UBC Theses and Dissertations

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UBC Theses and Dissertations

Study of hypervitaminosis E in the chick 1970

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A S T U D Y OF H Y P E R V I T A M I N O S I S E I N T H E C H I C K B Y F O O K C H U E N WONG B . S . A . , N A T I O N A L T A I W A N U N I V E R S I T Y , 1961 A T H E S I S S U B M I T T E D IN P A R T I A L F U L F I L M E N T OF T H E R E Q U I R E M E N T S F O R T H E D E G R E E OF M A S T E R OF S C I E N C E I N T H E D E P A R T M E N T OF P O U L T R Y S C I E N C E WE A C C E N T T H I S T H E S I S A S C O N F O R M I N G TO T H E R E Q U I R E D S T A N D A R D T H E U N I V E R S I T Y OF B R I T I S H C O L U M B I A O C T O B E R , 1970 In p r e s e n t i n g t h i s t h e s i s i n p a r t i a l f u l f i l m e n t o f the r e q u i r e m e n t s f o r an advanced d e g r e e a t t h e U n i v e r s i t y o f B r i t i s h C o l u m b i a , I a g r e e t h a t t h e L i b r a r y s h a l l make i t f r e e l y a v a i l a b l e f o r r e f e r e n c e and s t u d y . I f u r t h e r a g r e e t h a t p e r m i s s i o n f o r e x t e n s i v e c o p y i n g o f t h i s t h e s i s f o r s c h o l a r l y p u r p o s e s may be g r a n t e d by the Head o f my Depar tment o r by h i s r e p r e s e n t a t i v e s . I t i s u n d e r s t o o d t h a t c o p y i n g o r p u b l i c a t i o n o f t h i s t h e s i s f o r f i n a n c i a l g a i n s h a l l not be a l l o w e d w i t h o u t my w r i t t e n p e r m i s s i o n . Depar tment o f The U n i v e r s i t y o f B r i t i s h C o l u m b i a V a n c o u v e r 8 , Canada Date j£l^_^£_jllf. ACKNOWLEDGEMENT I WISH TO T H A N K D R . W. D . K l T T S , H E A D O F T H E D E P A R T M E N T OF P O U L T R Y S C I E N C E , F O R P R O V I D I N G T H E F A C I L I T Y U S E D I N T H I S S T U D Y . I AM G R A T E F U L TO M R S . B . E . M A R C H , OF T H E D E P A R T M E N T OF P O U L T R Y S C I E N C E , WHO S U P E R V I S E D T H E P L A N N I N G AND E X E C U T I O N OF T H E E X P E R I M E N T S . I A L S O T H A N K D R S . J . B L E L Y , R. F L T Z S I M M O N S AND M . T A I T FOR T H E I R E N C O U R A G E M E N T T H R O U G H O U T M Y P R O G R A M . A B S T R A C T A S T U D Y WAS M A D E OF T H E E F F E C T S OF F E E D I N G E X C E S S V I T A M I N E TO C H I C K S . T H R E E G R O U P S OF E X P E R I M E N T S WERE C O N D U C T E D TO I N V E S T I G A T E ( 1 ) T H Y R O I D A L R E S P O N S E TO E X C E S S V I T A M I N E , (2) R E S P I R A T I O N R A T E OF M U S C L E M I T O C H O N D R I A F R O M C H I C K S F E D E X C E S S V I T A M I N E ; AND (3) S Y M P T O M S OF H Y P E R V I T A M I N O S I S E . |N TWO S E P A R A T E E X P E R I M E N T S , C H I C K S WERE F E D N O R M A L A N D E X C E S S L E V E L S (220 I . U . / K G . OF D I E T ) OF V I T A M I N E A N D WERE S U B J E C T E D TO T E M P E R A T U R E S OF 1 4 . 5 AND 3 1 . 5 ° C . T H E G O I T R O G E N I C E F F E C T OF T H I O U R A C I L ON T H E B I R D S I N T H E D I F F E R E N T T R E A T M E N T S WAS M E A S U R E D . AT B O T H T E M P E R A T U R E S T H E T H I O U R A C I L - T R E A T E D C H I C K S F E D E X C E S S V I T A M I N E E X H I B I T E D A L E S S E R E N L A R G E M E N T OF T H E T H Y R O I D G L A N D S T H A N D I D C H I C K S R E C E I V I N G A N O R M A L L E V E L OF V I T A M I N E . T H I S F I N D I N G I N D I C A T E S A R E D U C T I O N I N T H E S E C R E T I O N OF T H Y R O I D S T I M U L A T I N G H O R M O N E ( T S H ) I N B I R D S F E D E X C E S S V I T A M I N E . T H E L E V E L OF V I T A M I N E W H I C H WAS F E D D I D NOT A F F E C T T H E GROWTH R A T E OR F E E D C O N S U M P T I O N A T E I T H E R T E M P E R A T U R E . I T , T H E R E F O R E , A P P E A R S T H A T T H E M E T A B O L I C R A T E S OF T H E C H I C K S F E D T H E LOW AND E X C E S S L E V E L S OF V I T A M I N E WERE S I M I L A R D E S P I T E D I F F E R E N C E S I N T H Y R O I D A C T I V I T Y AND T H A T T I S S U E R E S P