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https://www.readbyqxmd.com/read/29782894/screening-of-the-mmv-and-gsk-open-access-chemical-boxes-using-a-viability-assay-developed-against-the-kinetoplastid-crithidia-fasciculata
#1
Wakisa Kipandula, Simon A Young, Stuart A MacNeill, Terry K Smith
Diseases caused by the pathogenic kinetoplastids continue to incapacitate and kill hundreds of thousands of people annually throughout the tropics and sub-tropics. Unfortunately, in the countries where these neglected diseases occur, financial obstacles to drug discovery and technical limitations associated with biochemical studies impede the development of new, safe, easy to administer and effective drugs. Here we report the development and optimisation of a Crithidia fasciculata resazurin viability assay, which is subsequently used for screening and identification of anti-crithidial compounds in the MMV and GSK open access chemical boxes...
May 18, 2018: Molecular and Biochemical Parasitology
https://www.readbyqxmd.com/read/29778650/obesity-surgery-makes-patients-healthier-and-more-functional-real-world-results-from-the-united-kingdom-national-bariatric-surgery-registry
#2
Alexander Dimitri Miras, Kamocka Anna, Patel Darshan, Dexter Simon, Finlay Ian, Hopkins C James, Khan Omar, Reddy Marcus, Sedman Peter, Small Peter, Somers Shaw, Suzie Cro, Walton Peter, le Roux Carel W, Welbourn Richard
BACKGROUND: The National Bariatric Surgery Registry (NBSR) is the largest bespoke database in the field in the United Kingdom. OBJECTIVES: Our aim was to analyze the NBSR to determine whether the effects of obesity surgery on associated co-morbidities observed in small, randomized controlled clinical trials could be replicated in a "real life" setting within U.K. healthcare. SETTING: United Kingdom. METHODS: All NBSR entries for operations between 2000 and 2015 with associated demographic and co-morbidity data were analyzed retrospectively...
February 15, 2018: Surgery for Obesity and related Diseases: Official Journal of the American Society for Bariatric Surgery
https://www.readbyqxmd.com/read/29778466/in-vitro-susceptibility-of-trypanosoma-brucei-brucei-to-selected-essential-oils-and-their-major-components
#3
Sonya Costa, Cláudia Cavadas, Carlos Cavaleiro, Lígia Salgueiro, Maria do Céu Sousa
Aiming for discovering effective and harmless antitrypanosomal agents, 17 essential oils and nine major components were screened for their effects on T. b. brucei. The essential oils were obtained by hydrodistillation from fresh plant material and analyzed by GC and GC-MS. The trypanocidal activity was assessed using blood stream trypomastigotes cultures of T. b. brucei and the colorimetric resazurin method. The MTT test was used to assess the cytotoxicity of essential oils on macrophage cells and Selectivity Indexes were calculated...
May 17, 2018: Experimental Parasitology
https://www.readbyqxmd.com/read/29742915/redox-regulation-of-hexokinases
#4
Petr Heneberg
Significance Hexokinases are key enzymes that are responsible for the first reaction of glycolysis, but they also moonlight other cellular processes, including mitochondrial redox signaling regulation. Modulation of hexokinase activity and spatiotemporal location by reactive oxygen and nitrogen species as well as other gasotransmitters serves as the basis for a unique, underexplored method of tight and flexible regulation of these fundamental enzymes. Recent advances Redox modifications of thiols serve as a molecular code that enables the precise and complex regulation of hexokinases...
May 10, 2018: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/29742443/fluorine-walk-the-impact-of-fluorine-in-quinolone-amides-on-their-activity-against-african-sleeping-sickness
#5
Michael Berninger, Christine Erk, Antje Fuß, Joseph Skaf, Ehab Al-Momani, Ina Israel, Martina Raschig, Paul Güntzel, Samuel Samnick, Ulrike Holzgrabe
Human African Trypanosomiasis, also known as African sleeping sickness, is caused by the parasitic protozoa of the genus Trypanosoma. If there is no pharmacological intervention, the parasites can cross the blood-brain barrier (BBB), inevitably leading to death of the patients. Previous investigation identified the quinolone amide GHQ168 as a promising lead compound having a nanomolar activity against T. b. brucei. Here, the role of a fluorine substitution at different positions was investigated in regard to toxicity, pharmacokinetics, and antitrypanosomal activity...
