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https://www.readbyqxmd.com/read/29791525/2-3-8-trisubstituted-quinolines-with-antimalarial-activity
#1
Pablo D G Martinez, Susann H Krake, Maitia L Poggi, Simon F Campbell, Paul A Willis, Luiz C Dias
Combination therapy drugs are considered a fundamental way to control malaria as it mimimizes the risk of emergence of resistance to the individual partner drugs. Consequently, this type of therapy constitutes a driving force for the discovery of new drugs with different modes of action, since this will provide options for combining different drugs to achieve the optimum antimalarial treatment. In this context, a 2,3,8-trisubstitued quinoline compound was found in a high throughput screen (HTS) to show an excellent inhibition of P...
May 21, 2018: Anais da Academia Brasileira de Ciências
https://www.readbyqxmd.com/read/29784846/pharmacokinetics-of-piperaquine-and-safety-profile-of-dihydroartemisinin-piperaquine-co-administered-with-antiretroviral-therapy-in-malaria-uninfected-hiv-positive-malawian-adults
#2
Clifford G Banda, Fraction Dzinjalamala, Mavuto Mukaka, Jane Mallewa, Victor Maiden, Dianne J Terlouw, David G Lalloo, Saye H Khoo, Victor Mwapasa
There are limited data on the pharmacokinetic and safety profiles of dihydroartemisinin-piperaquine (DHA-PQ) among human immunodeficiency virus infected (HIV+) individuals taking antiretroviral therapy (ART). In a two step (parallel-group) pharmacokinetic trial with intensive blood sampling, we compared area under the concentration-time curve (AUC0-28 days ) and safety outcomes of piperaquine among malaria-uninfected HIV+ adults. In step 1, half the adult dose of DHA-PQ was administered for three days as an intitial safety check in four groups (n=6/group) of HIV+ adults (age≥18 years): (i) antiretroviral-naïve, (ii) on nevirapine-based ART, (iii) on efavirenz-based ART, and (iv) on ritonavir-boosted lopinavir-based ART...
May 21, 2018: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29784841/the-metabolism-of-piperaquine-to-its-antiplasmodial-metabolites-and-their-pharmacokinetic-profiles-in-healthy-volunteers
#3
Huixiang Liu, Hongchang Zhou, Tianyu Cai, Aijuan Yang, Meitong Zang, Jie Xing
As a partner antimalarial for artemisinin drug-based combination therapy (ACT), piperaquine (PQ) can be metabolized into two major metabolites, including piperaquine N -oxide (M1) and N , N -dioxide (M2). To better understand the antimalarial potency of PQ, the antimalarial activity of PQ metabolites (M1 and M2) was studied in vitro ( Plasmodium strains Pf 3D7 and Pf Dd2) and in vivo (murine Plasmodium yoelii ) in this study. The recrudescence and survival time of infected mice were also recorded after drug treatment...
May 21, 2018: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29780817/clinical-profile-and-outcome-of-patients-with-acute-kidney-injury-requiring-hemodialysis-two-years-experience-at-a-tertiary-hospital-in-rwanda
#4
Grace Igiraneza, Benedicte Ndayishimiye, Menelas Nkeshimana, Vincent Dusabejambo, Onyema Ogbuagu
Introduction: Acute kidney injury (AKI) requiring renal replacement therapy is associated with high mortality. The study assessed the impact of the introduction of hemodialysis (HD) on outcomes of patients with AKI in Rwanda. Methods: A single center retrospective study that evaluated the clinical profile and survival outcomes of patients with AKI requiring HD [AKI-D] at a tertiary hospital in Rwanda. Data was collected on patients who received HD for AKI from September 2014 to December 2016...
2018: BioMed Research International
https://www.readbyqxmd.com/read/29779499/efficacy-of-artemisinin-naphthoquine-phosphate-against-schistosoma-haematobium-adult-flukes-dose-effect-relationship-and-tegumental-alterations
#5
S N El-Beshbishi, S El Bardicy, M Tadros, M Ayoub, A Taman
Schistosoma haematobium and Schistosoma mansoni infections have broadly overlapping geographical distributions. Praziquantel is the only treatment for human schistosomiasis, so drug tolerance and/or resistance are major concerns. Artemisinin-naphthoquine phosphate (CO-ArNp), an artemisinin-based combination therapy endorsed by the World Health Organization as a gold standard therapy for malaria, has also been identified as a promising treatment for S. mansoni. In this in vitro study, we tested the effect of 1-40 μg/ml CO-ArNp on S...
