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Background: Plasmodium falciparum is the parasite responsible for most malaria cases globally. The risk of transfusion‐transmitted malaria (TTM) is mitigated by donor deferrals and blood screening strategies, which adversely impact blood availability. Previous studies showed robust inactivation of P. falciparum using nucleic acid‐targeting pathogen reduction technologies (PRT) for the treatment of plasma and platelet components or whole blood (WB). The efficacy of the amustaline–glutathione (GSH) PRT to inactivate P. falciparum is here evaluated in red blood cells (RBC), as well the impact of PRT on parasite loads, stages, and strains. Study Design and Methods: RBC units resuspended in AS‐1 or AS‐5 additive solutions were spiked with ring stage‐infected RBC and treated with the amustaline–GSH PRT. Parasite loads and viability were measured in samples at the time of contamination, and after treatment, using serial 10‐fold dilutions of the samples in RBC cultures maintained for up to 4 weeks. Results: P. falciparum viability assays allow for the detection of very low levels of parasite. Initial parasite titer was >5.2 log10/ml in AS‐1/5 RBC. No infectious parasites were detected in amustaline–GSH‐treated samples after 4 weeks of culture. Amustaline–GSH inactivated high parasite loads regardless of parasite stages and strains. Amustaline readily penetrates the parasite, irreversibly blocks development, and leads to parasite death and expulsion from RBC. Discussion: Amustaline–GSH PRT demonstrated robust efficacy to inactivate malaria parasites in RBC concentrates. This study completes the portfolio of studies demonstrating the efficacy of nucleic acid‐targeting PRTs to mitigate TTM risks as previously reported for platelet concentrates, plasma, and WB. [ABSTRACT FROM AUTHOR]

Background: Risk of transfusion-transmitted (TT) malaria is mainly associated with whole blood (WB) or red blood cell (RBC) transfusion. Risk mitigation relies mostly on donor deferral while a limited number of countries perform blood testing, both negatively impacting blood availability. This study investigated the efficacy of the pathogen reduction system using amustaline and glutathione (GSH) to inactivate Plasmodium falciparum in WB.Study Design and Methods: WB units were spiked with ring stage P. falciparum infected RBCs. Parasite loads were measured in samples at time of infection, after 24 hours at room temperature (RT), and after a 24-hour incubation at RT post-treatment with 0.2 mM amustaline and 2 mM GSH. Serial 10-fold dilutions of the samples were inoculated to RBC cultures and maintained up to 4 weeks. Parasitemia was quantified by cytometry.Results: The P. falciparum viability assay has a limit of detection of a single live parasite per sample. Input parasite titer was >5.7 log10 TCID50 per mL. A 24-hour incubation at RT paused parasite development in controls, but they retained viability and infectivity when tested in culture. In contrast, no infectious parasites were detected in the amustaline/GSH-treated sample after 4 weeks of culture.Conclusion: A robust level of P. falciparum inactivation was achieved in WB using amustaline/GSH treatment. Parasite log reduction was >5.7 log10 TCID50 per mL. Development of such a pathogen reduction system may provide an opportunity to reduce the risk of TT malaria and improve blood availability. [ABSTRACT FROM AUTHOR]

Abstract: This paper presents novel QSAR models for the prediction of antitrypanosomal activity among thiazolidines and related heterocycles. The performance of four machine learning algorithms: Random Forest regression, Stochastic gradient boosting, Multivariate adaptive regression splines and Gaussian processes regression have been studied in order to reach better levels of predictivity. The results for Random Forest and Gaussian processes regression are comparable and outperform other studied methods. The preliminary descriptor selection with Boruta method improved the outcome of machine learning methods. The two novel QSAR‐models developed with Random Forest and Gaussian processes regression algorithms have good predictive ability, which was proved by the external evaluation of the test set with corresponding Q2ext=0.812 and Q2ext=0.830. The obtained models can be used further for in silico screening of virtual libraries in the same chemical domain in order to find new antitrypanosomal agents. Thorough analysis of descriptors influence in the QSAR models and interpretation of their chemical meaning allows to highlight a number of structure‐activity relationships. The presence of phenyl rings with electron‐withdrawing atoms or groups in para‐position, increased number of aromatic rings, high branching but short chains, high HOMO energy, and the introduction of 1‐substituted 2‐indolyl fragment into the molecular structure have been recognized as trypanocidal activity prerequisites. [ABSTRACT FROM AUTHOR]

The formation of methylenebis(chalcone)s has been discovered during deprotection with methoxymethyl groups from trihydroxychalcones. Studies on this methylenation reaction led to a mechanism hypothesis that was extended to other chalcones and to dihydrochalcone, acetophenone, benzophenone and flavone derivatives. This new method was applied to the rapid synthesis of natural product piperanduncin C. These original methylenebis compounds were also evaluated for their antiparasitic activity. [ABSTRACT FROM AUTHOR]