I R A T I O N I N B I R D S F E D E X C E S S V I T A M I N E C A N BE M A I N T A I N E D W I T H A R E D U C E D S U P P L Y OR T U R N O V E R OF T H Y R O I D H O R M O N E . T H E A C T I V I T Y OF T H E T H Y R O I D G L A N D I T S E L F WAS S T U D I E D I N R E S P O N S E TO 131 E X C E S S V I T A M I N E I N A N O T H E R E X P E R I M E N T . U S I N G R A D I O I O D I N E ( l ) A S A T R A C E R , I T WAS F O U N D T H A T T H E R A T E S OF I O D I N E U P T A K E A N D R E L E A S E B Y T H E T H Y R O I D G L A N D WERE B O T H S L O W E R I N B I R D S F E D E X C E S S V I T A M I N E (220 I . U . / K G . 0 F D I E T ) T H A N I N C O N T R O L B I R D S . B E C A U S E V I T A M I N E A C T S A S A B I O L O G I C A L A N T I O X I D A N T , I T M A Y , I N E X C E S S A M O U N T S , D E P R E S S T H E R A T E OF O E I O D I N A T I O N OF T H Y R O X I N E I N T H E P E R I P H E R A L T I S S U E AT W H I C H T H Y R O I D H O R M O N E I S R E M O V E D F R O M T H E . C I R C U L A T I O N . AS A C O N S E Q U E N C E , T H E S E C R E T I O N OF T S H WOULD B E R E D U C E D . I N O R D E R TO O B T A I N S O M E I N D I C A T I O N OF C A U S E AND E F F E C T I N T H E M E C H A N I S M B Y W H I C H T H E E X C E S S V I T A M I N E A F F E C T S T H Y R O T R O P I C H O R M O N E S E C R E T I O N R A T E A N D T H Y R O I D A C T I V I T Y , T H E R E S P I R A T I O N R A T E OF M I T O C H O N D R I A I S O L A T E D F R O M T H E P E C T O R A L M U S C L E O F C H I C K S W H I C H HAD B E E N F E D E X C E S S V I T A M I N E (2200 I . U . / K G . 0 F D I E T ) WAS C O M P A R E D W I T H T H A T O F T H E C O N T R O L B I R D S . T H E R E S U L T S S H O W E D A S I G N I F I C A N T R E D U C T I O N I N O X Y G E N U P T A K E B Y T H E M U S C L E M I T O C H O N D R I A O F C H I C K S F E D T H E E X C E S S A M O U N T OF V I T A M I N E . T H E G R O W T H R A T E OF T H E C H I C K S F E D T H E E X C E S S L E V E L OF V I T A M I N E I N T H I S E X P E R I - M E N T WAS M A R K E D L Y L O W E R T H A N T H A T O F T H E C O N T R O L C H I C K S . I T I S S U G G E S T E D T H A T T H E C H I C K M A Y M A I N T A I N A N O R M A L R E S P I R A T I O N R A T E WHEN F E D E X C E S S V I T A M I N E U P TO A C E R T A I N L E V E L T H R O U G H A R E D U C T I O N I N T H Y R O I D A C T I V I T Y . W I T H A L A R G E E X C E S S O F V I T A M I N E, H O W E V E R , NO F U R T H E R C O M P E N S A T I O N I S P O S S I B L E . A N D R E S P I R A T I O N R A T E I S D E P R E S S E D B E L O W N O R M A L . E X C E S S V I T A M I N E C A U S E D H Y P O P R O T H R O M B I N E M I A , I N D I C A T I V E O F V I T A M I N K ~ D E F I C I E N C Y . O T H E R S Y M P T O M S N O T E D WERE A R E D U C T I O N I N H E M A T O C R I T V A L U E S , R E T I C U L O C Y T O S I S AND A N A B N O R M A L L Y F L U I D- A P P E A R A N C E OF T H E B O N E M A R R O W . B A S E D U P O N O B S E R V A T I O N S OF B O N E C A L C I F I C A T I O N , T H E C A L C I U M R E Q U I R E M E N T A P P E A R E D TO B E I N C R E A S E D I N T H E P R E S E N C E OF E X C E S S V I T A M I N E . T A B L E OF C O N T E N T S P A G E L I S T OF T A B L E S v L I S T OF F I G U R E S v i I N T R O D U C T I O N 1 R E V I E W OF L I T E R A T U R E 3 E X P E R I M E N T I 12 T H Y R O I D A L R E S P O N S E TO E X C E S S D I E T A R Y V I T A M I N E . 12 E X P E R I M E N T |A 12 M A T E R I A L S A N D M E T H O D S 12 E X P E R i M E N T I B 14 R E S U L T S AND D I S C U S S I O N 14 E X P E R I M E N T I C 2 0 M A T E R I A L S AND M E T H O D S 2 0 R E S U L T S A N D D I S C U S S I O N 22 E X P E R I M E N T I I 26 R E S P I R A T I O N R A T E OF M U S C L E M I T O C H O N O R I A F R O M C H I C K S F E D E X C E S S D I E T A R Y V I T A M I N E 26 M A T E R I A L S A N D M E T H O D S . 