[Leish-l] Fwd: Articles found by RefScout 2006/02/08 2006/6
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Date: Wed, 8 Feb 2006 04:28:38
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This is RefScout-Newsletter 6/2006
REQUEST: [ leishmaniasis ]
(18 articles match this request. 1 article matching other requests removed)
PMID: 16447104
TITLE: Amphotericin B colloidal dispersion for the treatment of Indian visceral
leishmaniasis.
AUTHORS: Shyam Sundar, Himanshu Mehta, Amit Chhabra, Vikram Singh, Vineet
Chauhan, Philippe Desjeux, Madhukar Rai
AFFILIATION: Kala-Azar Medical Research Center, Department of Medicine,
Institute of Medical Sciences, Banaras Hindu University, Varanasi, India.
drshyamsundar at dataone.in.
REFERENCE: Clin Infect Dis 2006 Mar 42(5):608-13
Background. In Bihar, India, where visceral leishmaniasis (VL) is
hyperendemic and refractory to antimony, amphotericin B is the most
effective option for the treatment of VL. Lipid formulations of
amphotericin B are able to circumvent the toxic effect of conventional
amphotericin B, and the total dose of these formulations can be
administered over a short duration. However, cost is a major constraint
in the use of lipid formulations of amphotericin B. Amphotericin B
colloidal dispersion (ABCD), which is a less expensive lipid formulation
, has not been tested for the treatment of VL in India.Methods. In an
open-label, randomized clinical trial, we evaluated the efficacy and
safety of a 6-day course of ABCD administered to 3 different dose groups
(total dose: 7.5 mg/kg [group A], 10 mg/kg [group B], and 15 mg/kg [
group C]), each of which included a cohort of 135 patients.Results.
Although infusion-related fever and chills occurred in 56%-68% of
patients in the 3 different dose groups, 401 of 405 patients completed
the treatment. All 135 patients in group A completed treatment, and the
final cure rate for this group was 97%. In the group that received the
highest dose of ABCD (group C), severe backache, an unusual side effect
, was observed in 8 patients (5.92%). Serious adverse effects led to the
withdrawal of 2 patients (1.48%) each from group B and group C.
Conclusions. Although the cost of ABCD is prohibitive, the high level of
efficacy associated with short-term treatment with low-dose ABCD
provides another alternative for the treatment of VL, especially in
regions where VL is antimony refractory.
PMID: 16445499
TITLE: Leishmaniasis recidiva cutis due to Leishmania (Viannia) panamensis in
subtropical Ecuador: isoenzymatic characterization.
AUTHORS: Manuel Calvopina, Hiroshi Uezato, Eduardo A Gomez, Masataka Korenaga,
Shigeo Nonaka, Yoshihisa Hashiguchi
AFFILIATION: From the Department of Parasitology, School of Medicine, Kochi
University, Kochi, Japan.
REFERENCE: Int J Dermatol 2006 Feb 45(2):116-20
Abstract Background Information regarding leishmaniasis recidiva cutis (
LRC), a clinical variant of cutaneous leishmaniasis, in the New World is
scarce. LRC is characterized by slowly progressing lesion(s) that
appear after a variable period of time, from months to years, in or
around the scar of an apparently clinically healed sore. Patients and
methods Six patients are reported who presented with crusted, papular
lesions located on the edge of a healed scar, with a mean of 18.2 months
of slowly progressive evolution. The isolated strains of Leishmania
parasites were characterized by enzyme electrophoresis. Eleven enzyme
systems were assayed. Skin biopsies from the active border of the
lesions were taken for histopathology. Results Tissue sections showed a
granulomatous, lymphohistiocytic, dermal infiltrate containing Langhans
' giant cells. The anamnestic data, together with the clinical and
histopathologic findings, support the diagnosis of LRC. The isoenzyme
profile of Leishmania parasites isolated from five of the six patients
identified them as Leishmania (Viannia) panamensis. Conclusions These
findings are the first reported evidence of LRC within the clinical
spectrum of American tegumentary leishmaniasis in Ecuador, and of its
causative agent. The existence of LRC has future implications for both
disease treatment and vaccine development.
PMID: 16445503
TITLE: Psoriasiform cutaneous leishmaniasis.
AUTHORS: Stefano Veraldi, Chiara Galloni, Raffaella Cremonesi, Riccardo Cavalli
AFFILIATION: From the Institute of Dermatological Sciences, I.R.C.C.S.,
University of Milan, Milan, Italy.
REFERENCE: Int J Dermatol 2006 Feb 45(2):129-30
PMID: 16451340
TITLE: Accessibility of diagnostic and treatment centres for visceral
leishmaniasis in Gedaref State, northern Sudan.
