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Sent on Wednesday, 2012 May 23Search: kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"
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PubMed Results |
1. | PLoS Negl Trop Dis. 2012 May;6(5):e1626. Epub 2012 May 15.In Vitro and In Vivo Activity of a Palladacycle Complex on Leishmania (Leishmania) amazonensis.Paladi Cde S, Pimentel IA, Katz S, Cunha RL, Judice WA, Caires AC, Barbiéri CL.SourceDepartamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de São Paulo, São Paulo, São Paulo, Brazil. AbstractBACKGROUND:Antitumor cyclopalladated complexes with low toxicity to laboratory animals have shown leishmanicidal effect. These findings stimulated us to test the leishmanicidal property of one palladacycle compound called DPPE 1.2 on Leishmania (Leishmania) amazonensis, an agent of simple and diffuse forms of cutaneous leishmaniasis in the Amazon region, Brazil. METHODOLOGY/PRINCIPAL FINDINGS:Promastigotes of L. (L.) amazonensis and infected bone marrow-derived macrophages were treated with different concentrations of DPPE 1.2. In in vivo assays foot lesions of L. (L.) amazonensis-infected BALB/c mice were injected subcutaneously with DPPE 1.2 and control animals received either Glucantime or PBS. The effect of DPPE 1.2 on cathepsin B activity of L. (L.) amazonensis amastigotes was assayed spectrofluorometrically by use of fluorogenic substrates. The main findings were: 1) axenic L. (L.) amazonensis promastigotes were destroyed by nanomolar concentrations of DPPE 1.2 (IC50 = 2.13 nM); 2) intracellular parasites were killed by DPPE 1.2 (IC50 = 128.35 nM), and the drug displayed 10-fold less toxicity to macrophages (CC50 = 1,267 nM); 3) one month after intralesional injection of DPPE 1.2 infected BALB/c mice showed a significant decrease of foot lesion size and a reduction of 97% of parasite burdens when compared to controls that received PBS; 4) DPPE 1.2 inhibited the cysteine protease activity of L. (L.) amazonensis amastigotes and more significantly the cathepsin B activity. CONCLUSIONS/SIGNIFICANCE:The present results demonstrated that DPPE 1.2 can destroy L. (L.) amazonensis in vitro and in vivo at concentrations that are non toxic to the host. We believe these findings support the potential use of DPPE 1.2 as an alternative choice for the chemotherapy of leishmaniasis. |
PMID: 22616018 [PubMed - in process] | |
2. | PLoS Negl Trop Dis. 2012 May;6(5):e1615. Epub 2012 May 15.Modeling the control of trypanosomiasis using trypanocides or insecticide-treated livestock.Hargrove JW, Ouifki R, Kajunguri D, Vale GA, Torr SJ .SourceDST/NRF Centre of Excellence in Epidemiological Modelling and Analysis (SACEMA), University of Stellenbosch, Stellenbosch, South Africa. AbstractBACKGROUND:In Uganda, Rhodesian sleeping sickness, caused by Trypanosoma brucei rhodesiense, and animal trypanosomiasis caused by T. vivax and T. congolense, are being controlled by treating cattle with trypanocides and/or insecticides. We used a mathematical model to identify treatment coverages required to break transmission when host populations consisted of various proportions of wild and domestic mammals, and reptiles. METHODOLOGY/PRINCIPAL FINDINGS:An Ro model for trypanosomiasis was generalized to allow tsetse to feed off multiple host species. Assuming populations of cattle and humans only, pre-intervention Ro values for T. vivax, T. congolense, and T. brucei were 388, 64 and 3, respectively. Treating cattle with trypanocides reduced R(0) for T. brucei to <1 if >65% of cattle were treated, vs 100% coverage necessary for T. vivax and T. congolense. The presence of wild mammalian hosts increased the coverage required and made control of T. vivax and T. congolense impossible. When tsetse fed only on cattle or humans, R(0) for T. brucei was <1 if 20% of cattle were treated with insecticide, compared to 55% for T. congolense. If wild mammalian hosts were also present, control of the two species was impossible if proportions of non-human bloodmeals from cattle were <40% or <70%, respectively. R(0) was <1 for T. vivax only when insecticide treatment led to reductions in the tsetse population. Under such circumstances R(0)<1 for T. brucei and T. congolense if cattle make up 30% and 55%, respectively of the non-human tsetse bloodmeals, as long as all cattle are treated with insecticide. CONCLUSIONS/SIGNIFICANCE:In settled areas of Uganda with few wild hosts, control of Rhodesian sleeping sickness is likely to be much more effectively controlled by treating cattle with insecticide than with trypanocides. |
