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https://www.readbyqxmd.com/read/28719180/heterologous-expression-purification-and-functional-analysis-of-plasmodium-falciparum-phosphatidylinositol-3-kinase
#1
Matthew Hassett, Anna Sternberg, Bryce Riegel, Craig J Thomas, Paul David Roepe
The Plasmodium falciparum malarial parasite genome appears to encode one and only one phosphatidylinositol 3'-kinase (PI3K) and sequence analysis suggests that the enzyme is a "class III" or "Vps34" type PI3K. The PfVps34 has generated excitement as a possible druggable target and potentially a key target of artemisinin-based antimalarials. In this study, we optimize the PfVps34 gene for heterologous expression in yeast, purify the protein to homogeneity, use a recently validated quantitative assay for phosphatidylinositol 3'-phosphate (PI3P) production from phosphatidylinositol (PI) (Hassett et al...
July 18, 2017: Biochemistry
https://www.readbyqxmd.com/read/28717937/clinical-presentation-and-outcomes-of-childhood-onset-membranous-lupus-nephritis
#2
Maria Pereira, Eyal Muscal, Karen Eldin, M John Hicks, Anna Carmela P Sagcal-Gironella, Marietta DeGuzman, Scott E Wenderfer
BACKGROUND: Best practices for managing childhood-onset membranous lupus nephritis (MLN) are not yet established. Most studies involve primarily or exclusively adult cohorts or pediatric cohorts with combinations of pure or mixed membranous and proliferative nephritis. METHODS: We performed a single-center cohort study of consecutively diagnosed children with pure MLN from 1990 and 2016. Patients received care in Houston, Texas, one of the most diverse metropolitan areas in North America...
July 17, 2017: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/28716094/an-analytical-approach-to-reduce-between-plate-variation-in-multiplex-assays-that-measure-antibodies-to-plasmodium-falciparum-antigens
#3
Rui Fang, Andrew Wey, Naveen K Bobbili, Rose F G Leke, Diane Wallace Taylor, John J Chen
BACKGROUND: Antibodies play an important role in immunity to malaria. Recent studies show that antibodies to multiple antigens, as well as, the overall breadth of the response are associated with protection from malaria. Yet, the variability and reliability of antibody measurements against a combination of malarial antigens using multiplex assays have not been well characterized. METHODS: A normalization procedure for reducing between-plate variation using replicates of pooled positive and negative controls was investigated...
July 17, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28712788/antimalarial-agent-artesunate-protects-concanavalin-a-induced-autoimmune-hepatitis-in-mice-by-inhibiting-inflammatory-responses
#4
Xin Zhao, MingJiang Liu, JinGui Li, ShaoJie Yin, YangYang Wu, AnYuan Wang
The anti-malarial drug artesunate (ARS) has been shown to possess anti-inflammatory activity. Its effect on autoimmune hepatitis remains unclear. Concanavalin A (Con A)-induced hepatitis was used in this study to reveal the potential action of ARS and the related mechanism. Mice were pretreated with ARS followed by Con A challenge. Con A caused obvious hepatic injury with higher levels of liver enzymes, elevated pro-inflammatory cytokines and activation of nuclear factor-κB (NF-κB) and mitogen activated protein kinase (MAPK) signaling pathways...
July 13, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28712169/analytic-study-in-patients-presenting-to-a-tertiary-care-hospital-regarding-the-artemether-lumefantrine-induced-qtc-interval-changes-in-ecg
#5
Aliena Badshah, Iqbal Haider, Shams Suleman
BACKGROUND: Malaria is one of the most common causes of morbidity and mortality in our part of the world. Artemether-Lumefantrine (AL) Combination therapy is widely used for the treatment of malaria both in outpatients and inpatients hospital settings. Some of the previous anti-malarial were associated with prolongation of QTc interval. Similar query was raised about AL therapy. This study was conducted to determine the risk of QTc interval prolongation in ECG of patients with Falciparum malaria using oral Artemether-Lumefantrine (AL) combination therapy...
