Wednesday, July 15, 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: Turkiye Parazitol Derg. 2009;33(2):114-115.

[In vitro Activity of Arbutus unedo Against Leishmania tropica Promastigotes.]

[Article in Turkish]

Kivçak B, Mert T, Ertabaklar H, Balcioğlu IC, Töz SO.

Ege University Faculty of Pharmacy, Department of Pharmacognosy, Izmir, Turkey.

Pentavalent antimonials are the first choice for the treatment of anthroponotic cutaneous leishmaniasis (ACL) in health centers in Turkey, however in rural areas, traditional plants may be prefered for the treatment of lesions. In recent years a number of papers are published related to the natural products especially plant derivates. Our aim is to investigate the antileishmanial effect of Arbutus unedo which is a wild plant mainly grown in maquis and rocky places of the seabord in South Europe. In the present study, the ethanolic, water and n-hexane extracts from the leaves of Arbutus unedo were originally tested in vitro against Leishmania tropica promastigotes. The ethanol extract of Arbutus unedo leaves at the concentrations of 100, 250, 500 μg/ml were found to be more effective than the other extracts (p:0.000). Our study showed that the ethanolic extract of Arbutus unedo leaves can be a promising antileishmanial agent and further experiments are needed.

PMID: 19598085 [PubMed - as supplied by publisher]

2: Turkiye Parazitol Derg. 2009;33(2):109-113.

[The Serological and Entomological Survey of Zoonotic Visceral Leishmaniasis in Ayvacik Region of Canakkale Province, Turkey.]

[Article in Turkish]

Tok H, Sevıl N, Töz SO, Ertabaklar H, Balcioğlu IC, Demır S, Ozbel Y, Coşkun M.

Canakkale Onsekiz Mart Universitesi Fen Edebiyat Fakültesi Biyoloji Bölümü, Canakkale, Turkey.

The field studies were carried out in Ilyasfaki village belonging to Ayvacik town, Kalabakli village and center of Kepez town belonging to Canakkale province to determine the epidemiological situation of visceral leishmaniasis between June and August 2007. A total of 27 blood samples were taken from the dogs which are known as reservoir of Leishmania infantum causing visceral leishmaniasis in human and dogs. The dogs were also examined physically for clinical symptoms of the disease. A total of 789 sand fly specimens were collected using CDC miniature light traps and examined. Six Phlebotomus and one Sergentomyia species were identified as: Phlebotomus negletus, P. tobbi, P. simici, P. papatisi, P. perfiliewi, P. halepensis and S. theodori. Among these species P. neglectus, was found to be a dominant species in Ilyasfaki village by the rate of 94.4%, while P. tobbi was also found to be a dominant species in city center (including Kepez) and Kalabaki village by the rate of 50% and 48.1%, respectively. No seropositive dogs were found by IFA test. Seropositivity below cut-off level was only observed in two dogs from Kepez, in dilutions of 1/16 and 1/64. The risk level for human and canine visceral is found to be high and it requires more field studies on canine leishmaniasis in and around the area.

PMID: 19598084 [PubMed - as supplied by publisher]

3: PLoS Negl Trop Dis. 2009 Jul 14;3(7):e480.

Local suppression of T cell responses by arginase-induced L-arginine depletion in nonhealing leishmaniasis.

Modolell M, Choi BS, Ryan RO, Hancock M, Titus RG, Abebe T, Hailu A, Müller I, Rogers ME, Bangham CR, Munder M, Kropf P.

Department of Cellular Immunology, Max-Planck-Institute for Immunobiology, Freiburg, Germany.

