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Sent on Wednesday, 2011 Oct 12Search kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"
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| PubMed Results |
| 1. | J Antimicrob Chemother. 2011 Oct 10. [Epub ahead of print]The in vivo activity of 1,3,4-thiadiazolium-2-aminide compounds in the treatment of cutaneous and visceral leishmaniasis.Rodrigues RF, Charret KS, Campos MC, Amaral V, Echevarria A, Dos Reis C, Canto-Cavalheiro MM, Leon LL.SourceFundação Oswaldo Cruz, Instituto Oswaldo Cruz, Laboratório de Bioquímica de Tripanosomatídeos, Rio de Janeiro, Brasil. AbstractObjectivesResearchers have recently investigated the biological activities of mesoionic (MI) compounds, which have shown in vitro activity against many species of Leishmania, as well as Trypanosoma cruzi. The main goal of this study was to evaluate and compare the activity of three MI compounds against Leishmania amazonensis and Leishmania infantum infection in vivo.MethodsThe experiments were carried out using BALB/c mice infected with L. amazonensis or L. infantum as a highly sensitive murine model. The infected mice were treated with MI-HH, MI-4-OCH(3), MI-4-NO(2) or meglumine antimoniate by different routes (intralesional, topical or intraperitoneal).ResultsTreatment with MI-4-OCH(3) and MI-4-NO(2) efficiently contained the progression of cutaneous and visceral leishmaniasis in comparison with the control group or mice treated with meglumine antimoniate. Interestingly, these MI compounds did not produce toxicological effects after treatment. Furthermore, treatment with these compounds led to a modulation of the immune response that was correlated with disease control. In this study, MI compounds, and MI-4-NO(2) in particular, exhibited high activity in the L. infantum murine model. In the L. amazonensis model, intralesional treatment with MI-4-OCH(3) or MI-4-NO(2) showed greater therapeutic efficacy than treatment with meglumine antimoniate, and the new topical formulations of these compounds also displayed great activity in the cutaneous leishmaniasis model.ConclusionsUpon comparison of each MI compound, MI-4-NO(2) was clearly the compound with the greatest activity in these two in vivo infection models by each administration route tested. |
| 2. | An Bras Dermatol. 2011 Aug;86(4):708-15.Genetic risk factors for human susceptibility to infections of relevance in dermatology.Sardinha JF, Tarlé RG, Fava VM, Francio AS, Ramos GB, Ferreira LC, Schriefer NA, Mira MT, Talhari S.SourceTropical Medicine Foundation of Amazonas, Manaus, AM, Brazil. AbstractBACKGROUND: In the pre-microbiological era, it was widely accepted that diseases, today known to be infectious, were hereditary. With the discovery of microorganisms and their role in the pathogenesis of several diseases, it was suggested that exposure to the pathogen was enough to explain infection. Nowadays, it is clear that infection is the result of a complex interplay between pathogen and host, therefore dependant on the genetic make-up of the two organisms. Dermatology offers several examples of infectious diseases in different stages of understanding of their molecular basis. In this review, we summarize the main advances towards dissecting the genetic component controlling human susceptibility to infectious diseases of interest in dermatology. Widely investigated diseases such as leprosy and leishmaniasis are discussed from the genetic perspective of both host and pathogen. Others, such as rare mycobacterioses, fungal infections and syphilis, are presented as good opportunities for research in the field of genetics of infection. |
| 3. | BMC Ecol. 2011 Oct 10;11(1):24. [Epub ahead of print]Expression plasticity of Phlebotomus papatasi salivary gland genes in distinct ecotopes through the sand fly season.Coutinho-Abreu IV, Mukbel R, Hanafi HA, Fawaz EY, El-Hossary SS, Wadsworth M, Stayback G, Pitts DA, Abo-Shehada M, Hoel DF, Kamhawi S, Ramalho-Ortigao M, McDowell MA.AbstractABSTRACT: BACKGROUND:Sand fly saliva can drive the outcome of Leishmania infection in animal models, and salivary components have been postulated as vaccine candidates against leishmaniasis. In the sand fly Phlebotomus papatasi, natural sugar-sources modulate the activity of proteins involved in meal digestion, and possibly influence vectorial capacity. However, only a handful of studies have assessed the variability of salivary components in sand flies, focusing on the effects of environmental factors in natural habitats. In order to better understand such interactions, we compared the expression profiles of nine P. papatasi salivary gland genes of specimens inhabiting different ecological habitats in Egypt and Jordan and throughout the sand fly season in each habitat. RESULTS:The majority of investigated genes were up-regulated in specimens from Swaymeh late in the season, when the availability of sugar sources is reduced due to water deprivation. On the other hand, these genes were not up-regulated in specimens collected from Aswan, an irrigated area less susceptible to drought effects. CONCLUSION:Expression plasticity of genes involved with vectorial capacity in disease vectors may play an important epidemiological role in the establishment of diseases in natural habitats. |