January 2017: Journal of Ayub Medical College, Abbottabad: JAMC
https://www.readbyqxmd.com/read/28705498/-hepatonephritis-during-the-treatment-of-malaria-by-the-therapeutic-combinations-from-a-pharmacovigilance-database
#6
Mamadou Kamagaté, Check Oumar Diallo, David Meless, Thérèse Daubrey-Potey, Augustine Kakou, Éric Balayssac, Kanga Sita N'zue, Jean Claude Yavo, Henri Die-Kakou
INTRODUCTION: Prior studies have shown an association between the onset of hepatonephritis and the use of arteminisin-based combination therapy (ACT) during the treatment of uncomplicated malaria. The objective of this study was to identify the risk factors of hepatonephritis occurrence because of the uncertainty regarding the appearance and the aggravation of this syndrome. METHODS: A case-non case study was carried out on 428 notifications of pharmacovigilance extracted from the database of the clinical pharmacology department of the teaching hospital of Cocody from 2008 to 2012...
April 6, 2017: Thérapie
https://www.readbyqxmd.com/read/28699823/the-gmz2-malaria-vaccine-from-concept-to-efficacy-in-humans
#7
Michael Theisen, Bright Adu, Benjamin Mordmüller, Subhash Singh
GMZ2 is a recombinant protein consisting of conserved domains of GLURP and MSP3, two asexual blood-stage antigens of Plasmodium falciparum, and is designed with the aim of mimicking naturally acquired anti-malarial immunity. The rationale for combining these two antigens is based on a series of immune epidemiological studies from geographically diverse malaria endemic regions; functional in vitro studies; and pre-clinical studies in rodents and New World monkeys. GMZ2 adjuvanted with alhydrogel® (alum) was well tolerated and immunogenic in three phase 1 studies...
July 12, 2017: Expert Review of Vaccines
https://www.readbyqxmd.com/read/28698001/biolayer-interferometry-predicts-elisa-performance-of-monoclonal-antibody-pairs-for-plasmodium-falciparum-histidine-rich-protein-2
#8
C F Markwalter, I K Jang, R A Burton, G J Domingo, D W Wright
Predicting antibody pair performance in a sandwich format streamlines development of antibody-based diagnostics and laboratory research tools, such as enzyme-linked immunosorbent assays (ELISAs) and lateral flow immunoassays (LFAs). We have evaluated panels of monoclonal antibodies against the malarial parasite biomarker Plasmodium falciparum histidine rich protein 2 (HRP2), including 9 new monoclonal antibodies, using biolayer interferometry (BLI) and screened antibody pairs in a checkerboard ELISA. This study showed BLI predicts antibody pair ELISA performance for HRP2...
July 8, 2017: Analytical Biochemistry
https://www.readbyqxmd.com/read/28697732/an-assessment-of-equity-in-the-distribution-of-non-financial-health-care-inputs-across-public-primary-health-care-facilities-in-tanzania
#9
August Kuwawenaruwa, Josephine Borghi, Michelle Remme, Gemini Mtei
BACKGROUND: There is limited evidence on how health care inputs are distributed from the sub-national level down to health facilities and their potential influence on promoting health equity. To address this gap, this paper assesses equity in the distribution of health care inputs across public primary health facilities at the district level in Tanzania. METHODS: This is a quantitative assessment of equity in the distribution of health care inputs (staff, drugs, medical supplies and equipment) from district to facility level...
July 11, 2017: International Journal for Equity in Health
https://www.readbyqxmd.com/read/28695709/-fe-s-cluster-assembly-in-the-apicoplast-and-its-indispensability-in-mosquito-stages-of-the-malaria-parasite
#10
Manish Charan, Hadi Hasan Choudhary, Nidhi Singh, Mohammad Sadik, Mohammad Imran Siddiqi, Satish Mishra, Saman Habib
The relict plastid (apicoplast) of the malaria parasite is the site for important biochemical pathways and is essential for parasite survival. The SUF pathway of [Fe-S] cluster assembly in the apicoplast of Plasmodium spp. is of interest due to its absence in the human host suggesting the possibility of anti-malarial intervention through apicoplast [Fe-S] biogenesis. We report biochemical characterization of components of the Plasmodium falciparum apicoplast SUF pathway after the first step of sulfur mobilization...
