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diagnosis of symptomatic kala-azar by polymerase chain reaction using patient's blood.detection of leishmania parasite in patients by classical methods at the early stage of infection is limited. several studies have shown that polymerase chain reaction (pcr) is more effective for the diagnosis of visceral leishmaniasis (vl) in clinical samples. the purpose of this study was to develop a simple, specific and sensitive pcr-based assay for detecting vl caused by any species of the genus leishmania.200414704640
transmembrane domain 5 of the ldnt1.1 nucleoside transporter is an amphipathic helix that forms part of the nucleoside translocation pathway.transporters of the equilibrative nucleoside transporter (ent) family promote the uptake of nucleosides, nucleobases, and a variety of therapeutic drugs in eukaryotes from protozoa to mammals. despite its importance, the translocation pathway that mediates the internalization of these substrates has not been identified yet in any of the ent carriers. previous genetic studies on the ldnt1.1 nucleoside transporter from leishmania donovani defined two amino acid residues in predicted transmembrane ...200415157113
a leishmania donovani gene that confers accelerated recovery from stationary phase growth arrest.we have isolated a gene, ldgf1, from the protozoan parasite leishmania donovani. overexpression of this gene confers a strong selective advantage in liquid culture after stationary phase growth arrest. we could show that recombinant l. donovani or leishmania major, when overexpressing ldgf1, recover faster from a stationary phase growth arrest than control parasite strains. while no advantage of ldgf1 overexpression could be observed in log phase cultures or after a hydroxyurea-induced s-phase g ...200415157763
visceral leishmaniasis with multiple nodular lesions of the liver and spleen: ct and sonographic findings.visceral leishmaniasis is a severe disease caused by the intracellular protozoa leishmania donovani. diagnosis is based on examination of bone marrow or serology. the role of imaging techniques as diagnostic tools remains to be established in visceral leishmaniasis. we report multiple nodular lesions in the liver and spleen on ultrasonography and computed tomography in a patient with visceral leishmaniasis. to our knowledge, this is the first reported case of multiple nodular hepatosplenic lesio ...200415160758
the ribosomal rna gene promoter and adjacent cis-acting dna sequences govern plasmid dna partitioning and stable inheritance in the parasitic protozoan leishmania.detailed analysis of the leishmania donovani ribosomal rna (rrna) gene promoter region has allowed the identification of cis-acting sequences involved in plasmid dna partitioning and stable plasmid inheritance. we report that plasmids bearing the 350 bp rrna promoter along with the 200 bp region immediately 3' to the promoter exhibited a 6.5-fold increase in transformation frequency and were transmitted to daughter cells as single-copy molecules. this is in contrast to what has been observed for ...200415161957
ancistrotanzanine c and related 5,1'- and 7,3'-coupled naphthylisoquinoline alkaloids from ancistrocladus tanzaniensis.three new naphthylisoquinoline alkaloids, the 7,3'-coupled ancistrotanzanine c (6), the 5,1'-coupled o-methylancistrocladinine (7), and the likewise 5,1'-coupled o,n-dimethylancistrocladine (8, previously known only as a partial-synthetic compound), have been isolated from the highland liana ancistrocladus tanzaniensis, along with the two known 7,3'-coupled naphthylisoquinoline alkaloids ancistrocladidine (4) and ancistrotectorine (5). all of the compounds are s-configured at c-3 and bear an oxy ...200415165131
a new antimalarial quassinoid from simaba orinocensis.a new antimalarial quassinoid, namely, orinocinolide (1), was isolated from the root bark of simaba orinocensis, together with the previously reported simalikalactone d (2). the structure of 1 was determined primarily from 1d and 2d nmr analysis, as well as by chemical derivatization. compound 1 was found to be as equally potent as 2 against plasmodium falciparum clones d6 and w2 (ic(50) 3.27 and 8.53 ng/ml vs 3.0 and 3.67 ng/ml, respectively), but was 4- and 28-fold less toxic than 2 against ve ...200415165136
arbitrary-primed pcr for genomic fingerprinting and identification of differentially regulated genes in indian isolates of leishmania donovani.the arbitrary-primed pcr (ap-pcr) technique was employed with the twin goals of identifying genetic polymorphisms within the indian isolates and to identify differentially expressed gene sequences. the parasite isolates from indian kala-azar patients could be differentiated from leishmania donovani isolates from distinct geographic regions. moreover, differences within the indian isolates could also be identified. a majority (17/19) of the indian isolates gave identical ap-pcr pattern, while two ...200415172218
infection and blood transfusion: a guide to donor screening.in recent years, blood-component therapy has become more accessible in veterinary practice. as with human medicine, care must be taken to minimize the risk of disease transmission from donor to recipient. determining the appropriate diseases to screen for is complicated by regional variations in disease incidence, the existence of chronic carrier states for some diseases, the difficulty in screening-test selection, and testing cost. the feline diseases considered include retroviral infections, f ...200415179926
synthesis and antileishmanial activity of novel buparvaquone oxime derivatives.novel oxime derivatives (2, 3 and 5) of buparvaquone (1) and o-methyl-buparvaquone (4) were synthesized and their in vitro activities against leishmania donovani, the causative agent of visceral leishmaniasis (vl), were determined. buparvaquone-oxime (2) was also studied as a bioreversible prodrug structure of buparvaquone (1). buparvaquone-oxime (2) released buparvaquone (1) in vitro when it was incubated with induced rat liver microsomes, which suggests that the oxime-structure is a useful pro ...200415186834
evaluation of a urinary antigen-based latex agglutination test in the diagnosis of kala-azar in eastern nepal.we evaluated the diagnostic accuracy as well as the reproducibility of the urine latex agglutination test 'katex' in the diagnosis of kala-azar in patients recruited at a tertiary care centre in dharan, nepal, between november 2000 and january 2002.200415189464
protective vaccination against murine visceral leishmaniasis using aldehyde-containing quillaja saponaria sapogenins.the presence of aldehyde groups at c-23 and c-24 of the triterpen aglycon moiety was disclosed in 1h nmr spectra of both the riedel de haen saponin (r) (delta 9.336) and quillaja saponaria quila saponin (delta 9.348). the sign of the c-28 acylated linked moiety (delta 176) was present in both saponins, while the delta 171 at c-28 (carboxy group) corresponding to the deacylated saponin, was only detected in the quila preparation, indicating 50% of hydrolysis of the ester moiety, probably due to t ...200415193411
