[leish-l] Fwd: Articles found by RefScout 15/04/05 - 15/2005

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    Date: Fri, 15 Apr 2005 06:47:11
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This is RefScout-Newsletter 15/2005

REQUEST: [ leishmaniasis ]

(34 articles match this request. 4 articles matching other requests removed)

PMID: 15808423

TITLE: Therapeutic use of quercetin in the control of infection and anemia
associated with visceral leishmaniasis.

AUTHORS: Gargi Sen, Suparna Mandal, Sudipa Saha Roy, Sibabrata Mukhopadhyay,
Tuli Biswas

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

REFERENCE: Free Radic Biol Med 2005 May 38(9):1257-64

Flavonoids are a broad class of plant phenolics that are known to 
possess a well-established protective effect against membrane 
lipoperoxidative damages. Oxidative damage of erythrocytes has been 
implicated in the reduced survival of erythrocytes during leishmanial 
infection. This study reveals the efficacy of five naturally occurring 
flavonoids in arresting the development of anemia during the 
postinfection period. Among the compounds studied, quercetin was most 
successful in inhibiting the oxidation of proteins and lipids on the red
 cell membranes of infected animals. Apart from its antianemic property
, quercetin also seemed to be highly potent in lowering the parasite 
load in the spleen. Combination therapy of quercetin with the 
antileishmanial drug stibanate produced a better decay of ()OH in the 
erythrocytes of the infected animals compared to that induced by 
quercetin or drug treatment alone. Similar results were obtained in 
successful prevention of proteolytic degradation resulting in an 
aversion to early lysis of red cells after simultaneous treatment with 
quercetin and stibanate. Subsequent studies demonstrated the therapeutic
 efficacy of the combination treatment in the abatement of both anemia 
and parasitemia under the diseased condition.

PMID: 15811527

TITLE: Novobiocin induces apoptosis-like cell death in topoisomerase II
over-expressing arsenite resistant Leishmania donovani.

AUTHORS: Gaganmeet Singh, K G Jayanarayan, Chinmoy S Dey

AFFILIATION: Department of Biotechnology, National Institute of Pharmaceutical
Education and Research, Sec. 67, S.A.S. Nagar, Punjab 160062, India.

REFERENCE: Mol Biochem Parasitol 2005 May 141(1):57-69

Leishmaniasis affects millions of people worldwide every year. Lack of 
effective vaccination, co-infection with other dreaded diseases like 
AIDS and generation of drug resistant strains demand immediate attention
 into this neglected area of research. The sodium m-arsenite (NaAsO(2)) 
resistant Leishmania donovani used in this study is resistant to 20muM 
NaAsO(2), which shows a 13-fold increase in resistance compared with 
wild type. Here we report that the arsenite resistant strain of L. 
donovani promastigotes shows cross-resistance to novobiocin, a catalytic
 inhibitor of topoisomerase II, with IC(50) value of 320mugml(-1) as 
compared with 242mugml(-1) for wild type L. donovani. Leishmanicidal 
action of novobiocin induces dose- and time-dependent increase in cell 
death. Treatment with IC(50) of novobiocin caused morphological and 
biochemical changes which lead to induction of cell death exhibiting 
characteristic features of metazoan apoptosis. Phosphatidylserine 
externalization, cytochrome C release to cytoplasm, activation of 
caspases, oligonucleosomal DNA fragmentation and in situ labelling of 
condensed and fragmented nuclei in both wild type and arsenite resistant
 L. donovani promastigotes strongly suggest the apoptosis-like mode of 
cell death. Cross-resistance to novobiocin in arsenite resistant strain 
has been correlated to over-expression of topoisomerase II and 
substantiated by differential inhibition of enzyme activity in wild type
 and arsenite resistant L. donovani.

PMID: 15819858

TITLE: Cutaneous leishmaniasis: an increasing threat for travellers.

AUTHORS: S Antinori, E Gianelli, S Calattini, E Longhi, M Gramiccia, M

AFFILIATION: Istituto di Malattie Infettive e Tropicali, Università di Milano,

REFERENCE: Clin Microbiol Infect 2005 May 11(5):343-6

Analysis of the literature on cutaneous leishmaniasis in low-prevalence 
countries suggests an increase in imported cases that is attributable to
 the growing phenomenon of international tourism, migration and military
 operations in highly endemic regions. Cases of imported cutaneous 
leishmaniasis are often missed initially, but diagnosis can be made non-
invasively by PCR using skin scrapings of lesions as starting material. 
Cutaneous leishmaniasis is an emerging threat for travellers and should 
be considered in all patients presenting with slow-to-heal ulcers.

PMID: 15807861

TITLE: Dichotomy of protective cellular immune responses to human visceral

AUTHORS: E A G Khalil, N B Ayed, A M Musa, M E Ibrahim, M M Mukhtar, E E
Zijlstra, I M Elhassan, P G Smith, P M Kieny, H W Ghalib, F Zicker, F Modabber,
A M Elhassan

AFFILIATION: Institute of Endemic Diseases, University of Khartoum, Khartoum,

REFERENCE: Clin Exp Immunol 2005 May 140(2):349-53

Summary Healing/protective responses in human visceral leishmaniasis (VL
) are associated with stimulation/production of Th1 cytokines, such as 
interferon IFN-gamma, and conversion in the leishmanin skin test (LST). 
Such responses were studied for 90 days in 44 adult healthy volunteers 
from VL non-endemic areas, with no past history of VL/cutaneous 
leishmaniasis (CL) and LST non-reactivity following injection with one 
of four doses of Alum-precipitated autoclaved Leishmania major (Alum/ALM
) +/- bacille Calmette-Guerin (BCG), a VL candidate vaccine. The vaccine
 was well tolerated with minimal localized side-effects and without an 
increase in antileishmanial antibodies or interleukin (IL)-5. Five 
volunteers (5/44; 11.4%) had significant IFN-gamma production by 
peripheral blood mononuclear cells (PBMCs) in response to Leishmania 
antigens in their prevaccination samples (P = 0.001) but were LST non-
reactive. On day 45, more than half the volunteers (26/44; 59.0%) had 
significantly high LST indurations (mean 9.2 +/- 2.7 mm) and high IFN-
gamma levels (mean 1008 +/- 395; median 1247 pg/ml). Five volunteers had
 significant L. donovani antigen-induced IFN-gamma production (mean 873
 +/- 290; median 902; P = 0.001), but were non-reactive in LST. An 
additional five volunteers (5/44; 11.4%) had low IFN-gamma levels (mean 
110 +/- 124 pg/ml; median 80) and were non-reactive in LST (induration
 = 00 mm). The remaining eight volunteers had low IFN-gamma levels, but 
significant LST induration (mean 10 +/- 2.9 mm; median 11). By day 90 
the majority of volunteers (27/44; 61.4%) had significant LST induration
 (mean 10.8 +/- 9.9 mm; P < 0.001), but low levels of L. donovani 
antigen-induced IFN-gamma (mean 66.0 +/- 62 pg/ml; P > 0.05). Eleven 
volunteers (11/44; 25%) had significantly high levels of IFN-gamma and 
LST induration, while five volunteers had low levels of IFN-gamma (<
100 pg/ml) and no LST reactivity (00 mm). One volunteer was lost to 
follow-up. In conclusion, it is hypothesized that cellular immune 
responses to human VL are dichotomatous, and that IFN-gamma production 
and the LST response are not in a causal relationship. Following 
vaccination and probably cure of VL infection, the IFN-gamma response 
declines with time while the LST response persists. LST is a simple test
 that can be used to assess candidate vaccine efficacy.

PMID: 15817953

TITLE: Diagnosis & management of leishmania/HIV co-infection.

AUTHORS: P K Sinha, K Pandey, S K Bhattacharya

AFFILIATION: Rajendra Memorial Research Institute of Medical Sciences
(ICMR)Patna, India.

REFERENCE: Indian J Med Res 2005 Apr 121(4):407-14

Leishmaniasis, a globally prevalent parasitic disease occurs in three 
forms viz., visceral, cutaneous and mucocutaneous, transmitted by the 
bite of infected female Phlebotomus sandflies. Visceral leishmaniasis (
VL) has 100 per cent fatality rate, if left untreated. India has the 
largest burden of this disease. HIV infection is also increasing 
worldwide and several reports indicate rising trend of VL/ HIV co-
infection, modifying the traditional anthroponotic pattern of VL 
transmission. Both VL and HIV tend to lower the cell mediated immunity (
CMI) resulting in poor drug response and opportunistic infections 
involving gastrointestinal, cutaneous, respiratory tract and central 
nervous system (CNS) may occur. Diagnosis of such co-infected cases is 
quite difficult. However, newer tests like nested PCR, rk39 
immunochromatographic test etc., can be of help. Response to different 
antileishmanial drugs like sodium antimony gluconate (SAG), amphotericin
 B is far from satisfactory. However, a new oral drug miltefosine has 
been found to be promising. Highly active antiretroviral therapy (HAART
) need to be given for management of HIV infection along with treatment 
of other opportunistic infections.

PMID: 15817202

TITLE: Osteolytic osteomyelitis associated with visceral leishmaniasis in a

AUTHORS: Alda Izabel de Souza, Raquel Soares Juliano, Tatiana Scanoni Gomes,
Soraia de Araujo Diniz, Alan Maia Borges, Wagner Luiz Tafuri, Renato de Lima

AFFILIATION: Curso de Medicina Veterinária, Centro de Ciências Biológicas,
Agrárias e da Saúde (CCBAS), Universidade para o Desenvolvimento do Estado e
da Região do Pantanal (UNIDERP), Rua Alexandre Herculano 1400, 79037-280 Campo
Grande, MS, Brazil.

