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https://www.readbyqxmd.com/read/27926944/targeting-neutrophils-to-prevent-malaria-associated-acute-lung-injury-acute-respiratory-distress-syndrome-in-mice
#1
Michelle K Sercundes, Luana S Ortolan, Daniela Debone, Paulo V Soeiro-Pereira, Eliane Gomes, Elizabeth H Aitken, Antonio Condino Neto, Momtchilo Russo, Maria R D' Império Lima, José M Alvarez, Silvia Portugal, Claudio R F Marinho, Sabrina Epiphanio
Malaria remains one of the greatest burdens to global health, causing nearly 500,000 deaths in 2014. When manifesting in the lungs, severe malaria causes acute lung injury/acute respiratory distress syndrome (ALI/ARDS). We have previously shown that a proportion of DBA/2 mice infected with Plasmodium berghei ANKA (PbA) develop ALI/ARDS and that these mice recapitulate various aspects of the human syndrome, such as pulmonary edema, hemorrhaging, pleural effusion and hypoxemia. Herein, we investigated the role of neutrophils in the pathogenesis of malaria-associated ALI/ARDS...
December 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27926919/plasmodium-falciparum-infection-status-among-children-with-schistosoma-in-sub-saharan-africa-a-systematic-review-and-meta-analysis
#2
Abraham Degarege, Dawit Degarege, Emir Veledar, Berhanu Erko, Mathieu Nacher, Consuelo M Beck-Sague, Purnima Madhivanan
BACKGROUND: It has been suggested that Schistosoma infection may be associated with Plasmodium falciparum infection or related reduction in haemoglobin level, but the nature of this interaction remains unclear. This systematic review synthesized evidence on the relationship of S. haematobium or S. mansoni infection with the occurrence of P. falciparum malaria, Plasmodium density and related reduction in haemoglobin level among children in sub-Saharan Africa (SSA). METHODOLOGY/PRINCIPAL FINDINGS: A systematic review in according with PRISMA guidelines was conducted...
December 2016: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/27924931/global-proteomic-analysis-of-prenylated-proteins-in-plasmodium-falciparum-using-an-alkyne-modified-isoprenoid-analogue
#3
Kiall F Suazo, Chad Schaber, Charuta C Palsuledesai, Audrey R Odom John, Mark D Distefano
Severe malaria due to Plasmodium falciparum infection remains a serious threat to health worldwide and new therapeutic targets are highly desirable. Small molecule inhibitors of prenyl transferases, enzymes that catalyze the post-translational isoprenyl modifications of proteins, exhibit potent antimalarial activity. The antimalarial actions of prenyltransferase inhibitors indicate that protein prenylation is required for malaria parasite development. In this study, we used a chemical biology strategy to experimentally characterize the entire complement of prenylated proteins in the human malaria parasite...
December 7, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27923949/novel-bumped-kinase-inhibitors-are-safe-and-effective-therapeutics-in-the-calf-clinical-model-for-cryptosporidiosis
#4
Deborah A Schaefer, Dana P Betzer, Kylie D Smith, Zachary G Millman, Hannah C Michalski, Sarah E Menchaca, Jennifer A Zambriski, Kayode K Ojo, Matthew A Hulverson, Samuel L M Arnold, Kasey L Rivas, Rama S R Vidadala, Wenlin Huang, Lynn K Barrett, Dustin J Maly, Erkang Fan, Wesley C Van Voorhis, Michael W Riggs
Cryptosporidiosis, caused by the apicomplexan parasite Cryptosporidium parvum, is a diarrheal disease that has produced a large global burden in mortality and morbidity in humans and livestock. There are currently no consistently effective parasite-specific pharmaceuticals available for this disease. Bumped kinase inhibitors (BKIs) specific for parasite calcium-dependent protein kinases (CDPKs) have been shown to reduce infection in several parasites having medical and veterinary importance, including Toxoplasma gondii, Plasmodium falciparum, and C...
December 15, 2016: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/27923947/short-term-impact-of-mass-drug-administration-with-dihydroartemisinin-plus-piperaquine-on-malaria-in-southern-province-zambia-a-cluster-randomized-controlled-trial
#5
Thomas P Eisele, Adam Bennett, Kafula Silumbe, Timothy P Finn, Victor Chalwe, Mulakwa Kamuliwo, Busiku Hamainza, Hawela Moonga, Emmanuel Kooma, Elizabeth Chizema Kawesha, Joshua Yukich, Joseph Keating, Travis Porter, Ruben O Conner, Duncan Earle, Richard W Steketee, John M Miller
BACKGROUND:  Mass drug administration (MDA) using dihydroartemisinin plus piperaquine (DHAp) represents a potential strategy to clear Plasmodium falciparum infections and reduce the human parasite reservoir. METHODS:  A cluster-randomized controlled trial in Southern Province, Zambia, was used to assess the short-term impact of 2 rounds of community-wide MDA and household-level (focal) MDA with DHAp compared with no mass treatment. Study end points included parasite prevalence in children, infection incidence, and confirmed malaria case incidence...
