Search results for "MALARIA"
showing 10 items of 169 documents
Least-squares community extraction in feature-rich networks using similarity data
2021
We explore a doubly-greedy approach to the issue of community detection in feature-rich networks. According to this approach, both the network and feature data are straightforwardly recovered from the underlying unknown non-overlapping communities, supplied with a center in the feature space and intensity weight(s) over the network each. Our least-squares additive criterion allows us to search for communities one-by-one and to find each community by adding entities one by one. A focus of this paper is that the feature-space data part is converted into a similarity matrix format. The similarity/link values can be used in either of two modes: (a) as measured in the same scale so that one may …
Chloroquine for COVID-19: rationale, facts, hopes
2020
The tragedy of the pandemic coronavirus disease 2019 (COVID-19) led to a desperate search for effective treatments. Chloroquine (CQ), an aminoquinoline used for many years for the prophylaxis and therapy of malaria and autoimmune diseases, has been put forward as a treatment option. The fact that CQ is not patented and has been in clinical use for years is a major advantage. CQ has been shown to have antiviral effects in SARS, MERS, Ebola, and HIV infections, but without data showing clinical effectiveness [1, 2]. Does the current level of evidence suffice for prescribing CQ for COVID-19?
Dip Pen Lithography of oligonucleotides on flexible substrates for point-of-care malaria disease testing
2015
The first step for prevention and treatment of diseases is the accurate diagnosis. However, proper diagnostic technologies are not available in developing countries due to the lack of reliable electrical power, refrigeration and trained personnel. For this reason, there is an urgent need of low cost, rapid assays not requiring any external support. By coupling such technologies to communication infrastructures, healthcare in areas without access to medical personnel would be possible. “Paper” like substrates are ideal for fabricating such devices since they are cheap, easy to degradate after use and compatible with most of existing printing technologies [1]. We had previously shown the poss…
Polyoxygenated Cyclohexenes and Other Constituents of Cleistochlamys kirkii Leaves.
2016
Thirteen new metabolites, including the polyoxygenated cyclohexene derivatives cleistodiendiol (1), cleistodienol B (3), cleistenechlorohydrins A (4) and B (5), cleistenediols A-F (6-11), cleistenonal (12), and the butenolide cleistanolate (13), 2,5-dihydroxybenzyl benzoate (cleistophenolide, 14), and eight known compounds (2, 15-21) were isolated from a MeOH extract of the leaves of Cleistochlamys kirkii. The purified metabolites were identified by NMR spectroscopic and mass spectrometric analyses, whereas the absolute configurations of compounds 1, 17, and 19 were established by single-crystal X-ray diffraction. The configuration of the exocyclic double bond of compound 2 was revised base…
Use of poly(amidoamine) drug conjugates for the delivery of antimalarials to Plasmodium
2013
Current malaria therapeutics demands strategies able to selectively deliver drugs to Plasmodium-infected red blood cells (pRBCs) in order to limit the appearance of parasite resistance. Here, the poly(amidoamines) AGMA1 and ISA23 have been explored for the delivery of antimalarial drugs to pRBCs. AGMA1 has antimalarial activity per se as shown by its inhibition of the in vitro growth of Plasmodium falciparum, with an IC50 of 13.7 μM. Fluorescence-assisted cell sorting data and confocal fluorescence microscopy and transmission electron microscopy images indicate that both polymers exhibit preferential binding to and internalization into pRBCs versus RBCs, and subcellular targeting to the par…
Design of novel artemisinin-like derivatives with cytotoxic and anti-angiogenic properties
2010
Abstract Artemisinins are plant products with a wide range of medicinal applications. Most prominently, artesunate is a well tolerated and effective drug for treating malaria, but is also active against several protozoal and schistosomal infections, and additionally exhibits anti-angiogenic, anti-tumorigenic and anti-viral properties. The array of activities of the artemisinins, and the recent emergence of malaria resistance to artesunate, prompted us to synthesize and evaluate several novel artemisinin-like derivatives. Sixteen distinct derivatives were therefore synthesized and the in vitro cytotoxic effects of each were tested with different cell lines. The in vivo anti-angiogenic proper…
Biowaiver Monographs for Immediate Release Solid Oral Dosage Forms: Proguanil Hydrochloride
2018
Abstract Literature data relevant to the decision to waive in vivo bioequivalence testing for the approval of generic immediate release solid oral dosage forms of proguanil hydrochloride are reviewed. To elucidate the Biopharmaceutics Classification System (BCS) classification, experimental solubility and dissolution studies were also carried out. The antimalarial proguanil hydrochloride, effective via the parent compound proguanil and the metabolite cycloguanil, is not considered to be a narrow therapeutic index drug. Proguanil hydrochloride salt was shown to be highly soluble according to the U.S. Food and Drug Administration, World Health Organization, and European Medicines Agency guide…
Molecular interaction of artemisinin with translationally controlled tumor protein (TCTP) of Plasmodium falciparum
2012
Malaria causes millions of death cases per year. Since Plasmodium falciparum rapidly develops drug resistance, it is of high importance to investigate potential drug targets which may lead to novel rational therapy approaches. Here we report on the interaction of translationally controlled tumor protein of P. falciparum (PfTCTP) with the anti-malarial drug artemisinin. Furthermore, we investigated the crystal structure of PfTCTP. Using mass spectrometry, bioinformatic approaches and surface plasmon resonance spectroscopy, we identified novel binding sites of artemisinin which are in direct neighborhood to amino acids 19-46, 108-134 and 140-163. The regions covered by these residues are know…
Differential interactions of the broad spectrum drugs artemisinin, dihydroartemisinin and artesunate with serum albumin
2013
Artemisinin is a drug, widely used in malaria treatment. As the binding affinity of artemisinin and its derivatives dihydroartemisinin and artesunate to blood serum proteins might influence the effectiveness of the drug, binding of artemisinin and derivatives to serum albumin was studied under near physiological conditions. Binding kinetics indicate a simple, single-step association process for all artemisinin derivatives. The determined changes in enthalpy and entropy upon drug binding clearly indicate that hydrophobic forces are most important for artemisinin and dihydroartemisinin binding, whereas binding of artesunate is governed by both hydrophilic and hydrophobic forces. Key residues,…
Coalition: Advocacy for prospective clinical trials to test the post-exposure potential of hydroxychloroquine against COVID-19
2020
Our coalition of public health experts, doctors, and scientists worldwide want to draw attention to the need for high-quality evaluation protocols of the potential beneficial effect of hydroxychloroquine (HCQ) as a post-exposure drug for exposed people. In the absence of an approved, recognized effective pre or post-exposure prophylactic drug or vaccine for COVID-19, nor of any approved and validated therapeutic drug, coupled with social and political pressure raised by publicity both regarding the potential beneficial effect of hydroxychloroquine (HCQ) as well as potential risks from HCQ, we urge the immediate proper clinical trials. Specifically, we mean using HCQ for post-exposure of peo…