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https://www.readbyqxmd.com/read/28647427/first-molecular-detection-of-leishmania-infantum-in-sergentomyia-minuta-diptera-psychodidae-in-alentejo-southern-portugal
#1
S Pereira, D Pita-Pereira, T Araujo-Pereira, C Britto, T Costa-Rego, J Ferrolho, M Vilhena, E F Rangel, M L Vilela, M O Afonso
Protozoan parasites, such as Leishmania spp., are the causative agents of many insect-borne infectious diseases with medical and veterinary importance. Leishmaniasis, caused by Leishmania spp., is transmitted by female phlebotomine sand flies. In the Alentejo region of Portugal, located at the north of Algarve, cases of human and canine leishmaniasis caused by Leishmania infantum have been notified. However, no recent studies regarding the sand fly fauna in the region are available. We therefore aimed to explore the phlebotomine sand fly species found in both, Évora and Beja Districts, to gain an insight about the leishmaniasis epidemiology in these areas...
June 21, 2017: Acta Tropica
https://www.readbyqxmd.com/read/28647378/leishmaniasis-drug-discovery-recent-progress-and-challenges-in-assay-development
#2
REVIEW
Bilal Zulfiqar, Todd B Shelper, Vicky M Avery
Leishmaniasis, caused by the trypanosomatid protozoan Leishmania, is endemic in 98 countries worldwide, with morbidity and mortality increasing daily. Despite available drugs, leishmaniasis faces the challenge of emerging resistance and toxicity concerns for current drug regimes. Identification of anti-leishmanial compounds representing new chemistry and novel mechanisms of action is essential to populate the drug discovery pipeline. The in vitro assays currently available have shown poor translational outcomes, with high compound attrition rates...
June 21, 2017: Drug Discovery Today
https://www.readbyqxmd.com/read/28647347/differential-activation-of-human-keratinocytes-by-leishmania-spp-causing-localized-or-disseminated-disease
#3
Breanna M Scorza, Mark A Wacker, Kelly Messingham, Peter Kim, Aloysius Klingelhutz, Janet Fairley, Mary E Wilson
All Leishmania spp. parasites are introduced into mammalian skin through a sand fly bite, but different species cause distinct clinical outcomes. Mouse studies suggest early responses are critical determinants of subsequent adaptive immunity in leishmaniasis, yet few studies address the role of keratinocytes, the most abundant cell in the epidermis. We hypothesized Leishmania infection causes keratinocytes to produce immunomodulatory factors that influence the outcome of infection. Incubation of primary or immortalized human keratinocytes with Leishmania infantum or Leishmania major, which cause visceral or cutaneous leishmaniasis, respectively, elicited dramatically different responses...
June 21, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28646156/mahanine-exerts-in-vitro-and-in-vivo-antileishmanial-activity-by-modulation-of-redox-homeostasis
#4
Saptarshi Roy, Devawati Dutta, Eswara M Satyavarapu, Pawan K Yadav, Chhabinath Mandal, Susanta Kar, Chitra Mandal
Earlier we have established a carbazole alkaloid (mahanine) isolated from an Indian edible medicinal plant as an anticancer agent with minimal effect on normal cells. Here we report for the first time that mahanine-treated drug resistant and sensitive virulent Leishmania donovani promastigotes underwent apoptosis through phosphatidylserine externalization, DNA fragmentation and cell cycle arrest. An early induction of reactive oxygen species (ROS) suggests that the mahanine-induced apoptosis was mediated by oxidative stress...
