In the current study, we evaluated the mechanism of action of miltefosine, which is the first effective and safe oral treatment for visceral leishmaniasis, in Leishmania amazonensis promastigotes. Miltefosine induced a process of programmed cell death, which was determined by the externalization of phosphatidylserine, the incorporation of propidium iodide, cell-cycle arrest at the sub-G0/G1 pha...

Leishmania donovani promastigotes survive inside macrophage phagosomes by inhibiting phagosomal maturation. The main surface glycoconjugate on promastigotes, lipophosphoglycan (LPG), is crucial for survival and mediates the formation of a protective shell of F-actin around the phagosome. Previous studies have demonstrated that this effect involves inhibition of protein kinase C alpha. The prese...

Cytokine-inducible (or type 2) nitric oxide synthase (iNOS) is indispensable for the resolution of Leishmania major or Leishmania donovani infections in mice. In contrast, little is known about the expression and function of iNOS in human leishmaniasis. Here, we show by immunohistological analysis of skin biopsies from Mexican patients with local (LCL) or diffuse (DCL) cutaneous leishmaniasis t...

Bis-(4-hydroxycoumarin-3-yl) methane derivatives 3(a-l) were synthesized from 4-hydroxycoumarin and substituted aromatic aldehydes using succinimide-N-sulfonic acid as catalyst and evaluated for their in vitro antileishmanial activity against promastigotes form of Leishmania donovani. Compounds 3a (IC50= 155 μg/mL), 3g (IC50= 157.5 μg/mL) and 3l (IC50= 150 μg/mL) were shown significant antileis...

The present study includes cloning and expression of recombinant Leishmania donovani histone proteins (rLdH2B, rLdH3, rLdH2A and rLdH4), assessment of their immunogenicity in Leishmania infected cured patients/endemic contacts as well as in cured hamsters and finally evaluation of their prophylactic efficacy in hamsters against L. donovani challenge. All recombinant proteins were expressed and ...

The investigation of microsatellite markers has recently superseded that of isoenzymes for many population-biology applications. Microsatellites have the advantages of being dominant, neutral, highly polymorphic and easily scored by high-throughput methods. However, it is necessary to develop a new panel of markers for each group of organisms of interest. Previously, only about 5% of the marker...

BACKGROUND Post-kala-azar dermal leishmaniasis follows an attack of visceral leishmaniasis and is caused by the same organism, i.e. Leishmania donovani. METHODS In the present study, biopsy specimens from hypopigmented macules, nodules or plaques of 25 patients clinically diagnosed as PKDL were evaluated for epidermal and dermal changes and for the presence or absence of Leishmania donovani b...

T-bet and STAT1 regulate IFN-gamma gene transcription in CD4+ T cells, which mediate protection against Leishmania. Here we show that T-bet and STAT1 are required for the induction of an efficient Th1 response during Leishmania donovani infection, but they play distinct roles in determining disease outcome. Both STAT1(-/-) and T-bet(-/-) mice failed to mount a Th1 response, but STAT1(-/-) mice ...

Arylimidamide (AIA) compounds containing two pyridylimidamide terminal groups (bis-AIAs) possess outstanding in vitro antileishmanial activity, and the frontrunner bis-AIA DB766 (2,5-bis[2-(2-isopropoxy)-4-(2-pyridylimino)aminophenyl]furan) is active in visceral leishmaniasis models when given orally. Eighteen compounds containing a single pyridylimidamide terminal group (mono-AIAs) were synthe...

Cytokines produced by mononuclear cells are important regulatory and effector molecules and evidence has been presented to support a role at least for tumor necrosis factor-a (TNF-a) and interferon-y (IFN-y) in host defense against Leishmania. In the present study, we examined the production of TNF-a and interleukin 1 (IL-I) by resting and IFN-y-primed peripheral blood monocytes infected in vit...