Saturday, March 21, 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 -9 of 9

1: Am J Ther. 2009 Mar-Apr;16(2):178-82.

Current treatment for cutaneous leishmaniasis: a review.

Department of Pediatric, Hospital of Sondrio, Foggia, Italy. emipalu2003@yahoo.it

Cutaneous leishmaniasis is the most common form of leishmaniasis. It is a skin infection caused by a single-celled parasite that is transmitted by sand fly bites. There are about 20 species of Leishmania that may cause cutaneous leishmaniasis. Some Leishmania species are closely linked to humans and are therefore found in cities (Leishmania tropica), whereas some are more traditionally associated with animal species and are therefore considered zoonoses (Leishmania major). The evidence for optimal treatment of cutaneous leishmaniasis is patchy. Although the cutaneous form of the disease is often self-limiting, it does result in significant scarring and can spread to more invasive, mucocutaneous disease. Therefore, treatment may be considered to prevent these complications. Drugs for systemic and topical treatment are presented and discussed with regard to their application, use, and adverse effects.

PMID: 19300044 [PubMed - in process]

2: Genome Res. 2009 Mar 19. [Epub ahead of print]Click here to read

The apolipoprotein L family of programmed cell death and immunity genes rapidly evolved in primates at discrete sites of host-pathogen interactions.

Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.

Apolipoprotein L1 (APOL1) is a human protein that confers immunity to Trypanosoma brucei infections but can be countered by a trypanosome-encoded antagonist SRA. APOL1 belongs to a family of programmed cell death genes whose proteins can initiate host apoptosis or autophagic death. We report here that all six members of the APOL gene family (APOL1-6) present in humans have rapidly evolved in simian primates. APOL6, furthermore, shows evidence of an adaptive sweep during recent human evolution. In each APOL gene tested, we found rapidly evolving codons in or adjacent to the SRA-interacting protein domain (SID), which is the domain of APOL1 that interacts with SRA. In APOL6, we also found a rapidly changing 13-amino-acid cluster in the membrane-addressing domain (MAD), which putatively functions as a pH sensor and regulator of cell death. We predict that APOL genes are antagonized by pathogens by at least two distinct mechanisms: SID antagonists, which include SRA, that interact with the SID of various APOL proteins, and MAD antagonists that interact with the MAD hinge base of APOL6. These antagonists either block or prematurely cause APOL-mediated programmed cell death of host cells to benefit the infecting pathogen. These putative interactions must occur inside host cells, in contrast to secreted APOL1 that trafficks to the trypanosome lysosome. Hence, the dynamic APOL gene family appears to be an important link between programmed cell death of host cells and immunity to pathogens.

PMID: 19299565 [PubMed - as supplied by publisher]

3: Res Vet Sci. 2009 Mar 17. [Epub ahead of print]Click here to read

Comparison of PCR methods for diagnosis of canine visceral leishmaniasis in conjunctival swab samples.

Centro de Desenvolvimento da Tecnologia Nuclear (CDTN), Rua Professor Mário Werneck S/N, Cidade Universitária-Campus da UFMG, 31120-970 Belo Horizonte, MG, CEP, Brazil.

Four PCR assays for detection of Leishmania DNA in conjunctival swab samples were compared. All methods had two steps: a first amplification followed by hybridization or by a new amplification (nested or seminested). Two methods (kDNA PCR-hybridization and kDNA snPCR) used primers targeted to the minicircles of kinetoplast DNA (kDNA) and the other two methods to the coding (LnPCR) and intergenic noncoding regions (ITS-1 nPCR) of ribosomal rRNA genes. kDNA PCR-hybridization was positive for 22/23 dogs (95.6%) and for 40/46 samples (86.9%), considering the right and the left conjunctivas. kDNA snPCR was positive for 21/23 dogs (91.3%) and for 40/46 samples (86.9%). The ITS-1 nPCR and LnPCR were both able to detect the parasites in 17/23 dogs (73.9%) and 29/46 (63%) and 30/46 (65.2%) samples, respectively. The positivities of the kDNA based methods were significantly higher; however the choice of the best method will depend on the kind of information required with the diagnosis.

PMID: 19298988 [PubMed - as supplied by publisher]

4: Trop Med Int Health. 2009 Mar 2. [Epub ahead of print]Click here to read

Increased CXCL-13 levels in human African trypanosomiasis meningo-encephalitis.