REFERENCE: Vet Parasitol 2005 Apr 129(1-2):51-4

A dog was examined with a history of weight loss and lameness of the 
left hind limb. A painful response to examination of the left hip joint
, and lymphadenopathy were noted. Amastigote forms of Leishmania sp. 
were observed by cytology in samples from the popliteus lymph node, and 
anti-Leishmania sp. antibodies at a titer of 1:640 were detected in 
serum by indirect immunofluorescence. Radiological changes included 
osteolysis and a periosteal proliferative reaction in the left femoral 
greater trochanter. These changes were histologically characterized as 
an osteolytic granulomatous osteomyelitis associated with amastigotes 
within macrophages. Non-decalcified fragments of the periosteum were 
processed for immunohistochemistry, observed with prominent 
immunolabelling of amastigotes of Leishmania sp. within macrophages. The
 diagnosis was further confirmed by positive PCR for Leishmania sp., 
belonging to the Leishmania donovani complex.

PMID: 15814719

TITLE: Prevention of relapse after chemotherapy in a chronic intracellular
infection: mechanisms in experimental visceral leishmaniasis.

AUTHORS: Henry W Murray

AFFILIATION: Department of Medicine, Weill Medical College of Cornell
University, New York, NY 10021.

REFERENCE: J Immunol 2005 Apr 174(8):4916-23

In visceral leishmaniasis, chemotherapy probably seldom eradicates all 
parasites in tissue macrophages; nevertheless, most T cell-intact 
patients show long-lasting clinical cure after treatment despite 
residual intracellular infection. To characterize prevention of 
posttreatment relapse, amphotericin B was used to kill approximately 90-
95% of Leishmania donovani in livers of mice deficient in mechanisms of 
acquired antileishmanial resistance. Recrudescence subsequently 
developed 1) in animals deficient in both CD4 and CD8 T cells as well as
 CD40L-mediated T cell costimulation, but not in a) CD4 or CD8 cells 
alone, b) NK cell lytic activity, or c) ICAM-1-recruited monocytes; and 
2) in mice deficient in IFN-gamma, but not in the IFN-gamma-inducing 
cytokines, a) IL-12, b) IL-12 and IL-23, or c) IL-18. Posttreatment 
recrudescence also did not develop in animals deficient in macrophage 
phagocyte NADPH oxidase (phox) or inducible NO synthase (iNOS) alone or
, surprisingly, in those deficient in both phox and iNOS. Therefore, 
regulation of the intracellular replication of residual Leishmania 
donovani that escape chemotherapy evolves to a host mechanism 
distinguishable from initial acquired resistance at the T cell, cytokine
, and macrophage levels. Posttreatment, either CD8 or CD4 cells can 
direct the response, IL-12 is not required, and iNOS and phox, the 
activated macrophage's primary IFN-gamma-inducible leishmanicidal 
pathways, both become dispensable.

PMID: 15811095

TITLE: Changing geography of cutaneous leishmaniasis in the Indian subcontinent
and in neighboring Arab states.

AUTHORS: Virendra N Sehgal

REFERENCE: Int J Dermatol 2005 Apr 44(4):344

PMID: 15756639

TITLE: Impaired Th1 responses in mice deficient in Epstein-Barr virus-induced
gene 3 and challenged with physiological doses of Leishmania major.

AUTHORS: Sabine Zahn, Stefan Wirtz, Mark Birkenbach, Richard S Blumberg, Markus
F Neurath, Esther von Stebut

AFFILIATION: Department of Dermatology, Johannes Gutenberg-University of Mainz,
Mainz, Germany.

REFERENCE: Eur J Immunol 2005 Apr 35(4):1106-12

Protection against Leishmania major is dependent on IL-12 release from L
. major-infected dendritic cells (DC) that induce IFN-gamma-producing 
Th1/Tc1 cells. IL-27, a novel member of the IL-12 family, is a 
heterodimer composed of p28 and IL-12p40-related Epstein-Barr virus-
induced gene 3 (EBI3), and was shown to be produced by DC. In this study
, we utilized EBI3-deficient mice to investigate the role of IL-27 in 
leishmaniasis using physiological low-dose infections that mimic natural
 transmissions. Lesions in EBI3(-/-) mice were significantly larger 
between weeks 3 and 10 post infection, reaching up to approximately 
threefold increased lesion volumes compared to wild types. In parallel, 
dermal lesions of EBI3(-/-) mice contained greater parasite numbers, 
reaching a peak load that was 2-log higher than in C57BL/6 mice. However
, lesions in EBI3(-/-) and wild-type mice resolved after 12 weeks. At 
early time points, the antigen-specific cytokine response in EBI3(-/-) 
lymph nodes showed increased levels of IL-4, IL-10 and IL-13 and 
decreased IFN-gamma production. IL-27 production was restricted to the 
DC population, since the majority of EBI3 expression in lymph nodes of 
infected mice was found in CD11c(+) cells. In conclusion, our data show 
that DC-derived IL-27 is critical for the timely initiation of efficient
 anti-parasite Th1 immunity early in infections.

PMID: 15777720

TITLE: Polymerase chain reaction (PCR) is highly sensitive for diagnosis of
mucosal leishmaniasis.

AUTHORS: Jene Greyce S Oliveira, Fernanda O Novais, Camila I de Oliveira,
Antonio C da Cruz Junior, Léon Fábio Campos, Any V da Rocha, Viviane
Boaventura, Almério Noronha, Jackson M L Costa, Aldina Barral

AFFILIATION: Fundação Hospital do Acre, Rodovia BR364, km 2, Distrito
Industrial, Rio Branco, AC 69914-220, Brazil.

REFERENCE: Acta Trop 2005 Apr 94(1):55-9

We evaluated the use of polymerase chain reaction (PCR) for diagnosis of
 mucosal leishmaniasis (ML) in an endemic area in Acre, Brazil, where 
Leishmania braziliensis is present. Leishmania DNA was detected 34 of 35
 cases, yielding a positivity rate of 97.1%, which was higher than the 
positivity rates for all of the other diagnostic methods studied, namely
 Montenegro skin test (MST), anti-Leishmania serological testing and 
microscopic examination of lesion biopsy specimens. These findings have 
led us to propose guidelines for the diagnosis of ML that use PCR as the
 principal method of parasitological confirmation of cases.

PMID: 15814038

TITLE: Relative abundances of sandfly species (Diptera: Phlebotominae) in two
villages in the same area of Campeche, in southern Mexico.

AUTHORS: E A Rebollar-Téllez, E Tun-Ku, P C Manrique-Saide, F J

AFFILIATION: Centro de Investigaciones Regionales 'Dr Hideyo Noguchi',
Universidad Autónoma de Yucatán, Avenida Itzaes 490, Mérida, Yucatán 97000,

REFERENCE: Ann Trop Med Parasitol 2005 Mar 99(2):193-201

Leishmania mexicana is the parasite causing most cases of human 
cutaneous leishmaniasis in southern Mexico, where Lutzomyia olmeca 
olmeca and Lu. cruciata are the most probable vectors. In the present 
study, sandflies were collected during one transmission season (November
 2001-March 2002) in the village of La Guadalupe and the nearby village 
of Dos Naciones, in the southern Mexican county of Calakmul. Using 
Shannon traps, Disney traps and CDC light traps, 5983 sandflies (
Brumptomyia and Lutzomyia) were caught. In Dos Naciones the numbers of 
Lu. panamensis caught in Shannon or CDC traps outnumbered those of the 
other sandfly species. In La Guadalupe, in contrast, the most abundant 
species in the collections made with Shannon or CDC traps was Lu. 
cruciata , followed by Lu. olmeca olmeca and Lu. deleoni. In both 
locations, the numbers of sandflies attracted to Shannon traps peaked 
between 18.00 and 22.00 hours. Given the abundance of Lu. olmeca olmeca 
in the collections made with Shannon and Disney traps (it was the only 
species caught in the latter), this species is probably the primary 
vector of Le. mexicana in Calakmul county.

PMID: 15814048

TITLE: Visceral childhood leishmaniasis in Kagizman, eastern Turkey: a new
endemic area.

AUTHORS: Mustafa Buyukavci, Mehmet Karacan, Huseyin Tan, Recep Akdag

AFFILIATION: Department of Pediatrics, Faculty of Medicine, Ataturk University,
Erzurum, Turkey.

REFERENCE: Ann Trop Paediatr 2005 Mar 25(1):41-3

Visceral leishmaniasis is endemic in some areas of Turkey; however, it 
has not been reported previously from the eastern part of the country. 
We reviewed 21 cases of visceral leishmaniasis admitted from eastern 
Turkey, 60% of whom were from the same region, Kagizman.

PMID: 15812130

TITLE: Sodium stibogluconate and polymorphic ventricular tachycardia.

AUTHORS: Arun K Baranwal, Ravi N Mandal, Rupa Singh, Sunit C Singhi

AFFILIATION: Department of Pediatrics, B. P. Koirala Institute of Health
Sciences, Dharan, India. Baranwal1970@ yahoo.com.

REFERENCE: Indian J Pediatr 2005 Mar 72(3):269

Numerous antimicrobials including pentavalent antimonials are implicated
 in causing prolong QT-interval and ventricular tachycardia. Torsades de
 pointes is rarely documented with use of sodium stibogluconate. Here is
 described a 12-yr-old girl with visceral leishmaniasis, who developed 
syncopal attacks, prolong QT-interval, polymorphic ventricular 
tachycardia and torsades de pointes after completing a course of 
Stibogluconate (20 mg/kg/day for 30 days). Prolong lidocaine infusion 
and cardioversion were life saving.

