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Antimalarial drug

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https://www.readbyqxmd.com/read/28939626/remission-and-low-disease-activity-status-ldas-protect-lupus-patients-from-damage-occurrence-data-from-a-multiethnic-multinational-latin-american-lupus-cohort-gladel
#1
Manuel Francisco Ugarte-Gil, Daniel Wojdyla, Guillermo J Pons-Estel, Luis J Catoggio, Cristina Drenkard, Judith Sarano, Guillermo A Berbotto, Eduardo F Borba, Emilia Inoue Sato, João C Tavares Brenol, Oscar Uribe, Luis A Ramirez Gómez, Marlene Guibert-Toledano, Loreto Massardo, Mario H Cardiel, Luis H Silveira, Rosa Chacón-Diaz, Graciela S Alarcón, Bernardo A Pons-Estel
OBJECTIVE: To evaluate disease activity statuses' (DAS') impact on systemic lupus erythematosus (SLE) outcomes. MATERIALS AND METHODS: Four DAS were defined: remission off-therapy: SLE Disease Activity Index (SLEDAI)=0, no prednisone or immunosuppressive drugs (IS); remission on-therapy: SLEDAI=0, prednisone ≤5 mg/day and/or IS (maintenance); low (L) DAS: SLEDAI ≤4, prednisone ≤7.5 mg/day and/or IS (maintenance); non-optimally controlled: SLEDAI >4 and/or prednisone >7...
September 22, 2017: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/28939120/synthesis-characterization-and-cellular-localization-of-a-fluorescent-probe-of-the-antimalarial-8-aminoquinoline-primaquine
#2
Adonis McQueen, Lynn D Blake, Ala Azhari, M Trent Kemp, Tommy W McGaha, Niranjan Namelikonda, Randy W Larsen, Roman Manetsch, Dennis E Kyle
Primaquine (PQ) is the only commercially available drug that clears dormant liver stages of malaria and blocks transmission to mosquito vectors. Although an old drug, much remains to be known about the mechanism(s) of action. Herein we develop a fluorescent tagged PQ to discover cellular localization in the human malaria parasite, Plasmodium falciparum. Successful synthesis and characterization of a primaquine-coumarin fluorescent probe (PQCP) demonstrated potency equivalent to the parent drug and the probe was not cytotoxic to HepG2 carcinoma cells...
September 14, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28936796/biosurfactants-produced-by-bacillus-subtilis-a1-and-pseudomonas-stutzeri-na3-reduce-longevity-and-fecundity-of-anopheles-stephensi-and-show-high-toxicity-against-young-instars
#3
Punniyakotti Parthipan, Raja Kumaresan Sarankumar, Anitha Jaganathan, Pandian Amuthavalli, Ranganathan Babujanarthanam, Pattanathu K S M Rahman, Kadarkarai Murugan, Akon Higuchi, Giovanni Benelli, Aruliah Rajasekar
Anopheles stephensi acts as vector of Plasmodium parasites, which are responsible for malaria in tropical and subtropical areas worldwide. Currently, malaria management is a big challenge due to the presence of insecticide-resistant strains as well as to the development of Plasmodium species highly resistant to major antimalarial drugs. Therefore, the present study focused on biosurfactant produced by two bacteria Bacillus subtilis A1 and Pseudomonas stutzeri NA3, evaluating them for insecticidal applications against malaria mosquitoes...
September 21, 2017: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/28935919/split-dosing-of-artemisinins-does-not-improve-antimalarial-therapeutic-efficacy
#4
N J White, J Watson, E A Ashley
It has been suggested recently, based on pharmacokinetic-pharmacodynamic modelling exercises, that twice daily dosing of artemisinins increases malaria parasite killing and so could "dramatically enhance and restore drug effectiveness" in artemisinin resistant P. falciparum malaria infections. It was recommended that split dosing should be incorporated into all artemisinin combination regimen designs. To explain why parasite clearance rates were not faster with split dose regimens it was concluded that splenic malaria parasite clearance capacity was readily exceeded, resulting in the accumulation of dead parasites in the circulation, that parasite clearance was therefore an unreliable measure of drug efficacy, and instead that human immunity is the primary determinant of clearance rates...