mast cells at the host-pathogen interface: host-protection versus immune evasion in leishmaniasis.infection of a susceptible host with leishmania, a protozoan parasite, causes the disease leishmaniasis, which is characterized by neutrophil, eosinophil, macrophage, lymphocyte and mast cell infiltration into the infected tissue followed by parasite growth. although the roles played by other cells in leishmaniasis are known, the role of mast cells remains to be ascertained. here, we demonstrate that leishmania regulates mast cell infiltration to the site of infection, mast cell production and m ...200415196239
nerve involvement in indian post kala-azar dermal leishmaniasis. 200415202852
incomplete glycosylation and defective intracellular targeting of mutant solute carrier family 11 member 1 (slc11a1).solute carrier family 11 member 1 (slc11a1, formerly nramp1) is a highly glycosylated, 12 transmembrane domain protein expressed in macrophages. it resides in the membrane of late endosomes and lysosomes, where it functions as a bivalent cation transporter. mice susceptible to infection by various intracellular pathogens including leishmania donovani and salmonella typhimurium carry a glycine to aspartic acid substitution at position 169 (g169d, gly(169)-->asp), within transmembrane domain 4 of ...200415202932
harmine: evaluation of its antileishmanial properties in various vesicular delivery systems.harmine, a beta-carboline amine alkaloid isolated from peganum harmala, was tested for its antileishmanial properties both in vitro and in vivo. in vitro antileishmanial activity of harmine was encouraging and prompted us to confirm the activity in vivo in hamster models. harmine was tested both in free form and in different vesicular forms viz. liposomes, niosomes and nanoparticles. the different vesicles were prepared by the published protocols. the percent intercalation of harmine in liposome ...200415203896
mutational analysis of methionine adenosyltransferase from leishmania donovani.the methionine adenosyltransferase (mat; ec 2.5.1.6) mediated synthesis of s-adenosylmethionine (adomet) is a two-step process, consisting of the formation of adomet and the subsequent cleavage of the tripolyphosphate (pppi) molecule, a reaction induced, in turn, by adomet. the fact that the two activities--adomet synthesis and tripolyphosphate hydrolysis--can be measured separately is particularly useful when the site-directed mutagenesis approach is used to determine the functional role of the ...200415206944
genetic polymorphism within the leishmania donovani complex: correlation with geographic origin.random amplified polymorphic dna (rapd) was used to detect intraspecific diversity for the leishmania donovani complex. fifty-two decameric to 21-meric primers of arbitrary sequence were applied to 15 strains that belong to nine zymodemes. strains belonging to the species l. major and l. tropica were used as outgroups. a total of 902 amplicons generated by rapd were scored. most primers produced species-specific profiles, only 0.6% amplicons were shared by all species, while 4.3% amplicons were ...200415211001
cloning of s-adenosyl-l-methionine:c-24-delta-sterol-methyltransferase (erg6) from leishmania donovani and characterization of mrnas in wild-type and amphotericin b-resistant promastigotes.the 24-alkylated sterols have been shown previously to be absent in membranes of amphotericin b (amb)-resistant leishmania donovani promastigotes, suggesting that the s- adenosyl-l-methionine:c-24-delta-sterol-methyltransferase (scmt or erg6) was not functional or not expressed in amb-resistant (amb-r) parasites. from an l. donovani wild-type clone, we cloned two cdnas with an identical open reading frame encoding a putative scmt, the enzyme responsible for a first sterol methylation at the c-24 ...200415215088
altered expression, polymerisation and cellular distribution of alpha-/beta-tubulins and apoptosis-like cell death in arsenite resistant leishmania donovani promastigotes.studies in mammalian systems have shown specific affinity of arsenite for tubulin proteins. the sodium m-arsenite (naaso2) resistant leishmania donovani used in this study is resistant to 20 microm naaso2, which is a 13-fold increase in resistance compared to the wild type. data presented in this study shows decreased expression of alpha- and beta-tubulin in wild type l. donovani promastigotes on exposure to naaso2 from 0.0016 to 5.0 microm (ic50 in the wild type strain) in a dose-dependent mann ...200415217730
immune response to leishmania infection.antileishmanial immune response is shown to be host genotype dependent so that some inbred strains of mouse are susceptible while others are resistant. the resistance is conferred by t-helper type-1 (th1) cells while the susceptibility is conferred by th2 cells. th1 cells secrete il-2 and ifn-gamma but th2 cells secrete il-4, il-5 and il-10. it has been shown that ifn-gamma activates macrophages to express inos2, the enzyme catalyzing the formation of nitric oxide. nitric oxide kills the intrace ...200415243162
comparison between splenic and lymph node aspirations as sampling methods for the parasitological detection of leishmania chagasi infection in dogs.the sensitivities of spleen and lymph node cultures for the diagnosis of canine visceral leishmaniasis were compared in 64 anti-leishmania antibody positive dogs from an endemic area in brazil. the sensitivity of spleen cultures for leishmania detection was 97.9%; in lymph node cultures it was 25%. positive spleen culture was more frequent (p = 0.048, fisher's exact probability test) in symptomatic (28 out of 33 animals) than in asymptomatic animals (19 out of 31 animals). these results support ...200415250475
dual action of antimonial drugs on thiol redox metabolism in the human pathogen leishmania donovani.despite extensive use of antimonial compounds in the treatment of leishmaniasis, their mode of action remains uncertain. here we show that trivalent antimony (sb(iii)) interferes with trypanothione metabolism in drug-sensitive leishmania parasites by two inherently distinct mechanisms. first, sb(iii) decreases thiol buffering capacity by inducing rapid efflux of intracellular trypanothione and glutathione in approximately equimolar amounts. second, sb(iii) inhibits trypanothione reductase in int ...200415252045
identification of sialic acids on leishmania donovani amastigotes.the presence of neu5ac on promastigotes of leishmania donovani, the causative organism of indian visceral leishmaniasis, has been reported recently. here we report the occurrence of neu5ac as a major component on amastigotes, as well as neu5gc, neu5,9ac2 and neu9ac5gc as indicated by fluorimetric high performance liquid chromatography and gas liquid chromatography/electron impact mass spectrometry. furthermore, binding studies with sambucus nigra agglutinin (sna), maackia amurensis agglutinin (m ...200414977047