PMID: 15716043

TITLE: Interleukin 10 receptor blockade-pentavalent antimony treatment in
experimental visceral leishmaniasis.

AUTHORS: Henry W Murray

AFFILIATION: Department of Medicine, Weill Medical College of Cornell
University, Box 136, 1300 York Avenue, NY 10021, USA.

REFERENCE: Acta Trop 2005 Mar 93(3):295-301

Interleukin 10 (IL-10), a suppressive Th2 cell-type cytokine, promotes 
disease progression in experimental visceral leishmaniasis. To extend 
testing the therapeutic effects of applying IL-10 receptor (IL-10R) 
blockade with antileishmanial chemotherapy, BALB/c mice with established
 intracellular Leishmania donovani infection were injected once with 
anti-IL-10R mAb at the time low-dose, daily pentavalent antimony (Sb) 
therapy was initiated. In this treatment model, simultaneous 
administration of anti-IL-10R enhanced overall antileishmanial activity 
in the liver in an interferon-gamma-dependent fashion, and accelerated 
the kinetics of Sb-associated killing, induced a >10-fold Sb dose-
sparing effect and shortened the required duration of Sb treatment. 
These results suggest the possibility of using mAb-induced IL-10R 
blockade to develop low-dose and/or short-course immunochemotherapeutic 
regimens in visceral leishmaniasis.

PMID: 15716050

TITLE: Cutaneous leishmaniasis associated with extensive lymphadenopathy during
an epidemic in Ceara State, northeast Brazil.

AUTHORS: Gundel Harms, Francisco Fraga, Björn Batroff, Fabíola Oliveira,
Hermann Feldmeier

AFFILIATION: Institute of Tropical Medicine, Charité University Medicine
Berlin, Spandauer Damm 130, 14050 Berlin, Germany.

REFERENCE: Acta Trop 2005 Mar 93(3):303-10

During an epidemic of cutaneous leishmaniais in northeast Brazil a 
prospective study was conducted in order to assess clinical, 
parasitological and immunological features of cutaneous leishmaniasis in
 a representative sample of patients. A general examination was done and
 demographic and anthropometric data as well as numbers, duration, 
location, size, consistency and tenderness of enlarged lymph nodes and 
lesions recorded. Hematologic and biochemical parameters as well as 
Leishmania-specific antibodies were measured in the blood. Lymph node 
aspirations were performed to detect Leishmania-specific DNA by PCR. 
Cellular immunity was assessed by a leishmanin skin test. Ninety-seven 
patients with cutaneous leishmaniasis presented with a total of 181 
lesions and 127 enlarged regional lymph nodes. In 36% the lymph node 
enlargement had been observed 2 days to 2 months before the development 
of a lesion. In 59% the lesions were followed by lymphadenopathy by 3 
days to 3 months. The skin test was positive in all patients tested. PCR
 of the lymph node aspirates was positive in 63.2%. No significant 
correlations were found between positive PCR results, antibody levels or
 number of lesions. In northeast Brazil cutaneous leishmaniasis due to 
Leishmania braziliensis is constantly accompanied by an extensive 
lymphadenopathy. This may help to identify patients when lesions are 
still small or have not even developed and lymphadenopathy is the only 
clinical sign.

PMID: 15814031

TITLE: Fatal visceral leishmaniasis, with massive bone-marrow infection, in an
immunosuppressed but HIV-negative Spanish patient, after the initiation of
treatment with meglumine antimoniate.

AUTHORS: F Garcia-Cordoba, F J Ortuño, M Segovia, G Gonzalez Diaz

AFFILIATION: Intensive Care Unit, Hospital Morales Meseguer, Marques de los
Velez s/n, E-30008, Murcia, Spain.

REFERENCE: Ann Trop Med Parasitol 2005 Mar 99(2):125-30

Although visceral leishmaniasis is often fatal in the developing world, 
Leishmania-attributable deaths in Europe are relatively rare and 
nowadays almost always linked to HIV infection. In Spain, however, a HIV
-negative man with a history of chronic obstructive pulmonary disease 
and prednisone treatment was recently hospitalized because of 
hypotension and asthenia. Although the patient was afebrile, a bone-
marrow aspirate, collected after thrombo- and leuco-cytopenia had been 
observed, was found to contain huge numbers of amastigotes. A course of 
antileishmanial treatment with meglumine antimoniate was initiated but 
the patient went into refractory shock and died within 6 h. The 
significance of this case, in terms of the routine investigation and 
treatment of immunosuppressed patients who may have leishmaniasis, is 

PMID: 15747661

TITLE: Papular-like glossitis in a dog with leishmaniosis.

AUTHORS: V Foglia Manzillo, A Pagano, O Paciello, T Di Muccio, L Gradoni, G

AFFILIATION: Dipartimento di Scienze Cliniche Veterinarie, Facoltà di Medicina
Veterinaria, Università degli Studi di Napoli Federico II, Via F. Delpino 1,
80137 Napoli, Italy.

REFERENCE: Vet Rec 2005 Feb 156(7):213-5

PMID: 15725387

TITLE: Macrophages at intermediate stage of maturation produce high levels of
IL-12 p40 upon stimulation with Leishmania.

AUTHORS: Milton A P Oliveira, Carlos E Tadokoro, Glória M C A Lima, Tainá
Mosca, Leda Q Vieira, Pieter J M Leenen, Ises A Abrahamsohn

AFFILIATION: Departamento de Imunologia, Instituto de Ciências Biomédicas,
Universidade de São Paulo, Av. Prof. Lineu Prestes 1730, CEP 05508-900, São
Paulo SP, Brazil.

REFERENCE: Microbes Infect 2005 Feb 7(2):213-23

IL-12 is one of the main cytokines driving the immune response to a 
resistant phenotype in leishmaniasis and in several other diseases 
involving intracellular microbes. In this study, we investigated IL-12 
production by mononuclear phagocytes at several developmental stages 
when stimulated with Leishmania major, L. amazonensis or L. chagasi. 
Bone marrow cells were cultured for 4-6 days in vitro in the presence of
 M-CSF, GM-CSF or IL-3. After density separation, only cells banding at 
the 40-50% Percoll interface, but not those at 20-40% or 50-80% 
interfaces, produced large amounts of IL-12 p40 when stimulated with LPS
 or live Leishmania promastigotes. However, only low levels of IL-12 p70
 were produced under these conditions. The high IL-12 p40-producing 
cells could be similarly derived from mouse strains with different 
susceptibility to Leishmania. Quantitative analysis of monocyte/
macrophage lineage marker expression, in combination with positive and 
negative selection, led to the conclusion that the high IL-12 p40-
producing cells are macrophages at an intermediate stage of maturation 
between immature and fully differentiated cells, expressing ER-HR3 but 
only low levels of the mature markers, scavenger receptor and CD11b/Mac-
1. They do not express any of the precursor markers CD31/ER-MP12, Ly-6C/
ER-MP20 or ER-MP58. Because recruitment of monocytes to an infection 
site and its draining lymph node is a general phenomenon, the notion 
that, developing from these monocytes, a population of mononuclear 
phagocytes at an intermediate maturation stage has the capacity to 
synthesize large amounts of IL-12 p40 has significant bearing on our 
understanding of immune regulation in leishmaniasis and also in 
infections by other pathogens.

PMID: 15821792

TITLE: [Prevalence of canine infection from endemic areas of American cutaneous
leishmaniasis in Paracambi District, Rio de Janeiro State, between 1992 and

AUTHORS: Ginelza Peres Lima Dos Santos, Argemiro Sanavria, Mauro Célio de
Almeida Marzochi, Elizabeth Glória Oliveira Barbosa Dos Santos, Valmir
Laurentino Silva, Raquel da Silva Pacheco, Eliame Mouta-Confort, Cleber Barreto
Espíndola, Marcos Barbosa de Souza, Cesar Santos Ponte, Nilton Francisco da
Conceição, Moacir Vieira de Andrade

AFFILIATION: Serviço de Zoonoses, Instituto de Pesquisa Clínica Evandro
Chagas, Fundação Oswaldo Cruz, Rio de Janeiro, RJ.

REFERENCE: Rev Soc Bras Med Trop 2005 Mar-Apr 38(2):161-6

In the district of Paracambi, State of Rio de Janeiro an epidemiological
 survey for American tegumentary leishmaniasis in canine population was 
carried out in endemic localities. A total of 179 dogs was registered 
and 138 (77.1%) examined for their clinical aspects, development of 
delayed hypersensitivity (DHS) with Imunoleish(R) antigen and 
serological responses by indirect immunofluorescent reaction and enzyme-
linked immunosorbent assay. In 9 (6.5%) dogs with active cutaneous 
lesions or suspect scars, 66.7% were caused by Leishmania sp; 44.4% 
produced infection in hamsters and showed growth in culture media, which
 was considered to be compatible with the species of Leishmania 
braziliensis complex. The molecular characterization (isoenzyme and KDNA
 restriction profiles) defined two strains with similar profiles for L
. (Viannia) braziliensis. The prevalence of canine infection estimated 
by the cutaneous test, IFR and ELISA was 10.1%, 16.7% and 27.8%, 
respectively. The presence of clinical / sub-clinical form of ATL in 
canine population associated with human infections suggested that the 
dog can act as source of infection as well as for dissemination of the 

PMID: 15821787

TITLE: [Immunoglobulin isotype and IgG subclass profiles in american tegumentary

AUTHORS: Maria Aparecida de Souza, Adriano Gomes da Silva, Sandra Regina
Afonso-Cardoso, Silvio Favoreto Junior, Marcelo Simão Ferreira

AFFILIATION: Laboratório de Imunologia, Instituto de Ciências Biomédicas,
Universidade Federal de Uberlândia, Uberlândia, MG.