AUTHORS: S Gerstl, R Amsalu, K Ritmeijer
AFFILIATION: Médecins Sans Frontières Holland, Amsterdam, The Netherlands.
REFERENCE: Trop Med Int Health 2006 Feb 11(2):167-75
Summary Objective To evaluate the accessibility of visceral
leishmaniasis (VL) treatment. Method Community-based study using in-
depth qualitative interviews and focus group discussions with key
informants, as well as quantitative questionnaires with 448 randomly
selected heads of households in nine representative villages in three
geographical sub-regions. Results Despite the high incidence of the
disease, most people in Gedaref State know little about VL, and help at
a treatment centre is usually sought only after traditional remedies and
basic allopathic drugs have failed. Factors barring access to treatment
are: lack of money for treatment and transport, impassability of roads
, work priorities, severe cultural restrictions of women's decision-
making power and distance to the next health center. Conclusions To
provide more VL patients with access to treatment in this highly endemic
area, diagnostic and treatment services should be decentralized. Health
education would be a useful tool to rationalise people's health-seeking
behaviour.
PMID: 16455899
TITLE: Use of PCR-Restriction Fragment Length Polymorphism Analysis To Identify
the Main New World Leishmania Species and Analyze Their Taxonomic Properties
and Polymorphism by Application of the Assay to Clinical Samples.
AUTHORS: Brice Rotureau, Christophe Ravel, Pierre Couppié, Francine Pratlong,
Mathieu Nacher, Jean-Pierre Dedet, Bernard Carme
AFFILIATION: Laboratoire Hospitalo-universitaire de Parasitologie et Mycologie
Médicale, Equipe EA 3593, UFR de Médecine de l'Université des Antilles et de
la Guyane, Campus Saint-Denis, BP 718, 97336 Cayenne, Guyane Française.
ufrmedag2 at wanadoo.fr.
REFERENCE: J Clin Microbiol 2006 Feb 44(2):459-67
At least 13 characterized Leishmania species are known to infect humans
in South America. Five of these parasites are transmitted in the
sylvatic ecotopes of the whole French Guianan territory and responsible
for cutaneous leishmaniasis. For the diagnosis of cutaneous
leishmaniasis, restriction fragment length polymorphism (RFLP) analyses
have shown promising results. Thus, the end of the small subunit and
internal transcribed spacer 1 of the rRNA genes were sequenced and
targeted by PCR-RFLP analysis in the 10 main New World (NW) Leishmania
species from the two subgenera. Then, the procedure was tested on 40
samples from patients with cutaneous leishmaniasis, and its results were
compared with those of conventional methods. (i) The results of this
simple genus-specific method were in agreement with those of previous
isoenzyme analyses. (ii) This method distinguished the most medically
relevant Leishmania species with only one enzyme (RsaI). (iii) This
method could be performed directly on human biopsy specimens (
sensitivity of 85.7%). Performing NW Leishmania species typing rapidly
and easily in the field constitutes a very valuable improvement for
detection of Leishmania spp. Revealing great diversity with several
enzymes, this method could also be useful for taxonomic, ecological, and
epidemiological studies in space and time.
PMID: 16455904
TITLE: Multilocus Microsatellite Typing as a New Tool for Discrimination of
Leishmania infantum MON-1 Strains.
AUTHORS: Sebastian Ochsenreither, Katrin Kuhls, Matthias Schaar, Wolfgang
Presber, Gabriele Schönian
AFFILIATION: Institute of Microbiology and Hygiene, Charité
Universitätsmedizin Berlin, Dorotheenstr. 96, 10117 Berlin, Germany.
gabriele.schoenian at charite.de.
REFERENCE: J Clin Microbiol 2006 Feb 44(2):495-503
The Leishmania donovani complex, which consists of L. donovani, L.
infantum-L. chagasi, and L. archibaldi, is responsible for visceral
manifestations of leishmaniasis. Multilocus enzyme electrophoresis is
the standard method for the characterization and identification of
strains of Leishmania. For L. infantum, the predominance of zymodeme MON
-1 significantly reduces the discriminative power of this approach. In
the present study, we developed 17 independent polymorphic
microsatellite markers for the typing of strains of L. infantum, with
the main emphasis on zymodeme MON-1. The discriminative powers of 11
markers selected from among these markers were tested by using a panel
of 63 isolates of the L. donovani complex. Unique multilocus genotypes
were observed for the strains analyzed, with only three exceptions.
