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https://www.readbyqxmd.com/read/28636311/insights-into-integrated-lead-generation-and-target-identification-in-malaria-and-tuberculosis-drug-discovery
#1
John Okombo, Kelly Chibale
New, safe and effective drugs are urgently needed to treat and control malaria and tuberculosis, which affect millions of people annually. However, financial return on investment in the poor settings where these diseases are mostly prevalent is very minimal to support market-driven drug discovery and development. Moreover, the imminent loss of therapeutic lifespan of existing therapies due to evolution and spread of drug resistance further compounds the urgency to identify novel effective drugs. However, the advent of new public-private partnerships focused on tropical diseases and the recent release of large data sets by pharmaceutical companies on antimalarial and antituberculosis compounds derived from phenotypic whole cell high throughput screening have spurred renewed interest and opened new frontiers in malaria and tuberculosis drug discovery...
June 21, 2017: Accounts of Chemical Research
https://www.readbyqxmd.com/read/28635544/heparin-new-life-for-an-old-drug
#2
Carlos Raúl Aláez-Versón, Elena Lantero, Xavier Fernàndez-Busquets
Heparin is one of the oldest drugs, which nevertheless remains in widespread clinical use as an inhibitor of blood coagulation. The history of its identification a century ago unfolded amid one of the most fascinating scientific controversies turning around the distribution of credit for its discovery. The composition, purification and structure-function relationship of this naturally occurring glycosaminoglycan regarding its classical role as anticoagulant will be dealt with before proceeding to discuss its therapeutic potential in, among other, inflammatory and infectious disease, cancer treatment, cystic fibrosis and Alzheimer's disease...
June 21, 2017: Nanomedicine
https://www.readbyqxmd.com/read/28633997/nicotinamide-inhibits-the-growth-of-p-falciparum-and-enhances-the-antimalarial-effect-of-artemisinin-chloroquine-and-pyrimethamine
#3
Sergey O Tcherniuk, Olga Chesnokova, Irina V Oleinikov, Andrew V Oleinikov
Nicotinamide (vitamin B3) - is a water soluble amide derivative of nicotinic acid, which has been used at high doses for a variety of therapeutic applications. However, its antimalarial effect has not been intensively explored. In this work we analysed the effect of nicotinamide alone and in combination with artemisinin, chloroquine andpyrimethamine on the growth of blood stages of P. falciparum. Our results demonstrate that nicotinamide effectively inhibits the growth of blood stage parasites with IC50 of 6...
June 17, 2017: Molecular and Biochemical Parasitology
https://www.readbyqxmd.com/read/28630942/antimalarial-drugs-and-the-prevalence-of-mental-and-neurological-manifestations-a-systematic-review-and-meta-analysis
#4
Mary A Bitta, Symon M Kariuki, Clifford Mwita, Samson Gwer, Leah Mwai, Charles R J C Newton
Background: Antimalarial drugs affect the central nervous system, but it is difficult to differentiate the effect of these drugs from that of the malaria illness. We conducted a systematic review to determine the association between anti-malarial drugs and mental and neurological impairment in humans.  Methods: We systematically searched online databases, including Medline/PubMed, PsychoInfo, and Embase, for articles published up to 14th July 2016. Pooled prevalence, heterogeneity and factors associated with prevalence of mental and neurological manifestations were determined using meta-analytic techniques...
2017: Wellcome Open Research
https://www.readbyqxmd.com/read/28627846/drug-induced-myopathies
#5
Romain Guemara, Ilias Lazarou, Ierre-André Guerne
Drug myopathies are frequent and their identification important because of their potential morbidity. Apart from statins, the drugs most often involved are glucocorticoids, antimalarials, colchicine, and antiretrovirals. These myopathies are largely preventable, particularly those that occur in combinations of treatments or in the presence of comorbidities. Their relatively specific presentation often makes it possible to approach the diagnosis and to target the possible molecule to be interrupted. In general, they are spontaneously and rapidly reversible upon discontinuation of the drug, with the exception of statin-induced autoimmune necrotizing myopathy ; however, the latter is reversible under immunosuppressants, when initiated early enough...