PMID: 22616017 [PubMed - in process] | |
3. | Front Immunol. 2012;3:99. Epub 2012 May 15.Vaccine Development Against Leishmania donovani.Das A, Ali N.SourceInfectious Diseases and Immunology Division, Indian Institute of Chemical Biology Kolkata, India. AbstractVisceral leishmaniasis (VL) caused by Leishmania donovani and Leishmania infantum/chagasi represents the second most challenging infectious disease worldwide, leading to nearly 500,000 new cases and 60,000 deaths annually. Zoonotic VL caused by L. infantum is a re-emergent canid zoonoses which represents a complex epidemiological cycle in the New world where domestic dogs serve as a reservoir host responsible for potentially fatal human infection and where dog culling is the only measure for reservoir control. Life-long immunity to VL has motivated development of prophylactic vaccines against the disease but very few have progressed beyond the experimental stage. No licensed vaccine is available till date against any form of leishmaniasis. High toxicity and increasing resistance to the current chemotherapeutic regimens have further complicated the situation in VL endemic regions of the world. Advances in vaccinology, including recombinant proteins, novel antigen-delivery systems/adjuvants, heterologous prime-boost regimens and strategies for intracellular antigen presentation, have contributed to recent advances in vaccine development against VL. Attempts to develop an effective vaccine for use in domestic dogs in areas of canine VL should be pursued for preventing human infection. Studies in animal models and human patients have revealed the pathogenic mechanisms of disease progression and features of protective immunity. This review will summarize the accumulated knowledge of pathogenesis, immune response, and prerequisites for protective immunity against human VL. Authors will discuss promising vaccine candidates, their developmental status and future prospects in a quest for rational vaccine development against the disease. In addition, several challenges such as safety issues, renewed and coordinated commitment to basic research, preclinical studies and trial design will be addressed to overcome the problems faced in developing prophylactic strategies for protection against this lethal infection. |
PMID: 22615707 [PubMed - in process] | |
4. | PLoS Pathog. 2012 May;8(5):e1002695. Epub 2012 May 17.ATG5 Is Essential for ATG8-Dependent Autophagy and Mitochondrial Homeostasis in Leishmania major.Williams RA, Smith TK, Cull B, Mottram JC, Coombs GH .SourceStrathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, United Kingdom. AbstractMacroautophagy has been shown to be important for the cellular remodelling required for Leishmania differentiation. We now demonstrate that L. major contains a functional ATG12-ATG5 conjugation system, which is required for ATG8-dependent autophagosome formation. Nascent autophagosomes were found commonly associated with the mitochondrion. L. major mutants lacking ATG5 (Δatg5) were viable as promastigotes but were unable to form autophagosomes, had morphological abnormalities including a much reduced flagellum, were less able to differentiate and had greatly reduced virulence to macrophages and mice. Analyses of the lipid metabolome of Δatg5 revealed marked elevation of phosphatidylethanolamines (PE) in comparison to wild type parasites. The Δatg5 mutants also had increased mitochondrial mass but reduced mitochondrial membrane potential and higher levels of reactive oxygen species. These findings indicate that the lack of ATG5 and autophagy leads to perturbation of the phospholipid balance in the mitochondrion, possibly through ablation of membrane use and conjugation of mitochondrial PE to ATG8 for autophagosome biogenesis, resulting in a dysfunctional mitochondrion with impaired oxidative ability and energy generation. The overall result of this is reduced virulence. |
PMID: 22615560 [PubMed - in process] | |
5. | Indian J Dermatol. 2012 Mar;57(2):133-135.Blastomycosis Presenting as Solitary Nodule: A Rare Presentation.Dhamija A, D'Souza P, Salgia P, Meherda A, Kothiwala R.SourceDepartment of Dermatology,Venereology and Leprosy, JLN Medical College and Hospitals, Ajmer, Rajasthan, India. AbstractBlastomycosis is a chronic granulomatous and suppurative mycosis, caused by Blastomyces dermatitidis, which in the great majority of cases presents as a primary pulmonary disease. Primary cutaneous blastomycosis is very rare. We present a 57-year-old female patient with a solitary, slowly progressive nodule over upper lip of 2½ months duration. Initially, differential diagnosis of cutaneous leishmaniasis, pyoderma and deep mycoses were entertained. Slit smear preparation was suspicious of deep mycotic infection which was subsequently confirmed by biopsy and culture. |