Model-based and distance-based analyses of the data set showed
comparable results. It was possible to discriminate between L. donovani
sensu stricto, a non-MON-1 group of L. infantum isolates, and a MON-1
group of L. infantum isolates. Within MON-1, three clusters with
geographical correlations became apparent. The frequency of
heterozygosity in the alleles analyzed varied extremely between the
different groups of isolates. The main clusters described are not
consistent with species definitions based on isoenzyme analysis but
confirm the results of former PCR-based investigations.
PMID: 16428780
TITLE: Biogenesis of Leishmania major-harboring vacuoles in murine dendritic
cells.
AUTHORS: Ulrich Körner, Veronika Fuss, Jutta Steigerwald, Heidrun Moll
AFFILIATION: Institut für Molekulare Infektionsbiologie, Universität
Würzburg, Röntgenring 11, D-97070 Würzburg, Germany.
REFERENCE: Infect Immun 2006 Feb 74(2):1305-12
In mammalian hosts, Leishmania sp. parasites are obligatory
intracellular organisms that invade macrophages and dendritic cells (DC
), where they reside in endocytic organelles termed parasitophorous
vacuoles (PV). Most of the present knowledge of the characteristics of
PV harboring Leishmania sp. is derived from studies with infected
macrophages. Since DC play a key role in host resistance to
leishmaniasis, there is a need to understand the properties and
biogenesis of PV in Leishmania sp.-infected DC. Therefore, we determined
the acquisition of endosomal and lysosomal molecules by Leishmania
major-containing compartments in DC at different maturation stages,
using fluorescence labeling and confocal microscopy. The results show
that newly formed phagosomes in DC rapidly develop into late endosomal
compartments. However, the small GTPase Rab7, which regulates late
fusion processes, was found only in PV of mature bone marrow-derived DC
(BMDC); it was absent in immature BMDC, suggesting an arrest of their
PV biogenesis at the stage of late endosomes. Indeed, fusion assays with
endocytic tracers demonstrated that the fusion activity of L. major-
harboring PV toward lysosomes is higher in mature BMDC than in immature
BMDC. The inhibition of PV-lysosome fusion in DC is dependent upon the
viability and life cycle stage of the parasite, because live
promastigotes blocked the fusion almost completely, whereas killed
organisms and amastigotes induced a considerable level of fusion
activity. The differences in the fusion competences of immature and
mature DC may be relevant for their distinct functional activities in
the uptake, transport, and presentation of parasite antigens.
PMID: 16451339
TITLE: Clinical value of anti-live Leishmania (Viannia) braziliensis
immunoglobulin G subclasses, detected by flow cytometry, for diagnosing active
localized cutaneous leishmaniasis.
AUTHORS: R D R Rocha, C M F Gontijo, S M Elói-Santos, A Teixeira-Carvalho, R
Corrêa-Oliveira, T C A Ferrari, M J Marques, W Mayrink, O A Martins-Filho
AFFILIATION: Laboratório de Doença de Chagas, CPqRR-FIOCRUZ/BH, Belo
Horizonte, Brazil.
REFERENCE: Trop Med Int Health 2006 Feb 11(2):156-66
Summary objective To evaluate the clinical value of flow cytometry anti-
live promastigate antibody (FC-ALPA), for diagnosing active cutaneous
leishmaniasis. method Serum samples from 145 individuals living in
endemic areas for localized cutaneous leishmaniasis (population 1) were
classified as having the disease or not and then tested for their IgG
reactivity by indirect immunofluorescence assay and FC-ALPA-IgG. The
results of FC-ALPA-IgG were expressed as percentage of positive
fluorescent parasite. Both tests were also evaluated in serum samples of
people with visceral leishmaniasis and Chagas disease (population 1A).
results In population 1, FC-ALPA-IgG performed better than the
immunofluorescence assay regarding sensitivity, specificity and
predictive values. Analysis of the results according to the likelihood
ratios indicated that a percentage of positive fluorescent parasite <
;/=60 practically excludes the diagnosis of localized cutaneous
leishmaniasis (likelihood ratio = 0.07), whereas at >60% it reinforces
diagnosis of the disease (likelihood ratio = 7.0). Immunofluorescent
assay is of little value (likelihood ratio = 2.04). In population 1A,
both tests performed worse, but FC-ALPA-IgG achieved better statistical
indexes than immunofluorescent assay. conclusion The FC-ALPA-IgG is a
valuable method for serological diagnosis of localized cutaneous
leishmaniasis. FC-ALPA-IgG1/ALPA-IgG2 combined analysis is an additional
serological tool for discriminating localized visceral leishmaniasis,
Chagas disease and visceral leishmaniasis in areas where these
infections co-exist.
PMID: 16323026
TITLE: Nocturnal activity of phlebotomine sandflies (Diptera: Psychodidae) in a
cutaneous leishmaniasis focus in Chichaoua, Morocco.