REFERENCE: Rev Soc Bras Med Trop 2005 Mar-Apr 38(2):137-41

The present work investigated the serum antibody profiles in 37 patients
 with American tegumentary leishmaniasis, who were attended at Hospital 
de Clinicas - Universidade Federal de Uberlandia, MG, Brazil. The 
immunoglobulin class and IgG subclass profiles were analyzed by indirect
 ELISA using Leishmania (Leishmania) amazonensis soluble antigen. The 
antibody avidity was determined by 6 M urea treatment after incubation 
with immunoenzymatic conjugate. It was observed that 97% of the serum 
samples presented anti-Leishmania antibodies for IgE class, 94.6% IgG, 
57.5% IgA and 21.5% IgM class. For IgG subclasses the profiles were in 
the following order of frequency: IgG1>IgG3>IgG2>IgG4. High avidity of 
anti-Leishmania IgE antibodies was found in 44.4% of the samples. On the
 other hand, moderate avidity of specific IgG and IgA was observed in 62
.8% and 47.8% of samples, respectively. These results indicate a very 
complex antibody response profile against American tegumentary 

PMID: 15821789

TITLE: [Visceral leishmaniasis: a study on phlebotomine sand flies and canine
infection in Montes Claros, State of Minas Gerais.]

AUTHORS: Erika Michalsky Monteiro, João Carlos França da Silva, Roberto
Teodoro da Costa, Daniela Camargos Costa, Ricardo Andrade Barata, Edvá Vieira
de Paula, George Luis Lins Machado-Coelho, Marília Fonseca Rocha, Consuelo
Latorre Fortes-Dias, Edelberto Santos Dias

AFFILIATION: Centro de Pesquisas René Rachou, Fundação Oswaldo Cruz, Belo
Horizonte, MG.

REFERENCE: Rev Soc Bras Med Trop 2005 Mar-Apr 38(2):147-52

Visceral leishmaniasis in Brazil was initially associated with rural 
areas. However, due to several environmental modifications such as 
deforestation, urbanization and intense migratory processes, there has 
been an expansion of endemic areas, leading to urbanization of the 
disease, mainly in the central and northeastern regions of Brazil. In 
the municipality of Montes Claros, located in the north of the state of 
Minas Gerais, an epidemiological survey on VL was carried out. A canine 
serological inquiry was carried out in 2002 and an entomological survey
, using luminous CDC traps, was performed from September 2002 to August 
2003. Canine VL prevalence showed an average infection rate of 
approximately 5%. An estimated 16 species comprised the phlebotomine 
sand fly fauna, based on a total of 1043 specimens. The predominant 
species was Lutzomyia longipalpis with a rate of 74%, suggesting its 
participation in the transmission of VL in the municipality of Montes 

PMID: 15716079

TITLE: Role of costimulatory molecules in immune response of patients with
cutaneous leishmaniasis.

AUTHORS: Cecilia Favali, Dirceu Costa, Lilian Afonso, Viviane Conceição,
Andréa Rosato, Fabiano Oliveira, Jackson Costa, Aldina Barral, Manoel
Barral-Netto, Claudia Ida Brodskyn

AFFILIATION: Laboratório de Imunoparasitologia, Centro de Pesquisas Gonçalo
Moniz, Fundação Oswaldo Cruz (FIOCRUZ), Rua Waldemar Falcão, 121, Salvador,
Bahia 40295-001, Brazil.

REFERENCE: Microbes Infect 2005 Jan 7(1):86-92

T cell-mediated immunity is critical in resistance against Leishmania 
parasites, and T cell activation requires signals provided by 
costimulatory molecules. Herein we evaluated the role of costimulatory 
molecules on cytokine production and T cell surface molecule expression 
by peripheral blood mononuclear cells (PBMC) from cutaneous 
leishmaniasis (CL) patients. PBMC from CL patients were stimulated with 
soluble Leishmania antigen (SLA, 10 mug/ml), in the presence or absence 
of soluble CTLA4-Ig to block CD28-B7 interaction or in the presence or 
absence of anti-human CD40L to block CD40-CD40L interaction. 
Supernatants were harvested to evaluate tumor necrosis factor alpha (TNF
-alpha), interleukin 10 (IL-10), transforming growth factor beta (TGF-
beta) and interferon gamma (IFN-gamma) production by ELISA. Cells were 
harvested after 48 h of culture, stained for specific activation markers
 and analyzed by flow cytometry. Results show that the blockade of CD28-
B7 interaction by CTLA4-Ig downmodulated IFN-gamma, IL-10, and TNF-alpha
 secretion by PBMC from CL patients. No alteration was detected on 
either TGF-beta production or the expression of CTLA44 or CD25 on CD4
(+) and CD8(+) T cells. When the CD40-CD40L interaction was blockade 
using anti-CD40L, we did not observe changes in cytokine production or 
in surface molecule expression. The blockade of the CD28-B7 interactions
 by CTLA4-Ig also did not alter cytokine production in volunteers 
immunized against tetanus toxoid (TT). Taken together, these data 
suggest that the interaction of CTLA4 and CD28-B7 is a TGF-beta-
independent mechanism that specifically downmodulates the immune 
response in cutaneous leishmaniasis patients.

PMID: 15700843

TITLE: 2-propen-1-amine derivatives and their synthetic intermediates: activity
against pathogenic trypanosomatids.

AUTHORS: A O de Souza, F P Hemerly, L Gomes-Cardoso, R M Santa-Rita, L L Leon, S
L de Castro, N Durán

AFFILIATION: Departamento de Bioquímica e Immunologia, Faculdade de Medicina de
Ribeirão, Universidade de São Paulo, Avenida Bandeirantes, 3900, CEP
14015-049, Ribeirão Preto, SP, Brazil.

REFERENCE: J Chemother 2004 Dec 16(6):530-3

The potential activity of three new derivatives of 3-(4'-Y-[1,1'-
biphenyl]-4-yl)-3-(4-X-phenyl)-N,N-dimethyl-2-propen-1-amine (2-PAMs) 
was assayed against Trypanosoma cruzi and Leishmania amazonensis. They 
showed higher activity against trypomastigotes and epimastigotes of T. 
cruzi than the standard drugs, crystal violet and nifurtimox. Besides 
these derivatives, a series of eleven 2-PAMs derivatives and the 
corresponding intermediates, biphenyl methanones (BPMs) were assayed 
against promastigotes of L. amazonensis, showing that the 2-PAMs were 
remarkably more active than the BPMs. The PAMs 2c, 2e and 2j were about 
2-fold more active that pentamidine isothionate and between 27.2- and 46
.4-fold less toxic to V79 mammalian cells. The present results encourage
 further studies, especially against intracellular parasites and in 
experimental animals.

PMID: 15546389

TITLE: The role of IL-27 in the development of T-cell responses during parasitic

AUTHORS: Christopher A Hunter, Alejandro Villarino, David Artis, Phillip Scott

AFFILIATION: Department of Pathobiology, University of Pennsylvania School of
Veterinary Medicine, Philadelphia, PA 19104, USA. chunter at phl.vet.upenn.edu

REFERENCE: Immunol Rev 2004 Dec 202():106-14

The recognition that CD4+ T-cell responses could be divided into at 
least two functional subsets either dominated by production of 
interferon (IFN)-gamma and associated with cell-mediated immunity (Th1) 
or characterized by production of interleukin (IL)-4 and IL-5 and 
associated with humoral immunity (Th2) provided a basis to understand 
the role of T cells in resistance or susceptibility to different types 
of pathogens. As a consequence, many studies have focused on the 
identification of cytokines that influence these events. For example, 
the development of Th1-type responses is largely dependent on IL-12. 
However, other cytokines also affect this process, and initial studies 
revealed that IL-27, a cytokine with close structural and functional 
similarity to IL-12, can promote Th1 responses required for immunity to 
Leishmania major. Subsequent work with IL-27R (WSX-1)-deficient mice 
infected with Toxoplasma gondii or Trypanosoma cruzi revealed that the 
IL-27/IL-27R system can act as a negative regulator of inflammatory T-
cell responses. The aim of this review is to discuss recent studies from
 these laboratories on the role of IL-27 in immunity to parasitic 
infections in the context of previous work and to highlight the 
pleiotropic effects of the IL-27/IL-27R system in the development and 
regulation of Th1 and Th2 responses.

PMID: 15711695

TITLE: Leishman staining in field diagnosis of corneal ulcer.

AUTHORS: Raj Anand, Nirmala Agarwal, Subhash C Arya, Himesh K Shah, Mukesh

AFFILIATION: Department of Ophthalmology, Sant Parmanand Hospital, Delhi,

REFERENCE: Saudi Med J 2004 Dec 25(12):2026-7


 The following references are revised files and are brought to you in accordance
to license agreement with the NLM.


PMID: 15715010

TITLE: Detection of Leishmania infantum in canine peripheral blood.

AUTHORS: V Foglia Manzillo, D Piantedosi, L Cortese

AFFILIATION: Dipartimento di Scienze Cliniche Veterinarie, Sezione Clinica
Medica, Università degli Studi di Napoli Federico II, via F. Delpino 1,80137
Naples, Italy.

REFERENCE: Vet Rec 2005 Jan 156(5):151-2

PMID: 15275252

TITLE: Impaired NFATc translocation and failure of Th2 development in
Itk-deficient CD4+ T cells.

AUTHORS: D J Fowell, K Shinkai, X C Liao, A M Beebe, R L Coffman, D R Littman, R
M Locksley

AFFILIATION: Department of Medicine, University of California San Francisco
94143, USA.

