[Leish-l] Articles found by RefScout 2006/07/17

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  REQUEST: [ leishmania ]
(18 articles match this request. 1 article matching other requests removed)

PMID:
16790764<http://refscout.com/cgi-bin/exportAbstract.pl?base=medline-28-9.xml&id=16790764>
TITLE: *Leishmania* infection impairs beta1-integrin function and chemokine
receptor expression in mononuclear
phagocytes.<http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=16790764>
AUTHORS: Nathanael F Pinheiro, Micely D R Hermida, Mariana P Macedo, JosÃ(c)
Mengel, Andre Bafica, Washington L C dos-Santos
AFFILIATION: LPBI, Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo
Cruz, Rua Waldemar Falcão no. 121, Candeal, Salvador, BA 40296-710, Brazil.
REFERENCE: Infect Immun 2006 Jul 74(7):3912-21
*Leishmania* spp. are intracellular parasites that cause lesions in the
skin, mucosa, and viscera. We have previously shown that
*Leishmania*infection reduces mononuclear phagocyte adhesion to
inflamed connective
tissue. In this study, we examined the role of adhesion molecules and
chemokines in this process. Infection rate (r = -0.826, P = 0.003) and
parasite burden (r = -0.917, P = 0.028) negatively correlated to mouse
phagocyte adhesion. The decrease (58.7 to 75.0% inhibition, P = 0.005) in
phagocyte adhesion to connective tissue, induced by *Leishmania*, occurred
as early as 2 h after infection and was maintained for at least 24 h.
Interestingly, impairment of cell adhesion was sustained by phagocyte
infection, since it was not observed following phagocytosis of killed
parasites (cell adhesion varied from 15.2% below to 24.0% above control
levels, P > 0.05). In addition, *Leishmania* infection diminished cell
adhesion to fibronectin (54.1 to 96.2%, P < 0.01), collagen (15. 7 to 83.7%,
P < 0.05), and laminin (59.1 to 82.2%, P < 0.05). The CD11b(hi)
subpopulation was highly infected (49.6 to 97.3%). Calcium and Mg(2+)
replacement by Mn(2+), a treatment that is known to induce integrins to a
high state of affinity for their receptors, reverted the inhibition in
adhesion caused by *Leishmania*. This reversion was completely blocked by
anti-VLA4 antibodies. Furthermore, expression of CCR4 and CCR5, two
chemokine receptors implicated in cell adhesion, was found to be
downregulated 16 h after infection (2.8 to 4.1 times and 1.9 to 2.8 times,
respectively). Together, these results suggest that mechanisms regulating
integrin function are implicated in the change of macrophage adhesion in
leishmaniasis.


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PMID:
16790767<http://refscout.com/cgi-bin/exportAbstract.pl?base=medline-28-9.xml&id=16790767>
TITLE: Cloning, characterization, and serodiagnostic evaluation of *
Leishmania* infantum tandem repeat
proteins.<http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=16790767>
AUTHORS: Yasuyuki Goto, Rhea N Coler, Jeffrey Guderian, Raodoh Mohamath,
Steven G Reed
AFFILIATION: Infectious Disease Research Institute, 1124 Columbia St., Suite
400, Seattle, WA 98104, USA.
REFERENCE: Infect Immun 2006 Jul 74(7):3939-45
Visceral leishmaniasis (VL) is a form of leishmaniasis, which is caused by
infection with the protozoan parasite *Leishmania*, and is often fatal
unless it is treated. Rapid and accurate diagnosis of VL is important for
effective treatment. Here we report the cloning of previously undescribed
tandem repeat (TR) proteins of *Leishmania* infantum and an evaluation of VL
patient antibody responses to the corresponding proteins. By screening an L.
infantum expression library with sera from human VL patients or infected
hamsters, we identified 43 genes encoding B-cell antigens. Surprisingly, 19
of the 43 genes (44%) were TR proteins , and that percentage was
significantly higher than that for genes picked randomly from the database.
We then expressed the TR regions of LinJ16.1750, LinJ22.1590, and
LinJ33.2870 and the entire LinJ28.2310 protein. These recombinant proteins
were all recognized by Sudanese VL patient sera in an enzyme-linked
immunosorbent assay. Recombinant LinJ16 .1750 (rLinJ16.1750) showed the best
performance among these antigens in terms of both sensitivity and
specificity. Serological evaluation revealed that 97% (34 of 35) of Sudanese
VL patients had significantly elevated antibody levels to rLinJ16.1750.
Furthermore, when eight of the patient sera which had low reactivities to
rK39 were tested with the novel recombinant antigens, some of the sera
showed stronger antibody responses to these antigens than to rK39. Our
results suggest that TR regions from the novel L. infantum proteins
identified in this study are immunodominant B-cell epitopes and may
represent good candidates for serodiagnosis of VL.