May 2017: Revue Médicale Suisse
https://www.readbyqxmd.com/read/28625144/detection-of-poor-quality-artemisinin-based-combination-therapy-act-medicines-marketed-in-benin-using-simple-and-advanced-analytical-techniques
#6
Achille Yemoa, Védaste Habyalimana, Jérémie K Mbinze, Victoria Crickboom, Benjamin Muhigirwa, Agnès Ngoya, Pierre-Yves Sacré, Fernand Gbaguidi, Joëlle Quetin-Leclercq, Philippe Hubert, Roland D Marini
BACKGROUND: Poor quality antimalarial medicines still represent a threat to the public health, especially in Sub-Saharan Africa who bears a disproportionate share of the global burden of malaria. It is essential and urgent to strengthen mechanisms against counterfeit medicines. One of the approaches is regular market surveillance through quality controls. METHODS: 12 samples of artemether/lumefantrine were collected from formal and informal drug sellers in Cotonou (Benin) as well as additional other similar samples from Rwanda (13 samples) and from D...
June 15, 2017: Current Drug Safety
https://www.readbyqxmd.com/read/28624010/lupus-mastitis-as-a-first-manifestation-of-systemic-disease-about-two-cases-with-a-review-of-the-literature
#7
REVIEW
Béatrice Voizard, Lucie Lalonde, Lilia Maria Sanchez, Johanne Richard-Chesnay, Julie David, Maude Labelle, Mona El Khoury, Isabelle Trop
Lupus mastitis is an uncommon manifestation of systemic lupus erythematosus (SLE) that affects the subcutaneous fat in the breast, much like lupus panniculitis, but additionally involves the mammary gland. We report on two women for whom lupus mastitis was the initial manifestation of SLE and provide a literature review of 34 additional cases reported in the Anglo-Saxon and French literature since 1971, making this the largest review to date. Lupus mastitis (LM) can manifest clinically as subcutaneous masses that may be painful, or may present cutaneous involvement such as thickening and discolouration...
July 2017: European Journal of Radiology
https://www.readbyqxmd.com/read/28621561/a-patent-review-of-two-fruitful-decades-1997-2016-of-isocoumarin-research
#8
Hidayat Hussain, Ivan R Green
Isocoumarins comprise a six-membered oxygen heterocycle (α-pyranone) along with one aromatic ring and are known to possess interesting biological properties. During the last two decade (1997-2016), isocoumarin chemistry has attracted attention due to its biological and pharmaceutical effects viz., anticancer, anti-diabetic, antibacterial, antimalarial, and fungicidal effects. Areas covered: This review covers the patents on the therapeutic activities of natural and synthetic isocoumarins over the last two decades (1997-2016)...
June 16, 2017: Expert Opinion on Therapeutic Patents
https://www.readbyqxmd.com/read/28619452/the-role-of-lecithin-degradation-on-the-ph-dependent-stability-of-halofantrine-encapsulated-fat-nano-emulsions
#9
Iman Haidar, Ian H Harding, Ian C Bowater, Daniel S Eldridge, William N Charman
We report on the successful incorporation of the antimalarial drug, halofantrine, into laboratory based soybean oil emulsions which were designed to mimic the commercially available parenteral fat emulsion, Intralipid(®). A high pH (minimum of pH 9, preferable pH of 11) was required for the drug laden emulsion to remain stable on storage and also to resist breaking under various stresses. Ageing of lecithin samples on storage was noted to result in degradation and a decrease in pH. We argue that this is the main reason for a similar decrease in pH for lecithin based emulsions and subsequent instability in drug laden emulsions...
June 13, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28612497/pharmacotherapy-follow-up-role-in-active-malaria-surveillance-in-a-travel-medicine-centre-outside-the-transmission-area-in-brazil
#10
R S Pedro, P Brasil, A Pina-Costa, C R Machado, L S Damasceno, C T Daniel-Ribeiro, L Guaraldo
WHAT IS KNOWN AND OBJECTIVE: Malaria is a potentially severe disease, widespread in tropical and subtropical areas. Apart from parasite drug resistance, which receives the largest share of attention, several factors directly influence the response to antimalarial treatment such as incorrect doses, adverse drug events, lack of adherence to treatment, drug quality and drug-drug interactions. Pharmacotherapy follow-up can be used to monitor and improve the effectiveness of treatment, prevent drug-related problems and ensure patient safety...
