[leish-l] Fwd: Articles found by RefScout -2005/10/26 - 2005/43

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Thu Oct 27 10:29:49 BRST 2005


    Date: Wed, 26 Oct 2005 05:36:21
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This is RefScout-Newsletter 43/2005.






REQUEST: [ leishmaniasis ]

(17 articles match this request)



PMID: 16150644
 

TITLE: Chemotherapy of trypanosomiases and leishmaniasis.

AUTHORS: Simon L Croft, Michael P Barrett, Julio A Urbina

AFFILIATION: Drugs for Neglected Diseases Initiative, 1 Place Saint-Gervais,
CH-1201 Geneva, Switzerland.

REFERENCE: Trends Parasitol 2005 Nov 21(11):508-12

New formulations, therapeutic switching of the established drugs 
amphotericin B and paromomycin, and the serendipitous discovery of 
miltefosine have markedly improved leishmaniasis chemotherapy in the 
past 21 years. The situation for the two trypanosomiases has been less 
encouraging. Apart from the introduction of eflornithine for the 
treatment of late-stage human African trypanosomiasis, with its serious 
limitations in terms of cost and difficulty of administration, no new 
drugs have been incorporated into the chemotherapeutic arsenal in the 
past 25 years, despite important advances in knowledge of the biology of
 the etiological agents and the pathophysiology of these diseases. In 
the case of Chagas disease, several classes of compound that target the 
validated biochemical pathways of the parasite (e.g. inhibitors of 
sterol biosynthesis and cysteine proteases) are in the pipeline. With 
the availability of complete genome sequences for all three pathogens, 
and methods for rapid validation of targets, it is hoped that much-
needed amelioration will occur soon. Financial constraints continue to 
represent a major hurdle to drug development. However, the appearance of
 not-for-profit product-development partnerships offers a new paradigm 
for bringing new drugs to patients.








PMID: 16239566
 

TITLE: Interleukin-4 (IL-4) and IL-10 Collude in Vaccine Failure for Novel
Exacerbatory Antigens in Murine Leishmania major Infection.

AUTHORS: Mark T M Roberts, Carmel B Stober, Andrew N McKenzie, Jenefer M
Blackwell

AFFILIATION: Cambridge Institute for Medical Research, Wellcome Trust/MRC
Building, Addenbrooke's Hospital, Hills Rd., Cambridge CB2 2XY, United Kingdom.
jennie.blackwell at cimr.cam.ac.uk.

REFERENCE: Infect Immun 2005 Nov 73(11):7620-8

Leishmaniasis affects 12 million people but there are no vaccines in 
routine use. Recently, we used DNA vaccination in a susceptible BALB/c 
high-dose model of infection to screen 100 novel Leishmania major genes 
as vaccine candidates. In addition to finding novel protective antigens
, we identified several antigens that reproducibly exacerbated disease. 
Here we examined the immune response to two of these antigens, lmd29 and
 584C, that were originally identified in an expressed sequence tag cDNA
 sequencing project. We show that, in addition to exacerbating disease 
in susceptible BALB/c mice, these antigens retain a propensity to 
exacerbate disease in resistant C57BL/6 mice. This ability to exacerbate
 disease was lost when susceptible BALB/c mice were rendered resistant 
by disruption of the genes encoding interleukin-4 (IL-4) alone, IL-4/IL-
13, or IL-4, IL-5, IL-9, and IL-13. Failure to exacerbate disease was 
associated with reduced IL-5 and IL-10 production in IL-4 knockout mice
. Treatment of lmd29-vaccinated mice with anti-IL-10 receptor antibody 
prior to challenge infection converted exacerbation in wild-type BALB/c 
mice into highly significant antigen-specific protection. These studies 
demonstrate that some highly immunogenic antigens of L. major, while 
having an intrinsic capacity to exacerbate disease in the context of 
otherwise T helper 1-promoting DNA vaccine delivery, can be rendered 
protective by the removal of functional IL-10.




PMID: 16235183
 

TITLE: Tegumentary leishmaniasis as a manifestation of immune reconstitution
inflammatory syndrome in 2 patients with AIDS.

AUTHORS: Maria P Posada-Vergara, Jose A L Lindoso, Jose Eduardo Tolezano, Vera
Lucia Pereira-Chioccola, Marcos Vinicius Silva, Hiro Goto

AFFILIATION: Laboratorio de Soroepidemiologia e Imunobiologia, Instituto de
Medicina Tropical de Sao Paulo, Departamento de Doencas Infecciosas e
Parasitarias and Instituto de Infectologia Emilio Ribas, Sao Paulo, Brazil.