September 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28934933/medicine-use-practices-in-management-of-symptoms-of-acute-upper-respiratory-tract-infections-in-children-%C3%A2-12%C3%A2-years-in-kampala-city-uganda
#5
Moses Ocan, Mary Aono, Clare Bukirwa, Emmanuel Luyinda, Cathy Ochwo, Elastus Nsambu, Stella Namugonza, Joseph Makoba, Enock Kandaruku, Hannington Muyende, Aida Nakawunde
BACKGROUND: Medicines are commonly accessed and used for management of illness in children without a prescription. This potentially increases the risk of unwanted treatment outcomes. We investigated medicine use practices in management of symptoms of acute upper respiratory tract infections among children (≤12 years) in households in Nakawa division, Kampala city. METHODS: This was a cross-sectional study conducted among 390 randomly selected children. Data on use of medicines in children (≤12 years) during recent episode of acute upper respiratory tract infection was collected from their care takers using an interviewer administered questionnaire...
September 21, 2017: BMC Public Health
https://www.readbyqxmd.com/read/28934264/profiling-molecular-factors-associated-with-pyknosis-and-developmental-arrest-induced-by-an-opioid-receptor-antagonist-and-dihydroartemisinin-in-plasmodium-falciparum
#6
Hiroko Asahi, Shin-Ichi Inoue, Mamoru Niikura, Keisuke Kunigo, Yutaka Suzuki, Fumie Kobayashi, Fujiro Sendo
Malaria continues to be a devastating disease, largely caused by Plasmodium falciparum infection. We investigated the effects of opioid and cannabinoid receptor antagonists on the growth of intraerythrocytic P. falciparum. The delta opioid receptor antagonist 7-benzylidenenaltrexone (BNTX) and the cannabinoid receptor antagonists rimonaband and SR144528 caused growth arrest of the parasite. Notably BNTX and the established antimalarial drug dihydroartemisinin induced prominent pyknosis in parasite cells after a short period of incubation...
2017: PloS One
https://www.readbyqxmd.com/read/28932226/immunomodulatory-properties-of-coriolus-versicolor-the-role-of-polysaccharopeptide
#7
REVIEW
Mohammad H Saleh, Iran Rashedi, Armand Keating
Traditional uses of herbal medicine have depended mostly on anecdotal evidence for much of history. The increasing application of scientific rigor to the study some of these traditional therapies in recent years has revealed potent bioactivity, notably demonstrated by the 2015 Nobel Prize for the discovery of an antimalarial compound from traditional Chinese herbs. Given the recent successes of immunotherapy and checkpoint blockade, there is a renewed interest in identifying new drugs with immunomodulatory effects...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28932197/antiplasmodial-activity-and-toxicological-assessment-of-curcumin-plga-encapsulated-nanoparticles
#8
Zulaikha A Busari, Kabiru A Dauda, Olajumoke A Morenikeji, Funmilayo Afolayan, Oyetunde T Oyeyemi, Jairam Meena, Debasis Sahu, Amulya K Panda
Curcumin is a polyphenolic pigment isolated from the rhizomes of Curcuma longa (turmeric), a medicinal plant widely used in the ancient Indian and Chinese medicine. The antiplasmodial activity of curcumin is often hampered by its fast metabolism and poor water solubility, thus its incorporation into a delivery system could circumvent this problem. This study aimed to evaluate the in vivo antiplasmodial activity and the toxicity assessment of curcumin incorporated into poly (lactic-co-glycolic) acid (PLGA) nanoparticles...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28929019/heterologous-expression-of-plasmodium-vivax-apical-membrane-antigen-1-pvama1-for-binding-peptide-selection
#9
Ching Hoong Chew, Yvonne Ai Lian Lim, Kek Heng Chua
BACKGROUND: Plasmodium is an obligate intracellular parasite. Apical membrane antigen 1 (AMA1) is the most prominent and well characterized malarial surface antigen that is essential for parasite-host cell invasion, i.e., for sporozoite to invade and replicate within hepatocytes in the liver stage and merozoite to penetrate and replicate within erythrocytes in the blood stage. AMA1 has long served as a potent antimalarial drug target and is a pivotal vaccine candidate. A good understanding of the structure and molecular function of this Plasmodium protein, particularly its involvement in host-cell adhesion and invasion, is of great interest and hence it offers an attractive target for the development of novel therapeutics...
