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Sent on Saturday, 2011 Oct 01Search kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"
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| PubMed Results |
| 2. | Blood. 2011 Sep 29. [Epub ahead of print]SIV infection of rhesus macaques results in dysfunctional T- and B-cell responses to neo and recall Leishmania major vaccination.Klatt NR, Vinton CL, Lynch RM, Canary LA, Ho J, Darrah PA, Estes JD, Seder RA, Moir SL, Brenchley JM.SourceNIH/NIAID/Program in Barrier Immunity and Repair and Laboratory of Molecular Microbiology, Bethesda, MD, United States; AbstractHIV infection is characterized by immune system dysregulation, including depletion of CD4+ T-cells, immune activation and abnormal B- and T-cell responses. However, the immunological mechanisms underlying lymphocytic dysfunctionality, and whether it is restricted to immune responses against neo and/or recall antigens, is unclear. Here, we immunized SIV-infected and uninfected rhesus macaques to induce immune responses against neo and recall antigens using a Leishmania major polyprotein (MML) vaccine given with Poly-ICLC adjuvant. We found that vaccinated SIV-uninfected animals induced high frequencies of polyfunctional MML-specific CD4+ T-cells. However, in SIV-infected animals, CD4+ T-cell functionality decreased after both neo (P=0.0025) and recall MML vaccination (P=0.0080). Furthermore, after SIV infection, the frequency of MML-specific antibody-secreting classical memory B-cells (cmASCs) was decreased compared to vaccinated, SIV-uninfected animals. Specifically, cmASCs that produced IgA in response to either neo (P=0.0221) or recall (P=0.0356) MML vaccinations were decreased. Furthermore, we found that T-follicular helper (Tfh) cells, which are essential for priming B cells, are preferentially infected with SIV. These data indicate that SIV infection results in dysfunctional T-cell responses to neo and recall vaccinations, and direct SIV infection of Tfh cells, both of which likely contribute to deficient B-cell responses and, presumably, susceptibility to certain opportunistic infections. |
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| 3. | Peptides. 2011 Sep 19. [Epub ahead of print]Effect of Pam3Cys induced protection on the therapeutic efficacy of miltefosine against experimental visceral leishmaniasis.S hakya N, Sane SA, Shankar S, Gupta S.SourceDivision of Parasitology, Central Drug Research Institute (CSIR), Chattar Manzil Palace, M.G. Road, Lucknow 226001, UP, India. AbstractProphylactic potential of synthetic bacterial lipopeptide and a TLR2 agonist, Pam3Cys was first evaluated against experimental visceral leishmaniasis in rodent model. After establishing the potential its effect on therapeutic efficacy of miltefosine was also studied. Pam3Cys showed 74.64% inhibition in parasitic establishment when administered by ip route at a dose of 100μg/animal spaced at two weeks, i.e. on day -7 and +7 of challenge with Leishmania donovani amastigotes. However, when aforesaid dose of Pam3Cys was given with sub-curative dose of miltefosine (2.5mg/kg for 5 days) its efficacy enhanced from 49.80% to 92.25%. These findings revealed that this lipopeptide has potential protective efficacy which significantly enhanced the therapeutic efficacy of miltefosine used at low dose against Leishmania infection and warrants detailed investigations on its possible immunopotentiatory actions. Copyright © 2011. Published by Elsevier Inc. |
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| 4. | Parasit Vectors. 2011 Sep 29;4(1):189. [Epub ahead of print]Characterization of simple sequence repeats (SSRs) from Phlebotomus papatasi (Diptera: Psychodidae) expressed sequence tags (ESTs).Hamarsheh O, Amro A.AbstractABSTRACT: BACKGROUND:Phlebotomus papatasi is a natural vector of Leishmania major which causes cutaneous leishmaniasis in many countries. Simple sequence repeats (SSRs), or microsatellites, are common in eukaryotic genomes and are short, repeated nucleotide sequence elements arrayed in tandem and flanked by non-repetitive regions. The enrichment methods used previously for finding new microsatellite loci in sand flies remain laborious and time consuming; in silico mining which include, retrieval and screening of microsatellites from large amounts of sequence data from sequence data bases using microsatellite search tools can yield many new candidate markers. RESULTS:Simple sequence repeats (SSRs) were characterized in P. papatasi