No abstract

Monitoring of pyridostigmine therapy in patients with myasthenia gravis is not routinely performed, since the daily pyridostigmine doses are adjusted to the patient's actual clinical status rather than to pyridostigmine plasma concentrations (PPC). Moreover, PPC determination is time-consuming and needs much technical equipment. Since pyridostigmine reversible blocks acetylcholinesterase (AChE) at the neuromuscular junction, we studied the correlation between the enzyme's blood activity (erythrocyte-bound AChE) and PPC, on the one hand, and between blood AChE activity and the clinical status of the individual patient, on the other. In five previously untreated patients with myasthenia gravis blood AChE activity decreased in accordance with the actual PPC after a single oral dose of 60 mg pyridostigmine (group A). Amelioration of the clinical status corresponded to the decrease of AChE activity in the same way. In another five patients, who were on stable pyridostigmine medication for at least 1 week, AChE activity and PPC were constant during the day (group B). Since it is easier to perform than PPC, our results suggest that the determination of AChE activity may be superior to measuring PPC for monitoring cholinesterase inhibitor therapy in selected cases.

the 5-position over that of the parent compound by coordination with cobalt(1n) cations. Studies are in progress to determine whether the difference in reactivity derives from reduction of the effective charge on the nitrogen or whether there is also an important degree of x-electron donation to the ring from the filled Co de orbitals.Phenazine 5-oxide undergoes nitration at the 3-(and to a minor extent the 1-) position; kinetic criteria show that the monocation (40) is the reactive speciesL331.[33] A . R. Katritzky and B. Swedlund, unpublished. E. ConclusionVery much remains to be accomplished. On the experimental side it is necessary to gain quantitative data as to the effect on rate of substitution (by a wide variety of electrophiles) of the replacement of a CH-group by an uncharged nitrogen atom, by various types of group incorporating a partially charged nitrogen (N@H, Ne-00, N@-R,N@-OH, etc.), and by charged ==S@-or =O@-. Only when more is known of the effects of these replacements towards the ortho, meta, and para positions, as well as effects relayed from one ring to another, will it be possible to develop and test the theoretical treatments, and, hopefully, to gain a real understanding of the field. Acetylcholinesterase plays a vifal part in the functioning of nerves, andseriousphysioIogica1 damage arises from its blockage by esters ofphosphonic andphosphoric acid used e.g. in pesticides. The properties and the mechanismof action of acetylcholinesterase, which show many similarities to those of other hydrolases, are described. Therapeutic agents (reactivators) for the toxic phosphorus compounds specified are also discussed. P. Schade' and D. H. Ford: Basic neurology, an introduction to the structure and function of the nervous system. Elsevier, Amsterdam-London-New York 1965 ; b) W. Blasius in Landois-Rosemann: Lehrbuch der Physiologiedes Menschen,

Simultaneous determination of the acetylcholinesterase activity of whole blood > plasma and erythrocytes with the automatic titratorAutomatic titration allows a rapid and precise, determination of acetylcholinesterase activity in whole blood, plasma and erythrocytes. In contrast with other methods, acetylcholinesterase activity is determined in diluted whole blood and in an erythrocyte-free supernatant prepared from the same dilution. In this way difficulties in the separation of plasma, loss of time by repeated washing and centrifuging of the erythrocytes and errors in sampling are greatly diminished. Activity is determined at pH7.4 and 37° C in the presence of 3mM acetylcholine. The standard test (performed in duplicate) uses 2 m/ of blood. This volume may be reduced. From the determination of the activity of diluted whole blood and the supernatant the acetylcholinesterase activity of whole blood, plasma and erythrocytes is calculated by use of the hematocrit value. Activity is given in //moles acetylcholine m/-1 min-1 . Normal values are given for a group of 12 men and 8 women.Für die Diagnose und besonders zur initialen Kontrolle des Therapie-Erfolgs bei Organophosphatvergiftungen gewinnt die Bestimmung der Aktivität der Acetylcholin-Esterase (EC 3.1.1.7) im Blut bzw. in den Erythrocyten immer mehr an Bedeutung, da sie im Gegensatz zum Verhalten der Plasma-Cholinesterase (EG 3.1.1.8) eine vertretbare Korrelation zum Vergiftungszustand zeigt (l, 2, 3). Für die klinische Routine-Untersuchung sind die bisher üblichen Methoden zur Bestimmung der Acetylcholinesterase-Aktivität wenig geeignet.Bei der manometrischen Methode (4, 5) wird das durch die enzymatisch gebildete Essigsäure freigesetzte CO 2 bestimmt. Die Methode hat den Vorteil, daß 12 Proben gleichzeitig gemessen werden können. Ihre Nachteile sind lange Vorbereitungs-und Meßzeiten, hohe Störanfälligkeit und die Verwendung einer Substratkonzentration von 20,6 mM Acetylcholin, bei der bereits eine beträchtliche Substrathemmung vorliegt. Die Variationsmöglichkeiten der Versuchsbedingungen sind gering.Die potentiometrische Methode nach MICHEL (6) arbeitet mit dem geringsten apparativen Aufwand, hat aber den Nachteil, daß nicht bei konstantem pH-Wert gemessen wird. Außerdem handelt es sich um eine Zweipunkt-Messung mit langer Inkubationszeit, deren Ergebnis (JpH/Std.) keine Umrechnung in molare Umsatzgrößen erlaubt. Die Meßergebnisse können folglich nicht mit denen anderer Methoden verglichen werden.Bei den photometrischen Methoden wird die Abnahme des Substrats (7) oder die Reaktion eines Produktes der enzymati §chen Hydrolyse mit einem spezifischen Reagenz (8, 9) gemessen. Diese photometrischen Methoden arbeiten rasch und zuverlässig, sind aber in der Wahl der Substrate begrenzt und auf Lösungen mit störender Eigenabsorption (Erythrocytensuspensionen, Hämolysate) nicht anwendbar.

The experiments presented here deal with the effects of the inhalation of dichlorvos [dimethyl-(2,2 dichlorvinyl)-phosphate, DDVP] vapor on acetylcholinesterase (ACHE) activity in rat bronchial tissue. Exposure to DDVP concentrations of 0.8 and 1.8 micrograms/l for 3 days reduced ACHE activity in the bronchial tissue (62.8 +/- 0.8 and 51.6 +/- 1.6% of the control), but did not elicit any changes in blood ACHE activity (101 +/- 4.5% of the control each). Higher concentrations (4.3 micrograms/l) induced a decline in ACHE activity also in the blood (38.2 +/- 1.1% of the control). In the histochemical preparations used to demonstrate ACHE activity in bronchial tissue (thiolacetic acid method), a staining of the bronchial glands and smooth muscles characteristic of the enzyme activity was strongly reduced after exposure of the animals to even the lowest dose applied (0.2 microgram/l). The question of whether localized inhibition of ACHE in the bronchial tissue might cause increases in airway resistance due to activation of a broncho-bronchial reflex is discussed. This efferent cholinergic mechanism has been found to be at least partly responsible for maintenance of bronchospasm and hypersecretion in chronic obstructive diseases of the respiratory system.