Toxins, Volume 3, Issue 2 (February 2011) – 3 articles , Pages 120-162

The 6-hydroxytrypargine (6-HT) is an alkaloidal toxin of the group of tetrahydro-b-carbolines (THbC) isolated from the venom of the colonial spider Parawixia bistriata. These alkaloids are reversible inhibitors of the monoamine-oxidase enzyme (MAO), with hallucinogenic, tremorigenic and anxiolytic properties. The toxin 6-HT was the first THbC chemically reported in the venom of spiders; however, it was not functionally well characterized up to now. The action of 6-HT was investigated by intracerebroventricular (i.c.v.) and intravenous (i.v.) applications of the toxin in adult male Wistar rats, followed by the monitoring of the expression of fos-protein, combined with the use of double labeling immunehistochemistry protocols for the detection of some nervous receptors and enzymes related to the metabolism of neurotransmitters in the central nervous system (CNS). We also investigated the epileptiform activity in presence of this toxin. The assays were carried out in normal hippocampal neurons and also in a model of chronic epilepsy obtained by the use of neurons incubated in free-magnesium artificial cerebro-spinal fluid (ACSF). Trypargine, a well known THbC toxin, was used as standard compound for comparative purposes. Fos-immunoreactive cells (fos-ir) were observed in hypothalamic and thalamic areas, while the double-labeling identified nervous receptors of the sub-types rGlu2/3 and NMR1, and orexinergic neurons. The 6-HT was administrated by perfusion and ejection in “brain slices” of hippocampus, inducing epileptic activity after its administration; the toxin was not able to block the epileptogenic crisis observed in the chronic model of the epilepsy, suggesting that 6-HT did not block the overactive GluRs responsible for this epileptic activity. Full article

Zearalenone (ZON) is a mycotoxin with estrogenic activity, produced by members of Fusarium species, and is found worldwide in a number of cereal crops. It is known to have four active metabolites (a-zearalenol (a-ZOL), b-zearalenol (b-ZOL), a-zearalanol (a-ZAL), and b-zearalanol (b-ZAL)). A highly sensitive analytical method using liquid chromatography/tandem mass spectrometry using electrospray ionization (LC-ESI-MS/MS) has been established and validated in order to analyze ZON and its metabolites in beer and malt samples. The metabolism of ZON in the course of beer fermentation was further characterized using the artificially contaminated wort by this established method. In the fermented sample, 85.9% of ZON was converted to b-ZOL, which has lower estrogenic activity than that of ZON. These findings indicate that the health risk to humans due to ZON in beer is reduced during the fermentation process. Full article

The frequency and severity of bacteremic infections has increased over the last decade and bacterial endovascular infections (i.e., sepsis or endocarditis) are associated with high morbidity and mortality. Bacteria or secreted bacterial products modulate platelet function and, as a result, affect platelet accumulation at sites of vascular infection and inflammation. However, whether bacterial products regulate synthetic events in platelets is not known. In the present study, we determined if prolonged contact with staphylococcal α-toxin signals platelets to synthesize B-cell lymphoma (Bcl-3), a protein that regulates clot retraction in murine and human platelets. We show that α-toxin induced α_IIbβ₃-dependent aggregation (EC₅₀ 2.98 µg/mL ± 0.64 µg/mL) and, over time, significantly altered platelet morphology and stimulated de novo accumulation of Bcl-3 protein in platelets. Adherence to collagen or fibrinogen also increased the expression of Bcl-3 protein by platelets. α-toxin altered Bcl-3 protein expression patterns in platelets adherent to collagen, but not fibrinogen. Pretreatment of platelets with inhibitors of protein synthesis or the mammalian Target of Rapamycin (mTOR) decreased Bcl-3 protein expression in α-toxin stimulated platelets. In conclusion, Staphylococcus aureus-derived α-toxin, a pore forming exotoxin, exerts immediate (i.e., aggregation) and prolonged (i.e., protein synthesis) responses in platelets, which may contribute to increased thrombotic events associated with gram-positive sepsis or endocarditis. Full article