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This is RefScout-Newsletter 43/2004.


REQUEST: [ leishmaniasis ]

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



PMID: 15487964
 

TITLE: Visceral leishmaniasis: a trip to the Greek Islands is not always
idyllic.

AUTHORS: Oui Ju, David I Grove, Wilfrid J Jaksic, Geoffrey W Dart

AFFILIATION: Microbiology, Queen Elizabeth Hospital, Woodville Road, Woodville,
SA 5111, Australia. Oui.Ju at fmc.sa.gov.au.

REFERENCE: Med J Aust 2004 Oct 181(8):446-7

Although cutaneous leishmaniasis is occasionally seen in Australia in 
overseas travellers and migrants, visceral leishmaniasis has been 
reported rarely and only in people who were immunocompromised. We 
describe an 18-year-old immunocompetent man who presented with 
pancytopenia and a 2-week history of fever and lethargy a year after 
visiting the Greek Islands. Visceral leishmaniasis was diagnosed after a
 bone marrow biopsy showed protozoa, and the patient responded well to 
treatment with liposomal amphotericin. To our knowledge, this is the 
first case of visceral leishmaniasis in an immunocompetent patient in 
Australia.








PMID: 15470762
 

TITLE: Emergency initiative to reduce leishmaniasis in Afghanistan.

AUTHORS: Josephine Querido

REFERENCE: Lancet Infect Dis 2004 Oct 4(10):599




PMID: 15485530
 

TITLE: Evaluation of CO laser efficacy in the treatment of cutaneous
leishmaniasis.

AUTHORS: A Asilian, A Sharif, G Faghihi, Sh Enshaeieh, F Shariati, A H Siadat

AFFILIATION: From the Department of Dermatology, Leishmaniasis Research Center,
Isfahan University School of Medicine, XXX, Iran.

REFERENCE: Int J Dermatol 2004 Oct 43(10):736-8

Abstract Background Cutaneous leishmaniasis is a common disease in Iran
, especially in the north-east, central and southern parts of the 
country. Many treatments have been suggested for this disease but none 
is completely effective and without side-effects such as pain, 
arthralgia and renal or cardiac complications. Lasers have been used for
 treatment of several skin diseases since 1970, and CO(2) lasers are now
 being used for treatment of leishmaniasis. In this study, a CO(2) laser
 (Sonic 500 machine) was used as a source of a continuous CO(2) laser 
wave. Methods A total of 123 patients (68 female and 55 male) with 183 
lesions were treated with the CO(2) laser. The maximum power was 100 W 
and the pulse width was 0.5-5 s. For the control group, 110 patients (
with 250 lesions) were treated with glucantime 50 mg/kg/day for 15 days 
and, after 15 days of rest, this treatment was repeated (Glucantime Amps
, 1.5 g in a 50-mL solution, was used). For follow-up, the patients were
 visited 1, 3, 4, 8, 12 and 24 weeks after treatment and any 
complications, recurrences or other wound characteristics were recorded
. In the second group, Finally, all collected data were analyzed 
statistically. Results Statistical analysis with the chi(2) test showed 
that treatment with the CO(2) laser was more effective than treatment 
with glucantime (P = 0.0007). Complications were also seen less often 
with the laser treatment than with glucantime and were limited to the 
ulcer site. The CO(2) laser was more effective in treating cutaneous 
leishmaniasis than glucantime (1.12 times), had fewer side-effects (4.5
% vs. 24%) and resulted in a shorter healing time (1 month vs. 3 months
), and treatment could be applied in a single session. Conclusions The 
results of this and previous studies suggest that cutaneous 
leishmaniasis can be treated effectively with CO(2) laser if those 
providing the treatment are sufficiently experienced. Laser treatment is
 more cost-effective than other treatments and can be used as first-line
 therapy for cutaneous leishmaniasis (wet and dry types).




PMID: 15472268
 

TITLE: Mucocutaneous leishmaniasis: an imported infection among travellers to
central and South America.

AUTHORS: Sukhbir Ahluwalia, Stephen D Lawn, Jeevendra Kanagalingam, Henry Grant,
Diana N J Lockwood

AFFILIATION: Royal National Throat, Nose and Ear Hospital, London.