2017: PeerJ
https://www.readbyqxmd.com/read/28927276/alkoxycarbonate-ester-prodrugs-of-preclinical-drug-candidate-elq-300-for-prophylaxis-and-treatment-of-malaria
#10
Lisa Frueh, Yuexin Li, Michael Mather, Qigui Li, Sovitj Pou, Aaron Nilsen, Rolf W Winter, Isaac Forquer, April Pershing, Lisa H Xie, Martin J Smilkstein, Diana Caridha, Robert F Campbell, Richard J Sciotti, Mara Kreishman-Deitrick, Jane X Kelly, Brian Andrew Vesely, Akhil Vaidya, Michael K Riscoe
ELQ-300 is a preclinical antimalarial drug candidate that is active against liver, blood, and transmission stages of Plasmodium falciparum. While ELQ-300 is highly effective when administered in a low multi-dose regimen, poor aqueous solubility and high crystallinity have hindered its clinical development. To overcome its challenging physiochemical properties, a number of bioreversible alkoxycarbonate ester prodrugs of ELQ-300 were synthesized. These bioreversible prodrugs are converted to ELQ-300 by host and parasite esterase action in the liver and bloodstream of the host...
September 19, 2017: ACS Infectious Diseases
https://www.readbyqxmd.com/read/28923866/changing-antimalarial-drug-sensitivities-in-uganda
#11
Stephanie A Rasmussen, Frida G Ceja, Melissa D Conrad, Patrick K Tumwebaze, Oswald Byaruhanga, Thomas Katairo, Samuel L Nsobya, Philip J Rosenthal, Roland A Cooper
Dihydroartemisinin-piperaquine (DP) has demonstrated excellent efficacy for the treatment and prevention of malaria in Uganda. However, resistance to both components of this regimen has emerged in Southeast Asia. The efficacy of artemether-lumefantrine, the first-line regimen to treat malaria in Uganda, has also been excellent, but continued pressure may select for parasites with decreased sensitivity to lumefantrine. To gain insight into current drug sensitivity patterns, ex vivo sensitivities were assessed and genotypes previously associated with altered drug sensitivity were characterized for 58 isolates collected in Tororo, Uganda from subjects presenting in 2016 with malaria from the community or as part of a clinical trial comparing DP chemoprevention regimens...
September 18, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28917450/a-novel-class-of-plasmodial-clpp-protease-inhibitors-as-potential-antimalarial-agents
#12
Sourabh Mundra, Vandana Thakur, Angelica M Bello, Sumit Rathore, Mohd Asad, Lianhu Wei, Jane Yang, Sai Kumar Chakka, Radhakrishnan Mahesh, Pawan Malhotra, Asif Mohmmed, Lakshmi P Kotra
The prokaryotic ATP-dependent ClpP protease, localized in the relict plastid of malaria parasite, represents a potential drug target. In the present study, we utilized in silico structure-based screening and medicinal chemistry approaches to identify a novel pyrimidine series of compounds inhibiting P. falciparum ClpP protease activity and evaluated their antiparasitic activities. Structure-activity relationship indicated that morpholine moiety at C2, an aromatic substitution at N3 and a 4-oxo moiety on the pyrimidine are important for potent inhibition of ClpP enzyme along with antiparasiticidal activity...
