[Leish-l] Articles found by RefScout 2006/03/01 2006/09

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Thu Mar 2 12:00:23 BRT 2006

    Date: Wed, 1 Mar 2006 15:32:54
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REQUEST: [ leishmaniasis ]

(23 articles match this request)

PMID: 16376333

TITLE: Leishmania major: Species specific delayed hypersensitivity reaction
induced by exogenous secreted antigen in the guinea pig.

AUTHORS: A R Khabiri, F Bagheri, M Assmar

AFFILIATION: Department of Parasitology, Pasteur Institute of Iran, Tehran,

REFERENCE: Exp Parasitol 2006 Mar 112(3):184-6

The cellular response to Leishmania major (L. major) is usually 
evaluated in vivo by the delayed-type-hypersensitivity (DTH) test using 
leishmanin. Leishmanin can give false-positive reactions in areas where 
there is a background of leishmaniasis. In a previous study, it was 
shown that a 56kDa antigen purified from promastigote and culture 
supernatant of L. major induce strong DTH reactions in sensitized guinea
 pigs. In this study, the species-specificity of this antigen was 
further investigated. Three groups of guinea pigs were sensitized with L
. major, L. tropica, and L. infantum and both flanks of sensitized 
animal were injected intradermally with purified 56kDa antigen or 
soluble leishmania antigen (SLA). The extent of indurations were 
measured after 24, 48, and 72h. In animals which were sensitized with 
three species of leishmania, only those immunized with L. major showed 
skin reactions to purified antigen by an increase in skin thickness. 
Since complex antigen mixtures such as SLA and leishmanin show cross-
reactivity and can be non-specific, the result obtained here suggest 
that 56kDa antigen may be a useful diagnostic tool for species specific 
diagnosis in field studies of leishmaniasis.

PMID: 16310900

TITLE: Non PC liposome entrapped promastigote antigens elicit parasite specific
CD8(+) and CD4(+) T-cell immune response and protect hamsters against visceral

AUTHORS: Sharad Kumar Sharma, Anuradha Dube, Ahmad Nadeem, Shazia Khan, Iram
Saleem, Ravendra Garg, Owais Mohammad

AFFILIATION: Inter-Disciplinary Biotechnology Unit, Aligarh Muslim University,
Aligarh-202002, India.

REFERENCE: Vaccine 2006 Mar 24(11):1800-10

Leishmania donovani promastigote soluble antigens (sLAg) were 
encapsulated in non-phosphatidylcholine (non-PC) liposomes (
escheriosomes) prepared from E. coli lipids. The escheriosome-based 
vaccine was investigated for its potential to elicit a protective immune
 response against experimental visceral leishmaniasis. The vaccine 
administration induced strong humoral as well as cell mediated immune 
responses both in hamsters and BALB/c mice. Immunization of BALB/c mice 
with escheriosome entrapped sLAg (EL-sLAg) elicited stronger CD8(+) 
cytotoxic T lymphocyte (CTL) response as compared to sLAg entrapped in 
egg PC/chol liposome (EPC-sLAg) or sLAg administered with incomplete 
Freund's adjuvant (IFA-sLAg). EL-sLAg also induced the release of mixed
 (Th1 and Th2) types of cytokines in the immunized BALB/c mice. In 
addition, the delivery of sLAg via escheriosomes enhanced the expression
 of costimulatory signals (CD80 and CD86) as determined in peritoneal 
macrophages obtained from BALB/c mice. In another set of experiments, 
the EL-sLAg immunized hamsters were found to be better protected than 
those immunized with EPC-sLAg. The prophylaxis coincided with increased 
lymphocyte proliferation as well as high nitric oxide (NO) production by
 peritoneal macrophages among EL-sLAg immunized hamsters. Escheriosomes 
thus seem to have potential in delivering the antigen to cytosol of the 
antigen presenting cells (APCs) and in the development of liposome-based
 vaccine against leishmaniasis as well as other intracellular infections.

PMID: 16325969

TITLE: Prime-boost vaccination using cysteine proteinases type I and II of
Leishmania infantum confers protective immunity in murine visceral

AUTHORS: Sima Rafati, Farnaz Zahedifard, Fereshteh Nazgouee

AFFILIATION: Molecular Immunology and Vaccine Research Lab., Pasteur Institute
of Iran, P.O. Box 11365-6699, Tehran, Iran.

REFERENCE: Vaccine 2006 Mar 24(12):2169-75

Vaccination with a cocktail of DNA encoding cysteine proteinases has 
been previously shown to confer protection against experimental 
cutaneous leishmaniasis (CL). In the present study we test the efficacy 
of immunization against Leishmania infantum in a murine model of 
infection, using a prime-boost strategy. BALB/c mice were immunized 
twice, in a 3 weeks interval, with cocktail of plasmids DNA encoding 
type I (cpb) and II (cpa) cysteine proteinases. DNA immunization was 
then followed by a boost with rCPA/rCPB in addition to CpG ODN and 
Montanide720 as adjuvant. Analysis of the immune response showed that 
vaccination mainly elicited antigen-specific IgG2a antibodies, 
suggesting the induction of a Th1 immune response. This was further 
confirmed by the analysis of the splenic cytokine production: at all 
time points the ratio of IFN-gamma/IL-5 induced upon restimulation with 
rCPA and rCPB was always significantly higher in vaccinated group 
compared to both control groups.

PMID: 16499285

TITLE: Diamidines as antitrypanosomal, antileishmanial and antimalarial agents.

AUTHORS: Karl Werbovetz

AFFILIATION: The Ohio State University, Division of Medicinal Chemistry and
Pharmacognosy, College of Pharmacy, Columbus 43210-1291, USA.
werbovetz.1 at osu.edu

REFERENCE: Curr Opin Investig Drugs 2006 Feb 7(2):147-57

Diamidine-containing compounds have a long history of use in the 
treatment of African trypanosomiasis and leishmaniasis. The discovery 
that diamidine prodrugs possess in vivo antimicrobial activity when 
administered orally has led to a renewed interest in this class of 
compounds for the treatment of parasitic infections. In this review, the
 selectivity of diamidines against trypanosomes, Leishmania and 
Plasmodium is rationalized through mechanism-of-action studies. An 
overview of the antiprotozoal activities of newer diamidines and 
diamidine prodrugs is also presented, along with a summary of the 
progress made toward the clinical development of new diamidines for use 
against these parasitic diseases.

PMID: 16490074

TITLE: Pediatric visceral Leishmaniasis in Turkey.

AUTHORS: Gönül Tanir, Aysegül Taylan Ozkan, Eda Dağlar

AFFILIATION: Department of Pediatrics, Sami Ulus Children's Hospital, Ankara,

REFERENCE: Pediatr Int 2006 Feb 48(1):66-9

Abstract Background: Visceral Leishmaniasis (VL) type in Turkey is 
consistent with the Mediterranean type of VL, a fatal debilitating 
disease, which is mostly seen in infants. Methods: Hospital records of 
19 children with VL were retrospectively reviewed. The period of the 
study was from January 2000 to December 2003. Results: The median age of
 the patients was 36 months. None was coinfected with human 
immunodeficiency virus or known to be immunocompromised. Fever, pallor, 
hepatomegaly, splenomegaly, thrombocytopenia and elevated C-reactive 
protein were observed in all cases, anemia in 18 (95%), leucopenia in 17
 (89.4%) and elevated erythrocyte sedimentation rate in 14 (77.7%) of 
the cases. A bone marrow aspirate was obtained in all cases and 
Leishmania amastigotes were detected in 15 (78.9%). Fifteen patients (78
.9%) were treated initially with meglumine antimonate and four (21%) 
with sodium stibogluconate. The four patients who received sodium 
stibogluconate suffered from adverse side-effects during treatment and 
were subsequently treated with lipid formulations of amphotericin B. 
Conclusions: Presentation of VL in the pediatric age group in Turkey is 
characterized by pallor, fever, splenomegaly and hepatomegaly. 
Hematological and biochemical indices are typical with cytopenias, 
hypoalbuminemia, and hyperproteinemia. In most of the cases, microscopic
 examination provided a positive diagnosis and the remaining patients 
were diagnosed by serology. Lipid formulations of amphotericin B may be 
useful in cases of treatment failure with antimonials or significant 
adverse effects of the drug.