REFERENCE: BMJ 2004 Oct 329(7470):842-4




PMID: 15482407
 

TITLE: Evaluation of the direct agglutination test based on freeze-dried
Leishmania donovani promastigotes for the serodiagnosis of visceral
leishmaniasis in Sudanese patients.

AUTHORS: Khalid A A Abdallah, Bakri Y M Nour, Henk D F H Schallig, Adil Mergani,
Zohal Hamid, Abdallah Abd Elkarim, Osman K Saeed, Ahmed A Mohamadani

AFFILIATION: Blue Nile Research and Training Institute, University of Gezira,
Gezira, Sudan.

REFERENCE: Trop Med Int Health 2004 Oct 9(10):1127-31

Summary The direct agglutination test (DAT) based on freeze-dried (FD) 
Leishmania donovani antigen was evaluated for the serodiagnosis of kala-
azar in a rural setting in eastern Sudan. The performance of the FD-DAT 
was compared with standard liquid antigen (LQ) by testing serum samples 
and blood samples collected on filter paper of microscopically and PCR-
confirmed VL patients, apparently healthy endemic controls and patients 
with other relevant infectious diseases for the region. In the present 
study, the FD-DAT had a sensitivity of 96.8% and a specificity of 96.2
%. The LQ-DAT had a sensitivity of 91.0% and a specificity of 96.6%. A 
high degree of agreement (97.3%; r-value 0.94) was observed between the 
FD-DAT and the LQ-DAT, as well as between the FD-DAT performed on serum 
samples and corresponding blood samples collected on filter paper (
agreement 97.8%; r-value 0.79). The FD-DAT is very suitable as 
diagnostic test for kala-azar in remote rural conditions as it is 
sensitive, specific and stable. The antigen is affordable, reproducible 
and available, which contributes to the sustainability of the DAT as a 
diagnostic test for VL.




PMID: 15482725
 

TITLE: [Visceral leishmaniasis and consumption coagulopathy: a case report and
review of the literature.]

AUTHORS: José Ramón Paño Pardo, María Del Carmen Fernández Capitán, María
de Los Llanos Soler Rangel, Francisco Arnalich Fernández

AFFILIATION: Servicio de Medicina Interna. Hospital Universitario La Paz.
Madrid. España.

REFERENCE: Med Clin (Barc) 2004 Oct 123(11):438-9




PMID: 15328135
 

TITLE: Combination therapy using sodium antimony gluconate in
stearylamine-bearing liposomes against established and chronic Leishmania
donovani infection in BALB/c Mice.

AUTHORS: Swati Pal, Rajesh Ravindran, Nahid Ali

AFFILIATION: Infectious Diseases Group, Indian Institute of Chemical Biology, 4
Raja S.C. Mullick Rd., Calcutta 700032, India.

REFERENCE: Antimicrob Agents Chemother 2004 Sep 48(9):3591-3

In this work we report the activity seen with combination therapy using 
sodium antimony gluconate in liposomes composed of egg phosphatidyl 
choline and stearylamine for elimination of Leishmania donovani 
parasites from the liver and spleen of BALB/c mice with established and 
chronic infections.








PMID: 15482193
 

TITLE: Progress in the treatment of a neglected infectious disease: visceral
leishmaniasis.

AUTHORS: Henry W Murray

AFFILIATION: Department of Medicine, Weill Medical College of Cornell
University, 1300 York Avenue, New York, NY 10021, USA.
hmurray at med.cornell.edu.

REFERENCE: Expert Rev Anti Infect Ther 2004 Apr 2(2):279-92

Visceral leishmaniasis (kala-azar) is a disseminated intracellular 
protozoal infection. Most cases (90%) occur in the rural regions of five
 countries: India, Sudan, Nepal, Bangladesh and Brazil. As with other 
infectious diseases embedded in high-level poverty, developing and/or 
delivering new treatments for visceral leishmaniasis had been painfully 
slow or nonexistent. However, despite persistent unresolved obstacles (e
.g., drug affordability), renewed interest in visceral leishmaniasis and
 numerous successful treatment trials have combined to turn a 
therapeutic corner in the past 5 years, yielding new alternatives to 
conventional pentavalent antimony. Advances include the use of low-cost 
generic pentavalent antimony, rediscovery of amphotericin B, short-
course regimens via lipid formulations of amphotericin B, retesting 
injectible paromyomycin and, of clear-cut importance, identifying 
miltefosine (Impavido((R)), Zentaris) as the first effective oral 
therapy for this neglected disease.