miltefosine induces apoptosis-like death in leishmania donovani promastigotes.miltefosine (hexadecylphosphocholine [hepc]) has proved to be a potent oral treatment for human visceral leishmaniasis due to leishmania donovani. the molecular mechanisms that contribute to the antileishmanial activity of hepc are still unknown. we report that in wild-type promastigotes of leishmania donovani hepc is able to induce a cell death process with numerous cytoplasmic, nuclear, and membrane features of metazoan apoptosis, including cell shrinkage, dna fragmentation into oligonucleosom ...200414982775
targeting of parasite-specific immunoliposome-encapsulated doxorubicin in the treatment of experimental visceral leishmaniasis.a parasite-specific 51-kda protein has been isolated from the membrane of macrophages infected with leishmania donovani, the causative agent of visceral leishmaniasis. active targeting of doxorubicin to infected macrophages was studied by incorporating it in immunoliposomes prepared by grafting f(ab)'(2) of anti-51-kda antibody onto the liposomal surface. in a 45-day mouse model of visceral leishmaniasis, complete elimination of spleen parasite burden was achieved by doxorubicin incorporated in ...200414999606
antigen genes for molecular epidemiology of leishmaniasis: polymorphism of cysteine proteinase b and surface metalloprotease glycoprotein 63 in the leishmania donovani complex.efficient monitoring of endemic and resurgent visceral leishmaniasis (vl) requires discriminatory molecular tools that allow direct characterization of etiological agents (i.e., the leishmania donovani complex) in host tissues. this characterization is possible through restriction fragment-length polymorphism (rflp) analysis of polymerase chain reaction (pcr)-amplified sequences (pcr-rflp).200414999607
a mixed th1/th2 response elicited by a liposomal formulation of leishmania vaccine instructs th1 responses and resistance to leishmania donovani in susceptible balb/c mice.in this study, we have developed a vaccine with leishmania donovani promastigote membrane antigens (leishmanial antigens (lag)) encapsulated in a liposome carrier formulated with distearyol (dspc, transition temperature (tc) = 54 degrees c) derivative of l-alpha-phosphatidyl choline, for immunizing balb/c mice against progressive visceral leishmaniasis. this formulation could limit hepatosplenomegaly to almost normal levels and conferred strong levels of protection in both liver and spleen again ...200415003644
hexadecylphosphocholine interaction with lipid monolayers.the phospholipid analogue miltefosine or hexadecylphosphocholine (hepc) is a drug of high interest in the treatment for fatal visceral leishmaniasis (vl) due to leishmania donovani particularly because of its activity by oral route. in this study, the interaction of hepc with a monolayer of beta-palmitoyl-gamma-oleyl-phosphatidylcholine (popc) as membrane model or sterol (ergosterol or cholesterol) was investigated. at a constant pressure of 25 mn/m, the adsorption kinetics of hepc into the mono ...200415003884
subcellular localization of adenine and xanthine phosphoribosyltransferases in leishmania donovani.the subcellular location of a protein is a critical factor in its physiological function and an important consideration in therapeutic paradigms that target the protein. because leishmania donovani cannot synthesize purine nucleotides de novo, they rely predominantly upon therapeutically germane phosphoribosyltransferase (prt) enzymes, hypoxanthine-guanine prt (hgprt), adenine prt (aprt), and xanthine prt (xprt), for purine acquisition from the host. previous studies have shown that the l. donov ...200414747142
a novel form of actin in leishmania: molecular characterisation, subcellular localisation and association with subpellicular microtubules.to study the occurrence and subcellular distribution of actin in trypanosomatid parasites, we have cloned and overexpressed leishmania donovani actin gene in bacteria, purified the protein, and employed the affinity purified rabbit polyclonal anti-recombinant actin antibodies as a probe to study the organisation and subcellular distribution of actin in leishmania cells. the leishmania actin did not cross react with antimammalian actin antibodies but was readily recognized by the anti-leishmania ...200414747148
in vitro antiprotozoal and cytotoxic activities of some alkaloids, quinones, flavonoids, and coumarins. 200414765298
sensitivity of splenic and bone marrow aspirate study for diagnosis of kala-azar.fifty adult patients of kala-azar were included in this prospective study from medicine unit-i of mymensingh medical college hospital. splenic and bone marrow aspiration were done simultaneously to compare the sensitivity and other related merits and demerits of each procedure. splenic aspiration appeared to be more sensitive procedure than bone marrow aspiration. leishman - donovan (ld) bodies were found in 90 percent and 72 percent of the spleen and bone marrow aspirates respectively. splenic ...200415284686
involvement of leishmania donovani major surface glycoprotein gp63 in promastigote multiplication.the major surface glycoprotein gp63 of the kinetoplastid protozoal parasite leishmania is implicated as a ligand mediating uptake of the parasite into, and survival within, the host macrophage. by expressing gp63 antisense rna from an episomal vector in l. donovani promastigotes, gp63-deficient transfectants were obtained. reduction of the gp63 level resulted in increased generation times, altered cell morphology, accumulation of cells in the g2/m phase of the cell cycle, and increased numbers o ...200415286399
substrate specificity of the leishmania donovani myo-inositol transporter: critical role of inositol c-2, c-3 and c-5 hydroxyl groups.inositol is an essential precursor for the formation of glycosyl-phosphatidylinositol (gpi)-anchors found in the majority of surface molecules in trypanosomatids, in addition to its requirement for phoshatidylinositol signal transduction pathways. in leishmania donovani, high-affinity inositol transport is catalyzed by the active myo-inositol/h+ transporter mit, which is driven by a proton gradient across the parasite membrane. we have characterized the substrate specificity and pharmacology of ...200415287594
combination of ascorbate and alpha-tocopherol as a preventive therapy against structural and functional defects of erythrocytes in visceral leishmaniasis.the redox unbalance in erythrocytes has been found to contribute significantly in the development of anemia in visceral leishmaniasis (vl). the present study revealed enhanced production of reactive oxygen species (ros) and gradual depletion of alpha-tocopherol and ascorbate in the erythrocytes of infected animals. the response of erythrocytes to chronic treatment with antioxidants was studied in hamsters during leishmanial infection. treatment with a combination of alpha-tocopherol and ascorbat ...200415293561