PMID: 16443435

TITLE: Persisting afebrile swelling of the lips and tongue: an unusual case of
granulomatous glossitis.

AUTHORS: Emmanuel J Diamantopoulos, Emmanuel A Andreadis, Georgios I Tsourous,
Constantina D Petraki, Dimitra P Rontogianni

AFFILIATION: 4th Department of Internal Medicine, Evangelismos State General
Hospital, Athens, Greece. dpathologiki at evaggelismos_hosp.gr

REFERENCE: Am J Med 2006 Feb 119(2):182-3

PMID: 16501768

TITLE: [Study of the sand flies in American cutaneous leishmaniasis area, in the
municipality of Alto Caparaó and Caparaó, Minas Gerais State.]

AUTHORS: Lara Saraiva, Juliana Dos Santos Lopes, Gisele Brandão Machado
Oliveira, Francisco de Assis Batista, Alda Lima Falcão, José Dilermando
Andrade Filho

AFFILIATION: Colégio Técnico, Universidade Federal de Minas Gerais, Belo
Horizonte, MG, Brasil.

REFERENCE: Rev Soc Bras Med Trop 2006 Jan-Feb 39(1):56-63

In the period from November of 2000 to November of 2001, a study of sand
 flies was realized in the municipalities of Alto Caparaó and Caparaó 
with the objective of determining their seasonal variation, comparing 
the points of study related to the occurrence of these insects and 
detecting their ideal environments. Monthly collections were carried out
, with Falcão light traps at nine points, four traps per point, in the 
following environments: of animals shelter, forest (bush), coffee 
plantation and the external walls of houses. Lutzomyia intermedia (Lutz
 & Neiva, 1912) was the predominant species, and animal shelter the 
environment with the largest occurrence of sand flies. A significant 
difference in the composition of sand fly species was found in the 
studied points. Lutzomyia intermedia is the species suspected of 
transmitting Leishmania in the region.

PMID: 16500783

TITLE: Successful treatment of visceral leishmaniasis with fluconazole and
allopurinol in a patient with renal failure.

AUTHORS: Murat Colakoglu, Guzin Fidan Yaylali, Nagihan Yalcin Colakoglu, Mustafa

AFFILIATION: From the Department of Nephrology, School of Medicine, Pamukkale
University, Denizli, Turkey.

REFERENCE: Scand J Infect Dis 2006  38(3):208-10

Standard treatments for visceral leishmaniasis (antimonials, 
amphotericin B and pentamidine) pose several problems. Failure of 
antimonials or severe toxicity is particularly troublesome in patients 
with renal insufficiency. We report a case of visceral leishmaniaisis 
and renal insufficiency successfully treated with fluconazole and 
allopurinol for 4 months.

PMID: 16495850

TITLE: [Leishmania infantum/HIV co-infection: cutaneous lesions following
treatment of visceral leishmaniasis.]

AUTHORS: G Catorze, J Alberto, A Afonso, R Vieira, S Cortes, L Campino

AFFILIATION: Serviço de Dermatologia, Hospital de Curry Cabral, Lisboa,

REFERENCE: Ann Dermatol Venereol 2006 Jan 133(1):39-42

BACKGROUND: The Mediterranean basin is an endemic region of 
leishmaniasis caused by Leishmania infantum. With the advent of human 
immunodeficiency virus (HIV) infection, the number of cases of visceral 
leishmaniasis has dramatically increased in this area over the last 
years, mainly in adults. Moreover, the presence of cutaneous lesions 
infested with Leishmania has been frequently reported in these patients.
CASE-REPORT: A 35-year-old Portuguese woman, a former intravenous drug 
user HIV1-positive since 1997, developed visceral leishmaniasis in 2000
, with several relapses in 2001 and 2002, treated successively with 
pentavalent antimonial salts (Glucantime(R)), liposomal amphotericin B 
and Glucantime(R) associated with itraconazole. Several weeks after 
therapy for the second relapse of visceral leishmaniasis, physical 
examination revealed asymptomatic erythematous papules on the face that 
later spread to the trunk and upper limbs. Histopathologic studies of a 
skin biopsy revealed a granulomatous infiltrate in the dermis with the 
presence of Leishmania amastigotes. After culture, the parasite was 
identified as L. infantum MON-1. In spite of improvement of the patient'
s visceral leishmaniasis with the above-mentioned treatment, the 
cutaneous lesions became increasingly numerous and infiltrated. After 2 
months of therapy with intravenous pentamidine (4 mg/kg/3 times a week) 
and oral dapsone (100 mg b.i.d), the cutaneous lesions disappeared 
completely. Prevention with dapsone was successfully maintained for 6 
months. Several weeks after discontinuation of treatment, further 
lesions appeared. The patient improved again on reintroduction of 
dapsone.DISCUSSION: This case confirmed the existence of a clinical form
 similar to post-kala-azar dermal leishmaniasis in a patient co-infected
 with L. infantum MON-1/HIV. The cutaneous lesions were resistant to 
classical antileishmanial drugs but disappeared on treatment with 

PMID: 16495859

TITLE: [Linear cutaneous leishmaniasis: a new clinical form.]

AUTHORS: A Masmoudi, N Ayedi, S Bouassida, S Marrekchi, S Boudaya, N Elleuch, H
Turki, A Zahaf

AFFILIATION: Service de Dermatologie, CHU Hédi Chaker, Sfax, Tunisie.

REFERENCE: Ann Dermatol Venereol 2006 Jan 133(1):70

PMID: 16501761

TITLE: [Clinical findings of tegumentary leishmaniasis in children under five
years of age in an endemic area of Leishmania (Viannia) braziliensis.]

AUTHORS: Julia Ampuero, Vanize Macêdo, Philip Marsden

AFFILIATION: Núcleo de Medicina Tropical, Universidade de Brasília, Brasília,
DF, Brasil.

REFERENCE: Rev Soc Bras Med Trop 2006 Jan-Feb 39(1):22-6

A retrospective study was performed in a field clinic to characterize 
the clinical findings of tegumentary leishmaniasis in children from 0 to
 5 years old. The clinical records of 4,464 patients were analyzed at 
the Primary Health Center of Corte de Pedra, Presidente Tancredo Neves, 
Bahia, Brazil, from May 1987 to December 1995. Four hundred and ninety 
one (11.8%) children were identified among 4,275 new cases of 
tegumentary leishmaniasis registered at this Unit. The gender ratio (M:F
) for children under six years was 1.1:1. Cutaneous lesions predominated
 (98%), mainly skin ulcers (99%) located above the waist (p<0.05). 
Thirty five percent had multiple lesions. The observed magnitude of the 
disease in children, the similar proportion of cases in both genders and
 the location of the lesions suggest the possibility of peri or 
intradomiciliary transmission.

PMID: 16501764

TITLE: [Comparative study about the specific antileishmania of immunoglobulin G
and E as markers of infection and illness among dwellers of a visceral
leishmaniasis endemic area in São Luis, MA.]

AUTHORS: Maria do Desterro Soares Brandão Nascimento, Geusa Felipa de Barros
Bezerra, Abderval Pinto Bandeira Neto, Leopoldo Muniz da Silva, José de
Macêdo Bezerra, Graça Maria de Castro Viana

AFFILIATION: Núcleo de Imunologia Básica e Aplicada, Departamento de
Patologia, Universidade Federal do Maranhão, São Luís, MA.