REFERENCE: J Infect Dis 2005 Nov 192(10):1819-22

Immune reconstitution inflammatory syndromes (IRISs) have been reported 
in patients with human immunodeficiency virus/acquired immunodeficiency 
syndrome (AIDS) since the introduction of highly active antiretroviral 
therapy (HAART). This syndrome is characterized by clinical 
manifestations of opportunistic infections when signs of immune 
reconstitution are observed during therapy. We report on leishmaniasis, 
suggestive of HAART-induced IRIS, in 2 patients with AIDS. After 
beginning HAART, 1 patient presented with disseminated, tegumentary 
lesions, whereas the other patient's preexisting lesions worsened and 
became more extensive; however, at the same time, their CD4(+) T cell 
counts were recovering and their virus loads were decreasing 
significantly. The lesions healed with anti-Leishmania therapy.




PMID: 16243129
 

TITLE: Leishmania tropica in northern Israel: a clinical overview of an emerging
focus.

AUTHORS: Ayelet Shani-Adir, Stephanie Kamil, Dganit Rozenman, Eli Schwartz,
Michal Ramon, Lucia Zalman, Abed Nasereddin, Charles L Jaffe, Moshe Ephros

AFFILIATION: Department of Dermatology, Emek Medical Center, Afula, Israel.
adir-sh at zahav.net.il

REFERENCE: J Am Acad Dermatol 2005 Nov 53(5):810-5

BACKGROUND: In Israel, most cutaneous leishmaniasis (CL) is caused by 
Leishmania major. Recently a new focus of CL caused by Leishmania 
tropica has been described in Tiberias and the surrounding area of 
northern Israel. OBJECTIVE: The aim of this study was to evaluate 
clinical (size, number, location, and type of lesion) and laboratory (
culture and polymerase chain reaction [PCR] analysis) parameters at 
diagnosis, response to treatment, and outcome of patients with CL due to
 L tropica. METHODS: Between September 2002 and March 2004, patients 
with direct smear-confirmed CL were evaluated; clinical records were 
reviewed and a telephone survey was performed. RESULTS: Forty nine 
patients, 34 (69%) male and 15 (31%) female, were studied. Mean age was 
31.1 years (median 26 years, range 1-70); 76% of patients live in 
Tiberias and the surrounding area. The mean number of lesions was 2.6 (
median 2, range 1-10). Lesions were commonly located on the face (61%) 
and upper limbs (57%). PCR analysis was performed in 27 patients and was
 positive for L tropica in 26. Fifty percent of patients studied 
received multiple therapeutic regimens because of incomplete response or
 treatment failure. Topical paromomycin was used in 44 patients (90%), 
with a complete response reported in only 17 (39%); of the 9 patients 
treated with intralesional sodium stibogluconate, a complete response 
was reported in 6 (67%); of the 5 patients treated with intravenous 
sodium stibogluconate, 4 (80%) were cured. LIMITATIONS: The relatively 
small number of patients studied combined with the fact that some were 
assessed retrospectively limit our conclusions. In addition, 50% of the 
patients studied received multiple therapeutic regimens because of 
failure of, or incomplete responses to, their initial therapy, thereby 
making comparisons difficult. CONCLUSIONS: The cure rate in those 
completing a course of antimony therapy, either 10 or more days of 
intravenous therapy or therapy administered intralesionally, was 75% (95
% confidence interval [CI], 50.5-99.5%) as compared with 45% (95% CI, 28
.9-60.5%) among those completing at least 10 days of topical paromomycin
. To date, no standardized, simple, safe, and highly effective regimen 
for treating L tropica exists. Large, controlled clinical trials to 
evaluate current treatment regimens as well as new medications for CL, 
and especially CL attributed to L tropica, are urgently needed.




PMID: 16211660
 

TITLE: Effect of Pyrazoloquinoline Derivatives on the Growth of Leishmania
donovani Promastigotes.

AUTHORS: Ahmed Al-Qahtani, Yunus M Siddiqui, Adnan A Bekhit, Ola A El-Sayed,
Hassan Y Aboul-Enein, Mohammed N Al-Ahdalb

AFFILIATION: Zoology Department, College of Science, King Saud University,
Riyadh, Saudi Arabia.

REFERENCE: Arch Pharm (Weinheim) 2005 Oct 338(10):484-7

A screening study was conducted to examine the effect of a series of 
synthesized pyrazoloquinoline derivatives on the growth of Leishmania 
donovani promastigotes. Sixteen compounds were tested, ten of which 
showed an inhibitory effect on the growth of promastigotes. Compound 1 
demonstrated potent antileishmanial activity, followed by compounds 3 
and 7. Some compounds showed less significant activities, while others 
exhibited little or no activity. Some of these compounds may be 
potential candidates for future treatment of leishmaniasis.




PMID: 16244972
 

TITLE: Pancreatitis associated with N-methyl-glucamine therapy in a dog with
leishmaniasis.