December 15, 2016: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/27923926/reduced-activity-of-mutant-calcium-dependent-protein-kinase-1-is-compensated-in-plasmodium-falciparum-through-the-action-of-protein-kinase-g
#6
Abhisheka Bansal, Kayode K Ojo, Jianbing Mu, Dustin J Maly, Wesley C Van Voorhis, Louis H Miller
: We used a sensitization approach that involves replacement of the gatekeeper residue in a protein kinase with one with a different side chain. The activity of the enzyme with a bulky gatekeeper residue, such as methionine, cannot be inhibited using bumped kinase inhibitors (BKIs). Here, we have used this approach to study Plasmodium falciparum calcium-dependent protein kinase 1 (PfCDPK1). The methionine gatekeeper substitution, T145M, although it led to a 47% reduction in transphosphorylation, was successfully introduced into the CDPK1 locus using clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9...
December 6, 2016: MBio
https://www.readbyqxmd.com/read/27923381/economic-evaluation-of-artesunate-and-three-quinine-regimens-in-the-treatment-of-severe-malaria-in-children-at-the-ebolowa-regional-hospital-cameroon-a-cost-analysis
#7
Daniel Ethe Maka, Andreas Chiabi, Bolaji Obadeyi, Evelyn Mah, Séraphin Nguefack, Pamela Nana, Wilfred Mbacham, Elie Mbonda
BACKGROUND: Severe malaria is a leading cause of morbidity and mortality in under-fives in sub-Saharan Africa. Recently quinine has been replaced by artesunate as the first-line drug in the treatment of severe malaria in Cameroon. Artesunate has been shown to be cost-effective in African children, but whether these findings are transferable to Cameroonian children remains to be explored. OBJECTIVES: To conduct a cost-analysis of four different regimens used in the treatment from the perspective of the healthcare payer...
December 7, 2016: Malaria Journal
https://www.readbyqxmd.com/read/27923179/structural-dynamics-of-casein-kinase-i-cki-from-malarial-parasite-plasmodium-falciparum-isolate-3d7-insights-from-theoretical-modelling-and-molecular-simulations
#8
Budheswar Dehury, Santosh Kumar Behera, Namita Mahapatra
The protein kinases (PKs), belonging to serine/threonine kinase (STKs), are important drug targets for a wide spectrum of diseases in human. Among protein kinases, the Casein Kinases (CKs) are vastly expanded in various organisms, where, the malarial parasite Plasmodium falciparum possesses a single member i.e., PfCKI, which can phosphorylate various proteins in parasite extracts in vitro condition. But, the structure-function relationship of PfCKI and dynamics of ATP binding is yet to be understood. Henceforth, an attempt was made to study the dynamics, stability, and ATP binding mechanisms of PfCKI through computational modelling, docking, molecular dynamics (MD) simulations, and MM/PBSA binding free energy estimation...
November 21, 2016: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/27922118/mining-visualizing-and-comparing-multidimensional-biomolecular-data-using-the-genomics-data-miner-gmine-web-server
#9
Carla Proietti, Martha Zakrzewski, Thomas S Watkins, Bernard Berger, Shihab Hasan, Champa N Ratnatunga, Marie-Jo Brion, Peter D Crompton, John J Miles, Denise L Doolan, Lutz Krause
Genomics Data Miner (GMine) is a user-friendly online software that allows non-experts to mine, cluster and compare multidimensional biomolecular datasets. Various powerful visualization techniques are provided, generating high quality figures that can be directly incorporated into scientific publications. Robust and comprehensive analyses are provided via a broad range of data-mining techniques, including univariate and multivariate statistical analysis, supervised learning, correlation networks, clustering and multivariable regression...
December 6, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27920569/does-calcium-channel-blockade-have-a-role-in-prevention-of-expression-of-sepsis-in-renal-transplant-recipients
#10
REVIEW
John A D'Elia, Ray E Gleason, Anthony P Monaco, Larry A Weinrauch
Many antihypertensive agents have been demonstrated to assist in preservation of kidney function, among them those that modulate calcium channels. Calcium channel blockers may also be of value in protecting hemodialysis patients from complications of sepsis. In diabetic recipients of kidney transplant allografts treated with cyclosporine, calcium channel blockade has been retrospectively linked to improved graft preservation and to fewer episodes of sepsis. This brief review outlines clinical and experimental publications on potential protection from sepsis by addition of calcium channel blockers to standard antibiotic therapy in individuals who may or may not have normal kidney function, or in the presence or absence of immunosuppression...