REFERENCE: Rev Soc Bras Med Trop 2006 Jan-Feb 39(1):38-42

Comparative study regarding IgG and IgE anti-leishmania as markers of 
infection and illness among residents of a visceral leishmaniasis 
visceral leishmaniasis endemic area, São Luis, MA in the period from 
May 1999 to May 2000. All the 1,016 individuals younger than 16 years 
old were tested for the presence of IgG by ELISA. A total of 174 (17,1
%) children revealed a positive IgG test and 4 children showed symptoms 
of classical visceral leishmaniasis during the time of the survey: 85 
IgE anti-leishmania ELISA tests with positivity of 43,5% were realized. 
In this sample, all 7 children with past-visceral leishmaniasis in the 
sample were IgG positive and 4 (57,1%) were IgE positive, even after a 7
 year post treatment period. Three children with current visceral 
leishmaniasis were evaluated, and all of them were positive for both 
tests. The detection of antileishman IgE antibodies presented as a good 
marker for infection by Leishmania chagasi in endemic areas but not as a
 disease marker.

PMID: 16501765

TITLE: [Occurrence of American tegumentary leishmaniasis in the Mato Grosso do
Sul State associated to the infection for Leishmania (Leishmania)

AUTHORS: Maria Elizabeth Moraes Cavalheiros Dorval, Elisa Teruya Oshiro, Elisa
Cupollilo, Ana Cristina Camargo de Castro, Tulia Peixoto Alves

AFFILIATION: Departamento de Patologia, Centro de Ciências Biológicas e da
Saúde, Universidade Federal de Mato Grosso do Sul, Campo Grande, MS.

REFERENCE: Rev Soc Bras Med Trop 2006 Jan-Feb 39(1):43-6

Nine cases of American tegumentary leishmaniasis were reported at a 
Training Military Unit located in Bela Vista City, State of Mato Grosso 
do Sul. Parasites obtained from lesions of six patients were isolated in
 culture media followed by identification, through isoenzymes analysis, 
as being Leishmania amazonensis. This is the first evidence of the 
presence of the parasite in Mato Grosso do Sul.

PMID: 16501766

TITLE: [Antimicrobial susceptibility of aerobic bacteria isolated from
leishmaniotic ulcers in Corte de Pedra, BA.]

AUTHORS: Luis Angel Vera, Jefferson Lessa Soares de Macedo, Isolina Allen
Ciuffo, Conceição Guerra Santos, João Barberino Santos

AFFILIATION: Núcleo de Medicina Tropical e Nutrição, Universidade de
Brasília, Brasília, DF.

REFERENCE: Rev Soc Bras Med Trop 2006 Jan-Feb 39(1):47-50

A prospective study regarding aspects of antimicrobial susceptibility 
aspects was realized among patients with tegumentary leishmaniasis in 
Corte de Pedra, Bahia. Cases were composed mainly of adolescent and 
adult farmer patients with single lesions. Staphylococcus aureus 
predominated (83%) in the culteres with susceptibility to the majority 
of antibiotics. A mixed bacterial flora in ulcers was encountered in 37
 (44,1%) patients. Among the gram-negative bacteria isolated, 
Enterobacter sp (13.1%), Proteus sp (8.3%), Pseudomonas aeruginosa (7.1
%) and Klebsiella sp (7.1%) were mainly found with susceptibility to 
ciprofloxacin, aminoglycosides, third generation cephalosporin and 

PMID: 16491946

TITLE: Zinc: an essential trace element with potential benefits to soldiers.

AUTHORS: James P McClung, Angus G Scrimgeour

AFFILIATION: Military Nutrition Division, U.S. Army Research Institute of
Environmental Medicine, Natick, MA 01760, USA.

REFERENCE: Mil Med 2005 Dec 170(12):1048-52

Zinc is a trace element known to be an essential nutrient for life. It 
functions as a cofactor for numerous enzymes, including those involved 
in DNA and RNA replication and protein synthesis. Soldiers represent a 
unique population faced with intense metabolic and mental demands, as 
well as exposure to various immune challenges. Some of these factors may
 affect their dietary zinc requirements. Although severe zinc deficiency
 is unlikely to occur, some soldiers may experience less than optimal 
zinc status because of diminished intake coupled with increased 
requirements. For those soldiers, supplemental dietary zinc may serve a 
protective function in numerous disease states affecting modern 
warfighters. This review highlights the importance of adequate zinc 
nutriture to soldiers and discusses the potential benefits of 
supplemental zinc in a number of diseases currently affecting soldiers, 
including diarrhea, respiratory diseases, malaria, and leishmaniasis.

PMID: 16214217

TITLE: Complexation of antimony (Sb(V)) with guanosine 5'-monophosphate and
guanosine 5'-diphospho-D-mannose: formation of both mono- and bis-adducts.

AUTHORS: Yi Chai, Siucheong Yan, Iris L K Wong, Larry M C Chow, Hongzhe Sun

AFFILIATION: Department of Chemistry and Open Laboratory of Chemical Biology,
The University of Hong Kong, Pokfulam Road, Hong Kong, PR China.

REFERENCE: J Inorg Biochem 2005 Dec 99(12):2257-63

In spite of the extensive use of pentavalent antimony chemotherapy, the 
mechanism of its anti-leishmania action is still not clear. Here, we 
report the interactions of Sb(V), including the clinically used drug 
stibogluconate, with guanosine 5'-monophosphate (5'-GMP) and guanosine 5
'-diphospho-d-mannose (5'-GDP-mannose) in aqueous solution. The 
deprotonated hydroxyl groups (-OH) of the ribose ring are shown to be 
the binding site for Sb(V), probably via chelation. Both mono- and bis-
adducts were formed as determined by NMR, high performance liquid 
chromatography (HPLC) and electrospray ionization mass spectrometry (ESI
-MS), and both of them are stable in the pH range of 4 to around 9.5. 
The formation of the mono-adduct (k(1)=1.67x10(-3) and 3.43x10(-3) mM(-1
) min(-1) for Sb(5'-GMP) and Sb(5'-GDP-mannose), respectively, at 298 K
) was 10-fold faster than that of the bis-adduct (k(2)=0.16x10(-3) and 0
.21x10(-3) mM(-1) min(-1), for Sb(5'-GMP)(2) and Sb(5'-GDP-mannose)(2), 
respectively), and the mono-adduct was the major species in solution 
with the [bis-adduct]/[mono-adduct]<0.5. The reactions of 
stibogluconate with 5'-GMP and 5'-GDP-mannose were slower than that of 
antimonate under similar conditions.

PMID: 16410962

TITLE: Occurrence of co-infection by Leishmania (Leishmania) chagasi and
Trypanosoma (Trypanozoon) evansi in a dog in the state of Mato Grosso do Sul,

AUTHORS: Elisa San Martin Mouriz Savani, Vania Lúcia Brandão Nunes, Eunice
Aparecida Bianchi Galati, Tiago Moreno Castilho, Fernando Shiroma de Araujo,
Iêda Maria Novaes Ilha, Maria Cecília Gibrail de Oliveira Camargo, Sandra
Regina Nicoletti D'Auria, Lucile Maria Floeter-Winter

AFFILIATION: Laboratório de Zoonoses e Doenças Transmitidas por Vetores da
Vigilância em Saúde, Prefeitura do Município de São Paulo, 02031-020 São
Paulo, SP, Brazil. elisasanmar at yahoo.com.br

REFERENCE: Mem Inst Oswaldo Cruz 2005 Nov 100(7):739-41

A natural case of co-infection by Leishmania and Trypanosoma is reported
 in a dog (Canis familiaris) in south- western state of Mato Grosso do 
Sul, Brazil. Both amastigote and trypomastigote forms were observed 
after Giemsa staining of cytological preparations of the dog's bone 
marrow aspirate. No parasite was detected using medium culture 
inoculation of the sample. DNA obtained from the bone marrow aspirate 
sample and from the blood buffy coat was submitted to polymerase chain 
reaction (PCR) with a set of rDNA-based primers S4/S12. The nucleotide 
sequence of the PCR product was identical to that of Trypanosoma (
Trypanozoon) evansi. The S4/S12 PCR was then used as template in a 
nested-PCR using a specific Leishmania set S17/S18 as primers, to 
explain the amastigote forms. The nucleotide sequence of the new PCR 
product was identical to that of Leishmania (Leishmania) chagasi. This 
case, as far as we know, is the first report of a dog co-infected with 
these parasites, suggesting that besides L. (L.) chagasi, the natural 
transmission of T. (T.) evansi occurs in the area under study.