AUTHORS: S Guernaoui, S Boussaa, B Pesson, A Boumezzough
AFFILIATION: UR Geodes, Institut de Recherche pour le Développement, 32 avenue
Henri Varagnat, 93140, Bondy, Cedex, France.
REFERENCE: Parasitol Res 2006 Feb 98(3):184-8
The nocturnal activity of phlebotomine sandflies (Diptera: Psychodidae)
was studied "at an epidemic focus" on human cutaneous
leishmaniasis due to Leishmania tropica Wright in Chichaoua province, in
Morocco. Sandflies were collected using light and sticky-paper traps
changed at 2-h intervals, inside and around houses, in August and
October 2004. Overall, 633 sandflies, belonging to six species of
Phlebotomus and three of Sergentomyia, were collected. Sandfly activity
was nocturnal and higher at twilight. Several activity patterns were
observed according to the species. Phlebotomus (Paraphlebotomus)
sergenti Parrot, 1917, the suspected vector of L. tropica in this focus
, was caught during each collection performed from 1900 to 0500 hours,
the numbers of species caught peaked at 1900-2100 hours. There were
seasonal variations of the nocturnal activity, which could be related to
the variations in temperature and relative humidity.
PMID: 16445420
TITLE: Cutaneous Leishmaniasis: Three Children with Leishmania major
Successfully Treated with Itraconazole.
AUTHORS: J M L White, J R Salisbury, J Jones, E M Higgins, F Vega-Lopez
AFFILIATION: Department of Dermatology, King's College Hospital, London, United
Kingdom.
REFERENCE: Pediatr Dermatol 2006 Jan-Feb 23(1):78-80
We report the rare instance of four family members with numerous
cutaneous lesions of Leishmania major contracted while on holiday in
Algeria. Treatment was successful with oral itraconazole for the
children and intralesional sodium stibogluconate for the mother.
Cutaneous leishmaniasis should be considered in those with apparently
sterile plaques returning from endemic areas. These results suggest that
itraconazole, which is ideally suited for use in children, is an
effective monotherapy for L. major.
PMID: 16449014
TITLE: Successful treatment of visceral leishmaniasis with fluconazole and
allopurinol in a patient with renal failure.
AUTHORS: Murat Colakoglu, Guzin Fidan Yaylali, Nagihan Yalcin Colakoglu, Mustafa
Yilmaz
AFFILIATION: From the Departments of Nephrology.
REFERENCE: Scand J Infect Dis 2006 38(2):152-4
Standard treatments for visceral leishmaniasis (antimonials,
amphotericin B and pentamidine) pose several problems. Failure of
antimonials or severe toxicity is particularly troublesome in patients
with renal insufficiency. We report a case of visceral leishmaniasis and
renal insufficiency successfully treated with fluconazole and
allopurinol for 4 months.
PMID: 16457386
TITLE: First report on the presence of morphospecies A and B of Phlebotomus
argentipes sensu lato (Diptera: Psychodidae) in Sri Lanka--implications for
leishmaniasis transmission.
AUTHORS: S N Surendran, A Kajatheepan, N J Hawkes, R Ramasamy
AFFILIATION: Department of Zoology, University of Jaffna, Sri Lanka.
noble at jfn.ac.lk
REFERENCE: J Vector Borne Dis 2005 Dec 42(4):155-8
PMID: 16319783
TITLE: Characterization of cell cultures derived from Lutzomyia spinicrassa
(Diptera: Psychodidae) and their susceptibility to infection with Leishmania
(Viannia) braziliensis.
AUTHORS: Angela Cristina Zapata Lesmes, Estrella Cárdenas Castro, Felio Bello
AFFILIATION: Entomology, Cell Biology, and Genetics Laboratory, Universidad de
La Salle, Bogotá, Colombia.
REFERENCE: Med Sci Monit 2005 Dec 11(12):BR457-464
Background: The sand fly Lutzomyia spinicrassa (Morales, Osorno-Mesa,
Osorno & de Hoyos, 1969) is a vector of Leishmania (Viannia)
braziliensis, an etiological agent of cutaneous leishmaniasis in
Colombia. The present article describes, for the first time, the
morphological, karyotypical, and isozymatic characteristics of cell
cultures derived from L. Spinicrassa embryonic tissues as well as the
interaction of L. Braziliensis with these cell cultures. Material/
Methods: L. Spinicrassa embryonated eggs and neonate larvae were taken
for tissue explants. These were seeded in Grace, L-15, Grace/L-15, MM/
VP12, and MK/VP12 culture media. The pH range in these media was 6.7 to
6.9 and the cultures were incubated at 28 degrees C. The MHOM/CO/86/
CL250 strain of L. Braziliensis was used for experimental infection of
cell cultures of L. Spinicrassa. Results: Cell growth was achieved in L-
15 medium and a confluent monolayer was obtained 180 days after the
embryonated eggs were explanted. The cell morphology of the primary cell
cultures was initially heterogeneous, but in the confluent monolayer of
these cell cultures and in the subcultures the predominant cell types
were later fibroblast-like and epithelial-like. Cultured cells were
predominantly diploid (2n=8); however, significant percentages of
aneuploids were also recorded. The cell culture isozyme patterns of L.