2016: International Journal of Nephrology and Renovascular Disease
https://www.readbyqxmd.com/read/27920563/assessing-parasite-clearance-during-uncomplicated-plasmodium-falciparum-infection-treated-with-artesunate-monotherapy-in-suriname
#11
Stephen Gs Vreden, Rakesh D Bansie, Jeetendra K Jitan, Malti R Adhin
BACKGROUND: Artemisinin resistance in Plasmodium falciparum is suspected when the day 3 parasitemia is >10% when treated with artemisinin-based combination therapy or if >10% of patients treated with artemisinin-based combination therapy or artesunate monotherapy harbored parasites with half-lives ≥5 hours. Hence, a single-arm prospective efficacy trial was conducted in Suriname for uncomplicated P. falciparum infection treated with artesunate-based monotherapy for 3 days assessing day 3 parasitemia, treatment outcome after 28 days, and parasite half-life...
2016: Infection and Drug Resistance
https://www.readbyqxmd.com/read/27920499/smart-nanocrystals-of-artemether-fabrication-characterization-and-comparative-in-vitro-and-in-vivo-antimalarial-evaluation
#12
Syed Muhammad Hassan Shah, Farhat Ullah, Shahzeb Khan, Syed Muhammad Mukarram Shah, Marcel de Matas, Zahid Hussain, Muhammad Usman Minhas, Naser M AbdEl-Salam, Khaled Hafez Assi, Mohammad Isreb
Artemether (ARTM) is a very effective antimalarial drug with poor solubility and consequently low bioavailability. Smart nanocrystals of ARTM with particle size of 161±1.5 nm and polydispersity index of 0.172±0.01 were produced in <1 hour using a wet milling technology, Dena(®) DM-100. The crystallinity of the processed ARTM was confirmed using differential scanning calorimetry and powder X-ray diffraction. The saturation solubility of the ARTM nanocrystals was substantially increased to 900 µg/mL compared to the raw ARTM in water (145...
2016: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/27919903/high-throughput-screening-and-prediction-models-building-for-novel-hemozoin-inhibitors-using-physicochemical-properties
#13
Nguyen Tien Huy, Pham Lan Chi, Jun Nagai, Tran Ngoc Dang, Evaristus Chibunna Mbanefo, Ali Mahmoud Ahmed, Nguyen Phuoc Long, Le Thi Bich Thoa, Le Phi Hung, Titouna Afaf, Kaeko Kamei, Hiroshi Ueda, Kenji Hirayama
It is essential to continue the search for novel antimalarial drugs due to current spread of resistance against artemisinin by Plasmodium falciparum parasites. In this study, we developed in silico models to predict hemozoin inhibitors as a potential first-step screening for novel antimalarials. The in vitro colorimetric high throughput screening assay of hemozoin formation was used to identify hemozoin inhibitors from 9600 structurally diverse compounds. Physicochemical properties of positive hits and randomly selected compounds were extracted from ChemSpider database; they were used for developing prediction models to predict hemozoin inhibitors using two different approaches, i...
December 5, 2016: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27919892/significant-divergence-in-sensitivity-to-antimalarial-drugs-between-neighboring-plasmodium-falciparum-populations-along-the-eastern-border-of-myanmar
#14
Weilin Zeng, Yao Bai, Meilian Wang, Zenglei Wang, Shuang Deng, Yonghua Ruan, Shi Feng, Zhaoqing Yang, Liwang Cui
Malaria parasites in different endemic areas display different levels of resistance to antimalarial drugs as the result of varied drug use histories. To provide updated knowledge of drug sensitivities during the malaria elimination phase in Southeast Asia, an epicenter of multidrug resistance, we determined in vitro susceptibilities of culture-adapted Plasmodium falciparum isolates from two eastern border regions (Wa and Kachin) of Myanmar to ten drugs. Despite their close proximity, the Kachin parasites displayed higher IC50 values than the Wa parasites to chloroquine, piperaquine, naphthoquine, mefloquine, quinine, pyrimethamine, pyronaridine, lumefantrine and dihydroartemisinin...
December 5, 2016: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27919755/anemia-iron-supplementation-and-susceptibility-to-plasmodium-falciparum-malaria
#15
Ishag Adam
No abstract text is available yet for this article.
