies, University of Nairobi, P.O. Box, 30197-00100, Nairobi, Kenya.

Although early diagnosis and treatment are key factors in the effective control of human African trypanosomiasis (HAT), many cases of the disease delay taking appropriate action, leading to untold suffering. As a better understanding of treatment-seeking behaviour should help in identifying the obstacles to early diagnosis and effective treatment, the treatment pathways followed by 203 former HAT cases in western Kenya and eastern Uganda have recently been explored. About 86% of the HAT cases had utilized more than two different healthcare options before being correctly diagnosed for HAT, with about 70% each using more than three different health facilities. Only about 8% of the cases reported that they had been correctly diagnosed the first time they sought treatment. Just over half (51%) of the HAT cases had been symptomatic for >2 months before being correctly diagnosed for HAT, and such time lags in diagnosis contributed to 72% of the cases receiving their first appropriate treatment only in the late stage of the disease. The likelihood of a correct diagnosis increased with the time the case had been symptomatic. These observations indicate an urgent need to build the diagnostic capacity of the primary healthcare facilities in the study area, so that all HAT cases can be identified and treated in the early stage of the disease.

PMID: 19341536 [PubMed - in process]

7: Chem Pharm Bull (Tokyo). 2009 Mar;57(3):245-51. LinkOut

Leishmanicidal active constituents from Nepalese medicinal plant Tulsi (Ocimum sanctum L.).

Suzuki A, Shirota O, Mori K, Sekita S, Fuchino H, Takano A, Kuroyanagi M.

Faculty of Life and Environmental Sciences, Prefectural University of Hiroshima, Shobara, Hiroshima 727-0023, Japan.

In the course of screening leishmanicidal active compounds from Asian and South American medicinal plants, a Nepalese medicinal plant, Tulsi (Ocimum sanctum L.), showed strong activity. We therefore studied the isolation and structural elucidation of the active constituents from O. sanctum L. From the ethyl acetate soluble fraction of the plant, seven new novel neolignan derivatives were isolated along with 16 known compounds. The structures of the new compounds (1-7) were elucidated as 6-allyl-3',8-dimethoxy-flavan-3,4'-diol (1), 6-allyl-3-(4-allyl-2-methoxyphenoxy)-3',8-dimethoxyflavan-4'-ol (2), 5-allyl-3-(4-allyl-2-methoxyphenoxymethyl)-2-(4-hydroxy-3-methoxyphenyl)-7-methoxy-2,3-dihydrobenzofuran (3), 1,2-bis(4-allyl-2-methoxyphenoxy)-3-(4-hydroxy-3-methoxyphenyl)-3-methoxypropane (4), 1-(4-hydroxy-3-methoxyphenyl)-1,2,3-tris(4-allyl-2-methoxyphenoxy)propane (5), 1-allyl-4-(5-allyl-2-hydroxy-3-methoxyphenoxy)-3-(4-allyl-2-methoxyphenoxy)-5-methoxybenzene (6), and 3-(5-allyl-2-hydroxy-3-methoxyphenyl)-1-(4-hydroxy-3-methoxyphenoxy)-prop-1-ene (7) by means of (1)H-NMR, (13)C-NMR, and 2D-NMR spectral data. Some of these compounds showed leishmanicidal activity.

PMID: 19252314 [PubMed - indexed for MEDLINE]

8: J Med Chem. 2008 Dec 11;51(23):7344-7.Click here to read LinkOut

In pursuit of natural product leads: synthesis and biological evaluation of 2-[3-hydroxy-2-[(3-hydroxypyridine-2-carbonyl)amino]phenyl]benzoxazole-4-carboxylic acid (A-33853) and its analogues: discovery of N-(2-benzoxazol-2-ylphenyl)benzamides as novel antileishmanial chemotypes.

Tipparaju SK, Joyasawal S, Pieroni M, Kaiser M, Brun R, Kozikowski AP.

Drug Discovery Program, Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, 833 S. Wood Street, Chicago, Illinois 60612, USA.

The first synthesis and biological evaluation of antibiotic 31 (A-33853) and its analogues are reported. Initial screening for inhibition of L. donovani, T. b. rhodesiense, T. cruzi, and P. falciparum cultures followed by determination of IC(50) in L. donovani and cytotoxicity on L6 cells revealed 31 to be 3-fold more active than miltefosine, a known antileishmanial drug. Compounds 14, 15, and 25 selectively inhibited L. donovani at nanomolar concentrations and showed much lower cytotoxicity.

PMID: 18989953 [PubMed - indexed for MEDLINE]

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