June 13, 2017: Journal of Clinical Pharmacy and Therapeutics
https://www.readbyqxmd.com/read/28607017/high-accumulation-and-in-vivo-recycling-of-the-new-antimalarial-albitiazolium-rapidly-condemn-the-parasite-to-death
#11
Sharon Wein, Nicolas Taudon, Marjorie Maynadier, Christophe Tran Van Ba, Delphine Margout, Yann Bordat, Laurent Fraisse, Kai Wengelnik, Rachel Cerdan, Françoise Bressolle-Gomeni, Henri J Vial
Albitiazolium is the lead compound of bis-thiazolium choline analogues and exerts powerful in vitro and in vivo antimalarial activities. Here we provide new insight into the fate of albitiazolium in vivo in mice and how it exerts its pharmacological activity. We show that the drug exhibits a rapid and potent activity and has very favorable pharmacokinetic and pharmacodynamic properties. Pharmacokinetic studies in Plasmodium vinckei-infected mice indicated that albitiazolium rapidly and specifically accumulates to a great extent (cellular accumulation ratio > 150) in infected erythrocytes...
June 12, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28606818/investigating-unlicensed-retail-drug-vendors-preparedness-and-knowledge-about-malaria-an-exploratory-study-in-rural-uganda
#12
Eric Liow, Rosemin Kassam, Richard Sekiwunga
BACKGROUND: Despite major efforts to increase the uptake of preventive measures and timely use of the first line antimalarial treatment artemisinin-based combination therapies (ACT), Uganda continues to fall short of meeting its national malaria control targets. One of the challenges has been scaling up effective measures in rural and remote areas where the unlicensed private retail sector remains the first point of contact and a common source of treatment. The current paper discusses unlicensed vendors' (1) training related to malaria case management for children aged five and under, and (2) knowledge related to the cause of malaria, preventive measures, common signs, and symptoms, diagnostic procedures, and best treatment options...
June 9, 2017: Acta Tropica
https://www.readbyqxmd.com/read/28605993/in-vitro-sensitivity-to-antimalarial-drugs-and-polymorphisms-in-pfg377-gene-in-plasmodium-falciparum-field-isolates-from-mewat-india
#13
Vineeta Singh, Amit Kumar, Purva Gupta
The malaria infection is the interplay of several complex factors, among which drug resistance and gametocyte biology are the crucial ones. Measurements of the drug sensitivity assays and prevalence of gametocyte genes play a major role in malaria eradication programmes. The purpose of this study was to assess the current drug sensitivity profile in the field isolates and type the Pfg377 gene. In vitro drug sensitivity assay was used to assess the susceptibility of Plasmodium falciparum field isolates collected from Mewat (Haryana), located in Northern region of India to four anti-malarial drugs...
June 12, 2017: Pathogens and Global Health
https://www.readbyqxmd.com/read/28601826/study-protocol-of-a-phase-ib-ii-clinical-trial-of-metformin-and-chloroquine-in-patients-with-idh1-mutated-or-idh2-mutated-solid-tumours
#14
Remco J Molenaar, Robert Js Coelen, Mohammed Khurshed, Eva Roos, Matthan Wa Caan, Myra E van Linde, Mathilde Kouwenhoven, Jos Am Bramer, Judith Vmg Bovée, Ron A Mathôt, Heinz-Josef Klümpen, Hanneke Wm van Laarhoven, Cornelis Jf van Noorden, W Peter Vandertop, Hans Gelderblom, Thomas M van Gulik, Johanna W Wilmink
INTRODUCTION: High-grade chondrosarcoma, high-grade glioma and intrahepatic cholangiocarcinoma are aggressive types of cancer with a dismal outcome. This is due to the lack of effective treatment options, emphasising the need for novel therapies. Mutations in the genes IDH1 and IDH2 (isocitrate dehydrogenase 1 and 2) occur in 60% of chondrosarcoma, 80% of WHO grade II-IV glioma and 20% of intrahepatic cholangiocarcinoma. IDH1/2-mutated cancer cells produce the oncometabolite D-2-hydroxyglutarate (D-2HG) and are metabolically vulnerable to treatment with the oral antidiabetic metformin and the oral antimalarial drug chloroquine...
June 10, 2017: BMJ Open
https://www.readbyqxmd.com/read/28599096/proteases-as-antimalarial-targets-strategies-for-genetic-chemical-and-therapeutic-validation
#15
REVIEW
Edgar Deu
Malaria is a devastating parasitic disease affecting half of the world's population. The rapid emergence of resistance against new antimalarial drugs, including artemisinin-based therapies, has made the development of drugs with novel mechanisms of action extremely urgent. Proteases are enzymes proven to be well suited for target-based drug development due to our knowledge of their enzymatic mechanisms and active site structures. More importantly, Plasmodium proteases have been shown to be involved in a variety of pathways that are essential for parasite survival...
