[Leish-l] Articles found by RefScout 2006/03/01 2006/09
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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,
Iran.
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
leishmaniasis.
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
leishmaniasis.
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 DaÄlar
AFFILIATION: Department of Pediatrics, Sami Ulus Children's Hospital, Ankara,
Turkey.
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
Yilmaz
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,
Portugal.
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
dapsone.
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 BrasÃlia, BrasÃlia,
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 LuÃs, 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)
amazonensis.]
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
BrasÃlia, BrasÃlia, 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
carbapenems.
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,
Brazil.
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 CecÃlia 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 MunicÃpio 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.
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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,
USA.
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-MartÃnez, M Campillo, I L
Bazzocchi, L Pardo, A G Ravelo, S Castanys, F Gamarro
AFFILIATION: Instituto de ParasitologÃa y Biomedicina López-Neyra, Consejo
Superior de Investigaciones CientÃficas, 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 BiofÃsica 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
future.
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
activities.
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
Phenotype.
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
Immunity.
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
slants.
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 RodrÃguez-Romero, Marieta Tuena de
Gómez-Puyou, Armando Gómez Puyou
AFFILIATION: Instituto de FisiologÃa Celular, Facultad de QuÃmica, and
Instituto de QuÃmica, Universidad Nacional Autónoma de México, México, D.
F., México, and Departamento de QuÃmica 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 BioquÃmica y BiologÃa Molecular, Campus
Universitario, Universidad de Alcalá, 28871, Alcalá de Henares, Madrid,
Spain.
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
I.
PMID: 16391494
TITLE: Diterpenoid alkaloid derivatives as potential chemotherapeutic agents in
american trypanosomiasis.
AUTHORS: Patricia González, Clotilde MarÃn, Isabel RodrÃguez-González,
Antonio Illana, Hector Mateo, Silvia Stefánia Longoni, MarÃa Jose Rosales,
Azucena González-Coloma, MatÃas Reina, Manuel Sánchez-Moreno
AFFILIATION: Departamento de ParasitologÃa, Instituto de BiotecnologÃa,
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
1-(4-X-phenyl)-N'-[(4-Y-phenyl)methylene]-1H-pyrazole-4-carbohydrazides.
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 QuÃmica Orgânica, Instituto de QuÃmica, Programa
de Pós-graduação em QuÃmica 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 BiofÃsica 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
to license agreement with the NLM.
********************************************************************************************************************
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, OtÃlio de Oliveira, Elcio Silvestre Dos Santos, Herintha Coeto
Neitzke, Wuelton Marcelo Monteiro, Robson Marcelo Rossi, Maria Valdrinez
Campana Lonardoni, ThaÃs Gomes Verzignassi Silveira
AFFILIATION: Departamento de Análises ClÃnicas, 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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