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F Hardt

Publications and source records attributed to F Hardt.

95 records · Page 6Linked to original sources
PubMedDate not supplied

L-lactate reduces in vitro the inhibition of butyrylcholinesterase (BChE) by paraoxon (E 600).

Intoxication with the organophosphorus compound paraoxon (POX), an inhibitor of serine hydrolases, is frequent. Oximes are the only enzyme reactivators clinically available. Serendipitous observation led us to the hypothesis that lactate might attenuate some of the POX effects. In vitro effects of lactate on the inhibition of butyrylcholinesterase (BChE) by POX were assessed in plasma of 12 healthy human volunteers. The determinations were repeated using different lactate and different POX concentrations. The BChE activity determinations were performed in the following settings: (i) baseline untreated plasma (BL); (ii) after addition of POX to plasma (pl+POX); (iii) after POX and plasma were incubated and then lactate was added (pl+POX/lact); (iv) after addition of lactate to plasma (pl+lact); (v) after lactate and plasma were incubated and then POX was added (pl+lact/POX); (vi) after lactate and POX were incubated and then added to plasma (lact+POX/pl). In the micro- and millimolar ranges, lactate is able to abolish in vitro the inhibition of BChE by POX in human plasma when added to plasma prior to POX or when incubated with POX prior to addition to plasma. Lactate added to plasma after POX has no protective effect. In a second set of experiments, the effect of lactate on BChE activity was determined. At high millimolar concentrations, lactate itself inhibits BChE to an extent comparable to POX. Lactate is a mixed inhibitor of BChE, being able to interfere with the enzyme-substrate complex (inhibition constant for the enzyme-inhibitor-substrate complex K'I(EIS) = 81 mM) and the enzyme (inhibition constant for the enzyme-inhibitor complex K(I) (EI) = 26 mM).

Butyrylcholinesterase↗
PubMedDate not supplied

High-dose intravenous paraoxon exposure does not cause organophosphate-induced delayed neuropathy (OPIDN) in mini pigs.

Organophosphorus compounds are inhibitors of serine hydrolases. Some of these compounds produce, in addition to their high acute toxicity, a more persistent effect: organophosphate-induced delayed neuropathy (OPIDN). The putative molecular entity whose inhibition is thought to be responsible for OPIDN is the neuropathy target esterase (NTE). Although in vitro NTE is resistant to paraoxon (PX), occasional case reports have associated PX with OPIDN. To assess clinically whether or not high-dose i.v. PX causes OPIDN in mini pigs, 14 mini pigs were anaesthesized, intubated and mechanically ventilated. In a first set of experiments eight pigs received 1 mg PX kg(-1) body weight (BW) dissolved in alcohol. Two control animals received alcohol in a corresponding amount. After infusion of PX, survival of the animals during the acute phase of intoxication was achieved by intensive-care support, using appropriate drugs and fluids according to a pre-established protocol. The mini pigs were extubated 1036 +/- 363 min later (mean +/- SD). The pigs were observed prior to PX application and for 6 weeks thereafter for any abnormalities and/or signs of OPIDN, such as leg weakness, ataxia and paralysis. Observations were graded on a scale for three categories (position, motor deficiency, reaction), with a maximal cumulative score of 9. In a second set of experiments (four additional pigs) larger PX doses were used (3, 9, 27 and 81 mg kg(-1) BW). After recovering from general anaesthesia/surgery, within 2 weeks all animals reached the initial score on the scale. It can be concluded that high-dose i.v. PX exposure does not induce OPIDN in mini pigs during the 6-week observation period.

Animals↗