The balance between T helper (Th) 1 and Th2 cell responses is a major determinant of the outcome of experimental leishmaniasis, but polarized Th1 or Th2 responses are not sufficient to account for healing or nonhealing. Here we show that high arginase activity, a hallmark of nonhealing disease, is primarily expressed locally at the site of pathology. The high arginase activity causes local depletion of L-arginine, which impairs the capacity of T cells in the lesion to proliferate and to produce interferon-gamma, while T cells in the local draining lymph nodes respond normally. Healing, induced by chemotherapy, resulted in control of arginase activity and reversal of local immunosuppression. Moreover, competitive inhibition of arginase as well as supplementation with L-arginine restored T cell effector functions and reduced pathology and parasite growth at the site of lesions. These results demonstrate that in nonhealing leishmaniasis, arginase-induced L-arginine depletion results in impaired T cell responses. Our results identify a novel mechanism in leishmaniasis that contributes to the failure to heal persistent lesions and suggest new approaches to therapy.

PMID: 19597544 [PubMed - in process]

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4: J Immunol. 2009 Jul 13. [Epub ahead of print]

The p110{delta} Isoform of Phosphatidylinositol 3-Kinase Controls Susceptibility to Leishmania major by Regulating Expansion and Tissue Homing of Regulatory T Cells.

Liu D, Zhang T, Marshall AJ, Okkenhaug K, Vanhaesebroeck B, Uzonna JE.

*Department of Immunology, University of Manitoba, Winnipeg, Manitoba, Canada.

Resistance to Leishmania major and most intracellular pathogens is usually associated with a strong T cell-mediated immunity, particularly a CD4(+) Th1 response. Mice with an inactivating knock-in mutation in the p110delta isoform of PI3K (referred to as p110delta(D910A)) show severely impaired T cell responses. Because a strong T cell response is thought to mediate resistance to intracellular pathogens, we examined the outcome of L. major infection in p110delta(D910A) mice. Paradoxically, p110delta(D910A) mice on "resistant" and "susceptible" genetic backgrounds showed more robust resistance manifested as significantly reduced lesion size and accelerated parasite clearance. This enhanced resistance was associated with dramatically diminished immune responses, including impaired cell proliferation and effector cytokine (IFN-gamma and TNF) production. Interestingly, the ability of macrophages and dendritic cells from p110delta(D910A) mice to produce NO and destroy Leishmania parasites was similar to those of wild-type mice. We show that the enhanced resistance of p110delta(D910A) mice was due to impaired expansion and effector functions of regulatory T cells (Tregs). Adoptive transfer studies demonstrated that p110delta(D910A) mice lost their increased resistance when given enriched Tregs from wild-type mice. We suggest on the basis of these and further observations that the lack of this enzyme prominently affects Treg expansion and homing to infection sites, and that in the absence of Tregs, weak Th1 responses are capable of containing parasites and prevent pathology. We also suggest that temporary pharmacological inhibition of this enzyme may be a very effective form of treatment against cutaneous leishmaniasis.

PMID: 19596993 [PubMed - as supplied by publisher]

5: Acta Trop. 2009 Jul 9. [Epub ahead of print]

Canine visceral leishmaniasis: asymptomatic infected dogs as a source of L. infantum infection.

Moshfe A, Mohebali M, Edrissian G, Zarei Z, Akhoundi B, Kazemi B, Jamshidi S, Mahmoodi M.

Department of Medical Parasitology and Mycology, School of Public Health and Institute of Public Health Research, Tehran University of Medical Sciences, P.O. Box 14155-6446, Tehran, Iran; Department of Medical Parasitology and Mycology, Faculty of Medicine, Yasuj University of Medical Sciences, Kohgiloyeh and Booyerahmad, Iran.