December 1, 2016: EBioMedicine
https://www.readbyqxmd.com/read/27919743/dual-antiplasmodial-activity-of-vitamin-d3-and-its-analog-22-oxacalcitriol-by-direct-and-indirect-mechanisms
#16
Kiichi Yamamoto, Moritoshi Iwagami, Takenori Seki, Shigeyuki Kano, Nobuo Ota, Manabu Ato
Recent evidence suggests that 1α,25-dihydroxyvitamin D3 (calcitriol, VD3), the active form of vitamin D (VD), can inhibit the proliferation of microorganisms. In the present study, we conducted in vitro experiments and utilized in vivo murine models to investigate the antimalarial activity of VD3 and its analog, 22-oxacalcitriol (22-OCT), which was designed to cause less hypercalcemia than VD3. VD3 and 22-OCT treatments effectively resolved a Plasmodium chabaudi (Pc) infection in wild-type mice. Reduced parasitemia was observed during the acute phase of infection in the presence of VD3 and 22-OCT, followed by a delayed peak during the chronic stage of infection...
December 2, 2016: Parasitology International
https://www.readbyqxmd.com/read/27919256/the-return-of-chloroquine-susceptible-plasmodium-falciparum-malaria-in-zambia
#17
Sydney Mwanza, Sudhaunshu Joshi, Michael Nambozi, Justin Chileshe, Phidelis Malunga, Jean-Bertin Bukasa Kabuya, Sebastian Hachizovu, Christine Manyando, Modest Mulenga, Miriam Laufer
BACKGROUND: Plasmodium falciparum resistance to anti-malarial drugs remains a major obstacle to malaria control and elimination. The parasite has developed resistance to every anti-malarial drug introduced for wide-scale treatment. However, the spread of resistance may be reversible. Malawi was the first country to discontinue chloroquine use due to widespread resistance. Within a decade of the removal of drug pressure, the molecular marker of chloroquine-resistant malaria had disappeared and the drug was shown to have excellent clinical efficacy...
December 5, 2016: Malaria Journal
https://www.readbyqxmd.com/read/27917875/exploring-experimental-cerebral-malaria-pathogenesis-through-the-characterisation-of-host-derived-plasma-microparticle-protein-content
#18
Natalia Tiberti, Sharissa L Latham, Stephen Bush, Amy Cohen, Robert O Opoka, Chandy C John, Annette Juillard, Georges E Grau, Valéry Combes
Cerebral malaria (CM) is a severe complication of Plasmodium falciparum infection responsible for thousands of deaths in children in sub-Saharan Africa. CM pathogenesis remains incompletely understood but a number of effectors have been proposed, including plasma microparticles (MP). MP numbers are increased in CM patients' circulation and, in the mouse model, they can be localised within inflamed vessels, suggesting their involvement in vascular damage. In the present work we define, for the first time, the protein cargo of MP during experimental cerebral malaria (ECM) with the overarching hypothesis that this characterisation could help understand CM pathogenesis...
December 5, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27917203/population-genomics-diversity-of-plasmodium-falciparum-in-malaria-patients-attending-okelele-health-centre-okelele-ilorin-kwara-state-nigeria
#19
Olatunji Matthew Kolawole, Olugbenga Ayodeji Mokuolu, Yetunde Adeola Olukosi, Tolulope Ololade Oloyede
BACKGROUND: Plasmodium falciparum, the most dangerous malaria parasite species to humans remains an important public health concern in Okelele, a rural community in Ilorin, Kwara State, Nigeria. There is however little information about the genetic diversity of Plasmodium falciparum in Nigeria. OBJECTIVE: To determine the population genomic diversity of Plasmodium falciparum in malaria patients attending Okelele Community Healthcare Centre, Okelele, Ilorin, Kwara State...
September 2016: African Health Sciences
https://www.readbyqxmd.com/read/27912985/immunogenicity-and-malaria-transmission-reducing-potency-of-pfs48-45-and-pfs25-encoded-by-dna-vaccines-administered-by-intramuscular-electroporation
#20
Dibyadyuti Datta, Geetha P Bansal, Dietlind L Gerloff, Barry Ellefsen, Drew Hannaman, Nirbhay Kumar
Pfs48/45 and Pfs25 are leading candidates for the development of Plasmodium falciparum transmission blocking vaccines (TBV). Expression of Pfs48/45 in the erythrocytic sexual stages and presentation to the immune system during infection in the human host also makes it ideal for natural boosting. However, it has been challenging to produce a fully folded, functionally active Pfs48/45, using various protein expression platforms. In this study, we demonstrate that full-length Pfs48/45 encoded by DNA plasmids is able to induce significant transmission reducing immune responses...
November 29, 2016: Vaccine
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