June 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28645659/synthesis-in-vitro-and-in-vivo-giardicidal-activity-of-nitrothiazole-nsaid-chimeras-displaying-broad-antiprotozoal-spectrum
#5
Blanca Colín-Lozano, Ismael León-Rivera, Manuel Jesús Chan-Bacab, Benjamín Otto Ortega-Morales, Rosa Moo-Puc, Vanessa López-Guerrero, Emanuel Hernández-Núñez, Raúl Argüello-Garcia, Thomas Scior, Elizabeth Barbosa-Cabrera, Gabriel Navarrete-Vázquez
We designed and synthesized five new 5-nitrothiazole-NSAID chimeras as analogues of nitazoxanide, using a DCC-activated amidation. Compounds 1-5 were tested in vitro against a panel of five protozoa: 2 amitochondriates (Giardia intestinalis, Trichomonas vaginalis) and 3 kinetoplastids (Leishmania mexicana, Leishmania amazonensis and Trypanosoma cruzi). All chimeras showed broad spectrum and potent antiprotozoal activities, with IC50 values ranging from the low micromolar to nanomolar order. Compounds 1-5 were even more active than metronidazole and nitazoxanide, two marketed first-line drugs against giardiasis...
May 24, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28645315/role-of-inhibitors-of-serine-peptidases-in-protecting-leishmania-donovani-against-the-hydrolytic-peptidases-of-sand-fly-midgut
#6
Sudha Verma, Sushmita Das, Abhishek Mandal, Md Yousuf Ansari, Sujata Kumari, Rani Mansuri, Ajay Kumar, Ruby Singh, Savita Saini, Kumar Abhishek, Vijay Kumar, Ganesh Chandra Sahoo, Pradeep Das
BACKGROUND: In vector-borne diseases such as leishmaniasis, the sand fly midgut is considered to be an important site for vector-parasite interaction. Digestive enzymes including serine peptidases such as trypsin and chymotrypsin, which are secreted in the midgut are one of the obstacles for Leishmania in establishing a successful infection. The presence of some natural inhibitors of serine peptidases (ISPs) has recently been reported in Leishmania. In the present study, we deciphered the role of these ISPs in the survival of Leishmania donovani in the hostile sand fly midgut environment...
June 23, 2017: Parasites & Vectors
https://www.readbyqxmd.com/read/28643086/gallic-and-ellagic-acids-two-natural-immunomodulator-compounds-solve-infection-of-macrophages-by-leishmania-major
#7
Michel Muálem de Moraes Alves, Lucas Moreira Brito, Adriana Cunha Souza, Bárbara Cristina Silva Holanda Queiroz, Thaynara Parente de Carvalho, Joilson Ferreira Batista, Jéssica Sara de Sousa Macêdo Oliveira, Ivete Lopes de Mendonça, Silvéria Regina de Sousa Lira, Mariana Helena Chaves, Juan Carlos Ramos Gonçalves, Sabrina Maria Portela Carneiro, Daniel Dias Rufino Arcanjo, Fernando Aécio de Amorim Carvalho
Leishmaniasis is a complex of parasitic protozoan diseases caused by more than 20 different species of parasites from Leishmania genus. Conventional treatments are high costly, and promote a sort of side effects. Besides, protozoan resistance to treatments has been reported. Natural products have been investigated as a source of new therapeutic alternatives, not only acting directly against the parasite but also being able to synergistically act on the host immune system in order to control parasitemia. Gallic acid (GA) and ellagic acid (EA) are plant-derived phenolic compounds which are able to induce antiinflammatory, gastroprotective, and anticarcinogenic activities...
June 22, 2017: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/28642199/chemical-profile-and-anti-leishmanial-activity-of-three-ecuadorian-propolis-samples-from-quito-guayaquil-and-cotacachi-regions
#8
Osmany Cuesta-Rubio, Mercedes Campo Fernández, Ingrid Márquez Hernández, Carmita Gladys Jaramillo Jaramillo, Victor Hugo González, Rodny Montes De Oca Porto, David Marrero Delange, Lianet Monzote Fidalgo, Anna Lisa Piccinelli, Luca Campone, Luca Rastrelli
Three propolis samples were collected from different regions of Ecuador (Quito, Guayaquil and Cotacachi) and their methanolic extracts were prepared. Preliminary information supplied by TLC and NMR data, allowed us to define two main types of propolis: Cotacachi propoli sample (CPS), rich in flavonoids and Quito and Guayaquil samples (QPS and GPS) containing triterpenic alcohols and acetyl triterpenes as the main constituents. Two different approaches based on RP-HPLC preparative procedure and NMR structural determination (CPS) and GC-MS analysis (QPS and GPS) were successfully used for the chemical characterization of their major compounds...