26 R E S U L T S AND D I S C U S S I O N 2 9 E X P E R I M E N T I I I 35 S Y M P T O M S OF K Y P E R V I T A M I N O S I S E I N C H I C K 35 M A T E R I A L S A N D M E T H O D S 35 R E S U L T S 38 D I S C U S S I O N 44 i 11 P A G E S U M M A R Y 47 B I B L I O G R A P H Y 4 9 IV L I S T OF T A B L E S T A B L E - P A G E 1 A . B A S A L D I E T S I N E X P E R I M E N T |A 61 1 B . B A S A L D I E T S I N E X P E R I M E N T I B 61 2 . A V E R A G E T H Y R O I D W E I G H T S , B O D Y W E I G H T S AND F E E D C O N S U M P T I O N OF C H I C K S I N E X P E R I M E N T I A 62 3 . A V E R A G E T H Y R O I D W E I G H T S , B O D Y W E I G H T S A N D F E E D C O N S U M P T I O N OF C H I C K S I N E X P E R I M E N T |B 63 4 . A N A L Y S I S OF V A R I A N C E OF T H Y R O I D A L R E S P O N S E TO T H E E X C E S S V I T A M I N E A N D / O R T H I O U R A C I L AT D I F F E R E N T T E M P E R A T U R E S I N E X P E R I M E N T I A 64 5 . A N A L Y S I S OF V A R I A N C E OF T H Y R O I D A L R E S P O N S E TO E X C E S S V I T A M I N E A N D / O R T H I O U R A C I L AT D I F F E R E N T T E M P E R A T U R E S I N E X P E R I M E N T I B 65 6 . A V E R A G E T H Y R O I D W E I G H T S , B O D Y W E I G H T S A N D F E E D C O N S U M P T I O N OF E T H O X Y Q U I N ( E Q ) - T R E A T E D C H I C K S AT 2 2 ° C I N E X P E R I M E N T I B 66 7 . E F F E C T OF E X C E S S D I E T A R Y V I T A M I N E ON T H Y R O I D A L I O D I N E (|131) U P T A K E A N D R E L E A S E I N W H I T E L E G H O R N M A L E C H I C K S 67 8 . R E S P I R A T I O N R A T E S O F M U S C L E M I T A O C H O N D R I A F R O M C H I C K S F E D T H E C O N T R O L D I E T , E X C E S S V I T A M I N E A N D / O R T H I O U R A C I L . . . 68 9 . B A S A L D I E T I N E X P E R I M E N T I I I 69 1 0 . E F F E C T O F E X C E S S V I T A M I N E ON H E M A T O C R I T V A L U E , P R O T H R O M B I N T I M E A N D R E T I C U L O C Y T E C O U N T 70 1 1 . P R O T H R O M B I N T I M E OF C H I C K S F E D E X C E S S V I T A M I N E , 24 H O U R S A F T E R I N J E C T I O N OF M E N A D I O N E . . 71 1 2 . E F F E C T OF E X C E S S V I T A M I N E ON B O N E C A L C I F I C A T I O N I N C H I C K S F E D D I E T S A D E Q U A T E AND D E F I C I E N T I N C A L C I U M 72 v L I S T OF F I G U R E S F I G U R E ' P A G E 1 . T H Y R O I D A L R E S P O N S E OF C H I C K S R E C E I V I N G TWO L E V E L S OF V I T A M I N E A N D / O R E T H O X Y Q U I N TO T H I O U R A C I L AT D I F F E R E N T A M B I E N T T E M P E R A T U R E S I N E X P E R I M E N T |A 16 2 . T H Y R O I D A L R E S P O N S E OF C H I C K S R E C E I V I N G TWO L E V E L S OF V I T A M I N E A N D / O R E T H O X Y Q U I N TO T H I O U R A C I L AT D I F F E R E N T A M B I E N T T E M P E R A T U R E S I N E X P E R I M E N T I B 17 3 . E F F E C T OF E X C E S S D I E T A R Y V I T A M I N E ON T H Y R O I D A L I O D I N E (|131) U P T A K E A N D R E L E A S E I N W H I T E L E G H O R N M A L E C H I C K S 2 3 4 . E F F E C T OF E X C E S S D I E T A R Y V I T A M I N E ON T H Y R O I D A L I O D I N E ( l ) U P T A K E AND R E L E A S E I N W H I T E L E G H O R N M A L E C H I C K S 24 5 . E L E C T R O N M I C R O G R A P H OF B R E A S T M U S C L E M I T O C H O N D R I A F R O M A C H I C K F E D A N O R M A L L E V E L OF V I T A M I N E 32 6 . E L E C T R O N M I C R O G R A P H OF B R E A S T M U S C L E M I T O C H O N D R I A F R O M A C H I C K F E D E X C E S S V I T A M I N E 33 7 . E L E C T R O N M I C R O G R A P H OF B R E A S T M U S C L E M I T O C H O N D R I A F R O M A C H I C K F E D A N O R M A L L E V E L OF V I T A M I N E S H O W I N G I N T A C T M I T O C H O N D R I A 34 8 . E R Y T H R O C Y T E S F R O M A 4 0 - D A Y OLD C H I C K F E D A N O R M A L L E V E L OF V I T A M i N E 4 0 9 . R E T I C U L O C Y T E S F R O M A 4 0 - D A Y OLD C H I C K F E D E X C E S S V I T A M I N E 4 0 1 0 . E R Y T H R O B L A S T O B S E R V E D ON T H E B L O O D S M E A R F R O M A • 4 0 - D A Y OLD C H I C K 41 1 1 . A B N O R M A L B O N E M A R R O W OF C H I C K S F E D E X C E S S V I T A M I N E 42 v I F I G U R E P A G E 1 2 A . T H E I N F L U E N C E OF E X C E S S V I T A M I N E ON P E R C E N T OF T I B I A A S H A T D I F F E R E N T A G E S 45 1 2 B . T H E I N F L U E N