PMID:
16790814<http://refscout.com/cgi-bin/exportAbstract.pl?base=medline-28-9.xml&id=16790814>
TITLE: Responses to *Leishmania* donovani in mice deficient in
interleukin-12 (IL-12), IL-12/IL-23, or
IL-18.<http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=16790814>
AUTHORS: Henry W Murray, Christine W Tsai, Jianguo Liu, Xiaojing Ma
AFFILIATION: Department of Medicine, Weill Medical College of Cornell
University, 1300 York Avenue, New York, NY 10021, USA.
hwmurray at med.cornell.edu
REFERENCE: Infect Immun 2006 Jul 74(7):4370-4
Interleukin-12 (IL-12) orchestrates acquired resistance in intracellular *
Leishmania* donovani infection in the liver, inducing gamma interferon and,
in turn, macrophage activation and parasite killing. Nevertheless, testing
in IL-18(-/-) mice compared to wild-type mice and in IL-12p40 (-/-) compared
to IL-12p35(-/-) mice also suggested both early-acting ( IL-18) and
late-acting (IL-23) antileishmanial effects independent of IL -12.


PMID:
16243007<http://refscout.com/cgi-bin/exportAbstract.pl?base=medline-28-9.xml&id=16243007>
TITLE: Evidence for the existence of two distinct species: Psammomys obesus
and Psammomys vexillaris within the sand rats (Rodentia, Gerbillinae),
reservoirs of cutaneous leishmaniasis in
Tunisia.<http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=16243007>
AUTHORS: Ben Hamou Mostafa, Ben Abderrazak Souha, Frigui Sabeh, Chatti
Noureddine, Ben Ismail Riadh
AFFILIATION: Laboratoire d'EpidÃ(c)miologie et d'Ecologie Parasitaire,
Institut Pasteur de Tunis, BP 74, 1002 Tunis BelvÃ(c)dère, Tunisia.
REFERENCE: Infect Genet Evol 2006 Jul 6(4):301-8
A thorough taxonomic knowledge about putative animal reservoirs of
transmissible diseases is an absolute prerequisite to any ecological
investigation and epidemiological survey of zoonoses. Indeed, accurate
identification of these reservoirs is essential for predicting species-
specific population outbreaks and therefore to develop accurate ecological
control strategies. The systematic status of sand rats (genus Psammomys)
remains unclear despite the pivotal role of these rodents in the
epidemiology of Zoonotic Cutaneous Leishmaniasis (ZCL) disease as sand rats
are the main known reservoir hosts of the protozoan parasite
*Leishmania*major. In the present work, we expose morphological,
biochemical, genetic
and cytogenetic evidence supporting the identification of at least two
cryptic species within the genus Psammomys in Tunisia. First, significant
morphometric differences were observed and were correlated associated with
external features and biogeographic origins. Second, differences in patterns
of two isoenzymic systems (Glutamate Oxaloacetate Transaminase (GOT) and 6-
PhosphoGluconate Dehydrogenase (6PGD)) were found, which makes it possible
to amount these isoenzyme characters to two diagnostic loci. Third, based on
the mitochondrial cytochrome b (cyt b) gene, a high magnitude of genetic
distance (13.89%) was also observed. Fourth, cytogenetic analysis showed
that these two populations groups differ in their diploid chromosome
numbers, i.e. 2N=46 versus 2N=48. We consider that all these variations are
enough important to be considered as demonstrative and we propose that these
two lineages should be considered as two distinct species that we refer to
the fat sand rat Psammomys obesus Cretzschmar, 1828 and the thin sand rat
Psammomys vexillaris Thomas, 1925. Implications of such results on the eco-
epidemiology of ZCL in Tunisia are discussed.


PMID:
16597468<http://refscout.com/cgi-bin/exportAbstract.pl?base=medline-28-9.xml&id=16597468>
TITLE: *Leishmania* donovani singly deficient in HGPRT, APRT or XPRT are
viable in vitro and within mammalian
macrophages.<http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=16597468>
AUTHORS: Jan M Boitz, Buddy Ullman
AFFILIATION: Department of Biochemistry and Molecular Biology, Oregon Health
and Science University, Portland, 97239, USA.
REFERENCE: Mol Biochem Parasitol 2006 Jul 148(1):24-30
*Leishmania* species express three phosphoribosyltransferase enzymes,
hypoxanthine-guanine phosphoribosyltransferase (HGPRT), adenine
phosphoribosyltransferase (APRT), and xanthine phosphoribosyltransferase
(XPRT), which enable this genus to acquire purine nutrients from their
hosts. To test whether any of these enzymes is essential for viability,
transformation into amastigotes, and infectivity and proliferation within
mammalian macrophages, Deltahgprt, Deltaaprt, and Deltaxprt null mutants
were created by targeted gene replacement within a virulent background of *
Leishmania* donovani. Each of the three knockout strains was viable as
promastigotes and axenic amastigotes and capable of maintaining an infection
in bone marrow-derived murine macrophages. These data support the hypothesis
that none of the three phosphoribosyltransferases is essential for purine
salvage or viability by itself and that purine salvage occurs through
multiple anabolic routes in both parasite life cycle stages. In addition
these studies revealed the presence of an adenine aminohydrolase enzyme in
L. donovani axenic amastigotes, an activity previously thought to be
restricted to promastigotes.


