BioAssay record AID 1063 submitted by University of Pittsburgh Molecular Library Screening Center: Leishmania major promastigote HTS.
FIG. 2. Vaccination with live Δlpg2 mutant parasites and CpG ODNs confers significant resistance to L. major. (A) Naïve unvaccinated mice and mice vaccinated for 10 weeks with 5 × 106 stationary-phase Δlpg2 promastigotes alone or in combination with either 50 μg of CpG ODNs or 50 μg of non-CpG ODNs were challenged with 2 × 106 WT L. major parasites in their contralateral uninfected footpads, and the parasite load was estimated by limiting dilution analysis 5 weeks after challenge. Data shown represent the mean increases ± standard deviations for three mice per group. (B) The increase in footpad thickness was measured after 72 h to assess the DTH response in naïve and challenged mice. Asterisks and NS indicate statistically significant or not significant differences, respectively. (C) Prior to challenge, draining LNs from three mice per group were isolated, single-cell suspensions were restimulated in the presence of leishmanial freeze-thawed antigen for 72 h, and the production of ...
Activated CD4(+) T helper cells (Th) comprise at least two functionally distinct subsets, Th1 and Th2, which mediate different immunological effector functions. Experimental leishmaniasis is widely used to study the effector function of Th cell subsets in vivo. Healing and nonhealing Leishmania major infections have been correlated with polarized Th1 and Th2 responses, respectively. In the study presented here, a stable cell surface marker expressed on Th2 cells, T1/ST2, has been used to assess the distribution of CD4(+)T1/ST2(+) T cells in different organs of healer and nonhealer strains of mice during the course of L. major infection. The frequency of CD4(+) T cells expressing the T1/ST2 cell surface marker and Th2 cytokines in the lymphoid organs was low in both strains of infected mice; however, CD4(+) T1/ST2(+) T cells could be enriched from the lymphoid organs of infected nonhealer but riot from healer strains of mice. The highest frequency of CD4(+) T1/ST2(+)T cells was detected in the ...
Leishmania major parasites reside and multiply in late endosomal compartments of host phagocytic cells. Immune control of Leishmania growth absolutely requires expression of inducible Nitric Oxide Synthase (iNOS/NOS2) and subsequent production of NO. Here, we show that CD11b+ CD11c+ Ly-6C+ MHC-II+ cells are the main iNOS-producing cells in the footpad lesion and in the draining lymph node of Leishmania major-infected C57BL/6 mice. These cells are phenotypically similar to iNOS-producing inflammatory DC (iNOS-DC) observed in the mouse models of Listeria monocytogenes and Brucella melitensis infection. The use of DsRed-expressing parasites demonstrated that these iNOS-producing cells are the major infected population in the lesions and the draining lymph nodes. Analysis of various genetically deficient mouse strains revealed the requirement of CCR2 expression for the recruitment of iNOS-DC in the draining lymph nodes, whereas their activation is strongly dependent on CD40, IL-12, IFN-gamma and ...
Objective(s):Cutaneous Leishmaniasis is a common and endemic disease in Khorasan province in North-East of Iran. The pentavalant antimony (Sb V) is the mainstay of treatment that has many side effects and resistance to the drug has been reported. The microbicidal effect of ozone was proven in different microorganisms. Since there is no study in this respect and to achieve a low cost and effective treatment, we decided to evaluate the efficacy of ozone against promastigotes of Leishmania major,in vitro. Materials and Methods: Ozonated olive oil was prepared after production of ozone by bubbling ozone-oxygen gas produced by ozone generator through olive oil until it solidified. Promastigotes of L. major were cultivated in two phasic media. After calculation of the number of promastigotes, they were incubated with ozonated olive oil (0, 0.626, 0.938, 1.25, 2.5, 5, 10 mcg/ml) at 28 °c for 24 hr. Parasites survival percentage was evaluated using MTS and microscopic assay, and then compared with Glucantime
Free Online Library: Combination and monotherapy of Leishmania major infection in BALB/c mice using plant extracts and herbicides.(Research Articles, Report) by Journal of Vector Borne Diseases; Health, general Biological products Health aspects Herbicides Infection Care and treatment Diagnosis Materia medica, Vegetable Medical research Medicine, Experimental Parasitic diseases Plant extracts
