What's new for 'Trypanosomatids' in PubMed

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Sent on Friday, 2012 May 04
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 - 10 of 10

1.	Proc Natl Acad Sci U S A. 2012 May 2. [Epub ahead of print] Transcription factor IRF4 determines germinal center formation through follicular T-helper cell differentiation. Bollig N, Brüstle A, Kellner K, Ackermann W, Abass E, Raifer H, Camara B, Brendel C, Giel G, Bothur E, Huber M, Paul C, Elli A, Kroczek RA, Nurieva R, Dong C, Jacob R, Mak TW, Lohoff M. Source Institut für Medizinische Mikrobiologie und Krankenhaushygiene, and Klinik für Innere Medizin, Universität Marburg, 35043 Marburg, Germany. Abstract Follicular T-helper (T(FH)) cells cooperate with GL7(+)CD95(+) germinal center (GC) B cells to induce antibody maturation. Herein, we identify the transcription factor IRF4 as a T-cell intrinsic precondition for T(FH) cell differentiation and GC formation. After immunization with protein or infection with the protozoon Leishmania major, draining lymph nodes (LNs) of IFN-regulatory factor-4 (Irf4(-/-)) mice lacked GCs and GC B cells despite developing normal initial hyperplasia. GCs were also absent in Peyer's patches of naive Irf4(-/-) mice. Accordingly, CD4(+) T cells within the LNs and Peyer's patches failed to express the T(FH) key transcription factor B-cell lymphoma-6 and other T(FH)-related molecules. During chronic leishmaniasis, the draining Irf4(-/-) LNs disappeared because of massive cell death. Adoptive transfer of WT CD4(+) T cells or few L. major primed WT T(FH) cells reconstituted GC formation, GC B-cell differentiation, and LN cell survival. In support of a T-cell intrinsic IRF4 activity, Irf4(-/-) T(FH) cell differentiation was not rescued by close neighborhood to transferred WT T(FH) cells. Together with its known B lineage-specific roles during plasma cell maturation and class switch, our study places IRF4 in the center of antibody production toward T-cell-dependent antigens.
	PMID: 22552227 [PubMed - as supplied by publisher]

2.	J Parasitol. 2012 May 2. [Epub ahead of print] Cutaneous Leishmaniasis in Nalut District, The Libyan Arab Jamahiriya: A Clinicoepidemiological Study and Leishmania Species Identification. Belal US, Abdel-Hafeez EH, Naoi K, Norose K. Source a Department of Parasitology, Faculty of Medicine, Minia University. Abstract Abstract ABSTRACT: Cutaneous leishmaniasis (CL), an endemic disease in the littoral zones of the Mediterranean area, the Middle East, East Africa, and especially in Libya, has not been fully documented. The present study clarifies the clinico-epidemiologic profile of CL and the molecular genotyping of the Leishmania spp. in the Nalut district, Libya. Two hundred and twenty-three CL patients were examined at the out-patient clinics of Nalut Hospital from March 2006 to February 2007. Cutaneous leishmaniasis was diagnosed by clinical, microscopic, culture, polymerase chain reaction (PCR), and PCR-restriction fragment length polymorphism (PCR-RFLP) analyses. The disease was observed throughout the year, with the highest incidence rate between November and February. Fifty-nine percent of patients were younger than 20 yr. Nodulo-ulcerative lesions, indurated ulcer, papulo-ulcerative lesions, and subcutaneous nodular lesions were observed in 170, 25, 15, and 13 patients, respectively. Two hundred patients (89.7%) had dry type of lesions, while 23 patients (10.3%) presented a wet type. One hundred and fifty-nine (71.3%) of 223 patients were confirmed positive for CL by the presence of the amastigote form of Leishmania by stained Giemsa smear, and 170 (76.2%) were positive according to the presence of the promastigote form of Leishmania by culture in RPMI medium supplemented with 10% fetal bovine serum (FBS). On the other hand, PCR confirmed 203 (91.0%) positive cases. Genotyping of Leishmania spp. by RFLP analysis revealed that L. tropica was the most common spp. at all ages, and L. infantum was second under 20 yr of age. Cutaneous leishmaniasis is endemic in the Nalut district, Libya; PCR was the most sensitive parasite diagnostic test, and L. tropica was the most common spp.
	PMID: 22551502 [PubMed - as supplied by publisher]

