Tuesday, April 14, 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 -7 of 7

1: Vet Parasitol. 2009 Mar 13. [Epub ahead of print]

Leukocyte entry into the CNS of Leishmania chagasi naturally infected dogs.

Melo GD, Marcondes M, Vasconcelos RO, Machado GF.

UNESP-FO-Veterinary Medicine, Araçatuba, SP, Brazil.

In dogs, there is an association of chronic visceral leishmaniasis with neurological symptoms, and very few publications have investigated whether these neurological manifestations correlate with specific alterations in brain. A total of 42 mixed-breed adult dogs were selected from the Veterinary Hospital of UNESP-Araçatuba and the Control Zoonosis Center in Araçatuba, São Paulo State, Brazil, which is an endemic area for visceral leishmaniasis. Animals presenting positive ELISA and/or positive parasitological diagnosis of Leishmania were enrolled in the group of infected dogs (n=32). Animals with negative ELISA results and parasitological tests for Leishmania, including a negative immunofluorescence test for toxoplasmosis and neosporosis, were included as the control group (n=10). Brain samples were collected, stored in 10% buffered formalin and subjected to routine histological procedures, following by staining with haematoxylin-eosin (HE) and immunohistochemical examination for T and B lymphocytes and phagocytic cells. Cerebrospinal fluid was collected to determine the anti-Leishmania antibody titers. Histological examination of HE stains demonstrated intense inflammatory infiltrate, primarily in the choroid plexus, which was composed of mononuclear cells with no detectable parasites. Immunohistochemistry revealed that CD3(+) T lymphocytes were the major components of the inflammatory infiltrate at the choroid plexus and in the brain. Infected dogs had more CD3(+) T cells than uninfected animals (P=0.0002). Cerebrospinal fluid from infected dogs contained high titers of anti-Leishmania antibodies in comparison with control animals (P<0.0001), which suggests a compromise of the blood-cerebrospinal fluid barrier. Leukocyte entry into the brain suggests the participation of these cells in the pathogenesis of neurological disorders during the advanced stages of leishmaniasis and confirms that the choroid plexus is an important structure for T cell influx.

PMID: 19362424 [PubMed - as supplied by publisher]

2: J Inorg Biochem. 2009 Mar 17. [Epub ahead of print]

Synthesis and characterization of a pyridine-2-thiol N-oxide gold(I) complex with potent antiproliferative effect against Trypanosoma cruzi and Leishmania sp. insight into its mechanism of action.

Vieites M, Smircich P, Guggeri L, Marchán E, Gómez-Barrio A, Navarro M, Garat B, Gambino D.

Cátedra de Química Inorgánica, Facultad de Química, Universidad de la República, Gral. Flores 2124, C. C. 1157, 11800 Montevideo, Uruguay.

In the search for new therapeutic tools against parasitic diseases caused by the Kinetoplastids Leishmania spp. and Trypanosoma cruzi, a novel gold(I) triphenylphosphine complex with the bioactive coligand pyridine-2-thiol N-oxide (mpo) was synthesized and characterized by using analytical and conductometric measurements, electrospray ionization-mass spectrometry (ESI) and electronic, FTIR and (1)H and (31)P NMR spectroscopies. A dinuclear structure is suggested for the complex. At a 1 microM concentration the complex induced in vitro after 30min a potent leishmanicidal effect (LD(50)) against promastigotes of Leishmania (L.) mexicana while on Leishmania (V.) braziliensis with the same concentration only a leishmanistatic effect (IC(75)) was observed 48h after treatment. Similar differential susceptibilities were also found when testing the ligand mpo, but at a higher dose (5muM). In addition, the compound showed growth inhibitory effect on Dm28c T. cruzi epimastigotes in culture (IC(50) 0.09muM), being even more active than the anti-trypanosomal reference drug Nifurtimox (IC(50) 6muM). DNA interaction studies showed that this biomolecule does not constitute a main target for the mpo complex currently tested. Instead, the significant potentiation of the antiproliferative effect against both Leishmania species and T. cruzi could be associated to the inhibition of NADH fumarate reductase, a kinetoplastid parasite-specific enzyme absent in the host. Furthermore, due to its low unspecific cytotoxicity on mammalian cells (J774 macrophages), the new gold complex showed a selective anti-parasite activity. It constitutes a promising new potent chemotherapeutic alternative to be evaluated in vivo in experimental models of leishmaniasis and Chagas disease.

PMID: 19361864 [PubMed - as supplied by publisher]

3: Phytochemistry. 2009 Apr 8. [Epub ahead of print]

Antiparasitic activity of prenylated benzoic acid derivatives from Piper species.

Flores N, Jiménez IA, Giménez A, Ruiz G, Gutiérrez D, Bourdy G, Bazzocchi IL.

