Tuesday, March 31, 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 -10 of 15

1: Exp Parasitol. 2009 Mar 26. [Epub ahead of print]Click here to read

Leishmania donovani lacking the Golgi GDP-Man transporter LPG2 exhibit attenuated virulence in mammalian hosts.

Departments of Internal Medicine, Epidemiology and Microbiology, University of Iowa and the Veterans Affairs Medical Center, Iowa City IA 52242 USA.

Surface phosophoglycans such as lipophosphoglycan (LPG) or proteophosphoglycan (PPG) and glycosylinositol phospholipids (GIPLs) modulate essential interactions between Leishmania and mammalian macrophages. Phosphoglycan synthesis depends on the Golgi GDP-mannose transporter encoded by LPG2. LPG2-null (lpg2(-)) L. majorcannot establish macrophage infections or induce acute pathology, whereas lpg2(-)L. mexicana retain virulence. lpg2(-)L. donovanihas been reported to survive poorly in cultured macrophages but in vivo survival has not been explored. Herein we discovered that, similar to lpg2(-)L. major, lpg2(-)L. donovanipromastigotes exhibited diminished virulence in mice, but persisted at consistently low levels. lpg2(-)L. donovanipromastigotes could not establish infections macrophages and could not transiently inhibit phagolysosomal fusion. Furthermore, lpg2(-)promastigotes of L. major, L. donovani and L. mexicana were highly susceptible to complement mediated lysis. We conclude that phosphoglycan assembly and expression mediated by L. donovani LPG2 are important for promastigote and amastigote virulence, unlike L. mexicana but similar to L. major.

PMID: 19328787 [PubMed - as supplied by publisher]

2: Bioorg Med Chem Lett. 2009 Mar 13. [Epub ahead of print]Click here to read

Synthesis and biological evaluation of novel 4-(hetero) aryl-2-piperazino quinazolines as anti-leishmanial and anti-proliferative agents.

Division of Medicinal Chemistry, Central Drug Research Institute, Lucknow, India.

A series of new class of 4-(hetero)aryl-2-piperazino quinazolines were synthesized and assessed for in vitro activity against extracellular promastigotes and intracellular amastigotes of Leishmania donovani. Among the compounds evaluated, compound 4bb and 4cb showed the selectivity index (SI) value>8.03 and 4.21, respectively, which is promising as compared with sodium stilbogluconate (SSG) and pentamidine with the SI of 6.38 and 2.07, respectively. The synthesized compounds were also tested for anti-proliferation activity in a panel of mammalian cell lines. Compound 4aa which is quite inactive and 4ab which is hardly selective in anti-leishmanial assay are found to have significant activity in anti-proliferative assay.

PMID: 19328690 [PubMed - as supplied by publisher]

3: Ann Dermatol Venereol. 2009 Mar;136(3):278-9. Epub 2008 Dec 3.Click here to read

[Cryotherapy with or without intralesional antimony in the treatment of cutaneous leishmaniasis.]

[Article in French]

Service de dermatologie, EPS Hedi-Chaker, 3029 Sfax, Tunisie.

PMID: 19328314 [PubMed - in process]

4: Expert Opin Drug Deliv. 2009 Mar;6(3):271-84.Click here to read

The reformulation of Amphotericin B for oral administration to treat systemic fungal infections and visceral leishmaniasis.

SJT Research Associate The University of British Columbia, Division of Pharmaceutics and Biopharmaceutics, 2146 East Mall, Vancouver, BC, V6T 1Z3, Canada Distinguished University Scholar Professor.

Amphotericin B (AmB) is a parenterally administered broad-spectrum antifungal and leishmanicidal drug that has been on the market for over sixty years. Unfortunately, significant infusion-related side effects and renal toxicity often accompany treatment, limiting its clinical applications. Lipid-based formulations have somewhat ameliorated the associated toxicity, but the increased cost of formulations restricts widespread use. AmB is amphipathic and exhibits low solubility and permeability, resulting in negligible absorption when administered orally. Advances in drug delivery systems have overcome some of the solubility issues that prevent oral bioavailability and new formulations are currently in development. The existence of an effective, safe and inexpensive oral formulation of amphotericin B would have significant applications for the treatment of disseminated fungal infections and would dramatically expand access to treatment of visceral leishmaniasis by introducing a readily available highly tolerated oral formulation of a drug with known efficacy.

PMID: 19327044 [PubMed - in process]

5: J Vector Borne Dis. 2009 Mar;46(1):52-6.

Karyosystematic and morphometric characterization of the rodents as reservoir hosts of zoonotic cutaneous leishmaniasis in an endemic focus of Isfahan Province, Iran.