REFERENCE: Immunity 1999 Oct 11(4):399-409

Naive Itk-deficient CD4+ T cells were unable to establish stable IL-4 
production, even when primed in Th2-inducing conditions. In contrast, 
IFNgamma production was little affected. Failure to express IL-4 
occurred even among cells that had gone through multiple cell divisions 
and was associated with a delay in the kinetics and magnitude of NFATc 
nuclear localization. IL-4 production was restored genetically by 
retroviral reconstitution of Itk or biochemically by augmenting the 
calcium flux with ionomycin. In vivo, Itk-deficient mice were unable to 
establish functional Th2 cells. Development of protective Th1 cells was 
unimpeded. These data define a nonredundant role for Itk in modulating 
signals from the TCR/CD28 pathways that are specific for the 
establishment of stable IL-4 but not IFNgamma expression.

PMID: 8265673

TITLE: Malnutrition, age and the risk of parasitic disease: visceral
leishmaniasis revisited.

AUTHORS: C Dye, B G Williams

AFFILIATION: Isaac Newton Institute for Mathematical Sciences, University of
Cambridge, U.K.

REFERENCE: Proc Biol Sci 1993 Oct 254(1339):33-9

Children are said to be at greater risk of developing visceral 
leishmaniasis (VL) when they are younger and more malnourished. If 
malnutrition really is associated with VL, this potentially fatal and 
visible disease may be a general indicator of community health among the
 rural and suburban poor. Previous conclusions reached about the roles 
of malnutrition and age in VL epidemiology are questionable because they
 may have been confounded by transmission rate, because they have not 
been able to distinguish between different mechanisms of acquiring 
immunity, and because empirical observations have not been compared with
 theoretical expectations. Here we offer a framework with which to 
investigate these questions quantitatively, and do so with published 
data from endemic areas of Brazil. We conclude that children are indeed 
more susceptible to VL when they are younger and more malnourished, but 
it remains unclear whether the immunity to VL acquired with age is 
always acquired as a result of infection. The significance for 
leishmaniasis control, and for the control of other diseases associated 
with malnutrition, will depend on underlying mechanisms, which are not 
yet understood.

PMID: 43976

TITLE: Leishmania in phlebotomid sandflies. VII. On the taxonomic status of
Leishmania peruviana, causative agent of Peruvian 'uta', as indicated by its
development in the sandfly, Lutzomyia longipalpis.

AUTHORS: R Lainson, P D Ready, J J Shaw

REFERENCE: Proc R Soc Lond B Biol Sci 1979 Dec 206(1164):307-18

The name Leishmania peruviana was given by Velez (1913) to the parasite 
responsible for a form of cutaneous leishmaniasis known as 'uta'; this 
disease occurs in the Peruvian Andes. Clinical similarities between uta 
and 'oriental sore', which is caused by Leishmania tropica of the 
Eastern Hemisphere, have, however, led to the suggestion that uta is 
simply due to L. tropica, which was introduced into Latin America by 
African slaves or European immigrants. Leishmania species are divisible 
into three distinct sections, according to their pattern of development 
in their natural (phlebotomine) vectors. One of these sections, the 
PERIPYLARIA, contains the subspecies of Leishmania braziliensis, and is 
characterized by parasites that undergo a phase of development attached 
to the wall of the hindgut (pylorus and ileum), in addition to 
multiplication in the midgut and subsequent invasion of the foregut. 
Such development is unknown in any other group of leishmaniae, including
 those groups of the section SUPRAPYLARIA, which includes parasites of 
the L. tropica complex. Three isolates of L. peruviana were studied in 
laboratory-bred sandflies, Lutzomyia longipalpis (Lutz & Neiva), and
 all showed consistent and prolific development of rounded or stumpy 
flagellates attached to the wall of the hindgut and, in some instances, 
growth of free, elongate promastigotes throughout the midgut. 
Development of both L. tropica and L. major, in the same insect, was 
restricted to massive development of free flagellates in the midgut, up 
to the cardial valve. From the behaviour of L. peruviana in the sandfly
, its slow growth in hamster skin and the small size of its amastigotes
, it is concluded that this parasite is (a) distinctly different from 
both L. tropica and L. major, and (b) closely related to subspecies of L
. braziliensis within the section PERIPYLARIA. On this evidence it is 
also concluded that L. peruviana is indigenous to the American continent
. The specific name is best retained for the time being (rather than L. 
braziliensis peruviana).

PMID: 15270

TITLE: Leishmania in phlebotomid sandflies. IV. The transmission of Leishmania
mexicana amazonensis to hamsters by the bite of experimentally infected
Lutzomyia longipalpis.

AUTHORS: R Killick-Kendrick, A J Leaney, P D Ready, D H Molyneux

REFERENCE: Proc R Soc Lond B Biol Sci 1977 Feb 196(1122):105-15

REQUEST: [ leishmania ]

(46 articles match this request. 22 articles matching other requests removed)

PMID: 15811523

TITLE: Characterization of two T. gondii CK1 isoforms.

AUTHORS: Robert G K Donald, Tanya Zhong, Laurent Meijer, Paul A Liberator

AFFILIATION: Department of Human/Animal Infectious Disease Research, Merck
Research Laboratories, Merck & Co., P.O. Box 2000, R80Y-260, Rahway, NJ
07065-0900, USA.

REFERENCE: Mol Biochem Parasitol 2005 May 141(1):15-27

Previous affinity chromatography experiments have described the 
unexpected binding of an isoform of casein kinase I (CK1) from 
Leishmania mexicana, Trypanosoma cruzi, Plasmodium falciparum and 
Toxoplasma gondii to an immobilized cyclin-dependent kinase (CDK) 
inhibitor (purvalanol B). In order to further evaluate CK1 as a 
potential anti-parasitic target, two T. gondii CK1 genes were cloned by 
PCR using primers derived from a putative CK1 gene fragment identified 
from a T. gondii EST database. The genes are predicted to encode a 
smaller polypeptide of 38kDa (TgCK1alpha) and larger 49kDa isoform 
bearing a C-terminal extension (TgCK1beta). Enzymatically active 
recombinant FLAG-epitope tagged TgCK1alpha and TgCK1beta enzymes were 
immuno-precipitated from transiently transfected T. gondii parasites. 
While TgCK1alpha expression was found to be cytosolic, TgCK1beta was 
expressed predominantly at the plasma membrane. Deletion mapping showed 
that the C-terminal domain of TgCK1beta confers this membrane-
association. Recombinant TgCK1alpha and TgCK1beta isoforms were also 
expressed in E. coli and biochemically characterized. A 38kDa native CK1
 activity was partially purified from T. gondii tachyzoites by ion-
exchange and hydrophobic interaction chromatography with biochemical and
 serological properties closely resembling those of recombinant 
TgCK1alpha. In contrast, we were not able to identify a native CK1 
activity corresponding to the larger TgCK1beta 49kDa isoform in 
tachyzoite lysates. Purvalanol B and the related compound 
aminopurvalanol A selectively inhibit TgCK1alpha, confirming the 
existence of potentially exploitable structural differences between host
 and parasite CK1 enzymes. Since the more cell-permeable aminopurvalanol
 also inhibits parasite growth, these results provide further impetus to
 investigate inhibitors of CK1 as anti-parasitic agents.

PMID: 15811531

TITLE: Differentiation of Leishmania donovani in host-free system: analysis of
signal perception and response.

AUTHORS: Efrat Barak, Sigal Amin-Spector, Elena Gerliak, Sophie Goyard, Neta
Holland, Dan Zilberstein

AFFILIATION: Department of Biology, Technion - Israel Institute of Technology,
Haifa 32000, Israel.

REFERENCE: Mol Biochem Parasitol 2005 May 141(1):99-108

Leishmania donovani are the causative agents of kala-azar in humans. 
They undergo a developmental program following changes in the 
environment, resulting in the reversible transformation between the 
extracellular promastigote form in the sand fly vector and the 
obligatory intracellular amastigote form in phagolysosomes of 
macrophages. A host-free differentiation system for L. donovani was used
 to investigate the initial process of promastigote to amastigote 
differentiation. Within an hour after exposing promastigotes to 
differentiation signal (concomitant exposure to 37 degrees C and pH 5.5
), they expressed the amastigote-specific A2 protein family. At 5h they 
started to transform to amastigote-shaped cells, a process that was 
completed 7h later. This morphological transformation occurred 
synchronously, while cells arrested at G1. By sequential exposure to 
elevated temperature (for 24h) and then acidic pH, we found that heat 
was responsible for the growth arrest and acidic pH to its release and 
subsequent route to differentiation into amastigotes. Lastly, ethanol 
and Azetidine 2 carboxylic acid (a synthetic proline analog) that 
induced heat shock response in promastigotes were capable of replacing 
heat in the differentiation signal.

PMID: 15819633

TITLE: The initial step of glycerolipid metabolism in Leishmania major
promastigotes involves a single glycerol-3-phosphate acyltransferase enzyme
important for the synthesis of triacylglycerol but not essential for

AUTHORS: Rachel Zufferey, Choukri Ben Mamoun

AFFILIATION: Center for Microbial Pathogenesis, University of Connecticut Health
Center, 263 Farmington Ave, Farmington, CT 06030, USA.

