What's new for 'Trypanosomatids' in PubMed

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Sent on Thursday, 2009 Nov 26
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 12

1.	ChemMedChem. 2009 Nov 20. [Epub ahead of print] Bisnaphthalimidopropyl Derivatives as Inhibitors of Leishmania SIR2 Related Protein 1. Tavares J, Ouaissi A, Kong Thoo Lin P, Loureiro I, Kaur S, Roy N, Cordeiro-da-Silva A. IBMC - Instituto de Biologia Molecular e Celular, Universidade do Porto, Rua do Campo Alegre 823, 4150-180 Porto (Portugal). The NAD(+)-dependent deacetylases, namely sirtuins, are involved in the regulation of a variety of biological processes such as gene silencing, DNA repair, longevity, metabolism, apoptosis, and development. An enzyme from the parasite Leishmania infantum that belongs to this family, LiSIR2RP1, is a NAD(+)-dependent tubulin deacetylase and an ADP-ribosyltransferase. This enzyme's involvement in L. infantum virulence and survival underscores its potential as a drug target. Our search for selective inhibitors of LiSIR2RP1 has led, for the first time, to the identification of the antiparasitic and anticancer bisnaphthalimidopropyl (BNIP) alkyl di- and triamines (IC(50) values in the single-digit micromolar range for the most potent compounds). Structure-activity studies were conducted with 12 BNIP derivatives that differ in the length of the central alkyl chain, which links the two naphthalimidopropyl moieties. The most active and selective compound is the BNIP diaminononane (BNIPDanon), with IC(50) values of 5.7 and 97.4 muM against the parasite and human forms (SIRT1) of the enzyme, respectively. Furthermore, this compound is an NAD(+)-competitive inhibitor that interacts differently with the parasite and human enzymes, as determined by docking analysis, which might explain its selectivity toward the parasitic enzyme.
	PMID: 19937668 [PubMed - as supplied by publisher]

2.	Indian J Pediatr. 2009 Nov 20. [Epub ahead of print] Post-treatment fulminant hepatic failure in an infant with visceral Leishmaniasis: Immune injury or Stibogluconate toxicity? Baranwal AK, Ravi RN, Singh R. Department of Pediatric Critical Care, Postgraduate Institute of Medical Education and Research, Chandigarh, India, baranwal1970@yahoo.com.
	PMID: 19936650 [PubMed - as supplied by publisher]

3.	J Immunol. 2009 Nov 23. [Epub ahead of print] Ubiquitin Conjugation of ORFF DNA Vaccine Leads to Enhanced Cell-Mediated Immune Response and Induces Protection against Both Antimony-Susceptible and -Resistant Strains of Leishmania donovani. Sharma A, Madhubala R. School of Life Sciences, Jawaharlal Nehru University, New Delhi, India. Resistance of Leishmania donovani to sodium antimony gluconate has become a critical issue in the current, prolonged epidemic in India. Hence, there is an urgent need for a vaccine that is protective against both antimony-susceptible and -resistant strains of L. donovani. The multigene LD1 locus located on chromosome 35 of Leishmania is amplified in approximately 15% of the isolates examined. The open reading frame F (ORFF), a potential vaccine candidate against visceral leishmaniasis, is part of the multigene LD1 locus. ORFF was expressed as a chimeric conjugate of ubiquitin to elicit an Ag-specific cell-mediated immune response. Analysis of the cellular immune responses of ubiquitin-conjugated ORFF (UBQ-ORFF) DNA-immunized, uninfected BALB/c mice demonstrated that the vaccine induced enhanced IFN-gamma-producing CD4(+) and CD8(+) T cells compared with nonubiquitinated ORFF DNA vaccine. Higher levels of IL-12 and IFN-gamma and the low levels of IL-4 and IL-10 further indicated that the immune responses with UBQ-ORFF were mediated toward the Th1 rather than Th2 type. Infection of immunized mice with either the antimony-susceptible (AG83) or -resistant (GE1F8R) L. donovani strain showed that UBQ-ORFF DNA vaccine induced higher protection when compared with ORFF DNA. UBQ-ORFF DNA-immunized and -infected mice showed a significant increase in IL-12 and IFN-gamma and significant down-regulation of IL-10. High levels of production of nitrite and superoxide, two macrophage-derived oxidants that are critical in controlling Leishmania infection, were observed in protected mice. The feasibility of using ubiquitinated-conjugated ORFF DNA vaccine as a promising immune enhancer for vaccination against both antimony-susceptible and -resistant strains of L. donovani is reported.
	PMID: 19933862 [PubMed - as supplied by publisher]