| 4. | Clin Microbiol Infect. 2011 Sep 14. doi: 10.1111/j.1469-0691.2011.03674.x. [Epub ahead of print]Tumor necrosis factor alpha antagonist drugs and leishmaniasis in Europe.Zanger P, Kötter I, Kremsner PG, Gabrysch S.SourceInstitut für Tropenmedizin, Eberhard Karls Universität, Wilhelmstraße Medizinische Klinik, Eberhard Karls Universität, Otfried-Müller-Straße, Tübingen Institut für Public Health, Ruprecht Karls Universität, Im Neuenheimer Feld, Heidelberg, Germany. AbstractClin Microbiol Infect ABSTRACT: Leishmaniasis is endemic in Europe and the prevalence of latent infection in the Mediterranean region is high. Reports describing opportunistic leishmaniasis in European patients treated with tumor necrosis factor (TNF) alpha antagonist drugs are rapidly accumulating. For other granulomatous infections, risk of opportunistic disease varies by mode of TNF-alpha antagonism. This study explores whether this may also be the case for leishmaniasis. We ascertained the relative frequency of exposure to different TNF antagonist drugs among published cases of opportunistic leishmaniasis in Europe and compared this with the prescription of these drugs in Europe. We found that risk of opportunistic leishmaniasis is higher in patients receiving anti-TNF monoclonal antibodies (infliximab or adalimumab) compared with patients treated with the TNF-receptor construct etanercept. Clinicians may want to consider these observations, which suggest that etanercept should be favoured over anti-TNF monoclonal antibodies in individuals living in or visiting areas endemic for leishmaniasis until evidence from prospective research is available. A European adverse event reporting system is required to identify rare opportunistic infections associated with immunosuppressive and immunomodulatory biotherapies. © 2011 The Authors. Clinical Microbiology and Infection © 2011 European Society of Clinical Microbiology and Infectious Diseases. |
| 5. | Parasit Vectors. 2011 Oct 10;4(1):197. [Epub ahead of print]One Health: the Global Challenge of Epidemic and Endemic Leishmaniasis.Palatnik-de-Sousa CB, Day MJ.AbstractABSTRACT: 'One Health' proposes the unification of medical and veterinary sciences with the establishment of collaborative ventures in clinical care, surveillance and control of cross-species disease, education, and research into disease pathogenesis, diagnosis, therapy and vaccination. The concept encompasses the human population, domestic animals and wildlife, and the impact that environmental changes ('environmental health') such as global warming will have on these populations. Visceral leishmaniasis is a perfect example of a small companion animal disease for which prevention and control might abolish or decrease the suffering of canine and human patients, and which aligns well with the One Health approach. In this review we discuss how surveillance for leishmaniases is undertaken globally through the control of anthroponootic visceral leishmaniasis (AVL) and zoonotic visceral leishmaniasis (ZVL). The ZVL epidemic has been managed to date by the culling of infected dogs, treatment of human cases and control of the sandfly vector by insecticidal treatment of human homes and the canine reservoir. Recently, preventive vaccination of dogs in Brazil has led to reduction in the incidence of the canine and human disease. Vaccination permits greater dog owner compliance with control measures than a culling programme. Another advance in disease control in Africa is provided by a surveillance programme that combines remote satellite sensing, ecological modelling, vector surveillance and geo-spatial mapping of the distribution of vectors and of the animal-to-animal or animal-to-human pathogen transmission. This coordinated programme generates advisory notices and alerts on emerging infectious disease outbreaks that may impede or avoid the spreading of visceral leishmaniasis to new areas of the planet as a consequence of global warming. |
| 6. | J Am Chem Soc. 2011 Jun 29;133(25):9923-31. Epub 2011 Jun 3.Transition-state analysis of Trypanosoma cruzi uridine phosphorylase-catalyzed arsenol ysis of uridine.Silva RG, Vetticatt MJ, Merino EF, Cassera MB, Schramm VL.SourceDepartment of Biochemistry, Albert Einstein College of Medicine of Yeshiva University, 1300 Morris Park Avenue, Bronx, New York 10461, USA. AbstractUridine phosphorylase catalyzes the reversible phosphorolysis of uridine and 2'-deoxyuridine to generate uracil and (2-deoxy)ribose 1-phosphate, an important step in the pyrimidine salvage pathway. The coding sequence annotated as a putative nucleoside phosphorylase in the Trypanosoma cruzi genome was overexpressed in Escherichia coli , purified to homogeneity, and shown to be a homodimeric uridine phosphorylase, with similar specificity for uridine and 2'-deoxyuridine and undetectable activity toward thymidine and purine nucleosides. Competitive kinetic isotope effects (KIEs) were measured and corrected for a forward commitment factor using arsenate as the nucleophile. The intrinsic KIEs are: 1'-(14)C = 1.103, 1,3-(15)N(2) = 1.034, 3-(15)N = 1.004, 1-(15)N = 1.030, 1'-(3)H = 1.132, 2'-(2)H = 1.086, and 5'-(3)H(2) = 1.041 for this reaction. Density functional theory was employed to quantitatively interpret the KIEs in terms of transition-state structure and geometry. Matching of experimental KIEs to proposed transition-state structures suggests an almost synchronous, S(N)2-like transition-state model, in which the ribosyl moiety possesses significant bond order to both nucleophile and leaving groups. Natural bond orbital analysis allowed a comparison of the charge distribution pattern between the ground-state and the transition-state models. |
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