Institut de Neurologie Tropicale, Université de Limoges, Limoges, France.

Summary Objectives To determine the role of the B-cell attracting chemokine CXCL-13, which may initiate B-cell trafficking and IgM production in diagnosing HAT meningo-encephalitis. Methods We determined CXCL-13 levels by ELISA on paired sera and CSF of 26 patients from Angola and of 16 controls (six endemic and ten non-endemic). Results were compared to standard stage determination markers and IgM intrathecal synthesis. Results CXCL-13 levels in patients' sera had a median value of 386.6 pg/ml and increased levels were associated with presence of trypanosomes in the CSF but not with other stage markers. CXCL-13 levels in patients' CSF had a median value of 80.9 pg/ml and increased levels were associated with all standard stage determination markers and IgM intrathecal synthesis. Conclusion CXCL-13 levels in CSF increased significantly during the course of HAT. Hence the value of CXCL-13 for diagnosis, follow-up or as a marker of disease severity should be tested in a well-defined cohort study.

PMID: 19298637 [PubMed - as supplied by publisher]

5: J Eur Acad Dermatol Venereol. 2009 Feb 24. [Epub ahead of print]Click here to read

Treatment of cutaneous leishmaniasis with intralesional sodium stibogluconate.

Department of Dermatology, Chaim Sheba Medical Center, Tel Hashomer, The Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.

Abstract Background Cutaneous leishmaniasis is endemic in Israel. Leishmania major is the most prevalent species that cause cutaneous leishmaniasis. Current treatment options are limited and there are few investigations in search of alternative ones. Objective This study aims to assess our experience with intralesional sodium stibogluconate (SSG) in the treatment of cutaneous leishmaniasis. Methods A retrospective evaluation for all adult cases of cutaneous leishmaniasis treated by intralesional and intravenous SSG (Pentostam((R)), GlaxoSmithKline) between 2004 and 2006 was performed, for cases referred to a tertiary care university-affiliated medical centre in Israel. Intralesional SSG was injected at 0.5 mL per lesion (50 mg). Treatment was repeated every 2-3 weeks for a total of 12 weeks. Intravenous SSG was administered at a dose of 20 mg/kg for 10-20 days. Results Thirty-three cases of cutaneous leishmaniasis were treated with intralesional SSG during the study period. The patients consist of 26 males and 7 females, mostly Israeli military personnel, and there were a total of 93 lesions. Within 3 months from treatment onset, 91% (30/33) had completed healing of the cutaneous lesions after an average of 3 treatments (range 1-6). Side-effects were mild and were mostly pain during injection, with two patients developing mild local site reaction after the injection. Conclusions Intralesional SSG treatment is safe, effective and well tolerated with minimal side-effects. Conflicts of interest None declared.

PMID: 19298486 [PubMed - as supplied by publisher]

6: FEMS Microbiol Lett. 2009 Mar;292(1):27-32. Epub 2009 Jan 8.Click here to read LinkOut

Characterization of Trypanosoma cruzi L-cysteine transport mechanisms and their adaptive regulation.

Laboratorio de Biología Molecular de Trypanosoma cruzi, Instituto de Investigaciones Médicas Alfredo Lanari, Consejo Nacional de Investigaciones Científicas y Té cnicas, Universidad de Buenos Aires, Buenos Aires, Argentina.

L-Cysteine and methionine are unique amino acids that act as sulfur donors in all organisms. In the specific case of Trypanosomatids, L-cysteine is particularly relevant as a substrate in the synthesis of trypanothione. Although it can be synthesized de novo, L-cysteine is actively transported in Trypanosoma cruzi epimastigote cells. L-Cysteine uptake is highly specific; none of the amino acids assayed yield significant differences in terms of transport rates. L-Cysteine is transported by epimastigote cells with a calculated apparent K(m) of 49.5 microM and a V(max) of about 13 pmol min(-1) per 10(7) cells. This transport is finely regulated by amino acid starvation, extracellular pH, and between the parasite growth phases. In addition, L-cysteine is incorporated post-translationally into proteins, suggesting its role in iron-sulfur core formation. Finally, the metabolic fates of Lcysteine were predicted in silico.