June 19, 2017: Fitoterapia
https://www.readbyqxmd.com/read/28641584/crotoxin-stimulates-an-m1-activation-profile-in-murine-macrophages-during-leishmania-amazonensis-infection
#9
L H S Farias, A P D Rodrigues, E C Coêlho, M F Santos, S C Sampaio, E O Silva
American tegumentary leishmaniasis is caused by different species of Leishmania. This protozoan employs several mechanisms to subvert the microbicidal activity of macrophages and, given the limited efficacy of current therapies, the development of alternative treatments is essential. Animal venoms are known to exhibit a variety of pharmacological activities, including antiparasitic effects. Crotoxin (CTX) is the main component of Crotalus durissus terrificus venom, and it has several biological effects. Nevertheless, there is no report of CTX activity during macrophage - Leishmania interactions...
June 23, 2017: Parasitology
https://www.readbyqxmd.com/read/28641558/bis-2-aminoimidazolines-and-bisguanidines-synthetic-approaches-antiparasitic-activity-and-dna-binding-properties
#10
Christophe Dardonville, J Jonathan Nué Martínez
BACKGROUND: Parasitic diseases caused by protozoan parasites of the genus Trypanosoma and Plasmodium cause some of the deadliest and disabling human infections in tropical and subtropical areas. Diphenyl-based bis(2-phenylimino)imidazolidines and bisguanidines are extremely potent antiparasitic agents against Trypanosoma brucei (etiological agent of African trypanosomiasis) and Plasmodium falciparum (etiological agent of severe malaria). Many of these compounds are also curative in mouse models of stage 1 African trypanosomiasis representing promising leads for the development of antitrypanosomal drugs...
June 22, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28638689/visceral-leishmaniasis-in-a-patient-with-rheumatoid-arthritis-undergoing-treatment-with-methotrexate-case-report-and-review-of-the-literature
#11
Kyriakos Trigkidis, Eleni Geladari, Evangelos Kokkinakis, Natalia Vallianou
There is growing concern regarding the emergence of visceral leishmaniasis (VL), a disseminated parasitic disease caused by protozoa of the genus Leishmania, as an opportunistic infection in immunocompromised patients. This association has been principally studied in the context of human immunodeficiency virus infection, but VL has also been reported in patients undergoing treatment with immunosuppressive medication for various indications. Here a case of VL in a patient with rheumatoid arthritis undergoing treatment with methotrexate and corticosteroid is presented...
June 2017: European Journal of Rheumatology
https://www.readbyqxmd.com/read/28638238/a-computational-methodology-to-overcome-the-challenges-associated-with-the-search-for-specific-enzyme-targets-to-develop-drugs-against-leishmania-major
#12
Larissa Catharina, Carlyle Ribeiro Lima, Alexander Franca, Ana Carolina Ramos Guimarães, Marcelo Alves-Ferreira, Pierre Tuffery, Philippe Derreumaux, Nicolas Carels
We present an approach for detecting enzymes that are specific of Leishmania major compared with Homo sapiens and provide targets that may assist research in drug development. This approach is based on traditional techniques of sequence homology comparison by similarity search and Markov modeling; it integrates the characterization of enzymatic functionality, secondary and tertiary protein structures, protein domain architecture, and metabolic environment. From 67 enzymes represented by 42 enzymatic activities classified by AnEnPi (Analogous Enzymes Pipeline) as specific for L major compared with H sapiens, only 40 (23 Enzyme Commission [EC] numbers) could actually be considered as strictly specific of L major and 27 enzymes (19 EC numbers) were disregarded for having ambiguous homologies or analogies with H sapiens...
