[Leish-l] Fwd: Articles found by RefScout 14/2007

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(19 articles match this request)

PMID: 17376453<http://refscout.com/cgi-bin/exportAbstract.pl?base=medline-2007-14.xml&id=17376453>
TITLE: Increased transmission potential of *Leishmania*
major/*Leishmania*infantum
hybrids.<http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=17376453>
AUTHORS: Petr Volf, Ivana Benkova, Jitka Myskova, Jovana Sadlova, Lenea
Campino, Christophe Ravel
AFFILIATION: Department of Parasitology, Faculty of Science, Charles
University, Vinicna 7, Prague 2, 128 44, Czech Republic.
REFERENCE: Int J Parasitol 2007 May 37(6):589-93
Development of *Leishmania* infantum/*Leishmania* major hybrids was studied
in two sand fly species. In Phlebotomus papatasi, which supported
development of L. major but not L. infantum, the hybrids produced heavy
late-stage infections with high numbers of metacyclic promastigotes. In the
permissive vector Lutzomyia longipalpis, all *Leishmania* strains included
in this study developed well. Hybrids were found to express L. major
lipophosphoglycan, apparently enabling them to survive in P. papatasi
midgut. The genetic exchange of the hybrids thus appeared to have enhanced
their transmission potential and fitness. A potentially serious consequence
is the future spread of the hybrids using this peridomestic and
antropophilic vector.


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PMID: 17239885<http://refscout.com/cgi-bin/exportAbstract.pl?base=medline-2007-14.xml&id=17239885>
TITLE: A long term experimental study of canine visceral
leishmaniasis.<http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=17239885>
AUTHORS: Alhelí Rodríguez-CortÃ(c)s, Ana Ojeda, Laura López-Fuertes, Marcos
Timón, Laura Altet, Laia Solano-Gallego, Elisenda Sánchez-Robert, Olga
Francino, Jordi Alberola
AFFILIATION: Departament de Farmacologia, Terapeutica i Toxicologia
Veterinaria, Facultat de Veterinà ria, Universitat Autònoma de Barcelona,
Spain.
REFERENCE: Int J Parasitol 2007 May 37(6):683-93
Previous studies on *Leishmania* infantum and the canine immune response are
derived mainly from short-term studies. To date, there have been no
longitudinal studies that perform a serial analysis of the intensity of
infection in conjunction with immunological parameters and clinical signs in
*Leishmania*-infected dogs. For this purpose, six dogs were infected
experimentally by the i.v. route and were monitored for 1 year . Clinical,
immunological (humoral and cellular response) and parasitological
(parasitaemia) parameters were evaluated monthly. Four dogs developed
clinico-pathological signs compatible with leishmaniasis , whereas two dogs
showed few abnormalities during the study. Evaluation of clinical,
immunological and parasitological parameters showed that the intensity of *
Leishmania* infection in blood samples, as indicated by the amount of *
Leishmania* DNA, was correlated significantly with IgG, IgG1, IgG2, IgA, and
IgM concentrations and with clinical signs. Parasitaemia and
*Leishmania*-specific
cell-mediated immunity were inversely correlated. Moreover, higher
quantities of *Leishmania* DNA were detected in the liver, spleen, lymph
node, skin and bone marrow of dogs exhibiting clinical signs than those
exhibiting few such signs. These findings suggest that progressive disease
in experimental canine leishmaniasis is associated with specific T-cell
unresponsiveness and unprotective humoral responses which allow the
dissemination and multiplication of L. infantum in different tissues.


