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https://www.readbyqxmd.com/read/27912879/how-do-the-alkaloids-emetine-and-homoharringtonine-kill-trypanosomes-an-insight-into-their-molecular-modes-of-action
#1
Sonja Krstin, Tamer Mohamed, Xiaojuan Wang, Michael Wink
BACKGROUND: Although Trypanosoma brucei causes deadly sleeping sickness, the number of the registered medications is rather limited. Some plant alkaloids are potent trypanocidal agents. PURPOSE: In this study, we wanted to elucidate the molecular modes of trypanocidal activity of the alkaloids emetine and homoharringtonine against Trypanosoma brucei brucei. METHODS: We investigated the activity of both alkaloids regarding growth recovery from alkaloid-induced stress...
December 15, 2016: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/27884172/spatial-distribution-and-trypanosome-infection-of-tsetse-flies-in-the-sleeping-sickness-focus-of-zimbabwe-in-hurungwe-district
#2
William Shereni, Neil E Anderson, Learnmore Nyakupinda, Giuliano Cecchi
BACKGROUND: In Zimbabwe, cases of human African trypanosomiasis (HAT) are caused by the unicellular protozoan Trypanosoma brucei, sub-species T. b. rhodesiense. They are reported from the tsetse-infested area in the northern part of the country, broadly corresponding to the valley of the Zambezi River. Tsetse-transmitted trypanosomes, in particular T. congolense and T. vivax, also cause morbidity and mortality in livestock, thus generating poverty and food insecurity. Two species of tsetse fly, Glossina morsistans morsitans and G...
November 25, 2016: Parasites & Vectors
https://www.readbyqxmd.com/read/27876111/the-remarkable-dr-robertson
#3
Tansy C Hammarton
Muriel Robertson (1883-1973) was a pioneering protozoologist who made a staggering number of important contributions to the fields of parasitology, bacteriology and immunology during her career, which spanned nearly 60 years. These contributions were all the more remarkable given the scientific and social times in which she worked. While Muriel is perhaps best known for her work on the life cycle and transmission of the African trypanosome, Trypanosoma brucei, which she carried out in Uganda at the height of a major Sleeping Sickness epidemic, her work on the Clostridia during the First and Second World Wars made significant contributions to the understanding of anaerobes and to the development of anti-toxoid vaccines, and her work on the immunology of Trichomonas foetus infections in cattle, carried out in collaboration with the veterinarian W...
November 23, 2016: Parasitology
https://www.readbyqxmd.com/read/27870653/apolipoprotein-l1-and-apolipoprotein-a-iv-and-their-association-with-kidney-function
#4
Florian Kronenberg
PURPOSE OF REVIEW: Chronic kidney disease (CKD) is a common disease with an estimated prevalence of 10-12%. There are pronounced differences between ethnicities with a 3-fold to 4-fold higher lifetime risk for end-stage kidney disease in African Americans compared to European Americans. The purpose of this review was to discuss recent findings on two apolipoproteins (apolipoprotein L1 and A-IV) in the context of kidney disease and kidney function. RECENT FINDINGS: The observation that certain apolipoprotein L1 risk genotypes that are only present in African Americans might explain a major fraction of the ethnic differences for nondiabetic CKD has set the stage for this otherwise under-researched apolipoprotein...
November 18, 2016: Current Opinion in Lipidology
https://www.readbyqxmd.com/read/27856732/trypanosoma-brucei-metabolite-indolepyruvate-decreases-hif-1%C3%AE-and-glycolysis-in-macrophages-as-a-mechanism-of-innate-immune-evasion
#5
Anne F McGettrick, Sarah E Corcoran, Paul J G Barry, Jennifer McFarland, Cécile Crès, Anne M Curtis, Edward Franklin, Sinéad C Corr, K Hun Mok, Eoin P Cummins, Cormac T Taylor, Luke A J O'Neill, Derek P Nolan
The parasite Trypanasoma brucei causes African trypanosomiasis, known as sleeping sickness in humans and nagana in domestic animals. These diseases are a major burden in the 36 sub-Saharan African countries where the tsetse fly vector is endemic. Untreated trypanosomiasis is fatal and the current treatments are stage-dependent and can be problematic during the meningoencephalitic stage, where no new therapies have been developed in recent years and the current drugs have a low therapeutic index. There is a need for more effective treatments and a better understanding of how these parasites evade the host immune response will help in this regard...