July 11, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28693488/donor-support-for-quality-assurance-and-pharmacovigilance-of-anti-malarials-in-malaria-endemic-countries
#11
Stephanie D Kovacs, Brianna M Mills, Andy Stergachis
BACKGROUND: Malaria control efforts have been strengthened by funding from donor groups and government agencies. The Global Fund to Fight AIDS, Tuberculosis and the Malaria (Global Fund), the US President's Malaria Initiative (PMI) account for the majority of donor support for malaria control and prevention efforts. Pharmacovigilance (PV), which encompasses all activities relating to the detection, assessment, understanding, and prevention of adverse effects or any other drug-related problem, is a necessary part of efforts to reduce drug resistance and improve treatment outcomes...
July 11, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28690382/qsar-based-predictive-modeling-for-anti-malarial-molecules
#12
Deepak R Bharti, Andrew M Lynn
Malaria is a predominant infectious disease, with a global footprint, but especially severe in developing countries in the African subcontinent. In recent years, drug-resistant malaria has become an alarming factor, and hence the requirement of new and improved drugs is more crucial than ever before. One of the promising locations for antimalarial drug target is the apicoplast, as this organelle does not occur in humans. The apicoplast is associated with many unique and essential pathways in many Apicomplexan pathogens, including Plasmodium...
2017: Bioinformation
https://www.readbyqxmd.com/read/28683649/in-vitro-and-in-vivo-delivery-of-artemisinin-loaded-pcl-peg-pcl-micelles-and-its-pharmacokinetic-study
#13
Hamidreza Kheiri Manjili, Hojjat Malvandi, Mir Sajjad Mousavi, Elahe Attari, Hossein Danafar
Artemisinin (ART) is a natural anti-malarial sesquiterpene lactone with anticancer properties, but its application is limited because of its low water solubility. To increase the bioavailability and water solubility of ART, we synthesized three series of poly (ɛ-caprolactone)-poly (ethylene glycol)-poly (ɛ-caprolactone) (PCL-PEG-PCL) tri-block copolymers. The structure of the copolymers was characterized by HNMR, FTIR, DSC and GPC techniques. ART was encapsulated inside micelles by a nanoprecipitation method which leading to the formation of ART/PCL-PEG-PCL micelles...
July 7, 2017: Artificial Cells, Nanomedicine, and Biotechnology
https://www.readbyqxmd.com/read/28681555/the-structure-of-plasmodium-falciparum-3d7_0606800-reveals-a-bi-lobed-architecture-that-supports-re-annotation-as-a-venus-flytrap-protein
#14
Michelle L Parker, Raghavendran Ramaswamy, Kyle van Gordon, Cameron Powell, Jürgen Bosch, Martin J Boulanger
Plasmodium falciparum, the causative agent of malaria, employs a diverse array of surface displayed proteins to promote dissemination and establish infection in the human host. Of these, Pf3D7_0606800 is highly immunogenic and has been designated a potential top 10 candidate for inclusion in a multicomponent malarial vaccine. The role of Pf3D7_0606800 in parasite biology, however, is unknown and its characterization has been complicated by a lack of sequence identity with proteins of known structure or function...
July 6, 2017: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/28680804/functions-of-tryptophan-residues-in-ewgws-insert-of-plasmodium-falciparum-enolase
#15
Sneha Dutta, Anasuya Moitra, Debanjan Mukherjee, Gotam K Jarori
Plasmodium falciparum enolase (Pfeno) is a dimeric enzyme with multiple moonlighting functions. This enzyme is thus a potential target for anti-malarial treatments. A unique feature of Pfeno is the presence of a pentapeptide insert (104) EWGWS (108). The functional role of tryptophan residues in this insert was investigated using site-directed mutagenesis. Replacement of these two Trp residues with alanines (or lysines) resulted in a near complete loss of enolase activity and dissociation of the normal dimeric form into monomers...