C E OF E X C E S S V I T A M I N E ON P E R C E N T OF T I B I A A S H R E L A T I V E TO B O D Y W E I G H T 4 5 v I I I N T R O D U C T I ON A D E F I C I E N C Y OF V I T A M I N E C A U S E S A V A R I E T Y OF S Y M P T O M S I N D I F F E R E N T S P E C I E S OF A N I M A L S A N D M A Y A F F E C T M A N Y T I S S U E S ( S E E R E V I E W B Y M A S O N , 1 9 4 9 ; M A T T I L L , 1 9 5 2 ; D A M , 1 9 5 7 ; R O E L S , 1 9 6 7 ; S C O T T _ET _ A L . , 1 9 6 9 ) . O T H E R D I E T A R Y C O M P O N E N T S S U C H A S M E T H I O N I N E ( C A L V E R T _ET _ A L . , 1 9 6 2 ) , S E L E N I U M ( S C H W A R Z , 1 9 6 0 ; D E S A I A N D S C O T T , 1965) A N D U N S A T U R A T E D F A T T Y A C I D S ( C E N T U R Y A N D H O R W I T T , 1 9 5 8 ; W I T T I N G A N D H O R W I T T , 1962) M A Y A F F E C T T H E R E Q U I R E M E N T OF T H E A N I M A L F O R V I T A M I N E AND T H E M A N N E R I N W H I C H A D E F I C I E N C Y OF T H E V I T A M I N M A N I F E S T S I T S E L F . \T I S A P P A R E N T T H A T V I T A M I N E H A S S E V E R A L D I F F E R E N T M E T A B O L I C F U N C T I O N S B U T . T H E P R I M A R Y M E C H A N I S M OF A C T I O N OF V I T A M I N E I N T H E L I V I N G C E L L HAS NOT Y E T B E E N D E T E R M I N E D . O N E F U N C T I O N OF V I T A M I N E I S A S A B I O L O G I C A L A N T I O X I D A N T ( T A P P E L , 1 9 6 2 ) . AS A R E S U L T OF I T S A N T I O X I D A N T P R O P E R T I E S V I T A M I N E A C T S A S A N O N S P E C I F I C P R O T E C T O R OF M E M B R A N E L I P I D S I N C E L L S (H 0 R W I T T _ET _AL . , 1968) OR O R G A N E L L E S S U C H A S M I T O C H O N D R I A ( T A P P E L A N D Z A L K 1 N , 1 9 5 9 A ) , L Y S O S O M E S ( D E S A I _E_T _ A L . , 1 9 6 4 ) , A N D M I C R O S O M E S ( T A P P E L AND Z A L K I N , 1 9 6 0 ) . L A C K OF S U F F I C I E N T T O C O P H E R O L TO P R E V E N T U N C O N T R O L L E D O X I D A T I O N C A U S E S T H E E V E N T U A L R U P T U R E OF M E M B R A N E S A N D T H E R E L E A S E OF E N Z Y M E S P E C U L I A R TO A S U B C E L L U L A R P A R T I C L E . V I T A M I N E A L S O P R O T E C T S V I T A M I N A A G A I N S T O X I D A T I O N ( D A M _ E T _ A L . , 1 9 5 2 ; P U D E L K I EW I CZ _ET _AL . 1 9 6 4 ) A N D H A S B E E N SHOWN TO R E A C T I V A T E A S C O R B I C A C I D S Y N T H E S I S B Y L I V E R P R E P A R A T I O N S I N V I T R O F R O M V I T A M I N E D E F I C I E N T A N I M A L S ( C A P U T T O _E_T _A_L • , 1 9 5 8 ) . T H E F A C T T H A T T H E 1 2 T O C O P H E R O L S R E A D I L Y U N D E R G O R E V E R S I B L E O X I D A T I O N - R E D U C T I O N , H A S L E D TO T H E S U G G E S T I O N T H A T O T - T O C O P H E R O L M A Y F U N C T I O N I N T E R M I N A L E L E C T R O N - T R A N S F E R E N Z Y M E S A S A C O E N Z Y M E OR A S A S T R U C T U R A L A G E N T ( V AS I NG TON _ET _AL . , 1 960J DETW I L E R _ET _AL . , 1 9 6 6 ) . B E C A U S E V I T A M I N E HAS A N T I O X I D A N T P R O P E R T I E S A N D U N D E R G O E S R E V E R S I B L E OX I D A T 1 O N - R E D U C T I O N , IT I S P O S S I B L E T H A T AN E X C E S S OF V I T A M I N E M A Y I N T E R F E R E I N T H E A C T I O N OF O T H E R B I O L O G I C A L R E D O X S U B S T A N C E S . A L T H O U G H T H E R E I S A L A R G E V O L U M E OF L I T E R A T U R E D E A L I N G W I T H V I T A M I N E D E F I C I E N C Y , T H E R E H A V E B E E N FEW S T U D I E S R E G A R D I N G T H E E F F E C T S OF E X C E S S V I T A M I N E . S Y M P T O M S OF H Y P E R V I T A M I N 0 S I S E H A V E NOT B E E N D E S C R I B E D , NOR I S T H E R E E V I D E N C E T H A T T O C O P H E R O L S P E R S E E X E R T A N Y D E L E T E R I O U S E F F E C T I N A N I M A L S OR MAN ( D E M O L E , 1 9 3 9 ; H L L L M A N , 1 9 5 7 ) . T H E P R E S E N T I N V E S T I G A T I O N WAS C O N D U C T E D TO D E T E R M I N E WHAT E F F E C T S E X C E S S D I E T A R Y V I T A M I N E M A Y H A V E I N C H I C K S . T H R E E G R O U P S OF E X P E R I M E N T S WERE C A R R I E D OUT TO S T U D Y (1) T H