542 ANNALS NEW YORK ACADEMY OF SCIENCES 



indicated to explore the actions of various cholinesterases, with respect 

 to the criteria indicated in Table 10. 



IN VIVO CHANGES OF CHOLINESTERASE 



Alterations of Cholinesterase Activity in Disease. Considerable clin- 

 ical and pharmacological investigation into the in vivo changes of 

 cholinesterase activity has been conducted, with a view to determining 

 the physiological significance of cholinesterase. The pathological con- 

 dition which has attracted most attention, in this respect, is Myasthenia 

 gravis. In this condition, which is characterized by muscle weakness 

 and inclination to fatigue, it has been postulated that there is a defi- 

 ciency of acetylcholine at the neuromuscular junction. Such a postu- 

 lated deficiency may, of course, be brought about by a failure to syn- 

 thesize acetylcholine, or by an excessive amount, or excessive activity, 

 of cholinesterase at the neuromuscular junctions. That the latter 

 mechanism is operative has been assumed, because .of the finding that 

 prostigmine, an inhibitor of cholinesterase activity in vitro and of 

 serum cholinesterase activity in vivo, results in clinical improvement.*® 

 There is, however, no conclusive evidence of increased cholinesterase 

 concentration or activity at the myoneural junctions. A number of 

 investigators**^"^^ have failed to find increased cholinesterase activity 

 in the serum in Myasthenia gravis, and, although the cholinesterase 

 activity of muscle may perhaps not be regarded as too specific, there 

 has been a similar inability to find increase of cholinesterase activity 

 in muscle.^'' Other explanations of the physiological fault in Myas- 

 thenia gravis and of the action of various drugs have been submitted 

 by Gammon, Harvey, and Masland.^' 



There are, however, several conditions in which definite changes in 

 serum cholinesterase activity have been reported. There is fairly 

 general agreement that debilitating diseases, such as tuberculosis, can- 

 cer, and liver disease, are characterized by low serum cholinesterase 

 activities. °®"'^* For example, Faber'^* found ranges of 65 to 150 units in 

 normal men and 57 to 184 in normal women. In acute hepatitis, values 

 ranging from 41 to 51 units were obtained; in liver cirrhosis, activities 

 ranging from 77 to 92; in cancer, from 33 to 99; and in uremia, from 

 32 to 56 units. High serum cholinesterase activities have been re- 

 ported in hyperthyroidism.*^'*' ®^ 



The author does not know, however, of any evidence to indicate that 

 the low serum cholinesterase values found in debilitating diseases are 

 of any special significance, so far as transmission of nervous impulses 

 is concerned. Indeed, these low cholinesterase activities appear to be 