May 21, 2018: Journal of Helminthology
https://www.readbyqxmd.com/read/29776367/malaria-determining-risk-factors-at-the-household-level-in-two-rural-villages-of-mainland-equatorial-guinea
#6
Mónica Guerra, Bruno de Sousa, Nicolas Ndong-Mabale, Pedro Berzosa, Ana Paula Arez
BACKGROUND: After the introduction of an artemisinin-based combination therapy, the reduction of prevalence of malaria infections has shown a remarkable progress during the last decade. However due to the lack of a consistent malaria control programme and socioeconomic inequalities, Plasmodium infection is still one of the major cause of disease in Equatorial Guinea, namely in the rural communities. This study explored the associated risk factors of malaria transmission at the microeconomic level (households) in two rural villages of mainland Equatorial Guinea...
May 18, 2018: Malaria Journal
https://www.readbyqxmd.com/read/29770278/-2tm-proteins-an-antigenically-diverse-superfamily-with-variable-functions-and-export-pathways
#7
Jasweer Kaur, Rachna Hora
Malaria is a disease that affects millions of people annually. An intracellular habitat and lack of protein synthesizing machinery in erythrocytes pose numerous difficulties for survival of the human pathogen Plasmodium falciparum . The parasite refurbishes the infected red blood cell (iRBC) by synthesis and export of several proteins in an attempt to suffice its metabolic needs and evade the host immune response. Immune evasion is largely mediated by surface display of highly polymorphic protein families known as variable surface antigens...
2018: PeerJ
https://www.readbyqxmd.com/read/29769072/provider-and-patient-perceptions-of-malaria-rapid-diagnostic-test-use-in-nigeria-a-cross-sectional-evaluation
#8
Olugbenga A Mokuolu, Olufemi O Ajumobi, Godwin N Ntadom, Olanrewaju T Adedoyin, Alero A Roberts, Chimere O Agomo, Kate U Edozieh, Henrietta U Okafor, Robinson D Wammanda, Friday A Odey, Ibrahim K Maikore, Olatayo O Abikoye, Adekunle D Alabi, Chiomah Amajoh, Bala M Audu
BACKGROUND: Nigeria commenced a phased programmatic deployment of rapid diagnostic tests (RDT) at the primary health care (PHC) facility levels since 2011. Despite various efforts, the national testing rate for malaria is still very low. The uptake of RDT has been variable. This study was undertaken to determine the provider and patient perceptions to RDT use at the PHC level in Nigeria with their implications for improving uptake and compliance. METHODS: A cross-sectional survey was conducted in 120 randomly selected PHCs across six states, across the six-geopolitical zones of Nigeria in January 2013...
May 16, 2018: Malaria Journal
https://www.readbyqxmd.com/read/29768302/pharmacogenomics-in-papua-new-guineans-unique-profiles-and-implications-for-enhancing-drug-efficacy-while-improving-drug-safety
#9
Joseph D Tucci, Paul P Pumuye, Nuala A Helsby, Daniel T Barratt, Percy P Pokeya, Francis Hombhanje, Andrew A Somogyi
Papua New Guinea (PNG) can be roughly divided into highland, coastal and island peoples with significant mitochondrial DNA differentiation reflecting early and recent distinct migrations from Africa and East Asia, respectively. Infectious diseases such as tuberculosis, malaria and HIV severely impact on the health of its peoples for which drug therapy is the major treatment and pharmacogenetics has clinical relevance for many of these drugs. Although there is generally little information about known single nucleotide polymorphisms in the population, in some instances, their frequencies have been shown to be higher than anywhere worldwide...
June 2018: Pharmacogenetics and Genomics
https://www.readbyqxmd.com/read/29764451/phenotypic-and-genotypic-characterization-of-thai-isolates-of-plasmodium-falciparum-after-an-artemisinin-resistance-containment-project
#10
Thunyapit Thita, Pimrat Jadsri, Jarupatr Thamkhantho, Toon Ruang-Areerate, Nantana Suwandittakul, Naruemon Sitthichot, Kittiya Mahotorn, Peerapan Tan-Ariya, Mathirut Mungthin
BACKGROUND: In Thailand, artemisinin-based combination therapy (ACT) has been used to treat uncomplicated falciparum malaria since 1995. Unfortunately, artemisinin resistance has been reported from Thailand and other Southeast Asian countries since 2003. Malarone® , a combination of atovaquone-proguanil (ATQ-PG), has been used to cease artemisinin pressure in some areas along Thai-Cambodia border, as part of an artemisinin resistance containment project since 2009. This study aimed to determine genotypes and phenotypes of Plasmodium falciparum isolates collected from the Thai-Cambodia border after the artemisinin resistance containment project compared with those collected before...