November 29, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27855598/designing-potential-antitrypanosomal-thiazol-2-ethylamines-through-predictive-regression-based-and-classification-based-qsar-analyses
#6
Sk Abdul Amin, Nilanjan Adhikari, Sonam Bhargava, Tarun Jha, Shovanlal Gayen
BACKGROUND: Thiazole-2-ethylamine is recently reported to be an interesting scaffold having antitrypansomal activity for the treatment of sleeping sickness. METHODS: Statistically significant, robust and validated regression-based QSAR models are constructed for a series of antitrypansomal thiazol-2-ethylamines. Moreover, classification-based QSAR analyses (linear discriminate analysis and Bayesian classification modelling) are also performed to identify the important structural features controlling antitrypanosomal activity...
November 17, 2016: Current Drug Discovery Technologies
https://www.readbyqxmd.com/read/27855164/trypanosoma-brucei-cyp51-essentiality-and-targeting-therapy-in-an-experimental-model
#7
Frédéric-Antoine Dauchy, Mélanie Bonhivers, Nicolas Landrein, Denis Dacheux, Pierrette Courtois, Florian Lauruol, Sylvie Daulouède, Philippe Vincendeau, Derrick R Robinson
Trypanosoma brucei gambiense is the main causative agent of Human African Trypanosomiasis (HAT), also known as sleeping sickness. Because of limited alternatives and treatment toxicities, new therapeutic options are urgently needed for patients with HAT. Sterol 14alpha-demethylase (CYP51) is a potential drug target but its essentiality has not been determined in T. brucei. We used a tetracycline-inducible RNAi system to assess the essentiality of CYP51 in T. brucei bloodstream form (BSF) cells and we evaluated the effect of posaconazole, a well-tolerated triazole drug, within a panel of virulent strains in vitro and in a murine model...
November 2016: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/27855156/novel-financing-model-for-neglected-tropical-diseases-development-impact-bonds-applied-to-sleeping-sickness-and-rabies-control
#8
Susan Christina Welburn, Kevin Louis Bardosh, Paul Gerard Coleman
No abstract text is available yet for this article.
November 2016: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/27849517/a-targeted-door-to-door-strategy-for-sleeping-sickness-detection-in-low-prevalence-settings-in-c%C3%A3-te-d-ivoire
#9
Mathurin Koffi, Martial N'Djetchi, Hamidou Ilboudo, Dramane Kaba, Bamoro Coulibaly, Emmanuel N'Gouan, Lingué Kouakou, Bruno Bucheton, Philippe Solano, Fabrice Courtin, Stephan Ehrhardt, Vincent Jamonneau
Significant efforts to control human African trypanosomiasis (HAT) over the three past decades have resulted in drastic reductions of disease prevalence in Côte d'Ivoire. In this context, the costly and labor-intensive active mass screening strategy is no longer efficient. In addition to a more cost-effective passive surveillance system being implemented in this low-prevalence context, our aim was to develop an alternative targeted active screening strategy. In 2012, we carried out a targeted door-to-door (TDD) survey focused on the immediate vicinities of former HAT patients detected in the HAT focus of Bonon and compared the results to those obtained during classical active mass screening (AMS) surveys conducted from 2000 to 2012 in the same area...