Skin Diseases and Leishmaniasis Research Center (Sedigheh Tahereh), Isfahan University of Medical Sciences, Isfahan, Iran. L_shirani@mui.ac.ir

BACKGROUND & OBJECTIVES: Rodents belonging to Gerbillinae subfamily are the main reservoir hosts of zoonotic cutaneous leishmaniasis (ZCL) in Iran. Regarding the important role of these rodents in the maintenance of Leishmania major in the nature, their identification with morphometric, cytogenetic and molecular methods seems to be essential. The karyotype study of these species, captured from a new focus of zoonotic cutaneous leishmaniasis located in the south of Isfahan Province was carried out in 2007. METHODS: Twenty specimens containing seventeen Meriones persicus and three Nesokia indica were captured from Mobarakeh rural district south of Isfahan. Giemsa-stained karyotypes of these two species were prepared from bone marrow chromosome preparations. Systematic important characters of the body and cranium (incisors, molars, occipitonasal, condylobasal, zygomatic, tympanic bullae, etc.) of these rodents were studied. Cranium size was measured using a Vernier calipers. RESULTS: Specimens of M. persicus and N. indica had 2n = 42. The karyotype study of these species included metacentric, sub-metacentric and acrocentric chromosomes. Morphological studies were completely matched with the reported characters of these species and further confirmed the diagnoses. INTERPRETATION & CONCLUSION: Based on the results of this study, M. persicus and N. indica are two completely differentiated rodents species that were collected from a new focus and they can also be differentiated morphologically.

PMID: 19326708 [PubMed - in process]

6: J Vector Borne Dis. 2009 Mar;46(1):36-42.

Emergence of cutaneous leishmaniasis in a border area at south-east of Iran: an epidemiological survey.

Zahedan Research Centre for Infectious Diseases and Tropical Medicine, Zahedan University of Medical Sciences, Iran. afparm1@yahoo.co.uk

BACKGROUND & OBJECTIVES: Cutaneous leishmaniasis (CL) has been recently emerged in new foci, posing a public health problem. Increasing cases of CL have been reported during recent years from a border area between Iran and Pakistan, a previously non-endemic area. The present study was designed for epidemiological and parasitological characterization of the disease for the first time in this area. METHODS: A total of 3100 individuals from the city of Mirjaveh and its four rural districts were randomly selected and surveyed from March 2005 to February 2006. Microscopic examination, in vitro culture, mouse inoculations and species-specific kDNA-PCR assay were carried out for Leishmania detection and species identification. RESULTS: CL was endemic in an important rural district of Mirjaveh, presenting active lesions and scars in 6.6 and 9.5%, respectively. The highest rates of both active lesions and scars were found in the age group of 10 years or under with significant differences (p < 0.05) comparing to the older age groups. No association between genders and the rate of leishmaniasis was observed (p > 0.05). The most affected location was upper limb, 39.2% of ulcers and 41.7% of scars. Inoculation of the clinical isolates on Balb/c mice, led to the development of ulcers in the animals, implying that the causative parasite is Leishmania major. The PCR amplification also generated amplicons specific to L. major. CONCLUSION: It can be concluded that Mirjaveh is an endemic region of cutaneous leishmaniasis as a new focus due to the recent emergence in this border area of south-east of Iran with a major contribution of L. major, as the causative parasite species.

PMID: 19326706 [PubMed - in process]

7: J Vector Borne Dis. 2009 Mar;46(1):18-25.

Temporal and spatial epidemiology of sleeping sickness and use of geographical information system (GIS) in Kenya.

Kenya Agricultural Research Institute-Trypanosomiasis Research Centre, Kikuyu, Kenya. jjrutto@yahoo.co.uk

BACKGROUND & OBJECTIVES: In Kenya, sleeping sickness (SS) caused by Trypanosoma brucei rhodesiense is confined to the Nyanza and Western Provinces tsetse belts. Over the last two decades, the disease has exhibited great spatial variability in its spread and distribution. The objectives of the study were to map the spatial and temporal distribution of SS and determine possible risk factors associated with the disease in western Kenya. METHODS: Geographical coordinates of villages were obtained using a Global Positioning System (GPS). SS data were analyzed retrospectively and the mapping of villages was done using MapInfo Software. Epidemiological data of villages affected by SS were then correlated to human and cattle population. RESULTS: SS has spread northwards affecting the western parts of Busia, Teso, and of Bungoma districts in the late 1990s. Most of the SS cases were reported between March and June. The mainly affected age groups were from 20 to 49 years. SS was highest in areas with low human population density, ranging from 0-340/km2 and high livestock population, ranging from 5000 to 10,000 cattle. INTERPRETATION & CONCLUSION: There was a shift of SS occurrence from the old foci into new foci occurring at low transmission levels and causing occasional epidemic outbreaks. The study concludes that seasons influenced disease incidences with higher numbers of SS cases being recorded during the wet seasons. Gender and age determined the disease occurrence with most productive age groups being at higher risk. Areas with high livestock populations had low human population densities and had higher SS cases.