4.	Photodiagnosis Photodyn Ther. 2009 September - December;6(3-4):170-188. Photodynamic therapy for localized infections-State of the art. Dai T, Huang YY, Hamblin MR. Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA, United States; Department of Dermatology, Harvard Medical School, Boston, MA, United States. Photodynamic therapy (PDT) was discovered over 100 years ago by observing the killing of microorganisms when harmless dyes and visible light were combined in vitro. Since then it has primarily been developed as a treatment for cancer, ophthalmologic disorders and in dermatology. However, in recent years interest in the antimicrobial effects of PDT has revived and it has been proposed as a therapy for a large variety of localized infections. This revival of interest has largely been driven by the inexorable increase in drug resistance among many classes of pathogen. Advantages of PDT include equal killing effectiveness regardless of antibiotic resistance, and a lack of induction of PDT resistance. Disadvantages include the cessation of the antimicrobial effect when the light is turned off, and less than perfect selectivity for microbial cells over host tissue. This review will cover the use of PDT to kill or inactivate pathogens in ex vivo tissues and in biological materials such as blood. PDT has been successfully used to kill pathogens and even to save life in several animal models of localized infections such as surface wounds, burns, oral sites, abscesses and the middle ear. A large number of clinical studies of PDT for viral papillomatosis lesions and for acne refer to its antimicrobial effect, but it is unclear how important this microbial killing is to the overall therapeutic outcome. PDT for periodontitis is a rapidly growing clinical application and other dental applications are under investigation. PDT is being clinically studied for other dermatological infections such as leishmaniasis and mycobacteria. Antimicrobial PDT will become more important in the future as antibiotic resistance is only expected to continue to increase.
	PMID: 19932449 [PubMed - as supplied by publisher]

5.	Vet Clin North Am Small Anim Pract. 2009 Nov;39(6):1065-1074. Canine Leishmaniasis in Nor th America: Emerging or Newly Recognized? Petersen CA, Barr SC. Department of Veterinary Pathology, 2714 Vet. Med., Iowa State University, Ames, IA 50014, USA. Canine leishmaniasis is a fatal zoonotic visceralizing disease usually associated with tropical areas. The etiologic agent is an obligate intracellular protozoan, Leishmania infantum. In 1999, an outbreak of a canine leishmaniasis was reported in a Foxhound kennel in New York, and since that report, several other outbreaks have occurred across the United States in additional Foxhound kennels. Because of the high mortality and transmissibility associated with these outbreaks, it is essential that clinicians be aware of this disease to permit its rapid recognition and institution of control measures. Cases with a travel history may suggest imported disease; these are mainly observed from Southern Europe (eg, south of France, Spain, and Italy). Breeds from these and other endemic areas may be at higher risk of infection with Leishmania because of vertical transmission. The purpose of this report is to discuss the clinical signs, epidemiology, diagnosis, control, and treatment of canine leishmaniasis with focus on the aspects of this disease within North America.
	PMID: 19932363 [PubMed - as supplied by publisher]

6.	Exp Parasitol. 2009 Nov 18. [Epub ahead of print] Trypanosoma cruzi TBP shows preference for C/G-rich DNA sequences in vitro. Cribb P, Esteban L, Trochine A, Girardini J, Serra E. Instituto de Biología Molecular y Celular de Rosario, CONICET. Facultad de Ciencias Bioquímicas y Farmacéuticas, UNR, Suipacha 351, 2000, Rosario, Argentina. Recent findings associate transcription start in trypanosomatids with chromatin regions containing modified and variant histones. TATA-binding protein (TBP) and other fundamental transcription factors have been also found at these Transcription Start Sites (TSS). Results of Systematic Evolution of Ligands by Exponential Enrichment (SELEX) experiments show that Trypanosoma cruzi TBP (TcTBP) has an in vitro binding preference for G-rich sequences. This finding correlates with the presence of G-rich stretches at the Strand Switch Regions (SSR) and at some putative internal TSS in Trypanosoma brucei and Leishmania. A scanning study of partially assembled T. cruzi genomic contigs determined the presence of G-rich stretches in the coding strands. TcTBP affinity for G-rich sequences suggests that this factor could play a role in locating the initiation complex in the right TSS, probably by "sensing" the G-content on the strand to be transcribed.
	PMID: 19931528 [PubMed - as supplied by publisher]

7.	Mol Biochem Parasitol. 2009 Nov 17. [Epub ahead of print] Characterizaion of a leucine aminopeptidase from Toxoplasma gondii. Jia H, Nishikawa Y, Luo Y, Yamagishi J, Sugimoto C, Xuan X. National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Hokkaido 080-8555, Japan; Department of Collaboration and Education, Research Center for Zoonosis Control, Hokkaido University, Sapporo, Hokkaido 001-0020, Japan. The M17 family leucine aminopeptidase (LAP) hydrolyzes amino acids from the N-terminus of peptides. Many LAPs from parasitic protozoa, including Plasmodium, Trypanosoma, and Leishmania, have been intensely investigated because of their crucial roles in parasite biology. In this study, the functional recombinant Toxoplasma gondii LAP (rTgLAP) was expressed in Escherichia coli (E. coli), and its enzymatic activity against synthetic substrates for aminopeptidase, as well as cellular localization, were determined. The activity was strongly dependent on metal divalent cations, and was inhibited by bestatin, which is an inhibitor for metalloprotease. Our results indicated that TgLAP is a functional aminopeptidase in the cytoplasm of T. gondii.
	PMID: 19931316 [PubMed - as supplied by publisher]