REFERENCE: Mol Microbiol 2005 May 56(3):800-10

Summary The synthesis of the major phospholipids, including those that 
play an essential role in Leishmania virulence, initiates with the 
acylation of glycerol-3-phosphate and dihydroxyacetonephosphate at the 
sn-1 position by glycerol-3-phosphate and dihydroxyacetonephosphate 
acyltransferases respectively. In this study, we show that Leishmania 
major promastigotes express a single glycerol-3-phosphate 
acyltransferase activity important for triacylglycerol synthesis but not
 essential for virulence. The encoding gene, LmGAT, expressed in yeast 
results in full complementation of the lethality of a mutant, 
gat1Deltagat2Delta, lacking glycerol-3-phosphate activity. Biochemical 
analyses revealed that LmGAT is a low-affinity glycerol-3-phosphate 
acyltransferase and exhibits higher specific activity with unsaturated 
long fatty acyl-CoA donors. A L. major null mutant, Deltalmgat/
Deltalmgat, was created and a thorough analysis of its lipid composition
 was performed. Deletion of LmGAT resulted in a complete loss of 
Leishmania glycerol-3-phosphate acyltransferase activity and a major 
reduction in triacylglycerol synthesis. Consistent with the specificity 
of LmGAT for glycerol-3-phosphate but not dihydroxyacetonephosphate, 
Deltalmgat/Deltalmgat mutant expressed normal levels of the ether-lipid 
derivatives and virulence factors, lipophosphoglycan and GPI-anchored 
proteins, gp63, and its virulence was not affected in mice.

PMID: 15808452

TITLE: Synthesis and in vitro leishmanicidal activity of 2-(5-nitro-2-furyl) and

AUTHORS: Alireza Foroumadi, Shirin Pournourmohammadi, Fatemeh Soltani, Mitra
Asgharian-Rezaee, Shahriar Dabiri, Arsalan Kharazmi, Abbas Shafiee

AFFILIATION: Faculty of Pharmacy, Kerman University of Medical Sciences, Kerman
76351, Iran.

REFERENCE: Bioorg Med Chem Lett 2005 Apr 15(8):1983-5

A series of 2-(5-nitro-2-furyl) and 2-(5-nitro-2-thienyl)-5-substituted-
1,3,4-thiadiazoles (5a-d and 6a-j) were synthesized and evaluated 
against Leishmania major promastigotes using (3)H-thymidine 
incorporation. Most of the compounds showed activity better than the 
reference drug sodium stibogluconate (Pentostam). The most active 
compound was 6c (IC(50)=0.1muM).

PMID: 15632173

TITLE: Identification and Characterization of a Polyamine Permease from the
Protozoan Parasite Leishmania major.

AUTHORS: Marie-Pierre Hasne, Buddy Ullman

AFFILIATION: Department of Biochemistry and Molecular Biology, Oregon Health and
Science University, Portland, Oregon 97239.

REFERENCE: J Biol Chem 2005 Apr 280(15):15188-94

The proteins that mediate polyamine translocation into eukaryotic cells 
have not been identified at the molecular level. To define the polyamine
 transport pathways in eukaryotic cells we have cloned a gene, LmPOT1, 
that encodes a polyamine transporter from the protozoan pathogen, 
Leishmania major. Sequence analysis of LmPOT1 predicted an unusual 803-
residue polytopic protein with 9-12 transmembrane domains. Expression of
 LmPOT1 cRNA in Xenopus laevis oocytes revealed LmPOT1 to be a high 
affinity transporter for both putrescine and spermidine, whereas 
expression of LmPOT1 in Trypanosoma brucei stimulated putrescine uptake 
that was sensitive to inhibition by pentamidine and proton ionophores. 
Immunoblot analysis established that LmPOT1 was expressed predominantly 
in the insect vector form of L. major, and immunofluorescence 
demonstrated that LmPOT1 was localized predominantly to the parasite 
plasma membrane. To our knowledge this is the first molecular 
identification and characterization of a cell surface polyamine 
transporter in eukaryotic cells.

PMID: 15821136

TITLE: Mitochondrial DNA Ligases of Trypanosoma brucei.

AUTHORS: Nick Downey, Jane C Hines, Krishna M Sinha, Dan S Ray

AFFILIATION: Paul D. Boyer Hall, 611 Charles Young Dr., University of
California, Los Angeles, CA 90095-1570. danray at ucla.edu.

REFERENCE: Eukaryot Cell 2005 Apr 4(4):765-74

The mitochondrial DNA of Trypanosoma brucei, termed kinetoplast DNA or 
kDNA, consists of thousands of minicircles and a small number of 
maxicircles catenated into a single network organized as a nucleoprotein
 disk at the base of the flagellum. Minicircles are replicated free of 
the network but still contain nicks and gaps after rejoining to the 
network. Covalent closure of remaining discontinuities in newly 
replicated minicircles after their rejoining to the network is delayed 
until all minicircles have been replicated. The DNA ligase involved in 
this terminal step in minicircle replication has not been identified. A 
search of kinetoplastid genome databases has identified two putative DNA
 ligase genes in tandem. These genes (LIG kalpha and LIG kbeta) are 
highly diverged from mitochondrial and nuclear DNA ligase genes of 
higher eukaryotes. Expression of epitope-tagged versions of these genes 
shows that both LIG kalpha and LIG kbeta are mitochondrial DNA ligases. 
Epitope-tagged LIG kalpha localizes throughout the kDNA, whereas LIG 
kbeta shows an antipodal localization close to, but not overlapping, 
that of topoisomerase II, suggesting that these proteins may be 
contained in distinct structures or protein complexes. Knockdown of the 
LIG kalpha mRNA by RNA interference led to a cessation of the release of
 minicircles from the network and resulted in a reduction in size of the
 kDNA networks and rapid loss of the kDNA from the cell. Closely related
 pairs of mitochondrial DNA ligase genes were also identified in 
Leishmania major and Crithidia fasciculata.

PMID: 15788098

TITLE: Heterologous expression of the filarial nematode alt gene products
reveals their potential to inhibit immune function.

AUTHORS: Natalia Gomez-Escobar, Clare Bennett, Lidia Prieto-Lafuente, Toni
Aebischer, Clare C Blackburn, Rick M Maizels

AFFILIATION: Institute of Immunology and Infection Research, University of
Edinburgh, UK. n.gomez at ed.ac.uk

REFERENCE: BMC Biol 2005 Mar 3(1):8

BACKGROUND: Parasites exploit sophisticated strategies to evade host 
immunity that require both adaptation of existing genes and evolution of
 new gene families. We have addressed this question by testing the 
immunological function of novel genes from helminth parasites, in which 
conventional transgenesis is not yet possible. We investigated two such 
novel genes from Brugia malayi termed abundant larval transcript (alt), 
expression of which reaches ~5% of total transcript at the time 
parasites enter the human host. RESULTS: To test the hypothesis that ALT
 proteins modulate host immunity, we adopted an alternative transfection
 strategy to express these products in the protozoan parasite Leishmania
 mexicana. We then followed the course of infection in vitro in 
macrophages and in vivo in mice. Expression of ALT proteins, but not a 
truncated mutant, conferred greater infectivity of macrophages in vitro
, reaching 3-fold higher parasite densities. alt-transfected parasites 
also caused accelerated disease in vivo, and fewer mice were able to 
clear infection of organisms expressing ALT. alt-transfected parasites 
were more resistant to IFN-gamma-induced killing by macrophages. 
Expression profiling of macrophages infected with transgenic L. mexicana
 revealed consistently higher levels of GATA-3 and SOCS-1 transcripts, 
both associated with the Th2-type response observed in in vivo filarial 
infection. CONCLUSION: Leishmania transfection is a tractable and 
informative approach to determining immunological functions of single 
genes from heterologous organisms. In the case of the filarial ALT 
proteins, our data suggest that they may participate in the Th2 bias 
observed in the response to parasite infection by modulating cytokine-
induced signalling within immune system cells.

PMID: 15814032

TITLE: The mechanism behind the antileishmanial effect of zinc sulphate. II.
Effects on the enzymes of the parasites.

AUTHORS: Y M Al-Mulla Hummadi, N M Al-Bashir, R A Najim

AFFILIATION: Department of Pharmacology, College of Medicine, University of
Baghdad, P.O. Box 61208, Baghdad 12114, Iraq.

REFERENCE: Ann Trop Med Parasitol 2005 Mar 99(2):131-9

When used in vitro, zinc sulphate has a direct antileishmanial effect. 
To see if this effect involved the inhibition of the parasites' enzymes
, extracts of the promastigotes and axenic amastigotes of Leishmania 
major (MHOM/IQ/93/MRC6) and L. tropica (MHOM/IQ/93/MRC2) were prepared. 
Zinc sulphate, at various concentrations, was then added to samples of 
these extracts before the activities, in the samples, of certain key 
enzymes of the Embden-Meyerhof pathway, hexose-monophosphate shunt and 
citric-acid cycle, and of two enzymes associated with virulence (
protease and acid phosphatase), were determined. The zinc was found to 
inhibit every enzyme investigated, usually in a dose-dependent manner. 
Thus the direct antileishmanial effect of zinc may result, partially or 
entirely, from the inhibition of enzymes that are necessary for the 
parasites' carbohydrate metabolism and virulence.

PMID: 15816188

TITLE: Granulomatous lesion on a bitch's nipple caused by Leishmania infantum.

AUTHORS: P Gómez-Ochoa, M Gascón, M C Aceña, F J Miana-Mena, J A Castillo

AFFILIATION: Hospital Clinico Veterinario, Animal Pathology Department,
Veterinary Faculty of Zaragoza, c/ Miguel Servet 177, CP 50013 Zaragoza,

REFERENCE: Vet Rec 2005 Mar 156(12):389

PMID: 15814284

TITLE: European strategies against the parasite transfusion risk.

AUTHORS: H W Reesink

AFFILIATION: Sanquin Blood Bank North-West Region, Sanquin Diagnostic Services,
P.O. Box 9137, NL - 1006 AC Amsterdam, The Netherlands.