Spinicrassa coincided with pupae samples from the same species.
Promastigote forms of L. Braziliensis could invade cells and transform
into amastigote-like forms inside them Conclusions: The characteristics
of cell cultures derived from L. Spinicrassa embryonic tissues were
determined. These cultures emerge as a new model to study the life-cycle
of L. Braziliensis.
PMID: 16355672
TITLE: Utility of diagnostic tests used in diagnosis of infection in dogs
experimentally inoculated with a North American isolate of Leishmania infantum
infantum.
AUTHORS: A C Rosypal, G C Troy, R B Duncan, A M Zajac, D S Lindsay
AFFILIATION: Department of Biomedical Sciences and Pathobiology, Virginia
Maryland Regional College of Veterinary Medicine, Virginia Tech, Blacksburg, VA
24061, USA. arosypal at vt.edu
REFERENCE: J Vet Intern Med 2005 Nov-Dec 19(6):802-9
Eight female beagles were infected with 1 x 10(7) (low dose, LD) or 2 x
10(8) (high dose, HD) promastigotes of a North American isolate of
Leishmania infantum infantum (LIVT-1 strain) isolated from naturally
infected Virginia Foxhounds. Two female beagles served as negative
controls and 2 male beagles chronically infected (> 3 years) with
Leishmania infantum chagasi were positive controls. Bone marrow (BM) and
lymph node (LN) aspirates were collected every 6-8 weeks for cytologic
evaluation, parasite culture, and polymerase chain reaction (PCR). Serum
samples were collected monthly for determination of serologic responses
by indirect fluorescent antibody test (IFAT) and diagnostic rK39
antigen. Cultures of BM and LN aspirates and cytology evaluation were
consistently positive in positive control dogs during the course of
study. Negative control dogs were negative on BM and LN cultures and on
cytologic evaluation of aspirates. Amastigotes were present on
cytological examination of BM aspirates in 2 experimentally infected
dogs. Cultures of LN aspirates were positive on 22 samples, whereas BM
cultures were positive on 12 samples for all dogs. IFA titers ranged
from 0 to 1 :400 in experimentally infected dogs during the course of
the study. Recombinant K39 immunoassay tests were consistently positive
in positive control dogs and in the HD dogs by approximately 8 weeks
after infection. BM PCR products were identified more consistently in
the HD dogs compared with the LD dogs. Kappa statistics indicated PCR
correlated better with cultures and cytology than did IFAT or the rK39
immunoassay results in the experimentally infected dogs.
PMID: 16450910
TITLE: Fine needle aspiration of subcutaneous masses caused by Aspergillus: a
report of 2 cases.
AUTHORS: Bita Geramizadeh, Parastoo Kheirandish, Payam Fatheezadeh, Ramin
Jannesar
AFFILIATION: Pathology Department, Shiraz University of Medical Sciences,
Shiraz, Iran. geramib at sums.ac.ir
REFERENCE: Acta Cytol 2005 Nov-Dec 49(6):666-8
BACKGROUND: Fine needle aspiration biopsy is a well-established method
for dijfrrentiation of infective from neoplastic lesions. Varions
infective agents, such as mycobacteria, leishmaniasis and microfaria can
be diagnosed from aspirates, but there are few case reports on fungal
infections in aspirates. Cytologic diagnosis of Aspergillus has
occasionally occurred on sputum, pulmonary samples, vaginal secretions,
endometrial washings and maxillary sinus specimens. One case of hepatic
and subcutaneous masses was diagnosed as Aspergillus by fine needle
aspiration and confirmed by culture and histology. CASES: Two cases of
subcutaneous aspergillosis were diagnosed by fine needle aspiration and
confirmed by culture and histology. CONCLUSION: Fine needle aspiration
cytology is a rapid, sensitive and important method of diagnosing
Aspergillus and provides a rapid diagnosis, which may be life saving in
an immunocompromised patient.
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PMID: 16047575
TITLE: Leishmaniasis: early diagnosis is key.
AUTHORS: Michael Roscoe
AFFILIATION: US Army, USA.