PMID: 15480215
 

TITLE: Ultrasound of tropical and infectious diseases that affect the scrotum.

AUTHORS: Osmar de Cassio Saito, Nestor de Barros, Maria Cristina Chammas, Ilka
Regina Souza Oliveira, Giovanni Guido Cerri

AFFILIATION: Assistant Doctors, Department of Radiology, School of Medicine,
University of São Paulo, São Paulo, Brazil. ocsaito at yahoo.com.br

REFERENCE: Ultrasound Q 2004 Mar 20(1):12-8

Ultrasonography of the scrotum permits assessment of testicular and 
extratesticular masses with high sensitivity. It can differentiate a 
variety of conditions involving the scrotum, testicles, and epididymis 
with similar clinical manifestations, including infectious and tropical 
diseases. The authors performed conventional and color Doppler 
ultrasonographic examinations in 76 patients who presented with scrotal 
pain, swelling, and/or tenderness. Their diagnoses included sexually 
transmitted disease (eg, gonorrhea, syphilis, chlamydial infection), 
tuberculosis, mumps, and various tropical diseases (eg, filariasis, 
leishmaniasis, schistosomiasis, paracoccidioidomycosis). The most common
 imaging findings were enlarged hypoechoic testes, hypervascularity, 
small hydroceles, and cutaneous edema. This report reviews these and 
other possible presentations of tropical and infectious diseases 
affecting the scrotum, emphasizing ultrasound findings that facilitate 
diagnosis.




PMID: 15482153
 

TITLE: Cutaneous leishmaniasis: current and future management.

AUTHORS: Neill C Hepburn

AFFILIATION: Lincoln County Hospital, Lincoln, LN2 5QY, UK.
Neill.Hepburn at ULH.NHS.UK.

REFERENCE: Expert Rev Anti Infect Ther 2003 Dec 1(4):563-70

Leishmaniasis remains a major world health problem that continues to 
increase in incidence. This review considers epidemiology, clinical 
features, diagnosis and current treatment options. Recent developments 
in the treatment of simple cutaneous leishmaniasis are discussed 
followed by speculation about future therapies.




PMID: 15459981
 

TITLE: [Epidemiology and Prevention of kala-azar in China]

AUTHORS: Z Wang, G Xiong, L Guan

AFFILIATION: Shandong Province Parasitic Disease Control and Prevention
Institute,Jinan 272133, China

REFERENCE: Zhonghua Liu Xing Bing Xue Za Zhi 2000 Feb 21(1):51-4




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PMID: 11544330
 

TITLE: Sodium stibogluconate is a potent inhibitor of protein tyrosine
phosphatases and augments cytokine responses in hemopoietic cell lines.

AUTHORS: M K Pathak, T Yi

AFFILIATION: Department of Cancer Biology, Lerner Research Institute, Cleveland
Clinic Foundation, Cleveland, OH 44195, USA.

REFERENCE: J Immunol 2001 Sep 167(6):3391-7

Using in vitro protein tyrosine phosphatase (PTPase) assays, we found 
that sodium stibogluconate, a drug used in treatment of leishmaniasis, 
is a potent inhibitor of PTPases Src homology PTPase1 (SHP-1), SHP-2, 
and PTP1B but not the dual-specificity phosphatase mitogen-activated 
protein kinase phosphatase 1. Sodium stibogluconate inhibited 99% of SHP
-1 activity at 10 micrograms/ml, a therapeutic concentration of the drug
 for leishmaniasis. Similar degrees of inhibition of SHP-2 and PTP1B 
required 100 micrograms/ml sodium stibogluconate, demonstrating 
differential sensitivities of PTPases to the inhibitor. The drug 
appeared to target the SHP-1 domain because it showed similar in vitro 
inhibition of SHP-1 and a mutant protein containing the SHP-1 PTPase 
domain alone. Moreover, it forms a stable complex with the PTPase: in 
vitro inhibition of SHP-1 by the drug was not removed by a washing 
process effective in relieving the inhibition of SHP-1 by the reversible
 inhibitor suramin. The inhibition of cellular PTPases by the drug was 
suggested by its rapid induction of tyrosine phosphorylation of cellular
 proteins in Baf3 cells and its augmentation of IL-3-induced Janus 
family kinase 2/Stat5 tyrosine phosphorylation and proliferation of Baf3
 cells. The augmentation of the opposite effects of GM-CSF and IFN-alpha
 on TF-1 cell growth by the drug indicated its broad activities in the 
signaling of various cytokines. These data represent the first evidence 
that sodium stibogluconate inhibits PTPases and augments cytokine 
responses. Our results provide novel insights into the pharmacological 
effects of the drug and suggest potential new therapeutic applications.