April 30, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29741971/impact-of-sleeping-altitude-on-symptoms-of-acute-mountain-sickness-on-mt-fuji
#6
Masahiro Horiuchi, Tadashi Uno, Junko Endo, Yoko Handa, Tatsuya Hasegawa
Horiuchi, Masahiro, Tadashi Uno, Junko Endo, Yoko Handa, and Tatsuya Hasegawa. Impact of sleeping altitude on symptoms of acute mountain sickness on Mt. Fuji. High Alt Med Biol. 00:000-000, 2018. AIMS: We sought to investigate the factors influencing acute mountain sickness (AMS) on Mt. Fuji in Japan, in particular, to assess the effects of sleeping altitude, by means of a questionnaire survey. This study involved 1932 participants who climbed Mt. Fuji, and obtained information regarding sex, age, and whether participants stayed at the mountain lodges...
May 9, 2018: High Altitude Medicine & Biology
https://www.readbyqxmd.com/read/29713290/high-altitude-affects-nocturnal-non-linear-heart-rate-variability-patch-ha-study
#7
Christopher J Boos, Kyo Bye, Luke Sevier, Josh Bakker-Dyos, David R Woods, Mark Sullivan, Tom Quinlan, Adrian Mellor
Background: High altitude (HA) exposure can lead to changes in resting heart rate variability (HRV), which may be linked to acute mountain sickness (AMS) development. Compared with traditional HRV measures, non-linear HRV appears to offer incremental and prognostic data, yet its utility and relationship to AMS have been barely examined at HA. This study sought to examine this relationship at terrestrial HA. Methods: Sixteen healthy British military servicemen were studied at baseline (800 m, first night) and over eight consecutive nights, at a sleeping altitude of up to 3600 m...
2018: Frontiers in Physiology
https://www.readbyqxmd.com/read/29705579/melarsoprol-resistance-in-african-trypanosomiasis
#8
REVIEW
Alan H Fairlamb, David Horn
Arsenicals were introduced as monotherapies for the treatment of human African trypanosomiasis, or sleeping sickness, over 100 years ago. Toxicity has always been an issue but these drugs have proven to be both effective and quite durable. Unfortunately, melarsoprol-resistant parasites emerged as early as the 1970s and were widespread by the late 1990s. Resistance was due to mutations affecting an aquaglyceroporin (AQP2), a parasite solute and drug transporter. This is the only example of widespread drug resistance in trypanosomiasis patients for which the genetic basis is known...
April 25, 2018: Trends in Parasitology
https://www.readbyqxmd.com/read/29693583/adenylate-cyclases-of-trypanosoma-brucei-environmental-sensors-and-controllers-of-host-innate-immune-response
#9
REVIEW
Didier Salmon
Trypanosoma brucei , etiological agent of Sleeping Sickness in Africa, is the prototype of African trypanosomes, protozoan extracellular flagellate parasites transmitted by saliva ( Salivaria ). In these parasites the molecular controls of the cell cycle and environmental sensing are elaborate and concentrated at the flagellum. Genomic analyses suggest that these parasites appear to differ considerably from the host in signaling mechanisms, with the exception of receptor-type adenylate cyclases (AC) that are topologically similar to receptor-type guanylate cyclase (GC) of higher eukaryotes but control a new class of cAMP targets of unknown function, the cAMP response proteins (CARPs), rather than the classical protein kinase A cAMP effector (PKA)...
April 25, 2018: Pathogens
https://www.readbyqxmd.com/read/29672758/explaining-the-gender-gap-in-sickness-absence
#10
K A Østby, A Mykletun, W Nilsen
Background: In many western countries, women have a much higher rate of sickness absence than men. To what degree the gender differences in sickness absence are caused by gender differences in health is largely unknown. Aims: To assess to what degree the gender gap in sickness absence can be explained by health factors and work- and family-related stressors. Methods: Norwegian parents participating in the Tracking Opportunities and Problems (TOPP) study were asked about sickness absence and a range of factors possibly contributing to gender differences in sickness absence, including somatic and mental health, sleep problems, job control/demands, work-home conflicts, parent-child conflicts and stressful life events...