Radikale Wirkung: Ferroquin ist ein Ferrocen ‐ basiertes Analogon des Antimalariamittels Chloroquin. Wie Fluoreszenzsonden in infizierten roten Blutzellen zeigen, läuft zusätzlich zum primären Mechanismus der Chinolinwirkung noch ein anderer Mechanismus ab. Er beruht auf der Bildung von HO. in der sauren und oxidierenden Umgebung der Verdauungsvakuole des Malariaparasiten und könnte bewirken, dass mit Ferroquin eine Reinvasion verhindert werden kann. [ABSTRACT FROM AUTHOR]

The study of the EtOAc extract of the leaves of Dilobeia thouarsii led to the isolation and identification of seven new diprenylated dihydroxyflavonols named dilobenol A-G ( 1-7). Their structures were elucidated by spectroscopic analysis including UV, IR, 1D and 2D NMR and MS as well as by chemical hydrolysis. The isolated compounds were assessed for their antibacterial, antiplasmodial and cytotoxic activities. They exhibited moderate growth inhibitory activities against Staphylococcus aureus, Vibrio spp., Bacillus spp, and Plasmodium falciparum without significant toxicity against mammalian cell line L-6. [ABSTRACT FROM AUTHOR]

ABSTRACT Introduction The Derris genus is known to contain flavonoid derivatives, including prenylated flavanones and isoflavonoids such as rotenoids, which are generally associated with significant biological activity. Objective To develop an efficient preparative isolation procedure for bioactive cajaflavanone. Methodology Fast centrifugal partition chromatography (FCPC) was optimised to purify cajaflavanone from Derris ferruginea stems in a single step as compared to fractionation from the cyclohexane extract by successive conventional solid-liquid chromatography procedures. The purification yield, purity, time and solvent consumption per procedure are described. The anti-fungal, anti-bacterial, anti-leishmanial, anti-plasmodial, anti-oxidant activities and the inhibition of advanced glycation end-products (AGEs) by cajaflavanone accumulation are described. Results FCPC enabled cajaflavanone purification in a single separation step, yielding sufficient quantities to perform in vitro biological screening. Interestingly, cajaflavanone had an inhibitory effect on the formation of AGEs, without displaying any in vitro anti-oxidant activity. Conclusion A simple and efficient procedure, in comparison with other preparative methods, for bioactive cajaflavone purification has been developed using FCPC. Copyright © 2011 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Spilanthes spp. are used as traditional herbal medicines in Africa and India to treat malaria. Yet, to date, there are no data on the active constituents or the most effective extraction methods for this indication. The isolated alkylamides, spilanthol and undeca-2E-ene-8,10-diynoic acid isobutylamide, found in S. acmella Murr., were shown to have IC₅₀s of 16.5 μg/mL and 41.4 μg/mL on Plasmodium falciparum strain PFB and IC₅₀s of 5.8 μg/mL and 16.3 μg/mL for the chloroquine resistant P. falciparum K1 strain, respectively. Further investigations revealed that at relatively low concentrations, spilanthol and the water extract of S. acmella reduced the parasitemia 59% and 53% in mice infected with P. yoelii yoelii 17XNL at 5 mg/kg and 50 mg/kg, respectively. Unexpectedly, the 95% ethanol extract of S. acmella was less effective (36% reduction in parasitemia) at 50 mg/kg. These results provide the first evidence supporting S. acmella against malaria and demonstrating active constituents in S. acmella against P. falciparum. [ABSTRACT FROM AUTHOR]

Probiotics are defined as live organisms, which confer benefits to the host. Their efficiency was demonstrated for the treatment of gastrointestinal disorders, respiratory infections, and allergic symptoms, but their use is mostly limited to bacterial and viral diseases. During the last decade, probiotics as means for the control of parasite infections were reported covering mainly intestinal diseases but also some nongut infections, that are all of human and veterinary importance. In most cases, evidence for a beneficial effect was obtained by studies using animal models. In a few cases, cellular interactions between probiotics and pathogens or relevant host cells were also investigated using in vitro culture systems. However, molecular mechanisms mediating the beneficial effects are as yet poorly understood. These studies indicate that probiotics might indeed provide a strain-specific protection against parasites, probably through multiple mechanisms. But more unravelling studies are needed to justify probiotic utilisation in therapeutics. [ABSTRACT FROM AUTHOR]