PMID: 16174412

TITLE: Germ-free mice produce high levels of interferon-gamma in response to
infection with Leishmania major but fail to heal lesions.

AUTHORS: M R Oliveira, W L Tafuri, L C C Afonso, M A P Oliveira, J R Nicoli, E C
Vieira, P Scott, M N Melo, L Q Vieira

AFFILIATION: Departamento de Parasitologia, ICB, Universidade Federal de Minas
Gerais, CP486, 30161-970, Belo Horizonte, MG, Brazil.

REFERENCE: Parasitology 2005 Oct 131(Pt 4):477-88

In order to investigate the importance of the host microbiota on 
differentiation of T cell subsets in response to infection, Swiss/NIH 
germ-free mice and conventional (microbiota-bearing) mice were infected 
with Leishmania major, and lesion development, parasite loads, and 
cytokine production were assessed. Germ-free mice failed to heal lesions
 and presented a higher number of parasites at the site of infection 
than their conventional counterparts. In addition, histopathological 
analysis indicated a higher density of parasitized macrophages in 
lesions from germ-free mice than in conventional mice. The initial 
production of interleukin (IL)-12 and interferon-gamma (IFN-gamma) in 
germ-free mice was comparable to the conventional controls. Also, germ-
free mice produced elevated levels of IFN-gamma and lower levels of IL-4
 throughout the course of infection, suggesting the development of a Th1
 response. Macrophages from germ-free mice exposed to IFN-gamma and 
infected with amastigotes in vitro were not as efficient at killing 
parasites as macrophages from conventional animals. These observations 
indicate that the microbiota is not essential for the development of Th1
 immune responses, but seems to be important for macrophage activation.


 The following references are revised files and are brought to you in accordance
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PMID: 16177338

TITLE: Antigen requirements for efficient priming of CD8+ T cells by Leishmania
major-infected dendritic cells.

AUTHORS: Sylvie Bertholet, Alain Debrabant, Farhat Afrin, Elisabeth Caler,
Susana Mendez, Khaled S Tabbara, Yasmine Belkaid, David L Sacks

AFFILIATION: Laboratory of Parasitic Diseases, National Institute of Allergy and
Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892,

REFERENCE: Infect Immun 2005 Oct 73(10):6620-8

CD4(+) and CD8(+) T-cell responses have been shown to be critical for 
the development and maintenance of acquired resistance to infections 
with the protozoan parasite Leishmania major. Monitoring the development
 of immunodominant or clonally restricted T-cell subsets in response to 
infection has been difficult, however, due to the paucity of known 
epitopes. We have analyzed the potential of L. major transgenic 
parasites, expressing the model antigen ovalbumin (OVA), to be presented
 by antigen-presenting cells to OVA-specific OT-II CD4(+) or OT-I CD8
(+) T cells. Truncated OVA was expressed in L. major as part of a 
secreted or nonsecreted chimeric protein with L. donovani 3' 
nucleotidase (NT-OVA). Dendritic cells (DC) but not macrophages infected
 with L. major that secreted NT-OVA could prime OT-I T cells to 
proliferate and release gamma interferon. A diminished T-cell response 
was observed when DC were infected with parasites expressing nonsecreted
 NT-OVA or with heat-killed parasites. Inoculation of mice with 
transgenic parasites elicited the proliferation of adoptively 
transferred OT-I T cells and their recruitment to the site of infection 
in the skin. Together, these results demonstrate the possibility of 
targeting heterologous antigens to specific cellular compartments in L. 
major and suggest that proteins secreted or released by L. major in 
infected DC are a major source of peptides for the generation of 
parasite-specific CD8(+) T cells. The ability of L. major transgenic 
parasites to activate OT-I CD8(+) T cells in vivo will permit the 
analysis of parasite-driven T-cell expansion, differentiation, and 
recruitment at the clonal level.

PMID: 16178749

TITLE: Dihydro-beta-agarofuran sesquiterpenes: a new class of reversal agents of
the multidrug resistance phenotype mediated by P-glycoprotein in the protozoan
parasite Leishmania.

AUTHORS: F Cortés-Selva, I A Jiménez, F Munoz-Martínez, M Campillo, I L
Bazzocchi, L Pardo, A G Ravelo, S Castanys, F Gamarro

AFFILIATION: Instituto de Parasitología y Biomedicina López-Neyra, Consejo
Superior de Investigaciones Científicas, Parque Tecnológico de Ciencias de la
Salud, Avda. del Conocimiento s/n, 18100-Armilla, Granada, Spain.

REFERENCE: Curr Pharm Des 2005  11(24):3125-39

Leishmaniasis is the most important emerging and uncontrolled infectious
 disease and the second cause of death among parasitic diseases, after 
Malaria. One of the main problems concerning the control of infectious 
diseases is the increased resistance to usual drugs. Overexpression of P
-glycoprotein (Pgp)-like transporters represents a very efficient 
mechanism to reduce the intracellular accumulation of drugs in cancer 
cells and parasitic protozoans, thus conferring a multidrug resistance (
MDR) phenotype. Pgps are active pumps belonging to the ATP-binding 
cassette (ABC) superfamily of proteins. The inhibition of the activity 
of these proteins represents an interesting way to control drug 
resistance both in cancer and in infectious diseases. Most conventional 
mammalian Pgp-MDR modulators are ineffective in the modulation of Pgp 
activity in the protozoan parasite Leishmania. Consequently, there is a 
necessity to find effective modulators of Pgp-MDR for protozoan 
parasites. In this review we describe a rational strategy developed to 
find specific Pgp-MDR modulators in Leishmania, using natural and 
semisynthetic dihydro-beta-agarofuran sesquiterpenes from Celastraceae 
plants. A series of these compounds have been tested on a MDR Leishmania
 tropica line overexpressing a Pgp transporter to determine their 
ability to revert the resistance phenotype and to modulate intracellular
 drug accumulation. Almost all of these natural compounds showed potent 
reversal activity with different degrees of selectivity and a 
significant low toxicity. The three-dimensional quantitative structure-
activity relationship using the comparative molecular similarity indices
 analysis (CoMSIA), was employed to characterize the requirements of 
these sesquiterpenes as modulators at Pgp-like transporter in Leishmania.

PMID: 11860368

TITLE: Cell biology of Leishmania spp.: invading and evading.

AUTHORS: M A Vannier-Santos, A Martiny, W de Souza

AFFILIATION: Laboratório de Biologia Celular Parasitária, Programa de Biologia
Celular e Parasitologia, Instituto de Biofísica Carlos Chagas Filho,
Universidade Federal do Rio de Janeiro, Brasil. vannier at biof.ufrj.br

REFERENCE: Curr Pharm Des 2002  8(4):297-318

Parasitic protozoa of the genus Leishmania infect mammalian mononuclear 
phagocytic cells causing a potentially fatal disease with a broad 
spectrum of clinical manifestations. The drugs of choice used in the 
leishmaniasis therapy are significantly toxic, expensive and faced with 
a growing frequency of refractory infections. Thus the search for new 
leishmanicidal compounds is urgently required. In order to perform a 
proper drug design and to understand the modes of action of such 
compounds it is necessary to elucidate the intricate cellular and 
molecular events that orchestrate the parasite biology. In order to 
invade the host cell Leishmania are able to recruit different surface 
receptors which may assist engaging the microbicidal responses. In the 
intracellular milieu these pathogens can deactivate and/or subvert the 
phagocyte signal transduction machinery rendering these cells permissive
 to infection. In the present review we attempted to approach some of 
the most relevant cellular and biochemical invasion and evasion 
strategies employed by Leishmania parasites.