PMID: 22615513 [PubMed - as supplied by publisher] | |
6. | Indian J Dermatol. 2012 Mar;57(2):123-125.Treatment of Cutaneous Lesion of 20 Years' Duration Caused by Leishmanization.Khamesipour A, Abbasi A, Firooz A, Mohammadi AM, Eskandari SE, Jaafari MR.SourceCenter for Research and Training in Skin Diseases and Leprosy, Tehran University of Medical Sciences, Tehran, Iran. AbstractThe inoculation of live Leishmania (L.) major to produce a single lesion is called leishmanization (LZ). LZ lesion upon cure prevents further natural infection which might be multiple lesions on unwanted sites such as face. Cutaneous leishmaniasis (CL) usually leads to a self healing lesion; though rarely the lesion persists and becomes refractory to all types of remedies. Here, we present a 41-year-old patient with a 20-year history of cutaneous lesion caused by leishmanization. The causative agent is identified as L. major. The patient did not respond to treatment with meglumine antimoniate, 20 mg/kg/day Sb(+5) for three weeks and allopurinol 10 mg/kg for four weeks. After two months, the same treatment was repeated. In addition, a topical liposomal preparation containing 10% paromomycin sulfate was administered twice a day for four weeks. The lesion showed marked improvement during the treatment and was eventually completely healed. |
PMID: 22615509 [PubMed - as supplied by publisher] | |
7. | Indian J Dermatol. 2012 Mar;57(2):118-122.Comparison of Intralesional Two Percent Zinc Sulfate and Glucantime Injection in Treatment of Acute Cutaneous Leishmaniasis.Maleki M, Karimi G, Tafaghodi M, Raftari S, Nahidi Y.SourceResearch Center for Skin Diseases and Cutaneous Leishmanaisis, Imam Reza Hospital, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. AbstractINTRODUCTION:Cutaneous leishmaniasis is an endemic disease in developing countries caused by different species of leishmania parasite, and if left untreated, it will result in a deformed scar after a relatively long period. Although various systemic and topical treatments have been proposed for leishmaniasis, pentavalent Antimony compounds remain the first-line treatment for it. Considering the cases with treatment failure, potential side effects and reluctance of patients to receive the drug, there are continuing efforts to find better treatment alternatives. AIM:Comparison of the effect of intralesional 2% zinc sulfate injection with Glucantime in treatment of acute cutaneous leishmaniasis. MATERIALS AND METHODS:In this clinical trial, 45 patients with clinical diagnosis of cutaneous leishmaniasis and positive direct smear for leishman body were treated by intralesional injection of either 2% zinc sulfate or Glucantime. After simple randomization, in one group the patients were treated with 2 bouts of intralesional 2% zinc sulfate with a 2-week interval, and in the other group they were treated with 6 weekly bouts of intralesional Glucantime. The patients were monitored in two week intervals for 8 weeks. Healing of the lesions was evaluated clinically and by direct smear, and the data were analyzed using SPSS (11.5) software, t-Student, Mann-Whitney and Analysis of covariance (ANCOVA) statistical tests. FINDINGS:In the end of study, 34 patients completed the study, 10 of whom received intralesional Glucantime and 24 of whom received intralesional 2% zinc sulfate. The healing rate after 8 weeks was 80% in the group receiving intralesional Glucantime and 33.3% in the one receiving 2% zinc sulfate (P=0.009). CONCLUSION:Based on the results of this study, intralesional injection of 2% zinc sulfate was less effective in treatment of cutaneous leishmaniasis than intralesional Glucantime. |
PMID: 22615508 [PubMed - as supplied by publisher] | |