PMID: 17242145<http://refscout.com/cgi-bin/exportAbstract.pl?base=medline-2007-14.xml&id=17242145>
TITLE: Miltefosine Affects Lipid Metabolism in *Leishmania* donovani
Promastigotes.<http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=17242145>
AUTHORS: M Rakotomanga, S Blanc, K Gaudin, P Chaminade, P M Loiseau
AFFILIATION: ChimiothÃ(c)rapie Antiparasitaire, UMR 8076 CNRS, FacultÃ(c) de
Pharmacie, UniversitÃ(c) Paris-Sud XI, F-92290 Châtenay-Malabry, France.
philippe.loiseau at u-psud.fr.
REFERENCE: Antimicrob Agents Chemother 2007 Apr 51(4):1425-30
Miltefosine (hexadecylphosphocholine [HePC]) is the first orally active
antileishmanial drug. Transient HePC treatment of *Leishmania* donovani
promastigotes at 10 muM significantly reduced the phosphatidylcholine
content and enhanced the phosphatidylethanolamine (PE) content in parasite
membranes, suggesting a partial inactivation of PE-N- methyltransferase.
Phospholipase D activity did not seem to be affected by HePC. In addition,
the enhancement of the lysophosphatidylcholine content could be ascribed to
phospholipase A2 activation. Moreover, transient HePC treatment had no
effect on the fatty acid alkyl chain length or the fatty acid unsaturation
rate. Concerning sterols, we found a strong reduction of the C(24) alkylated
sterol content, and the enhancement of the cholesterol content could be the
result of the HePC condensation effect with sterols. Because some of the
effects observed after transient HePC treatment were different from those
previously observed in HePC-resistant parasites, it could be hypothesized
that continuous in vitro drug pressure induces the mechanisms of regulation
in *Leishmania* lipid metabolism.


PMID: 17283192<http://refscout.com/cgi-bin/exportAbstract.pl?base=medline-2007-14.xml&id=17283192>
TITLE: Miltefosine (Hexadecylphosphocholine) Inhibits Cytochrome c Oxidase
in *Leishmania* donovani
Promastigotes.<http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=17283192>
AUTHORS: Juan Román Luque-Ortega, Luis Rivas
AFFILIATION: Centro de Investigaciones Biológicas (C.S.I.C.), Ramiro de
Maeztu 9, E-28040 Madrid, Spain. luis.rivas at cib.csic.es.
REFERENCE: Antimicrob Agents Chemother 2007 Apr 51(4):1327-32
Miltefosine (hexadecylphosphocholine [HePC]) is currently on trial as a
first-choice, orally active drug for the treatment of visceral leishmaniasis
when resistance to organic pentavalent antimonials becomes epidemic.
However, data on the targets involved in its leishmanicidal mechanism have,
until now, been only fragmentary. We have carried out a systematic study of
the alterations induced on the bioenergetic metabolism of
*Leishmania*donovani promastigotes by HePC. Overnight incubation with
HePC caused a
significant decline in the intracellular ATP levels of the parasites,
together with a reduction in the oxygen consumption rate and mitochondrial
depolarization, while the integrity of the plasma membrane remained
undamaged. In a further step, the effects of HePC on the respiratory chain
were addressed in digitonized parasites. The inhibition of the oxygen
consumption rate caused by HePC was not reverted either with the uncoupling
agent carbonyl cyanide p- trifluoromethoxyphenylhydrazone or with
tetramethyl-p-phenylenediamine plus ascorbate, which feeds the electron
transport chain at the level of cytochrome c. These results suggest that
cytochrome c oxidase is a likely target in the complex leishmanicidal
mechanism of HePC. This was further confirmed from the finding that this
enzyme was specifically inhibited in a dose-dependent manner by HePC, but
not the cytochrome c reductase, ruling out an unspecific effect of HePC on
the respiratory chain.