April 17, 2018: Occupational Medicine
https://www.readbyqxmd.com/read/29672041/targeting-a-subpocket-in-trypanosoma-brucei-phosphodiesterase-b1-tbrpdeb1-enables-the-structure-based-discovery-of-selective-inhibitors-with-trypanocidal-activity
#11
Antoni R Blaazer, Abhimanyu Kumar Singh, Erik de Heuvel, Ewald Edink, Kristina M Orrling, Johan J N Veerman, Toine van den Bergh, Chimed Jansen, Erin Balasubramaniam, Wouter J Mooij, Hans Custers, Maarten Sijm, Daniel N A Tagoe, Titilola D Kalejaiye, Jane C Munday, Hermann Tenor, An Matheeussen, Maikel Wijtmans, Marco Siderius, Chris de Graaf, Louis Maes, Harry P de Koning, David S Bailey, Geert Jan Sterk, Iwan J P De Esch, David G Brown, Rob Leurs
Several trypanosomatid cyclic nucleotide phosphodiesterases (PDEs) possess a unique, parasite-specific cavity near the ligand-binding region that is referred to as the P-pocket. One of these enzymes, Trypanosoma brucei PDE B1 (TbrPDEB1), is considered a drug target for the treatment of African sleeping sickness. Here, we elucidate the molecular determinants of inhibitor binding and reveal that the P-pocket is amenable to directed design. By iterative cycles of design, synthesis, pharmacological evaluation, and by elucidating the structures of inhibitor-bound TbrPDEB1, hPDE4B and hPDE4D complexes, we have developed 4a,5,8,8a-tetrahydrophthalazinones as the first selective TbrPDEB1 inhibitor series...
April 19, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29666191/flagellum-inheritance-in-trypanosoma-brucei-requires-a-kinetoplastid-specific-protein-phosphatase
#12
Qing Zhou, Gang Dong, Ziyin Li
Trypanosoma brucei causes sleeping sickness in humans and nagana in cattle in sub-Saharan Africa and alternates between its mammalian hosts and its insect vector, the tsetse fly. T. brucei uses a flagellum for motility, cell division, and cell-cell communication. Proper positioning and attachment of the newly assembled flagellum rely on the faithful duplication and segregation of flagellum-associated cytoskeletal structures. These processes are regulated by the polo-like kinase homolog TbPLK, whose activity and abundance are under stringent control to ensure spatiotemporally regulated phosphorylation of its substrates...
April 17, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29664207/how-sleep-problems-contribute-to-simulator-sickness-preliminary-results-from-a-realistic-driving-scenario
#13
Ellemarije Altena, Yannick Daviaux, Ernesto Sanz-Arigita, Emilien Bonhomme, Étienne de Sevin, Jean-Arthur Micoulaud-Franchi, Stéphanie Bioulac, Pierre Philip
Virtual reality and simulation tools enable us to assess daytime functioning in environments that simulate real life as close as possible. Simulator sickness, however, poses a problem in the application of these tools, and has been related to pre-existing health problems. How sleep problems contribute to simulator sickness has not yet been investigated. In the current study, 20 female chronic insomnia patients and 32 female age-matched controls drove in a driving simulator covering realistic city, country and highway scenes...
April 17, 2018: Journal of Sleep Research
https://www.readbyqxmd.com/read/29649664/autophagic-related-cell-death-of-trypanosoma-brucei-induced-by-bacteriocin-as-48
#14
Marta Martínez-García, Jean-Mathieu Bart, Jenny Campos-Salinas, Eva Valdivia, Manuel Martínez-Bueno, Elena González-Rey, Miguel Navarro, Mercedes Maqueda, Rubén Cebrián, José M Pérez-Victoria
The parasitic protozoan Trypanosoma brucei is the causative agent of human African trypanosomiasis (sleeping sickness) and nagana. Current drug therapies have limited efficacy, high toxicity and/or are continually hampered by the appearance of resistance. Antimicrobial peptides have recently attracted attention as potential parasiticidal compounds. Here, we explore circular bacteriocin AS-48's ability to kill clinically relevant bloodstream forms of T. brucei gambiense, T. brucei rhodesiense and T. brucei brucei...
March 12, 2018: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/29624584/the-impact-of-passive-case-detection-on-the-transmission-dynamics-of-gambiense-human-african-trypanosomiasis
#15
Francesco Checchi, Sebastian Funk, Daniel Chandramohan, François Chappuis, Daniel T Haydon
Gambiense Human African Trypanosomiasis (HAT), or sleeping sickness, is a vector-borne disease affecting largely rural populations in Western and Central Africa. The main method for detecting and treating cases of gambiense HAT are active screening through mobile teams and passive detection through self-referral of patients to dedicated treatment centres or hospitals. Strategies based on active case finding and treatment have drastically reduced the global incidence of the disease over recent decades. However, little is known about the coverage and transmission impact of passive case detection...