REFERENCE: JAAPA 2005 Jul 18(7):47-50, 53-4
A patient presents with nasal congestion, a history of nosebleed, and
painful lesions on his body and in his mouth. What questions should you
ask to ensure that you make an accurate diagnosis?
PMID: 16148377
TITLE: [Study of intravascular coagulation activation markers in patients with
visceral leishmaniasis]
AUTHORS: M L Lomtadze, M A Khochava, I A Shalamberidze, V I Kharaishvili, E O
Vorob'eva
REFERENCE: Georgian Med News 2005 Jul-Aug (124-125):47-50
During last decades significant attention has been paid to the increase
of protozoal infections including leishmaniasis. The management of this
disease is rather problematic. Significant increase of cases of this
disease was observed in Georgia as well. The problem of visceral
leishmaniasis is very important nowadays. According to references and
our clinical experience patients with visceral leishmaniasis are
predisposed to bleeding. The objective of our study was the assessment
of functional status of hemostasis in patients with visceral
leishmaniasis. We have studied the intravascular activation markers of
blood coagulation -- the soluble fibrin-monomeric complexes (SFMC) and
fibrinogen/fibrin degradation products (D-dimer) in order to reveal the
disorders of hemocoagulation. SFMC and D-dimer we studied in 45 patients
with visceral leishmaniasis before and after treatment (with 20-25 day
intervals). One patient with severe generalized bleeding died within 72
hours of admission. SFMC measurements were conducted by the
orthophenantroline test (Renam, Russia). D-dimer level was measured
using FDP-Slidex Direct kit (Bio-Meriou, France). Especially high levels
of SFMC and D-dimer have been revealed in cases of severe form of
visceral leishmaniasis. SFMC level was increased by 80% (p=0,003), and D
-dimer level by 95,6% (p=0,023). There was correlation between numbers
of platelets and intravascular blood coagulation markers. Investigation
of SFMC and D-dimer showed that in case of visceral leishmaniasis
activation of intravascular coagulation takes place, particularly during
the severe forms of the disease. Study of these markers is of the
diagnostic and prognostic importance and for the initiation of treatment
at an early stage of infection, which may potentially avoid the
possibility of developing an uncompensated DIC.
REQUEST: [ leishmania ]
(14 articles match this request. 8 articles matching other requests removed)
PMID: 16271040
TITLE: Homology-model-guided site-specific mutagenesis reveals the mechanisms of
substrate binding and product-regulation of adenosine kinase from Leishmania
donovani.
AUTHORS: Rupak Datta, Ishita Das, Banibrata Sen, Anutosh Chakraborty, Subrata
Adak, Chhabinath Mandal, Alok K Datta
AFFILIATION: Division of Infectious Diseases, Leishmania Group, Indian Institute
of Chemical Biology, 4 Raja S.C. Mullick Road, Kolkata 700032, India.
REFERENCE: Biochem J 2006 Feb 394(Pt 1):35-42
Despite designating catalytic roles of Asp299 and Arg131 during the
transfer of gamma-phosphate from ATP to Ado (adenosine) [R. Datta, Das,
Sen, Chakraborty, Adak, Mandal and A. K. Datta (2005) Biochem. J. 387,
591-600], the mechanisms that determine binding of substrate and cause
product inhibition of adenosine kinase from Leishmania donovani remained
unclear. In the present study, employing homology-model-guided site-
specific protein mutagenesis, we show that Asp16 is indispensable, since
its replacement with either valine or arginine resulted in a >200-fold
increase in K(m) (Ado) with a 1000-fold decrease in k(cat)/K(m),
implying its critical importance in Ado binding. Even glutamate
replacement was not tolerated, indicating the essentiality of Asp16 in
the maintenance of steric complementarity of the binding pocket. Use of
2'or 3'-deoxygenated Ado as substrates indicated that, although both the
hydroxy groups play important roles in the formation of the enzyme-Ado
complex, the binding energy (DeltaDeltaG(B)) contribution of the former
was greater than the latter, suggesting possible formation of a
bidentate hydrogen bond between Asp16 and the adenosyl ribose.
Interestingly, AMP-inhibition and AMP-binding studies revealed that,
unlike the R131A mutant, which showed abrogated AMP-binding and
insensitivity towards AMP inhibition despite its unaltered K(m) (Ado),
all the Asp16 mutants bound AMP efficiently and displayed AMP-sensitive
catalytic activity, suggesting disparate mechanisms of binding of Ado
and AMP. Molecular docking revealed that, although both Ado and AMP
apparently occupied the same binding pocket, Ado binds in a manner that
is subtly different from AMP binding, which relies heavily on hydrogen-
bonding with Arg131 and thus creates an appropriate environment for
competition with Ado. Hence, besides its role in catalysis, an
additional novel function of the Arg131 residue as an effector of
product-mediated enzyme regulation is proposed.