immunostimulatory oligodeoxynucleotides are potent enhancers of protective immunity in mice immunized with recombinant orff leishmanial antigen.unmethylated cpg dinucleotides in bacterial dna or synthetic oligonucleotides (odn) have proved as promising adjuvants for promotion of t helper 1 (th1) type immune response. the potent th1 like immune activation by cpg-odns suggests a possible utility for vaccination against leishmaniasis. we therefore investigated the effect of odn containing immunostimulatory cg motifs as adjuvant with recombinant orff (rorff) leishmanial antigen. balb/c mice were vaccinated with the rorff with or without cpg ...200415297055
detection of high rates of in-village transmission of leishmania donovani in eastern sudan. 200415301978
disseminated intravascular coagulation as an unusual presentation of kala-azar: report of two cases.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.200415307590
modulation of the leishmania donovani peroxin 5 quaternary structure by peroxisomal targeting signal 1 ligands.the import of proteins containing the peroxisomal targeting signal 1 (pts1) into the leishmania glycosome is dependent on the docking of the pts1-loaded ldpex5 cytosolic receptor with ldpex14 on the glycosome surface. here we show that, in the absence of pts1, ldpex5 is a tetramer that is stabilized by two distinct interaction domains; the first is a coiled-coil motif encompassing residues 277 to 310, whereas the second domain is localized to residues 1 to 202. by using microcalorimetry, surface ...200415314146
impact of a co-factor on the dynamics of leishmania donovani infection: does hiv infection encourage the recurrence of visceral leishmaniasis following post-kala-azar dermal leishmaniasis? 200415324473
dynamics of cd62l/cd45rb cd4+ and cd8+ lymphocyte subsets in hepatic and splenic tissues during murine visceral leishmaniasis.this study aimed to characterise, for the first time, the dynamics of cd4+ and cd8+ lymphocyte cd62l/cd45rb subsets, during visceral leishmaniasis. memory/activated status of hepatic and splenic t cells was compared in mice strains with "cure" and "non-cure" phenotypes to leishmania infantum infection. in both mice strains, a correlation between the dynamics of the memory cd4+ and cd8+ t cells (cd62llow/cd45rblow) subsets in the liver and the pre-activated phenotype of lymphocytes (cd62llow/cd45 ...200415325799
inhibiting activities of the secondary metabolites of phlomis brunneogaleata against parasitic protozoa and plasmodial enoyl-acp reductase, a crucial enzyme in fatty acid biosynthesis.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, ...200415326547
combination therapy using sodium antimony gluconate in stearylamine-bearing liposomes against established and chronic leishmania donovani infection in balb/c mice.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.200415328135
short report: fluorescent leishmania: application to anti-leishmanial drug testing.classic techniques for detecting the susceptibility of leishmania to different drugs are time-consuming, laborious, and require the use of macrophages. the use of flow cytometry for monitoring leishmania susceptibility to drugs is beginning to be implemented. using green fluorescent protein (gfp), we have improved and simplified the screening procedure. we introduced a gfp marker into field strains of leishmania causing kala-azar (visceral leishmaniasis) and explored the suitability of transgeni ...200415516633
adjunct effect of immunostimulating hexapeptide analogous to human beta-casein fragment (54-59) to sodium stibogluconate against experimental visceral leishmaniasis.visceral leishmaniasis (vl) is a major public health problem in many tropical countries of the world. the available chemotherapeutics require parenteral administration and have other limitations like cost, toxicity, variable efficacy or restricted supplies. there is no effective treatment for immunosuppressed patients with leishmaniasis- hiv co-infection. hence, new therapies, that are effective when treatment with the currently available drugs fails, must be developed. one of the major strategi ...200415518175
leishmania donovani is the only cause of visceral leishmaniasis in east africa; previous descriptions of l. infantum and "l. archibaldi" from this region are a consequence of convergent evolution in the isoenzyme data.isoenzyme-based studies have identified 3 taxa/species/'phylogenetic complexes' as agents of visceral leishmaniasis in sudan: l. donovani, l. infantum and "l. archibaldi". however, these observations remain controversial. a new chitinase gene phylogeny was constructed in which stocks of all 3 putative species isolated in sudan formed a monophyletic clade. in order to construct a more robust classification of the l. donovani complex, a panel of 16 microsatellite markers was used to describe 39 st ...200415521628
in vivo selection for leishmania donovani miniexon genes that increase virulence in leishmania major.different species of leishmania are responsible for the diverse pathologies associated with leishmaniasis including leishmania donovani which results in fatal visceral infection and leishmania major which causes non-fatal cutaneous infection. in an attempt to identify genotypic differences between these related old world leishmania species which contribute to their distinct phenotypic characteristics, we have introduced a l. donovani cosmid library into l. major to select for l. donovani sequenc ...200415522086
novel motifs in amino acid permease genes from leishmania.eight amino acid permease genes from the protozoan parasite leishmania donovani (aaplds) were cloned, sequenced, and shown to be expressed in promastigotes. seven of these belong to the amino acid transporter-1 and one to the amino acid polyamino-choline superfamilies. using these sequences as well as known and characterized amino acid permease genes from all kingdoms, a training set was established and used to search for motifs, using the meme motif discovery tool. this study revealed two motif ...200415522240
contribution of electron and confocal microscopy in the study of leishmania-macrophage interactions.promastigotes of the protozoan parasite genus leishmania are inoculated into a mammalian host when an infected sand fly takes a bloodmeal. following their opsonization by complement, promastigotes are phagocytosed by macrophages. there, promastigotes differentiate into amastigotes, the form of the parasite that replicates in the phagolysosomal compartments of host macrophages. although the mechanisms by which promastigotes survive the microbicidal consequence of phagocytosis remain, for the most ...200415525438