BACKGROUND: Transfusion-transmitted cases of malaria and babesiosis have been well documented. Current efforts to screen out contaminated blood products result in component wastage due to the lack of specific detection methods while donor deferral does not always guarantee safe blood products. This study evaluated the efficacy of a photochemical treatment (PCT) method with amotosalen and long-wavelength ultraviolet light (UVA) to inactivate these agents in red blood cells (RBCs) contaminating platelet (PLT) and plasma components. STUDY DESIGN AND METHODS: Plasmodium falciparum– and Babesia microti–contaminated RBCs seeded into PLT and plasma components were treated with 150 µmol per L amotosalen and 3 J per cm2 UVA. The viability of both pathogens before and after treatment was measured with infectivity assays. Treatment with 150 µmol per L amotosalen and 1 J per cm2 UVA was used to assess the robustness of the PCT system. RESULTS: No viable B. microti was detected in PLTs or plasma after treatment with 150 mol per L amotosalen and 3 J per cm2 UVA, demonstrating a mean inactivation of greater than 5.3 log in PLTs and greater than 5.3 log in plasma. After the same treatment, viable P. falciparum was either absent or below the limit of quantification in three of four replicate experiments both in PLTs and in plasma demonstrating a mean inactivation of at least 6.0 log in PLTs and at least 6.9 log in plasma. Reducing UVA dose to 1 J per cm2 did not significantly affect the level of inactivation. CONCLUSION: P. falciparum and B. microti were highly sensitive to inactivation by PCT. Pathogen inactivation approaches could reduce the risk of transfusion-transmitted parasitic infections and avoid unnecessary donor exclusions. [ABSTRACT FROM AUTHOR]

We measured the biological activities of a selected sample (84 crude extracts) of 24 species eaten by wild chimpanzees (Pan troglodytes schweinfurthii) in the Kibale National Park, western Uganda, to assess their potential chemotherapeutic values. Antibacterial, antimalarial, and/or antileishmania activities were observed in some crude extracts, and five of these extracts showed a significant cytotoxicity against human tumor cells. Active compounds isolated from three plant parts occasionally ingested by chimpanzees (Diospyros abyssinica (Ebenaceae) bark, Uvariopsis congensis (Annonaceae) leaves, and Trichilia rubescens (Meliaceae) leaves) showed highly significant medicinal properties. Two novel antiparasitic limonoids were isolated from Trichilia rubescens and their molecular structures were determined. In addition to elucidating the natural equilibrium maintained between hosts and pathogens, our investigation of the diet of wild chimpanzees may serve as a guideline to discovering plants with bioactive properties that should be preserved from destruction because of their health maintenance value for great ape populations. Am. J. Primatol. 68:51–71, 2006. © 2006 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

One hundred and ninety plants, of which 51 are used to treat malaria in traditional medicine, were collected in five different ecosystems of Madagascar for a screening programme devoted to the search of naturally-occurring antimalarial compounds. Thirty-nine plants, of which 12 are used as herbal antimalarials, were found to display in vitro activity against Plasmodium falciparum with a median inhibitory concentration (IC50) lower than 5 µg/ml while 9 had an IC50 ranging from 5 to 7.5 µg/ml. Seventeen of them exhibited cytotoxic effects on murine P388 leukemia cells with an IC50 < 10 µg/ml. The biological activities were mostly located in the ethyl acetate fractions. Bioassay-directed fractionation is underway to isolate the active constituents. Copyright © 2004 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Sexual development is an essential phase in the Plasmodium life cycle, where male gametogenesis is an unusual and extraordinarily rapid process. It produces 8 haploid motile microgametes, from a microgametocyte within 15 minutes. Its unique achievement lies in linking the assembly of 8 axonemes in the cytoplasm to the three rounds of intranuclear genome replication, forming motile microgametes, which are expelled in a process called exflagellation. Surprisingly little is known about the actors involved in these processes. We are interested in kinesins, molecular motors that could play potential roles in male gametogenesis. We have undertaken a functional characterization in Plasmodium berghei of kinesin‐8B (PbKIN8B) expressed specifically in male gametocytes and gametes. By generating Pbkin8B‐gfp parasites, we show that PbKIN8B is specifically expressed during male gametogenesis and is associated with the axoneme. We created a ΔPbkin8B knockout cell line and analysed the consequences of the absence of PbKIN8B on male gametogenesis. We show that the ability to produce sexually differentiated gametocytes is not affected in ΔPbkin8B parasites and that the 3 rounds of genome replication occur normally. Nevertheless, the development to free motile microgametes is halted and the life cycle is interrupted in vivo. Ultrastructural analysis revealed that intranuclear mitoses are unaffected whereas cytoplasmic microtubules, although assembled in doublets and elongated, fail to assemble in the normal axonemal '9+2' structure and become motile. Absence of a functional axoneme prevented microgamete assembly and release from the microgametocyte, severely reducing infection of the mosquito vector. This is the first functional study of a kinesin involved in male gametogenesis. These results reveal a previously unknown role for PbKIN8B in male gametogenesis, providing new insights into Plasmodium flagellar formation. [ABSTRACT FROM AUTHOR]

The article lists the scientists who have acted as referees during the 2010-2011 issue of "Basic & Clinical Pharmacology & Toxicology" including Michael Berger, Jose Agundez and Adriana Campos.

An author index for the 2010 issue of "Federation of European Biochemical Societies" is presented.