PMID: 16455872
TITLE: Purified Excreted-Secreted Antigens from Trypanosoma cruzi
Trypomastigotes as Tools for Diagnosis of Chagas' Disease.
AUTHORS: Mariolga Berrizbeitia, Momar Ndao, José Bubis, Marcelo Gottschalk,
Alberto Aché, Sonia Lacouture, Mehudy Medina, Brian J Ward
AFFILIATION: McGill Center for Tropical Diseases, Montreal General Hospital,
Room D7-153, Montreal, Quebec H3G IA4 Canada. brian.ward at mcgill.ca.
REFERENCE: J Clin Microbiol 2006 Feb 44(2):291-6
There is currently no "gold standard" test for the diagnosis
of late-stage Chagas' disease. As a result, protection of the blood
supply in areas where Chagas' disease is endemic remains problematic. A
panel of 709 serum samples from subjects with confirmed Chagas' disease
(n = 195), healthy controls (n = 400), and patients with other
parasitic diseases (n = 114) was used to assess enzyme-linked
immunosorbent assays (ELISAs) based on a concentrated extract of
excretory-secretory antigens from either Brazil or Tulahuen strain
Trypanosoma cruzi trypomastigotes (total trypomastigote excretory-
secretory antigens [TESAs]). The total TESA-based assays had excellent
overall sensitivity (100%) and specificity (>94%), except for cross-
reactivity with Leishmania-infected sera. In an attempt to increase the
specificity of the assay, immunoaffinity chromatography was used to
purify the TESA proteins (TESA(IA) proteins). By Western blotting, a
series of polypeptide bands with molecular masses ranging from 60 to 220
kDa were recognized by pooled sera positive for Chagas' disease. An
ELISA based on TESA(IA) proteins had a slightly lower sensitivity (98.6
%) but an improved specificity (100%) compared to the sensitivity and
specificity of the total TESA protein-based ELISAs. A 60-kDa polypeptide
was identified as a major contributor to the cross-reactivity with
Leishmania. These data suggest the need for field validation studies of
TESA- and TESA(IA)-based assays in regions where Chagas' disease is
endemic.
PMID: 16455900
TITLE: Molecular Epidemiology of Leishmania (Viannia) guyanensis in French
Guiana.
AUTHORS: Brice Rotureau, Christophe Ravel, Mathieu Nacher, Pierre Couppié,
Isabelle Curtet, Jean-Pierre Dedet, Bernard Carme
AFFILIATION: Laboratoire Hospitalo-universitaire de Parasitologie et Mycologie
Médicale, Equipe EA 3593, UFR de Médecine de l'Université des Antilles et de
la Guyane, Campus Saint-Denis, BP 718, 97336 Cayenne, Guyane Française.
ufrmedag2 at wanadoo.fr.
REFERENCE: J Clin Microbiol 2006 Feb 44(2):468-73
Little information is available about the genetic variability of
Leishmania populations and the possible correlations with
ecoepidemiological features of leishmaniases. The present study was
carried out in French Guiana, a country where cutaneous leishmaniases (
CL) are endemic over the whole territory. The genetic polymorphism of a
nuclear sequence encompassing the end of the ribosomal small subunit and
the internal transcribed spacer 1 of 265 isolates from patients with CL
was examined by restriction fragment length polymorphism analysis.
Genotypes based on the fingerprinting phenetic integration were compared
to epidemiological, clinical, and geographical data. In agreement with
previous reports, five different Leishmania species were identified, but
Leishmania (Viannia) guyanensis represented 95.8% of the samples. Two
distinct L. (V.) guyanensis populations were found to originate in two
ecologically characterized regions. Higher lesional parasite densities
and the need for additional treatments were significantly linked to
genotype group I. Parasites of genotype group II were more likely to
cause chronic and disseminated cutaneous forms in patients. L. (V.)
guyanensis was previously said not to be very polymorphic; however, the
present analysis resulted in a significant degree of discrimination
among L. (V.) guyanensis isolates from diverse ecological areas and with
different clinical implications.
PMID: 16438675
TITLE: Regulating immunity to malaria.