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PMID:
16600399<http://refscout.com/cgi-bin/exportAbstract.pl?base=medline-28-9.xml&id=16600399>
TITLE: Isolation and characterization of mitochondrial ribosomes and
ribosomal subunits from *Leishmania*
tarentolae.<http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=16600399>
AUTHORS: Dmitri A Maslov, Manjuli R Sharma, Evelin Butler, Arnold M Falick,
Mari Gingery, Rajendra K Agrawal, Linda L Spremulli, Larry Simpson
AFFILIATION: Department of Biology, University of California, Riverside,
92521, USA. maslov at ucr.edu
REFERENCE: Mol Biochem Parasitol 2006 Jul 148(1):69-78
We have analyzed *Leishmania* tarentolae mitochondrial ribonucleoprotein (
RNP) complexes using the 9S small subunit (SSU) rRNA and the 12S large
subunit (LSU) rRNA as markers, and have identified a 50S RNP particle as the
putative mitochondrial monosome, a 40S particle as the putative LSU and a
30S particle as the putative SSU. These assignments are supported by
morphological analysis by cryo-electron microscopy and proteomics analyses
by mass spectrometry. The presence of additional rRNA- containing particles
complicated the analysis and most likely was the basis for previous
difficulties in identification of these ribosomes; thus, in addition to the
monosomes and their subunits, there are abundant stable 45S particles
(SSU(*)) containing only 9S rRNA, which may represent homodimers of the SSU
or SSU associated with additional proteins, and variable minor amounts of
65S and 70S particles, which represent homodimers of the LSU and SSU(*),
respectively. These additional rRNA particles might be due to the lengthy
mitochondrial isolation and ribosome isolation procedures or may be present
in vivo and play yet undetermined roles.


PMID:
16835450<http://refscout.com/cgi-bin/exportAbstract.pl?base=medline-28-9.xml&id=16835450>
TITLE: Farnesyl Diphosphate Synthase Is a Cytosolic Enzyme in
*Leishmania*major Promastigotes and Its Overexpression Confers
Resistance to
Risedronate.<http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=16835450>
AUTHORS: Aurora Ortiz-Gómez, Carmen JimÃ(c)nez, Antonio M EstÃ(c)vez, Juana
Carrero-LÃ(c)rida, Luis M Ruiz-PÃ(c)rez, Dolores González-Pacanowska
AFFILIATION: Instituto de Parasitología y Biomedicina López-Neyra, Consejo
Superior de Investigaciones Científicas, Avda. del Conocimiento s/n, Parque
Tecnológico Ciencias de la Salud, 18100 Armilla, Granada, Spain.
dgonzalez at ipb.csic.es.
REFERENCE: Eukaryot Cell 2006 Jul 5(7):1057-64
Farnesyl diphosphate synthase is the most likely molecular target of
aminobisphosphonates (e.g., risedronate), a set of compounds that have been
shown to have antiprotozoal activity both in vitro and in vivo. This
protein, together with other enzymes involved in isoprenoid biosynthesis, is
an attractive drug target, yet little is known about the
compartmentalization of the biosynthetic pathway. Here we show the
intracellular localization of the enzyme in wild-type *Leishmania* major
promastigote cells and in transfectants overexpressing farnesyl diphosphate
synthase by using purified antibodies generated towards a homogenous
recombinant *Leishmania* major farnesyl diphosphate synthase protein.
Indirect immunofluorescence, together with immunoelectron microscopy,
indicated that the enzyme is mainly located in the cytoplasm of both
wild-type cells and transfectants. Digitonin titration experiments also
confirmed this observation. Hence, while the initial step of isoprenoid
biosynthesis catalyzed by 3-hydroxy-3-methylglutaryl- coenzyme A reductase
is located in the mitochondrion, synthesis of farnesyl diphosphate by
farnesyl diphosphate synthase is a cytosolic process. *Leishmania* major
promastigote transfectants overexpressing farnesyl diphosphate synthase were
highly resistant to risedronate, and the degree of resistance correlated
with the increase in enzyme activity . Likewise, when resistance was induced
by stepwise selection with the drug, the resulting resistant promastigotes
exhibited increased levels of farnesyl diphosphate synthase. The
overproduction of protein under different conditions of exposure to
risedronate further supports the hypothesis that this enzyme is the main
target of aminobisphosphonates in *Leishmania* cells.


PMID:
16735512<http://refscout.com/cgi-bin/exportAbstract.pl?base=medline-28-9.xml&id=16735512>
TITLE: The {alpha}-Subunit of *Leishmania* F1 ATP Synthase Hydrolyzes ATP in
Presence of
tRNA.<http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=16735512>
AUTHORS: Srikanta Goswami, Samit Adhya
AFFILIATION: Genetic Engineering Laboratory, Indian Institute of Chemical
Biology, 4 Raja S.C. Mullick Road, Calcutta 700032, India.
REFERENCE: J Biol Chem 2006 Jul 281(28):18914-7
Import of tRNAs into the mitochondria of the kinetoplastid protozoon *
Leishmania* requires the tRNA-dependent hydrolysis of ATP leading to the
generation of membrane potential through the pumping of protons. Subunit
RIC1 of the inner membrane RNA import complex is a bi-functional protein
that is identical to the alpha-subunit of F(1)F(0) ATP synthase and
specifically binds to a subset (Type I) of importable tRNAs. We show that
recombinant, purified RIC1 is a Type I tRNA-dependent ATP hydrolase. The
activity was insensitive to oligomycin, sensitive to mutations within the
import signal of the tRNA, and required the cooperative interaction between
the ATP-binding and C-terminal domains of RIC1. The ATPase activity of the
intact complex was inhibited by anti -RIC1 antibody, while knockdown of RIC1
in *Leishmania* tropica resulted in deficiency of the tRNA-dependent ATPase
activity of the mitochondrial inner membrane. Moreover, RIC1 knockdown
extracts failed to generate a membrane potential across reconstituted
proteoliposomes, as shown by a rhodamine 123 uptake assay, but activity was
restored by adding back purified RIC1. These observations identify RIC1 as a
novel form of the F (1) ATP synthase alpha-subunit that acts as the major
energy transducer for tRNA import.