expressed sequence tags (ESTs) derived from a public database, National Center for Biotechnology Information (NCBI). A total of 42,784 sequences were mined, and 1,499 SSRs were identified with a frequency of 3.5% and an average density of 15.55 kb per SSR. Dinucleotide motifs were the most common SSRs, accounting for 67% followed by tri-, tetra-, and penta-nucleotide repeats, accounting for 31.1%, 1.5%, and 0.1%, respectively. The length of microsatellites varied from 5 to 16 repeats. Dinucleotide types; AG and CT have the highest frequency. Dinucleotide SSR-ESTs are relatively biased toward an excess of (AX)n repeats and a low GC base content. Forty primer pairs were designed based on motif lengths for further experimental validation. CONCLUSION:The first large-scale survey of SSRs derived from P. papatasi is presented; dinucleotide SSRs identified are more frequent than other types. EST data mining is an effective strategy to identify functional microsatellites in P. papatasi. |
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| 5. | J Eur Acad Dermatol Venereol. 2011 Sep 29. doi: 10.1111/j.1468-3083.2011.04266.x. [Epub ahead of print]Chronic cutaneous leishmaniasis, a great mimicker with various clinical presentations: 12 years experience from Aleppo.Douba MD, Abbas O, Wali A, Nassany J, Aouf A, Tibbi MS, Kibbi AG, Kurban M.SourceCenter for Dermatology Diseases, El Hamdanieh-Aleppo, Syria Department of Dermatology, American University of Beirut, Beirut, Lebanon Department of Biochemistry and Molecular Genetics, American University of Beirut, Beirut, Lebanon. AbstractBackground Cutaneous leishmaniasis (CL) has been an endemic disease in Aleppo, Syria for many decades. During the past 12 years, there was a clear increase in the overall incidence of the disease in the region. Treatment using intralesional method of antimonial compounds became ineffective in a considerable proportion of cases and more patients developed the chronic form of the disease. Objectives To categorize chronic cutaneous leishmaniasis (CCL) into different subtypes that mimic a wide spectrum of skin diseases, and to analyse the cause of this increase in the incidence of the disease as a whole and of the chronic type in particular. Methods A total number of 6200 patients with CL were seen in our centre, among which 1880 were initially diagnosed with CCL. Inclusion criteria for CCL included CL for more than 1 year. The diagnosis of CCL was made based on the clinical presentation and a positive Giemsa smear test. Biopsies were performed whenever the Giemsa smear was negative. Patients who had immunosuppression due to a medical condition or intake of immunosuppressive medications were excluded. Results Of 1880 patients, 1750 patients fit the inclusion criteria. Based on the lesion morphology, three different types of CCL were defined, among which five subtypes were observed based on clinical pattern and distribution of lesions. The two most common types of CCL were the papulonodular and plaque forms. Around 80% of all CCL cases occurred in individuals under 16 years of age and the most common location was the face (88.6% of cases). Conclusions CCL due to Leishmania tropica can mimic many other dermatological conditions which might lead to a delay in making the correct diagnosis resulting in increased resistance to treatment. We have illustrated eight different clinical presentations of CCL and their differential diagnoses to make physicians more aware of the atypical presentations of CCL. A new treatment plan is suggested for the high-risk group of acute cutaneous leishmaniasis patients to decrease the likelihood of progressing to chronicity. © 2011 The Authors. Journal of the European Academy of Dermatology and Venereology © 2011 European Academy of Dermatology and Venereology. |
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| 6. | Future Microbiol. 