PMID: 17200144<http://refscout.com/cgi-bin/exportAbstract.pl?base=medline-2007-14.xml&id=17200144>
TITLE: IL-4 induces a wide-spectrum intracellular signaling cascade in CD8+
T cells.<http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=17200144>
AUTHORS: Ana Acacia de Sa Pinheiro, Alexandre Morrot, Sumana Chakravarty,
Michael Overstreet, Jay H Bream, Pablo M Irusta, Fidel Zavala
AFFILIATION: Malaria Research Institute, Bloomberg School of Public Health,
Johns Hopkins University, 615 N. Wolfe St., Baltimore, MD 21205, USA.
fzavala at jhsph.edu.
REFERENCE: J Leukoc Biol 2007 Apr 81(4):1102-10
IL-4 has distinct effects on the differentiation and functional properties
of CD8(+) T cells. In vivo studies have shown that it is critical for the
development of protective memory responses against tumors and infections by
*Leishmania* and Plasmodium parasites. The intracellular signaling events
mediated by IL-4/IL-4 receptor (IL-4R) interactions on CD4(+) T cells have
been studied extensively; however, the nature of IL-4-induced signaling on
CD8(+) T cells has not been characterized. Using naïve, activated, as well
as differentiated CD8 (+) T cells, we show that IL-4 has a strong in vivo
and in vitro antiapoptotic effect on activated and resting CD8(+) T cells.
We demonstrate that IL-4 induces the phosphorylation of the IL-4R, which is
followed by the activation of at least two distinct intracellular signaling
cascades: the Jak1/STAT6 and the insulin receptor substrate/PI -3K/protein
kinase B pathways. We also found that IL-4 induces the Jak3- mediated
phosphorylation and nuclear migration of STAT1, STAT3, and STAT5 in naïve,
activated, as well as differentiated, IFN-gamma- producing CD8(+) T cells.
The induction of this broad signaling activity in CD8(+) T cells coincides
with a transcriptional activity of suppressors of cytokine signaling genes,
which are decreased significantly in comparison with CD4(+) T cells. To our
knowledge, this report constitutes the first comprehensive analysis of the
signaling events that shape CD8(+) T cell responses to IL-4.


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PMID: 17276541<http://refscout.com/cgi-bin/exportAbstract.pl?base=medline-2007-14.xml&id=17276541>
TITLE: Liposomal amphotericin B in comparison to sodium stibogluconate for
cutaneous infection due to *Leishmania*
braziliensis.<http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=17276541>
AUTHORS: Michal Solomon, Sharon Baum, Aviv Barzilai, Alon Scope, Henry Trau,
Eli Schwartz
AFFILIATION: Department of Dermatology, Chaim Sheba Medical Center, Tel
Hashomer, Israel.
REFERENCE: J Am Acad Dermatol 2007 Apr 56(4):612-6
BACKGROUND: New World cutaneous leishmaniasis among Israeli travelers is
mostly acquired in the Amazon Basin of Bolivia where *Leishmania* viannia
(V.) braziliensis is endemic. Treatment with systemic pentavalent antimonial
compounds is effective in achieving clinical cure in only 75 % of cases. In
this study, we assessed liposomal amphotericin B ( AmBisome) as an
alternative treatment for cutaneous L (V.) braziliensis infection. METHODS:
A prospective evaluation was performed for cutaneous leishmaniasis due to L
(V.) braziliensis, proven by polymerase chain reaction. A 3-mg/kg AmBisome
dose was given for 5 consecutive days, and a sixth dose on day 10, all in an
outpatient setting. This therapy was compared with a series of historical
patients who were treated with sodium stibogluconate (SSG). RESULTS: Seven
consecutive patients, 5 males and 2 females, received AmBisome treatment.
All were returned travelers infected in Bolivia; their mean age was
23.1years; 5 had failed to respond to a full course of SSG; two had a
primary
lesion; none had mucosal lesions. All achieved complete clinical cure within
less than 1 month. Mean follow-up of 12 months revealed no relapses. Side
effects were mild, and none had to terminate treatment prematurely .
Comparison of AmBisome to SSG treatment shows that the former is safer ,
with fewer recurrence rates. Additionally, the expense of the total care
with AmBisome is less than with SSG: 45% less if SSG was given in an
inpatient setting; 15% less when SSG was given in an outpatient setting.
LIMITATIONS: This was a nonrandomized study, with relatively few patients.
CONCLUSION: AmBisome treatment for L (V.) braziliensis appears to be
effective, better tolerated, and to have more cost benefit in countries
where hospital-care costs are significant.