REFERENCE: Transfus Clin Biol 2005 Feb 12(1):1-4

Protozoal infections are endemic in mainly tropical low income countries
, affecting millions of people. Malaria, American trypanosomiasis (
Trypanosoma cruzi/Chagas disease) and protozoal tickborne diseases (e.g
. Babesia) can be efficiently transmitted by transfusion of cellular 
blood components. In non-endemic areas like Europe malaria, Chagas 
disease and Babesia are imported diseases resulting of travelling to 
endemic areas and migration of autochthons from these endemic areas. A 
recent International Forum showed that in Europe, as well as the USA, 
prevention of transfusion-associated protozoal infections depend mainly 
on selection of donors using questionnaires. Most countries divide 
donors at risk for malaria in two groups: individuals who have lived in 
the first 5 years of their life in malaria endemic areas and those who 
are borne and residing in non-endemic areas and visited the endemic area
(s). The first category of donors is rejected for 3 years after their 
last visit to the endemic area, and in one country such donors are 
permanently rejected. In some countries such donors are accepted after 4
 months-3 years, provided a test for malaria is non-reactive. Persons 
from non-endemic areas, who visited the malaria endemic area, are 
rejected for 4-12 months. Some countries reject these donors for 3 years
 or permanently when they resided for more than 6 months in the endemic 
area. The rejection rate of donors for malaria risk in the various 
countries was 0.003-0.43% of all donations. Over the last decade only a 
few cases of TT-malaria were reported in the various countries. In 
several countries donors are questioned for risk of T. cruzi infection. 
In some countries donors are excluded when they (or their mothers) were 
born in South or Central America, if they received a blood transfusion 
in these areas and if they lived in rural areas in these endemic 
countries for more than 4 weeks. In none of the countries donors are 
asked if they had Babesia or Leishmania. At present implemented measures
 to prevent TT-malaria in the European countries are probably highly 
effective. More research is needed to establish the theoretical risk of 
TT-T. cruzi and TT-Leishmania infection in Europe, before preventive 
measures may be considered.

PMID: 15716069

TITLE: Genetic and biological diversity among populations of Leishmania major
from Central Asia, the Middle East and Africa.

AUTHORS: Mustafa Elfari, Lionel F Schnur, Margarita V Strelkova, Carol L
Eisenberger, Raymond L Jacobson, Charles L Greenblatt, Wolfgang Presber,
Gabriele Schönian

AFFILIATION: Department of Parasitology, Institute of Microbiology and Hygiene,
Charité University Medicine Berlin, Dorotheenstr. 96, D-10098 Berlin,

REFERENCE: Microbes Infect 2005 Jan 7(1):93-103

Evidence is provided for genetic and biological variation among 
Leishmania major strains that correlates with their geographical origin
. The host-parasite relationship also appears to be specific. Great 
gerbils, Rhombomys opimus, and fat sand rats, Psammomys obesus, are the 
main reservoir hosts in Central Asia and the Middle East, respectively. 
However, the Central Asian parasite failed to infect the Middle Eastern 
rodent host in the laboratory, and vice versa. A permissively primed 
intergenic polymorphic (PPIP)-PCR and a single-stranded conformation 
polymorphism (SSCP)-PCR exposed genetic polymorphism among 30 strains of
 L. major from different geographical regions. This was verified by 
subsequent sequencing of DNA from the same strains using four genomic 
targets: (a) the NADH-dehydrogenase (NADH-DH) gene, (b) the 6-
phosphogluconate dehydrogenase (6PGD) gene, (c) the ribosomal internal 
transcribed spacers, and (d) an anonymous DNA sequence originally 
amplified with random primers. All the genetic markers indicated that 
the nine Central Asian strains were a separate homogenous genetic group
. The Middle Eastern strains formed another geographical group that 
displayed heterogeneity corresponding with their different Middle 
Eastern locations. Molecular markers and host-parasite relationships 
confirmed that Central Asian and Middle Eastern strains are genetically 
and biologically distinct sub-populations of L. major. Three African 
strains of L. major were genetically closer to the Middle Eastern 
strains, and a representative one did infect fat sand rats, but they had
 distinct permissively primed inter-genic polymorphic PCR patterns and 
internal transcribed spacer 2 types.

PMID: 15716074

TITLE: CD40 signaling induces reciprocal outcomes in Leishmania-infected
macrophages; roles of host genotype and cytokine milieu.

AUTHORS: Marise P Nunes, Lea Cysne-Finkelstein, Bruna C Monteiro, Daniel M de
Souza, Nitza A Gomes, George A Dosreis

AFFILIATION: Instituto Oswaldo Cruz, FIOCRUZ, Avenida Brasil, 4365, Rio de
Janeiro, RJ, 21045-900, Brazil.

REFERENCE: Microbes Infect 2005 Jan 7(1):78-85

We investigated the influence of CD40-CD40 ligand-mediated signaling on 
induction of microbicidal activity against Leishmania major in 
macrophages from resistant (B6) and susceptible (BALB) mouse strains. 
CD40 engagement induced leishmanicidal activity in resistant macrophages
, but increased parasite replication in susceptible macrophages. CD40 
engagement induced comparable TNF-alpha production in macrophages from 
both strains. However, increased IL-10 production was restricited to 
susceptible macrophages. Increased parasite replication in susceptible 
macrophages was prevented by a neutralizing anti-IL-10 antibody. In the 
presence of IFN-gamma, CD40 engagement induced Leishmania killing by 
macrophages from both strains. Therefore, the outcome of CD40 signaling 
on effector responses against L. major depends on host genotype and the 
cytokine milieu, and a source of IFN-gamma is required for a protective 

PMID: 15225696

TITLE: A convenient and biogenetic type synthesis of few naturally occurring
chromeno dihydrochalcones and their in vitro antileishmanial activity.

AUTHORS: Tadigoppula Narender, Shweta, Suman Gupta

AFFILIATION: Division of Medicinal and Process Chemistry, Central Drug Research
Institute, Lucknow 226 001, India. tnarender at rediffmail.com

REFERENCE: Bioorg Med Chem Lett 2004 Aug 14(15):3913-6

2',2'-Dimethyl chromeno dihydrochalcones are very rare in nature as 
plant secondary metabolites. Recently we have reported three such 
compounds from the plant Crotalaria ramosissima. Chromeno 
dihydrochalcones contain a 2',2'-dimethyl benzopyran system, which are 
frequently encountered in many natural products and exhibit a variety of
 biological activities. We here report the strategy to conveniently 
synthesize naturally occurring chromeno dihydrochalcones by biogenetic 
type pyridine or Amberlyst-15 catalyzed chromenylation of 
dihydrochalcones and in vitro antileishmanial activity of chromeno 
dihydrochalcones and their intermediates.

PMID: 15225725

TITLE: Leishmanicidal activity of phenylene bridged C2 symmetric glycosyl

AUTHORS: Neetu Tewari, Ramesh, R C Mishra, R P Tripathi, V M L Srivastava, Suman

AFFILIATION: Medicinal and Process Chemistry Division, Central Drug Research
Institute, Lucknow 226001, India.

REFERENCE: Bioorg Med Chem Lett 2004 Aug 14(15):4055-9

A number of phenylene bridged C2 symmetric glycosyl uerides with ester (
3a-f), alcohol (4a-c) and acid (5a-d) functionalities were prepared by 
addition of glycosyl amino esters with phenyl diisocyanates and their 
further reaction with LiAlH(4) or hydrolysis with LiOH. All the 
compounds were screened for their in vitro and in vivo antileishmanial 
activity. Most of the compounds exhibited good activity while two of the
 compounds 3e and 3f reduced the clinical dose of standard drug SSG.

PMID: 15813385

TITLE: A serine protease from a detergent-soluble extract of Leishmania
(Leishmania) amazonensis.

AUTHORS: Raquel Elisa da Silva Lopez, Salvatore Giovanni De Simone

AFFILIATION: Laboratório de Bioquímica de Proteínas e Peptídeos,
Departamento de Bioquímica e Biologia Molecular, Instituto Oswaldo Cruz,
FIOCRUZ, Rio de Janeiro, RJ, Brasil. rlopez at ioc.fiocruz.br

REFERENCE: Z Naturforsch [C] 2004 Jul-Aug 59(7-8):590-8

Proteases mediate important crucial functions in parasitic diseases, and
 their characterization contributes to the understanding of host-
parasite interaction. A serine protease was purified about 43-fold with 
a total recovery of 60% from a detergent-soluble extract of 
promastigotes of Leishmania amazonensis. The purification procedures 
included aprotinin-agarose affinity chromatography and gel filtration 
high performance liquid chromatography. The molecular mass of active 
enzyme was 110 kDa by native gel filtration HPLC and by SDS-PAGE gelatin
 under non-reducing conditions. Under conditions of reduction using SDS-
PAGE gelatin analyses the activity of enzyme was observed in two 
proteins of 60 and 45 kDa, suggesting that the enzyme may be considered 
as a dimer. The Leishmania protease was not glycosylated, and its 
isoelectric point (pI) was around 4.8. The maximal protease activity was
 at pH 7.0 and 28 degrees C, using a-N-o-tosyl-L-arginyl-methyl ester (L
-TAME) as substrate. Assays of thermal stability indicated that this 
enzyme was totally denatured after pre-treatment at 42 degrees C for 12 
min and preserved only 20% of its activity after pre-treatment at 37 
degrees C for 24 h, in the absence of substrate. Hemoglobin, bovine 
serum albumin (BSA), ovalbumin and gelatin were hydrolyzed by Leishmania
 protease. Inhibition studies indicated that the enzyme belonged to a 
serine protease class because of a significant impediment by serine 
protease inhibitors such as benzamidine, aprotinin, and antipain. The 
activity of the present serine protease is negatively modulated by 
calcium and zinc and positively modulated by manganese ions. This is the
 first study that reports the purification of a protease from a 
detergent-soluble extract of Leishmania species.