8.	J Travel Med. 2009 Nov-Dec;16(6):395-401. Imported leishmaniasis: a heterogeneous group of diseases. Pérez-Ayala A, Norman F, Pérez-Molina JA, Herrero JM, Monge B, López-Vélez R. Tropical Medicine & Clinical Parasitology, Infectious Diseases Department, Ramón y Cajal Hospital, Madrid, Spain. Background. Leishmaniasis is endemic in many countries. The existence of different species combined with host factors may condition clinical presentation, treatment options, and disease outcome. In an endemic country, a predominance of certain species and presentations may be expected, whereas from the perspective of a tropical medicine referral unit a wider variety of cases from diverse geographical areas may be observed. Methods. Retrospective study of imported leishmaniasis cases diagnosed at a Tropical Medicine referral unit in Spain, during the period of January 1995 to June 2008. Results. In total, 18 cases were diagnosed: 12 cutaneous leishmaniasis (CL), 4 mucocutaneous leishmaniasis (ML), and 2 visceral leishmaniasis (VL) cases. Two patients were immunosuppressed. The majority of CL cases (9/12) occurring in travelers were acquired in New World countries and were treated with pentavalent antimonials. Three ML cases were acquired in the New World, two received initial treatment with pentavalent antimonials and two with liposomal amphotericin B (LAmB). For all four ML cases, a change in drug choice and multiple treatment courses were necessary, and one remained refractory to treatment. Both VL cases were acquired in Africa and responded well to LAmB treatment. Conclusion. The management of leishmaniasis in non-endemic countries is still a challenge for physicians. With the variety of cases presented, both in immigrants and travelers from different geographical areas, this series illustrates the great diversity of imported leishmaniasis in terms of presentation, treatment options, and outcome. We consider this entity is becoming increasingly more frequent and clinicians should be aware of strategies for its correct management.
	PMID: 19930379 [PubMed - in process]

9.	Immunology. 2009 Dec;128(4):484-99. The contribution of Toll-like receptor 2 to the innate recognition of a Leishmania infantum silent information regulator 2 protein. Silvestre R, Silva AM, Cordeiro-da-Silva A, Ouaissi A. Parasite Disease Group, Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal. Summary We have characterized a Leishmania protein belonging to the silent information regulator 2 (SIR2) family [SIR2 related protein 1 (SIR2RP1)] that might play an immunoregulatory role during infection through its capacity to trigger B-cell effector functions. We report here that SIR2RP1 leads to the proliferation of activated B cells, causing increased expression of major histocompatibility complex (MHC) II and the costimulatory molecules CD40 and CD86, which are critical ligands for T-cell cross-talk during the development of adaptive immune responses. In contrast, B cells isolated from Toll-like receptor 2 (TLR2) knockout mice were unable to respond to the SIR2RP1 stimulus. Similarly, SIR2RP1 induced the maturation of dendritic cells (DCs) in a TLR2-dependent manner with the secretion of pro-inflammatory cytokines [interleukin (IL)-12 and tumour necrosis factor (TNF)-alpha] and enhanced the costimulatory properties of DCs. Nevertheless, immunization assays demonstrated that TLR2-deficient mice were able to mount a specific humoral response to SIR2RP1. Interestingly, further investigations showed that macrophages were activated by SIR2RP1 even in the absence of TLR2. Therefore, a different type of interplay between SIR2RP1 and the major antigen-presenting cells in vivo could explain the immune response observed in TLR2-deficient mice. Together, these results demonstrate that TLR2 signalling contributes to SIR2RP1 recognition by innate immune host cells.
	PMID: 19930041 [PubMed - in process]

10.	J Med Chem. 2009 Nov 23. [Epub ahead of print] Synthesis and Antiprotozoal Activity of Cationic 1,4-Diphenyl-1H-1,2,3-triazoles. Bakunov SA, Bakunova SM, Wenzler T, Ghebru M, Werbovetz KA, Brun R, Tidwell RR. Department of Pathology and Laboratory Medicine, School of Medicine, The University of North Carolina, Chapel Hill, North Carolina 27599-7525. Novel dicationic triazoles 1-60 were synthesized by the Pinner method from the corresponding dinitriles, prepared via the copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC). The type and the placement of cationic moieties as well as the nature of aromatic substituents influenced in vitro antiprotozoal activities of compounds 1-60 against Trypanosoma brucei rhodesiense, Plasmodium falciparum, and Leishmania donovani and their cytotoxicity for mammalian cells. Eight congeners displayed antitrypanosomal IC(50) values below 10 nM. Thirty-nine dications were more potent against P. falciparum than pentamidine (IC(50) = 58 nM), and eight analogues were more active than artemisinin (IC(50) = 6 nM). Diimidazoline 60 exhibited antiplasmodial IC(50) value of 0.6 nM. Seven congeners administered at 4 x 5 mg/kg by the intraperitoneal route cured at least three out of four animals in the acute mouse model of African trypanosomiasis. At 4 x 1 mg/kg, diamidine 46 displayed better antitrypanosomal efficacy than melarsoprol, curing all infected mice.
	PMID: 19928900 [PubMed - as supplied by publisher]