Parasite virulence genes are usually associated with telomeres. The clustering of the telomeres, together with their particular spatial distribution in the nucleus of human parasites such as Plasmodium falciparum and Trypanosoma brucei, has been suggested to play a role in facilitating ectopic recombination and in the emergence of new antigenic variants. Leishmania parasites, as well as other trypanosomes, have unusual gene expression characteristics, such as polycistronic and constitutive transcription of protein-coding genes. Leishmania subtelomeric regions are even more unique because unlike these regions in other trypanosomes they are devoid of virulence genes. Given these peculiarities of Leishmania, we sought to investigate how telomeres are organized in the nucleus of Leishmania major parasites at both the human and insect stages of their life cycle. We developed a new automated and precise method for identifying telomere position in the three-dimensional space of the nucleus, and we found that
Leishmania major is a species of parasites found in the genus Leishmania, and is associated with the disease zoonotic cutaneous leishmaniasis (also known as Aleppo boil, Baghdad boil, Bay sore, Biskra button, Chiclero ulcer, Delhi boil, Kandahar sore, Lahore sore, Oriental sore, Pian bois, and Uta). L. major is an intracellular pathogen which infects the macrophages and dendritic cells of the immune system. Though Leishmania species are found on every continent aside from Antarctica, Leishmania major is found only in the Eastern Hemisphere, specifically in Northern Africa, the Middle East, Northwestern China, and Northwestern India. As a trypanosomatid, L. major begins its lifecycle in promastigote form in the midgut of the main vector, female sand flies (Phlebotomus spp.). Once in the gut of the sand fly, the parasites change from aflagelated amastigotes into flagellated promastigotes for 1-2 weeks until they are fully developed, a which point they make their way to the proboscis. Upon biting a ...
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Author SummaryLeishmaniasis is a disease induced by a protozoan parasite and transmitted by the sandfly. Several forms of infection are identified, and the different diseases have wide-ranging symptoms from localized cutaneous sores to visceral disease affecting many internal organs. Animal models of human cutaneous leishmaniasis have been established in which disease is induced by infecting mice subcutaneously with Leishmania major. Different strains of inbred mice have been found to be susceptible or resistant to L. major infection.
Human leishmaniasis covers a broad spectrum of clinical manifestations ranging from self-healing cutaneous leishmaniasis to severe and lethal visceral leishmaniasis caused among other species by Leishmania major or Leishmania donovani, respectively. Some drug candidates are in clinical trials to substitute current therapies, which are facing emerging drug-resistance accompanied with serious side effects. Here, two cinnamic acid bornyl ester derivatives (1 and 2) were assessed for their antileishmanial activity. Good selectivity and antileishmanial activity of bornyl 3-phenylpropanoate (2) in vitro prompted the antileishmanial assessment in vivo. For this purpose, BALB/c mice were infected with Leishmania major promastigotes and treated with three doses of 50 mg/kg/day of compound 2. The treatment prevented the characteristic swelling at the site of infection and correlated with reduced parasite burden. Transmitted light microscopy and transmission electron microscopy of Leishmania major ...
Human leishmaniasis covers a broad spectrum of clinical manifestations ranging from self-healing cutaneous leishmaniasis to severe and lethal visceral leishmaniasis caused among other species by Leishmania major or Leishmania donovani, respectively. Some drug candidates are in clinical trials to substitute current therapies, which are facing emerging drug-resistance accompanied with serious side effects. Here, two cinnamic acid bornyl ester derivatives (1 and 2) were assessed for their antileishmanial activity. Good selectivity and antileishmanial activity of bornyl 3-phenylpropanoate (2) in vitro prompted the antileishmanial assessment in vivo. For this purpose, BALB/c mice were infected with Leishmania major promastigotes and treated with three doses of 50 mg/kg/day of compound 2. The treatment prevented the characteristic swelling at the site of infection and correlated with reduced parasite burden. Transmitted light microscopy and transmission electron microscopy of Leishmania major ...