PMID: 17350306<http://refscout.com/cgi-bin/exportAbstract.pl?base=medline-2007-14.xml&id=17350306>
TITLE: Antimonial treatment of visceral leishmaniasis: are current in vitro
susceptibility assays adequate for prognosis of in vivo therapy
outcome?<http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=17350306>
AUTHORS: Suman Rijal, Vanessa Yardley, François Chappuis, Saskia Decuypere,
Basudha Khanal, Rupa Singh, Marleen Boelaert, Simonne De Doncker, Simon
Croft, Jean-Claude Dujardin
AFFILIATION: B.P. Koirala Institute of Health Sciences, Ghopa, Dharan,
Nepal.
REFERENCE: Microbes Infect 2007 Apr 9(4):529-35
In most of the Indian subcontinent, the first line treatment for visceral
leishmaniasis (VL) is sodium stibogluconate (SSG), an antimonial drug, but
the efficacy of the drug varies according to region . We aimed to
characterize the in vitro antimony susceptibility of clinical isolates of
Nepalese VL patients, and to correlate this in vitro parasite phenotype to
clinical therapy outcome. Thirty-three clinical isolates of L. donovani were
taken from patients with known disease history. These isolates were typed
and the susceptibility of intracellular amastigotes to pentavalent (SbV) and
trivalent (SbIII) antimonials was determined. We observed (i) 22
SbV-resistant isolates out of 33 tested and (ii) 3 SbIII-resistant isolates
out of 12 tested. Amongst the latter, there were three combinations of in
vitro phenotypes : (i) parasites sensitive (n=4) or (ii) resistant to both
drugs (n=3) and (iii) resistant to SbV only (n=5). There was no geographical
clustering in terms of in vitro susceptibility. The relation between the in
vitro susceptibility to antimonials and the corresponding in vivo treatment
outcome was ambiguous. Our results highlight the need to adjust the
currently used *Leishmania* drug susceptibility assays if they are to be
used for prognosis of in vivo SSG treatment outcome.


PMID: 17384865<http://refscout.com/cgi-bin/exportAbstract.pl?base=medline-2007-14.xml&id=17384865>
TITLE: The hunt for an elusive source of pyrexia in a foreign
worker.<http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=17384865>
AUTHORS: J W Lew, C K Koh, V S Selvan, E Shen
AFFILIATION: Department of Medicine, Alexandra Hospital, 378 Alexandra Road,
Singapore 159964. selvan_senthamil at alexhosp.com.sg.
REFERENCE: Singapore Med J 2007 Apr 48(4):e111-3
We report a 23-year-old Bangladeshi man who presented with fever and
hepatosplenomegaly. The initial laboratory findings were bicytopenia with
elevated serum globulins. The diagnosis of visceral leishmaniasis ( Kala
Azar) was suspected. The parasite *Leishmania* donovani was found on bone
marrow aspiration. He was treated with liposomal amphotericin B and had a
good response to treatment. The case highlights the need to be aware of this
disease occurring in a foreign national from an endemic region when he
presents with fever and hepatosplenomegaly.


PMID: 17320480<http://refscout.com/cgi-bin/exportAbstract.pl?base=medline-2007-14.xml&id=17320480>
TITLE: Metabolism of *Leishmania*: proven and
predicted.<http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=17320480>
AUTHORS: Fred R Opperdoes, Graham H Coombs
AFFILIATION: Research Unit for Tropical Diseases and Laboratory of
Biochemistry, Christian de Duve Institute of Cellular Pathology and Catholic
University of Louvain, Avenue Hippocrate 74-75, B-1200 Brussels, Belgium.
REFERENCE: Trends Parasitol 2007 Apr 23(4):149-58
The complete analysis of the genomes of three major trypanosomatid parasites
has facilitated comparison of the metabolic capabilities of each, as
predicted from gene sequences. Not surprisingly, there are differences but
is it possible to correlate these with the lives of the parasites themselves
and make further predictions of the meaning and physiological importance of
the apparently parasite-specific metabolism ? In this article, we relate
gene predictions with the results from experimental studies. We also
speculate on the key metabolic adaptations of *Leishmania* and reasons why
it differs from Trypanosoma brucei and Trypanosoma cruzi.