April 6, 2018: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/29623044/long-term-intermittent-work-at-high-altitude-right-heart-functional-and-morphological-status-and-associated-cardiometabolic-factors
#16
Julio Brito, Patricia Siques, Rosario López, Raul Romero, Fabiola León-Velarde, Karen Flores, Nicole Lüneburg, Juliane Hannemann, Rainer H Böger
Background: Living at high altitude or with chronic hypoxia implies functional and morphological changes in the right ventricle and pulmonary vasculature with a 10% prevalence of high-altitude pulmonary hypertension (HAPH). The implications of working intermittently (day shifts) at high altitude (hypobaric hypoxia) over the long term are still not well-defined. The aim of this study was to evaluate the right cardiac circuit status along with potentially contributory metabolic variables and distinctive responses after long exposure to the latter condition...
2018: Frontiers in Physiology
https://www.readbyqxmd.com/read/29606092/rna-seq-analysis-validates-the-use-of-culture-derived-trypanosoma-brucei-and-provides-new-markers-for-mammalian-and-insect-life-cycle-stages
#17
Arunasalam Naguleswaran, Nicholas Doiron, Isabel Roditi
BACKGROUND: Trypanosoma brucei brucei, the parasite causing Nagana in domestic animals, is closely related to the parasites causing sleeping sickness, but does not infect humans. In addition to its importance as a pathogen, the relative ease of genetic manipulation and an innate capacity for RNAi extend its use as a model organism in cell and infection biology. During its development in its mammalian and insect (tsetse fly) hosts, T. b. brucei passes through several different life-cycle stages...
April 2, 2018: BMC Genomics
https://www.readbyqxmd.com/read/29602919/effect-of-prolonged-and-intermittent-treatment-on-the-clinical-course-of-peptic-ulcer
#18
Zhanetta A Chornenka, Elvira Ts Yasinska, Mariana I Grytsiuk
OBJECTIVE: Introduction: The number of patients with peptic ulcer increases annually. According to published data, patients with peptic ulcer constitute about 15% of those hospitalized with gastrointestinal diseases. The aim: That is why we set the task to evaluate the methods of preventive treatment and to choose the most effective one. PATIENTS AND METHODS: Materials and methods: For this purpose, we selected 103 patients with peptic ulcer without severe exacerbations and complications from one region (main group) and 101 patients from another region (control group) for observations...
2018: Wiadomości Lekarskie: Organ Polskiego Towarzystwa Lekarskiego
https://www.readbyqxmd.com/read/29601610/preventive-behaviors-adults-report-using-to-avoid-catching-or-spreading-influenza-united-states-2015-16-influenza-season
#19
Anup Srivastav, Tammy A Santibanez, Peng-Jun Lu, M Christopher Stringer, Jill A Dever, Michael Bostwick, Marshica Stanley Kurtz, Noreen L Qualls, Walter W Williams
INTRODUCTION: Influenza vaccination can prevent influenza and potentially serious influenza-related complications. Although the single best way to prevent influenza is annual vaccination, everyday preventive actions, including good hygiene, health, dietary, and social habits, might help, too. Several preventive measures are recommended, including: avoiding close contact with people who are sick; staying home when sick; covering your mouth and nose when coughing or sneezing; washing your hands often; avoiding touching your eyes, nose, and mouth; and practicing other good health habits like cleaning and disinfecting frequently touched surfaces, getting plenty of sleep, and drinking plenty of fluids...
2018: PloS One
https://www.readbyqxmd.com/read/29583031/the-2018-lake-louise-acute-mountain-sickness-score
#20
Robert C Roach, Peter H Hackett, Oswald Oelz, Peter Bärtsch, Andrew M Luks, Martin J MacInnis, J Kenneth Baillie
Roach, Robert C., Peter H. Hackett, Oswald Oelz, Peter Bärtsch, Andrew M. Luks, Martin J. MacInnis, J. Kenneth Baillie, and The Lake Louise AMS Score Consensus Committee. The 2018 Lake Louise Acute Mountain Sickness Score. High Alt Med Biol 00:000-000, 2018.- The Lake Louise Acute Mountain Sickness (AMS) scoring system has been a useful research tool since first published in 1991. Recent studies have shown that disturbed sleep at altitude, one of the five symptoms scored for AMS, is more likely due to altitude hypoxia per se, and is not closely related to AMS...
March 13, 2018: High Altitude Medicine & Biology
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