Development and validation of Triticum phytobiological method as an alternative procedure for investigating in vivo acute toxicity on mice

The goal of this study was to validate an alternative method for determining in vivo acute toxicity using vegetal material instead of laboratory animals, starting from the phytobiological method known also as the Triticum technique. We set out to demonstrate that vegetal cells have similar sensitivity to some toxic agents as animal cells, in which case a statistical correlation could be established. A series of new compounds synthesized by the Romanian National Institute for Chemical Pharmaceutical Research and Development as potential β3 adrenergic receptors agonists were tested for their acute toxicity using classic animal exposure models, before investigating possible anti-diabetic and anti-obesity effects. We then determined whether similar conclusions might be reached exposing vegetal material to the same agents. We successfully demonstrated that plants are affected in a very similar way as animals when exposed to some potentially toxic agents, providing new possibilities for ending unethical animal experiments

Should We Have or Should We Have Not, and Who Should Have Paid?

We analyze an overlapping generations model which explicitly includes a secondary asset market. The economy is affected by a onetime shock which causes some of these assets to become toxic. As a response the government may intervene by buying these assets at market value and removing them from trade. When the shock is not anticipated we find that government intervention cannot improve upon the laissez-faire equilibrium. However, when agents anticipate that a crisis may occur, removing the toxic assets dominates laissez-faire, particularly when the toxic asset holders are financing the intervention scheme. Finally, we show that curbing incentives which drive investors to find high yield opportunities decreases the severity of a crisis once it occurs, but also output.Crisis; Toxic Assets; Intervention

Vaginal Microbicides: Detecting Toxicities in Vivo that Paradoxically Increase Pathogen Transmission

BACKGROUND: Microbicides must protect against STD pathogens without causing unacceptable toxic effects. Microbicides based on nonoxynol-9 (N9) and other detergents disrupt sperm, HSV and HIV membranes, and these agents are effective contraceptives. But paradoxically N9 fails to protect women against HIV and other STD pathogens, most likely because it causes toxic effects that increase susceptibility. The mouse HSV-2 vaginal transmission model reported here: (a) Directly tests for toxic effects that increase susceptibility to HSV-2, (b) Determines in vivo whether a microbicide can protect against HSV-2 transmission without causing toxicities that increase susceptibility, and (c) Identifies those toxic effects that best correlate with the increased HSV susceptibility. METHODS: Susceptibility was evaluated in progestin-treated mice by delivering a low-dose viral inoculum (0.1 ID50) at various times after delivering the candidate microbicide to detect whether the candidate increased the fraction of mice infected. Ten agents were tested – five detergents: nonionic (N9), cationic (benzalkonium chloride, BZK), anionic (sodium dodecylsulfate, SDS), the pair of detergents in C31G (C14AO and C16B); one surface active agent (chlorhexidine); two non-detergents (BufferGel®, and sulfonated polystyrene, SPS); and HEC placebo gel (hydroxyethylcellulose). Toxic effects were evaluated by histology, uptake of a 'dead cell' dye, colposcopy, enumeration of vaginal macrophages, and measurement of inflammatory cytokines. RESULTS: A single dose of N9 protected against HSV-2 for a few minutes but then rapidly increased susceptibility, which reached maximum at 12 hours. When applied at the minimal concentration needed for brief partial protection, all five detergents caused a subsequent increase in susceptibility at 12 hours of ~20–30-fold. Surprisingly, colposcopy failed to detect visible sign of the N9 toxic effect that increased susceptibility at 12 hours. Toxic effects that occurred contemporaneously with increased susceptibility were rapid exfoliation and re-growth of epithelial cell layers, entry of macrophages into the vaginal lumen, and release of one or more inflammatory cytokines (Il-1β, KC, MIP 1α, RANTES). The non-detergent microbicides and HEC placebo caused no significant increase in susceptibility or toxic effects. CONCLUSION: This mouse HSV-2 model provides a sensitive method to detect microbicide-induced toxicities that increase susceptibility to infection. In this model, there was no concentration at which detergents provided protection without significantly increasing susceptibility.JHU Woodrow Wilson Fellowship; National Institutes of Health (Program Project A1 45967

Biohazards of Protein Biotoxins

Biotoxins are toxic substances produced by a living organism that cause diseases in humanbeings, animals, or plants. The agent may be lethal or incapacitating. The new, emerging threatagents are biotoxins produced by animals, plants, fungi, and bacteria. Many types of organismsproduce substances that are toxic to humans. Examples of such biotoxins are botulinum toxin,tetanus toxin, and ricin. Several bioactive molecules produced by the pharmaceutical industrycan be even more toxic than the classical chemical warfare agents. Such new agents, like thebiotoxins and bioregulators, often are called mid-spectrum agents. The threat to human beingsfrom agents developed by modern chemical synthesis and by genetic engineering also must beconsidered, since such agents may be more toxic or more effective in causing death orincapacitation than classical warfare agents. By developing effective medical protection andtreatment against the most likely chemical and mid-spectrum threat agents, the effects of suchagents in a war scenario or following a terrorist attack can be reduced. Toxin-mediated diseaseshave made human beings ill for millennia. The use of biological agents as weapons of terror hasnow been realised, and separating naturally occurring disease from bioterroristic events hasbecome an important public health goal

The status of Fusarium mycotoxins in Sub-Saharan Africa : a review of emerging trends and post-harvest mitigation strategies towards food control

Fusarium fungi are common plant pathogens causing several plant diseases. The presence of these molds in plants exposes crops to toxic secondary metabolites called Fusarium mycotoxins. The most studied Fusarium mycotoxins include fumonisins, zearalenone, and trichothecenes. Studies have highlighted the economic impact of mycotoxins produced by Fusarium. These arrays of toxins have been implicated as the causal agents of wide varieties of toxic health effects in humans and animals ranging from acute to chronic. Global surveillance of Fusarium mycotoxins has recorded significant progress in its control; however, little attention has been paid to Fusarium mycotoxins in sub-Saharan Africa, thus translating to limited occurrence data. In addition, legislative regulation is virtually non-existent. The emergence of modified Fusarium mycotoxins, which may contribute to additional toxic effects, worsens an already precarious situation. This review highlights the status of Fusarium mycotoxins in sub-Saharan Africa, the possible food processing mitigation strategies, as well as future perspectives

Biological Effects of Dispersants and Dispersed Oil in Surface and Deep Ocean Species

Beginning with the use of industrial-strength detergents, dispersing agents have been employed in spill response for decades. The Corexit series of agents in common use today generally consist of non-ionic and/or anionic surfactants in a solvent base designed to enhance miscibility under varying temperature and salinity conditions; cationic surfactants tend to be too toxic for use. While dispersants generally serve to decrease the interfacial surface tension of oil, thus facilitating its weathering under low-energy conditions, their surface-active nature also causes their interaction with cell surfaces – those of single-celled organisms as well as the gills of vertebrates and invertebrates