PMID: 11860369

TITLE: Chemotherapy of leishmaniasis.

AUTHORS: Simon L Croft, Vanessa Yardley

AFFILIATION: Department of Infectious and Tropical Diseases, London School of
Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK.
simon.croft at lshtm.ac.uk

REFERENCE: Curr Pharm Des 2002  8(4):319-42

Leishmaniasis, in its variety of visceral (VL), cutaneous (CL) and 
mucocutaneous (MCL) forms, directly affects about 2 million people per 
annum, with approximately 350 million individuals at risk worldwide. 
During the last 10 years there have been extensive epidemics of the 
visceral form of the disease, which is also emerging as an important 
opportunistic infection in immunocompromised patients, especially those 
co-infected with HIV. The control of leishmaniasis remains a problem 
principally a zoonotic infection, except in epidemics where it is 
anthroponotic, interruption of transmission is difficult, though not 
impossible. No vaccines exist for either VL, CL or MCL and chemotherapy 
is inadequate and expensive. Current regimes use pentavalent antimony as
 primary therapy, which must be administered parenterally. Should this 
fail, a number of other drugs may be employed, depending upon the 
species of Leishmania concerned and the resources available to the 
health professionals involved. Recommended secondary treatment employs a
 variety of drugs, again depending on the nature of the infection. The 
most widely used of these is amphotericin B, which is highly active but 
has extensive toxicity complications. The newer formulations of this 
drug are too expensive to use for the majority of endemic countries. 
Pentamidine and paromomycin are used in some instances, and a new anti-
leishmanial, miltefosine, may be used in the future. In short, there 
remains a pressing need for new anti-leishmanials and this chapter 
reviews the current status of chemotherapy, the various avenues being 
investigated by researchers and their potential application in the 

PMID: 11008103

TITLE: Mice unresponsive to GM-CSF are unexpectedly resistant to cutaneous
Leishmania major infection.

AUTHORS: C L Scott, L Roe, J Curtis, T Baldwin, L Robb, C G Begley, E Handman

AFFILIATION: The Walter and Eliza Hall Institute of Medical Research, Victoria,
3050, Australia.

REFERENCE: Microbes Infect 2000 Aug 2(10):1131-8

Granulocyte-macrophage colony-stimulating factor (GM-CSF) has been shown
 to play a protective role in leishmanial infection. Mice with a null 
mutation in the gene for the beta common (beta c) chain of the receptors
 for GM-CSF, interleukin(IL)-3 and IL-5 (beta c-null mice) display 
normal steady state hemopoiesis and develop lung disease similar to the 
human condition, alveolar proteinosis, due to a lack of signaling by GM-
CSF. We therefore expected to observe a heightened sensitivity to 
Leishmania major in the beta c-null mice. Surprisingly, the beta c-null 
mice were more resistant to cutaneous infection than wild-type (wt) mice
. Upon intradermal injection of L. major promastigotes, fewer beta c-
null mice developed cutaneous lesions than wt mice and these lesions 
were smaller and healed more rapidly than in wt mice. This resistance to
 disease was associated with a reduced percentage of in vitro infected 
beta c-null macrophages. Macrophages from beta c-null mice displayed a 
more activated phenotype and produced increased amounts of nitric oxide 
following infection with L. major, both in vivo and in vitro. 
Paradoxically, however, the parasite burden in the draining lymph nodes 
was similar in both beta c-null and wt mice, suggesting that at least a 
subpopulation of cells was susceptible to the parasite. The mechanism 
preventing normal lesion development remains to be elucidated.

REQUEST: [ leishmania ]

(32 articles match this request. 15 articles matching other requests removed)

PMID: 16313904

TITLE: Leishmania amazonensis: Chemotaxic and osmotaxic responses in
promastigotes and their probable role in development in the phlebotomine gut.

AUTHORS: V C Barros, J S Oliveira, M N Melo, N F Gontijo

AFFILIATION: Departamento de Parasitologia, Instituto de Ciências Biológicas,
Universidade Federal de Minas Gerais, Av. Antônio Carlos 6627, 31270-901 Belo
Horizonte, MG, Brazil.

REFERENCE: Exp Parasitol 2006 Mar 112(3):152-7

Taxic responses may play a role in development of Leishmania in their 
phlebotomine sand fly vectors. They are possibly responsible for 
movement of the parasites towards the anterior regions of the gut, from 
where they would be transmitted to the vertebrate host. A methodology 
capable to distinguish chemotaxic from osmotaxic responses was described
 and used to characterise taxic responses in Leishmania promastigotes. 
These were able to respond to chemotaxic as well as to osmotaxic stimuli
. Like bacteria, promastigotes were capable to undergo "adaptation
," a phenomenon by which they stop responding to a continuos 
stimulus. A model capable to explain how a relatively small number of 
different receptors works to perceive gradients in chemotaxic responses 
was proposed. According to this model, these receptors possess low 
specificity and a wide range of affinities varying from high to low. A 
low specificity makes the same receptor able to bind to a large number 
of different but structurally related molecules and; a wide range of 
affinities (considering a population of receptors), implies that the 
number of receptors "occupied" by attractant molecules along a
 gradient would go growing step by step.

PMID: 16487314

TITLE: The occurrence of free d-alanine and an alanine racemase activity in
Leishmania amazonensis.

AUTHORS: Rogério Panizzutti, Milane Souza Leite, Carla M Pinheiro, José
Roberto Meyer-Fernandes

AFFILIATION: Departamento de Anatomia, ICB, Centro de Ciências da Saúde,
Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.

REFERENCE: FEMS Microbiol Lett 2006 Mar 256(1):16-21

Abstract Free d-amino acids are implicated in several biological 
functions. This study examined the presence of d-alanine in Leishmania 
amazonensis. Measuring chiral amino acid content by high-performance 
liquid chromatography we detected a significant amount of free d-alanine
 in promastigotes of these parasites. d-Alanine accounts for 8.9% of 
total free alanine and is found primarily in the soluble fraction. 
Specific racemization of l-alanine to d-alanine was detected in cell 
lysates and this enzyme activity was inhibited by d-cycloserine, an 
alanine racemase inhibitor. Furthermore, we were able to decrease this 
pool of d-amino acid by treating our cultures with d-cycloserine. We 
demonstrate for the first time the existence of a significant amount of 
free d-alanine in L. amazonensis and an alanine racemase activity 
present in cell lysates. The restriction of d-alanine to bacteria, some 
fungi and now in L. amazonensis opens a new perspective on treatment of 
diseases caused by these microorganisms.

PMID: 16487322

TITLE: Leishmania donovani cyclin 1 (LdCyc1) forms a complex with cell cycle
kinase subunit CRK3 (LdCRK3) and is possibly involved in S-phase-related

AUTHORS: Sampali Banerjee, Abhik Sen, Pradeep Das, Partha Saha

AFFILIATION: Crystallography and Molecular Biology Division, Saha Institute of
Nuclear Physics, Kolkata, India.

REFERENCE: FEMS Microbiol Lett 2006 Mar 256(1):75-82

Abstract Expression of Leishmania donovani cyclin 1 (LdCyc1) mRNA during
 the cell cycle of promastigotes is S-phase specific. Here, we show that
 the LdCyc1 protein is periodically expressed and the activity of its 
associated kinase varies during the cell cycle in line with its 
expression pattern. In addition, we have shown that LdCRK3, homologous 
to CRK3 from L. mexicana, is the cognate Cdk partner of LdCyc1 and that 
the activity of the complex is inhibited specifically by heat stable 
factor(s) from the parasite.