PMID: 19175408 [PubMed - indexed for MEDLINE]

7: Neuroimmunomodulation. 2009 Jan;16(1):54-62. Epub 2008 Dec 15.Click here to read LinkOut

Neuropathy of gastrointestinal Chagas' disease: immune response to myelin antigens.

Neuroimmunology Unit, Department of Microbiology and Immunology, University of Campinas, Campinas, Brazil.

Most reports of autoimmune response during infection with the parasite Trypanosoma cruzi have dealt with the cardiomyopathic form of Chagas' disease, but little is known about the mechanisms of tissue damage involved in the gastrointestinal form, which was studied here. Chronically infected patients with a severe gastrointestinal form of Chagas' disease present increased antibody production and proliferative responses to peripheral myelin components, such as myelin basic protein (MBP), which is homologous to the P1 protein fraction of peripheral myelin. T lymphocytes preferentially recognize a region on the MBP molecule (1-30), which suggests that the MBP is a potential target on the peripheral nerve for autoimmune reactions in patients with gastrointestinal lesions resulting from Chagas' disease. Copyright 2008 S. Karger AG, Basel.

PMID: 19077446 [PubMed - indexed for MEDLINE]

8: Planta Med. 2008 Dec;74(15):1795-9. Epub 2008 Nov 7.Click here to read LinkOut

Trypanocidal activity of limonoids and triterpenes from Cedrela fissilis.

Departamento de Química, Universidade Federal de São Carlos, São Carlos, SP, Brasil.

Chagas' disease is an illness that affects millions of people in Central and South America. The search for both a prophylactic drug to be added to human blood as well as a safe and reliable therapeutic drug are greatly needed to control such disease. Herein, we report the trypanocidal activity of 15 crude extracts and 14 compounds (limonoids and triterpenes) as well as the isolation of 25 known compounds (6 limonoids, 12 triterpenes, 1 sesquiterpene, 5 steroids, and 1 flavonoid) from Cedrela fissilis. The present study shows that this plant is a promising source of active compounds for the control of Chagas' disease. The inhibitory activity found for odoratol indicates that it is potentially useful as an alternative for the chemoprophylactic gentian violet.

PMID: 18991203 [PubMed - indexed for MEDLINE]

9: Vet Immunol Immunopathol. 2009 Jan 15;127(1-2):19-25. Epub 2008 Sep 19.Click here to read LinkOut

Genetic resistance of carp (Cyprinus carpio L.) to Trypanoplasma borreli: influence of transferrin polymorphisms.

Polish Academy of Sciences, Institute of Ichthyobiology and Aquaculture, Chybie, Poland.

In serum most of the iron molecules are bound to transferrin (Tf), which is a highly polymorphic protein in fish. Tf is an essential growth factor for mammalian trypanosomes. We performed a series of experiments with Trypanoplasma borreli to detect putative correlations between different Tf genotypes of common carp (Cyprinus carpio L.) and susceptibility to this blood parasite. Five genetically different, commercially exploited carp lines (Israelian 'D', Polish 'R2' and 'K', Ukrainian 'Ur', Hungarian 'R0') and a reference laboratory cross ('R3xR8') were challenged with T. borreli and parasitaemia measured to determine susceptibility to the parasite. Among the commercial carp lines, Israelian 'D' carp were identified as most and Polish 'R2' carp as least susceptible, and used to produce a next generation and reciprocal crosses. These progenies were challenged with T. borreli and parasitaemia measured. We demonstrated significant effects of genetic background of the carp lines on susceptibility to T. borreli. This genetic effect was preserved in a next generation. We also observed a significant male effect on susceptibility to T. borreli in the reciprocal crosses. Serum samples from a representative number of fish from two infection experiments were used for Tf genotyping by polyacrylamide gel electrophoresis (PAGE), identifying DD, DG and DF as most frequent Tf genotypes. We could detect a significant association of the homozygous DD genotype with low parasitaemia in the least susceptible 'R2' (and 'K') carp lines and the lack of a such an association in the most susceptible 'D' carp line. Upon examination of parasite growth in vitro in culture media supplemented with 3% serum taken from fish with different Tf genotypes, we could show a faster decrease in number of parasites in culture media with serum from DD-typed animals.

PMID: 18980781 [PubMed - indexed for MEDLINE]

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