AUTHORS: G Aste, M Di Tommaso, J M Steiner, D A Williams, A Boari

AFFILIATION: Department of Veterinary Clinical Sciences, Section of Internal
Medicine, Faculty of Veterinary Medicine, University of Teramo, 64100, Teramo,
Italy, gaste at unite.it.

REFERENCE: Vet Res Commun 2005 Aug 29 Suppl 2():269-72




PMID: 16244980
 

TITLE: Real-time PCR in dogs treated for leishmaniasis with allopurinol.

AUTHORS: M G Pennisi, S Reale, S Lo Giudice, M Masucci, S Caracappa, M Vitale, F
Vitale

AFFILIATION: Department of Veterinary Medical Science, Faculty of Veterinary
Medicine, University of Messina, Polo Universitario dell'Annunziata, 98168,
Messina, Italy, MariaGrazia.Pennisi at unime.it.

REFERENCE: Vet Res Commun 2005 Aug 29 Suppl 2():301-3








PMID: 16244984
 

TITLE: Feline leishmaniasis and ehrlichiosis: serological investigation in
abruzzo region.

AUTHORS: S Vita, D Santori, I Aguzzi, E Petrotta, A Luciani

AFFILIATION: Dipartimento di Scienze Cliniche Veterinarie, Università degli
Studi di Teramo, Viale Crispi 212, I-64100, Teramo, Italy, boari at unite.it.

REFERENCE: Vet Res Commun 2005 Aug 29 Suppl 2():319-21




PMID: 16122087
 

TITLE: Vaccinations with live-attenuated Leishmania major promastigotes and
challenge infection with L. major in BALB/c mice.

AUTHORS: J A Onyalo, D M Mwala, C O Anjili, A S Orago, W K Tonui

AFFILIATION: Zoology Department, Kenyatta University, P.O. box 43844, Nairobi,
Kenya.

REFERENCE: East Afr Med J 2005 Apr 82(4):193-7

BACKGROUND: Currently there is no vaccine available in use against any 
form of leishmaniases worldwide. OBJECTIVE: To assess potential of a 
live-attenuated Leishmania major promastigates, for protection against a
 challenge infection with L. major in BALB/c mice. DESIGN: A laboratory 
based study. SETTING: Study was carried out at Centre for Biotechnology 
Research and Development, Kenya Medical Research Institute, Nairobi. 
RESULTS: The greatest protection against challenge with L. major was 
seen in mice immunised with live parasites (P < 0.001) compared to 
vaccinations with heat killed or soluble antigens. In general, immunised
 mice produced high level of antileishmanial antibodies and T cell 
stimulation to their respective antigens. CONCLUSIONS: Our live-
attenuated parasites produced by serial sub-culture of L. major 
parasites 118 times showed the capacity to induce appropriate cell-
mediated immune responses and protection against L. major infection in 
BALB/c mice. Data also suggests that these parasites do not revert to 
virulence when injected subcutaneously in mice.




********************************************************************************************************************

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

********************************************************************************************************************


PMID: 12117930
 

TITLE: Immunization with a polyprotein vaccine consisting of the T-Cell antigens
thiol-specific antioxidant, Leishmania major stress-inducible protein 1, and
Leishmania elongation initiation factor protects against leishmaniasis.

AUTHORS: Rhea N Coler, Yasir A W Skeiky, Karen Bernards, Kay Greeson, Darrick
Carter, Charisa D Cornellison, Farrokh Modabber, Antonio Campos-Neto, Steven G
Reed

AFFILIATION: Infectious Disease Research Institute, Seattle, Washington 98104,
USA. coler at idri.org

REFERENCE: Infect Immun 2002 Aug 70(8):4215-25

Development of an effective vaccine against Leishmania infection is a 
priority of tropical disease research. We have recently demonstrated 
protection against Leishmania major in the murine and nonhuman primate 
models with individual or combinations of purified leishmanial 
recombinant antigens delivered as plasmid DNA constructs or formulated 
with recombinant interleukin-12 (IL-12) as adjuvant. In the present 
study, we immunized BALB/c mice with a recombinant polyprotein 
comprising a tandem fusion of the leishmanial antigens thiol-specific 
antioxidant, L. major stress-inducible protein 1 (LmSTI1), and 
Leishmania elongation initiation factor (LeIF) delivered with adjuvants 
suitable for human use. Aspects of the safety, immunogenicity, and 
vaccine efficacy of formulations with each individual component, as well
 as the polyprotein referred to as Leish-111f, were assessed by using 
the L. major challenge model with BALB/c mice. No adverse reactions were
 observed when three subcutaneous injections of the Leish-111f 
polyprotein formulated with either MPL-squalene (SE) or Ribi 529-SE were
 given to BALB/c mice. A predominant Th1 immune response characterized 
by in vitro lymphocyte proliferation, gamma interferon production, and 
immunoglobulin G2A antibodies was observed with little, if any, IL-4. 
Moreover, Leish-111f formulated with MPL-SE conferred immunity to 
leishmaniasis for at least 3 months. These data demonstrate success at 
designing and developing a prophylactic leishmaniasis vaccine that 
proved effective in a preclinical model using multiple leishmanial 
antigens produced as a single protein delivered with a powerful Th1 
adjuvant suitable for human use.