quantification of leishmania infantum dna by a real-time pcr assay with high sensitivity.a real-time pcr was developed to quantify leishmania infantum kinetoplast dna and optimized to reach a sensitivity of 0.0125 parasites/ml of blood. in order to analyze the incidence of heterogeneity and number of minicircles, we performed comparative pcr by using the leishmania dna polymerase gene as a reporter. assays performed in both promastigote and amastigote stages showed variations among different l. infantum and leishmania donovani strains and the stability of the minicircle numbers for ...200415528722
antibodies directed against o-acetylated sialoglycoconjugates accelerate complement activation in leishmania donovani promastigotes.an enhanced presence of 9-o-acetylated sialoglycoconjugates (9-o-acsgs) triggers the alternate pathway (ap) in indian visceral leishmaniasis (vl). antibodies directed against these epitopes are present in high titers. the biological relevance of these antibodies, with regard to activation of the classical pathway (cp), was investigated.200415529267
efficacy of trypan: a diminazene based drug as antileishmanial agent.trypan, a diamidine based drug, was tested as an antileishmanial agent. duplicate cultures of both leishmania major and leishmania donovani promastigotes in m199 medium and trypan at various concentrations were tested. the cultures were incubated at 25 degrees c and parasites counted at 48 h interval, and the data generated was used to establish growth inhibition curves. drug-free cultures were included to serve as control. in the in vivo study, a total of 40 balb/c mice were divided into five g ...200415533297
a subset of liver nk t cells is activated during leishmania donovani infection by cd1d-bound lipophosphoglycan.natural killer (nk) t cells are activated by synthetic or self-glycolipids and implicated in innate host resistance to a range of viral, bacterial, and protozoan pathogens. despite the immunogenicity of microbial lipoglycans and their promiscuous binding to cd1d, no pathogen-derived glycolipid antigen presented by this pathway has been identified to date. in the current work, we show increased susceptibility of nk t cell-deficient cd1d(-/-) mice to leishmania donovani infection and leishmania-in ...200415466622
localization of marginal zone macrophages is regulated by c-c chemokine ligands 21/19.the marginal zone (mz) of the spleen is an important site for the capture of blood-borne pathogens and a gateway for lymphocytes entering the white pulp. we have recently reported that leishmania donovani infection results in a remarkably selective loss of mz macrophages (mzm) from the mz. to understand the basis of this observation, we have investigated how mzm maintain their anatomical distribution in the steady state in uninfected mice. we now report that plt/plt mice, which lack functional c ...200415470021
macrophages, pathology and parasite persistence in experimental visceral leishmaniasis.many infectious diseases are associated with parasite persistence, often restricted to certain tissue sites, yet the determinants of such persistence are poorly understood. infection with the protozoan parasite leishmania donovani has proved a useful experimental tool to address how immune responses can be differentially effective in clearing parasites from different tissues and, conversely, it might also provide a good model for understanding the basis of parasite persistence. this article revi ...200415471704
ldarf1 in trafficking and structural maintenance of the trans-golgi cisternal network in the protozoan pathogen leishmania donovani.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 gen ...200415479452
evaluation of the direct agglutination test based on freeze-dried leishmania donovani promastigotes for the serodiagnosis of visceral leishmaniasis in sudanese patients.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, ...200415482407
visceral leishmaniasis: a trip to the greek islands is not always idyllic.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 liposoma ...200415487964
[chromosomal localization of the kmp-11 genes in the kp1(+) and kp1(-) strains of trypanosoma rangeli].genes encoding for the kmp-11 protein were localized on the chromosomes of trypanosoma rangeli. these genes were located in two chromosomes of 3,100 and 3,400 kb in the kp1(-) strain whereas in the kp1(+) h14 and choachí strains, the genes are located in a chromosome of 1,600 kb. the choachí strain presents an additional band of 1,400 kb. in the shubacbarina and munanta strains of trypanosoma cruzi, the kmp-11 genes are located on a chromosomal band of 1,490 kb. therefore, the chromosomal locali ...200415495600
efficacy of human beta-casein fragment (54-59) and its synthetic analogue compound 89/215 against leishmania donovani in hamsters.the characteristic feature of visceral leishmaniasis (vl) is the profound impairment of immune system of the infected host, which contributes significantly to the partial success of antileishmanial chemotherapy. since in vl, cure is the combinatorial effect of drug and immune status of the host, the rationale approach towards antileishmanial chemotherapy would be to potentiate the immune functioning of the host to extract desired results. towards this direction several rationally designed analog ...200415501518
in vitro antileishmanial activity of acetogenins from annonaceae.twelve acetogenins from annonaceae were evaluated in vitro for their antileishmanial activities in order to search for new lead-compounds having antileishmanial properties. the compounds were comparatively evaluated by the 50% inhibitory concentrations (ic50) determination on promastigote forms of wild-type and four drug-resistant lines of leishmania donovani. in addition, after testing the toxicity on mouse peritoneal macrophages, the compounds were evaluated on amastigote infected macrophages ...200415271421
novel azasterols as potential agents for treatment of leishmaniasis and trypanosomiasis.this paper describes the design and evaluation of novel azasterols as potential compounds for the treatment of leishmaniasis and other diseases caused by trypanosomatid parasites. azasterols are a known class of (s)-adenosyl-l-methionine: delta24-sterol methyltransferase(24-smt) inhibitors in fungi, plants, and some parasitic protozoa. the compounds prepared showed activity at micromolar and nanomolar concentrations when tested against leishmania spp. and trypanosoma spp. the enzymatic and stero ...200415273104
role of positional hydrophobicity in the leishmanicidal activity of magainin 2.the emergence of membrane-active antimicrobial peptides as new alternatives against pathogens with multiantibiotic resistance requires the design of better analogues. among the different physicochemical parameters involved in the optimization of linear antimicrobial peptides, positional hydrophobicity has recently been incorporated. this takes into consideration the concept of the topological distribution of hydrophobic residues throughout the sequence rather than the classical concept of hydrop ...200415273109