2016: Parasite: Journal de la Société Française de Parasitologie
https://www.readbyqxmd.com/read/27815907/synchronization-of-pathogenic-protozoans
#10
Staffan Svärd, Karin Troell
Protozoans are single-celled eukaryotes and many of the best-studied protozoans are parasitic to humans (e.g., Plasmodium falciparum causing malaria and Trypanosoma brucei causing sleeping sickness). These organisms are distantly related to humans but with retained eukaryotic type of cellular processes, making them good model systems for studies of the evolution of basic processes like the cell cycle. Giardia intestinalis causes 250 million cases of diarrhea yearly and is one of the earliest diverging protozoans...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27805593/detection-of-trypanosoma-brucei-variant-surface-glycoprotein-switching-by-magnetic-activated-cell-sorting-and-flow-cytometry
#11
Danae Schulz, Monica R Mugnier, Catherine E Boothroyd, F Nina Papavasiliou
Trypanosoma brucei, a protozoan parasite that causes both Human and Animal African Trypanosomiasis (known as sleeping sickness and nagana, respectively) cycles between a tsetse vector and a mammalian host. It evades the mammalian host immune system by periodically switching the dense, variant surface glycoprotein (VSG) that covers its surface. The detection of antigenic variation in Trypanosoma brucei can be both cumbersome and labor intensive. Here, we present a method for quantifying the number of parasites that have 'switched' to express a new VSG in a given population...
October 19, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/27782591/a-new-system-for-continuous-and-remote-monitoring-of-patients-receiving-home-mechanical-ventilation
#12
L Battista
Home mechanical ventilation is the treatment of patients with respiratory failure or insufficiency by means of a mechanical ventilator at a patient's home. In order to allow remote patient monitoring, several tele-monitoring systems have been introduced in the last few years. However, most of them usually do not allow real-time services, as they have their own proprietary communication protocol implemented and some ventilation parameters are not always measured. Moreover, they monitor only some breaths during the whole day, despite the fact that a patient's respiratory state may change continuously during the day...
September 2016: Review of Scientific Instruments
https://www.readbyqxmd.com/read/27765637/the-wing-venation-patterns-to-identify-single-tsetse-flies
#13
D Kaba, D Berté, B T D Ta, J Tellería, P Solano, J-P Dujardin
This is the first study to explore the potential of various geometric morphometrics methods to help the morphological diagnostic of tsetse species, vectors of human and animal trypanosomiases in sub-Saharan Africa. We compared landmarks, semilandmarks and outlines techniques on male and female samples of species, and suggested adapted strategies according to the countries and their own Glossina fauna. We could compare up to 7 taxa belonging to the three main subgenera of the Glossina genus: Nemorhina (5 species), Glossina (1 species) and Austenina (1 species)...
October 17, 2016: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/27749469/protective-determinants-of-sickness-absence-among-employees-with-multisite-pain-a-7-year-follow-up
#14
Eija Haukka, Anneli Ojajärvi, Leena Kaila-Kangas, Päivi Leino-Arjas
We identified factors protective of all-cause sickness absence (SA) among subjects with multisite musculoskeletal pain (MSP). The nationally representative source sample comprised 3420 actively working Finns aged 30-55 in year 2000 and alive at follow-up. Pain in 18 body locations was combined into four sites (neck, low back, upper limbs, lower limbs). The baseline prevalence of MSP (pain in ≥ 2 sites) was 32 %. Baseline data on sociodemographic factors, work ability, work, health, and lifestyle were gathered by questionnaire, interview and clinical examination and linked with national registers on all-cause SA (periods lasting ≥10 workdays) for 2002-2008...