PMID: 12010969
 

TITLE: Vaccination with plasmid DNA encoding TSA/LmSTI1 leishmanial fusion
proteins confers protection against Leishmania major infection in susceptible
BALB/c mice.

AUTHORS: A Campos-Neto, J R Webb, K Greeson, R N Coler, Y A W Skeiky, S G Reed

AFFILIATION: Infectious Disease Research Institute. Corixa Corporation, Seattle,
Washington 98104, USA. acampos at idri.org

REFERENCE: Infect Immun 2002 Jun 70(6):2828-36

We have recently shown that a cocktail containing two leishmanial 
recombinant antigens (LmSTI1 and TSA) and interleukin-12 (IL-12) as an 
adjuvant induces solid protection in both a murine and a nonhuman 
primate model of cutaneous leishmaniasis. However, because IL-12 is 
difficult to prepare, is expensive, and does not have the stability 
required for a vaccine product, we have investigated the possibility of 
using DNA as an alternative means of inducing protective immunity. Here
, we present evidence that the antigens TSA and LmSTI1 delivered in a 
plasmid DNA format either as single genes or in a tandem digene 
construct induce equally solid protection against Leishmania major 
infection in susceptible BALB/c mice. Immunization of mice with either 
TSA DNA or LmSTI1 DNA induced specific CD4(+)-T-cell responses of the 
Th1 phenotype without a requirement for specific adjuvant. CD8 responses
, as measured by cytotoxic-T-lymphocyte activity, were generated after 
immunization with TSA DNA but not LmSTI1 DNA. Interestingly, vaccination
 of mice with TSA DNA consistently induced protection to a much greater 
extent than LmSTI1 DNA, thus supporting the notion that CD8 responses 
might be an important accessory arm of the immune response for acquired 
resistance against leishmaniasis. Moreover, the protection induced by 
DNA immunization was specific for infection with Leishmania, i.e., the 
immunization had no effect on the course of infection of the mice 
challenged with an unrelated intracellular pathogen such as 
Mycobacterium tuberculosis. Conversely, immunization of BALB/c mice with
 a plasmid DNA that is protective against challenge with M. tuberculosis
 had no effect on the course of infection of these mice with L. major. 
Together, these results indicate that the protection observed with the 
leishmanial DNA is mediated by acquired specific immune response rather 
than by the activation of nonspecific innate immune mechanisms. In 
addition, a plasmid DNA containing a fusion construct of the two genes 
was also tested. Similarly to the plasmids encoding individual proteins
, the fusion construct induced both specific immune responses to the 
individual antigens and protection against challenge with L. major. 
These results confirm previous observations about the possibility of DNA
 immunization against leishmaniasis and lend support to the idea of 
using a single polygenic plasmid DNA construct to achieve polyspecific 
immune responses to several distinct parasite antigens.




PMID: 11349082
 

TITLE: Protection against cutaneous leishmaniasis induced by recombinant
antigens in murine and nonhuman primate models of the human disease.

AUTHORS: A Campos-Neto, R Porrozzi, K Greeson, R N Coler, J R Webb, Y A Seiky, S
G Reed, G Grimaldi

AFFILIATION: Infectious Disease Research Institute, Seattle, Washington 98104,
USA. acampos at idri.org

REFERENCE: Infect Immun 2001 Jun 69(6):4103-8

Leishmaniasis affects approximately 2 million people each year 
throughout the world. This high incidence is due in part to the lack of 
an efficacious vaccine. We present evidence that the recombinant 
leishmanial antigens LmSTI1 and TSA, which we identified and 
characterized previously, induce excellent protection in both murine and
 nonhuman primate (rhesus monkey) models of human cutaneous 
leishmaniasis. The remarkable protection induced by LmSTI1 and TSA in an
 animal model that is evolutionarily close to humans qualifies this 
antigen combination as a promising candidate subunit vaccine against 
human leishmaniasis.




PMID: 13881433
 

TITLE: [Italian foci of kala-azar and the problem of leishmaniasis in Southern
Europe.]

AUTHORS: A CORRADETTI

REFERENCE: Rend Ist Sup Sanit 1961  24():281-4




PMID: 13420605
 

TITLE: [Epidemiological studies of kala azar in the Promontorio Garganico
(Puglie, Province of Foggia).]