Y R O I D A L R E S P O N S E TO E X C E S S D I E T A R Y V I T A M I N E J (2) R E S P I R A T I O N R A T E OF M U S C L E M I T O C H O N D R I A F R O M C H I C K S F E D E X C E S S V I T A M I N E J (3) S Y M P T O M S OF H Y P E R V I T A M I NOS I S E I N " C H I C K S . REVIEW OF L I T E R A T U R E G E N E R A L V I T A M I N E WAS D I S C O V E R E D I N 1922 B Y E V A N S AND B I S H O P A S A F A C T O R P R E S E N T I N V E G E T A B L E O I L W H I C H WAS N E C E S S A R Y F O R N O R M A L R E P R O D U C T I O N I N T H E R A T . T H E D E S I G N A T I O N OF T H E L E T T E R E , N E X T I N O R D E R F O L L O W I N G V I T A M I N D, WAS S U G G E S T E D B Y S U R E . P U R E V I T A M I N E WAS F I R S T I S O L A T E D B Y E V A N S A N D T H E E M E R S O N S (1936) F R O M T H E U N S A P O N I F I C A B L E F R A C T I O N OF WHEAT G E R M O I L . T H E N A M E T O C O P H E R O L WAS P R O P O S E D F R O M T H E G R E E K W O R D , T O K O S ( O F F S P R I N G ) , P E R E I N ( T O B E A R ) , A N D O L ( T O S I G N I F Y AN A L C O H O L ) . T H E P R E F I X E S CC, (i, Y, E T C . WERE U S E D TO I N D I C A T E V A R I O U S F O R M S OF T O C O P H E R O L . A L P H A - T OC O P H E ROL", H A V I N G H I G H B I O L O G I C A L A C T I V I T Y ( C E N T U R Y A N D H O R W I T T , 1965) WAS I D E N T I F I E D B Y F E R N H O L Z ( 1 9 3 7 , 1 9 3 8 ) . D L - C C - T O C O P H E R Y L A C E T A T E I S U S E D A S A R E F E R E N C E S T A N D A R D ( H U M E , 1941) AND F E E D S U P P L E M E N T . T H I S F O R M OF T H E V I T A M I N I S NOT R E A D I L Y A U T O X I D I Z A B L E A N D H A S A H I G H B I O P O T E N C Y . V I T A M I N E D E F I C I E N C Y I N A N I M A L S AND C H I C K S H A S B E E N R E P O R T E D B Y A N U M B E R OF I N V E S T I G A T O R S . V I T A M I N E D E F I C I E N C Y C A U S E S A W I D E V A R I E T Y OF S Y M P T O M S I N D I F F E R E N T S P E C I E S OF A N I M A L S A N D M A Y A F F E C T M A N Y D I F F E R E N T T I S S U E S , I N C L U D I N G T H E E M B R Y O ( F E T A L R E S O R P T I O N ) , G O N A D S ( S T E R I L I T Y ) , M U S C L E ( ' M U S C U L A R D Y S T R O P H Y ) , B R A I N ( E N C E P H A L OMAL AC I A ) , B L 0 0 0 ( H E M O L YS I S OF E R Y T H R O C Y T E S , A N D A N E M I A ) , C A P I L L A R Y W A L L S ( E X U D A T I V E D I A T H E S I S ) , L I V E R ( L I V E R N E C R O S I S ) , K I D N E Y ( D E G E N E R A T I O N OF T U B U L A R E P I T H E L I U M ) , D E P O T F A T 3 4 ( S T E A T I T I S ) ( S E E R E V I E W S B Y M A S O N , 1 9 4 9 ; M A T T I L , 1 9 5 2 ; D A M , 1 9 5 7 ; R O E L S , 1 9 6 7 ; S C O T T _ET _ A L . , 1 9 6 9 ) . ONE OF T H E M O S T W I D E L Y O C C U R I N G S Y M P T O M S OF V I T A M I N E D E F I C I E N C Y I N M A N Y A N I M A L S I S M U S C U L A R D Y S T R O P H Y . A S V I T A M I N E D E F I C I E N C Y A F F E C T S S U C H A W I D E V A R I E T Y OF A N I M A L T I S S U E S , A N D S E V E R A L F A C T O R S S U C H AS T H E D I E T A R Y L E V E L S OF M E T H I O N I N E ( C A L V E R T E T A L . , 1962) S E L E N I U M ( S C H W A R Z , 1 9 6 0 ) , A N D U N S A T U R A T E D F A T T Y A C I D S ( C E N T U R Y A N D H O R W I T T , 1 9 5 8 ; W I T T I N G A N D H O R W I T T , 1962) I N F L U E N C E V I T A M I N E D E F I C I E N C Y S Y N D R O M E S I N A V A R I E T Y OF A N I M A L S P E C I E S , I T I S A P P A R E N T T H A T V I T A M I N E H A S S E V E R A L D I F F E R E N T M E T A B O L I C F U N C T I O N S , B U T NO E X A C T M E T A B O L I C R O L E OF V I T A M I N E H A S Y E T B E E N D E F I N E D . V I T A M I N E I S F O U N D P R I N C I P A L L Y I N T H E O R G A N E L L A OF T H E C E L L S (W I S S _E_T _AL . , 1962) S U C H A S M I T O C H O N D R I A , M I C R O S O M E S , AND L Y S O S O M E S WHERE I T I S P R E S E N T M A I N L Y I N T H E R E D U C E D S T A T E ( M O O R E , 1 9 5 9 ) . T H E R E S E E M S TO B E L I T T L E D O U B T T H E R E F O R E T H A T I T F U N C T I O N S A S A B I O L O G I C A L A N T I O X I D A N T W H I C H P R O T