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PMID: 17157440<http://refscout.com/cgi-bin/exportAbstract.pl?base=medline-2007-14.xml&id=17157440>
TITLE: Infection by *Leishmania* infantum in cats: Epidemiological study in
Spain.<http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=17157440>
AUTHORS: J Martín-Sánchez, C Acedo, M Muñoz-PÃ(c)rez, B Pesson, O Marchal,
F Morillas-Márquez
AFFILIATION: Dep. Parasitología, Fac. Farmacia, Universidad de Granada,
18.011 Granada, Spain.
REFERENCE: Vet Parasitol 2007 Apr 145(3-4):267-73
More than 40 cases of feline leishmaniasis have been reported in the
scientific literature. The influence of some immunodepressive conditions of
viral origin, such as leukemia and feline immunodeficiency, are still
unknown. The purpose of this study was to assess the prevalence of *
Leishmania* infection in cats and possible relations with these viral
infections. Markers of *Leishmania* infection were searched in 183 cats from
Southern Spain by IFAT, PCR, Giemsa stain and culture, with a follow-up of
positive cats. Seropositivity was 60.0% (Ab titer >/=10) and 28.3% of
animals presented Ab titers >/=40. Around 25.7% of the cats studied were
parasitemic and some of them remained positive for months . Combining both
data, 70.6% of the feline population was, or could be, infected. We observed
a negative association between seropositivity to *Leishmania* and infection
by FeLV. Hence, production of antibodies against the parasite appears to be
compromised in cats with leukemia, which have a prevalence of 36% in our
study. In contrast, we found no association with feline immunodeficiency.
The results makes us doubt the value of conventional serological methods to
detect active *Leishmania* infection in cats.


PMID: 17174035<http://refscout.com/cgi-bin/exportAbstract.pl?base=medline-2007-14.xml&id=17174035>
TITLE: Infection of sandflies by a cat naturally infected with
*Leishmania*infantum.<http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=17174035>
AUTHORS: Michele Maroli, Maria Grazia Pennisi, Trentina Di Muccio, Cristina
Khoury, Luigi Gradoni, Marina Gramiccia
AFFILIATION: Unit of Vector-borne Diseases and International Health, MIPI
Department, Istituto Superiore di Sanità , Rome, Italy.
REFERENCE: Vet Parasitol 2007 Apr 145(3-4):357-60
Despite the recent reports of feline leishmaniosis from Southern Europe ,
cats are still regarded as unusual *Leishmania* hosts. A cat found
chronically infected with *Leishmania* was submitted to xenodiagnosis. After
being sedated, the animal was exposed to the bite of 100 laboratory-reared
Phlebotomus perniciosus in a fine net cage for 90min. Four out of 19
blood-fed sandflies (21%) showed motile promastigotes at the dissection.
Parasites cultured from cat's lymph node and an infected fly were identical
at PCR-RFLP genotyping and identified as *Leishmania* infantum MON-1, the
main zymodeme responsible for human and canine leishmaniosis in Southern
Europe. This is the first evidence of transmissibility of feline parasites
to a proven vector, suggesting that cats may represent an additional
domestic reservoir for L. infantum.


PMID: 17257762<http://refscout.com/cgi-bin/exportAbstract.pl?base=medline-2007-14.xml&id=17257762>
TITLE: Risk factors for canine neosporosis in farm and kennel dogs in
southern Italy.<http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=17257762>
AUTHORS: Paola Paradies, Gioia Capelli, Gabriella Testini, Cinzia
Cantacessi, Alexander J Trees, Domenico Otranto
AFFILIATION: Department of Animal Health and Welfare, Faculty of Veterinary
Medicine, University of Bari, Str. Prov. per Casamassima Km3, 70010
Valenzano (Bari), Italy.
REFERENCE: Vet Parasitol 2007 Apr 145(3-4):240-4
Neosporosis by Neospora caninum causes losses to livestock production
through abortion in cattle while, in dogs, it induces neuromuscolar disease.
This study investigated neosporosis seroprevalence associated risk factors
(including the seropositivity to leishmaniosis) in dogs of southern Italy,
determined the prevalence of N. caninum oocyst shedding and examined the
relationship between seroprevalence of neosporosis in farm dogs and cattle.
Using an inhibition ELISA, 20.9% of 306 dogs had percent inhibition values
>10 (indicative of exposure) and farm dogs had a significantly (p<0.001)
higher seroprevalence than dogs in a rescue kennel. Whilst N. caninum
seroprevalence was associated with increasing age in dogs (p</=0.01) there
was no association between seropositivity for N. caninum and for *Leishmania
* infantum. Oocysts of N . caninum were not detected in faecal samples from
230 dogs including 160 farm dogs. The results indicated that neosporosis
infection is common in southern Italy both in dogs and in cattle and that
dogs at higher risk of exposure are free-ranging ones living in farms. The
lack of correlation between canine seroprevalence for N. caninum and L.
infantum assumes a particular significance in an endemic area for
leishmaniosis.


