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At least 685 records · Page 38Linked to original sources
PubMed2005

Biologically active novel conformational state of botulinum, the most poisonous poison.

Botulinum neurotoxins (serotypes A-G), the most toxic substances known to humankind, cause flaccid muscle paralysis by blocking acetylcholine release at nerve-muscle junctions through a very specific and exclusive endopeptidase activity against SNARE proteins of presynaptic exocytosis machinery. We have examined polypeptide folding of the endopeptidase moiety of botulinum neurotoxin/A (the light chain) under conditions of its optimal enzymatic activity and have found that one of its stable conformational states is a molten-globule, which retains over 60% of its optimal enzyme activity. More importantly, we have discovered that the light chain acquires a novel pre-imminent molten-globule enzyme conformation at the physiologically relevant temperature, 37 degrees C. The pre-imminent molten-globule enzyme form also exhibited the maximum endopeptidase activity against its intracellular substrate, SNAP-25 (synaptosomal associated protein of 25 kDa). These findings will not only open new avenues to design effective diagnostics and antidotes against botulism but also provide new information on enzymatically active molten-globule or molten-globule like structures.

Botulinum Toxins, Type A↗
PubMed1990

Paracetamol poisoning in pregnancy: an analysis of the outcomes of cases referred to the Teratology Information Service of the National Poisons Information Service.

A study was carried out to investigate the outcome of pregnancy in 115 women who had been exposed to paracetamol overdose. Follow up was obtained in 48 cases. Exposure occurred in all trimesters, and the most striking feature of this series is that the majority of the pregnancy outcomes were normal. None of the mothers died. There were 39 live born infants with no malformation, 14 of whom had been exposed in the first trimester. Four babies, exposed in the third trimester had neonatal problems, but these seem unrelated to paracetamol. There were two live born infants with gross malformations (spina bifida occulta; and cleft lip and palate). However, as the overdoses occurred at weeks 26 and 28 respectively, long after the structural development of these organs, the malformations could not have been caused by the paracetamol. There were two spontaneous abortions, both in the first trimester, which occurred two weeks after the overdose which may be related to the paracetamol. The overall conclusion is that paracetamol overdose per se is not necessarily an indication for termination of pregnancy.

Abnormalities, Drug-Induced↗
PubMed1995

Detoxification of paraquat poisoning: effects of alkylsulfates and alkylsulfonates on paraquat poisoning in mice and rats.

The study revealed that high molecular polyvinyl sulfate (PVP) or sulfonate (PVS), and low molecular alkyldisulfonates (NaO3S(CH2)nSO3Na, n = 2--5: EDS, TDS, BDS and PDS) can alleviate acute toxicity of the herbicide, paraquat dichloride (PQ) in mice. Their activity as antidotes and the mode of the action varied depending on molecular size. The survival rate for mice receiving PQ at 200 mg/kg alone was increasingly improved when the dose of antidotes was increased from 8 to 10 times the dose of PQ; all the test compounds, except EDS (70% survival), achieved a survival rate of 100%. When test compounds were orally dosed to mice in a mixture with PQ, they improved LD50 of PQ alone. With the low molecular compounds EDS, TDS, BDS and PDS, the value increased to about 2 to 3 times (300-458 mg/kg) over that of PQ alone (140 mg/kg). With high molecular PVS and PVP, the combination reached about a 7 fold (900-1000 mg/kg) increase in LD50 value. The formation of lipid peroxide in lungs of rats due to PQ tended to be suppressed by concomitant administration of carbohydrate sulfate (DS and GS). PVP, BDS and TDS were more effective in depressing synthesis of lipid peroxide than DS or GS in the lungs, although BDS and TDS were less effective in suppressing PQ absorption from the rat small intestine than DS, GS or PVP.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