E C T S T H E S T R U C T U R A L A N D M E T A B O L I C I N T E G R I T Y OF I N T R A C E L L U L A R U N I T S ( T A P P E L , 1 9 6 2 ; G U H A A N D R O E L S , 1 9 6 5 ; R O E L S _ET _ A L . , 1 9 6 5 ; L U C Y AND D I N G L E , 1 9 6 4 ) . P R E V E N T I O N OF P E R O X I D A T I O N A P P E A R S TO BE V E R Y I M P O R T A N T I N T H E M A I N T E N A N C E OF T H E S T R U C T U R A L I N T E G R I T Y OF T H E C E L L U L A R M E M B R A N E S OR S U B C E L L U L A R M E M B R A N E S ( Z A L K I N A N D T A P P E L , 1960) I N T I S S U E S . ONE I N T E R E S T I N G F A C T I S T H A T T O C O P H E R O L S A D M I N I S T E R E D E I T H E R I N V I V O OR I N V I T R O I N H I B I T T H E D I A L U R I C A C I D - I N D U C E D H E M O L Y S I S OF E R Y T H R O C Y T E S I N R A T S ( R O S E A N D G Y O R G Y , 1 9 5 0 , 1 9 5 2 ) . T S E N A N D C O L L I E R (1960) A N D B U N Y A N _ET _ A L . ( I 9 6 0 ) H A V E P R E S E N T E D E V I D E N C E T H A T D I A L U R I C A C I D P R O M O T E S E R Y T H R O C Y T E H E M O L Y S I S B Y C A T A L Y Z I N G L I P I D P E R O X I D A T I O N AND T H A T V I T A M I N E A C T S A S A N A N T I O X I D A N T . C HR I S TE N S E N _E_T _AL . (1956) SHOWED T H A T T H E D I A L U R I C 5 A C I D - I N D U C E D H E M O L Y S I S M A Y BE U S E D F O R A S S E S S I N G V I T A M I N E D E F I C I E N C Y I N T H E R A T B U T T H A T I T I S NOT A R E L I A B L E C R I T E R I O N F O R D E T E R M I N I N G A D E F I C I E N C Y OF T H I S V I T A M I N I N T H E C H I C K . V I T A M I N E M A Y P L A Y A R O L E I N E N E R G Y M E T A B O L I S M . F O R E X A M P L E , I T M A Y BE A C O M P O N E N T O F T H E C Y T O C H R O M E C R E D U C T A S E S Y S T E M S OF T H E T E R M I N A L R E S P I R A T O R Y C H A I N F U N C T I O N I N G D I R E C T L Y A S A N E L E C T R O N C A R R I E R ( B I O L O G I C A L O X I D A T I O N A N D R E D U C T I O N ) OR I N D I R E C T L Y A S A B I N D I N G A G E N T ( V A S I N G T O N , R E I C H A R D A N D N A S O N , 1 9 6 0 ) . OL I V E R I RA _ET _AL . ( 1 9 6 9 ) D E M O N S T R A T E D T H A T CC- T O C O P H E R O L D I D NOT H A V E A D I R E C T Q U A N T I T A T I V E R E L A T I O N S H I P W I T H E N Z Y M A T I C A C T I V I T I E S . |T H A S A L S O B E E N S U G G E S T E D T H A T I T M A Y F U N C T I O N D I R E C T L Y OR I N D I R E C T L Y I N N O R M A L O X I D A T I V E P H O S P H O R Y L A T I O N I N T I S S U E R E S P I R A T I O N ( V A S I N G T O N , R E I C H A R D A N D N A S O N , 1 9 6 0 ) , OR I N T H E M E T A B O L I S M OF C O E N Z Y M E Q ( G R E E N , 1 9 6 2 ) . T H Y R O I D A L R E S P O N S E TO T E M P E R A T U R E A N D D I E T A L T H O U G H T H E M E C H A N I S M OF A C T I O N O F T H Y R O I D H O R M O N E S S T I L L R E M A I N S U N K N O W N , T H E T H Y R O I D G L A N D I S C O N S I D E R E D TO P L A Y AN I M P O R T A N T R O L E I N T H E A D A P T I V E P H E N O M E N A A S S O C I A T E D W I T H C H A N G E S I N E X T E R N A L E N V I R O N M E N T AND H A S B E E N T H E S U B J E C T OF N U M E R O U S I N V E S T I G A T I O N S I N T H I S R E G A R D . |N T H E S E S T U D I E S , T H Y R O I D A C T I V I T Y H A S B E E N E V A L U A T E D B Y D I F F E R E N T M E T H O D S U T I L I Z I N G A V A R I E T Y O F P A R A M E T E R S S U C H A S B A S A L M E T A B O L I C R A T E , T H Y R O I D W E I G H T , H I S T O L O G I C A L A P P E A R A N C E O F T H E T I S S U E , P R O T E I N - B O U N D I O D I N E L E V E L S , R A D I O I O D I N E U P T A K E A N D T H Y R O I D A L I O D I N E T U R N O V E R R A T E . M A N Y . F A C T O R S S U C H A S G E N E T I C S T R A I N , A G E , E N V I R O N M E N T A L T E M P E R A T U R E , A N D D I E T A R Y I N T A K E OF I O D I N E A R E KNOWN TO A F F E C T T H Y R O I D A C T I V I T Y . H O W E V E R , C O M P A R A T I V E L Y L I T T L E 6 I S KNOWN A B O U T T H E E F F E C T S OF N U T R I T I O N A L F A C T O R S O T H E R T H A N I O D I N E ON T H Y R O I D S E C R E T I O N R A T E . T H E R E I