PMID: 17292553<http://refscout.com/cgi-bin/exportAbstract.pl?base=medline-2007-14.xml&id=17292553>
TITLE: Heparin binding proteins from *Leishmania* (Viannia) braziliensis
promastigotes.<http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=17292553>
AUTHORS: R L Azevedo-Pereira, M C S Pereira, F O R Oliveria-Junior, R P
Brazil, L M C Côrtes, M F Madeira, A L S Santos, L Toma, C R Alves
AFFILIATION: Departamento de Bioquímica e Biologia Molecular, Instituto
Oswaldo Cruz, FIOCRUZ, Av. Brasil 4365, CEP 21.045-900, Manguinhos, Rio de
Janeiro, RJ, Brazil.
REFERENCE: Vet Parasitol 2007 Apr 145(3-4):234-9
We have examined the heparin binding proteins from *Leishmania* (Viannia)
braziliensis promastigotes (HBP-Lb) by chromatography assays. The proposed
strategy to isolate an enriched fraction of the HBP-Lb consisted of an
association of the Triton X-114 method with affinity chromatography in
heparin-Sepharose 4B column. SDS-PAGE analysis of the eluted proteins showed
two main protein bands (65.0 and 54.5kDa), while a single protein band was
observed in native electrophoresis gel. The hemagglutination property of
HBP-Lb over rabbit erythrocytes was confirmed up to 6.3+/-0.5mug of protein
mL(-1). Additionally, we have assayed the potential of HBP-Lb labeled with
sulfo-NHS-LC-biotin in binding to nitrocellulose-immobilized gut proteins
extracted of Lutzomyia intermedia and Lutzomyia whitmani. The results
indicated a similar profile of five ligands (67.0, 62.1, 59.5, 56.0 and
47.5kDa) in both studied Lutzomyia species. This is the first direct
description of this class of protein in L. (V.) braziliensis with a
suggestion of its biological activity in the interaction of
*Leishmania*with Lutzomyia gut cells, which maybe a crucial step
during this parasite's
life cycle.


PMID: 17298866<http://refscout.com/cgi-bin/exportAbstract.pl?base=medline-2007-14.xml&id=17298866>
TITLE: In vitro activity of dicationic compounds against a North American
foxhound isolate of *Leishmania*
infantum.<http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=17298866>
AUTHORS: Alexa C Rosypal, James E Hall, Svetlana Bakunova, Donald A Patrick,
Stanislav Bakunov, Chad E Stephens, Arvind Kumar, David W Boykin, Richard R
Tidwell
AFFILIATION: School of Medicine, Department of Pathology and Laboratory
Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
REFERENCE: Vet Parasitol 2007 Apr 145(3-4):207-16
Canine leishmaniasis caused by *Leishmania* infantum is enzootic in the
North American foxhound population. Currently available chemotherapy for
canine leishmaniasis is not completely effective and relapses are common in
treated dogs. Pentamidine and related aromatic diamidines possess broad
spectrum antiprotozoal activity. The in vitro antileishmanial activities of
35 aromatic cationic molecules were determined, using pentamidine as the
reference drug. The compounds were examined for activity against
promastigotes of L. infantum isolated from a foxhound from Virginia. The
compounds most active against *Leishmania* parasites were reversed amidines.
Compound 9, a reversed amidine, exhibited the highest activity against L.
infantum, with a 50% inhibitory concentration (IC(50)) of 0.0042muM compared
with 14.2muM for pentamidine. Antileishmanial activities of nine compounds
were at least 1000-fold higher relative to the reference drug. Results from
this study indicate that several pentamidine-related compounds warrant
further investigation as possible new agents for the treatment of canine
leishmaniasis.