2011 Sep;6:1037-47.Drug resistance in human African trypanosomiasis.Barrett MP, Vincent IM, Burchmore RJ, Kazibwe AJ, Matovu E.SourceWellcome Trust Centre for Molecular Parasitology, Institute of Infection, Immunity & Inflammation, College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow, G12 8QQ, Scotland. AbstractHuman African trypanosomiasis or 'sleeping sickness' is a neglected tropical disease caused by the parasite Trypanosoma brucei. A decade of intense international cooperation has brought the incidence to fewer than 10,000 reported cases per annum with anti-trypanosomal drugs, particularly against stage 2 disease where the CNS is involved, being central to control. Treatment failures with melarsoprol started to appear in the 1990s and their incidence has risen sharply in many foci. Loss of plasma membrane transporters involved in drug uptake, particularly the P2 aminopurine transporter and also a transporter termed the high affinity pentamidine transporter, relate to melarsoprol resistance selected in the laboratory. The same two transporters are also responsible for the uptake of the stage 1 drug pentamidine and, to varying extents, other diamidines. However, reports of treatment failures with pentamidine have been rare from the field. Eflornithine (difluoromethylornithine) has replaced melarsoprol as first-line treatment in many regions. However, a need for protracted and complicated drug dosing regimens slowed widespread implementation of eflornithine monotherapy. A combination of eflornithine with nifurtimox substantially decreases the required dose and duration of eflornithine administration and this nifurtimox-eflornithine combination therapy has enjoyed rapid implementation. Unfortunately, selection of resistance to eflornithine in the laboratory is relatively easy (through loss of an amino acid transporter believed to be involved in its uptake), as is selection of resistance to nifurtimox. The first anecdotal reports of treatment failures with eflornithine monotherapy are emerging from some foci. The possibility that parasites resistant to melarsoprol on the one hand, and eflornithine on the other, are present in the field indicates that genes capable of conferring drug resistance to both drugs are in circulation. If new drugs, that act in ways that will not render them susceptible to resistance mechanisms already in circulation do not appear soon, there is also a risk that the current downward trend in Human African trypanosomiasis prevalence will be reversed and, as has happened in the past, the disease will become resurgent, only this time in a form that resists available drugs. |
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| 7. | Orbit. 2011 Oct;30(5):255-7.Basal cell carcinoma in a full-thickness skin graft in the upper eyelid.Yazıcı B, Gönen T, Uçan G.SourceDepartment of Ophthalmology, Uludag University , Bursa , Turkey. AbstractA 75-year-old woman presented with a nodular lesion on a skin graft in her left upper eyelid. The lesion had grown gradually over the previous 2 years. She had undergone multiple surgeries and full-thickness skin graft procedures 61 years previously, because of cutaneous leishmaniasis. The diagnosis of nodular basal cell carcinoma was made by means of an excisional biopsy of the lesion. During a follow-up period of 27 months, the tumor did not recur. Malignant tumors may rarely develop at the site of traumatic or surgical scar. To our knowledge, this is the first reported case of basal cell carcinoma arising in a skin graft in the eyelid. |
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| 8. | PLoS One. 2011;6(9):e25112. Epub 2011 Sep 21.Is there a classical nonsense-mediated decay pathway in trypanosomes?Delhi P, Queiroz R, Inchaustegui D, Carrington M, Clayton C.SourceZentrum für Molekulare Biologie der Universität Heidelberg, DKFZ-ZMBH Alliance, Hedielberg, Germany. AbstractIn many eukaryotes, messenger RNAs with premature termination codons are destroyed by a process called "nonsense-mediated decay", which requires the RNA helicase Upf1 and also, usually, an interacting factor, Upf2. Recognition of premature termination codons may rely on their distance from either a splice site or the polyadenylation site, and long 3'-untranslated regions can trigger mRNA decay. The protist Trypanosoma brucei relies heavily on mRNA degradation to determine mRNA levels, and 3'-untranslated regions play a major role in control of mRNA decay. We show here that trypanosomes have a homologue of Upf1, TbUPF1, which interacts with TbUPF2 and (in an RNA-dependent fashion) with poly(A) binding protein 1, PABP1. Introduction of a premature termination codon in either an endogenous gene or a reporter gene decreased mRNA abundance, as expected for nonsense-mediated decay, but a dependence of this effect on TbUPF1 could not be demonstrated, and depletion of TbUPF1 by over 95% had no effect on parasite growth or the mRNA transcriptome. Further investigations of the reporter mRNA revealed that increases in open reading frame length tended to increase mRNA abundance. In contrast, inhibition of translation, either using 5'-secondary structures or by lengthening the 5'-untranslated region, usually decreased reporter mRNA abundance. Meanwhile, changing the length of the 3'-untranslated region had no consistent effect on mRNA abundance. We suggest that in trypanosomes, translation per se may inhibit mRNA decay, and interactions with multiple RNA-binding proteins preclude degradation based on 3'-untranslated region length alone. |