PMID:
16830009<http://refscout.com/cgi-bin/exportAbstract.pl?base=medline-28-9.xml&id=16830009>
TITLE: Progress towards a *Leishmania*
vaccine.<http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=16830009>
AUTHORS: Khaled S Tabbara
AFFILIATION: Department of Microbiology, Immunology and Infectious Diseases,
College of Medicine and Medical Sciences, Arabian Gulf University, PO Box
22979, Manama, Kingdom of Bahrain. Tel. +973 (1) 7239733. Fax. +973 (1)
7877195. E-mail: kst1 at batelco.com.bh.
REFERENCE: Saudi Med J 2006 Jul 27(7):942-50
Leishmaniasis is a vector-born protozoan disease. Approximately 12 million
individuals are affected worldwide with an estimated annual incidence of
1.5-2 million. Two clinical manifestations are recognized, cutaneous, and
visceral, both of which are common in the Middle East. In both forms,
infection is chronic, with potential deformities, persistence following
cure, and lifelong risk of reactivation. Attempts to develop an effective
human *Leishmania* vaccine have not yet succeeded . Leishmanization, a crude
form of live vaccination historically originated in this part of the world.
Experimental vaccination has been extensively studied in model animals in
the past 2 decades. In this review, major human killed vaccine trials are
surveyed, and modern trends in *Leishmania* vaccine development, including
subunit vaccines, naked DNA vaccines, and transmission blocking vaccines are
explored. Recent findings of a link between persistence of live parasites,
and maintenance of long-term immunity suggest live vaccination with
attenuated strains, as a future vaccination strategy.


PMID:
16783261<http://refscout.com/cgi-bin/exportAbstract.pl?base=medline-28-9.xml&id=16783261>
TITLE: [Visceral leishmaniasis in an immunocompetent subject, acquired in
the Pyrenees
region]<http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=16783261>
AUTHORS: Denis Malvy, FÃ(c)lix Djossou, C Ibanez, RÃ(c)my Vatan, MaïtÃ(c)
Longy-Boursier, Michel Le Bras
AFFILIATION: FÃ(c)dÃ(c)ration de mÃ(c)decine interne, maladies infectieuses et
tropicales, Hôpital Saint-AndrÃ(c), Bordeaux (33).
REFERENCE: Presse Med 2006 Jun 35(6 Pt 1):987-8
INTRODUCTION: Visceral leishmaniasis can develop in immunocompetent subjects
exposed to a risk of infestation during physical activities outdoors. CASE:
A 35-year-old woman was hospitalized for impaired health status with fever,
hepatomegaly, splenomegaly, and pancytopenia, which worsened during her
stay. Leishmaniasis was finally diagnosed, based on serologic testing and
the finding of *Leishmania* infantum in the sternal aspiration. Eight months
earlier, she had spent two weeks at a lake in the Pyrenees. Treatment with
meglumine antimoniate was efficacious. COMMENTS: This case is original
because of the extent of the organomegaly and its onset after vacation in an
area far from those where it is thought to be endemic.


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PMID:
16722639<http://refscout.com/cgi-bin/exportAbstract.pl?base=medline-28-9.xml&id=16722639>
TITLE: 2H-benzimidazole 1,3-dioxide derivatives: a new family of
water-soluble anti-trypanosomatid
agents.<http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=16722639>
AUTHORS: Mariana Boiani, Lucía Boiani, Ana Denicola, Susana Torres de
Ortiz, Elva Serna, Ninfa Vera de Bilbao, Luis Sanabria, Gloria Yaluff,
HÃ(c)ctor Nakayama, Antonieta Rojas de Arias, Celeste Vega, Miriam Rolan,
Alicia Gómez-Barrio, Hugo Cerecetto, Mercedes Gonzalez
AFFILIATION: Departamento de Química Organica, Facultad de
Ciencias-Facultad de Química, Universidad de la República, Uruguay.
REFERENCE: J Med Chem 2006 Jun 49(11):3215-24
Three series of benzimidazole N-oxide derivatives were developed and were
examined for their activity against trypanosomatid parasites ( Trypanosoma
cruzi and *Leishmania* spp.). 2H-benzimidazole 1,3-dioxides displayed
remarkable in vitro activities against both parasites, with derivatives 28,
29, and 32 being the most potent (IC50 < 5 microM) against the epimastigote
form of T. cruzi and 28, 33, and 35 the most potent against the promastigote
form of *Leishmania* spp. Unspecific cytotoxicity was evaluated using murine
macrophages, and derivative 33 was not toxic at a concentration 30 times
that of its IC50 against T. cruzi that was completely toxic for
*Leishmania*spp., implying that the series of 2H-benzimidazole
1,3-dioxides is selective
toward both trypanosomatid parasites. Derivatives 33 and 35 were submitted
to an in vivo assay using an acute model of Chagas' disease and a short-term
treatment (30 mg/kg/day orally administrated as aqueous solution, during 10
days). While in the control (untreated) and Benznidazole (50 mg/kg/ day)
groups survival fraction was 60.0% and 87.5%, respectively, none of the
animals treated with derivatives 33 and 35 died. From the preliminary
structure-activity relationship studies reduction potential and
electrophilicity were found relevant to anti-T. cruzi activity. Active
compounds are better electrophiles and more easily reduced than inactive
ones.