AUTHORS: A CORRADETTI, G SACCA, I NERI

REFERENCE: Rend Ist Sup Sanit 1956  19(12):1230-6








PMID: 13255107
 

TITLE: [A focus of kala-azar in Monte Argentario, Tuscan Tyrrhenian coast.]

AUTHORS: A CORRADETTI, I NERI

REFERENCE: Rend Ist Sup Sanit 1955  18(5):376-9




PMID: 13186193
 

TITLE: [The fight against leishmaniasis by means of the Phlebotomus control in
Italy.]

AUTHORS: A CORRADETTI

REFERENCE: Rend Ist Sup Sanit 1954  17(5):374-84




PMID: 14958069
 

TITLE: [Epidemiological studies on cutaneous leishmaniasis in Abruzzo and
experience with total interruption of transmission (1948-50).]

AUTHORS: A CORRADETTI

REFERENCE: Rend Ist Sup Sanit 1952  15(3):181-7




REQUEST: [ leishmania ]

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



PMID: 16239557
 

TITLE: Invariant NKT Cells Are Essential for the Regulation of Hepatic CXCL10
Gene Expression during Leishmania donovani Infection.

AUTHORS: Mattias Svensson, Soombul Zubairi, Asher Maroof, Fatima Kazi, Masaru
Taniguchi, Paul M Kaye

AFFILIATION: Immunology and Infection Unit, Department of Biology, University of
York, Heslington, York YO10 5YW, United Kingdom. pmk2 at york.ac.uk.

REFERENCE: Infect Immun 2005 Nov 73(11):7541-7

Gamma interferon (IFN-gamma)-regulated chemokines of the CXC family have
 been implicated as key regulators of a variety of T-cell-dependent 
inflammatory processes. However, the cellular source(s) of IFN-gamma 
that regulates their early expression has rarely been defined. Here, we 
have directly addressed this question in mice after Leishmania donovani 
infection. Comparison of CXCL10 mRNA accumulation in normal and IFN-
gamma-deficient mice confirmed an absolute requirement for IFN-gamma for
 sustained (24 h) expression of CXCL10 mRNA accumulation in this model. 
In normal mice, IFN-gamma was produced by both CD3(int) NK1.1(+) NKT 
cells and CD3(-) NK1.1(+) NK cells, as detected by intracellular flow 
cytometry. Strikingly, B6.Jalpha281(-/-) mice lacking NKT cells that 
express the invariant Valpha14Jalpha18 T-cell-receptor alpha chain, 
although retaining a significant population of IFN-gamma-producing NK 
cells and NKT cells, were unable to sustain CXCL10 mRNA accumulation. 
These data indicate that invariant NKT cells are indispensable for the 
regulation of hepatic CXCL10 gene expression during L. donovani 
infection.




PMID: 16237047
 

TITLE: Cutting edge: a critical role for gene silencing in preventing excessive
type 1 immunity.

AUTHORS: Anne S Hutchins, David Artis, Brian D Hendrich, Adrian P Bird, Phillip
Scott, Steven L Reiner

AFFILIATION: Abramson Family Cancer Research Institute and Department of
Medicine and.

REFERENCE: J Immunol 2005 Nov 175(9):5606-10

Immunity often depends on proper cell fate choice by helper T 
lymphocytes. A naive cell, with minimal expression of IFN-gamma and IL-4
, must give rise to progeny expressing high levels of either one, but 
not both, of those cytokines to defend against protozoan and helminthic 
pathogens, respectively. In the present study, we show that inactivation
 of the Mbd2 gene, which links DNA methylation and repressed chromatin, 
results in enhanced resistance to the protozoan parasite Leishmania 
major but impaired immunity to the intestinal helminth Trichuris muris. 
Helper T cells from methyl CpG-binding domain protein-2-deficient mice 
exhibit exuberant patterns of cytokine expression despite appropriate 
silencing of genes encoding the lineage-specifying factors T-bet and 
GATA-3. These results suggest that gene silencing can facilitate the 
ability of a progenitor cell to give rise to appropriately 
differentiated daughter cells in vivo. These findings also point to 
novel pathways that could participate in genetic control of resistance 
to infection and autoimmunity.




PMID: 16046090
 

TITLE: In vitro cytotoxic, antileishmanial and antifungal activities of
ethnopharmacologically selected Gabonese plants.

AUTHORS: M Lamidi, C Digiorgio, F Delmas, A Favel, C Eyele Mve-Mba, M L Rondi, E
Ollivier, L Nze-Ekekang, G Balansard

AFFILIATION: IPHAMETRA (Institute of Traditional Pharmacopoeia and Medicine),
CENAREST, BP 842 Libreville, Gabon.

