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Rajesh Deshwal
OBJECTIVE: The clinical presentations and laboratory profile of malaria has been changing over the years. Therefore this study was undertaken to study the clinical profile and laboratory parameters of malarial patients. METHODS: This prospective observational study was undertaken in military hospital with high prevalence of malaria. A total of 320 patients were studied. All patients tested positive by peripheral blood smear or rapid diagnostic test were included...
August 2016: Journal of the Association of Physicians of India
Aditi A Sidhaye, Kanchan C Bhuran, Sneha Zambare, Munna Abubaker, Niroshini Nirmalan, Kamalinder K Singh
AIM: The intra-erythrocytic development of the malarial parasite is dependent on active uptake of nutrients, including human serum albumin (HSA), into parasitized red blood cells (pRBCs). We have designed HSA-based nanoparticles as a potential drug-delivery option for antimalarials. METHODS: Artemether-loaded nanoparticles (AANs) were designed and antimalarial activity evaluated in vitro/in vivo using Plasmodium falciparum/Plasmodium berghei species, respectively...
October 19, 2016: Nanomedicine
Beatrice I Amboko, Philip Ayieko, Morris Ogero, Thomas Julius, Grace Irimu, Mike English
BACKGROUND: Up to 90 % of the global burden of malaria morbidity and mortality occurs in sub-Saharan Africa and children under-five bear a disproportionately high malaria burden. Effective inpatient case management can reduce severe malaria mortality and morbidity, but there are few reports of how successfully international and national recommendations are adopted in management of inpatient childhood malaria. METHODS: A descriptive cross-sectional study of inpatient malaria case management practices was conducted using data collected over 24 months in five hospitals from high malaria risk areas participating in the Clinical Information Network (CIN) in Kenya...
October 18, 2016: Malaria Journal
Abhishek Srivastava, Vijender Panduga, Ramanatha Saralaya, Prabhakar Kr, Shahul Hameed, Suresh Solapure, Vinayak Hosagrahara
During the course of metabolic profiling of lead Compound 1, glutathione (GSH) conjugates were detected in rat bile, suggesting the formation of reactive intermediate precursor(s). This was confirmed by the identification of GSH and N-acetylcysteine (NAC) conjugates in microsomal incubations. It was proposed that bioactivation of Compound 1 occurs via the formation of a di-iminoquinone reactive intermediate through the involvement of the C-2 and C-5 nitrogens of the pyrimidine core. To further investigate this hypothesis, structural analogues with modifications at the C-5 nitrogen were studied for metabolic activation in human liver microsomes supplemented with GSH/NAC...
October 18, 2016: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
Claire Le Manach, Aloysius T Nchinda, Tanya Paquet, Diego Gonzalez Cabrera, Yassir Younis Adam, Ze Han, Sridevi Bashyam, Mohammed Zabiulla, Dale Taylor, Nina Lawrence, Karen L White, Susan A Charman, David Waterson, Michael J Witty, Sergio Wittlin, Mariette E Botha, Sindisiswe H Nondaba, Janette Reader, Lyn-Marie Birkholtz, Maria Belen Jimenez-Diaz, Maria S Martínez-Martínez, Santiago Ferrer-Bazaga, Iñigo Angulo-Barturen, Stephan Meister, Yevgeniya Antonova-Koch, Elizabeth A Winzeler, Leslie J Street, Kelly Chibale
Introduction of water-solubilizing groups on the 5-phenyl ring of a 2-aminopyrazine series led to the identification of highly potent compounds against the blood life-cycle stage of the human malaria parasite Plasmodium falciparum. Several compounds displayed high in vivo efficacy in two different mouse models for malaria, P. berghei-infected mice and P. falciparum-infected NOD-scid IL-2Rγnull mice. One of the frontrunners, compound 3, was identified to also have good pharmacokinetics, and additionally, very potent activity against the liver and gametocyte parasite life-cycle stages...
October 17, 2016: Journal of Medicinal Chemistry
Dene R Littler, Hayley E Bullen, Katherine L Harvey, Travis Beddoe, Brendan S Crabb, Jamie Rossjohn, Paul R Gilson
The ubiquitous second messenger cAMP mediates signal transduction processes in the malarial parasite that regulate host erythrocyte invasion and the proliferation of merozoites. In Plasmodium falciparum the central receptor for cAMP is the single regulatory subunit (R) of Protein kinase A (PKA). To aid the development of compounds that can selectively dysregulate parasite PKA signalling we solved the structure of the PKA regulatory subunit in complex with cAMP and a related analog that displays antimalarial activity: Sp-2Cl-cAMPS...