PMID:
16697632<http://refscout.com/cgi-bin/exportAbstract.pl?base=medline-28-9.xml&id=16697632>
TITLE: Turkish freshwater and marine macrophyte extracts show in vitro
antiprotozoal activity and inhibit FabI, a key enzyme of Plasmodium
falciparum fatty acid
biosynthesis.<http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=16697632>
AUTHORS: I Orhan, B Sener, T Atici, R Brun, R Perozzo, D Tasdemir
AFFILIATION: Department of Pharmacognosy, Faculty of Pharmacy, Gazi
University, TR-06330 Ankara, Turkey.
REFERENCE: Phytomedicine 2006 Jun 13(6):388-93
The ethanolic extracts of a number of Turkish freshwater macrophytes (
Potamogeton perfoliatus, Ranunculus tricophyllus and Cladophora glomerata)
and marine macroalgae (Dictyota dichotoma, Halopteris scoparia, Posidonia
oceanica, Scinaia furcellata, Sargassum natans and Ulva lactuca) were
assayed for their in vitro antiprotozoal activity. Trypanosoma brucei
rhodesiense, Trypanosoma cruzi, *Leishmania* donovani and Plasmodium
falciparum were used as test organisms. The cytotoxicity of the extracts was
also assessed against primary rat skeletal myoblasts (L6 cells). Whereas
none of the extracts were active against T. cruzi, all crude extracts
displayed appreciable trypanocidal activity against T . brucei rhodesiense,
with S. natans being the most active one (IC(50) 7 .4microg/ml). Except for
the marine alga H. scoparia, all extracts also possessed leishmanicidal
potential. The best antileishmanial activity was exerted by U. lactuca and
P. oceanica (IC(50)'s 5.9 and 8.0microg/ml , respectively). Five extracts
that demonstrated inhibitory activity towards P. falciparum (IC(50)'s
18.1-48.8microg/ml) were simultaneously assayed against FabI, a crucial
enzyme of the fatty acid system of P. falciparum, to find out whether FabI
was their target. The extracts of C . glomerata and U. lactuca efficiently
inhibited the FabI enzyme with IC (50) values of 1.0 and 4.0microg/ml,
respectively. None of the extracts were cytotoxic towards mammalian L6
cells. This work reports for the first time antiprotozoal activity of some
Turkish marine and freshwater algae, as well as a target-based
antiplasmodial screening for the identification of P. falciparum FabI
inhibitors from aquatic and marine macrophytes.


PMID:
16635538<http://refscout.com/cgi-bin/exportAbstract.pl?base=medline-28-9.xml&id=16635538>
TITLE: Immunotherapy against visceral leishmaniasis with the nucleoside
hydrolase-DNA vaccine of *Leishmania*
donovani.<http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=16635538>
AUTHORS: R Gamboa-León, E Paraguai de Souza, G P Borja-Cabrera, F N Santos,
L M Myashiro, R O Pinheiro, E Dumonteil, C B Palatnik-de-Sousa
AFFILIATION: Instituto de Microbiologia, Prof. Paulo de Góes, Universidade
Federal do Rio de Janeiro, UFRJ, CCS, Cidade Universitária, Ilha do
Fundão, Caixa Postal 68040, CEP 21941-590, Rio de Janeiro, RJ, Brazil.
REFERENCE: Vaccine 2006 May 24(22):4863-73
The nucleoside hydrolase (NH36) of *Leishmania* (L.) donovani is a vital
enzyme which releases purines or pyrimidines of foreign DNA to be used in
the synthesis of parasite DNA. As a bivalent DNA vaccine, the VR1012- NH36
was immunoprotective against visceral and cutaneous murine leishmaniasis. In
this work we tested the immunotherapy against *Leishmania* (L.) chagasi
infection, using two doses of 100 or 20 microg VR1012-NH36 vaccine (i.m.
route), and, as a possible immunomodulator, aqueous garlic extract (8
mg/kg/day by the i.p. route), which was effective in immunotherapy of
cutaneous murine leishmaniasis. Liver parasitic load was significantly
reduced following treatment with 100 microg (91%) and 20 microg (77%) of the
DNA vaccine, and by 20 microg DNA vaccine and garlic extract (76%) (p=0.023).
Survival was 33% for saline controls, 100% for the 100 microg vaccine, and
83 and 67% for the 20 microg vaccine with and without garlic extract
addition, respectively. Garlic treatment alone did not reduce parasite load
(p>0. 05), but increased survival (100%). The NH36-DNA vaccine was highly
effective as a new tool for the therapy and control of visceral
leishmaniasis, while the mild protective effect of garlic might be related
to an unspecific enhancement of IFN-gamma secretion.


