Preclinical toxicity evaluation of a novel immunotoxin, D2C7-(scdsFv)-PE38KDEL, administered via intracerebral convection-enhanced delivery in rats

This study assessed the toxicity of intracerebral administration of D2C7-IT to support an initial Food and Drug Administration Investigational New Drug application. After the optimization of the formulation and administration, two cohorts (an acute and chronic cohort necropsied on study days 5 and 34) of Sprague–Dawley (SD) rats (four groups of 5 males and 5 females) were infused with the D2C7-IT formulation at total doses of 0, 0.05, 0.1, 0.4 μg (the acute cohort) and 0, 0.05, 0.1, 0.35 μg (the chronic cohort) for approximately 72 h by intracerebral convection-enhanced delivery using osmotic pumps. Mortality was observed in the 0.40 μg (5/10 rats) and 0.35 μg (4/10 rats) high-dose groups of each cohort. Body weight loss and abnormal behavior were only revealed in the rats treated with high doses of D2C7-IT. No dose-related effects were observed in clinical laboratory tests in either cohort. A gross pathologic examination of systemic tissues from the high-dose and control groups in both cohorts exhibited no dose-related or drug-related pathologic findings. Brain histopathology revealed the frequent occurrence of dose-related encephalomalacia, edema, and demyelination in the high-dose groups of both cohorts. In this study, the maximum tolerated dose of D2C7-IT was determined to be between 0.10 and 0.35 μg, and the no-observed-adverse-effect-level was 0.05 μg in SD rats. Both parameters were utilized to design the Phase...
Source: Investigational New Drugs - Category: Drugs & Pharmacology Source Type: research

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Abstract With the pressure to ban or limit the use of Bisphenol A (BPA), substitutes such as bisphenol F (BPF) are applied to various commodities and generally detected in aquatic systems worldwide. To understand the potential ecological risk of BPF, the acute toxicity as well as behavioural, physiological and biochemical parameters of the water flea Daphnia magna were assessed. Following BPF exposure at concentrations ranging from 0.1 μg L-1 to 100 μg L-1, phenotypic traits including growth development, fecundity and swimming activity were significantly inhibited in response to exposure to sublethal...
Source: Chemosphere - Category: Chemistry Authors: Tags: Chemosphere Source Type: research
This study demonstrates that the formation of stable zearalenone-cyclodextrin complexes can strongly decrease or even abolish the zearalenone-induced toxicity, both in vitro and in vivo. Therefore, cyclodextrins appear as promising new mycotoxin binders. PMID: 31726616 [PubMed - in process]
Source: Chemosphere - Category: Chemistry Authors: Tags: Chemosphere Source Type: research
This study systematically investigated the fate of AMT during the UV/chlorine process. It was observed that the combination of UV irradiation and chlorination degraded AMT synergistically. The results of the radical quenching experiments suggested that AMT degradation by the UV/chlorine process involved the participation of UV photolysis, hydroxyl radical (OH) reactions, and reactive chlorine species (RCS) reactions, which accounted for 45.4%, 36.4%, and 14.5% of the degradation, respectively. Moreover, we found that Cl- 2 was an important reactive radical for AMT degradation. The chlorine dose, pH, coexisting anions (Cl- ...
Source: Chemosphere - Category: Chemistry Authors: Tags: Chemosphere Source Type: research
Abstract The reuse of treated municipal wastewater (herein referred to as reclaimed water) in agricultural irrigation (RWAI) as a means to alleviate water scarcity is gaining increasing policy attention, particularly in areas where water demand mitigation measures have proved insufficient. However, reclaimed water reuse in practice is lagging behind policy ambition, with
Source: Chemosphere - Category: Chemistry Authors: Tags: Chemosphere Source Type: research
Abstract In this research, the continuous physiological changes of zebrafish (Danio rerio) in 0.1 μg/L thallium (Tl) in 15 days were investigated. The results showed that Tl(I) stress had a significant positive linear correlation with zebrafish ammonia nitrogen excretion (ANE) (p 
Source: Chemosphere - Category: Chemistry Authors: Tags: Chemosphere Source Type: research
Abstract To assess the role of citric acid, as a typical low-molecular-weight organic acid from root exudates, on cerium (Ce) uptake, accumulation and translocation in rice seedlings (Oryza sativa L.) exposed to two CeO2 nanoparticles (NPs) (14 nm and 25 nm). A hydroponic experiment was performed under two citric acid levels (0.01 and 0.04 mmol L-1) combined with iron plaque presence. Citric acid significantly enhanced surface-Ce, root-Ce and shoot-Ce accumulation, irrespective of NPs size and iron plaque presence. The increased surface-Ce was associated with the promoted interactive attraction between NPs...
Source: Chemosphere - Category: Chemistry Authors: Tags: Chemosphere Source Type: research
Abstract The occurrence, air-sea exchange, and gas-particle partitioning of polybrominated diphenyl ethers (PBDEs) were analyzed during a 2015 research expedition from the East China Sea (ECS) to the open Northwest Pacific Ocean (NWP). The sum of 13 PBDEs (Σ13PBDEs) in air and surface seawater varied in the range of 0.54-14.5. pg m-3 and 0.60-13.5 pg L-1, respectively, with the highest concentrations observed in the ECS. The Clausius-Clapeyron approach and air mass origin analysis indicated that continued primary emissions of PBDEs, particularly BDE-209, from East Asian sources governed the spatial varia...
Source: Chemosphere - Category: Chemistry Authors: Tags: Chemosphere Source Type: research
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Source: Chemosphere - Category: Chemistry Authors: Tags: Chemosphere Source Type: research
Abstract Biomimetic dynamic membrane (BDM) has been employed as a promising membrane separation technology regarding water/wastewater treatment (Model pollutant is methylene blue). Given its catalytic function on micro-pollutant removal and fouling control, detailed mechanism for impacts of fabrication method, carriers (CNT and GO) and laccase on the construction of biomimetic layer and enzyme immobilization have not been clear so far. In this work, the BDM performance with various fabrication methods, carriers and laccase were investigated and verified. The BDM fabrication tests demonstrated that BDM with mixed f...
Source: Chemosphere - Category: Chemistry Authors: Tags: Chemosphere Source Type: research
sada A, Fernández-Piñas F Abstract The hepatotoxic cyanotoxins microcystins (MCs) are emerging contaminants naturally produced by cyanobacteria. Yet their ecological role remains unsolved, previous research suggests that MCs have allelopathic effects on competing photosynthetic microorganisms, even eliciting toxic effects on other freshwater cyanobacteria. In this context, the bioluminescent recombinant cyanobacterium Anabaena sp. PCC7120 CPB4337 (hereinafter Anabaena) was exposed to extracts of MCs. These were obtained from eight natural samples from freshwater reservoirs that contained MCs with a c...
Source: Chemosphere - Category: Chemistry Authors: Tags: Chemosphere Source Type: research
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