possible mechanism of miltefosine-mediated death of leishmania donovani.miltefosine causes leishmanial death, but the possible mechanism(s) of action is not known. the mode of action of miltefosine was investigated in vitro in leishmania donovani promastigotes as well as in extra- and intracellular amastigotes. here, we demonstrate that miltefosine induces apoptosis-like death in l. donovani based on observed phenomena such as nuclear dna condensation, dna fragmentation with accompanying ladder formation, and in situ labeling of dna fragments by the terminal deoxyri ...200415273114
inhibitors of leishmania mexicana crk3 cyclin-dependent kinase: chemical library screen and antileishmanial activity.the crk3 cyclin-dependent kinase of leishmania has been shown by genetic manipulation of the parasite to be essential for proliferation. we present data which demonstrate that chemical inhibition of crk3 impairs the parasite's viability within macrophages, thus further validating crk3 as a potential drug target. a microtiter plate-based histone h1 kinase assay was developed to screen crk3 against a chemical library enriched for protein kinase inhibitors. twenty-seven potent crk3 inhibitors were ...200415273118
leishmania donovani activates nuclear transcription factor-kappab in macrophages through reactive oxygen intermediates.interaction of leishmania donovani with macrophages antagonizes host defense mechanisms by interfering with a cascade of cell signaling processes in the macrophages. an early intracellular signaling event that follows receptor engagement is the activation of transcription factor nf-kappab. it has been reported earlier that nf-kappab-dependent signaling pathway regulates proinflammatory cytokine release. we therefore investigated the effect of l. donovani infectivity on this nuclear transcription ...200415336576
camptothecin-induced imbalance in intracellular cation homeostasis regulates programmed cell death in unicellular hemoflagellate leishmania donovani.leishmania, a unicellular trypanosomatid protozoan parasite, causes a wide range of human diseases ranging from the localized self-healing cutaneous lesions to fatal visceral leishmaniasis. however, it undergoes a process of programmed cell death during treatment with the topoisomerase i poison camptothecin (cpt). the present study shows that cpt-induced formation of reactive oxygen species increases the level of cytosolic calcium through the release of calcium ions from intracellular stores as ...200415355995
leishmaniasis: current status of vaccine development.leishmaniasis, a spectrum of diseases caused by various forms of leishmania has become a major health problem all over the world. vaccination against leishmaniasis has passed through many developmental stages beginning with the ancient practice of 'leishmanization'. due to various problems and difficulties associated with traditional vaccines, the interest has been shifted to novel approaches of vaccination like dna vaccination, vaccination with live vectors encoding leishmanial antigens and fin ...200415357215
macrophage specific drug delivery in experimental leishmaniasis.macrophage-specific delivery systems are the subject of much interest nowadays, because of the fact that macrophages act as host cells for many parasites and bacteria, which give rise to outbreak of so many deadly diseases(eg. leishmaniasis, tuberculosis etc.) in humans. to combat these deadly diseases initially macrophage specific liposomal delivery system were thought of and tested in vivo against experimental leishmaniasis in hamsters using a series of indigenous or synthetic antileishmanial ...200415357216
progress in vaccine research and possible effector mechanisms in visceral leishmaniasis.visceral leishmaniasis represents a serious public health concern in endemic regions and is rapidly emerging as an opportunistic infection in hiv patients. the disease is difficult to diagnose and prevent, and available treatment is associated with toxicity and drug resistance. even though significant headway has been made in the development of vaccines against cutaneous leishmaniasis, visceral leishmaniasis has received limited attention. the fact that a large proportion of the people living in ...200415357218
does the leishmania major paradigm of pathogenesis and protection hold for new world cutaneous leishmaniases or the visceral disease?parasitic protozoa of the genus leishmania have provided a useful perspective for immunologists in terms of host defense mechanisms critical for the resolution of infection caused by intracellular pathogens. these organisms, which normally reside in a late endosomal, major histocompatibility complex (mhc) class ii(+) compartment within host macrophages cells, require cd4(+) t-cell responses for the control of disease. the paradigm for the cd4(+) t-helper 1 (th1)/th2 dichotomy is largely based on ...200415361243
the immunopathology of experimental visceral leishmaniasis.experimental murine infection with the parasites that cause human visceral leishmaniasis (vl) results in the establishment of infection in the liver, spleen, and bone marrow. in most strains of mice, parasites are eventually cleared from the liver, and hepatic resistance to infection results from a coordinated host response involving a broad range of effector and regulatory pathways targeted within defined tissue structures called granulomas. in contrast, parasites persist in the spleen and bone ...200415361245
activity of dihydroartemisinin against leishmania donovani both in vitro and vivo. 200415361310
isomerase-independent chaperone function of cyclophilin ensures aggregation prevention of adenosine kinase both in vitro and under in vivo conditions.using inactive aggregates of adenosine kinase (adk) from leishmania donovani as the model substrate, we recently demonstrated that a cyclophilin (ldcyp) from the same source in an isomerase-independent fashion reactivated the enzyme in vitro by disaggregating its inactive oligomers [chakraborty et al. (2002) j. biol. chem. 277, 47451-47460]. besides disrupting preformed aggregates, ldcyp also prevents reaggregation of the newly formed active protein that is generated after productive refolding f ...200415362872
vaccination with leishmania soluble antigen and immunostimulatory oligodeoxynucleotides induces specific immunity and protection against leishmania donovani infection.in this report, we investigated the effect of odn containing immunostimulatory cg motifs as adjuvant with soluble antigen (sa) from leishmania donovani. balb/c mice were vaccinated with the soluble antigen with or without cpg-odn as adjuvant and then challenged with l. donovani metacyclic promastigotes. cpg-odn alone resulted in partial protection against challenge with l. donovani. immunization of mice with sa and cpg-odn showed enhanced reduction in parasite load ( approximately 60%) when comp ...200415364110