T cells belong to either the alpha beta+ or gamma delta+ lineage as defined by their antigen receptor. Although both T-cell subsets have been shown to be involved in the immune response to the parasite Leishmania major, very little is known about possible interactions between these two populations. In this study, using a mouse model of infection with L. major, we showed that expansion of a subset of gamma delta+ T cells in vivo is dependent upon the presence of alpha beta+ CD4+ T cells. Moreover, this effect appears to be mediated via the secretion of lymphokines by CD4+ cells with a T-helper 2 (Th2) functional phenotype. Results showing that activation of Th2-type cells in mice treated with anti-immunoglobulin D antibodies or infected with Nippostrongylus brasiliensis also results in gamma delta+ T-cell expansion suggest that this effect of the Th2-type CD4+ cells is a general phenomenon not restricted to infection with L. major. Rosat, J. P.; Conceicao-Silva, F.; Waanders, G. A.; Beermann, F.; Wilson,
TY - JOUR. T1 - Expression profiling using random genomic DNA microarrays identifies differentially expressed genes associated with three major developmental stages of the protozoan parasite Leishmania major. AU - Akopyants, Natalia S.. AU - Matlib, Robin S.. AU - Bukanova, Elena N.. AU - Smeds, Matthew R.. AU - Brownstein, Bernard H.. AU - Stormo, Gary D.. AU - Beverley, Stephen M.. PY - 2004/7/1. Y1 - 2004/7/1. N2 - To complete its life cycle, protozoan parasites of the genus Leishmania undergo at least three major developmental transitions. However, previous efforts to identify genes showing stage regulated changes in transcript abundance have yielded relatively few. Here we used expression profiling to assess changes in transcript abundance in three stages: replicating promastigotes and infective non-replicating metacyclics, which occur in the sand fly vector, and in the amastigote stage residing with macrophage phagolysosomes in mammals. Microarrays were developed containing 11,484 PCR ...
The protozoan parasite Leishmania major causes cutaneous lesions to develop at the site of infection, which are resolved with a strong Th1 immune response in resistant hosts, such as C57BL/6 mice. In contrast, the lesions ulcerate in susceptible hosts which display a Th2 response, such as BALB/c mice. The migration of cells in the immune response to L. major is regulated by chemokines and their receptors. The chemokine receptor CCR7 is expressed on activated DCs and naïve T cells, allowing them to migrate to the correct micro-anatomical positions within secondary lymphoid organs. While there have been many studies on the function of CCR7 during homeostasis or using model antigens, there are very few studies on the role of CCR7 during infection. In this study, we show that B6.CCR7-/- mice were unable to resolve the lesion and developed a chronic disease. The composition of the local infiltrate at the lesion was significantly skewed toward neutrophils while the proportion of CCR2+ monocytes was ...
The skin microenvironment at the site of infection plays a role in the early events that determine protective T helper 1/type 1 immune responses during cutaneous leishmaniasis (CL) infection. During CL in nonhealing BALB/c mice, early interleukin-4 (IL-4) can instruct dendritic cells for protective Th1 immunity. ...
Evaluation of Alum-Naltrexone Adjuvant Activity, on Efficacy of Anti-Leishmania Immunization with Autoclaved Leishmania major (MRHO/IR/75/ER) Antigens in BALB/C Mice.
Mice with homologous disruption of the interferon gamma (IFN-gamma) gene on the C57BL/6 background were infected with Leishmania major and the immune response assessed. In contrast to wild-type or heterozygous knockout mice, deficient animals were unable to restrict growth of the parasite and suffered lethal infection over 6-8 wk. Although wild-type and heterozygous littermates developed CD4+ cells that contained transcripts for IFN-gamma and lymphotoxin, typical of T helper type 1 (Th1) cells, the knockout mice developed CD4+ cells that contained transcripts for interleukin 4 (IL-4), IL-5, and IL-13, typical of Th2 cells. ELISPOT assays confirmed the reciprocal patterns of IFN-gamma or IL-4 production by T cells in similar frequencies in the respective groups of mice, and antibody analysis confirmed the presence of Th2-mediated isotype switching in the knockout mice. These data suggest that CD4+ T cells that normally respond to antigens by differentiation to Th1 cells default to the Th2 pathway ...
b,Background,/b, ,i,Leishmania major,/i, is a protozoan parasite with a highly polarised cell shape that depends upon endocytosis and exocytosis from a single area of the plasma membrane, the flagellar pocket. SNAREs (soluble ,i,N,/i,-ethylmaleimide-sensitive factor adaptor proteins receptors) are key components of the intracellular vesicle-mediated transports that take place in all eukaryotic cells. They are membrane-bound proteins that facilitate the docking and fusion of vesicles with organelles. The recent availability of the genome sequence of ,i,L. major,/i, has allowed us to assess the complement of SNAREs in the parasite and to investigate their location in comparison with metazoans. ,b,Results,/b, Bioinformatic searches of the ,i,L. major,/i, genome revealed a total of 27 SNARE domain-containing proteins that could be classified in structural groups by phylogenetic analysis. 25 of these possessed the expected features of functional SNAREs, whereas the other two could represent ...