PMID:
16757380<http://refscout.com/cgi-bin/exportAbstract.pl?base=medline-28-9.xml&id=16757380>
TITLE: DNA topoisomerase I from parasitic protozoa: a potential target for
chemotherapy.<http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=16757380>
AUTHORS: R M Reguera, C M Redondo, R Gutierrez de Prado, Y PÃ(c)rez-Pertejo, R
Balaña-Fouce
AFFILIATION: Dpto. Farmacología y Toxicología (INTOXCAL), Universidad de
León, Campus de Vegazana s/n, 24071 León, Spain.
REFERENCE: Biochim Biophys Acta 2006 Mar-Apr 1759(3-4):117-31
The growing occurrence of drug resistant strains of unicellular prokaryotic
parasites, along with insecticide-resistant vectors, are the factors
contributing to the increased prevalence of tropical diseases in
underdeveloped and developing countries, where they are endemic. Malaria,
cryptosporidiosis, African and American trypanosomiasis and leishmaniasis
threaten human beings, both for the high mortality rates involved and the
economic loss resulting from morbidity. Due to the fact that effective
immunoprophylaxis is not available at present; preventive sanitary measures
and pharmacological approaches are the only sources to control the
undesirable effects of such diseases. Current anti-parasitic chemotherapy is
expensive, has undesirable side effects or, in many patients, is only
marginally effective. Under this point of view molecular biology techniques
and drug discovery must walk together in order to find new targets for
chemotherapy intervention. The identification of DNA topoisomerases as a
promising drug target is based on the clinical success of camptothecin
derivatives as anticancer agents. The recent detection of substantial
differences between trypanosome and *leishmania* DNA topoisomerase IB with
respect to their homologues in mammals has provided a new lead in the study
of the structural determinants that can be effectively targeted. The present
report is an up to date review of the new findings on type IB DNA
topoisomerase in unicellular parasites and the role of these enzymes as
targets for therapeutic agents.



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

PMID:
15876463<http://refscout.com/cgi-bin/exportAbstract.pl?base=medline-28-9.xml&id=15876463>
TITLE: Regulation of genes encoding the major surface protease of *
Leishmania* chagasi via mRNA
stability.<http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=15876463>
AUTHORS: Jay E Purdy, John E Donelson, Mary E Wilson
AFFILIATION: Department of Internal Medicine, University of Iowa, Iowa City,
IA 52242, USA. jay-purdy at uiowa.edu
REFERENCE: Mol Biochem Parasitol 2005 Jul 142(1):88-97
The intercoding regions between many *Leishmania* sp. genes regulate their
mRNA expression. The MSPL mRNA, encoding a subclass of the major surface
protease (MSP) of *Leishmania* chagasi, increases in abundance, when protein
synthesis is arrested, while alpha-tubulin (alpha-TUB) mRNA and most other
mRNAs do not. We found that the intercoding region between MSPL-coding
regions, when cloned downstream of the beta- galactosidase reporter gene
(beta-GAL), caused beta-GAL mRNA to increase 8- to 10-fold after inhibiting
protein synthesis with cycloheximide. Stable L. chagasi transfectants
containing hybrid MSPL/alpha-TUB intercoding regions cloned downstream of
beta-GAL were made. The alpha- TUB intercoding region induced high-level
baseline beta-GAL mRNA that increased only 1.3-fold after incubation with
cycloheximide. In contrast , the MSPL intercoding region, as well as
constructs containing nucleotides 303-505 from the MSPL 3'UTR, caused
steady-state beta-GAL mRNA levels in the absence of cycloheximide that were
approximately 10% of alpha-TUB constructs. These levels increased between
4.4- and 13.2- fold after cycloheximide was added. Constructs containing
half of this region (303-394 or 395-505) produced intermediate levels of
beta-GAL mRNA and intermediate levels of cycloheximide induction. The
kinetics of cycloheximide induction of beta-GAL mRNA was similar with region
303- 505 constructs as with constructs bearing the entire endogenous MSPL
intercoding region. Furthermore, region 303-505 increased reporter mRNA
abundance after cycloheximide by increasing mRNA half-life. Hence, we have
identified a 202-nucleotide region within the MSPL 3'UTR that is in part
responsible for cycloheximide induction. We hypothesize that this region may
interact with labile regulatory protein factor(s).