S M U C H D A T A TO I N D I C A T E T H A T T H E T H Y R O I D G L A N D OF B I R D S R E S P O N D S TO E N V I R O N M E N T A L T E M P E R A T U R E C H A N G E S ( H O F F M A N N AND S H A F F N E R , 1 9 5 0 ; J O I N E R A N D H U S T O N , 1 9 5 7 ; P R E M A C H A N D R A _ET _AL . , 1 9 5 8 ; H E N I N G E R E T A L . , 1 9 6 0 ; S T A H L A N D T U R N E R , 1 9 6 1 ; H U S T O N _E_T _ A L . , 1 9 6 2 ) . T H E Y O U N G B I R D H E L D I N A C O O L E N V I R O N M E N T A L T E M P E R A T U R E WAS SHOWN TO H A V E H E A V I E R T H Y R O I D G L A N D S A N D TO S E C R E T E MORE T H Y R O X I N E T H A N T H O S E E X P O S E D TO H I G H T E M P E R A T U R E S ( H O F F M A N N A N D S H A F F N E R , 1 9 5 0 ) . L A T E R R E P O R T S ( J O I N E R AND H U S T O N , 1 9 5 7 ; H U S T O N E T M . . , 1962) C O N F I R M E D T H E S E F I N D I N G S . H E N D R I C H AND T U R N E R (1963) A L S O D E M O N S T R A T E D T H A T S H O R T T E R M E X P O S U R E TO C O L D ,131 S T I M U L A T E D T H E T H Y R O I D OF T H E FOWL A S I N D I C A T E D B Y T H Y R O I D A L !. U P T A K E A N D R E L E A S E WAS SHOWN TO R E T U R N TO N O R M A L B Y L O N G E R T E R M E X P O S U R E TO C O L O . A S T U D Y B Y H E N D R I C H AND T U R N E R (1965) D E M O N S T R A T E D T H A T A C H A N G E F R O M S U M M E R T E M P E R A T U R E TO C O N S T A N T 4 .4°C C O L D HAD NO S I G N I F I C A N T E F F E C T ON T H E T2 OF T H Y R O X I N E - I I N F O W L S AND S U G G E S T E D T H A T F L U C T U A T I N G E N V I R O N M E N T A L T E M P E R A T U R E S P R O D U C E C H A N G E S I N T H E T H Y R O I D H O R M O N E U T I L I Z A T I O N . K O B A Y A S H I A N D G O R B M A N ( i 9 6 0 ) AND R O S E N B E R G _ET _A_L. (1964) R E P O R T E D ,131 T H A T T H E T I M E OF P E A K I - U P T A K E WAS I N F L U E N C E D B Y T H E C O N C E N T R A T I O N OF I O D I D E I N T H E D I E T . K O B A Y A S H I A N D G O R B M A N ( i 9 6 0 ) D E M O N S T R A T E D T H A T W I T H A LOW I O D I N E D I E T , R A D I O A C T I V I T Y F E L L R A P I D L Y A F T E R R E A C H I N G A P E A K A T 6 H O U R S . V E R Y L I T T L E I S KNOWN OF T H E R E L A T I O N OF T H Y R O I D F U N C T I O N A N D J 3 1 " c V I T A M I N E . T H E R A T E O F I U P T A K E B Y T H E T H Y R O I D I N V I T A M I N E E X C E S S H A S B E E N R E P O R T E D TO BE R E D U C E D I N T H E R A T ( V A L E N T I A N D B O T T A R E L L I , 1965) A N D 7 A S I M I L A R O B S E R V A T I O N I N H A M S T E R WAS R E P O R T E D ( D U R A N D _ET _AL . , 1 9 6 8 ) . |F A C O M P O U N D I S A D M I N I S T E R E D W H I C H I N H I B I T S T H E S Y N T H E S I S OF T H Y R O I D H O R M O N E S , A C O M P E N S A T O R Y H Y P E R T R O P H Y OF T H E T H Y R O I D G L A N D O C C U R S I N R E S P O N S E TO A N E L E V A T I O N I N TH YROTROPIF I C H O R M O N E ( T S H ) S E C R E T I O N R A T E . IN A N I M A L S S U B J E C T E D TO D I F F E R E N T E N V I R O N M E N T A L T E M P E R A T U R E S , T H E R E S U L T A N T D I F F E R E N C E S I N S E C R E T I O N R A T E S OF TSH ( H E N D R I C H A N D T U R N E R , 1964) A N D T H Y R O I D H O R M O N E W I L L B E R E F L E C T E D I N D I F F E R E N C E S I N T H E G O I T R O G E N I C R E S P O N S E TO A D M I N I S T R A T I O N OF A G O I T R O G E N I C C O M P O U N D S U C H A S T H I O U R A C I L . T H I O U R A C I L E X E R T S I T S E F F E C T B Y P R E V E N T I N G T H E F O R M A T I O N OF O R G A N I C I O D I N A T E D C O M P O U N D S I N T H E T H Y R O I D G L A N D A N D P R E V E N T I N G R E C Y C L I N G OF I O D I N E ( F R A N D L I N , L E R N E R AND C H A I K O F F , 1 9 4 4 ; A S T W O O D , 1 9 4 5 ; V A N D E R L A A N A N D B L S S E L , 1 9 4 6 ) . K O B A Y A S H I AND G O R B M A N ( I 9 6 0 ) O B S E R V E D I N C H I C K S T H A T T H E R A T I O OF MONO I ODOT YRO.S I N E ( M I T ) TO DL I OD 0 T Y R O S I N E ( D I T ) WAS G R E A T E R AT 4 6 H O U R S A F T E R A D M I N I S T R A T I O N O F T H I O U R A C I L T H A N A T 6 H O U R S , I