Leishmanien sind eukaryotische, einzellige Parasiten, die im Darm von Sandmücken persistieren und ihren Lebenszyklus im Säugetier vollenden. Dort leben und proliferieren die Parasiten in einer Vielzahl von professionellen Phagozyten. Sie durchlaufen Zyklen von Replikation, Freisetzung und erneuter Aufnahme in andere Phagozyten des Wirtsorganismus. Bis jetzt war es weitgehend unklar, ob die verschiedenen Phasen und Wirtszellen innerhalb dieser Zyklen die Pathogenproliferation begünstigen oder inhibieren. Dieses Thema hat eine hohe Relevanz, um einerseits das Überleben der Parasiten im Wirtsorganismus, und andererseits die erfolgreiche Induktion einer Immunantwort bei einer Infektion zu verstehen. Um diese Fragestellung auf Zellebene zu adressieren, wurde in der vorliegenden Arbeit ein neuartiger Fluoreszenzprotein-basierter Proliferationsreporter (mKikumeGR) angewendet. Leishmania major (L. major), die diesen photokonvertierbaren Reporter konstitutiv exprimieren, zeigen eine grüne ...
Double-Blind Randomized Efficacy Field Trial of Alum Precipi¬tated Autoclaved Leishmania major (Alum-ALM) Vaccine Mixed With BCG Plus Imiquimod Vs. Placebo Control Group
Zimara, Nicole, Chanyalew, Menberework, Aseffa, Abraham, van Zandbergen, Ger, Lepenies, Bernd, Schmid, Maximilian, Weiss, Richard, Rascle, Anne, Wege, Anja Kathrin, Jantsch, Jonathan, Schatz, Valentin, Brown, Gordon D. and Ritter, Uwe (2018) Dectin-1 Positive Dendritic Cells Expand after Infection with Leishmania major Parasites and Represent Promising Targets for Vaccine Development. Frontiers in Immunology 9 (263), pp. 1-20 ...
INNOVATIVE METHOD FOR CELLULAR GENOME TAGGING USING CELLS OWN REPLICAT PROTEINS TO INCORPORATE MODIFIED DEOXYNUCLEOTIDES Awadelkareem Masaad, Sara Abdelatif, , Mazin Ahmed , , Amna Adil, Moawia.M.Moawia.. Abstracts. Introduction : DNA sequencing lead to revolution in biology and breakthrough in diagnostic medicine and drug development via understanding of different genetic effect on disease manifestation and drug response. This breakthrough was facilitated via discovery of heat stable polymerases that used in thermal cyclers.. Objectives: Innovation of new method for cellular DNA tagging depending on cells own replication proteins to incorporate florescent dNTPS in their genome in various cells.. Material and method: Rhodamine-12-dCTP and Aminoallyl-dUTP-xx-AF488 fluroscent dNTPS along with natural dATP and dGTP. Isolated peripheral lymphocytes, , THP1 cell line , Leishmania major promastigotes, and fungi were incubated in RPMI1640 complete media supplemented with mm of tagged dNTPs for 48 ...
We describe the production of TCR transgenic mice that express an MHC class II-restricted TCR specific for the immunodominant Ag of L. major and demonstrate the capacity of mice that express only this TCR to affect substantial control over the replication of this intracellular protozoan parasite. Leishmania are complex organisms with an estimated 35.5-megabase genome expressing some 10,000 proteins (22). As best determined by protein fractionation and expression screening, the 18-amino acid determinant in the LACK Ag presented by I-Ad represents the only Leishmania-derived Ag recognized by the ABLE T cells (14, 17). The remarkable capacity to establish a healer phenotype despite such drastic reduction in the Th cell repertoire emphasizes the sensitivity of the adaptive immune response to single foreign determinants within pathogens and, further, the inability of Leishmania to escape immune surveillance of this epitope, at least under the conditions used in these experiments. Although control of ...
The sequence and gene group of the ribosomal RNA (rRNA) genes of Leishmania main Friedlin (LmjF) had been decided. Apparently, the rDNA repeat unit contained a duplicated 526 bp fragment on the 3′ finish of the unit with two copies of the LSUepsilon rRNA gene.. Our outcomes steered the presence of solely roughly 24 copies of the rRNA unit per diploid genome in LmjF. Repetitive components (IGSRE) of 63 bp occurred within the intergenic spacer (IGS) between the LSUepsilon and the SSU rRNA genes. Among the many completely different rDNA models, the area containing the IGSRE fluctuated in size from roughly 1.Three to roughly 18 kb.. The transcription initiation website (TIS) of the rRNA unit was localized by primer extension to 1043 bp upstream of the SSU gene and 184 bp downstream of the IGSRE. Sequence comparability amongst a number of species of Leishmania confirmed a excessive diploma of conservation across the TIS. Furthermore, the IGSRE additionally confirmed appreciable similarity between ...
