Wednesday, May 6, 2009

What's new for 'Trypanosomatids' in PubMed

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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 -4 of 4

1: PLoS Negl Trop Dis. 2009;3(5):e432. Epub 2009 May 5.

WR279,396, a Third Generation Aminoglycoside Ointment for the Treatment of Leishmania major Cutaneous Leishmaniasis: A Phase 2, Randomized, Double Blind, Placebo Controlled Study.

Institut Pasteur de Tunis, Tunis, Tunisia.

BACKGROUND: CUTANEOUS LEISHMANIASIS (CL) IS A DISFIGURING DISEASE THAT CONFRONTS CLINICIANS WITH A QUANDARY: leave patients untreated or engage in a complex or toxic treatment. Topical treatment of CL offers a practical and safe option. Accordingly, the treatment of CL with WR279,396, a formulation of paromomycin and gentamicin in a hydrophilic base, was investigated in a phase 2 clinical study in Tunisia and France. METHODS: A phase 2, randomized, double blind, vehicle-controlled study was conducted to assess the safety and efficacy of topical WR279,396 when applied twice a day for 20 days as treatment for parasitologically confirmed CL. The study protocol established the primary efficacy end point as complete clinical response (CCR) defined as 50% or greater reduction in the ulceration size of an index lesion by day 50 (D50) followed by complete re-epithelialization by D100, and no relapse through D180. RESULTS: Ninety-two subjects were randomized. Leishmania major was identified in 66 of 68 isolates typed (97%). In the intent-to-treat population, 47 of 50 WR279,396 treated participants (94%) met the definition of CCR, compared with 30 of 42 vehicle-placebo participants (71%) [p = 0.0045]. Erythema occurred in 30% and 24% of participants receiving WR279,396 and placebo, respectively [p = 0.64]. There was no clinical or laboratory evidence of systemic toxicity. CONCLUSION: Application of WR279,396 for 20 days was found to be safe and effective in treating L. major CL, and offers great potential as a new, simple, easily applicable, and inexpensive topical therapy for this neglected disease. TRIAL REGISTRATION: ClinicalTrials.gov NCT00703924.

PMID: 19415122 [PubMed - in process]

2: Vet Pathol. 2009 Mar;46(2):251-8.Click here to read LinkOut

Neuropathology of naturally occurring Trypanosoma evansi infection of horses.

Department of Veterinary Pathobiology, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, 4467 TAMU, College Station, TX 77843-4467, USA.

The clinical signs and pathology of the central nervous system in 9 horses with naturally occurring neurologic disease due to Trypanosoma evansi are described. The clinical course was 2 to 20 days; clinical signs included marked ataxia, blindness, head tilt and circling, hyperexcitability, obtundity, proprioceptive deficits, head pressing, and paddling movements. Grossly, asymmetric leukoencephalomalacia with yellowish discoloration of white matter and flattening of the gyri were observed in the brain of 7 of 9 horses. Histologically, all 9 horses had necrotizing encephalitis that was most severe in the white matter, with edema, demyelination, and lymphoplasmacytic perivascular cuffs. Mild to moderate meningitis or meningomyelitis was observed in the spinal cord of 5 of 7 horses. T. evansi was detected immunohistochemically in the perivascular spaces and neuropil of formalin-fixed, paraffin-embedded brain tissue in 8 of 9 horses.

PMID: 19261636 [PubMed - indexed for MEDLINE]

3: Enferm Infecc Microbiol Clin. 2008 Jul;26 Suppl 9:50-7.Click here to read LinkOut

[Molecular diagnosis of parasitic and fungal infections]

[Article in Spanish]

Departamento de Microbiología, Facultad de Medicina, Hospital Clínico Universitario, Valencia, España.

Conventional microbiological diagnosis of fungal infections and parasitic diseases has been characterized by low diagnostic sensitivity, laboriousness, and the need for expert microscopists. Consequently, diagnostic methods based on the detection of nucleic acids are a magnificent alternative to overcome these problems, but have not yet provided a satisfactory response in all situations. The molecular methods used are varied and most are based on techniques of nucleic acid amplification. These techniques have proved useful for mycological and parasitological diagnosis, for epidemiological and taxonomic studies, and for monitoring the response to different treatments and detection of resistance. The introduction of these techniques in developing countries may be hampered by their higher cost but molecular diagnostic methods are already beginning to spread in clinical microbiology laboratories and are competing successfully with traditional methods. The present article reviews the current status of molecular methods in the diagnosis of fungal and parasitic infections.

PMID: 19195447 [PubMed - indexed for MEDLINE]

4: Microbes Infect. 2009 Jan;11(1):29-39. Epub 2008 Nov 1.Click here to read LinkOut

Trypanosoma cruzi: parasite shed vesicles increase heart parasitism and generate an intense inflammatory response.

Departamento de Bioquímica, Instituto de Química, USP, Av. Lineu Prestes, 748, 05508-900 São Paulo, SP, Brazil.

Trypanosoma cruzi trypomastigotes continuously shed into the medium plasma membrane fragments sealed as vesicles enriched in glycoproteins of the gp85 and trans-sialidase (TS) superfamily and alpha-galactosyl-containing glycoconjugates. Injection of a vesicle fraction into BALB/c mice prior to T. cruzi infection led to 40% of deaths on the 16thday post-infection and 100% on day 20th whereas 20% of untreated animals survived for more than 30days. The vesicle-treated animals developed severe heart pathology, with intense inflammatory reaction and higher number of amastigote nests. Analysis of the inflammatory infiltrates 15days after infection showed predominance of TCD4(+) lymphocytes and macrophages, but not of TCD8(+) cells, as well as a decrease of areas labeled with anti-iNOS antibodies as compared to the control. Higher levels of IL-4 and IL-10 mRNAs were found in the hearts and higher IL-10 and lower NO levels in splenocytes of vesicles pretreated animals. Treatment of mice with neutralizing anti-IL-10 or anti-IL-4 antibodies precluded the effects of pre-inoculation of membrane vesicles on infection. These results indicate that T. cruzi shed membrane components increase tissue parasitism and inflammation by stimulation of IL-4 and IL-10 synthesis and thus may play a central role in the pathogenesis of Chagas' disease acute phase.

PMID: 19028594 [PubMed - indexed for MEDLINE]

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