Clinically infected dogs have been identified as the main reservoir hosts of visceral leishmaniasis (VL) caused by Leishmania infantum in the Mediterranean region. The objective of this study was to determine the potential of asymptomatic infected dogs compared with symptomatic ones as a source of L. infantum infection to golden hamster. For this purpose, anti-Leishmania antibodies were detected with direct agglutination test (DAT) in 13 symptomatic (7 seropositive=>/=1:320) and 53 asymptomatic (9 seropositive=>/=1:320 and 44 seronegative=<1:320) ownership dogs. DNA of Leishmania sp. was extracted from skin and peripheral blood tissues of each dog and tested by PCR. Sixty-six Syrian golden hamsters (Mesocricetus auratus) were used for the determination of infectivity and pathogenicity of L. infantum, isolated from the dogs. We used the internal transcribed spacer 2 (ITS2) rDNA sequence analysis. The results showed that 22 and 11 out of 66 inoculated golden hamsters were positive by PCR and parasitological examinations, respectively. From 22 PCR positive hamsters, 17 were related to asymptomatic dogs and 5 were from symptomatic ones. There was no significant difference between symptomatic and asymptomatic dogs in producing Leishmania infection in the susceptible animal model ((P=0.66). Smears and cultures of 5 dogs from 13 symptomatic dogs (38.5%) and 6 dogs from 53 asymptomatic ones (11.3%), were found to be positive at parasitological examination. All the L. infantum isolates from symptomatic and asymptomatic dogs were similar in sequencing. In conclusion, asymptomatic infected dogs as well as symptomatic ones can harbor L. infantum in their blood and skins which are virulent and infectious for inoculated golden hamster.

PMID: 19595664 [PubMed - as supplied by publisher]

6: Vet Parasitol. 2009 Jun 25. [Epub ahead of print]

Potential role for dog fleas in the cycle of Leishmania spp.

Ferreira MG, Fattori KR, Souza F, Lima VM.

Departamento de Clínica, Cirurgia e Reprodução Animal, Faculdade de Odontologia, Curso de Medicina Veterinária, Universidade Estadual Paulista, Araçatuba, São Paulo, Brazil.

Several species of Leishmania spp. cause diseases in humans that range from self-healing cutaneous lesions to fatal visceral leishmaniosis. It has been observed that besides being transmitted by sand flies, Leishmania spp. may also be transmitted by arthropods such as ticks and fleas. To investigate the possible role of dog fleas in the transmission of Leishmania spp., Ctenocefalides felis were removed from 22 dogs which were positive according to ELISA and rK-39 tests. A C. felis sample from each of the 22 dogs was used to infect a hamster. The 22 hamsters were euthanized 4 months after infection with the fleas and the blood was subjected to ELISA to detect antibody anti-Leishmania spp., and the spleen samples were submitted to PCR for detection of Leishmania spp. DNA. PCR and ELISA were both positive in 18.1% (4/22), with PCR alone being positive in 45% (10/22) and ELISA alone in only 9% (2/22). These results suggest the participation of dog fleas in the Leishmania spp. cycle. Confirmation that C. felis indeed transmit leishmaniosis to dogs requires new strategies against leishmaniosis to be enforced by public health authorities and which focus on better ways to keep dogs free of fleas.

PMID: 19595512 [PubMed - as supplied by publisher]

7: J Infect. 2009 Jul;59(1):1-18. Epub 2009 May 27.

Fever in returned travellers presenting in the United Kingdom: Recommendations for investigation and initial management.

Johnston V, Stockley JM, Dockrell D, Warrell D, Bailey R, Pasvol G, Klein J, Ustianowski A, Jones M, Beeching NJ, Brown M, Chapman AL, Sanderson F, Whitty CJ; On behalf of the British Infection Society and the Hospital for Tropical Diseases.

Hospital for Tropical Diseases, Mortimer Market Centre, Capper Street, London, UK.

International travel is increasing. Most physicians and general practitioners will encounter returned travellers with fever and the majority of travel-related infection is associated with travel to the tropics. In those returning from the tropics malaria must always be excluded, and HIV considered, from all settings. Common causes of non-malarial fever include from Africa rickettsial diseases, amoebic liver abscess and Katayama syndrome; from South and South East Asia, enteric fever and arboviral infection; from the Middle East, brucellosis and from the Horn of Africa visceral leishmaniasis. Other rare but important diseases from particular geographical areas include leptospirosis, trypanosomiasis and viral haemorrhagic fever. North and South America, Europe and Australia also have infections which are geographically concentrated. Empirical treatment may have to be started based on epidemiological probability of infection whilst waiting for results to return. The evidence base for much of the management of tropical infections is limited. These recommendations provide a pragmatic approach to the initial diagnosis and management of fever in returned travellers, based on evidence where it is available and on consensus of expert opinion where it is not. With early diagnosis and treatment the majority of patients with a potentially fatal infection related to travel will make a rapid and full recovery.