Intracellular parasites of the genus Leishmania generate severe diseases in humans, which are associated with a failure of the infected host to induce a
Leishmaniasis is a global disease found anywhere the temperature is warm enough for the sandfly vector to survive and anywhere that lacks rigorous vector control programs. Twelve million people are infected annually with this parasitic disease. Symptoms range from a minor cutaneous lesion at the bite site caused by dermotropic species such as L. major, to a life-threatening disease with multiple organ involvement, caused by viscerotropic species such as L. infantum. Both species of Leishmania co-occur in multiple countries, leading to the risk of co-infection. Previous research has shown that BALB/c mice first infected with the cutaneous form of leishmaniasis, followed by later infection with the visceral form of the disease, show increased disease severity. My research has focused on exploring how antibodies can be used to measure this disease exacerbation. Studies have shown that there is a strong association between L. major specific antibodies and increased disease upon secondary infection with L.
Belkaid (2003) has shown that IL-10 plays an essential role in L. major persistence in genetically resistant C57BL/6 mice after spontaneous healing of their lesions. They have demonstrated that a sterile cure was achieved in IL-10−/− mice but not in IL-10-sufficient mice. This requirement for IL-10 in establishing latency was determined in mice infected either by intradermal injection of L. major metacyclic promastigotes or by exposure of the skin to infected sandflies that mimic natural infection. Most importantly, IL-10-sufficient C57BL/6 mice treated transiently during the chronic phase with anti-IL-10 receptor antibodies achieved a sterile cure, suggesting that IL-10 was actively involved in preventing complete parasite elimination even in the presence of a Th1 response.. A role for Treg in the pathogenesis of Leishmania infection is not restricted to resistant strains. In susceptible BALB/c mice, cells that suppress L. major protective immunity have been shown to belong to an IL-4- and ...
PubMed comprises more than 30 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
Schistosomiasis is a major parasitic disease and considerable research goes into developing drugs to combat a parasitic infection. A new study suggests an ecological answer might be more effective: using prawns.
PubMed comprises more than 30 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
We have previously shown that mice lacking inducible NO synthase are markedly more susceptible to Leishmania major infection but developed a significantly enhanced Th1 cell response compared with wild-type mice. Furthermore, at high concentrations, NO inhibited IL-12 synthesis by activated macrophages, thereby indirectly suppressing the expansion of Th1 cells. We report here that at low concentrations, NO selectively enhanced the induction of Th1 cells and had no effect on Th2 cells. NO exerted this effect in synergy with IL-12 during Th1 cell differentiation and had no effect on fully committed Th1 cells. NO appears to affect CD4+ T cells directly and not at the antigen-presenting cells. These results therefore provide an additional pathway by which NO modulates the immune response and contributes to the homeostasis of the immune system.. ...
Lamour, SD; Veselkov, KA; Posma, JM; Giraud, E; Rogers, ME; Croft, S; Marchesi, JR; Holmes, E; Seifert, K; Saric, J; (2014) Metabolic, Immune, and Gut Microbial Signals Mount a Systems Response to Leishmania major Infection. Journal of proteome research, 14 (1). pp. 318-329. ISSN 1535-3893 DOI: 10.1021/pr5008202 Full text not available from this repository ...
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We purified poly(A)+ mRNA from the spleen and lymph nodes at designated times after infection with Leishmania major in genetically susceptible BALB/c and resist
iiii writes According to a Yahoo News story, half of the worlds human population is infected with Toxoplasma, a parasite shown to alter the brain function of rats, inducing them into behavior that benefits the parasite but is suicidal for the rat. So what affect does it have on humans? Article c...
iiii writes According to a Yahoo News story, half of the worlds human population is infected with Toxoplasma, a parasite shown to alter the brain function of rats, inducing them into behavior that benefits the parasite but is suicidal for the rat. So what affect does it have on humans? Article c...
iiii writes According to a Yahoo News story, half of the worlds human population is infected with Toxoplasma, a parasite shown to alter the brain function of rats, inducing them into behavior that benefits the parasite but is suicidal for the rat. So what affect does it have on humans? Article c...