REFERENCE: J Ethnopharmacol 2005 Nov 102(2):185-90

Seventy-seven crude extracts from leaves and stem barks of 15 Gabonese 
plants used in traditional medicine were evaluated for their cytotoxic, 
antileishmanial and antifungal activities. Most of the extracts 
exhibited cytotoxic activities toward human monocytes, and most 
particularly the hydromethanolic 50% (v/v) fraction of Ganophyllum 
giganteum leaves (IC(50)=1.3mug/ml) as well as the methanolic extracts 
of Polyalthia suaveolens, Dioscorea preussii, Augouardia letestui leaves
 and Cola lizae stem barks (IC(50)<5mug/ml). The methanolic extract 
of Polyalthia suaveolens displayed a strong antiproliferative activity 
against the promastigote form of Leishmania infantum parasites and 
presented a good antifungal activity on all the tested strains (IC(50)&
lt;1mg/ml). This extract was divided into six fractions: fraction F6 
demonstrated a cytotoxic activity stronger than those of the crude 
extract (IC(50)=0.6mug/ml), fractions F4 and F5 were devoid of 
cytotoxicity (IC(50)>100mug/ml) and displayed interesting 
antileishmanial activity against the intracellular amastigote form of 
the parasite (IC(50)=5.6 and 12.4mug/ml), respectively. However, the 
antifungal activity observed for the crude extract could not be 
recovered in the corresponding fractions.




PMID: 16212802
 

TITLE: Phlebotomine sandflies (Diptera: Psychodidae) of the Atlantic forest in
Recife, Pernambuco state, Brazil: the species coming to human bait, and their
seasonal and monthly variations over a 2-year period.

AUTHORS: V Q Balbino, I V Coutinho-Abreu, I V Sonoda, W Marques da Silva, C B
Marcondes

AFFILIATION: Department of Genetics, Federal University of Pernambuco, 50732-970
Recife, Pernambuco, Brazil.

REFERENCE: Ann Trop Med Parasitol 2005 Oct 99(7):683-93

In a study of the phlebotomine sandflies (Diptera: Psychodidae) in a 
forest reserve in Recife, Pernambuco state, north-eastern Brazil, the 
sandflies landing on human bait between 1.00 and 1.42 h after sunset 
were collected weekly for 2 years. Although 10,287 sandflies of 10 
Lutzomyia species were collected, almost all (96.5%) of the sandflies 
caught were Lu. umbratilis. This species and several others caught are 
potential vectors of some of the Leishmania parasites that cause human 
disease. The recorded landing rate for Lu. umbratilis peaked, at the 
high level of 333.3 flies/person-hour, during the collections made in 
May 2003.The relative rarity in the collections of males of some of the 
species caught probably indicates that these species do not lek on their
 bloodmeal sources.It is likely that the sizes of the local populations 
of species that are not very anthrophilic, such as Lu. flaviscutellata, 
are much larger than indicated by the collections made on human bait.








PMID: 16196248
 

TITLE: Parsing parasites.

AUTHORS: Kaspar Mossman

REFERENCE: Sci Am 2005 Oct 293(4):29-30




PMID: 16230473
 

TITLE: Notch signaling is an important regulator of type 2 immunity.

AUTHORS: Lili Tu, Terry C Fang, David Artis, Olga Shestova, Seth E Pross, Ivan
Maillard, Warren S Pear

AFFILIATION: Department of Pathology and Laboratory Medicine, School of
Veterinary Medicine.

REFERENCE: J Exp Med 2005 Oct 202(8):1037-42

Notch ligands and receptors have been implicated in helper T cell (Th 
cell) differentiation. Whether Notch signals are involved in 
differentiation of T helper type 1 (Th1) cells, Th2 cells, or both, 
however, remains unresolved. To clarify the role of Notch in Th cell 
differentiation, we generated mice that conditionally inactivate Notch 
signaling in mature T cells. Mice that lack Notch signaling in CD4(+) T 
cells fail to develop a protective Th2 cell response against the 
gastrointestinal helminth Trichuris muris. In contrast, they exhibit 
effective Th1 cell responses and are able to control Leishmania major 
infection. These data demonstrate that Notch signaling is a regulator of
 type 2 immunity.




PMID: 16002315
 

TITLE: Analysis of ribosomal DNA internal transcribed spacer sequences of the
Leishmania donovani complex.

AUTHORS: Katrin Kuhls, Isabel L Mauricio, Francine Pratlong, Wolfgang Presber,
Gabriele Schönian

AFFILIATION: Institute of Microbiology and Hygiene (Parasitology), Charité
Universitätsmedizin Berlin, Dorotheenstr, 96, 10117 Berlin, Germany.