8. | J Immunol. 2012 May 21. [Epub ahead of print]Loss of TNF Signaling Facilitates the Development of a Novel Ly-6Clow Macrophage Population Permissive for Leishmania major Infection.Fromm PD, Kling J, Mack M, Sedgwick JD, Körner H.SourceANZAC Research Institute, Concord Hospital, Sydney, New South Wales 2039, Australia; AbstractIn the absence of TNF, the normally resistant C57BL/6 (B6.WT) strain develops a fatal, progressive form of leishmaniasis after infection with Leishmania major. It is not yet understood which TNF activity or the lack thereof is responsible for the dramatic progression of leishmaniasis in TNF-negative (B6.TNF(-/-)) mice. To elucidate the underlying mechanisms resulting in the fatal outcome of L. major infection in this gene-deficient mouse strain, we analyzed the monocytic component of the inflammatory infiltrate in the draining popliteal lymph node and the site of the infection using multicolor flow cytometry. The leukocytic infiltrate within the draining lymph node and footpad of B6.TNF(-/-) mice resembled that of B6.WT mice over the first 2 wk of cutaneous L. major infection. Thereafter, the B6.TNF(-/-) mice showed an increase of CD11c(+)Ly-6C(+)CCR2(+) monocytic dendritic cells within the popliteal lymph node in comparison with B6.WT mice. This increase of inflammatory dendritic cells was paired with the accumulation of a novel CD11b(+)Ly-6C(low)CCR2(low) population that was not present in B6.WT mice. This B6.TNF(-/-)- and B6.TNFR1(-/-)-specific cell population was CD115(+)Ly-6G(-)iNOS(-), not apoptotic, and harbored large numbers of parasites. |
PMID: 22615203 [PubMed - as supplied by publisher] | |
9. | Genet Mol Res. 2012 May 9;11(2):1260-5.Characterization of Trypanosoma brucei gambiense variant surface glycoprotein LiTat 1.5.Van Nieuwenhove L, Rogé S, Lejon V, Guisez Y, Büscher P .SourceDepartment of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium. AbstractAt present, all available diagnostic antibody detection tests for Trypanosoma brucei gambiense human African trypanosomiasis are based on predominant variant surface glycoproteins (VSGs), such as VSG LiTat 1.5. During investigations aiming at replacement of the native VSGs by recombinant proteins or synthetic peptides, the sequence of VSG LiTat 1.5 was derived from cDNA and direct N-terminal amino acid sequencing. Characterization of the VSG based on cysteine distribution in the amino acid sequence revealed an unusual cysteine pattern identical to that of VSG Kinu 1 of T. b. brucei. Even though both VSGs lack the third of four conserved cysteines typical for type A N-terminal domains, they can be classified as type A. |
PMID: 22614354 [PubMed - in process] | |
10. | Parasit Vectors. 2012 May 21;5(1):98. [Epub ahead of print]Detection of Leishmania infantum DNA mainly in Rhipicephalus sanguineus male ticks removed from dogs living in endemic areas of canine leishmaniosis.Solano-Gallego L, Rossi L, Scroccaro AM, Montarsi F, Caldin M, Furlanello T, Trotta M.AbstractABSTRACT: BACKGROUND:Sand flies are the only biologically adapted vectors of Leishmania parasites, however, a possible role in the transmission of Leishmania has been proposed for other hematophagous ectoparasites such as ticks. In order to evaluate natural infection by Leishmania infantum in Rhipicephalus sanguineus ticks, taking into account its close association with dogs, 128 adult R. sanguineus ticks removed from 41 dogs living in endemic areas of canine leishmaniosis were studied. METHODS:Individual DNA extraction was performed from each tick and whole blood taken from dogs. Dog sera were tested for IgG antibodies to L. infantum antigen by ELISA and L. infantum real-time PCR was performed from canine whole blood samples and ticks. RESULTS:Leishmania infantum PCR was positive in 13 ticks (10.1%) including one female, (2.0%) and 12 males (15.2%), and in only five dogs (12.2%). Male ticks had a significantly higher infection rate when compared to female R. sanguineus. The percentage of L. infantum seroreactive dogs was 19.5%. All but two PCR positive dogs were seroreactive. Leishmania infantum PCR positive ticks were removed from seropositive and seronegative dogs with a variety of PCR results. CONCLUSIONS:This study demonstrates high prevalence of L. infantum DNA in R. sanguineus ticks removed from L. infantum seropositive and seronegative dogs. The presence of L. infantum DNA was detected mainly in male ticks possibly due to their ability to move between canine hosts and feed on several canine hosts during the adult life stage. Additional studies are needed to further explore the role of R. sanguineus ticks and in particular, male adults, in both the epidemiology and immunology of L. infantum infection in dogs in endemic areas. |
PMID: 22613502 [PubMed - as supplied by publisher] | |
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