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The cutoff value for HRR was taken as 0.61, and the cutoff value for LMR was taken as 3.28. Patients were divided into low HRR, high HRR, low LMR, and high LMR groups. OS of the patients with low HRR was found lower compared with high HRR (36.7 months for low HRR and 53.2 months for high HRR, p , 0.001). Also, OS was found lower in the low LMR group (39.4 months for low LMR and 51.7 months for high LMR, p = 0.016). On multivariate analysis, low HRR and low LMR were predictive factors of OS (hazard ratio (HR) 2.08, 95% confidence intervals (CI) 1.31-3.03, and p = 0.002 for low HRR; HR 1.47, 95% CI 0.92-2.29, and p = 0.010 for low LMR). ...
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CD4+ T helper 1 effector cells (Th1EFF) are critical for protective immunity against pathogens that employ phagocytic cells as hosts for replication and persistence. Despite this knowledge, the degree to which protective Th1EFF cells are reliant on the time at which they interact with infected phagocytic cells to mediate their protective effect is not fully understood. Employing the Leishmania major model organism of phagocyte infection, we report that Th1 TEFF cells must deliver effector function during an acute window post-challenge in order to mediate protection. Rapid CD4 + Th1 effector function was required for Th1EFF cells to capitalize on an early activation window in order to prevent the establishment of a pathogen niche, as evidenced by altered recruitment, gene expression and functional capacity of both innate and adaptive immune cells. Delayed Th1EFF availability was unable to overcome parasite niche establishment and mediate efficient protection, even when Leishmania-antigen specific ...
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Plant extracts from Warburgia ugandensis Sprague (Family: Canellaceae), Psiadia punctulata Vatke (Family: Compositae) and Chasmanthera dependens Hoschst (Family: Menispermaceae) were tested for activity on Leishmania major promastigotes (Strain IDU/KE/83 = NLB-144) and infected macrophages in vitro. Plants were collected from Baringo district, dried, extracted, weighed and tested for antileishmanial activity. Serial dilutions of the crude extracts were assayed for their activity against Leishmania major in cell free cultures and in infected macrophages in vitro. Inhibitory concentrations and levels of cytotoxicity were determined. Warburgia ugandensis, Psiadia punctulata and Chasmanthera dependens had an IC(50) of 1.114 mg/ml, 2.216 mg/ml and 4.648 mg/ml, respectively. The cytotoxicity of the drugs on BALB/c peritoneal macrophage cells was insignificant as compared to the highly toxic drug of choice Pentostam(®). The supernatants from control and Leishmania infected macrophages were analyzed ...
The effect of castor oil plant seed oil fractionally extracted with diethyl-ether and the aqueous extracts of its leaves was tested in vitro on Leishmania major (Yorkimov and Schokor, 1913) promastigotes and in vivo on Leishmania major lesions in inbred BALB/c mice. Four experimental groups of 35 female mice each were used namely seed oil group (oil topically applied); Aqueous leaf extract group (extract administered intraperitoneally); PentostamP (sodium stiboglnconate) group (drug administered intraperitoneally) and a control group (untreated infected mice). Before infection, footpad measurements were taken by measuring the left hind footpad (LHFD) and _the contralateral right hind footpad (RHFD). All the mice were infected intradermally with L. major stationary primary phase metacyclic promastigotes at a dosage of 1 x 106 per 10111on the left hind footpad of every mouse and lesion sizes measured weekly at 7 day intervals. Treatment was commenced 30 days post-infection. Within this time ...