June 9, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28596841/targeting-endosomal-acidification-by-chloroquine-analogs-as-a-promising-strategy-for-the-treatment-of-emerging-viral-diseases
#16
REVIEW
Md Abdul Alim Al-Bari
Emerging viruses such as HIV, dengue, influenza A, SARS coronavirus, Ebola, and other viruses pose a significant threat to human health. Majority of these viruses are responsible for the outbreaks of pathogenic lethal infections. To date, there are no effective therapeutic strategies available for the prophylaxis and treatment of these infections. Chloroquine analogs have been used for decades as the primary and most successful drugs against malaria. Concomitant with the emergence of chloroquine-resistant Plasmodium strains and a subsequent decrease in the use as antimalarial drugs, other applications of the analogs have been investigated...
February 2017: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/28595540/apicoplast-import-protein-tic20-a-promising-therapeutic-molecular-target-for-plasmodium-falciparum-an-insilico-approach-for-therapeutic-intervention
#17
Pavan C P K Srimath-Tirumala-Peddinti, Sandeep Solmon Kusuma, Deepthi Nammi, Nageswara Rao Reddy Neelapu
Malaria is a lethal disease causing mortality to over millions each year. Drug resistance in the malarial parasite encouraged to discover effective antimalarial drug targets and drugs. An objective of this current study is to identify drug targets for malarial parasite. Genes unique, non-homologous to humans and essential for parasite are identified using BLASTn by comparing genomes between parasite and host. Further open BLASTp was used to filter the targets specific to Plasmodium species and later were subjected to gene property analysis to identify 65 potential targets...
June 5, 2017: Infectious Disorders Drug Targets
https://www.readbyqxmd.com/read/28594960/a-portable-image-based-cytometer-for-rapid-malaria-detection-and-quantification
#18
Dahou Yang, Gowtham Subramanian, Jinming Duan, Shaobing Gao, Li Bai, Rajesh Chandramohanadas, Ye Ai
Increasing resistance by malaria parasites to currently used antimalarials across the developing world warrants timely detection and classification so that appropriate drug combinations can be administered before clinical complications arise. However, this is often challenged by low levels of infection (referred to as parasitemia) and presence of predominantly young parasitic forms in the patients' peripheral blood. Herein, we developed a simple, inexpensive and portable image-based cytometer that detects and numerically counts Plasmodium falciparum infected red blood cells (iRBCs) from Giemsa-stained smears derived from infected blood...
2017: PloS One
https://www.readbyqxmd.com/read/28584601/prevalence-and-risk-factors-for-sulfadoxine-antibody-among-patients-undergoing-treatment-for-malaria-in-benin-city-nigeria
#19
Kingsley Ikuoyogie, Helen Oroboghae Ogefere, Richard Omoregie
OBJECTIVES: Because of lack of data on the prevalence of sulfadoxine antibody, this study was conducted to determine the prevalence of sulfadoxine antibodies and its possible risk factors. METHODS: Blood specimens were collected from 500 patients undergoing treatment for malaria at Central Hospital, Benin City, Nigeria. A structured questionnaire was used to collect information and sociodemographic data. Sulfadoxine antibodies were detected by drug absorption (DAT) and immune complex (IMC) methods...
May 2017: Oman Medical Journal
https://www.readbyqxmd.com/read/28584157/menoctone-resistance-in-malaria-parasites-is-conferred-by-m133i-mutations-in-cytochrome-b-that-are-transmissible-through-mosquitos
#20
Lynn D Blake, Myles E Johnson, Sasha V Siegel, Adonis McQueen, Iredia D Iyamu, Abdul Kadar Shaikh, Michael W Shultis, Roman Manetsch, Dennis E Kyle
Malaria related mortality has slowly decreased over the past decade; however, eradication of malaria requires the development of new antimalarial chemotherapies that target liver stages and combat the emergence of drug resistance. The diminishing arsenal of anti-liver stage compounds sparked our interest in reviving the old and previously abandoned compound menoctone. In support of these studies we developed a new convergent synthesis method that was facile, required fewer steps, produced better yields, and utilized less expensive reagents than the previously published method...
June 5, 2017: Antimicrobial Agents and Chemotherapy
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