What's new for 'Trypanosomatids' in PubMed

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Sent on Wednesday, 2012 April 18
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 - 3 of 3

1.	PLoS Negl Trop Dis. 2012 Apr;6(4):e1610. Epub 2012 Apr 3. KSAC, a Defined Leishmania Antigen, plus Adjuvant Protects against the Virulence of L. major Transmitted by Its Natural Vector Phlebotomus duboscqi. Gomes R, Teixeira C, Oliveira F, Lawyer PG, Elnaiem DE, Meneses C, Goto Y, Bhatia A, Howard RF, Reed SG, Valenzuela JG, Kamhawi S. Source Vector Molecular Biology Section, Laboratory of Malaria and Vector Research, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, United States of America. Abstract BACKGROUND: Recombinant KSAC and L110f are promising Leishmania vaccine candidates. Both antigens formulated in stable emulsions (SE) with the natural TLR4 agonist MPL® and L110f with the synthetic TLR4 agonist GLA in SE protected BALB/c mice against L. major infection following needle challenge. Considering the virulence of vector-transmitted Leishmania infections, we vaccinated BALB/c mice with either KSAC+GLA-SE or L110f+GLA-SE to assess protection against L. major transmitted via its vector Phlebotomus duboscqi. METHODS: Mice receiving the KSAC or L110f vaccines were challenged by needle or L. major-infected sand flies. Weekly disease progression and terminal parasite loads were determined. Immunological responses to KSAC, L110f, or soluble Leishmania antigen (SLA) were assessed throughout vaccination, three and twelve weeks after immunization, and one week post-challenge. RESULTS: Following sand fly challenge, KSAC-vaccinated mice were protected while L110f-vaccinated animals showed partial protection. Protection correlated with the ability of SLA to induce IFN-γ-producing CD4(+)CD62L(low)CCR7(low) effector memory T cells pre- and post-sand fly challenge. CONCLUSIONS: This study demonstrates the protective efficacy of KSAC+GLA-SE against sand fly challenge; the importance of vector-transmitted challenge in evaluating vaccine candidates against Leishmania infection; and the necessity of a rapid potent Th1 response against Leishmania to attain true protection.
	PMID: 22509423 [PubMed - in process]

2.	PLoS Negl Trop Dis. 2012 Apr;6(4):e1609. Epub 2012 Apr 3. Incrimination of Phlebotomus kandelakii and Phlebotomus balcanicus as Vectors of Leishmania infantum in Tbilisi, Georgia. Giorgobiani E, Lawyer PG, Babuadze G, Dolidze N, Jochim RC, Tskhvaradze L, Kikaleishvili K, Kamhawi S. Source National Center for Disease Control and Public Health, Tbilisi, Georgia. Abstract A survey of potential vector sand flies was conducted in the neighboring suburban communities of Vake and Mtatsminda districts in an active focus of visceral Leishmaniasis (VL) in Tbilisi, Georgia. Using light and sticky-paper traps, 1,266 male and 1,179 female sand flies were collected during 2006-2008. Five Phlebotomus species of three subgenera were collected: Phlebotomus balcanicus Theodor and Phlebotomus halepensis Theodor of the subgenus Adlerius; Phlebotomus kandelakii Shchurenkova and Phlebotomus wenyoni Adler and Theodor of the subgenus Larroussius; Phlebotomus sergenti Perfil'ev of the subgenus Paraphlebotomus. Phlebotomus sergenti (35.1%) predominated in Vake, followed by P. kandelakii (33.5%), P. balcanicus (18.9%), P. halepensis (12.2%), and P. wenyoni (0.3%). In Mtatsminda, P. kandelakii (76.8%) comprised over three fourths of collected sand flies, followed by P. sergenti (12.6%), P. balcanicus (5.8%), P. halepensis (3.7%), and P. wenyoni (1.1%). The sand fly season in Georgia is exceptionally short beginning in early June, peaking in July and August, then declining to zero in early September. Of 659 female sand flies examined for Leishmania, 12 (1.8%) specimens without traces of blood were infected including 10 of 535 P. kandelakii (1.9%) and two of 40 P. balcanicus (5.0%). Six isolates were successfully cultured and characterized as Leishmania by PCR. Three isolates from P. kandelakii (2) and P. balcanicus (1) were further identified as L. infantum using sequence alignment of the 70 kDa heat-shock protein gene. Importantly, the sand fly isolates showed a high percent identity (99.8%-99.9%) to human and dog isolates from the same focus, incriminating the two sand fly species as vectors. Blood meal analysis showed that P. kandelakii preferentially feeds on dogs (76%) but also feeds on humans. The abundance, infection rate and feeding behavior of P. kandelakii and the infection rate in P. balcanicus establish these species as vectors in the Tbilisi VL focus.
	PMID: 22509422 [PubMed - in process]

3.	Antimicrob Agents Chemother. 2012 Apr 16. [Epub ahead of print] Evaluation of Arylimidamides DB1955 and DB1960 as Candidates against Visceral Leishmaniasis and Chagas Disease - In Vivo Efficacy, Acute Toxicity, Pharmacokinetics and Toxicology Studies. Zhu X, Liu Q, Yang S, Parman T, Green CE, Mirsalis JC, Soeiro MD, Souza EM, Silva CF, Batista DD, Stephens CE, Banerjee M, Farahat AA, Munde M, Wilson WD, Boykin DW, Wang MZ, Werbovetz KA. Source Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, OH 43210, USA. Abstract Arylimidamides (AIAs) have shown outstanding in vitro potency against intracellular kinetoplastid parasites, and the AIA 2,5-bis[2-(2-propoxy)-4-(2-pyridylimino)aminophenyl]furan dihydrochloride (DB766) displayed good in vivo efficacy in rodent models of visceral leishmaniasis and Chagas disease. In an attempt to further increase the solubility and in vivo antikinetoplastid potential of DB766, the mesylate salt of this compound and of the closely related AIA 2,5-bis[2-(2-cyclopentyloxy)-4-(2-pyridylimino)aminophenyl]furan hydrochloride (DB1852) were prepared. These two mesylate salts, designated DB1960 and DB1955, respectively, exhibited dose-dependent activity in the murine model of VL, with DB1960 inhibiting liver parasitemia by 51% at an oral dose of 100 mg/kg/day × 5 and DB1955 reducing liver parasitemia by 57% when given by the same dosing regimen. In a murine T. cruzi model, DB1960 decreased the parasitemia levels that peaked at 8 days post infection by 46% when given orally at 100 mg/kg/day × 5, while DB1955 had no effect on peak parasitemia levels when administered by the same dosing regimen. Distribution studies revealed that these compounds accumulated to micromolar levels in the liver, spleen, and kidney, but to a lesser extent in the heart, brain, and plasma. A 5-day repeat-dose toxicology study with DB1960 and DB1955 was also conducted in female BALB/c mice, with the compounds administered orally at 100, 200 and 500 mg/kg/day. In the high dose groups, DB1960 resulted in changes in serum chemistries, causing statistically significant increases in serum BUN, LDH, AST, and ALT levels, and a 21% decrease in body weight was observed in this group. These changes were consistent with microscopic findings in the liver and kidney of the treated animals. The incidences of observed clinical signs (hunched posture, tachypnea, tremors and ruffled fur) were more frequent in DB1960 treated groups than those treated with DB1955. However, histopathological examination of tissue samples indicated that both compounds caused adverse effects at all dose levels.
	PMID: 22508306 [PubMed - as supplied by publisher]