May 15, 2018: Malaria Journal
https://www.readbyqxmd.com/read/29764419/pyronaridine-artesunate-and-artemether-lumefantrine-for-the-treatment-of-uncomplicated-plasmodium-falciparum-malaria-in-kenyan-children-a-randomized-controlled-non-inferiority-trial
#11
Johanna M Roth, Patrick Sawa, Nicodemus Makio, George Omweri, Victor Osoti, Selpha Okach, Felix Choy, Henk D F H Schallig, Pètra Mens
BACKGROUND: Pyronaridine-artesunate is a novel artemisinin-based combination therapy. The efficacy and safety of pyronaridine-artesunate were compared with artemether-lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria in children. METHODS: This phase III open-label randomized controlled non-inferiority trial was conducted in Western Kenya. Children aged 6 months to ≤ 12 years with a bodyweight > 5 kg and microscopically confirmed P...
May 15, 2018: Malaria Journal
https://www.readbyqxmd.com/read/29760133/pharmacokinetics-and-safety-profile-of-artesunate-amodiaquine-co-administered-with-antiretroviral-therapy-in-malaria-uninfected-hiv-positive-malawian-adults
#12
Clifford G Banda, Fraction Dzinjalamala, Mavuto Mukaka, Jane Mallewa, Victor Maiden, Dianne J Terlouw, David G Lalloo, Saye H Khoo, Victor Mwapasa
There are limited data on the pharmacokinetic and safety profiles of artesunate-amodiaquine in human immnunodeficiency virus infected (HIV+) individuals receiving antiretroviral therapy. In a two-step intensive sampling pharmacokinetic trial, we compared area under the concentration-time curve from 0 to 28 days (AUC0-28 days ) of an active metabolite of amodiaquine, desethylamodiaquine, and treatment-emergent adverse events between antiretroviral therapy-naive HIV+ adults and those taking nevirapine and ritonavir-boosted lopinavir-based antiretroviral therapy...
May 14, 2018: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29758416/drug-targets-for-resistant-malaria-historic-to-future-perspectives
#13
REVIEW
Sahil Kumar, T R Bhardwaj, D N Prasad, Rajesh K Singh
New antimalarial targets are the prime need for the discovery of potent drug candidates. In order to fulfill this objective, antimalarial drug researches are focusing on promising targets in order to develop new drug candidates. Basic metabolism and biochemical process in the malaria parasite, i.e. Plasmodium falciparum can play an indispensable role in the identification of these targets. But, the emergence of resistance to antimalarial drugs is an escalating comprehensive problem with the progress of antimalarial drug development...
May 11, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29756212/optimization-of-artemisinin-extraction-from-artemisia-annua-l-with-supercritical-carbon-dioxide-ethanol-using-response-surface-methodology
#14
Ozan Nazim Ciftci, Jessica Cahyadi, Selma E Guigard, Marleny D A Saldaña
Malaria is a high priority life-threatening public health concern in developing countries, and therefore there is a growing interest to obtain artemisinin for the production of artemisinin-based combination therapy products. In this study, artemisinin was extracted from the Artemisia annua L. plant using supercritical carbon dioxide (SC-CO2 ) modified with ethanol. Response surface methodology (RSM) based on central composite rotatable design (CCRD) was employed to investigate and optimize the extraction conditions of pressure (9...
May 13, 2018: Electrophoresis
https://www.readbyqxmd.com/read/29748995/apigenin-inhibits-growth-of-the-plasmodium-berghei-and-disrupts-some-metabolic-pathways-in-mice
#15
Mahdi Amiri, Abbasali Nourian, Maryam Khoshkam, Ali Ramazani
Due to the challenges in the control, prevention, and eradication of parasitic diseases like malaria, there is an urgent need to discover new therapeutic agents. Plant-derived medicines may open new ways in the field of antiplasmodial therapy. This study is aimed to investigate the toxicity and in vivo antiplasmodial activity of apigenin, a dietary flavonoid. Apigenin cytotoxicity was investigated on Huh7 cell line, brine shrimp (Artemia salina) larva, and human red blood cells. In vivo toxicity of apigenin was assessed by metabolomics approaches...
May 11, 2018: Phytotherapy Research: PTR
https://www.readbyqxmd.com/read/29748832/optimization-and-evaluation-of-lipid-emulsions-for-intravenous-co-delivery-of-artemether-and-lumefantrine-in-severe-malaria-treatment
#16
Yinxian Yang, Hailing Gao, Shuang Zhou, Xiao Kuang, Zhenjie Wang, Hongzhuo Liu, Jin Sun
Parenteral therapy for severe and complicated malaria is necessary, but currently available parenteral antimalarials have their own drawbacks. As for recommended artemisinin-based combination therapy, antimalarial artemether and lumefantrine are limited in parenteral delivery due to their poor water solubility. Herein, the aim of this study was to develop the lipid-based emulsions for intravenous co-delivery of artemether and lumefantrine. The lipid emulsion was prepared by high-speed shear and high-pressure homogenization, and the formulations were optimized mainly by monitoring particle size distribution under autoclaved conditions...