2017: Bioinformatics and Biology Insights
https://www.readbyqxmd.com/read/28635366/redox-biology-of-leishmania-and-macrophage-targeted-nanoparticles-for-therapy
#13
Hafiz Shoaib Sarwar, Sohail Akhtar, Muhammad Farhan Sohail, Zaeema Naveed, Muhammad Rafay, Akhtar Nadhman, Masoom Yasinzai, Gul Shahnaz
Intramacrophage parasite 'Leishmania' has developed various mechanisms for proficient uptake into macrophages and phagosome regulation to avoid macrophage's oxidative burst induced by peroxide, hydroxyl radical, hypochlorous acid and peroxynitrite production. One major barrier for impairing the accession of old fashioned anti-Leishmanial drugs is intrinsic incapability to pass through cell membranes and limiting their abilities to ultimately destroy intracellular pathogens. Receptor-mediated targeted drug delivery to the macrophages by using nanoparticles emerges as promising strategy to improve therapeutic efficacy of old-fashioned drug...
June 21, 2017: Nanomedicine
https://www.readbyqxmd.com/read/28634775/hydrophilic-acylated-surface-protein-a-haspa-of-leishmania-donovani-expression-purification-and-biophysico-chemical-characterization
#14
Manoj Kumar, Kishu Ranjan, Vijay Singh, Chandramani Pathak, Anju Pappachan, Desh Deepak Singh
Hydrophilic acylated surface proteins (HASPs) are acidic surface proteins which get localized on the surface of Leishmania parasite during infective stages through a "non-classical" pathway. In this study, we report the heterologous expression and purification of Leishmania donovani HASPA (r-LdHASPA) in E. coli system and its partial characterization. The structural aspects of the purified protein were analyzed using CD spectroscopy and modeling studies which indicate that r-LdHASPA consists of random coils...
June 21, 2017: Protein Journal
https://www.readbyqxmd.com/read/28632488/vector-borne-pathogens-in-stray-dogs-in-northeastern-turkey
#15
Esin Guven, Hamza Avcioglu, Seyda Cengiz, Armagan Hayirli
This experiment was carried out to attain prevalence and molecular characterization of pathogens causing canine vector-borne diseases (CVBDs) including babesiosis, hepatozoonosis, leishmaniasis, filariosis (Dirofilaria immitis, Dirofilaria repens, and Acanthocheilonema reconditum), ehrlichiosis (Ehrlichia canis), and anaplasmosis (Anaplasma platys) in stray dogs. The study material consisted of 133 asymptomatic female (n = 96) and male (n = 37) stray dogs (≤1 year old, n = 16 and 1-6 years old, n = 117) housed in the Animal Care and Rehabilitation Center, Erzurum, Northeastern Turkey...
June 20, 2017: Vector Borne and Zoonotic Diseases
https://www.readbyqxmd.com/read/28630182/study-of-biodistribution-and-in-vivo-anti-leishmanial-activity-of-a-distigmasterylhemisuccinoyl-glycero-phosphocholine-liposome-intercalated-amphotericin-b
#16
Maryam Iman, Zhaohua Huang, Seyedeh Hoda Alavizadeh, Francis C Szoka, Mahmoud R Jaafari
Distigmasterylhemisuccinoyl-sn-glycero-3- phosphocholine (DSHemsPC) is a new lipid in which two molecules of stigmasterol (an inexpensive plant sterol) are covalently linked via a succinic acid to glycerophosphocholine. Our previous study revealed that a liposome-intercalated Amphotericin B prepared from DSHemsPC (DSHemsPC-Lip-AmB) possess excellent colloidal properties and in vitro antifungal and anti-leishmanial activity similar to AmBisome™. The aim of this study was to determine biodistribution and evaluate the anti-leishmanial effects of DSHemsPC-Lip-AmB in Leishmania major-infected BALB/c mice...