PMID: 10320373
 

TITLE: Requirement for type 2 NO synthase for IL-12 signaling in innate
immunity.

AUTHORS: A Diefenbach, H Schindler, M Röllinghoff, W M Yokoyama, C Bogdan

AFFILIATION: Institut für Klinische Mikrobiologie, Immunologie und Hygiene,
Universität Erlangen, Wasserturmstrasse 3, D-91054 Erlangen, Germany.

REFERENCE: Science 1999 May 284(5416):951-5

Interleukin-12 (IL-12) and type 2 NO synthase (NOS2) are crucial for 
defense against bacterial and parasitic pathogens, but their 
relationship in innate immunity is unknown. In the absence of NOS2 
activity, IL-12 was unable to prevent spreading of Leishmania parasites
, did not stimulate natural killer (NK) cells for cytotoxicity or 
interferon-gamma (IFN-gamma) release, and failed to activate Tyk2 kinase
 and to tyrosine phosphorylate Stat4 (the central signal transducer of 
IL-12) in NK cells. Activation of Tyk2 in NK cells by IFN-alpha/beta 
also required NOS2. Thus, NOS2-derived NO is a prerequisite for cytokine
 signaling and function in innate immunity.




PMID: 7591091
 

TITLE: Attenuation of gamma interferon-induced tyrosine phosphorylation in
mononuclear phagocytes infected with Leishmania donovani: selective inhibition
of signaling through Janus kinases and Stat1.

AUTHORS: D Nandan, N E Reiner

AFFILIATION: Department of Medicine (Division of Infectious Diseases, University
of British Columbia Faculty of Medicine, Vancouver, Canada.

REFERENCE: Infect Immun 1995 Nov 63(11):4495-500

The induction of gene transcription in response to gamma interferon is 
impaired in mononuclear phagocytes infected with Leishmania donovani, 
and the mechanisms involved are not fully understood. The changes in 
gene expression brought about by gamma interferon are thought to involve
 transient increases in the activities of cellular protein tyrosine 
kinases, including the Janus kinases Jak1 and Jak2, leading to tyrosine 
phosphorylation of the transcription factor Stat1. To investigate the 
mechanisms accounting for the impaired responses to gamma interferon, a 
model system for examining overall changes in protein tyrosine 
phosphorylation, activation of Jak1 and Jak2 and phosphorylation of 
Stat1 was developed in phorbol 12-myristate 13-acetate-differentiated U-
937 cells. Analysis of whole-cell lysates by antiphosphotyrosine 
immunoblotting showed that incubation with gamma interferon brought 
about specific increases in phosphotyrosine labeling of several proteins
. Increased labeling of these proteins occurred to similar extents in 
control cells and in cells that had been infected with L. donovani for 
16 h. Jak1, Jak2, and Stat1 were immunoprecipitated from control and 
interferon-treated cells, and tyrosine phosphorylation of these proteins
, detected by antiphosphotyrosine immunoblotting was used to measured 
their activation. Tyrosine phosphorylation of Jak1, Jak2, and Stat1 
increased markedly, in a dose-dependent manner, in U-937 cells incubated
 with gamma interferon. In contrast, in cells infected with L. donovani
, tyrosine phosphorylation of Jak1, Jak2, and Stat1 was markedly 
impaired. This effect was dependent upon the duration of exposure to L. 
donovani and was maximal and complete at 16 h. Results similar to those 
observed with U-937 cells were also obtained with human peripheral blood
 monocytes. These findings indicate that infection of human mononuclear 
phagocytes with L. donovani leads to impaired gamma interferon-mediated 
tyrosine phosphorylation and selective effects on the Jak-Stat1 pathway
. Unresponsiveness to gamma interferon for activation of this pathway 
may explain impaired transcriptional responses in leishmania-infected 
cells.