October 3, 2016: Pain
https://www.readbyqxmd.com/read/27744351/rna-editing-tutase-1-structural-foundation-of-substrate-recognition-complex-interactions-and-drug-targeting
#15
Lional Rajappa-Titu, Takuma Suematsu, Paola Munoz-Tello, Marius Long, Özlem Demir, Kevin J Cheng, Jason R Stagno, Hartmut Luecke, Rommie E Amaro, Inna Aphasizheva, Ruslan Aphasizhev, Stéphane Thore
Terminal uridyltransferases (TUTases) execute 3' RNA uridylation across protists, fungi, metazoan and plant species. Uridylation plays a particularly prominent role in RNA processing pathways of kinetoplastid protists typified by the causative agent of African sleeping sickness, Trypanosoma brucei In mitochondria of this pathogen, most mRNAs are internally modified by U-insertion/deletion editing while guide RNAs and rRNAs are U-tailed. The founding member of TUTase family, RNA editing TUTase 1 (RET1), functions as a subunit of the 3' processome in uridylation of gRNA precursors and mature guide RNAs...
October 15, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27740910/skin-deep
#16
Aitor Casas-Sánchez, Álvaro Acosta-Serrano
Trypanosome parasites are hiding in human skin, a discovery that may undermine efforts to eliminate sleeping sickness by 2020.
October 14, 2016: ELife
https://www.readbyqxmd.com/read/27739621/african-trypanosomes-and-brain-infection%C3%A2-%C3%A2-the-unsolved-question
#17
Stefan Mogk, Christian M Boßelmann, Celestin N Mudogo, Jasmin Stein, Hartwig Wolburg, Michael Duszenko
African trypanosomes induce sleeping sickness. The parasites are transmitted during the blood meal of a tsetse fly and appear primarily in blood and lymph vessels, before they enter the central nervous system. During the latter stage, trypanosomes induce a deregulation of sleep-wake cycles and some additional neurological disorders. Historically, it was assumed that trypanosomes cross the blood-brain barrier and settle somewhere between the brain cells. The brain, however, is a strictly controlled and immune-privileged area that is completely surrounded by a dense barrier that covers the blood vessels: this is the blood-brain barrier...
October 14, 2016: Biological Reviews of the Cambridge Philosophical Society
https://www.readbyqxmd.com/read/27733833/new-approaches-to-overcome-transport-related-drug-resistance-in-trypanosomatid-parasites
#18
Jose A Garcia-Salcedo, Juan D Unciti-Broceta, Javier Valverde-Pozo, Miguel Soriano
Leishmania and Trypanosoma are members of the Trypanosomatidae family that cause severe human infections such as leishmaniasis, Chagas disease, and sleeping sickness affecting millions of people worldwide. Despite efforts to eradicate them, migrations are expanding these infections to developing countries. There are no vaccines available and current treatments depend only on chemotherapy. Drug resistance is a major obstacle for the treatment of these diseases given that existing drugs are old and limited, with some having severe side effects...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27723399/african-sleeping-sickness
#19
Lucy Hedley, Douglas Fink, Dominic Sparkes, Peter L Chiodini
No abstract text is available yet for this article.
October 2016: British Journal of Hospital Medicine
https://www.readbyqxmd.com/read/27720295/targeting-the-hsp60-10-chaperonin-systems-of-trypanosoma-brucei-as-a-strategy-for-treating-african-sleeping-sickness
#20
Sanofar Abdeen, Nilshad Salim, Najiba Mammadova, Corey M Summers, Karen Goldsmith-Pestana, Diane McMahon-Pratt, Peter G Schultz, Arthur L Horwich, Eli Chapman, Steven M Johnson
Trypanosoma brucei are protozoan parasites that cause African sleeping sickness in humans (also known as Human African Trypanosomiasis-HAT). Without treatment, T. brucei infections are fatal. There is an urgent need for new therapeutic strategies as current drugs are toxic, have complex treatment regimens, and are becoming less effective owing to rising antibiotic resistance in parasites. We hypothesize that targeting the HSP60/10 chaperonin systems in T. brucei is a viable anti-trypanosomal strategy as parasites rely on these stress response elements for their development and survival...
September 22, 2016: Bioorganic & Medicinal Chemistry Letters
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