PMID: 16495525

TITLE: Antigen-Responsive CD4+ T Cells from C3H Mice Chronically Infected with
Leishmania amazonensis Are Impaired in the Transition to an Effector

AUTHORS: Amanda E Ramer, Yannick F Vanloubbeeck, Douglas E Jones

AFFILIATION: Department of Veterinary Pathology, College of Veterinary Medicine,
Iowa State University, Ames, IA 50011-1250. jonesdou at iastate.edu.

REFERENCE: Infect Immun 2006 Mar 74(3):1547-54

C3HeB/FeJ mice challenged with Leishmania major develop a polarized Th1 
response and subsequently heal, whereas Leishmania amazonensis challenge
 leads to chronic lesions with high parasite loads at 10 weeks 
postinfection. In this study, a comparison of draining lymph node cells 
from L. amazonensis- and L. major-infected mice at 10 weeks 
postinfection showed equivalent percentages of effector/memory phenotype
 CD44(hi) CD4(+) T cells producing interleukin-2 (IL-2) and 
proliferating after antigen stimulation. However, these cells isolated 
from L. amazonensis-infected mice were not skewed toward either a Th1 or
 Th2 phenotype in vivo, as evidenced by their unbiased Th1/Th2 
transcription factor mRNA profile. In vivo antigen stimulation with 
added IL-12 failed to enhance gamma interferon (IFN-gamma) production of
 CD4(+) T cells from L. amazonensis-infected mice. Antigen stimulation 
of CD4(+) T cells from L. amazonensis-infected mice in vitro in the 
presence of IL-12 resulted in production of only 10 to 15% of the IFN-
gamma produced by T cells from L. major-infected mice under identical 
conditions. These results suggest that the CD4(+) T-cell response during
 chronic L. amazonensis infection is limited during the transition from 
an early activated CD4(+) T-cell population to an effector cell 
population and demonstrate that these T cells have an intrinsic defect 
beyond the presence or absence of IL-12 during antigen stimulation.

PMID: 16501815

TITLE: Glutathione and the redox control system trypanothione/trypanothione
reductase are involved in the protection of Leishmania spp. against
nitrosothiol-induced cytotoxicity.

AUTHORS: P R T Romão, J Tovar, S G Fonseca, R H Moraes, A K Cruz, J S
Hothersall, A A Noronha-Dutra, S H Ferreira, F Q Cunha

AFFILIATION: Laboratório de Imunoparasitologia, Curso de Medicina, Universidade
do Sul de Santa Catarina (UNISUL), Tubarão, SC, Brasil.

REFERENCE: Braz J Med Biol Res 2006 Mar 39(3):355-63

Glutathione is the major intracellular antioxidant thiol protecting 
mammalian cells against oxidative stress induced by oxygen- and nitrogen
-derived reactive species. In trypanosomes and leishmanias, 
trypanothione plays a central role in parasite protection against 
mammalian host defence systems by recycling trypanothione disulphide by 
the enzyme trypanothione reductase. Although Kinetoplastida parasites 
lack glutathione reductase, they maintain significant levels of 
glutathione. The aim of this study was to use Leishmania donovani 
trypanothione reductase gene mutant clones and different Leishmania 
species to examine the role of these two individual thiol systems in the
 protection mechanism against S-nitroso-N-acetyl-D,L-penicillamine (SNAP
), a nitrogen-derived reactive species donor. We found that the 
resistance to SNAP of different species of Leishmania was inversely 
correlated with their glutathione concentration but not with their total
 low-molecular weight thiol content (about 0.18 nmol/10(7) parasites, 
regardless Leishmania species). The glutathione concentration in L. 
amazonensis, L. donovani, L. major, and L. braziliensis were 0.12, 0.10
, 0.08, and 0.04 nmol/10(7) parasites, respectively. L. amazonensis, 
that have a higher level of glutathione, were less susceptible to SNAP (
30 and 100 microM). The IC50 values of SNAP determined to L. amazonensis
, L. donovani, L. major, and L. braziliensis were 207.8, 188.5, 160.9, 
and 83 microM, respectively. We also observed that L. donovani mutants 
carrying only one trypanothione reductase allele had a decreased 
capacity to survive (~40%) in the presence of SNAP (30-150 microM). In 
conclusion, the present data suggest that both antioxidant systems, 
glutathione and trypanothione/trypanothione reductase, participate in 
protection of Leishmania against the toxic effect of nitrogen-derived 
reactive species.

PMID: 16407198

TITLE: The Structure of Leishmania mexicana ICP Provides Evidence for Convergent
Evolution of Cysteine Peptidase Inhibitors.

AUTHORS: Brian O Smith, Nichola C Picken, Gareth D Westrop, Krystyna Bromek,
Jeremy C Mottram, Graham H Coombs

AFFILIATION: Divisions of Biochemistry and Molecular Biology, Infection and

REFERENCE: J Biol Chem 2006 Mar 281(9):5821-8

Clan CA, family C1 cysteine peptidases (CPs) are important virulence 
factors and drug targets in parasites that cause neglected diseases. 
Natural CP inhibitors of the I42 family, known as ICP, occur in some 
protozoa and bacterial pathogens but are absent from metazoa. They are 
active against both parasite and mammalian CPs, despite having no 
sequence similarity with other classes of CP inhibitor. Recent data 
suggest that Leishmania mexicana ICP plays an important role in host-
parasite interactions. We have now solved the structure of ICP from L. 
mexicana by NMR and shown that it adopts a type of immunoglobulin-like 
fold not previously reported in lower eukaryotes or bacteria. The 
structure places three loops containing highly conserved residues at one
 end of the molecule, one loop being highly mobile. Interaction studies 
with CPs confirm the importance of these loops for the interaction 
between ICP and CPs and suggest the mechanism of inhibition. Structure-
guided mutagenesis of ICP has revealed that residues in the mobile loop 
are critical for CP inhibition. Data-driven docking models support the 
importance of the loops in the ICP-CP interaction. This study provides 
structural evidence for the convergent evolution from an immunoglobulin 
fold of CP inhibitors with a cystatin-like mechanism.

PMID: 16492365

TITLE: Long-term preservation of Leishmania donovani promastigotes on blood-agar

AUTHORS: M Muniaraj, A K Gupta, S Narayan, D Singh, P K Sinha, P Das

AFFILIATION: Rajendra Memorial Research Institute of Medical Sciences (Indian
Council of Medical Research), Agam Kuan, Patna - 800 007, India.

REFERENCE: Ann Trop Med Parasitol 2006 Mar 100(2):173-5

PMID: 16362336

TITLE: Antibodies against Leishmania cross-react with Crithidia luciliae:
indirect immunofluorescence and Dot-ELISA study in dogs.

AUTHORS: Franjo Martinkovic, Albert Marinculic

AFFILIATION: Department of Parasitology and Parasitic Diseases, Veterinary
Faculty, University of Zagreb, Heinzelova 55, 10000, Zagreb, Croatia,
q_franjo at yahoo.com.

REFERENCE: Parasitol Res 2006 Mar 98(4):378-80

Leismaniasis is zoonotic parasitic disease distributed in many areas of 
Mediterranean basin. Because of its pathogenicity and difficulty to grow
 in vitro, we used Leishmania infantum as primary and Crithidia luciliae
 as secondary source of antigen. We compared 100 canine sera by indirect
 immunofluorescence and Dot-ELISA. Both atigens showed same results.

PMID: 16489748

TITLE: Structural differences in triosephosphate isomerase from different
species and discovery of a multitrypanosomatid inhibitor.

