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Complex Interplay between Sphingolipid and Sterol Metabolism Revealed by Perturbations to the Leishmania Metabolome Caused by Miltefosine
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With the World Health Organization reporting over 30,000 deaths and 200,000 to 400,000 new cases annually, visceral leishmaniasis is a serious disease affecting some of the world's poorest people. As drug resistance continues to rise, there is a huge unmet need to improve treatment. Miltefosine remains one of the main treatments for leishmaniasis, yet its mode of action (MoA) is still unknown. Understanding the MoA of this drug and parasite response to treatment could help pave the way for new and more successful treatments for leishmaniasis. A novel method has been devised to study the metabolome and lipidome ofLeishmania donovaniaxenic amastigotes treated with miltefosine. Miltefosine caused a dramatic decrease in many membrane phospholipids (PLs), in addition to amino acid pools, while sphingolipids (SLs) and sterols increased.Leishmania majorpromastigotes devoid of SL biosynthesis through loss of the serine palmitoyl transferase gene (ΔLCB2) were 3-fold less sensitive to miltefosine than wild-type (WT) parasites. Changes in the metabolome and lipidome of miltefosine-treatedL. majormirrored those ofL. donovani. A lack of SLs in the ΔLCB2 mutant was matched by substantial alterations in sterol content. Together, these data indicate that SLs and ergosterol are important for miltefosine sensitivity and, perhaps, MoA.

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Publication Date
Wed Feb 22 2023
Journal Name
Iraqi Journal Of Science
Miltefosine Efficacy on Leishmania Donovani Promastigote
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In the current study, different concentrations of miltefosine drug, which is the first effective and safe oral treatment for visceral leishmaniasis, was evaluated against L. donovani promastigotes in comparison with pentosam drug. Direct counting microscopic assay was used to find 50% inhibitory concentration (IC50) of miltefosine and pentostam against L. donovani promastigotes. The IC50 of miltefosine drug was 45.42μg/ml, 46.76μg/ml and 36.68μg/ml after 24 hr, 48hr and 72hr respectively, In comparison with IC 50 of pentostam drug was 75.39 μg/ml after 72hr. There were significant differences (P˂0.05) between IC50 values of miltefosine and pentostam drugs from first day to third day.

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Publication Date
Sat Dec 01 2012
Journal Name
Advances In Bioresearch
Cytotoxicity of Miltefosine against Leishmania majorPromastigotes
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Publication Date
Sun Jan 01 2012
Journal Name
Biochemistry Research International
Endocytosis and Sphingolipid Scavenging in Leishmania mexicana Amastigotes
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Leishmaniaspecies are the causative agents of the leishmaniases, a spectrum of neglected tropical diseases. Amastigote stage parasites exist within macrophages and scavenge host factors for survival, for example,Leishmaniaspecies utilise host sphingolipid for synthesis of complex sphingolipid. In this studyL. mexicanaendocytosis was shown to be significantly upregulated in amastigotes, indicating that sphingolipid scavenging may be enhanced. However, inhibition of host sphingolipid biosynthesis had no significant effect on amastigote proliferation within a macrophage cell line. In addition, infection itself did not directly influence host biosynthesis.

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Publication Date
Sat Mar 01 2014
Journal Name
International Journal Of Advanced Research
Ex vivo study of the importance of sphingolipid in Leishmania amastigote
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Leishmania is the causative agent of leishmaniasis, a widely distributed disease. Amastigote forms of Leishmania are intracellular and reside within the macrophage of the vertebrate host. Previous studies showed that certain Leishmania species may scavenge host factors for survival, specially sphingolipids, the key element of the eukaryotic membranes. In this study we have investigated the survival of new world L. mexicana amastigotes in murine macrophage cell-line in the presence and absence of foetal bovine serum (FBS). Results showed that there was no significance in the infectivity of amastigotes and also the number of parasite per cell; such findings suggest that L. mexicana amastigotes have its own pathway of sphingolipid intake and c

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Publication Date
Thu Dec 31 2020
Journal Name
Iraqi Journal Of Market Research And Consumer Protection
SIMULATION AND MODELING OF HYDRO CRACKING REACTR TO REDUCE POLLUTION CAUSED BY REFINERIES: SIMULATION AND MODELING OF HYDRO CRACKING REACTR TO REDUCE POLLUTION CAUSED BY REFINERIES
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Hydro cracking of heavy oil is used in refinery to produce invaluable products. In this research, a model of hydro cracking reactor has been used to study the behavior of heavy oil in hydro cracking under the conditions recommended by literature in terms lumping of feed and products. The lumping scheme is based on five lumps include: heavy oil, vacuum oil, distillates, naphtha and gases. The first order kinetics was assumed for the conversion in the model and the system is modeled as an isothermal tubular reactor. MATLAB 6.1 was used to solve the model for a five lump scheme for different values of feed velocity, and temperature.

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Publication Date
Sat Jan 01 2011
Journal Name
North American Journal Of Medical Sciences
Urinary tract infections caused by staphylococcus aureus DNA in comparison to the candida albicans DNA
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Background: Bacterial DNA released upon bacterial autolysis or killed by antibiotics, hence, many inflammatogenic reactions will be established leading to serious tissue damage. Aim: the present work aimed to elucidate the histopathological changes caused by prokaryotic (bacterial) DNA and eukaryotic (candidal) DNA. Materials and methods: twenty one Staphylococcus aureus and 36 Candida albicans isolates were isolated from UTI patients. Viable cells and DNA of the highest antibiotic sensitive isolates were injected, intraurethraly, in mice. Results were evaluated via histopathological examination. Results: Mildest reactions were obtained from mice challenged with viable C. albicans compared with those challenged with viable S. aureus. Dos

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Publication Date
Mon Sep 14 2020
Journal Name
British Journal Of Neurosurgery
Head injuries caused by the ritual of ‘Tatbir’: a neurosurgical perspective
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Publication Date
Thu Apr 25 2019
Journal Name
Iraqi Journal Of Market Research And Consumer Protection
ECONOMIC LOSSES CAUSED BY ROSE BEETLE MALADERA INSANABILIS (BRENSKE) ON FRUIT AND ORNAMENTAL PLANTS AND ITS CONTROL BY PATHOGENIC FUNGI: ECONOMIC LOSSES CAUSED BY ROSE BEETLE MALADERA INSANABILIS (BRENSKE) ON FRUIT AND ORNAMENTAL PLANTS AND ITS CONTROL BY PATHOGENIC FUNGI
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The study aimed to evaluate injuries and economic losses which caused by rose beetle Maladerainsanabilis (Brenske) on ornamental and fruit plants as introduced insect in Iraq during 2015 and determine infested host plants in addition to evaluate efficacy of pathogenic fungi Metarhiziumanisopiliae (1x10⁹ spore/ ml) and Beauvariabassiana (1x10⁸spore/ ml) in mortality of insect larvae in laboratory and field.The results showed that the insect was polyphagous infested many host plants (20 host plant)Which caused degradation and dead the plants through adult feeding on leaves and flower but large injury caused by larvae feeding on root plants which caused obligate dead to infested plant, the percentage mortality of rose plants 68.6%, pear

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Publication Date
Thu Apr 17 2008
Journal Name
Anbar Journal Of Agricultural Sciences 6 (2)‏
Influence of foliar sprays with Copper and Zinc on the resistance of citrus rootstocks to gumosis caused by Phytophthora citropthora. ‏
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Publication Date
Tue Aug 07 2018
Journal Name
Oral And Maxillofacial Surgery
Mandibular war injuries caused by bullets and shell fragments: a comparative study
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