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PMID: 17276983<http://refscout.com/cgi-bin/exportAbstract.pl?base=medline-2007-14.xml&id=17276983>
TITLE: Molecular and Functional Analyses of a Novel Class I Secretory
Nuclease from the Human Pathogen, *Leishmania*
donovani.<http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=17276983>
AUTHORS: Manju B Joshi, Dennis M Dwyer
AFFILIATION: Cell Biology Section, Laboratory of Parasitic Diseases,
Division of Intramural Research, NIAID, National Institutes of Health,
Bethesda, Maryland 20892-0425.
REFERENCE: J Biol Chem 2007 Mar 282(13):10079-95
The primitive protozoan pathogen of humans, *Leishmania* donovani, resides
and multiplies in highly restricted micro-environments within their hosts (
i.e. as promastigotes in the gut lumen of their sandfly vectors and as
amastigotes in the phagolysosomal compartments of infected mammalian
macrophages). Like other trypanosomatid parasites, they are purine
auxotrophs (i.e. lack the ability to synthesize purines de novo) and
therefore are totally dependent upon salvaging these essential nutrients
from their hosts. In that context, in this study we identified a unique
35-kDa, dithiothreitol-sensitive nuclease and showed that it was
constitutively released/secreted by both promastigote and amastigote
developmental forms of this parasite. By using several different molecular
approaches, we identified and characterized the structure of LdNuc(s), a
gene that encodes this new 35-kDa class I nuclease family member in these
organisms. Homologous episomal expression of an epitope- tagged LdNuc(s)
chimeric construct was used in conjunction with an anti- LdNuc(s) peptide
antibody to delineate the functional and biochemical properties of this
unique 35-kDa parasite released/secreted enzyme. Results of coupled
immunoprecipitation-enzyme activity analyses demonstrated that this
"secretory" enzyme could hydrolyze a variety of synthetic polynucleotides as
well as several natural nucleic acid substrates, including RNA and single-
and double-stranded DNA. Based on these cumulative observations, we
hypothesize that within the micro-environments of its host, this leishmanial
"secretory" nuclease could function at a distance away from the parasite to
harness (i.e. hydrolyze/access) host-derived nucleic acids to satisfy the
essential purine requirements of these organisms. Thus, this enzyme might
play an important role(s) in facilitating the survival, growth, and
development of this important human pathogen.


PMID: 17396274<http://refscout.com/cgi-bin/exportAbstract.pl?base=medline-2007-14.xml&id=17396274>
TITLE: Leishmaniasis.<http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=17396274>
AUTHORS: Tonio V Piscopo, Charles Mallia Azzopardi
AFFILIATION: St Luke's Hospital, Guardamangia Hill, Guardamangia, MSD 09,
Malta. tonio.piscopo at gov.mt
REFERENCE: Postgrad Med J 2007 Feb 83(976):649-57
Epidemiology, disease patterns, immunology, diagnosis, treatment and control
measures of leishmaniasis are described. Various issues relating to
leishmaniasis are highlighted: the relative lack of importance given to this
disease compared with other infections, climate change and its possible
impact on extension of endemicity of this infection, and new diagnostic
tests which are improving diagnosis, especially in resource poor areas.
Other important aspects discussed include the potential for newer oral
therapy to change the way this disease is managed; *Leishmania* -HIV
coinfection and groups at risk; and development of an effective vaccine.


