Pharmacology 193 



In (hronic intoxication ol mice, after daily injections ol 12 to 15 

 fxg. lor 20 to 30 days a great niniiber ol liver nuclei are irregularly 

 shaped. More than 40 per cent ol these contain spherical bodies re- 

 sembling huge nucleoli. These are diffusely stained by acid dyes. They 

 persist 13 days after the end of the injections. No mitoses were seen, 

 a lailur surprising fact.-*^ It may be suggested that these intranuclear 

 bodies result from arrested mitoses, and represent sj)indle material, 

 similar to the hyaline globules and ))seudospindles (Chapter 3) . 



Kidnev damage has been mentioned repeatedly, ^'*- •'- but has never 

 been described in detail. It should be borne in mind while considering 

 in Chapter 9 the use of colchicine in studies on the mitotic growth ol 

 kidney tubules. 



-.5-5.- The "l/itc" mitoses. In many experiments on mitotic 

 ])oisons. and in jKUticular after the injection of trypaflavine (acri- 

 Haxine) , normal mitoses coidd be found in unusual locations several 

 davs after the mitotic poisoning itself."' Colchicine is also effective, 

 and this i^ one of the observations that led to the belief that a true 

 mitotic stimulation existed. Actually, things are probably iar more 

 comi:)licated. 



In adult mice,^' divisions could be observed in many locations: 

 liver cells and Kujiffer cells, endothelial and epithelial cells of the pan- 

 creas, sali\ar\ cells, histiocytes, and renal epithelial cells. Some of these 

 mav be abnormal, but normal mitoses are usually found in liver, 

 pancreas, kidney, and adrenals, from one to two days after an injection. 

 \vhile some of the divisions may be of a regenerative character, for 

 instance in liver and kidney, the important fact is that this is not a 

 phenomenon observed with colchicine alcjue. It obviously needs 

 further investigation, because very few authors appear to have taken 

 notice of it. In the light of all recent work on stress, the hypothesis 

 that pituitary-adrenal stimulation of cellular division has taken place 

 as a consec|uence of the general toxicity of colchicine, deserves notice. 



7.5-7; ChemicaJ changes of the blood, llie idea of the alkaloid 

 producing a stress effect may liel[-) to explain some unrelated facts 

 mentioned in the ]jharmacological literature. The hyperglycemia 

 following the intra\enous injection of 1 gm/kg of glucose in the dog 

 is increased 10 to 12 hours after colchicine.^^ The lethal dose of the 

 drug in this species is 1 mg/kg. It decreases the blood sugar and also 

 the body temperatine.''^ The action on the glycemia does not appear 

 to be related to j)ancreatic islet activity. The LD-,,, dose has the same 

 effeci. In j^ancreatectomized dogs, (;n the contiary, the glycemia again 

 reaches its normal level within (i to 11 hours.*'"' The influence of the 

 adrenal cortical hormones has not been studied in these experiments. 

 Evidence has been presented that the adrenal j^lays an imjiortant part 

 in controlling the temperature fall observed after colchicine poisoning 

 (Fig. 7.2) . 