REFERENCE: Microbes Infect 2005 Aug 7(11-12):1224-34

To understand phylogenetic relationships of species and strains within 
the Leishmania donovani complex, we have analyzed the ribosomal DNA 
internal transcribed spacer (ITS) sequences of 27 Leishmania infantum, 2
 Leishmania chagasi, 18 L. donovani and 5 Leishmania archibaldi strains 
of different zymodemes and geographical origin. Eight ITS sequence types
 were found. All detected sequence variation within ITS1 and ITS2 was 
based on 12 polymorphic microsatellites. The L. infantum strains from 
the Mediterranean region, China and L. chagasi from the New World formed
 a phylogenetic group well separated from the second main group 
including all strains from East Africa and India. Within the latter 
group three distinct phylogenetic subgroups could be differentiated: (1
) L. donovani (Sudan/Ethiopia, China)+L. archibaldi (Sudan), (2) L. 
donovani (Sudan/Ethiopia)+L. infantum (Sudan)+L. archibaldi (Sudan/
Ethiopia), and (3) L. donovani (Kenya, India). These groups are not 
consistent with previous species definitions based on isoenzyme analyses
, e.g. L. infantum is polyphyletic and L. archibaldi is not supported as
 a distinct species. Two groups of Indian strains could be 
differentiated, one of which has an identical sequence type to the 
strains from Kenya. Three main lineages of strains can thus be 
differentiated in East Africa: two quite distantly related groups of 
strains from Sudan/Ethiopia, and a third group including all strains 
from Kenya, which is more closely related to part of the Indian strains 
than to any of the Sudanese/Ethiopian groups. The ITS sequence analysis 
presented here supports the need for revision of the taxonomy of the L. 
donovani complex.




********************************************************************************************************************

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

********************************************************************************************************************


PMID: 12529367
 

TITLE: Role of peroxidoxins in Leishmania chagasi survival. Evidence of an
enzymatic defense against nitrosative stress.

AUTHORS: Stephen D Barr, Lashitew Gedamu

AFFILIATION: Department of Biological Sciences, University of Calgary, Alberta
T2N 1N4, Canada.

REFERENCE: J Biol Chem 2003 Mar 278(12):10816-23

The mechanisms by which Leishmania parasites survive exposure to highly 
reactive oxygen (ROS) and nitrogen (RNS) species within phagosomes of 
macrophages are not well known. Recently it has been shown that RNS 
alone is sufficient and necessary to control Leishmania donovani 
infection in mice (Murray, H. W., and Nathan, C. F. (1999) J. Exp. Med. 
189, 741-746). No enzymatic defense against RNS has been discovered in 
Leishmania to date. We have previously isolated two peroxidoxins (LcPxn1
 and LcPxn2) from Leishmania chagasi and showed that recombinant LcPxn1 
protein was capable of detoxifying hydrogen peroxide, hydroperoxide, and
 hydroxyl radicals (Barr, S. D., and Gedamu, L. (2001) J. Biol. Chem. 
276, 34279-34287). In further characterizing the physiological role of 
peroxidoxins in Leishmania survival, we show here that recombinant 
LcPxn1 protein can detoxify RNS in addition to ROS, whereas recombinant 
LcPxn2 protein can only detoxify hydrogen peroxide. LcPxn1 and LcPxn2 
are localized to the cytoplasm, and overexpression of LcPxn1 in L. 
chagasi parasites enhanced survival when exposed to exogenous ROS and 
RNS and enhanced survival within U937 macrophage cells. Site-directed 
mutagenesis studies revealed that the conserved Cys-52 residue is 
essential for detoxifying hydrogen peroxide, t-butyl hydroperoxide, and 
hydroxyl radicals, whereas the conserved Cys-173 residue is essential 
for detoxifying t-butyl hydroperoxide and peroxynitrite. This is the 
first report of an enzymatic defense against RNS in Leishmania.




PMID: 12446214
 

TITLE: Specificity and kinetics of a mitochondrial peroxiredoxin of Leishmania
infantum.

AUTHORS: Helena Castro, Heike Budde, Leopold Flohé, Birgit Hofmann, Heinrich
Lünsdorf, Joseph Wissing, Ana M Tomás

AFFILIATION: Institute for Molecular and Cell Biology, Porto, Portugal.