AUTHORS: Vanesa Olivares-Illana, Ruy Pérez-Montfort, Francisco
López-Calahorra, Miguel Costas, Adela Rodríguez-Romero, Marieta Tuena de
Gómez-Puyou, Armando Gómez Puyou

AFFILIATION: Instituto de Fisiología Celular, Facultad de Química, and
Instituto de Química, Universidad Nacional Autónoma de México, México, D.
F., México, and Departamento de Química Orgánica, Universidad de Barcelona,
Marti i Franqués 1-11, 08028 Barcelona, Spain.

REFERENCE: Biochemistry 2006 Feb 45(8):2556-60

We examined the interfaces of homodimeric triosephosphate isomerase (TIM
) from eight different species. The crystal structures of the enzymes 
showed that a portion of the interface is markedly similar in TIMs from 
Trypanosoma cruzi (TcTIM), Trypanosoma brucei, and Leishmania mexicana 
and significantly different from that of TIMs from human, yeast, chicken
, Plasmodium falciparum, and Entamoeba histolytica. Since this 
interfacial region is central in the stability of TcTIM, we hypothesized
 that it would be possible to find agents that selectively affect the 
stability of TIMs from the three trypanosomatids. We found that 6,6'-
bisbenzothiazole-2,2' diamine in the low micromolar range causes a 
desirable irreversible inactivation of the enzymes from the three 
trypanosomatids and has no effect on the other five TIMs. Thus, the data
 indicate that it is possible to find compounds that induce selective 
inactivation of the enzymes from three different trypanosomatids.

PMID: 16502255

TITLE: Heat-induced programmed cell death in Leishmania infantum is reverted by
Bcl-X(L) expression.

AUTHORS: J F Alzate, A Alvarez- Barrientos, V M González, A Jiménez-Ruiz

AFFILIATION: Departamento de Bioquímica y Biología Molecular, Campus
Universitario, Universidad de Alcalá, 28871, Alcalá de Henares, Madrid,

REFERENCE: Apoptosis 2006 Feb 11(2):161-71

An increasing number of reports indicate that single-celled organisms 
are able to die following what seems to be an ordered program of cell 
death with strong similarities to apoptosis from higher eukaryotes. DNA 
degradation and several other apoptotic-like processes have also been 
described in the parasitic protozoa Leishmania. However, the existence 
of an apoptotic death in this parasite is still a matter of controversy
. Our results indicate that most of the processes of macromolecular 
degradation and organelle dysfunction observed in mammalian cells during
 apoptosis can also be reproduced in promastigotes of the genus 
Leishmania when incubated at temperatures above 38 degrees C. These 
processes can be partially reversed by the expression of the anti-
apoptotic mammalian gene Bcl-X(L), which suggests that this family of 
apoptosis-regulating proteins was present very early in the evolution of
 eukaryotic cells.

PMID: 16488884

TITLE: Differential induction of Leishmania donovani bi-subunit topoisomerase
I-DNA cleavage complex by selected flavones and camptothecin: activity of
flavones against camptothecin-resistant topoisomerase I.

AUTHORS: Benu Brata Das, Nilkantha Sen, Amit Roy, Somdeb Bose Dasgupta, Agneyo
Ganguly, Bikash Chandra Mohanta, Biswanath Dinda, Hemanta K Majumder

AFFILIATION: Department of Molecular Parasitology, Indian Institute of Chemical
Biology, 4, Raja S.C Mullick Road, Kolkata 700032, India.

REFERENCE: Nucleic Acids Res 2006  34(4):1121-32

Emergence of the bi-subunit topoisomerase I in the kinetoplastid family
 (Trypanosoma and Leishmania) has brought a new twist in topoisomerase 
research related to evolution, functional conservation and preferential 
sensitivities to the specific inhibitors of type IB topoisomerase family
. In the present study, we describe that naturally occurring flavones 
baicalein, luteolin and quercetin are potent inhibitors of the 
recombinant Leishmania donovani topoisomerase I. These compounds bind to
 the free enzyme and also intercalate into the DNA at a very high 
concentration (300 microM) without binding to the minor grove. Here, we 
show that inhibition of topoisomerase I by these flavones is due to 
stabilization of topoisomerase I-DNA cleavage complexes, which 
subsequently inhibit the religation step. Their ability to stabilize the
 covalent topoisomerase I-DNA complex in vitro and in living cells is 
similar to that of the known topoisomerase I inhibitor camptothecin (CPT
). However, in contrast to CPT, baicalein and luteolin failed to inhibit
 the religation step when the drugs were added to pre-formed enzyme 
substrate binary complex. This differential mechanism to induce the 
stabilization of cleavable complex with topoisomerase I and DNA by these
 selected flavones and CPT led us to investigate the effect of baicalein
 and luteolin on CPT-resistant mutant enzyme LdTOP1Delta39LS lacking 1-
39 amino acids of the large subunit [B. B. Das, N. Sen, S. B. Dasgupta, 
A. Ganguly and H. K. Majumder (2005) J. Biol. Chem. 280, 16335-16344]. 
Baicalein and luteolin stabilize duplex oligonucleotide cleavage with 
LdTOP1Delta39LS. This observation was further supported by the 
stabilization of in vivo cleavable complex by baicalein and luteolin 
with highly CPT-resistant L.donovani strain. Taken together, our data 
suggest that the interacting amino acid residues of topoisomerase I may 
be partially overlapping or different for flavones and CPT. This study 
illuminates new properties of the flavones and provide additional 
insights into the ligand binding properties of L.donovani topoisomerase 

PMID: 16391494

TITLE: Diterpenoid alkaloid derivatives as potential chemotherapeutic agents in
american trypanosomiasis.

AUTHORS: Patricia González, Clotilde Marín, Isabel Rodríguez-González,
Antonio Illana, Hector Mateo, Silvia Stefánia Longoni, María Jose Rosales,
Azucena González-Coloma, Matías Reina, Manuel Sánchez-Moreno

AFFILIATION: Departamento de Parasitología, Instituto de Biotecnología,
Facultad de Ciencias, Universidad de Granada, Granada, España.

REFERENCE: Pharmacology 2006  76(3):123-8

The use of natural products for the treatment of protozoal infections (
Leishmania and Trypanosoma spp.) is well known and has been documented 
since ancient times. We have already established an in vitro culture 
system using mammalian host cells (Vero) infected with Trypanosoma cruzi
 in which the time course of parasite growth is determined 
quantitatively. This system was used to screen anti-T. cruzi agents 
using two experimental models: simultaneous cell infection and compound 
addition or preincubation of the parasite with the test compound prior 
to cell infection. Among 64 diterpenoid alkaloids tested, including C(19
) and C(20) skeletons, five C(20) compounds were active on T. cruzi 
epimastigotes: azitine, isoazitine and 15,22-O-diacetyl-19-
oxodihydroatisine had moderate effects on the parasite, while atisinium 
chloride and 13-oxocardiopetamine were potent T. cruzi epimastigote 
growth inhibitors with activity levels similar to that of benznidazole, 
used as the reference drug. Additionally, these compounds decreased the 
ability of metacyclic forms to invade mammalian cells, their 
intracellular replications and their transformation into trypomastigotes
, with no toxicity to the host cell. These results suggest that these 
alkaloids are structural leads of clinically active compounds against T
. cruzi and probably other members of the Trypanosomatidae. Copyright (c
) 2006 S. Karger AG, Basel.

PMID: 16300859

TITLE: Synthesis and leishmanicidal activities of

AUTHORS: Alice M R Bernardino, Adriana O Gomes, Karen S Charret, Antônio C C
Freitas, Gérzia M C Machado, Marilene M Canto-Cavalheiro, Leonor L Leon,
Veronica F Amaral

AFFILIATION: Departamento de Química Orgânica, Instituto de Química, Programa
de Pós-graduação em Química Orgânica, Universidade Federal Fluminense,
Outeiro de São João Baptista, CEP 24020-150, Niterói, RJ, Brazil.