AUTHORS: E M Riley, S Wahl, D J Perkins, L Schofield
AFFILIATION: Department of Infectious and Tropical Diseases, London School of
Hygiene and Tropical Medicine, London, UK. eleanor.riley at lshtm.ac.uk
REFERENCE: Parasite Immunol 2006 Jan-Feb 28(1-2):35-49
The optimal outcome of a malaria infection is that parasitized cells are
killed and degraded without inducing significant pathology. Since much
of the pathology of malaria infection can be immune-mediated, this
implies that immune responses have to be carefully regulated. The
mechanisms by which anti-malarial immune responses are believed to be
regulated were discussed at the recent Malaria Immunology Workshop (
Bloomberg School of Public Health, Johns Hopkins University, Baltimore,
Maryland, USA; February 2005). Potential regulatory mechanisms include
regulatory T cells, which have been shown to significantly modify
cellular immune responses to various protozoan infections, including
leishmania and malaria; neutralising antibodies to pro-inflammatory
malarial toxins such as glycosylphosphatidylinositol and haemozoin; and
self-regulating networks of effector molecules. Innate and adaptive
immune responses are further moderated by the broader immunological
environment, which is influenced by both the genetic background of the
host and by co-infection with other pathogens. A detailed understanding
of the interplay between these different immunoregulatory processes may
facilitate the rationale design of vaccines and novel therapeutics.
PMID: 16451193
TITLE: Insights into the role of gp63-like proteins in lower trypanosomatids.
AUTHORS: Claudia Masini d'Avila-Levy, Felipe Almeida Dias, Ana Cristina Nogueira
de Melo, Juliana Lopes Martins, Angela Hampshire De Carvalho Santos Lopes,
André Luis Souza Dos Santos, Alane Beatriz Vermelho, Marta Helena Branquinha
AFFILIATION: Departamento de Microbiologia Geral, Instituto de Microbiologia
Prof. Paulo de Góes, Centro de Ciências da Saúde, Universidade Federal do
Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
REFERENCE: FEMS Microbiol Lett 2006 Jan 254(1):149-56
Abstract Any actual understanding of trypanosomatids in general requires
a comprehensive analysis of the less-specialized species as thorough as
our knowledge of the more specialized Leishmania and Trypanosoma. In
this context, we have shown by antibody cross-reactivity that purified
extracellular metallopeptidases from Phytomonas françai, Crithidia
deanei (cured strain) and Crithidia guilhermei share common epitopes
with the leishmanial gp63. Flow cytometry and fluorescence microscopy
analyses indicated the presence of gp63-like molecules on the cell
surface of these lower trypanosomatids. Binding assays with explanted
guts of Aedes aegypti incubated with purified gp63 and the pretreatment
of trypanosomatids with anti-gp63 antibodies indicated that the gp63-
like molecules are involved in the adhesive process of these
trypanosomatids to the A. aegypti gut wall. In addition, our results
indicate for the first time that the gp63-like molecule binds to a
polypeptide of 50 kDa on the A. aegypti gut epithelium extract.
PMID: 16369458
TITLE: Macrophage may responses to androgen via its receptor.
AUTHORS: Kazem Ahmadi, Alan B McCruden
AFFILIATION: Department of Immunology, Faculty of Medicine and Research Centre
of Molecular Biology, Baqiyatallah Medical Science University, Tehran, I.R.
Iran.
REFERENCE: Med Sci Monit 2006 Jan 12(1):BR15-20
Background: Sex hormones have profound effects on immune responses and
may influence the disease which caused by intracellular parasite(
Leishmania) and bacterial (tuberculosis)and also autoimmune disease such
as rheumatoid arthritis (RA). It has also been demonstrated that 5alpha
-Dihydrotestosterone (5alpha-DHT) modulate nitric oxide and cytokine
release by macrophages. These effects seem to be exerted by specific
receptors for androgen in macrophages. Material/Methods: Protein
secretion: The effect of 5alpha-DHT on protein secretion by peritoneal
macrophages of NZB\BALBc mice was investigated using radiolabelled
protein secretion following SDS-PAGE and Fluorography. Binding Assay:
Androgen binding was also investigated using an autoradiography method.
Peritoneal macrophages were treated with [3H]- 5alpha-DHT and incubated
for 2 h before smearing on to microscope slides. Slides were air dried,
dipped in Kodak NTB photographic emulsion, sealed in light proof boxes
and left at 4 degrees C for 6 weeks. Results: The results showed that
protein secretion by macrophages changed under 5alpha-DHT treatment.
Analysis of the data according to quantitation of [(3)H]-5alphaDHT
binding receptors in fixed-slide mounted cells, identified a high
specific androgen binding at physiological concentration. The receptors
had a relatively high affinity for the 5alpha-DHT, So that binding
affinity was not inhibited in the presence of 100-fold excess of non
labelled 17-beta Estradiol. Conclusions: These results suggest that the
immunosuppressive action exerted by androgen is at least partially
achieved through a direct influence on macrophages.
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