anthranoid compounds with antiprotozoal activity from vismia orientalis.a phytochemical investigation of the 80% ethanolic extract of stem bark of vismia orientalis engl. (guttiferae or clusiaceae), a plant used in traditional medicine in tanzania, resulted in the isolation and spectroscopic characterisation of 3-geranyloxy-6-methyl-1,8-dihydroxyanthraquinone, emodin, vismione d and bianthrone a1. vismione d exhibited a broad range of antiprotozoal activities against trypanosoma brucei rhodesiense and t. cruzi (ic50 < 10 micrograms/ml), leishmania donovani (ic50 0.3 ...200415368649
purification, characterization of o-acetylated sialoglycoconjugates-specific igm, and development of an enzyme-linked immunosorbent assay for diagnosis and follow-up of indian visceral leishmaniasis patients.the surface expression of 9-o-acetylated sialic acid (9-oacsa) is elevated on hematopoietic cells and erythrocytes of visceral leishmaniasis (vl) patients. in this study, we show that vl patients contain elevated levels of igm antibodies directed against 9-o-acetylated sialoglycoconjugates (9-oacsg). these antibodies were affinity purified with bovine submaxillary protein as the affinity matrix containing the terminal epitope, 9-oacsaalpha2-6galnac. they also bound to 9-oacsgs on hematopoietic c ...200415380274
[cloning and sequence analysis of the ribosomal dna its gene of leishmania donovani isolates from hill foci of china].to determine the nucleotide sequence of the its (internal transcribed spacer) gene of leishmania donovani isolates from hill foci (l. d. sc10 and l. d. 6), and to find out the difference of the gene sequences between the two isolates.200415830885
elevated plasma levels of interferon (ifn)-gamma, ifn-gamma inducing cytokines, and ifn-gamma inducible cxc chemokines in visceral leishmaniasis.interferon (ifn)- gamma plays an important role during immune responses against leishmaniasis. production of ifn-gamma is regulated by interleukin (il)-12, il-18, and il-15. interferon-gamma-inducible protein (ip)-10 and monokine induced by ifn-gamma (mig) are cxc chemokines, the production of which, at least in part, is ifn-gamma dependent. a follow-up study of individuals infected with leishmania donovani was undertaken in an area of ethiopia endemic for visceral leishmaniasis (vl). plasma lev ...200415569785
leishmania parasites (kinetoplastida: trypanosomatidae) reversibly inhibit visceral muscle contractions in hemimetabolous and holometabolous insects.female sand flies can acquire protozoan parasites in the genus leishmania when feeding on an infected vertebrate host. the parasites complete a complex growth cycle in the sand fly gut until they are transmitted by bite to another host. recently, a myoinhibitory peptide was isolated from leishmania major promastigotes. this peptide caused significant gut distension and reversible, dose-dependent inhibition of spontaneous hindgut contractions in the enzootic sand fly vector, phlebotomus papatasi. ...200415579321
distinct roles for lymphotoxin-alpha and tumor necrosis factor in the control of leishmania donovani infection.tumor necrosis factor (tnf) is critical for the control of visceral leishmaniasis caused by leishmania donovani. however, the role of the related cytokine lymphotoxin (lt) alpha in this infection is unknown. here we report that c57bl/6 mice deficient in tnf (b6.tnf(-/-)) or lt alpha (b6.lt alpha(-/-)) have increased susceptibility to hepatic l. donovani infection. furthermore, the outcome of infection in bone marrow chimeric mice is dependent on donor hematopoietic cells, indicating that develop ...200415579454
hemoglobin receptor in leishmania is a hexokinase located in the flagellar pocket.hb endocytosis in leishmania is mediated through a 46-kda protein located in the flagellar pocket. to understand the nature of the hb receptor (hbr), we have purified the 46-kda protein to homogeneity from leishmania promastigote membrane. purified hbr specifically binds hb. the gene for hbr was cloned, and sequence analysis of the full-length hbr gene indicates the presence of hexokinase (hk) signature sequences, atp-binding domain, and pts-ii motif. four lines of evidence indicate that hbr in ...200415579464
trypanosomatid flagellum biogenesis: arl-3a is involved in several species.overexpression in leishmania amazonensis promastigotes of the gtpase-deficient small g protein ldarl-3a-q70l specifically provokes the loss of the flagella without affecting cell viability and body size. however, motility is lost and, remarkably, cells do not survive in the insect vector lutzomyia longipalpis gut, leading to interruption of parasite transmission. we report here that overexpression of the same protein in leishmania major, leishmania donovani, and crithidia fasciculata also led to ...200415582509
identification of novel parasitic cysteine protease inhibitors using virtual screening. 1. the chembridge database.trypanosomiasis, leishmaniasis, and malaria are major parasitic diseases in developing countries. the existing chemotherapy of these diseases suffers from lack of safe and effective drugs and/or the presence of widespread drug resistance. cysteine proteases are exciting novel targets for antiparasitic drug design. virtual screening was performed in an attempt to identify novel druglike nonpeptide inhibitors of parasitic cysteine proteases. the chembridge database consisting of approximately 241 ...200415588096
stromal cells direct local differentiation of regulatory dendritic cells.cd11c(hi) dendritic cells (dc) play an essential role during the initiation of cell-mediated immunity. recently, cd11c(lo)cd45rb(hi) dc with regulatory properties have been described. however, the origins of regulatory dc are poorly understood. here, we show that spleen-derived stromal cells promote selective development of cd11c(lo)cd45rb(+) il-10-producing regulatory dc from lineage-negative c-kit(+) progenitor cells. these dc have the capacity to suppress t cell responses and induce il-10-pro ...200415589169
infection rates with leishmania donovani and mycobacterium tuberculosis in a village in eastern sudan.leishmania-tuberculosis co-infection is not uncommon in clinical practice in east africa, but little is known about the epidemiology of this problem at population level. a cross-sectional household survey was carried out in an active visceral leishmaniasis (vl) focus in eastern sudan in february 2002.200415598262
evaluation of a latex agglutination test (katex) for detection of leishmania antigen in urine of patients with hiv-leishmania coinfection: value in diagnosis and post-treatment follow-up.the usefulness of antigen detection in urine as an alternative tool for diagnosis of leishmaniasis and post-treatment follow-up in patients with leishmania-hiv coinfection was evaluated with a latex agglutination test (katex; kalon biological, uk). forty-nine hiv-infected patients with visceral leishmaniasis were included in the study. antigen detection in urine (adu) was positive in 42 of 49 (sensitivity, 85.7%) samples obtained during a primary episode. after treatment, a follow-up study in 23 ...200415599651