September 5, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28917086/kostchyienones-a-and-b-new-antiplasmodial-and-cytotoxicity-of-limonoids-from-the-roots-of-pseudocedrela-kotschyi-schweinf-harms
#13
Lazare S Sidjui, Yves O D Nganso, Rufin M K Toghueo, Brussine N K Wakeu, Joel T Dameue, Pierre Mkounga, Achyut Adhikari, Mehreen Lateef, Gabriel N Folefoc, Muhammad S Ali
Two new limonoids, kostchyienones A (1) and B (2), along with 12 known compounds 3-14 were isolated from the roots of Pseudocedrela kostchyi. Compound (7) was isolated for the first time from a natural source. Their structures were elucidated on the basis of spectroscopic evidence. Compounds 1-6 and 13-14 gave IC50 values ranging from 0.75 to 5.62 μg/mL for antiplasmodial activity against chloroquine-sensitive (Pf3D7) and chloroquine-resistant (PfINDO) strains of Plasmodium falciparum. Compound 5 showed moderate potential cytotoxicity against the HEK239T cell line with an IC50 value of 22...
September 16, 2017: Zeitschrift Für Naturforschung. C, A Journal of Biosciences
https://www.readbyqxmd.com/read/28916443/aq-13-an-investigational-antimalarial-versus-artemether-plus-lumefantrine-for-the-treatment-of-uncomplicated-plasmodium-falciparum-malaria-a-randomised-phase-2-non-inferiority-clinical-trial
#14
Ousmane A Koita, Lansana Sangaré, Haiyan D Miller, Aliou Sissako, Moctar Coulibaly, Trevor A Thompson, Saharé Fongoro, Youssouf Diarra, Mamadou Ba, Ababacar Maiga, Boubakar Diallo, David M Mushatt, Frances J Mather, Jeffrey G Shaffer, Asif H Anwar, Donald J Krogstad
BACKGROUND: Chloroquine was used for malaria treatment until resistant Plasmodium falciparum was identified. Because 4-aminoquinolines with modified side chains, such as AQ-13, are active against resistant parasites, we compared AQ-13 against artemether plus lumefantrine for treatment of uncomplicated P falciparum malaria. METHODS: We did a randomised, non-inferiority trial. We screened men (≥18 years) with uncomplicated malaria in Missira (northeast Mali) and Bamako (capital of Mali) for eligibility (≥2000 asexual P falciparum parasites per μL of blood)...
September 12, 2017: Lancet Infectious Diseases
https://www.readbyqxmd.com/read/28914184/elements-of-effective-community-engagement-lessons-from-a-targeted-malaria-elimination-study-in-lao-pdr-laos
#15
Bipin Adhikari, Christopher Pell, Koukeo Phommasone, Xayaphone Soundala, Palingnaphone Kommarasy, Tiengkham Pongvongsa, Gisela Henriques, Nicholas P J Day, Mayfong Mayxay, Phaik Yeong Cheah
BACKGROUND: Mass drug (antimalarial) administration (MDA) is currently under study in Southeast Asia as part of a package of interventions referred to as targeted malaria elimination (TME). This intervention relies on effective community engagement that promotes uptake and adherence in target communities (above 80%). OBJECTIVE: Based on the experienced of designing and implementing the community engagement for TME in Laos, in this article we aim to present the elements of effective community engagement for mass antimalarial administration...
2017: Global Health Action
https://www.readbyqxmd.com/read/28913596/-perioperative-management-of-immunosuppressive-treatment-in-patients-undergoing-joint-surgery
#16
K Krüger
The perioperative management of patients on immunosuppressive drugs is uncertain due to a lack of controlled studies. Continuation of medication without a pause may increase the risk of postoperative infections and wound healing disorders and when the pause is too long this can induce a flare of the underlying rheumatic disease. Additional factors, such as rheumatic disease activity, comorbidities, previous infections and the type of surgical procedure also modulate the risk. The highest risk of infection is associated with corticosteroids depending on the dose, so that a dosage as low as possible but stable in the perioperative period is recommended...