REQUEST: [ leishmania ]

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



PMID: 15482882
 

TITLE: Comparison of different tissue sampling for PCR-based diagnosis and
follow-up of canine visceral leishmaniosis.

AUTHORS: Laura Manna, Fabrizio Vitale, Stefano Reale, Santo Caracappa, Luigi
Michele Pavone, Rossella Della Morte, Giuseppe Cringoli, Norma Staiano, Angelo
Elio Gravino

AFFILIATION: Dipartimento di Scienze Cliniche Veterinarie, Università di Napoli
Federico II, Via F. Delpino 1, 80137 Napoli, Italy.

REFERENCE: Vet Parasitol 2004 Nov 125(3-4):251-62

In this study, different types of tissue sampling for PCR-based 
diagnosis and follow-up of canine visceral leishmaniosis were compared. 
Skin, whole blood and lymph node samples were collected from 95 
naturally infected dogs living in South Italy, where the disease is 
endemic. Twenty-nine of these 95 dogs, treated with meglumine 
administered concurrently with allopurinol for 30 days, and then with 
allopurinol alone, were monitored during a period of 2 years. The DNA 
extracted from the clinical specimens was amplified by PCR using as 
target DNA a 116-bp fragment in the constant region of the kinetoplast 
DNA minicircle. PCR analysis was more sensitive than indirect 
immunofluorescence antibody test in detecting Leishmania infection in 
symptomatic dogs: 99% of lymph node samples resulted positive, whereas 
94% of blood samples and 95% of skin samples gave a positive result. PCR
 analysis of samples from dogs followed up 2 years showed that: (1) all 
subjects resulted positive in at least one of the three types of samples
; (2) all time the dogs had a relapse, PCR resulted positive in all 
three types of samples; (3) when dogs were apparently healthy, PCR 
analysis was positive on skin and lymph node samples, but not always on 
blood samples. Since lymph node sampling is invasive and sometimes 
difficult in healthy asymptomatic dogs, our results suggest that, 
independently from the presence or not of cutaneous lesions, skin biopsy
 represents a good substratum for PCR-based diagnosis and follow-up of 
canine visceral leishmaniosis.




PMID: 15479452
 

TITLE: LdARF1 in Trafficking and Structural Maintenance of the trans-Golgi
Cisternal Network in the Protozoan Pathogen Leishmania donovani.

AUTHORS: Johanna M Porter-Kelley, Noel J Gerald, Juan C Engel, Elodie Ghedin,
Dennis M Dwyer

AFFILIATION: Cell Biology Section, Laboratory of Parasitic Diseases, Division of
Intramural Research, National Institute of Allergy and Infectious Diseases,
National Institutes of Health, Bethesda, MD 20892-0425, USA.

REFERENCE: Traffic 2004 Nov 5(11):868-83

Adenosine diphosphate ribosylation factors (ARFs) are small guanosine-5
'-triphosphatases that are essential in vesicular trafficking and in the
 maintenance of the Golgi network. In this report, we identified a 
homolog of the mammalian ARF1 in the human pathogenic protozoan parasite
, Leishmania donovani (Ld). Ld ARF1 is a 549 bp gene encoding a 183-
amino acid deduced protein of approximately 20 kDa. We demonstrated by 
Southern blot analysis that there are at least two copies of ARF1 in the
 Ld genome. Moreover, Northern blot analysis revealed that Ld ARF1 is 
expressed on a 1.35 kb transcript in both the insect vector (
promastigotes) and mammalian host (amastigotes) forms of this parasite. 
Fluorescent microscopy studies using Ld promastigotes episomally 
transfected with an ARF1::GFP (green fluorescent protein) chimeric 
construct showed that such chimeras appeared to localize to the Golgi 
region of these organisms. This observation was verified by 
immunoelectron microscopy using an anti-GFP antibody. Such studies also 
revealed that Ld ARF1::GFP chimeras localized to trans-Golgi vesicles, 
the flagellar pocket/reservoir and other vesicles located between the 
trans-Golgi network and flagellar pocket in these apically polarized 
cells. Fluorescence recovery after photobleaching and fluorescence loss 
in photobleaching experiments revealed both the dynamic binding and 
releasing activity of Ld ARF1 from the Golgi network in these parasites
. Further, episomal expression of a constitutively active ("on") ARF1 (
Q71L mutation) resulted in the aberrant swelling and distended-structure
 of the trans-Golgi cisternae in these cells. These results show that Ld
 ARF1 is transiently associated with the Golgi network and plays a role 
in the structural maintenance of this organelle in these important human
 pathogens.