REFERENCE: Free Radic Biol Med 2002 Dec 33(11):1563-74

In Kinetoplastida, comprising the medically important parasites 
Trypanosoma brucei, T. cruzi, and Leishmania species, 2-Cys 
peroxiredoxins described to date have been shown to catalyze reduction 
of peroxides by the specific thiol trypanothione using tryparedoxin, a 
thioredoxin-related protein, as an immediate electron donor. Here we 
show that a mitochondrial peroxiredoxin from L. infantum (LimTXNPx) is 
also a tryparedoxin peroxidase. In an heterologous system constituted by
 nicotinamide adenine dinucleotide phosphate (NADPH), T. cruzi 
trypanothione reductase, trypanothione and Crithidia fasciculata 
tryparedoxin (CfTXN1 and CfTXN2), the recombinant enzyme purified from 
Escherichia coli as an N-terminally His-tagged protein preferentially 
reduces H(2)O(2) and tert-butyl hydroperoxide and less actively cumene 
hydroperoxide. Linoleic acid hydroperoxide and phosphatidyl choline 
hydroperoxide are poor substrates in the sense that they are reduced 
weakly and inhibit the enzyme in a concentration- and time-dependent way
. Kinetic parameters deduced for LimTXNPx are a k(cat) of 37.0 s(-1) and
 K(m) values of 31.9 and 9.1 microM for CfTXN2 and tert-butyl 
hydroperoxide, respectively. Kinetic analysis indicates that LimTXNPx 
does not follow the classic ping-pong mechanism described for other 
TXNPx (Phi(1,2) = 0.8 s x microM(2)). Although the molecular mechanism 
underlying this finding is unknown, we propose that cooperativity 
between the redox centers of subunits may explain the unusual kinetic 
behavior observed. This hypothesis is corroborated by high-resolution 
electron microscopy and gel chromatography that reveal the native enzyme
 to preferentially exist as a homodecameric ring structure composed of 
five dimers.




PMID: 12446213
 

TITLE: Complementary antioxidant defense by cytoplasmic and mitochondrial
peroxiredoxins in Leishmania infantum.

AUTHORS: Helena Castro, Carla Sousa, Marta Santos, Anabela Cordeiro-da-Silva,
Leopold Flohé, Ana M Tomás

AFFILIATION: Institute for Molecular and Cell Biology, Porto, Portugal.

REFERENCE: Free Radic Biol Med 2002 Dec 33(11):1552-62

In Kinetoplastida 2-Cys peroxiredoxins are the ultimate members of 
unique enzymatic cascades for detoxification of peroxides, which are 
dependent on trypanothione, a small thiol specific to these organisms. 
Here we report on two distinct Leishmania infantum peroxiredoxins, 
LicTXNPx and LimTXNPx, that may be involved in such a pathway. LicTXNPx
, found in the cytoplasm, is a typical 2-Cys peroxiredoxin encoded by 
LicTXNPx, a member of a multicopy gene family. LimTXNPx, encoded by a 
single copy gene, LimTXNPx, is confined to the mitochondrion and is 
unusual in possessing an Ile-Pro-Cys motif in the distal redox center, 
replacing the common peroxiredoxin Val-Cys-Pro sequence, apart from an N
-terminal mitochondrial leader sequence. Based on sequence and 
subcellular localization, the peroxiredoxins of Kinetoplastida can be 
separated in two distinct subfamilies. As an approach to investigate the
 function of both peroxiredoxins in the cell, L. infantum promastigotes 
overexpressing LicTXNPx and LimTXNPx were assayed for their resistance 
to H(2)O(2) and tert-butyl hydroperoxide. The results show evidence that
 both enzymes are active as peroxidases in vivo and that they have 
complementary roles in parasite protection against oxidative stress.




PMID: 11438539
 

TITLE: Cloning and characterization of three differentially expressed
peroxidoxin genes from Leishmania chagasi. Evidence for an enzymatic
detoxification of hydroxyl radicals.

AUTHORS: S D Barr, L Gedamu

AFFILIATION: Department of Biological Sciences, University of Calgary, Calgary,
Alberta T2N 1N4, Canada.

REFERENCE: J Biol Chem 2001 Sep 276(36):34279-87

Antioxidants have been implicated in protecting cells from oxygen 
radicals produced as a result of aerobic metabolism and in response to 
foreign pathogens by phagocytic cells. The mechanisms allowing pathogens
 to withstand the toxic prooxidant environment within the phagolysosome 
are poorly understood. We have cloned and characterized three 
antioxidant genes belonging to the 2-Cys family of peroxidoxins from 
Leishmania chagasi that may prove to provide these parasites with an 
enhanced defense mechanism against toxic oxidants. The 5'-untranslated 
regions and coding regions of each gene are highly conserved, whereas 
the 3'-untranslated regions have diverged significantly. L. chagasi 
peroxidoxin 1 (LcPxn1) is predominantly expressed in the amastigote 
stage, whereas LcPxn2 and LcPxn3 are expressed mainly in the 
promastigote stage, with LcPxn3 being far less abundant than LcPxn2. 
LcPxn2 and LcPxn3 possess a nine-amino acid extension at the carboxyl 
terminus, which LcPxn1 lacks. LcPxn1 appears to exist as high molecular 
weight multimers in vivo, and recombinant LcPxn1 was shown to detoxify 
hydrogen peroxide and alkyl hydroperoxides. We also present strong 
evidence that recombinant LcPxn1 can enzymatically detoxify hydroxyl 
radicals, an activity never before clearly demonstrated for a protein.




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