September 14, 2017: Zeitschrift Für Rheumatologie
https://www.readbyqxmd.com/read/28902434/biologically-active-quinoline-and-quinazoline-alkaloids-part-i
#17
REVIEW
Xiao-Fei Shang, Susan L Morris-Natschke, Ying-Qian Liu, Xiao Guo, Xiao-Shan Xu, Masuo Goto, Jun-Cai Li, Guan-Zhou Yang, Kuo-Hsiung Lee
Quinoline and quinazoline alkaloids, two important classes of N-based heterocyclic compounds, have attracted tremendous attention from researchers worldwide since the 19th century. Over the past 200 years, many compounds from these two classes were isolated from natural sources, and most of them and their modified analogs possess significant bioactivities. Quinine and camptothecin are two of the most famous and important quinoline alkaloids, and their discoveries opened new areas in antimalarial and anticancer drug development, respectively...
September 13, 2017: Medicinal Research Reviews
https://www.readbyqxmd.com/read/28901270/reappraisal-of-antimalarials-in-interferonopathies-new-perspectives-for-old-drugs
#18
Elisa Piscianz, Eva Cuzzoni, Rajan Sharma, Alessandra Tesser, Pooja Sapra, Alberto Tommasini
The story of antimalarials as antinflammatory drugs dates back several centuries. Chinin, the extract of the Cinchona bark, has been exploited since the 18th century for its antimalarial and antifebrile properties. Later, during the Second World War, the broad use of antimalarials allowed arguing their antirheumatic effect on soldiers. Since then, these drugs have been broadly used to treat Systemic Lupus Erythematosus, but, only recently, have the molecular mechanisms of action been partly clarified. Inhibitory action on vacuole function and trafficking has been considered for decades the main mechanism of the action of antimalarials, affecting the activation of phagocytes and dendritic cells...
September 11, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28898049/analysis-of-plasmodium-vivax-chloroquine-resistance-transporter-pvcrt-mutant-isoforms
#19
Matthew R Hassett, Bryce E Riegel, Paul Samuel Callaghan, Paul David Roepe
Chloroquine (CQ) resistance (CQR) in Plasmodium falciparum malaria is widespread and has limited the use of CQ in many regions of the globe. Malaria caused by the related human parasite P. vivax is as widespread as is P. falciparum malaria and has been treated with CQ as extensively as has P. falciparum, suggesting that P. vivax parasites have been selected with CQ as profoundly as have P. falciparum parasites. Indeed, a growing number of clinical reports have presented data suggesting increased P. vivax CQR...
September 12, 2017: Biochemistry
https://www.readbyqxmd.com/read/28893781/identification-of-heparin-modifications-and-polysaccharide-inhibitors-of-plasmodium-falciparum-merozoite-invasion-that-have-potential-for-novel-drug-development
#20
Michelle J Boyle, Mark Skidmore, Benjamin Dickerman, Lynsay Cooper, Antony Devlin, Edwin Yates, Paul Horrocks, Craig Freeman, Wengang Chai, James G Beeson
Despite recent successful control efforts, malaria remains a leading global health burden. Alarmingly, resistance to current antimalarials is increasing, and the development of new drug families is needed to maintain malaria control. Current antimalarials target the intra-erythrocytic developmental stage of the Plasmodium falciparum life cycle. However, the invasive extracellular parasite form, the merozoite, is also an attractive target for drug development. We have previously demonstrated that heparin-like-molecules, including those with low molecular weights and low anti-coagulant activities are potent and specific inhibitors of merozoite invasion and blood-stage replication...
September 11, 2017: Antimicrobial Agents and Chemotherapy
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