Background and objectives: Leishmaniasis is caused by the genus Leishmania. Medications such as antimony compounds for the treatment of the disease are associated with limitations along with several side effects and disease recurrence; thus, evaluation of natural compounds with history of antimicrobial properties such as Pleurotus ostreatus, is of a great importance. The purpose of this study was to evaluate the apoptotic and leishmanicidal effects of Pleurotus ostreatus alcoholic extract on Leishmania major promastigote in vitro. Methods: Different concentrations of Pleurotus ostreatus extract (50, 100, 150, 200 and 250 μg/mL) were tested at 6, 24, 48 and 72 h on Leishmania major (MRHO/IR/75/ER) promastigotes. The leishmanicidal effects were determined using MTT [3-(4,5-dimethyl thiazolyl- 2)-2,5-diphenyle tetrazolium bromide] assay. Also, apoptosis induction was measured by flow cytometry and DNA fragmentation analysis. Results:The MTT results showed that leishmanicidal effect of Pleurotus
Leishmania major (L. major) is a protozoan parasite that causes cutaneous leishmaniasis. About 12 million people are currently infected with an annual incidence of 1.3 million cases. The purpose of this study was to synthesize a small library of novel thiophene derivatives, and evaluate its parasitic activity, and potential mechanism of action (MOA). We developed a structure-activity relationship (SAR) study of the thiophene molecule 5A. Overall, eight thiophene derivatives of 5A were synthesized and purified by silica gel column chromatography. Of these eight analogs, the molecule 5D showed the highest in vitro activity against Leishmania major promastigotes (EC50 0.09 ± 0.02 µM), with an inhibition of the proliferation of intracellular amastigotes higher than 75% at only 0.63 µM and an excellent selective index. Moreover, the effect of 5D on L. major promastigotes was associated with generation of reactive oxygen species (ROS), and in silico docking studies suggested that 5D may play a role in
Autophagy participates in innate immunity by eliminating intracellular pathogens. Consequently, numerous microorganisms have developed strategies to impair the autophagic machinery in phagocytes. In the current study, interactions between Leishmania major (L. m.) and the autophagic machinery of bone marrow-derived macrophages (BMDM) were analyzed. BMDM were generated from BALB/c mice, and the cells were infected with L. m. promastigotes. Transmission electron microscopy (TEM) and electron tomography were used to investigate the ultrastructure of BMDM and the intracellular parasites. Affymetrix® chip analyses were conducted to identify autophagy-related messenger RNAs (mRNAs) and microRNAs (miRNAs). The protein expression levels of autophagy related 5 (ATG5), BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3), cathepsin E (CTSE), mechanistic target of rapamycin (MTOR), microtubule-associated proteins 1A/1B light chain 3B (LC3B), and ubiquitin (UB) were investigated through western blot
Autophagy participates in innate immunity by eliminating intracellular pathogens. Consequently, numerous microorganisms have developed strategies to impair the autophagic machinery in phagocytes. In the current study, interactions between Leishmania major (L. m.) and the autophagic machinery of bone marrow-derived macrophages (BMDM) were analyzed. BMDM were generated from BALB/c mice, and the cells were infected with L. m. promastigotes. Transmission electron microscopy (TEM) and electron tomography were used to investigate the ultrastructure of BMDM and the intracellular parasites. Affymetrix® chip analyses were conducted to identify autophagy-related messenger RNAs (mRNAs) and microRNAs (miRNAs). The protein expression levels of autophagy related 5 (ATG5), BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3), cathepsin E (CTSE), mechanistic target of rapamycin (MTOR), microtubule-associated proteins 1A/1B light chain 3B (LC3B), and ubiquitin (UB) were investigated through western blot
Aalami-Harandi, R. and Karamali, M. and Asemi, Z. (2015) The favorable effects of garlic intake on metabolic profiles, hs-CRP, biomarkers of oxidative stress and pregnancy outcomes in pregnant women at risk for pre-eclampsia: Randomized, double-blind, placebo-controlled trial. Journal of Maternal-Fetal and Neonatal Medicine, 28 (17). pp. 2020-2027. Abbasi, A. and Delavari, M. and Arbabi, M. and Arj, A. and Doroodgar, M. and Taherian, A.A. and Doroodgar, M. and Nikoueinejad, H. and Pourbabaee, M. and Doroodgar, A. (2015) The effect of tamoxifen on the growth of Leishmania major promastigotes and amastigotes in vitro. Feyz Journal of Kashan University of Medical Sciences, 19. Abdal, M. and Masoudi Alavi, N. and Adib-Hajbaghery, M. (2015) Clinical Self-Efficacy in Senior Nursing Students: A Mixed- Methods Study. Nurs Midwifery Stud, 4 (3). e29143. Abdoli, A. and Arbabi, M. and Dalimi, A. and Pirestani, M. (2015) Molecular detection of Neospora caninum in house sparrows (Passer domesticus) in Iran. ...
p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.,/p> ,p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.,/p> ,p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).,/p> ,p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x,sup>64,/sup> + x,sup>4,/sup> + x,sup>3,/sup> + x + 1. The algorithm is described in the ISO 3309 standard. ,/p> ,p class=publication>Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.,br /> ,strong>Cyclic redundancy and other checksums,/strong>,br /> ,a href=http://www.nrbook.com/b/bookcpdf.php>Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993),/a>),/p> Checksum:i ...
Unicellular eukaryotic pathogen Leishmania donovani, an intra-macrophage protozoan parasite, on exposure to phagolysosome conditions (PC) of mammalian macrophages, show increased cAMP level and cAMP-dependent protein kinase A (PKA) resulting in resistance to macrophage oxidative burst. In order to have a comprehensive understanding of cAMP signaling and their contribution to infectivity, studies were carried out on all the enzymes associated with cAMP metabolism such as adenylate cyclase, phosphodiesterase, pyrophosphatase and the regulatory and catalytic subunits of PKA. This chapter deals in detail the contribution of these components of cAMP signaling in cAMP homeostasis of the parasite as well as their role on successful host-parasite interaction leading to intracellular parasite survival and establishment of infection. Finally, a discussion is made about how these observations might be exploited for developing drug candidates targeting parasite specific features.