Instituto Universitario de Bio-Orgánica "Antonio González", Universidad de La Laguna, Avda. Astrofísico, Francisco Sánchez 2, La Laguna, 38206 Tenerife, Canary Islands, Spain; Instituto de Investigaciones Fármaco Bioquímicas, Facultad de Ciencias Farmacéuticas y Bioquímicas, Universidad Mayor de San Andrés, Avda. Saavedra 2224, Miraflores, La Paz, Bolivia.

Fractionation of dichloromethane extracts from the leaves of Piper heterophyllum and P. aduncum afforded three prenylated hydroxybenzoic acids, 3-[(2E,6E,10E)-11-carboxy-3,7,15-trimethyl-2,6,10,14-hexadecatetraenyl)-4,5-dihydroxybenzoic acid, 3-[(2E,6E,10E)-11-carboxy-13-hydroxy-3,7,15-trimethyl-2,6,10,14-hexadecatetraenyl]-4,5-dihydroxybenzoic acid and 3-[(2E,6E,10E)-11-carboxy-14-hydroxy-3,7,15-trimethyl-2,6,10,15-hexadecatetraenyl]-4,5-dihydroxybenzoic acid, along with the known compounds, 4,5-dihydroxy-3-(E,E,E-11-formyl-3,7,15-trimethyl-hexadeca-2,6,10,14-tetraenyl)benzoic acid (arieianal), 3,4-dihydroxy-5-(E,E,E-3,7,11,15-tetramethyl-hexadeca-2,6,10,14-tetraenyl)benzoic acid, 4-hydroxy-3-(E,E,E-3,7,11,15-tetramethyl-hexadeca-2,6,10,14-tetraenyl)benzoic acid, 3-(3,7-dimethyl-2,6-octadienyl)-4-methoxy-benzoic acid, 4-hydroxy-3-(3,7-dimethyl-2,6-octadienyl)benzoic acid and 4-hydroxy-3-(3-methyl-1-oxo-2-butenyl)-5-(3-methyl-2-butenyl)benzoic acid. Their structures were elucidated on the basis of spectroscopic data, including homo- and heteronuclear correlation NMR experiments (COSY, HSQC and HMBC) and comparison with data reported in the literature. Riguera ester reactions and optical rotation measurements established the compounds as racemates. The antiparasitic activity of the compounds were tested against three strains of Leishmania spp., Trypanosoma cruzi and Plasmodium falciparum. The results showed that 3-(3,7-dimethyl-2,6-octadienyl)-4-methoxy-benzoic acid exhibited potent and selective activity against L. braziliensis (IC(50) 6.5mug/ml), higher that pentamidine used as control. Moreover, 3-[(2E,6E,10E)-11-carboxy-3,7,15-trimethyl- 2,6,10,14-hexadecatetraenyl)-4,5-dihydroxybenzoic acid and 4-hydroxy-3-(3-methyl-1-oxo-2-butenyl)-5-(3-methyl-2-butenyl)benzoic acid showed moderate antiplasmodial (IC(50) 3.2mug/ml) and trypanocidal (16.5mug/ml) activities, respectively.

PMID: 19361822 [PubMed - as supplied by publisher]

4: Ann Dermatol Venereol. 2009 Apr;136(4):341-5. Epub 2009 Feb 26.

[Double trypanosomal chancre revealing West African trypanosomiasis in a Frenchman living in Gabon.]

[Article in French]

Hope-Rapp E, Moussa Coulibaly O, Klement E, Danis M, Bricaire F, Caumes E.

Service de maladies infectieuses et tropicales, hôpital Pitié-Salpêtrière, 47-83, boulevard de l'Hôpital, 75651 Paris cedex 13, France.

BACKGROUND: Human African trypanosomiasis (sleeping sickness), an endemic disease, is currently reemerging in Africa with an estimated incidence of 45,000new cases per year. It is caused by Trypanosoma brucei subspecies and transmitted by day-biting tsetse flies. PATIENTS AND METHODS: We report a case of West African trypanosomiasis due to Trypanosoma brucei gambiense involving a Frenchman living in Libreville, Gabon. The patient presented with fever and polyadenopathies as well as two skin ulcerations highly suggestive of trypanosomiasis. Microscopic examination of cutaneous and peripheral blood smears confirmed the diagnosis of haemolymphatic infection with T. b. gambiense with trypanosomal chancres. Examination of the cerebrospinal fluid was normal. The patient was successfully treated with pentamidine isethionate. CONCLUSIONS: Recognition of cutaneous manifestations may allow a rapid diagnosis of African trypanosomiasis that is essential for timely and efficient treatment and survival.

PMID: 19361701 [PubMed - in process]

5: Exp Parasitol. 2009 Apr 7. [Epub ahead of print]

Leishmania donovani: Thionins, antimicrobial peptides with leishmanicidal activity.

Berrocal-Lobo M, Molina A, Rodrı Guez-Palenzuela P, Garcı A-Olmedo F, Rivas L.

