Discovery and Development of an Advanced Lead for the Treatment of African Trypanosomiasis.

African trypanosomiasis is a widespread disease of human and veterinary importance caused by various with a globally devastating impact and a need for novel treatment options. We here provide a comprehensive preclinical evaluation of nucleoside analogues, 6-thioether-modified tubercidins, with curative activity against African trypanosomiasis. Promising hits were identified following screening against the most relevant trypanosome species.

Assessment of receptor-mediated activity (AhR and ERα), mutagenicity, and teratogenicity of metal shredder wastes in Wallonia, Belgium.

In this study, hazardous wastes including fluff, dust, and scrubbing sludge were sampled in 2019 from two metal shredding facilities located in Wallonia, Belgium. To assess the extent of the contamination, a global approach combining chemical and biological techniques was used, to better reflect the risks to health and the environment. The samples investigated induced significant in vitro aryl hydrocarbon receptor (AhR) agonistic bioactivities and estrogenic receptor (ERα) (ant)agonistic bioactivities in the respective CALUX (chemical activated luciferase gene expression) bioassays.

Effects of long-term exposure to 50 Hz magnetic fields on cell viability, genetic damage, and sensitivity to mutagen-induced damage.

Until today, it remains controversial whether long-term exposure to extremely low-frequency magnetic fields (ELF-MF) below the legislative exposure limits could result in adverse human health effects. In the present study, the effects of long-term MF exposure on three different study endpoints (cell viability, genetic damage, and sensitivity to damage induced by known mutagens) were investigated in the human B lymphoblastoid (TK6) cell line. Cells were exposed to 50 Hz MF at three selected magnetic flux densities (i.

Impact of experimental design factors on the potency of genotoxicants in in vitro tests.

Previous studies have shown that differences in experimental design factors may alter the potency of genotoxic compounds in in vitro genotoxicity tests. Most of these studies used traditional statistical methods based on the lowest observed genotoxic effect levels, whereas more appropriate methods, such as the benchmark dose (BMD) approach, are now available to compare genotoxic potencies under different test conditions. We therefore investigated the influence of two parameters, i.

Ecotoxicity profile of heavily contaminated surface water of two rivers in Tunisia.

Persistent organic and inorganic contaminants generated by industrial effluent wastes poses a threat to the maintenance of aquatic ecosystems and public health. The Khniss and Hamdoun rivers, located in the central-east of Tunisia, receive regularly domestic and textile wastewater load. The present study aimed to survey the water quality of these rivers using physicochemical, analytical and toxicological approaches.

Identification of flavouring substances of genotoxic concern present in e-cigarette refills.

E-cigarettes have become very popular, a trend that has been stimulated by the wide variety of available e-liquid flavours. Considering the large number of e-liquid flavours (>7000), there is an urgent need to establish a screening strategy to prioritize the flavouring substances of highest concern for human health. In the present study, a prioritization strategy combining analytical screening, in silico tools and literature data was developed to identify potentially genotoxic e-liquid flavourings.

50 Hz magnetic field long-term exposure: Cytogenetic tests on human lymphoblastoid TK6 cells and validation of the test environment.

Potential health effects of extremely low-frequency (electro)magnetic fields (ELF-(E)MFs) have long been investigated, but the results are still inconclusive. With respect to genotoxicity, sound data related to the effects of long-term exposure to ELF-(E)MFs on the genetic material and the impact of long-term pre-exposure to ELF-(E)MFs on the sensitivity of cells to the damage induced by known mutagens are needed. In this manuscript, an optimized protocol for a combined comet/micronucleus study to investigate these effects in a human lymphoblastoid cell line (TK6) is provided including the description of a well-validated exposure system.

Assessment of natural coagulants to remediate Tunisian textile wastewater by combining physicochemical, analytical, and toxicological data.

Due to the complexity and variability of textile wastewater composition, a constant search for new treatment strategies that are efficient, eco-friendly, and cost-effective is mandatory. In the present study, the efficiency of coagulation-flocculation using biocoagulants derived from cactus Opuntia ficus indica and eggplant Solanum melongena to remove toxic compounds from Tunisian textile wastewater samples was evaluated by combining assays to investigate physicochemical properties and in vitro (geno)toxicity with analytical chemistry. Both natural coagulants could significantly improve the physicochemical properties of the textile wastewater samples compared to the traditionally used chemical coagulant.

UPLC-MS/MS analysis of antibiotics in pharmaceutical effluent in Tunisia: ecotoxicological impact and multi-resistant bacteria dissemination.

The UPLC MS/MS analysis showed the presence of the two antibiotics in the pharmaceutical industry discharges during 3 months; norfloxacin and spiramycin which were quantified with the mean concentrations of 226.7 and 84.2 ng mL, respectively.

Identification and risk assessment of human and veterinary antibiotics in the wastewater treatment plants and the adjacent sea in Tunisia.

In the following study, we came up with and validated a prompt, sensitive and precise method for the simultaneous determination of 56 antimicrobial drugs (tetracyclines, sulfonamides, β-lactams, macrolides and quinolones) using the ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). This method was implemented with success to determine antibiotics in samples collected from four wastewater treatment plants and five coasts in Tunisia. Results showed the presence of high concentrations of antibiotics that ranged from 0.