October 13, 2016: Journal of Biological Chemistry
Praveen K Bharti, Man M Shukla, Pascal Ringwald, Sri Krishna, Pushpendra P Singh, Ajay Yadav, Sweta Mishra, Usha Gahlot, Jai P Malaiya, Amit Kumar, Shambhu Prasad, Pradeep Baghel, Mohan Singh, Jaiprakash Vadadi, Mrigendra P Singh, Maria Dorina G Bustos, Leonard I Ortega, Eva-Maria Christophel, Sher S Kashyotia, Gagan S Sonal, Neeru Singh
BACKGROUND: Anti-malarial drug resistance continues to be a leading threat to malaria control efforts and calls for continued monitoring of waning efficacy of artemisinin-based combination therapy (ACT). Artesunate + sulfadoxine/pyrimethamine (AS + SP) is used for the treatment of uncomplicated Plasmodium falciparum malaria in India. However, resistance against AS + SP is emerged in northeastern states. Therefore, artemether-lumefantrine (AL) is the recommended first line treatment for falciparum malaria in north eastern states...
October 13, 2016: Malaria Journal
Rapeephan R Maude, Aniruddha Ghose, Rasheda Samad, Hanna K de Jong, Masako Fukushima, Lalith Wijedoru, Mahtab Uddin Hassan, Md Amir Hossain, Md Rezaul Karim, Abdullah Abu Sayeed, Stannie van den Ende, Sujat Pal, A S M Zahed, Wahid Rahman, Rifat Karnain, Rezina Islam, Dung Thi Ngoc Tran, Tuyen Thanh Ha, Anh Hong Pham, James I Campbell, H Rogier van Doorn, Richard J Maude, Tom van der Poll, W Joost Wiersinga, Nicholas P J Day, Stephen Baker, Arjen M Dondorp, Christopher M Parry, Md Abul Faiz
BACKGROUND: Fever is a common cause of hospital admission in Bangladesh but causative agents, other than malaria, are not routinely investigated. Enteric fever is thought to be common. METHODS: Adults and children admitted to Chittagong Medical College Hospital with a temperature of ≥38.0 °C were investigated using a blood smear for malaria, a blood culture, real-time PCR to detect Salmonella Typhi, S. Paratyphi A and other pathogens in blood and CSF and an NS1 antigen dengue ELISA...
October 13, 2016: BMC Infectious Diseases
Thomas E Kraft, Monique R Heitmeier, Marina Putanko, Rachel L Edwards, Ma Xenia G Ilagan, Maria A Payne, Joseph M Autry, David D Thomas, Audrey R Odom, Paul W Hruz
The glucose transporter PfHT is essential to the survival of the malaria parasite Plasmodium falciparum and has been shown to be a druggable target with high potential for pharmacological intervention. Identification of compounds against novel drug targets is crucial to combating resistance against current therapeutics. Here, we describe the development of a cell-based assay system readily adaptable to high-throughput screening that directly measures compound effects on PfHT-mediated glucose transport. Intracellular glucose concentrations are detected using a genetically encoded fluorescence resonance energy transfer (FRET)-based glucose-sensor...
October 10, 2016: Antimicrobial Agents and Chemotherapy
Karin Blomqvist, Christen DiPetrillo, Vincent A Streva, Stewart Pine, Jeffrey D Dvorin
Emerging resistance to current anti-malarials necessitates a more detailed understanding of the biological processes of Plasmodium falciparum proliferation, thus allowing identification of new drug targets. The well-conserved protein Receptor for Activated C-Kinase 1 (RACK1) was originally identified in mammalian cells as an anchoring protein for protein kinase C (PKC) and has since been shown to be important for cell migration, cytokinesis, transcription, epigenetics, and protein translation. The P. falciparum ortholog, PfRACK1, is expressed in blood stages of the parasite and is diffusely localized in the parasite cytoplasm...
October 11, 2016: Molecular and Biochemical Parasitology
Ryan A Zander, Jenna J Guthmiller, Amy C Graham, Rosemary L Pope, Bradly E Burke, Daniel J J Carr, Noah S Butler
CD4 T cell-dependent antibody responses are essential for limiting Plasmodium parasite replication and the severity of malaria; however, the factors that regulate humoral immunity during highly inflammatory, Th1-biased systemic infections are poorly understood. Using genetic and biochemical approaches, we show that Plasmodium infection-induced type I interferons limit T follicular helper accumulation and constrain anti-malarial humoral immunity. Mechanistically we show that CD4 T cell-intrinsic type I interferon signaling induces T-bet and Blimp-1 expression, thereby promoting T regulatory 1 responses...
October 2016: PLoS Pathogens
Harini R, Karthik N Sasalu, K V Chandrashekhar
No abstract text is available yet for this article.
January 2016: Journal of the Association of Physicians of India
Parveen Malhotra, Ajay Chugh, Abhishek Chaturvedi, Yogesh Sanwariya
No abstract text is available yet for this article.