PMID: 15813368

TITLE: A new heptasubstituted (E)-aurone glucoside and other aromatic compounds
of Gomphrena agrestis with biological activity.

AUTHORS: Eliane O Ferreira, Marcos J Salvador, Elizabeth M F Pral, Silvia C
Alfieri, Izabel Y Ito, Diones A Dias

AFFILIATION: Departamento de Física e Química, Faculdade de Ciências
Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto,
SP, Brasil. elianeof at yahoo.com.br

REFERENCE: Z Naturforsch [C] 2004 Jul-Aug 59(7-8):499-505

A new aurone 1 and two known substances, aurantiamide acetate (2) and 
tiliroside (3), were isolated from the ethanolic extract of Gomphrena 
agrestis. The structural determination of 1 was based on spectroscopic 
and spectrometric data. The substance was defined as (E)-3'-O-beta-D-
glucopyranosyl-4,5,6,4'-tetrahydroxy-7,2'-dimethoxyaurone. Biological 
activity of the ethanolic crude extract and isolated compounds against 
bacteria, fungi and Leishmania amazonensis amastigotes was evaluated. 
This appears to be the first report documenting aurone and aurantiamide 
compounds in the Amaranthaceae family. In the evaluation of biological 
activity the ethanolic extract of G. agrestis and compounds 1, 2, and 3 
were shown to be active mainly against Staphylococcus aureus, 
Staphylococcus epidermidis and Pseudomonas aeruginosa.


 The following references are revised files and are brought to you in accordance
to license agreement with the NLM.


PMID: 10212451

TITLE: A theoretical study of random segregation of minicircles in

AUTHORS: N J Savill, P G Higgs

AFFILIATION: School of Biological Sciences, Manchester University, UK.
nicholas.savill at man.ac.uk

REFERENCE: Proc Biol Sci 1999 Mar 266(1419):611-20

The kinetoplast (k) DNA network of trypanosomatids is made up of 
approximately 50 maxicircles and the order of 10(4) minicircles. It has 
been proposed, based on various observations and experiments, that the 
minicircles are randomly segregated between daughter cells when the 
parent cell divides. In this paper, this random segregation hypothesis 
is theoretically tested in a population dynamics model to see if it can 
account for the observed phenomena. The hypothesis is shown to 
successfully explain, in Leishmania tarentolae, the observation that 
there are a few major and many minor minicircle classes, the 
fluctuations of minicircle class copy numbers over time, the loss of non
-essential minicircle classes, the long survival times of a few of these
 classes and that these classes are likely to be the major classes 
within the population. Implications of the model are examined for 
trypanosomatids in general, leading to several predictions. The model 
predicts variation in network size within a population, variation in the
 average network size and large-scale changes in class copy number over 
long time-scales, an evolutionary pressure towards larger network sizes
, the selective advantage of non-random over random segregation, very 
strong selection for the amplified class in Crithidia fasciculata if its
 minicircles undergo random segregation and that Trypanosoma brucei may 
use sexual reproduction to maintain its viability.

PMID: 1349176

TITLE: The regulation of immunological responses to parasitic infections and the
development of tolerance.

AUTHORS: A N Schweitzer, R M Anderson

AFFILIATION: Wellcome Research Centre for Parasitic Diseases, Biology
Department, Imperial College, London University, U.K.

REFERENCE: Proc Biol Sci 1992 Feb 247(1319):107-12

It is well established that specific unresponsiveness to immunization 
can be induced by prolonged exposure to antigenic proteins. More 
generally, many parasitic infections, such as the helminth worms and the
 Leishmania parasites, appear to be able to persist in some of their 
human hosts over long periods of time, via what appears to be an ability
 to induce defective or inappropriate T-cell responses (= tolerance). 
Recent research has suggested that cytokines, produced by specific 
subsets of CD4+ T-cells (characterized by cytokine secretory profiles 
and growth properties), have an important, and often complex, role in 
promoting or inhibiting host protective immunity to parasitic infections
. By examination of the population dynamics of the stimulation and 
regulation of cellular responses to infection, via the use of simple 
mathematical models, we show that nonlinear interactions between CD4+ T-
cell subsets and their secreted cytokines can result in either host 
protection or immunological unresponsiveness, depending on the magnitude
 and duration of exposure to parasitic infection. Analyses also identify
 a possible mechanism to explain the stimulation of two separate peaks 
of enhanced T-cell-mediated responses over a wide range of levels of 
antigenic exposure.

PMID: 1682935

TITLE: Chitinase secreted by Leishmania functions in the sandfly vector.

AUTHORS: Y Schlein, R L Jacobson, J Shlomai

AFFILIATION: Department of Parasitology, Hadassah Medical School, Jerusalem,

REFERENCE: Proc Biol Sci 1991 Aug 245(1313):121-6

Leishmania major parasites ingested with host blood by the sandfly 
Phlebotomus papatasi multiply confined within the peritrophic membrane. 
This membrane consists of a chitin framework and a protein carbohydrate 
matrix and it is secreted around the food by the insect midgut. 
Histological sections of infected flies show lysis of the chitin layer 
in the anterior region of the peritrophic membrane that permits the 
essential forward migration of a concentrated mass of parasites. Both 
the location and the nature of this disintegration are specific to 
infected flies. At a later stage the parasites concentrate in the 
cardiac valve region and subsequently this segment of the fore gut loses
 its cuticular lining. We have found that chitinase and N-
acetylglucosaminidase are secreted by cultured L. major promastigotes, 
but not by sandfly guts. Hence lysis of the chitin layer of the 
peritrophic membrane could be catalysed by these enzymes of the 
parasites. Activity of both enzymes was also observed in other 
trypanosomatids, including L. donovani, L. infantum, L. braziliensis, 
Leptomonas seymouri, Crithidia fasciculata and Trypanosoma lewisi.

PMID: 22860

TITLE: Leishmania in phlebotomid sandflies: VI. Importance of hindgut
development in distinguishing between parasites of the Leishmania mexicana and
L. braziliensis complexes.

AUTHORS: R Lainson, R D Ward, J J Shaw

REFERENCE: Proc R Soc Lond B Biol Sci 1977 Nov 199(1135):309-20

PMID: 20640

TITLE: Leishmania in phlebotomid sandflies. V. The nature and significance of
infections of the pylorus and ileum of the sandfly by leishmaniae of the
braziliensis complex.

AUTHORS: R Killick-Kendrick, D H Molyneux, M Hommel, A J Leaney, E S Robertson

REFERENCE: Proc R Soc Lond B Biol Sci 1977 Aug 198(1131):191-9

PMID: 240164

TITLE: Leishmania in phlebotomid sandflies. III. The ultrastructure of
Leishmania mexicana amazonensis in the midgut and pharynx of Lutzomyia

AUTHORS: D H Molyneux, R Killick-Kendrick, R W Ashford

REFERENCE: Proc R Soc Lond B Biol Sci 1975 Aug 190(1100):341-57

PMID: 235131

TITLE: Leishmania in phlebotomid sandflies. II. The insusceptibility of sandfly
larvae to Leishmania.

AUTHORS: R Killick-Kendrick, R D Ward

REFERENCE: Proc R Soc Lond B Biol Sci 1975 Feb 188(1091):229-31

PMID: 4155502

TITLE: Leishmania in phlebotomid sandflies. I. Modifications of the flagellum
associated with attachment to the mid-gut and oesophageal valve of the

AUTHORS: R Killick-Kendrick, D H Molyneux, R W Ashford

REFERENCE: Proc R Soc Lond B Biol Sci 1974 Nov 187(1089):409-19

REQUEST: [ sand fly ]

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

REQUEST: [ sandfly ]

(8 articles match this request. 7 articles matching other requests removed)


 The following references are revised files and are brought to you in accordance
to license agreement with the NLM.


PMID: 10821613

TITLE: Adaptive female choice for middle-aged mates in a lekking sandfly.

AUTHORS: T M Jones, A Balmford, R J Quinnell

AFFILIATION: Department of Animal Ecology, Evolutionary Biology Centre, Uppsala,
Sweden. theresa.jones at evolution.uu.se

REFERENCE: Proc Biol Sci 2000 Apr 267(1444):681-6

Most theoretical models of age-related mate choice predict that females 
should prefer older males because they have proven survival ability. An 
alternative view is that older males represent inferior mates because of
 negative genetic correlations between early and late fitness components
, or because older males have traded off longevity against other fitness
 components, have accumulated deleterious germ-line mutations, or are 
less well adapted to current conditions than more recently born 
individuals. While numerous studies have reported female choice for 
older males, few have explicitly examined the fitness consequences of 
such a preference. We present evidence from a lekking sandfly, Lutzomyia
 longipalpis, showing that choosy females discriminate against older 
males and gain a fitness benefit from their choice. When permitted free 
choice from an aggregation consisting of males aged zero to two days (
young), four to six days (middle-aged) and eight to ten days (old), 
females preferentially mated with middle-aged males, but all measures of
 female reproductive success were independent of male age. In contrast, 
when a second set of females was randomly assigned single virgin males 
of known age, the eggs of those paired to old mates exhibited lower 
hatching success than the eggs of females mated to young or middle-aged 
males. These results suggest that females avoid mating with older males 
because they represent poorer quality mates. Age-related differences in 
male quality may have a genetic basis, but could equally well arise 
through a phenotypic decline in sperm quality or sperm transfer ability 
with male age. The lack of evidence of female discrimination against 
older males from other studies may be because these did not explore the 
reproductive success of the full age range of males.

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