Antigenotoxic prenylated flavonoids from stem bark of Erythrina latissima.

A series of prenylated flavonoids was obtained from antigenotoxic extracts and fractions of stem bark of Erythrina latissima E. Mey (Leguminosae). In addition to five constituents never reported before, i.

Toxicity and Genotoxic Activity of Aqueous Leaf Extracts From Four Varieties of (L).

Aim: Despite its therapeutic value almost nothing is known about potential adverse health effects of . We therefore investigated the toxicity and genotoxicity of leaf extracts of this plant.

Material And Methods: Extracts from olive tree leaves were obtained from four different regions in Tunisia.

Evaluation of the Genotoxicity and Cytotoxicity of Semipurified Fractions from the Mediterranean Brown Algae, .

Unlabelled: , a species of Mediterranean brown algae, is believed to have potential pharmacological and nutritional applications. However, such potentials only make sense when devoid of any adverse health consequences. The present study should be seen in this context.

Co-exposure of ELF-magnetic fields and chemical mutagens: An investigation of genotoxicity with the SOS-based VITOTOX test in Salmonella typhimurium.

It is believed that extreme low frequency magnetic fields (ELF-MF) are not mutagenic, at least at exposure levels below 100 μT. Synergistic or co-operative effects with environmental mutagens remain possible yet. We therefore investigated the effects of ELF-MF in conjunction with 4 different well known chemical mutagens having different modes of action.

The Cytome Assay as a Tool to Investigate the Possible Association Between Exposure to Extremely Low Frequency Magnetic Fields and an Increased Risk for Alzheimer's Disease.

Exposure to extremely low frequency magnetic fields (ELF-MF) has been identified as one of the potential environmental risk factors for Alzheimer's disease (AD). However, this is far from being established. So far there is no experimental evidence supporting this alleged association.

Genotoxicity testing of 3,4,5-trimethylfuran-2(5H)-one, a compound from plant-derived smoke with germination inhibitory activity.

Plant-derived smoke and certain smoke compounds improve seed germination and enhance seedling growth of many species. Thus, smoke-infused water and the active smoke-derived compounds have the potential to be used in different agricultural and horticultural applications. However, despite these interesting and potentially practical properties, it should also be ascertained whether such compounds may pose a health risk, particularly if they are to be used in the production of food or fodder crops.

1,2,3,4,8,9,10,11-octahydrobenzo[j]phenanthridine-7,12-diones as new leads against Mycobacterium tuberculosis.

Tuberculosis (TB) continues to be a worldwide health problem with over 1.4 million deaths each year. Despite efforts to develop more effective vaccines, more reliable diagnostics, and chemotherapeutics, tuberculosis remains a threat to global health, fueled by the HIV pandemic and the rapid generation of drug resistance.

Biological evaluation of bisbenzaldehydes against four Mycobacterium species.

A series of bisbenzaldehydes and structurally related analogs, conveniently synthesized via microwave-assisted reactions, were evaluated in vitro against drug susceptible and multi-drug resistant Mycobacterium tuberculosis, against virulent Mycobacterium bovis, against Mycobacterium ulcerans and against two Mycobacterium avium subspecies. Among the 33 substances that were tested, compound 12, i.e.

Straightforward palladium-mediated synthesis and biological evaluation of benzo[j]phenanthridine-7,12-diones as anti-tuberculosis agents.

In 1991, WHO recognized the resurgence of tuberculosis as a global health problem. Although modern chemotherapy is effective against the causative pathogen Mycobacterium tuberculosis, the current drug regimens have failed to eradicate the disease. The success of the pathogen, partially attributed to drug resistance, necessitates the development of novel anti-tuberculosis drugs.

Genotoxicity investigation of ELF-magnetic fields in Salmonella typhimurium with the sensitive SOS-based VITOTOX test.

We performed a genotoxicity investigation of extremely low-frequency (ELF) magnetic fields (MFs, 50 Hz, 100 and 500 µT, 1 and 2 h exposure) alone and in combination with known chemical mutagens using the VITOTOX test. This test is a very sensitive reporter assay of Salmonella typhimurium bacteria based on the SOS response. Our study showed that ELF-MFs do not induce SOS-based mutagenicity in S.

Eco-, geno- and human toxicology of bio-active nanoparticles for biomedical applications.

Gene delivery has become an increasingly important strategy for treating a variety of human diseases, including infections, genetic disorders and tumours. To avoid the difficulties of using viral carriers, more and more non-viral gene delivery nanoparticles are developed. Among these new approaches polyethylene imine (PEI) is currently considered as one of the most effective polymer based method solution and considered as the gold standard.

A database of IC50 values and principal component analysis of results from six basal cytotoxicity assays, for use in the modelling of the in vivo and in vitro data of the EU ACuteTox project.

The main aim of the ACuteTox project (part of the EU 6th Framework programme) is to demonstrate that animal tests for acute systemic toxicity can be replaced by alternative in vitro assays. In this project, data for 97 reference chemicals were collected in the AcuBase database, designed to handle deposited in vitro and in vivo (human and animal) data. To demonstrate the applicability of in vitro basal cytotoxicity tests and in vitro-in vivo modelling, it was deemed necessary to obtain data that were generated via defined standard operating procedures.