Centro de Investigaciones Biológicas. Ramiro de Maeztu 9, E-28040 Madrid; Centro de Biotecnologi a y Genómica de Plantas (CBGP), (UPM-INIA). Campus Montegancedo. Universidad Politécnica de Madrid, Autopista M40 (Km. 38), 28223, Pozuelo de Alarcón, Madrid, Spain.

The leishmanicidal activity of plant antibiotic peptides (PAPs) from the principal families, such wheat thionins, a barley lipid transfer protein and potato defensins and snakins were tested in vitro against Leishmania donovani. Only thionins and defensins were active against this human pathogen at a low micromolar range of concentrations. Thionins resulted as the most active peptides tested until now. They collapsed ionic and pH gradients across the parasite plasma membrane together with a rapid depletion of intracellular ATP without affecting mitochondrial potential. Hence the letal effect of thionins was mostly associated to permeabilization of the plasma membrane leading to an immediate death of the parasite. The present work is the first evidence for leishmanicidal activity in plant peptides. Future prospects for their development as new antiparasite agents on human diseases are considered.

PMID: 19361504 [PubMed - as supplied by publisher]

6: PLoS ONE. 2009;4(2):e4534. Epub 2009 Feb 20.Click here to read Click here to read References for this PMC Article, Free in PMC, LinkOut

Actions of a proline analogue, L-thiazolidine-4-carboxylic acid (T4C), on Trypanosoma cruzi.

Magdaleno A, Ahn IY, Paes LS, Silber AM.

Departamento de Parasitología, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, Brazil.

It is well established that L-proline has several roles in the biology of trypanosomatids. In Trypanosoma cruzi, the etiological agent of Chagas' disease, this amino acid is involved in energy metabolism, differentiation processes and resistance to osmotic stress. In this study, we analyzed the effects of interfering with L-proline metabolism on the viability and on other aspects of the T. cruzi life cycle using the proline analogue L- thiazolidine-4-carboxylic acid (T4C). The growth of epimastigotes was evaluated using different concentrations of T4C in standard culture conditions and at high temperature or acidic pH. We also evaluated possible interactions of this analogue with stress conditions such as those produced by nutrient starvation and oxidative stress. T4C showed a dose-response effect on epimastigote growth (IC(50) = 0.89+/-0.02 mM at 28 degrees C), and the inhibitory effect of this analogue was synergistic (p<0.05) with temperature (0.54+/-0.01 mM at 37 degrees C). T4C significantly diminished parasite survival (p<0.05) in combination with nutrient starvation and oxidative stress conditions. Pre-incubation of the parasites with L-proline resulted in a protective effect against oxidative stress, but this was not seen in the presence of the drug. Finally, the trypomastigote bursting from infected mammalian cells was evaluated and found to be inhibited by up to 56% when cells were treated with non-toxic concentrations of T4C (between 1 and 10 mM). All these data together suggest that T4C could be an interesting therapeutic drug if combined with others that affect, for example, oxidative stress. The data also support the participation of proline metabolism in the resistance to oxidative stress.

PMID: 19229347 [PubMed - indexed for MEDLINE]

PMCID: PMC2645137

7: Fish Shellfish Immunol. 2009 Mar;26(3):352-8. Epub 2008 Sep 6.Click here to read LinkOut

Classical crosses of common carp (Cyprinus carpio L.) show co-segregation of antibody response with major histocompatibility class II B genes.

Rakus KŁ, Irnazarow I, Forlenza M, Stet RJ, Savelkoul HF, Wiegertjes GF.

Polish Academy of Sciences, Institute of Ichthyobiology and Aquaculture in Gołysz, Zaborze, ul. Kalinowa 2, 43-520 Chybie, Poland.

In cyprinids, two paralogous groups of major histocompatibility (MH) class II B genes, DAB1 and DAB3, have been reported but have not been studied in detail. In our study on MH association with immune responsiveness in common carp (Cyprinus carpio L.) we have taken a long-term approach using divergent selection for antibody production. We report the co-segregation of Cyca-DAB1-like and Cyca-DAB3-like genes with antibody response, in backcrosses to high- and low-responsive parental carp lines. We show that the presence of Cyca-DAB1-like, but not Cyca-DAB3-like genes, preferentially leads to a high DNP-specific antibody response in carp. Background genes other than Cyca-DAB genes also influenced the level of antibody response. Our data support the hypothesis of a genetic control by Cyca-DAB genes on the antibody response measured. We could not detect an association of the Cyca-DAB genes with disease resistance to the parasite Trypanoplasma borreli. Sequence information, constitutive transcription levels and our co-segregation data indicate that both paralogous Cyca-DAB1-like and Cyca-DAB3-like groups represent functional MH class II B genes. Previously defined differences in allelic diversity between Cyca-DAB1-like genes, especially, identify Cyca-DAB1 as the most interesting DAB gene for further study in common carp.

PMID: 18817879 [PubMed - indexed for MEDLINE]

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