May 10, 2018: Drug Delivery and Translational Research
https://www.readbyqxmd.com/read/29746932/prevention-of-carcinogenesis-and-metastasis-by-artemisinin-type-drugs
#17
Mohammed L Abba, Nitin Patil, Jörg Hendrik Leupold, Mohamed E M Saeed, Thomas Efferth, Heike Allgayer
Artemisia annua (sweet wormwood, qinhao) is an ancient Chinese herbal remedy for pyrexia. Nowadays, artemisinin (qinghaosu) and its derivatives belong to the standard therapies against malaria worldwide, and its discovery has led to the Nobel Prize in Physiology and Medicine to Youyou Tu in 2015. While most attention has been paid to the treatment of malaria, there is increasing evidence that Artemisinin-type drugs bear a considerable potential to treat and prevent cancer. Rather than reporting on therapy of cancer, this review gives a comprehensive and timely overview on the chemopreventive effects of artemisinin and its derivatives against carcinogenesis and metastasis formation, following the multistage model of carcinogenesis (initiation, promotion, progression)...
May 7, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29743474/a-comprehensive-model-for-assessment-of-liver-stage-therapies-targeting-plasmodium-vivax-and-plasmodium-falciparum
#18
Alison Roth, Steven P Maher, Amy J Conway, Ratawan Ubalee, Victor Chaumeau, Chiara Andolina, Stephen A Kaba, Amélie Vantaux, Malina A Bakowski, Richard Thomson Luque, Swamy Rakesh Adapa, Naresh Singh, Samantha J Barnes, Caitlin A Cooper, Mélanie Rouillier, Case W McNamara, Sebastian A Mikolajczak, Noah Sather, Benoît Witkowski, Brice Campo, Stefan H I Kappe, David E Lanar, François Nosten, Silas Davidson, Rays H Y Jiang, Dennis E Kyle, John H Adams
Malaria liver stages represent an ideal therapeutic target with a bottleneck in parasite load and reduced clinical symptoms; however, current in vitro pre-erythrocytic (PE) models for Plasmodium vivax and P. falciparum lack the efficiency necessary for rapid identification and effective evaluation of new vaccines and drugs, especially targeting late liver-stage development and hypnozoites. Herein we report the development of a 384-well plate culture system using commercially available materials, including cryopreserved primary human hepatocytes...
May 9, 2018: Nature Communications
https://www.readbyqxmd.com/read/29743062/-we-don-t-want-our-clothes-to-smell-smoke-changing-malaria-control-practices-and-opportunities-for-integrated-community-based-management-in-baringo-kenya
#19
Jacinter A Amadi, Daniel O Olago, George O Ong'amo, Silas O Oriaso, Isaac K Nyamongo, Benson B A Estambale
BACKGROUND: The decline in global malaria cases is attributed to intensified utilization of primary vector control interventions and artemisinin-based combination therapies (ACTs). These strategies are inadequate in many rural areas, thus adopting locally appropriate integrated malaria control strategies is imperative in these heterogeneous settings. This study aimed at investigating trends and local knowledge on malaria and to develop a framework for malaria control for communities in Baringo, Kenya...
May 9, 2018: BMC Public Health
https://www.readbyqxmd.com/read/29741150/comparison-of-the-pharmacokinetics-and-ex-vivo-antimalarial-activities-of-artesunate-amodiaquine-and-artemisinin-piperaquine-in-healthy-volunteers-for-preselection-malaria-therapy
#20
Nguyen Ngoc Quang, Marina Chavchich, Chu Xuan Anh, Geoffrey W Birrell, Karin van Breda, Thomas Travers, Kerryn Rowcliffe, Michael D Edstein
The pharmacokinetics (PK) and ex vivo activity (pharmacodynamics [PD]) of two artemisinin combination therapies (ACTs) (artemisinin-piperaquine [ARN-PPQ] [Artequick® ] and artesunate-amodiaquine [ARS-AQ] [Coarsucam™ ]) in healthy Vietnamese volunteers were compared following 3-day courses of the ACTs for the preselection of the drugs for falciparum malaria therapy. For PK analysis, serial plasma samples were collected from two separate groups of 22 volunteers after ACT administration. Of these volunteers, ex vivo activity was assessed in plasma samples from seven volunteers who received both ACTs...
May 7, 2018: American Journal of Tropical Medicine and Hygiene
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