July 2017: FEBS Open Bio
https://www.readbyqxmd.com/read/28676355/nanos-driven-expression-of-piggybac-transposase-induces-mobilization-of-a-synthetic-autonomous-transposon-in-the-malaria-vector-mosquito-anopheles-stephensi
#16
Vanessa M Macias, Alyssa J Jimenez, Bianca Burini-Kojin, David Pledger, Nijole Jasinskiene, Celine Hien Phong, Karen Chu, Aniko Fazekas, Kelcie Martin, Osvaldo Marinotti, Anthony A James
Transposons are a class of selfish DNA elements that can mobilize within a genome. If mobilization is accompanied by an increase in copy number (replicative transposition), the transposon may sweep through a population until it is fixed in all of its interbreeding members. This introgression has been proposed as the basis for drive systems to move genes with desirable phenotypes into target species. One such application would be to use them to move a gene conferring resistance to malaria parasites throughout a population of vector mosquitos...
July 1, 2017: Insect Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28673348/anti-malarial-treatment-outcomes-in-ethiopia-a-systematic-review-and-meta-analysis
#17
Eyob Alemayehu Gebreyohannes, Akshaya Srikanth Bhagavathula, Mohammed Assen Seid, Henok Getachew Tegegn
BACKGROUND: Ethiopia is among countries with a high malaria burden. There are several studies that assessed the efficacy of anti-malarial agents in the country and this systematic review and meta-analysis was performed to obtain stronger evidence on treatment outcomes of malaria from the existing literature in Ethiopia. METHODS: A systematic literature search using the preferred reporting items for systematic review and meta-analysis (PRISMA) statement was conducted on studies from Pubmed, Google Scholar, and ScienceDirect databases to identify published and unpublished literature...
July 3, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28673299/efficacy-and-safety-evaluation-of-a-novel-trioxaquine-in-the-management-of-cerebral-malaria-in-a-mouse-model
#18
Onyango C Odhiambo, Hannah N Wamakima, Gabriel N Magoma, Peter G Kirira, Bonface J Malala, Francis T Kimani, Francis W Muregi
BACKGROUND: The emergence of multidrug-resistant strains of Plasmodium falciparum poses a great threat of increased fatalities in cases of cerebral and other forms of severe malaria infections in which parenteral artesunate monotherapy is the current drug of choice. The study aimed to investigate in a mouse model of human cerebral malaria whether a trioxaquine chemically synthesized by covalent linking of a 4,7-dichloroquinoline pharmacophore to artesunate through a recent drug development approach termed 'covalent bitherapy' could improve the curative outcomes in cerebral malaria infections...
July 3, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28673292/effect-of-pharmacogenetics-on-plasma-lumefantrine-pharmacokinetics-and-malaria-treatment-outcome-in-pregnant-women
#19
Ritah F Mutagonda, Appolinary A R Kamuhabwa, Omary M S Minzi, Siriel N Massawe, Muhammad Asghar, Manijeh V Homann, Anna Färnert, Eleni Aklillu
BACKGROUND: Pregnancy has considerable effects on the pharmacokinetic properties of drugs used to treat uncomplicated Plasmodium falciparum malaria. The role of pharmacogenetic variation on anti-malarial drug disposition and efficacy during pregnancy is not well investigated. The study aimed to examine the effect of pharmacogenetics on lumefantrine (LF) pharmacokinetics and treatment outcome in pregnant women. METHODS: Pregnant women with uncomplicated falciparum malaria were enrolled and treated with artemether-lumefantrine (ALu) at Mkuranga and Kisarawe district hospitals in Coast Region of Tanzania...
July 3, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28670640/peripheral-parasitaemia-and-its-association-with-plasma-cytokines-levels-in-malaria-infected-pregnant-women-in-aba-abia-state-nigeria
#20
M O Ifeanyichukwu, O C Okamgba, G I Amilo, E A Nwokorie
BACKGROUND: Cytokines in pregnant female may not be a normal phenomenon as malarial infection is often associated with strong CD4+ cell activation and up-regulation of pro-inflammatory cytokines. We investigated the relationship between peripheral parasitaemia and plasma levels of cytokines among malaria infected pregnant women in Aba, Abia State, Nigeria. MATERIALS AND METHODS: A total of 206 non-HIV positive asymptomatic malaria parasitaemic (n=144) and non-parasitaemic (n=62) pregnant women were recruited for this study alongside 80 non-pregnant women who served as positive (n=40) and negative (n=40) controls...
2017: African Journal of Infectious Diseases
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