PMID: 15378352
 

TITLE: Immune response induced by New World Leishmania species in C57BL/6 mice.

AUTHORS: Tatiani Uceli Maioli, Erica Takane, Rosa Maria Esteves Arantes, Juliana
Lopes Rangel Fietto, Luís Carlos Crocco Afonso

AFFILIATION: Departamento de Ciências Biológicas, Instituto de Ciências
Exatas e Biológicas/NUPEB, Universidade Federal de Ouro Preto, 35400-000, Ouro
Preto, Minas Gerais, Brazil.

REFERENCE: Parasitol Res 2004 Oct 94(3):207-12

In the present study, C57BL/6 mice were inoculated with metacyclic 
Leishmania amazonensis or L. braziliensis promastigotes. While these 
animals were capable of controlling the infection by L. braziliensis, 
they developed chronic lesions with elevated numbers of parasites when 
infected by L. amazonensis. The differences in parasite control were 
associated with a decreased production of IFN-gamma and TNF by lymph 
node cells from L. amazonensis-infected mice. Furthermore, these animals
 presented decreased spleen cell proliferation and activation of 
germinal centers. In addition, we compared the ability of these 
parasites to hydrolyze extracellular ATP and AMP. While the ATPase 
activity of both parasite species was similar, L. amazonensis 
promastigotes presented higher AMP hydrolytic activity. This increased 
activity may lead to an increased production of adenosine, which has 
been shown to present anti-inflammatory activity and may thus be 
involved in the establishment of the immunosuppression observed in mice 
infected by L. amazonensis.




PMID: 15338282
 

TITLE: An improved method for detection of Leishmania amastigotes by an antibody
probe against the small subunit of leishmanial ribonucleotide reductase.

AUTHORS: Shu-Ching Chang, Oleg Kuzmenok, Su-Chi Chiang, Sho Tone Lee

AFFILIATION: Division of infectious diseases, Institute of Biomedical Sciences,
Academia Sinica, 11529, Taipei, Taiwan, R.O.C.

REFERENCE: Parasitol Res 2004 Oct 94(3):243-5

By taking advantage of an antibody raised against the small M(2) subunit
 of ribonucleotide reductase of Leishmania that reacts with the enzyme 
in the nucleus of the parasite but does not cross-react with the same 
enzyme of the host macrophage, an improved fluorescence-staining method 
is developed for enumeration of leishmanial amastigotes inside the 
macrophage. The method offers an accurate and easy way of counting, 
compared with Giemsa staining.




PMID: 15326547
 

TITLE: Inhibiting activities of the secondary metabolites of Phlomis
brunneogaleata against parasitic protozoa and plasmodial enoyl-ACP Reductase, a
crucial enzyme in fatty acid biosynthesis.

AUTHORS: Hasan Kirmizibekmez, Ihsan Calis, Remo Perozzo, Reto Brun, Ali A
Dönmez, Anthony Linden, Peter Rüedi, Deniz Tasdemir

AFFILIATION: Department of Pharmacognosy, Faculty of Pharmacy, Hacettepe
University, Ankara, Turkey.