January 2016: Journal of the Association of Physicians of India
Emma R Cold, Gerardo R Vasta, Josà A Fernà Ndez-Robledo
Perkinsus marinus is a protozoan parasite of molluscs that can be propagated in vitro in a defined culture medium, in the absence of host cells. We previously reported that P. marinus trophozoites can be transfected with high efficiency by electroporation using a plasmid based on MOE, a highly expressed gene, and proposed its potential use as a "pseudoparasite". This is a novel gene expression platform for parasites of medical relevance for which the choice of the surrogate organism is based on phylogenetic affinity to the parasite of interest, while taking advantage of the whole engineered surrogate organism as a vaccination adjuvant...
October 10, 2016: Journal of Parasitology
I Moghaddasifar, K B Lankarani, M Moosazadeh, M Afshari, A Ghaemi, M Aliramezany, R Afsar Gharebagh, M Malary
BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease in developing and developed countries. Estimating the total prevalence of NAFLD by means of appropriate statistical methods can provide reliable evidence for health policy makers. OBJECTIVE: To determine the prevalence of NAFLD in Iran using a systematic review and meta-analysis. METHODS: We identified relevant studies by searching national and international databases...
2016: International Journal of Organ Transplantation Medicine
Anju Singh, Mudasir Maqbool, Mohammad Mobashir, Nasimul Hoda
Malaria is a critical human disease with extensive exploration yet unestablished due to occurrence of frequent drug resistance. This aspect of malaria pharmacology calls for the introduction of new antimalarial. The drugs reported till date targeted different stages of the parasites in order to stop their growth and proliferation. Beside this, various drugs that could inhibit the imperative enzymes of the parasite have also been reported. Amid them, dihydroorotate dehydrogenase (DHODH) has a key worth. DHODH is involved in the de novo pyrimidine biosynthesis of the malarial parasite which acts as a primary source of energy for its survival...
September 27, 2016: European Journal of Medicinal Chemistry
Tomoyo Sakata-Kato, Dyann F Wirth
Given that resistance to all drugs in clinical use has arisen, discovery of new anti-malarial drug targets is eagerly anticipated. The Plasmodium mitochondrion has been considered a promising drug target largely based on its significant divergence from the host organelle as well as its involvement in ATP production and pyrimidine biosynthesis. However, the functions of Plasmodium mitochondrial protein complexes and associated metabolic pathways are not fully characterized. Here, we report the development of novel and robust bioenergetic assay protocols for Plasmodium falciparum asexual parasites utilizing a Seahorse Bioscience XFe24 Extracellular Flux Analyzer...
October 9, 2016: ACS Infectious Diseases
Saw Thu Wah, Hathairad Hananantachai, Usanee Kerdpin, Chotiros Plabplueng, Virapong Prachayasittikul, Pornlada Nuchnoi
Cerebral malaria is still a deleterious health problem in tropical countries. The wide spread of malarial drug resistance and the lack of an effective vaccine are obstacles for disease management and prevention. Parasite and human genetic factors play important roles in malaria susceptibility and disease severity. The malaria parasite exerted a potent selective signature on the human genome, which is apparent in the genetic polymorphism landscape of genes related to pathogenesis. Currently, much genomic data and a novel body of knowledge, including the identification of microRNAs, are being increasingly accumulated for the development of laboratory testing cassettes for cerebral malaria prevention...
2016: Tropical Medicine and Health
H Liu, G G Wu, J B Wang, X Wu, L Bai, W Jiang, B B Lv, A H Pan, J W Jia, P Li, K Zhao, L X Jiang, X M Tang
The anti-malarial drug, artemisinin, is quite expensive as a result of its slow content in Artemisia annua. Recent investigations have suggested that genetic engineering of A. annua is a promising approach to improve the yield of artemisinin. In this study, the transgenic A. annua strain GYR, which has high artemisinin content, was evaluated in an environmental release trial. First, GYR plants were compared with the wild-type variety NON-GYR, with regard to phenotypic characters (plant height, crown width, stem diameter, germination rate, leaf dry weight, 1000-seed weight, leave shape)...
August 26, 2016: Genetics and Molecular Research: GMR
Dev Bukhsh Singh, Seema Dwivedi
S-adenosyl-L-homocysteine hydrolase of Plasmodium falciparum (PfSAHH) is a potential drug target against malaria, and selective inhibition of PfSAHH is the excellent strategy to prevent the growth of parasite inside the host. Therefore, a comparative analysis of human S-adenosyl-L-homocysteine hydrolase (HsSAHH) and PfSAHH has been performed to explore the structural differences. Structural superimposition of PfSAHH and HsSAHH has generated the RMSD of 0.749 Å over 394 alpha carbon pairs. Residues of PfSAHH from position Tyr152 to Lys193 aligned with insertion/deletion region in HsSAHH, and these extra residues results in an extent of variation in cavity region of PfSAHH...
October 2016: Journal of Chemical Biology
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