June 19, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28629935/a-dicre-recombinase-based-system-for-inducible-expression-in-leishmania-major
#17
Renato E R S Santos, Gabriel L A Silva, Elaine V Santos, Samuel M Duncan, Jeremy C Mottram, Jeziel D Damasceno, Luiz R O Tosi
Here we present the establishment of an inducible system based on the dimerizable Cre recombinase (DiCre) for controlled gene expression in the protozoan parasite Leishmania. Rapamycin-induced DiCre activation promoted efficient flipping and expression of gene products in a time and dose-dependent manner. The DiCre flipping activity induced the expression of target genes from both integrated and episomal contexts broadening the applicability of the system. We validated the system by inducing the expression of both full length and truncated forms of the checkpoint protein Rad9, which revealed that the highly divergent C-terminal domain of Rad9 is necessary for proper subcellular localization...
June 16, 2017: Molecular and Biochemical Parasitology
https://www.readbyqxmd.com/read/28629934/recent-advances-in-leishmania-reverse-genetics-manipulating-a-manipulative-parasite
#18
REVIEW
Samuel M Duncan, Nathaniel G Jones, Jeremy C Mottram
In this review we describe the expanding repertoire of molecular tools with which to study gene function in Leishmania. Specifically we review the tools available for studying functions of essential genes, such as plasmid shuffle and DiCre, as well as the rapidly expanding portfolio of available CRISPR/Cas9 approaches for large scale gene knockout and endogenous tagging. We include detail on approaches that allow the direct manipulation of RNA using RNAi and protein levels via Tet or DiCre induced overexpression and destabilization domain mediated degradation...
June 16, 2017: Molecular and Biochemical Parasitology
https://www.readbyqxmd.com/read/28629727/antigenicity-of-phage-clones-and-their-synthetic-peptides-for-the-serodiagnosis-of-canine-and-human-visceral-leishmaniasis
#19
Lourena E Costa, Beatriz C S Salles, Thaís T O Santos, Fernanda F Ramos, Mariana P Lima, Mayara I S Lima, Áquila S B Portela, Miguel A Chávez-Fumagalli, Mariana C Duarte, Daniel Menezes-Souza, Ricardo A Machado-de-Ávila, Julia A G Silveira, Danielle F Magalhães-Soares, Luiz Ricardo Goulart, Eduardo A F Coelho
In the Americas, Brazil is responsible by 90% of the cases registered of visceral leishmaniasis (VL), and Leishmania infantum is the most common parasite species responsible by disease in Brazilian dogs and humans. A precise diagnosis may allow to a faster and more effective treatment against the disease, which increases the possibility of cure, as well as to induce less toxic effects, due to a lower time exposition for the chemotherapeutics. In a previous study, two L. infantum mimotopes, B10 and C01 clones, were recognized by antibodies in VL dogs sera by a phage display technology, and were well-successfully evaluated as vaccine candidates against visceral and tegumentary leishmaniasis...
June 16, 2017: Microbial Pathogenesis
https://www.readbyqxmd.com/read/28629171/cutaneous-manifestations-of-human-and-murine-leishmaniasis
#20
REVIEW
Breanna M Scorza, Edgar M Carvalho, Mary E Wilson
The leishmaniases are diseases caused by pathogenic protozoan parasites of the genus Leishmania. Infections are initiated when a sand fly vector inoculates Leishmania parasites into the skin of a mammalian host. Leishmania causes a spectrum of inflammatory cutaneous disease manifestations. The type of cutaneous pathology is determined in part by the infecting Leishmania species, but also by a combination of inflammatory and anti-inflammatory host immune response factors resulting in different clinical outcomes...
June 18, 2017: International Journal of Molecular Sciences
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