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PMID:
16020728<http://refscout.com/cgi-bin/exportAbstract.pl?base=medline-28-9.xml&id=16020728>
TITLE: The genome of the kinetoplastid parasite, *Leishmania*
major.<http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=16020728>
AUTHORS: Alasdair C Ivens, Christopher S Peacock, Elizabeth A Worthey, Lee
Murphy, Gautam Aggarwal, Matthew Berriman, Ellen Sisk, Marie-Adele
Rajandream, Ellen Adlem, Rita Aert, Atashi Anupama, Zina Apostolou, Philip
Attipoe, Nathalie Bason, Christopher Bauser, Alfred Beck, Stephen M
Beverley, Gabriella Bianchettin, Katja Borzym, Gordana Bothe, Carlo V
Bruschi, Matt Collins, Eithon Cadag, Laura Ciarloni, Christine Clayton,
Richard M R Coulson, Ann Cronin, Angela K Cruz, Robert M Davies, Javier De
Gaudenzi, Deborah E Dobson, Andreas Duesterhoeft, Gholam Fazelina, Nigel
Fosker, Alberto Carlos Frasch, Audrey Fraser, Monika Fuchs, Claudia Gabel,
Arlette Goble, AndrÃ(c) Goffeau, David Harris, Christiane Hertz-Fowler, Helmut
Hilbert, David Horn, Yiting Huang, Sven Klages, Andrew Knights, Michael
Kube, Natasha Larke, Lyudmila Litvin, Angela Lord, Tin Louie, Marco Marra,
David Masuy, Keith Matthews, Shulamit Michaeli, Jeremy C Mottram, Silke
Müller-Auer, Heather Munden, Siri Nelson, Halina Norbertczak, Karen Oliver,
Susan O'neil, Martin Pentony, Thomas M Pohl, Claire Price, BÃ(c)nÃ(c)dicte
Purnelle, Michael A Quail, Ester Rabbinowitsch, Richard Reinhardt, Michael
Rieger, Joel Rinta, Johan Robben, Laura Robertson, Jeronimo C Ruiz, Simon
Rutter, David Saunders, Melanie Schäfer, Jacquie Schein, David C Schwartz,
Kathy Seeger, Amber Seyler, Sarah Sharp, Heesun Shin, Dhileep Sivam, Rob
Squares, Steve Squares, Valentina Tosato, Christy Vogt, Guido Volckaert,
Rolf Wambutt, Tim Warren, Holger Wedler, John Woodward, Shiguo Zhou,
Wolfgang Zimmermann, Deborah F Smith, Jenefer M Blackwell, Kenneth D Stuart,
Bart Barrell, Peter J Myler
AFFILIATION: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus,
Hinxton, Cambridgeshire CB10 1SA, UK. alicat at sanger.ac.uk
REFERENCE: Science 2005 Jul 309(5733):436-42
*Leishmania* species cause a spectrum of human diseases in tropical and
subtropical regions of the world. We have sequenced the 36 chromosomes of
the 32.8-megabase haploid genome of *Leishmania* major (Friedlin strain )
and predict 911 RNA genes, 39 pseudogenes, and 8272 protein-coding genes, of
which 36% can be ascribed a putative function. These include genes involved
in host-pathogen interactions, such as proteolytic enzymes, and extensive
machinery for synthesis of complex surface glycoconjugates. The organization
of protein-coding genes into long, strand-specific, polycistronic clusters
and lack of general transcription factors in the L. major, Trypanosoma
brucei, and Trypanosoma cruzi (Tritryp) genomes suggest that the mechanisms
regulating RNA polymerase II-directed transcription are distinct from those
operating in other eukaryotes, although the trypanosomatids appear capable
of chromatin remodeling. Abundant RNA-binding proteins are encoded in the
Tritryp genomes, consistent with active posttranscriptional regulation of
gene expression.


PMID:
15888291<http://refscout.com/cgi-bin/exportAbstract.pl?base=medline-28-9.xml&id=15888291>
TITLE: *Leishmania* chagasi: the alpha-tubulin intercoding region results in
constant levels of mRNA abundance despite protein synthesis inhibition and
growth
state.<http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=15888291>
AUTHORS: Jay E Purdy, John E Donelson, Mary E Wilson
AFFILIATION: Department of Internal Medicine, University of Iowa, Iowa City,
IA 52242, USA.
REFERENCE: Exp Parasitol 2005 Jun 110(2):102-7
The intercoding regions of many *Leishmania* sp. genes have been implicated
in the regulation of mRNA processing, stability, and translation. Herein we
show that the intercoding region of the *Leishmania* chagasi alpha-tubulin
gene (alpha-TUB) confers stable beta- galactosidase (beta-GAL) reporter mRNA
levels during promastigote growth and development in vitro and during
protein synthesis inhibition. The abundance of both endogenous alpha-TUB
mRNA and beta-GAL mRNA from a beta-GAL coding region situated upstream of
the alpha-TUB intercoding region did not change significantly as
promastigotes grew from logarithmic to stationary phase in vitro and the
half-life of the beta- GAL mRNA remained constant. The abundance of both the
endogenous alpha- TUB and the beta-GAL mRNA increased by less than 2-fold
after protein synthesis inhibition corresponding to a moderate increase in
mRNA half- life. These data suggest that the alpha-TUB intercoding region is
an excellent control for the study of the regulation of other differentially
expressed genes.