3.	Transpl Int. 2012 May 3. doi: 10.1111/j.1432-2277.2012.01487.x. [Epub ahead of print] Visceral leishmaniasis in hematopoietic stem cell transplantation. Bautista G, Ramos A, Gil S. Source  Department of Hematology, Hospital Universitario Puerta de Hierro, Majadahonda, Madrid, Spain  Department of Internal Medicine (Infectious Disease Unit), Hospital Universitario Puerta de Hierro, Majadahonda, Madrid, Spain e-mail: aramos220@gmail.com.
	PMID: 22551448 [PubMed - as supplied by publisher]

4.	Org Med Chem Lett. 2012 May 2;2(1):16. [Epub ahead of print] Increase of leishmanicidal and tubercular activities using steroids linked to aminoquinoline. Antinarelli LM, Carmo AM, Pavan FR, Leite CQ, Da Silva AD, Coimbra ES, Salunke DB. Abstract ABSTRACT: BACKGROUND: Aminoquinoline/steroid conjugates were synthesized based on the fact that steroid transporters have been shown to accept and carry a variety of drugs. So, in continuing our research of antileishmanial and antitubercular drugs, aminoquinoline/steroid conjugates (12, 13, and 14) were regioselectively synthesized via 1,3-dipolar cycloaddition of alkynes 3, 5, and 7 with azide 12. The aminoquinoline/steroids conjugates were evaluated in vitro against Leishmania major and Mycobacterium tuberculosis. RESULTS: The regioselective synthesis of the novel aminoquinoline/steroid conjugates was achieved in very high yield. All aminoquinoline/steroid conjugates (12, 13, and 14) exhibited best results against Leishmania and M. tuberculosis than the respective alkyne intermediate structures (3, 5, and 7, respectively). Among them, the compound 12 exhibited the best activity for M. tuberculosis (MIC = 8.8 uM). This result is comparable to drugs commonly used in tuberculosis treatment. Also, for antileishmanial assay, the aminoquinoline/steroid conjugates demonstrated a significant activity against promastigote and amastigote forms of L. major. These results highlight the importance of steroids as carrier. KEYWORDS: antileishmanial drugs; antituberculosis drugs; click chemistry; quinoline; steroid.
	PMID: 22551300 [PubMed - as supplied by publisher]

5.	J Nat Prod. 2012 May 2. [Epub ahead of print] Indole Alkaloids from Geissospermum reticulatum. Reina M, Ruiz-Mesia W, López-Rodríguez M, Ruiz-Mesia L, González-Coloma A, Martínez-Díaz R. Source Instituto de Productos Naturales y Agrobiología (IPNA) , CSIC, La Laguna, Tenerife, Spain. Abstract Ten indole alkaloids were isolated from Geissospermum reticulatum, seven (1-7) from the leaves and three (8-10) from the bark. Seven were aspidospermatan-type alkaloids (1-3, 5-9), including four (5-8) with a 1-oxa-3-cyclopentene group in their molecule, which we named geissospermidine subtype. Compounds 1-3, 5-8, and 10 had not been reported previously as natural products, while 4 and 9 were the known alkaloids O-demethylaspidospermine and flavopereirine. Their structures were determined by spectroscopic techniques including 1D and 2D NMR experiments (COSY, NOESY, HSQC, HMBC). Additionally, X-ray crystallographic analyses of 1, 2, and 6 were performed. Antiparasitic activities of the ethanolic and alkaloidal extracts and of the pure alkaloids were tested against Trypanosoma cruzi and Leishmania infantum. In general, the extracts exhibited selective action and were more active against Leishmania than against Trypanosoma. Alkaloid 4 was also very active against L. infantum.
	PMID: 22551062 [PubMed - as supplied by publisher]