REFERENCE: Planta Med 2004 Aug 70(8):711-7

Anti-plasmodial activity-guided fractionation of Phlomis brunneogaleata
 (Lamiaceae) led to the isolation of two new metabolites, the iridoid 
glycoside, brunneogaleatoside and a new pyrrolidinium derivative (2 S,4 
R)-2-carboxy-4-( E)- p-coumaroyloxy-1,1-dimethylpyrrolidinium inner salt
 [(2 S,4 R)-1,1-dimethyl-4-( E)- p-coumaroyloxyproline inner salt]. 
Moreover, a known iridoid glycoside, ipolamiide, six known 
phenylethanoid glycosides, verbascoside, isoverbascoside, forsythoside B
, echinacoside, glucopyranosyl-(1-->G (i)-6)-martynoside and 
integrifolioside B, two flavone glycosides, luteolin 7- O-beta- D-
glucopyranoside ( 10) and chrysoeriol 7- O-beta- D-glucopyranoside ( 11
), a lignan glycoside liriodendrin, an acetophenone glycoside 4-
hydroxyacetophenone 4- O-(6'- O-beta- D-apiofuranosyl)-beta- D-
glucopyranoside and three caffeic acid esters, chlorogenic acid, 3-O-
caffeoylquinic acid methyl ester and 5- O-caffeoylshikimic acid were 
isolated. The structures of the pure compounds were elucidated by means 
of spectroscopic methods (UV, IR, MS, 1D and 2D NMR, [alpha] (D)) and X-
ray crystallography. Compounds 10 and 11 were determined to be the major
 anti-malarial principles of the crude extract (IC (50) values of 2.4 
and 5.9 micrograms/mL, respectively). They also exhibited significant 
leishmanicidal activity (IC (50) = 1.1 and 4.1 micrograms/mL, 
respectively). The inhibitory potential of the pure metabolites against 
plasmodial enoyl-ACP reductase (FabI), which is the key regulator of 
type II fatty acid synthases (FAS-II) in P. falciparum, was also 
assessed. Compound 10 showed promising FabI inhibiting effect (IC (50
) = 10 micrograms/mL) and appears to be the first anti-malarial natural 
product targeting FabI of P. falciparum.








PMID: 15478793
 

TITLE: Two linked genes of Leishmania infantum encode tryparedoxins localised to
cytosol and mitochondrion.

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

AFFILIATION: Institute for Molecular and Cell Biology, Rua do Campo Alegre 823,
4150-180 Porto, Portugal.

REFERENCE: Mol Biochem Parasitol 2004 Aug 136(2):137-47

Tryparedoxins are components of the hydroperoxide detoxification 
cascades of Kinetoplastida, where they mediate electron transfer between
 trypanothione and a peroxiredoxin, which reduces hydroperoxides and 
possibly peroxynitrite. Tryparedoxins may also be involved in DNA 
synthesis, by their capacity to reduce ribonucleotide reductase. Here we
 report on the isolation of two tryparedoxin genes from Leishmania 
infantum, Li7XN1 and LiTXN2, which share the same genetic locus. These 
genes are both single copy and code for two active tryparedoxin enzymes
, LiTXN1 and LiTXN2, with different biochemical and biological features
. LiTXN1 is located to the cytosol and is upregulated in the infectious 
forms of the parasite, strongly suggesting that it might play an 
important role during infection. LiTXN2 is the first mitochondrial 
tryparedoxin described in Kinetoplastida. Biochemical assays performed 
on the purified recombinant proteins have shown that LiTXN1 
preferentially reduces the cytosolic L. infantum peroxiredoxins, 
LicTXNPx1 and LicTXNPx2, whereas LiTXN2 has a higher specific activity 
for a mitochondrial peroxiredoxin, LimTXNPx. Kinetically, the two 
tryparedoxins follow a ping-pong mechanism and show no saturation. We 
suggest that LiTXN1 and LiTXN2 are part of two distinct antioxidant 
machineries, one cytosolic, the other mitochondrial, that complement 
each other to ensure effective defence from several sources of oxidants 
throughout the development of L. infantum.




PMID: 15305722
 

TITLE: [Clinical signs of visceral leishmaniasis in adults: is the manner of
presentation changing?]

AUTHORS: G B Gaeta

AFFILIATION: Centro di Riferimento Regionale per la Leishmaniosi Viscerale,
Dipartimento di Malattie Infettive, Seconda Università di Napoli.

REFERENCE: Parassitologia 2004 Jun 46(1-2):225-6

Although the typical clinical signs and symptoms of visceral 
leishmaniasis (VL) are always the same, in the recent years the disease 
has emerged in new settings, for example in HIV infected individuals, in
 organ transplant recipients, in patients with chronic liver disease, in
 pregnancy. At the same time, VL has emerged as a model for exploring 
the host-parasite interplay for intracellular infections. The common 
feature of VL is that it is fatal without treatment. Liposomal 
Amphotericin B is the first line treatment in developed countries. 
Unfortunately, the high cost makes this treatment unaffordable for 
developing countries.




PMID: 15307590
 

TITLE: Disseminated intravascular coagulation as an unusual presentation of
Kala-azar: report of two cases.