REFERENCE: Eur J Med Chem 2006 Jan 41(1):80-7

1H-pyrazole-4-carbohydrazides were synthesized and their leishmanicidal 
in vitro activities and cytotoxic effects were investigated. The drugs 
prototypes of these new compounds (ketoconazole, benznidazole, 
allopurinol and pentamidine) were also tested. It was found that among 
all the 1H-pyrazole-4-carbohydrazides derivatives examined, the most 
active compounds were those with X=Br, Y=NO(2) (27) and X=NO(2,) Y=Cl (
15) derivatives which showed to be most effective on promastigotes forms
 of L. amazonensis than on L. chagasi and L. braziliensis species. When 
tested against murine peritoneal macrophages as mammalian host cell 
controls of toxicity, 1-(4-Br-phenyl)-N'-[(4-NO(2)-phenyl)methylene]-1H-
pyrazole-4-carbohydrazides (27) (EC(50)=50 microM l(-1)) and 1-(4-NO(2)-
phenyl)-N'-[(4-Cl-phenyl)methylene]-1H-pyrazole-4-carbohydrazides (15) 
EC(50)=80 microM l(-1))] was reasonably toxic. However, both compounds 
were less toxic than pentamidine and ketoconazole. These results provide
 new perspectives on the development of drugs with activities against 
Leishmania parasite.

PMID: 16409282

TITLE: Comparing the efficiency of topical paromomycin with intralesional
meglumine antimoniate for cutaneous leishmaniasis.

AUTHORS: Zahra Moosavi, Abdolhamid Nakhli, Sima Rassaii

REFERENCE: Int J Dermatol 2005 Dec 44(12):1064-5

PMID: 16154349

TITLE: Protozoan parasite-specific carbohydrate structures.

AUTHORS: Lucia Mendonça-Previato, Adriane Regina Todeschini, Norton Heise, Jose
Osvaldo Previato

AFFILIATION: Laboratório de Glicobiologia, Instituto de Biofísica Carlos
Chagas Filho, Centro de Ciências da Saúde-Bloco G, Universidade Federal do
Rio de Janeiro, Cidade Universitária, 21 944 970, Rio de Janeiro, Brasil.
luciamp at biof.ufrj.br

REFERENCE: Curr Opin Struct Biol 2005 Oct 15(5):499-505

The carbohydrate moieties displayed by pathogenic protozoan parasites 
exhibit many unusual structural features and their expression is often 
developmentally regulated. These unique structures suggest a specific 
relationship between such carbohydrates and parasite pathogenicity. 
Studies of infected humans indicate that immune responses to protozoan 
parasites are elicited by glycan determinants on cell-surface or 
secreted molecules. Infections by protozoa are a major worldwide health 
problem, and no vaccines or efficacious treatments exist to date. Recent
 progress has been made in elucidating the structure and function of 
carbohydrates displayed by major protozoan parasites that infect man. 
These structures can be used as prototypes for the chemical or combined 
chemo-enzymatic synthesis of new compounds for diagnosis and vaccine 
development, or as inhibitors specifically designed to target parasite 
glycan biosynthesis.

PMID: 16046170

TITLE: Visceral leishmaniasis in organ transplant recipients: 11 new cases and a
review of the literature.

AUTHORS: Didier Basset, Françoise Faraut, Pierre Marty, Jacques Dereure, Eric
Rosenthal, Charles Mary, Francine Pratlong, Laurence Lachaud, Patrick Bastien,
Jean-Pierre Dedet

AFFILIATION: Laboratoire de Parasitologie-Mycologie and Centre National de
Référence des Leishmania, CHU de Montpellier, 163, rue Auguste-Broussonet,
34090 Montpellier, France.

REFERENCE: Microbes Infect 2005 Oct 7(13):1370-5

Eleven new cases of visceral leishmaniasis (VL) are reported in organ 
transplant patients in France. The epidemiological, clinical, biological
, diagnostic and therapeutic features are reviewed, based on these cases
 and 46 cases reported in the literature. VL was most commonly 
associated with renal transplantation (77% of the cases). Most patients 
were from Southern European countries. The main clinical symptom was 
fever. Leucopoenia and anaemia were the most frequent haematological 
disorders. Diagnosis was by direct finding of the parasite in smears of 
bone marrow (85.2%) or, by positive serology (90.9%). Without 
antileishmanial treatment, VL in transplant recipients was fatal. 
Treatment using either antimonials or amphotericine B gave similar cure 
rates of around 80% of the cases. But toxicity was higher for 
antimonials. Relapses occurred in 14.3%.


 The following references are revised files and are brought to you in accordance
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PMID: 11472257

TITLE: Trypanothione as a target in the design of antitrypanosomal and
antileishmanial agents.

AUTHORS: K Augustyns, K Amssoms, A Yamani, P K Rajan, A Haemers

AFFILIATION: Department of Medicinal Chemistry, University of Antwerp (UIA),
Universiteitsplein, Los Antwerpen, B-2610, Belgium.
Koen.Augustyns at uia.ua.ac.be

REFERENCE: Curr Pharm Des 2001 Aug 7(12):1117-41

Trypanothione is the key molecule in the defence mechanism of 
Trypanosoma and Leishmania against oxidative stress. The uniqueness of 
trypanothione makes the metabolism of this molecule an attractive target
 in antitrypanosomal and antileishmanial drug design. It became clear 
that this antioxidant cascade can be considered as the "Achilles 
heel" of these parasites. The following targets and their 
respective inhibitors will be discussed: biosynthesis of trypanothione 
with glutathionylspermidine synthetase and trypanothione synthetase; 
biosynthesis of glutathione with gamma-glutamylcysteine synthetase; 
biosynthesis of spermidine with ornithine decarboxylase; trypanothione 
hydroperoxide metabolism with tryparedoxine peroxidase, tryparedoxine 
and trypanothione reductase.

REQUEST: [ sand fly ]

(2 articles match this request. 2 articles matching other requests removed)

REQUEST: [ sandfly ]

(1 article matches this request)

PMID: 16501757

TITLE: [Evaluation of sandfly control in Lobato municipality, Paraná State,
southern Brazil.]

AUTHORS: Ueslei Teodoro, Demilson Rodrigues Dos Santos, Ademar Rodrigues Dos
Santos, Otílio de Oliveira, Elcio Silvestre Dos Santos, Herintha Coeto
Neitzke, Wuelton Marcelo Monteiro, Robson Marcelo Rossi, Maria Valdrinez
Campana Lonardoni, Thaís Gomes Verzignassi Silveira

AFFILIATION: Departamento de Análises Clínicas, Universidade Estadual de
Maringá, Maringá, Brasil.

REFERENCE: Cad Saude Publica 2006 Feb 22(2):451-5

Sandfly control measures were evaluated at the Da Barra Ranch, Lobato 
municipality, Paraná State, Brazil. The insects were captured with Falc
ão traps in houses, a cattle corral, and a forest area from July to 
November 1999 and from February to June 2000. In December 1999 and 
January 2000 the following measures were taken to decrease the sandfly 
density in peridomiciliary areas and domiciles: (i) screens were placed 
on windows of buildings (domiciles, dormitory, cafeteria); (ii) all 
organic material was cleaned from the peridomiciliary area; and (iii) 
buildings were sprayed for insects. There were more Nyssomyia whitmani, 
Pintomyia fischeri, P. monticola, and Brumptomyia brumpti specimens in 
the former period, while N. neivai, Migonemyia migonei, and N. pessoai 
predominated in the latter. In the initial period most of the sandflies 
were captured in the forest and in the latter period in the houses. The 
sandfly control measures did not reduce the sandfly population on the Da
 Barra Ranch, but they led to significant proportional changes in the 
insect fauna composition.

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