PMID: 19595360 [PubMed - as supplied by publisher]

8: J Med Chem. 2009 Jun 25;52(12):3703-15.Click here to read LinkOut

Structurally simple inhibitors of lanosterol 14alpha-demethylase are efficacious in a rodent model of acute Chagas disease.

Suryadevara PK, Olepu S, Lockman JW, Ohkanda J, Karimi M, Verlinde CL, Kraus JM, Schoepe J, Van Voorhis WC, Hamilton AD, Buckner FS, Gelb MH.

Department of Chemistry, University of Washington, Seattle, Washington 98195, USA.

We report structure-activity studies of a large number of dialkyl imidazoles as inhibitors of Trypanosoma cruzi lanosterol-14alpha-demethylase (L14DM). The compounds have a simple structure compared to posaconazole, another L14DM inhibitor that is an anti-Chagas drug candidate. Several compounds display potency for killing T. cruzi amastigotes in vitro with values of EC(50) in the 0.4-10 nM range. Two compounds were selected for efficacy studies in a mouse model of acute Chagas disease. At oral doses of 20-50 mg/kg given after establishment of parasite infection, the compounds reduced parasitemia in the blood to undetectable levels, and analysis of remaining parasites by PCR revealed a lack of parasites in the majority of animals. These dialkyl imidazoles are substantially less expensive to produce than posaconazole and are appropriate for further development toward an anti-Chagas disease clinical candidate.

PMID: 19463001 [PubMed - indexed for MEDLINE]

Patient Drug Information

  • Posaconazole (Noxafil® )

    Posaconazole is used to prevent serious fungal infections in people with a weakened ability to fight infection. Posaconazole is also used to treat yeast infections of the mouth and throat including yeast infections that ...

  • Source: AHFS Consumer Medication Information
9: Infect Immun. 2009 Jul;77(7):3023-32. Epub 2009 May 11.Click here to read LinkOut

Use of L-proline and ATP production by Trypanosoma cruzi metacyclic forms as requirements for host cell invasion.

Martins RM, Covarrubias C, Rojas RG, Silber AM, Yoshida N.

Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de São Paulo, São Paulo, Brazil.

The process of host cell invasion by Trypanosoma cruzi depends on parasite energy. What source of energy is used for that event is not known. To address this and other questions related to T. cruzi energy requirements and cell invasion, we analyzed metacyclic trypomastigote forms of the phylogenetically distant CL and G strains. For both strains, the nutritional stress experienced by cells starved for 24, 36, or 48 h in phosphate-buffered saline reduced the ATP content and the ability of the parasite to invade HeLa cells proportionally to the starvation time. Inhibition of ATP production by treating parasites with rotenone plus antimycin A also diminished the infectivity. Nutrient depletion did not alter the expression of gp82, the surface molecule that mediates CL strain internalization, but increased the expression of gp90, the negative regulator of cell invasion, in the G strain. When L-proline was given to metacyclic forms starved for 36 h, the ATP levels were restored to those of nonstarved controls for both strains. Glucose had no such effect, although this carbohydrate and L-proline were transported in similar fashions. Recovery of infectivity promoted by L-proline treatment of starved parasites was restricted to the CL strain. The profile of restoration of ATP content and gp82-mediated invasion capacity by L-proline treatment of starved Y-strain parasites was similar to that of the CL strain, whereas the Dm28 and Dm30 strains, whose infectivity is downregulated by gp90, behaved like the G strain. L-Proline was also found to increase the ability of the CL strain to traverse a gastric mucin layer, a property important for the establishment of T. cruzi infection by the oral route. Efficient translocation of parasites through gastric mucin toward the target epithelial cells in the stomach mucosa is an essential requirement for subsequent cell invasion. By relying on these closely associated ATP-driven processes, the metacyclic trypomastigotes effectively accomplish their internalization.

PMID: 19433547 [PubMed - indexed for MEDLINE]

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