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| 9. | Chembiochem. 2011 Sep 28. doi: 10.1002/cbic.201100421. [Epub ahead of print]The Chemistry and Biology of Trypanosomal trans-Sialidases: Virulence Factors in Chagas Disease and Sleeping Sickness.< a href="http://www.ncbi.nlm.nih.gov/pubmed?term=%22Schauer%20R%22%5BAuthor%5D">Schauer R, Kamerling JP.SourceBiochemisches Institut, Christian-Albrechts-Universität Kiel, Olshausenstrasse 40, 24098 Kiel (Germany). schauer@biochem.uni-kiel.de. Abstracttrans-Sialidases constitute a special group of the sialidase family. They occur in some trypanosome species and, in a unique reversible reaction, transfer sialic acids from one glycosidic linkage with galactose (donor) to another galactose (acceptor), to form (α2-3)-sialyl linkages. Trypanosomes cause such devastating human diseases as Chagas disease in South America (Trypanosoma cruzi) or sleeping sickness in Africa (Trypanosoma brucei). The trans-sialidases strongly contribute to the pathogenicity of the trypanosomes by scavenging sialic acids from the host or blood meal to coat the parasite surface; this aids their survival strategy in the insect's intestine, and in the blood circulation or cells of the host, and serves to compromise the immune system of the human or animal host. American and African trypanosomes express trans-sialidases at different stages of their vector/host development. They are transmitted to humans by insect vectors (tsetse fly or other insect "bug" species). trans-Sialidase activity with varying linkage specificity has also been found in a few bacteria species and in human serum. trans-Sialidases are of increasing practical importance for the chemo-enzymatic synthesis of sialylated glycans. The search for appropriate inhibitors of trans-sialidases and vaccination strategies is intensifying, as less toxic medicaments for the treatment of these widespread and often chronic tropical diseases are required. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. |
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| 10. | Interdiscip Sci. 2011 Sep;3(3):217-31. Epub 2011 Sep 29.Screening natural products database for identification of potential antileishmanial chemotherapeutic agents.Venkatesan SK, Saudagar P, Shukla AK, Dubey VK.SourceDepartment of Biotechnology, Indian Institute of Technology Guwahati, Assam, 781039, India. AbstractLeishmaniasis is a parasitic infection caused by unicellular protozoan organism belonging to the family Trypanosomatidae. Among various forms of the disease, visceral leishmaniasis is the most lethal and caused by Leishmania infantum or Leishmania donovani. The redox metabolism of parasite requires a key enzyme, trypanothione reductase which is a validated drug target. In the past decade, it was observed that these protozoan parasites had developed resistance against many of available drugs. Importantly in the case of visceral leishmaniasis drug resistance is very high in the Indian subcontinent, a major endemic region of Leishmania donovani infection. In search for new drugs, we aim to identify potential natural product inhibitors of trypanothione reductase which can be further developed as anti-leishmanial drug. We have performed in silico virtual screening of a natural product data set of 800 diverse chemical entities. Leishmania infantum trypanothione reductase crystal structure (PDB ID: 2JK6) was used in the virtual screening process, docking studies to identify potential lead compounds. The compounds were sorted based upon their binding energy and the top 50 ranked protein-inhibitor complexes were clustered using AuPosSOM to ligand foot print the interactions. We report a few alkaloids and sterols for the first time, which could be potential trypanothione reductase inhibitors. The footprinting of protein-inhibitor interactions into clusters has also provided clues on various possible orientations that inhibitors can attain at the active site of Trypanothione reductase. Moreover, biological significance of the interactions has also been discussed. |
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