B VITAMIN DEFICIENCY STATES 403 



used as assay animals in earlier work, both the cure of polyneuritis and 

 the maintenance of weight having been used as the measured criteria in 

 the assays. 51 Thiamine has also been measured by its effect on the oxygen 

 uptake of avitaminotic pigeon brain tissue, once referred to as the 

 "catatorulin effect." 52 It is of interest in this regard that differences 

 apparently occur in the ability of tissues from different species to take 

 up oxygen. 53 Deficient pigeons first exhibit a general lack of activity and 

 cease to eat normally. One of the most characteristic symptoms of 

 thiamine deficiency in the pigeon is head retraction, and this symptom 

 has been utilized as a criterion in assay work. The rapid cure by thiamine 

 administration of this grotesque, rumed-feather, drawn back neck with 

 upside down head appearance (opisthotonus) is one of the most sensa- 

 tional experimental pictures conceivable, particularly in view of the 

 convulsions and death which normally follow rapidly upon this stage. As 

 in rats, pigeons that are thiamine-deficient exhibit a marked bradycardia. 



The principal biochemical features involved in thiamine deficiency are 

 an increased blood and urinary pyruvate and lactate and decreased 

 thiamine and cocarboxylase. As previously discussed (p. 255), thiamine 

 retention in loading tests is increased. The pyruvism is obviously due to 

 the lack of ability to convert pyruvate to acetate, a reaction involving 

 thiamine. Since the oxidative metabolism of pyruvate is further blocked 

 in the cyclophorase system at the thiamine-mediated conversion of 

 ketoglutarate to succinate, the decreased oxygen uptake of thiamine- 

 deficient pigeon brain would certainly be expected. Studies on the pyru- 

 vate exchange in the heart of thiamine-deficient dogs indicate that the 

 heart normally oxidizes completely the products regularly formed within 

 it from carbohydrate metabolism, and in addition some of the products 

 derived from other organs via the blood, and that in thiamine deficiency 

 this function is so impaired that the increased blood pyruvate may to a 

 large extent originate from the heart. 54 Since many factors influence blood 

 pyruvate and lactate levels, it seems that pyruvate and lactate determi- 

 nations are not more sensitive and accurate as diagnostic tests for 

 thiamine deficiency than thiamine levels themselves. 55 



There is some evidence to indicate that episthotonos in the pigeon and 

 some other symptoms in other species are a consequence of lactate accu- 

 mulation, which may be demonstrated in the liver, heart, muscles, and 

 brain. There is similarly an accumulation of tissue pyruvate but the 

 actual amounts of either acid are so small as to make doubtful their 

 contribution to the toxic effect. Other evidences of a deranged carbo- 

 hydrate metabolism follow as a sequence to the blocked pyruvate oxida- 

 tion. Pigeons exhibit a hyperglycemia and depletion of liver glycogen, 

 and rats show abnormally high glucose tolerance curves (reduced glucose 