6.	J Med Chem. 2012 May 2. [Epub ahead of print] Novel 3-Nitro-1<italic>H</italic>-1,2,4-triazole-based Amides and Sulfonamides as Potential anti-Trypanosomal Agents. Papadopoulou MV, Bloomer WD, Rosenzweig HS, Chatelain E, Kaiser M, Wilkinson SR, McKenzie C, Ioset JR. Abstract A series of novel 3-nitro-1<italic>H</italic>-1,2,4-triazole-(and in some cases 2-nitro-1<italic>H</italic>-imidazole)-based amides and sulfonamides were characterized for their <italic>in vitro</italic> anti-trypanosomal and antileishmanial activities as well as mammalian toxicity. Out of 36 compounds tested, 29 (mostly 3-nitro-1<italic>H</italic>-1,2,4-triazoles) displayed significant activity against <italic>T. cruzi</italic> intracellular amastigotes (IC<sub>50</sub> ranging from 28 nM to 3.72 µM) without concomitant toxicity to L6 host cells (selectivity 66 to 2782). Twenty three of these active compounds were more potent (up to 58 fold) than the reference drug benznidazole, tested in parallel. In addition, 9 nitrotriazoles which were moderately active (0.5 µM ≤ IC<sub>50</sub> &lt; 6.0 µM) against <italic>T. b. rhodesiense</italic> trypomastigotes, were 5 to 31 fold more active against bloodstream-form <italic>T. b. brucei</italic> trypomastigotes engineered to overexpress NADH-dependent nitroreductase (TbNTR). Finally, 3 nitrotriazoles displayed a moderate activity against the axenic form of <italic>Leishmania donovani</italic>. Therefore, 3-nitro-1<italic>H</italic>-1,2,4-triazole-based amides and sulfonamides are potent anti-trypanosomal agents.
	PMID: 22550999 [PubMed - as supplied by publisher]