PMID: 17316586<http://refscout.com/cgi-bin/exportAbstract.pl?base=medline-2007-14.xml&id=17316586>
TITLE: H-2 complex influences cytokine gene expression in
*Leishmania*infantum-infected
macrophages.<http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=17316586>
AUTHORS: Olivia Roos Rodrigues, Rita Aguiar Moura, Sandra Gomes-Pereira,
Gabriela Maria Santos-Gomes
AFFILIATION: UEI Leishmanioses, Centro de Malária e Outras Doenças
Tropicais, Instituto de Higiene e Medicina Tropical, Universidade Nova de
Lisboa, Rua da Junqueira 96, 1349-008 Lisbon, Portugal.
REFERENCE: Cell Immunol 2006 Oct 243(2):118-26
This work aims to study the influence of H-2 locus in the control of *
Leishmania* infantum infection by evaluating whether cytokine responses by
host macrophages of different H-2 haplotype are differentially regulated,
either induced or actively impaired during parasite growth and replication.
This study shows that macrophages of "non-cure& quot; phenotype (H-2(d)) are
more susceptible to infection with virulent L. infantum promastigotes.
Virulent parasites lead to impaired IL-12 and inhibited TNF-alpha
expression. The degree of parasite virulence is an important contributing
factor to differences detected in cytokine expression. Virulent parasites
also induced TGF-beta, a deactivating cytokine that is known to suppress
Th-1 type responses, thus allowing the parasite to subvert antimicrobial
activity and increase its chances of survival. Depending on specific host
haplotype, cells differentially respond to infection since TNF-alpha
expression is inhibited and TGF- beta is enhanced by macrophages of
"non-cure" phenotype, thus perhaps determining their degree of
susceptibility in this strain of mice.


PMID: 17290905<http://refscout.com/cgi-bin/exportAbstract.pl?base=medline-2007-14.xml&id=17290905>
TITLE: [Visceral leishmaniasis in the Commonwealth of Independent States
(CIS): results and basic lines of further
study]<http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=17290905>
AUTHORS: E N PonirovskiÄ­, M V Strelkova, D B Goncharov, E N Zhirenkina, Iu
A Chernikova
REFERENCE: Med Parazitol (Mosk) 2006 Oct-Dec (4):25-31
The results of studies of visceral leishmaniasis (VL) made in the 20th
century in the Commonwealth of Independent States that are VL-endemic, such
as Azerbaijan, Armenia, Georgia, Kazakhstan, Kyrghyzstan, Tadjikistan,
Turkmenistan, and Uzbekistan are summed up. The magnitude of studies of VL
in different regions is different. The authors analyze the epidemiological
and epizootological situation and define the basic lines of further studies
of VL, which include the present view of the prevalence of VL in Central
Asia and Transcaucasia; identification of strains of the pathogen by
molecular genetic methods; study of its vectors; detection of natural
reservoirs of the pathogen, improvement of methods for VL diagnosis; and
their introduction into laboratories' work.


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

PMID: 17068275<http://refscout.com/cgi-bin/exportAbstract.pl?base=medline-2007-14.xml&id=17068275>
TITLE: Leishmaniasis.<http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=17068275>
AUTHORS: T V Piscopo, A C Mallia
AFFILIATION: Sir Temi Zammit Infectious Disease Unit, St Luke's Hospital,
Guardamangia Hill, Guardamangia, MSD 09, Malta. tonio.piscopo at gov.mt
REFERENCE: Postgrad Med J 2006 Oct 82(972):649-57
Epidemiology, disease patterns, immunology, diagnosis, treatment and control
measures of leishmaniasis are described. Various issues relating to
leishmaniasis are highlighted: the relative lack of importance given to this
disease is compared with other infections, climate change and its possible
effect on extension of endemicity of this infection, and new diagnostic
tests that are helping better diagnosis, especially in resource-poor areas.
Other important aspects discussed include the potential for newer oral
treatment to change the way this disease is managed; *leishmania*-HIV
coinfection and groups at risk; and the development of an effective vaccine.


REQUEST: [ sand fly NOT culicoides ]
(1 article matches this request. 1 article matching other requests removed)

REQUEST: [ sandfly NOT culicoides ]
(1 article matches this request. 1 article matching other requests removed)

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