the choice of animal model and reduction.careful choice of the animal model is essential, if research is to be conducted efficiently, by using the minimum number of animals in order to provide the maximum amount of information. inbred strains of rodents provide an excellent way of controlling and investigating genetic variation in characters of interest and in response to experimental treatments. outbred stocks, in which genetic and non-genetic factors are inextricably mixed, are much less suitable, because random and uncontrolled gene ...200415601228
slc11a1-mediated resistance to salmonella enterica serovar typhimurium and leishmania donovani infections does not require functional inducible nitric oxide synthase or phagocyte oxidase activity.solute carrier family 11a member 1 (slc11a1; formerly natural resistance-associated macrophage protein 1) encodes a late endosomal/lysosomal protein/divalent cation transporter, which regulates iron homeostasis in macrophages. during macrophage activation, slc11a1 exerts pleiotropic effects on gene regulation and function, including generation of nitric oxide (no) via inducible no synthase (inos; encoded by nos2a) and of reactive oxygen intermediates (roi) via the phagocyte oxidase complex. as n ...200415601666
overexpression in escherichia coli and purification of pteridine reductase (ptr1) from a clinical isolate of leishmania donovani.pteridine reductase 1 (ptr1) is part of a novel metabolic pathway in leishmania associated with folate metabolism. its main function is to salvage pterins but a second one is to reduce folates. the novelty and possible uniqueness of the pathway in which ptr1 is involved opens the possibility of developing specific inhibitors, which in combination with dihydrofolate reductase inhibitors could be highly effective against leishmania. in order to increase our understanding of this putative important ...200415555938
crystallographic and nmr studies of antiinfective tricyclic guanidine alkaloids from the sponge monanchora unguifera.three tricyclic guanidine alkaloids, including 1,8a;8b,3a-didehydro-8beta-hydroxyptilocaulin (1), 1,8a;8b,3a-didehydro-8alpha-hydroxyptilocaulin (2) and mirabilin b (3), were identified from the marine sponge monanchora unguifera. 1,8a;8b,3a-didehydro-8alpha-hydroxyptilocaulin (2) is a new stereoisomer of 1, the structure of which was elucidated by spectroscopic analysis, comparison of its spectral data with those of 1, and confirmed by x-ray analysis. compounds 1 and 2 co-crystallized in an unu ...200415556763
inhibition of leishmania donovani promastigote dna topoisomerase i and human monocyte dna topoisomerases i and ii by antimonial drugs and classical antitopoisomerase agents.we have compared the inhibitor sensitivities of dna topoisomerase i (topi) from leishmania donovani promastigotes and tops i and ii of human monocytes using pentavalent and trivalent antimonials (sbv, sbiii) and classical top inhibitors. bis-benzimidazoles (hoechst-33258 and -33342) were potent inhibitors of both parasite and human topi, but hoechst-33342 was markedly less cytotoxic to promastigotes than to monocytes in vitro. leishmania donovani was also considerably less sensitive than monocyt ...200415562618
[alithiasic cholecystitis in association with visceral leishmaniasis in an immunodepressed patient]. 200415615399
leishmania inhibits stat1-mediated ifn-gamma signaling in macrophages: increased tyrosine phosphorylation of dominant negative stat1beta by leishmania mexicana.previous studies have demonstrated that leishmania donovani attenuates stat1-mediated signaling in macrophages; however it is not clear whether other species of leishmania, which cause cutaneous disease, also interfere with macrophage ifn-gamma signaling. therefore, we determined the effect of leishmania major and leishmania mexicana infection on stat1-mediated ifn-gamma signaling pathway in j774a.1 and raw264.7 macrophages. we found that both l. major and l. mexicana suppressed ifngammaralpha ( ...200415619518
screening of new caledonian and vanuatu medicinal plants for antiprotozoal activity.sixty-seven extracts of 30 medicinal plants traditionally used in new caledonia or vanuatu by healers to treat inflammation, fever and in cicatrizing remedies were evaluated in vitro for their antiprotozoal activity against leishmania donovani, leishmania amazonensis and trypanosoma cruzi. among the selected plants, pagiantha cerifera was the most active against both leishmania species; four extracts were active against promastigotes of leishmania donovani at ec(50) values inferior to 5 microg/m ...200415619580
ancistrobenomine a, the first naphthylisoquinoline oxygenated at me-3, and related 5,1'-coupled alkaloids, from the "new" plant species ancistrocladusbenomensis.three new 5,1'-coupled naphthylisoquinoline alkaloids, ancistrobenomine a (1), 6-o-demethylancistrobenomine a (2), and 5'-o-demethylancistrocline (3), have been isolated from the stem bark of a botanically as yet undescribed highland liana ancistrocladus sp., proposed to be named "a. benomensis" according to the region in peninsular malaysia where it has been discovered on the mountain of gunung benom. two of the compounds possess an unprecedented structure with a novel hydroxymethylene group at ...200415620251
intake of nutrient supplements affects multiplication of leishmania donovani in hamsters.the role of the essential nutrients, vitamins a, b (complex), c and e and iron, as prophylactic as well as supportive therapy in experimental visceral leishmaniasis (vl), was studied in hamsters. prophylactic administration of vitamin c (50, 100 and 250 mg/kg) from day 15 to day 0 (15 doses) significantly reduced the intake of leishmania donovani in hamsters but had no therapeutic effect. in contrast, vitamins a, b complex and e and iron, whether used prophylactically or therapeutically, promote ...200415648691
liposomal amphotericin b and rhugm-csf for treatment of visceral leishmaniasis in aids.in recent years, several reports have emphasized the increasing importance of visceral leishmaniasis as an opportunistic infection among hiv-positive patients in areas where both infections are endemic. major challenges in the treatment of leishmaniasis include widespread resistance to pentavalent antimonial compounds, absence of safe chemotherapeutic agents, and treatment failure and relapses in hiv-leishmania coinfected patients. despite the associated adverse reactions and the need for prolon ...200415711134
regulation of k-cl cotransport: from function to genes.this review intends to summarize the vast literature on k-cl cotransport (cot) regulation from a functional and genetic viewpoint. special attention has been given to the signaling pathways involved in the transporter's regulation found in several tissues and cell types, and more specifically, in vascular smooth muscle cells (vsmcs). the number of publications on k-cl cot has been steadily increasing since its discovery at the beginning of the 1980s, with red blood cells (rbcs) from different sp ...200415711773
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