7.	BMJ. 2012 Mar 22;344:e2092. doi: 10.1136/bmj.e2092. A returning traveller with fever, facial swelling, and skin lesions. Richter J, Göbels S, Göbel T, Westenfeld R, Müller-Stöver I, Häussinger D. Source University Hospital for Gastroenterology, Hepatology and Infectious Diseases, Heinrich-Heine-University, D-40225 Düsseldorf, Germany. joachim.richter@med.uni-duesseldorf.de
	PMID: 22442353 [PubMed - indexed for MEDLINE]
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8.	Aquat Toxicol. 2012 Mar;109:143-9. Epub 2011 Dec 23. The acute and sub-chronic exposures of goldfish to naphthenic acids induce different host defense responses. Hagen MO, Garcia-Garcia E, Oladiran A, Karpman M, Mitchell S, El-Din MG, Martin JW, Belosevic M. Source Department of Biological Sciences, University of Alberta, Edmonton, AB T6G 2E9, Canada. Abstract Naphthenic acids (NAs) are believed to be the major toxic component in oil sands process-affected water (OSPW) produced by the oil sands mining industry in Northern Alberta, Canada. We recently reported that oral exposure to NAs alters mammalian immune responses, but the effect of OSPW or NAs on the immune mechanisms of aquatic organisms has not been fully elucidated. We analyzed the effects of acute and sub-chronic NAs exposures on goldfish immune responses by measuring the expression of three pro-inflammatory cytokine genes, antimicrobial functions of macrophages, and host defense after challenge with a protozoan pathogen (Trypanosoma carassii). One week after NAs exposure, fish exhibited increased expression of pro-inflammatory cytokines (IFNγ, IL-1β1, TNF-α2) in the gills, kidney and spleen. Primary macrophages from fish exposed to NAs for one week, exhibited increased production of nitric oxide and reactive oxygen intermediates. Goldfish exposed for one week to 20 mg/L NAs were more resistant to infection by T. carassii. In contrast, sub-chronic exposure of goldfish (12 weeks) to NAs resulted in decreased expression of pro-inflammatory cytokines in the gills, kidney and spleen. The sub-chronic exposure to NAs reduced the ability of goldfish to control the T. carassii infection, exemplified by a drastic increase in fish mortality and increased blood parasite loads. This is the first report analyzing the effects of OSPW contaminants on the immune system of aquatic vertebrates. We believe that the bioassays depicted in this work will be valuable tools for analyzing the efficacy of OSPW remediation techniques and assessment of diverse environmental pollutants. Copyright © 2011 Elsevier B.V. All rights reserved.
	PMID: 22227375 [PubMed - indexed for MEDLINE]
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9.	J Pharm Sci. 2012 Mar;101(3):888-94. doi: 10.1002/jps.23010. Epub 2011 Dec 12. First century of Chagas' disease: an overview on novel approaches to nifurtimox and benznidazole delivery systems. Salomon CJ. Source Area Técnica Farmacéutica, Departamento Farmacia, Facultad de Ciencias Bioquímicas y Farmacéuticas, Suipacha 531, 2000. Universidad Nacional de Rosario, IQUIR-CONICET, Rosario, Argentina. csalomon@fbioyf.unr.edu.ar Abstract Hundred years after the discovery of Chagas' disease, there is a lack of effective treatment to control this neglected disease caused by the parasite Trypanosoma cruzi. The transmission is primarily through vector-borne blood transfusion or during pregnancy, producing high mortality and morbidity among poor people in many countries of Latin America. In the last decades, the efforts have been focused mainly on the elimination of vectors. At the same time, screening of blood donors in order to avoid transfusional transmission has been improved all over the world. However, Chagas' disease is still a major public health problem, with estimates of nearly 90 million people at risk of infection and more than eight million infected in 18 endemic countries. Despite the high incidence in endemic regions and the dissemination of neglected diseases in North America and Europe, to date, there are only two drugs developed and prescribed for the treatment of Chagas' disease, nifurtimox (tablets of 120 mg) and benznidazole (tablets of 100 mg). In this review, different approaches carried out in the last decades for developing novel pharmaceutical formulations for the delivery of nifurtimox and benznidazole are discussed. Copyright © 2011 Wiley Periodicals, Inc.
	PMID: 22161779 [PubMed - indexed for MEDLINE]
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10.	PLoS One. 2011;6(11):e27904. Epub 2011 Nov 16. Protein synthesis attenuation by phosphorylation of eIF2α is required for the differentiation of Trypanosoma cruzi into infective forms. Tonelli RR, Augusto Lda S, Castilho BA, Schenkman S. Source Departamento de Microbiologia, Imunologia e Parasitologia, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brasil. Abstract Chagas' disease is a potentially life-threatening illness caused by the unicellular protozoan parasite Trypanosoma cruzi. It is transmitted to humans by triatomine bugs where T. cruzi multiplies and differentiates in the digestive tract. The differentiation of proliferative and non-infective epimastigotes into infective metacyclic trypomastigotes (metacyclogenesis) can be correlated to nutrient exhaustion in the gut of the insect vector. In vitro, metacyclic-trypomastigotes can be obtained when epimastigotes are submitted to nutritional stress suggesting that metacyclogenesis is triggered by nutrient starvation. The molecular mechanism underlying such event is not understood. Here, we investigated the role of one of the key signaling responses elicited by nutritional stress in all other eukaryotes, the inhibition of translation initiation by the phosphorylation of the eukaryotic initiation factor 2α (eIF2α), during the in vitro differentiation of T. cruzi. Monospecific antibodies that recognize the phosphorylated Tc-eIF2α form were generated and used to demonstrate that parasites subjected to nutritional stress show increased levels of Tc-eIF2α phosphorylation. This was accompanied by a drastic inhibition of global translation initiation, as determined by polysomal profiles. A strain of T. cruzi overexpressing a mutant Tc-eIF2α, incapable of being phosphorylated, showed a block on translation initiation, indicating that such a nutritional stress in trypanosomatids induces the conserved translation inhibition response. In addition, Tc-eIF2α phosphorylation is critical for parasite differentiation since the overexpression of the mutant eIF2α in epimastigotes abolished metacyclogenesis. This work defines the role of eIF2α phosphorylation as a key step in T. cruzi differentiation. PMCID: PMC3218062 Free PMC Article
	PMID: 22114724 [PubMed - indexed for MEDLINE]
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