REQUEST: [ sand fly NOT culicoides ]
(2 articles match this request)

PMID:
16830703<http://refscout.com/cgi-bin/exportAbstract.pl?base=medline-28-9.xml&id=16830703>
TITLE: Taxonomic revision of phlebotomine *sand fly* species in the series
davisi and panamensis of the subgenus Psychodopygus Mangabeira, 1941
(Diptera: Psychodidae:
Phlebotominae).<http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=16830703>
AUTHORS: Gustavo Mayr Lima de Carvalho, Alda Lima Falcão, JosÃ(c) Dilermando
Andrade Filho
AFFILIATION: Laboratório de Leishmanioses, Centro de Pesquisas RenÃ(c)
Rachou-Fiocruz, Av. Augusto de Lima 1715, 30190-002 Belo Horizonte, MG,
Brasil. gumayr at cpqrr.fiocruz.br
REFERENCE: Mem Inst Oswaldo Cruz 2006 Mar 101(2):129-36
Several species of the subgenus Psychodopygus Mangabeira, 1941 are known to
be leishmaniosis vectors in Brazil. Some of them are morphologically
similar, which makes their identification quite difficult concerning
epidemiological studies. The aim of the current work is to study the
morphology of adult specimens of the subgenus Psychodopygus, in accordance
with the morphological similarity and still taking into account the
epidemiological importance of some species. Thus 11 species have been
studied, including four subspecies of adult specimens deposited in the
phlebotomine collection of Centro de Pesquisas RenÃ(c) Rachou-Fiocruz.
Morphological characters found in the literature and new features observed
in this study were recorded in a taxonomic discussion format. These
characters make it easy to separate such species. Four taxa, previously
considered as subspecies, were raised to the category of species.


PMID:
16830705<http://refscout.com/cgi-bin/exportAbstract.pl?base=medline-28-9.xml&id=16830705>
TITLE: Description of Pintomyia (Pifanomyia) brazilorum sp. nov. a new
fossil species from the Dominican Republic (Diptera: Psychodidae:
Phlebotominae).<http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=16830705>
AUTHORS: JosÃ(c) Dilermando Andrade Filho, Eunice A Bianchi Galati, Alda Lima
Falcão
AFFILIATION: Laboratório de Leishmanioses, Centro de Pesquisas RenÃ(c)
Rachou-Fiocruz, Av. Augusto de Lima 1715, 30190-002 Belo Horizonte, MG,
Brasil. jandrade at cpqrr.fiocruz.br
REFERENCE: Mem Inst Oswaldo Cruz 2006 Mar 101(2):141-2
A *sand fly* fossil was found in amber; a vegetal resin, which allows all
the external phlebotomine structures to be seen. The piece that contains the
new species is 14 mm long x 8 mm wide x 3 mm high. All the structures from
the head, thorax, and abdomen were examined under the microscope and
measured with a calibrated micrometric eyepiece. The morphological aspects
of the new species suggest its inclusion in the Pintomyia genus, Pifanomyia
subgenus though it is not possible to include it in any of the series known
for this subgenus. The presence of two atrophied spines on the gonostyles
and gonocoxites without tufts of setae permit the exclusion of the new
species from the other species of the subgenus Pifanomyia. The new species
is named Pintomyia (Pifanomyia ) brazilorum sp. nov.


REQUEST: [ sandfly NOT culicoides ]
(1 article matches this request)

PMID:
16830711<http://refscout.com/cgi-bin/exportAbstract.pl?base=medline-28-9.xml&id=16830711>
TITLE: Phlebotomines (Diptera: Psychodidae) in forested areas of the Serra
da Bodoquena, state of Mato Grosso do Sul,
Brazil.<http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=16830711>
AUTHORS: Eunice A B Galati, Vânia L B Nunes, Paulo C Boggiani, Maria
Elizabeth C Dorval, Geucira Cristaldo, Hilda C Rocha, Elisa T Oshiro,
Geraldo A Damasceno-Júnior
AFFILIATION: Departamento de Epidemiologia, Faculdade de Saúde Pública,
USP, Av. Dr. Arnaldo 715, 01246-904 São Paulo, SP, Brasil. egalati at usp.br
REFERENCE: Mem Inst Oswaldo Cruz 2006 Mar 101(2):175-93
Investigation was undertaken on the behaviour of the phlebotomine fauna in
caves, forests, and anthropic environments of the Serra da Bodoquena ,
between January 1998 and January 2000. This paper reports on the
phlebotomines captured in forested areas with automatic light traps (ALT ),
Shannon traps (ST), aspiration (AN), at natural resting sites and by human
attractiveness (HA) during 24 h. The diversity and abundance of the species
were investigated with ALT installed at 16 points (ground level) and 6 in
the canopy. Natural infection by flagellates was investigated in females
captured with ST AN, and HA. The *sandfly* fauna was represented by 23
species. Twenty-two of these were captured with ALT 15 of them on the
western side, and 20 on the eastern. Lutzomyia longipalpis and Nyssomyia
whitmani were the most abundant on the former and this species together with
Lutzomyia almerioi on the latter side. On the eastern side the ecotopes
located close to caves rendered a significantly greater number (P < or =
0.01) of specimens than did more distant sites. On this side Lu. almerioi
contributed with 56% of the total number of specimens. Lu. almerioi females
were predominantly attracted by humans (96.4%) and by ST (93.2%) and three
of the 2173 dissected (0.138%) presented natural infection by flagellates.
The attraction of Lu. almerioi to humans occurred during all seasons,
predominantly in the summer, and in nocturnal and diurnal periods. Thus it
is bothersome to inhabitants of and visitors to the Bodoquena ridge and a
potential vector of flagellates.


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