Beverleys laboratory has focused on the introduction of modern concepts of microbial pathogenesis and molecular genetics into the study of protozoan parasites of humans, primarily the trypanosomatid Leishmania. Studies of drug resistance, extra-chromosomal gene amplification and transcription led to the development of the first transfection system enabling both forward and reverse genetics, and have been widely adopted in the field. Beverleys lab has put them to use in dissecting the role of major parasite surface glycoconjugates in parasite survival in both mammalian and insect hosts, immune recognition and evasion, identification of novel pathways of folate and pteridine metabolic amenable to chemotherapeutic attack, and the use of genetically modified parasites as safe live vaccine lines. Modified parasites also provide therapeutic opportunities for use as live nanoplatforms for delivery of therapeutic proteins, an approach pursued by a company Beverley co-founded. Leishmania genetic ...
To control internal parasites, its best to know your enemy. While internal parasites are the same the country over, they play the game differently from North to South.
From our locations in Pipestone, Minnesota; Independence, Iowa; Rensselaer Indiana; and Ottumwa, Iowa, we provide convenient services to our customers. In every instance, our clients know we truly have the best interest of their animal in mind. We use our combined professional expertise and team approach to provide our clients with the best services and products available.
From our locations in Pipestone, Minnesota; Independence, Iowa; Rensselaer Indiana; and Ottumwa, Iowa, we provide convenient services to our customers. In every instance, our clients know we truly have the best interest of their animal in mind. We use our combined professional expertise and team approach to provide our clients with the best services and products available.
Leishmania are protozoan parasites that fall under the genus Leishmania and the order Kinetoplastida. This parasite causes the vector borne disease known as leishmaniasis.
Leishmania parasites hijack macrophages turning them against their human hosts. New insights reveal how novel therapies can reverse this effect despite the parasites complex resistance.
Leishmania parasites and purified GP63 inhibit generation of ROS induced by inflammasome activator.(A and B) PMA-differentiated THP-1 cells (0.1x106 cells/100
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Leishmania is a fascinating parasite because it actively lives in our immune cells. First it must be injested by a sand fly, which feeds on human blood like a mosquito. Once inside the fly, it changes form and creates a very strange substance called promastigote secretory gel. The gel serves a very important purpose - it blockades the gut of the sand fly. For the fly to feed during its next meal, it must throw up this gel, which, conveniently, carries the parasites into the human host. There, the parasites wriggle their way inside our macrophages and reproduce. In short, they takes our best anti-parasite weaponry and turn them into comfy homes. How it does this has been a question of scientists for years ...
First, surely youll want to get your moneys worth, and youll want to know all about taking care of your new baby! That precious little free puppy needs to be kept free of harmful parasites, and he or she also needs protection from contagious illness. A veterinarian can recommend the appropriate treatments to control parasites and also an immunization schedule. Be sure to discuss both the puppy medical care and the adult requirements as well, with your veterinarian. Ensure you also ask questions about whatever you dont understand ...
Lately I have been wondering why there is so many cats on the internet. Now I understand - its their latest attempt at world domination. Introducing… Toxoplasmosis What would you say if I told you that cats are spreading a mind control parasite that lives in your brain and modifies your behavior. What if I […]. ...
Currently, more than 1 billion people are living in endemic areas at risk of infection with Leishmania, the agent of leishmaniases, with...
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We provide here four lines of evidence that an accumulation of mutations during a range expansion leads to a decrease in fitness. We first observe that the ability to grow on agar of HMR lines significantly decreases, on average by 33%, over time, whereas that of LMR lines remains constant (Figure 3). This latter constancy is not due to the smallest number of LMR lines, as a similarly small sample of HMR lines shows significantly reduced growth after 39 days. Second, direct competition of evolved strains with ancestral strains during a radial expansion (exactly similar to what occurs in our experimental setup) reveals that 9/10 HMR lines and 7/10 LMR lines are outcompeted by the ancestral line (Figure 4A). Third, a linear competition experiment different from the evolution condition, but allowing us to directly estimate the fitness of the evolved strains relative to that of their ancestor on the expansion front, shows on average a significant 19% fitness reduction for HMR lines, and a ...