AUTHORS: Pravas Mishra, Ashish Dixit, Tathagat Chatterjee, Maitreyee
Bhattacharya, Jina Bhattacharya, Pankhi Dutta, Manoranjan Mahapatra, Hara
Prasad Pati, Ved Prakash Choudhry, Renu Saxena

AFFILIATION: Department of Haematology, All India Institute of Medical Sciences,
New Delhi, India.

REFERENCE: Scand J Infect Dis 2004  36(6-7):519-21

Kala-azar (visceral leishmaniasis) is a common problem in various well-
defined areas of India. It is characterized by fever of long duration, 
enlarged liver and spleen, anaemia and leucopoenia. Bleeding is an 
uncommon manifestation of kala-azar. We report 2 cases, in which 
disseminated intravascular coagulation was an unusual complication.




PMID: 15481151
 

TITLE: Interaction of Leishmania parasites with dendritic cells and its
functional consequences.

AUTHORS: Monidipa Ghosh, Santu Bandyopadhyay

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

REFERENCE: Immunobiology 2004  209(1-2):173-7

Interaction between dendritic cells (DC) and T cells is essential for 
the generation of cell mediated immunity and thus DC play a critical 
role in the initiation of immune responses against Leishmania parasites
. Although macrophages (Mphi) are the major targets of all species of 
Leishmania, a number of studies demonstrated the infection of DC by 
Leishmania. DC specific intracellular adhesion molecule 3-grabbing 
nonintegrin (DC-SIGN), has been reported to be the receptor for 
Leishmania amastigotes. The functional consequences in DC after 
Leishmania infections appear to depend on species of Leishmania. Some 
species of Leishmania enhance the surface expression of co-stimulatory 
molecules and CD40-ligand-induced IL-12 production in DC. On the other 
hand other species down-regulate co-stimulatory molecules and inhibit IL
-12 production. The intrinsic differences among Leishmania species with 
regard to alteration of cell surface molecules and IL-12 production in 
DC may contribute to the healing and non-healing forms of the disease.




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PMID: 10556830
 

TITLE: Leishmania-induced increases in activation of macrophage SHP-1 tyrosine
phosphatase are associated with impaired IFN-gamma-triggered JAK2 activation.

AUTHORS: J Blanchette, N Racette, R Faure, K A Siminovitch, M Olivier

AFFILIATION: Centre de Recherche en Infectiologie Laval University Medical
Research Center, Université Laval, Ste-Foy, Canada.

REFERENCE: Eur J Immunol 1999 Nov 29(11):3737-44

Leishmania-induced macrophage (Mphi) dysfunctions have been correlated 
with altered signaling events. Recent findings from our laboratory 
suggest that modulation of host protein tyrosine phosphatase (PTP) 
following Leishmania infection could lead to these Mphi defects. To 
address this issue, Mphi PTP activity and IFN-gamma-inducible signaling 
events were evaluated in Leishmania donovani (Ld)-infected cells. We 
observed that Ld promastigotes can rapidly trigger host PTP activity 
simultaneously with dephosphorylation of Mphi protein tyrosyl residues 
and inhibition of protein tyrosine kinase (PTK). Our results further 
revealed that Mphi SHP-1 PTP was rapidly activated by the infection. 
This Ld-evoked signaling alteration was reflected by absence of IFN-
gamma-induced intracellular phosphorylation. IFN-gamma-inducible JAK2 
PTK phosphorylation was also markedly diminished in Ld-infected cells. 
We also observed that co-immunoprecipitation of JAK2 with SHP-1 was 
considerably higher in infected as compared to uninfected cells. 
Altogether, these results suggest that SHP-1-mediated JAK2 
dephosphorylation triggered by Leishmania is partly responsible for 
abnormal Mphi IFN-gamma signaling and represent an important mechanism 
supporting persistent parasitic infection.




REQUEST: [ sand fly ]

(1 article matches this request)



PMID: 15488671
 

TITLE: Letter to the Editor: Gulf war syndrome and sand fly saliva.

AUTHORS: Raymond Leonard Jacobson

AFFILIATION: Department of Parasitology, The Hebrew University-Hadassah Medical
School, P.O. Box 12272, Jerusalem 91120, Israel.

REFERENCE: Med Hypotheses 2004  63(5):917




REQUEST: [ sandfly ]

(0 articles match this request)














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