PMID: 19326704 [PubMed - in process]

8: J Vector Borne Dis. 2009 Mar;46(1):13-7.

Is leishmaniasis in Sri Lanka benign and be ignored?

Department of Parasitology, Faculty of Medicine, University of Colombo, Colombo, Sri Lanka. nadira@parasit.cmb.ac.lk

Cutaneous leishmaniasis is now an endemic disease in Sri Lanka. Many studies have focussed on various aspects of this disease but the knowledge, particularly on epidemiological and vector aspects is still poor and the awareness among the general public and even medical/paramedical personnel regarding this disease remains grossly inadequate. The steady increase in the numbers and spread of cutaneous leishmaniasis cases in Sri Lanka and the very close similarity (genotypic and phenotypic) between the local parasite Leishmania donovani MON-37 and the parasite causing visceral leishmaniasis in India (L. donovani MON-2), considered together with the more recent case reports of autochthonous cases of visceral disease in this country, calls for urgent action for setting up of a surveillance programme to estimate the true disease burden and to implement an organized control strategy, combined with operational and epidemiological research to aid control efforts to avert a potentially major catastrophe of more virulent form of leishmaniasis, particularly the visceral type becoming endemic in Sri Lanka.

PMID: 19326703 [PubMed - in process]

9: Am J Trop Med Hyg. 2009 Mar;80(3):410-5.Click here to read LinkOut

Geographic variation in the sensitivity of recombinant antigen-based rapid tests for chronic Trypanosoma cruzi infection.

Division of Parasitic Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia 30333, USA. jverani@cdc.gov

Chagas disease affects 8-11 million people throughout the Americas. Early detection is crucial for timely treatment and to prevent non-vectorial transmission. Recombinant antigen-based rapid tests had high sensitivity and specificity in laboratory evaluations, but no Peruvian specimens were included in previous studies. We evaluated Stat-Pak and Trypanosoma Detect rapid tests in specimens from Bolivia and Peru. Specimens positive by three conventional assays were confirmed positives; specimens negative by two or more assays were confirmed negatives. In Bolivian specimens, Stat-Pak and Trypanosoma Detect tests were 87.5% and 90.7% sensitive, respectively; both showed 100% specificity. Sensitivity in Peruvian specimens was much lower: 26.6-33.0% (Stat-Pak) and 54.3-55.2% (Trypanosoma Detect); both had specificities > 98%. Even in Bolivian specimens, these sensitivities are inadequate for stand-alone screening. The low sensitivity in Peru may be related to parasite strain differences. Chagas disease rapid tests should be field tested in each geographic site before widespread implementation for screening.

PMID: 19270291 [PubMed - indexed for MEDLINE]

10: Infect Immun. 2009 Apr;77(4):1368-75. Epub 2009 Jan 29.Click here to read LinkOut

Trypanosoma cruzi promotes neuronal and glial cell survival through the neurotrophic receptor TrkC.

Parasitology Research Center, Department of Pathology, Tufts University School of Medicine, 150 Harrison Avenue, Boston, MA 02111, USA.

Trypanosoma cruzi, the agent of Chagas' disease, promotes neuron survival through receptor tyrosine kinase TrkA and glycosylphosphatidylinositol-anchored glial cell-derived family ligand receptors (GFRalpha). However, these receptors are expressed by only a subset of neurons and at low levels or not at all in glial cells. Thus, T. cruzi might exploit an additional neurotrophic receptor(s) to maximize host-parasite equilibrium in the nervous system. We show here that T. cruzi binds TrkC, a neurotrophic receptor expressed by glial cells and many types of neurons, and that the binding is specifically inhibited by neurotrophin-3, the natural TrkC ligand. Coimmunoprecipitation and competition assays show that the trans-sialidase/parasite-derived neurotrophic factor (PDNF), previously identified as a TrkA ligand, mediates the T. cruzi-TrkC interaction. PDNF promotes TrkC-dependent mitogen-activated protein kinase signaling, neurite outgrowth, and survival of genetically engineered PC12 neuronal cells and glial Schwann cells in a TrkC-dependent manner. Thus, TrkC is a new neurotrophic receptor that T. cruzi engages to promote the survival of neuronal and glial cells. The results raise the possibility that T. cruzi recognition of TrkC underlies regenerative events in nervous tissues of patients with Chagas' disease.

PMID: 19179422 [PubMed - indexed for MEDLINE]

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