N D I C A T I N G A C C U M U L A T I O N OF M I T , A N D S U G G E S T E D T H A T T H I O U R A C I L P R O D U C E D A B L O C K I N T H Y R O X I N E S Y N T H E S I S B E T W E E N M I T A N D D I T . IN R E C E N T Y E A R S , S E V E R A L I N V E S T I G A T O R S ( C U N N I N G H A M , 1 9 6 4 ; M A L O O F AND S O O D A F , 1 9 6 3 J J L R O U S E K AND C U N N I N G H A M , 1 9 6 8 ) , S U G G E S T E D T H A T A P R O T E I N S U L F E N Y L I O D I D E A S AN A C T I V E C A R R I E R F O R | + I S A K E Y I N T E R M E D I A T E I N T H E E N Z Y M A T I C I O D I N A T I O N OF T Y R O S I N E I N T H E T H Y R O I D G L A N D . T H E S U L F E N Y L I O D I D E I N T E R M E D I A T E S E R V E S TO S T A B I L I Z E I W H I C H I S I N V O L V E D I N T H E I O D I N A T I O N OF T Y R O S I N E . A P O S S I B L E M E C H A N I S M I S T H A T A N T I T H Y R O I D A G E N T S S U C H A S T H I O U R A C I L A N D T H I O U R E A H A V E V E R Y H I G H R A T E S OF R E A C T I O N W I T H S U L F E N Y L I O D I D E TO F O R M AN I N A C T I V E M I X E D D I S U L F I D E ( C U N N I N G H A M , 1 9 6 4 ) . • T H I O U R A C I L NOT O N L Y B L O C K S T H E F O R M A T I O N O F T H Y R O X I N E I N T H E T H Y R O I D 8 B A R K E R _ET _ A L . ' (1 9 4 9 ) , A N D I K _ET _AJ_ . ( 1 9 4 9 ) , AND S T A S I L L I E T A L . ( 1 9 6 0 ) S H O W E D T H A T T H E C A L O R I G E N I C E F F E C T I V E N E S S OF T H Y R O X I N E WAS D E C R E A S E D B Y F E E D I N G E I T H E R T H I O U R A C I L OR M E T H Y L T H I O U R A C I L . T H E R E S U L T S OF S E V E R A L R E P O R T S ( V A N A R S D E L A N D W I L L I A M S , 1 9 5 6 ; H O G N E S S _ET _AL . , 1 9 5 4 ; S T A S I L L I _E_T . A L . , 1 9 6 0 ; J O N E S A N D M I D D L E S W O R T H , 1 9 6 0 ; E S C O B A R A N D E S C O B A R , 1 9 6 1 , 1 9 6 2 ; H E R R E R A _ET A_L . , 1 9 6 3 ) H A V E SHOWN T H A T P R O P Y L T H I O U R A C I L , 1 3 1 D E C R E A S E D T H E A M O U N T OF I E X C R E T E D I N T H E U R I N E AND I N C R E A S E D T H E , 1 3 1 , 1 3 1 F E C A L E X C R E T I O N OF I - T H Y R O X I N E A F T E R T H E A D M I N I S T R A T I O N OF I L A B E L E D T H Y R O X I N E , P R E S U M A B L Y B Y I N H I B I T I N G T H E I R D E I O D I N A T I O N . D E I O D I N A T I O N OF B O T H P H E N O L I C R I N G A N D I N N E R R I N G I O D I N E S I S A F F E C T E D ( F L O C K A N D B O L L M A N , 1 9 6 2 ; H E R R E R A _ET . A L . , 1 9 6 3 ) . J A G I E L L O W A N D M C K E N Z I E ( 1 9 6 0 ) H A V E O B S E R V E D THAT T H E P R O T E I N - B O U N D I O D I N E OF T H I O U R A C I L - T R E A T E D A N I M A L S G I V E N GO I T E R - P R E V E N T 1 N G D O S E S OF T H Y R O X I N E WAS H I G H E R T H A N T H A T OF T H Y R O X I N E - T R E A T E D , T H Y R O I D E C T O M I Z E D A N I M A L S . H E R S H M A N AND V A N M L D D L E S W O R T H ( 1 9 6 2 ) S U P P O R T E D T H E S E F I N D I N G S . I T H A S B E E N S U G G E S T E D T H A T T H I O U R A C I L AND P R O P Y L T H I O U R A C I L E N H A N C E T H E B I N D I N G OF T H E H O R M O N E B Y T H E P L A S M A P R O T E I N , T H E R E B Y D E C R E A S I N G T H E P E R I P H E R A L A C T I V I T Y OF T H Y R O X I N E ( H E R S H M A N AND V A N M I D D L E S W O R T H , 1 9 6 2 ) . R A D I O I O D I N E U P T A K E 1 3 1 T H E D I S C O V E R Y OF R A D I O I O D I N E I B Y E N R I C O F E R M I I N 1 9 3 5 L E D TO I T S U S E B Y H A M I L T O N A N D S O L E Y I N 1 9 3 9 I N T H E T E S T OF T H Y R O I D F U N C T I O N . R A D I O I O D I N E U P T A K E AS A P A R A M E T E R OF T H Y R O I D A C T I V I T Y I S B A S E D U P O N T H E D Y N A M I C S OF I O D I N E M E T A B O L I S M W H I C H M A Y BE C O N S I D E R E D F R O M T H R E E A S P E C T S : 9 ( 1 ) T H E I N O R G A N I C I O D I D E I S T A K E N U P R A P I D L Y F R O M T H E C I R C U L A T I N G B L O O D ( V A N D E R L A A N A N D V A N D E R L A A N , 1 9 4 7 ; T A U R O G _ET _AL . , 1 9 4 7 ; H A L M I , 1 9 6 1 ) ; ( 2 ) I O D I N E M A Y BE O R G A N I C A L L Y B O U N D A S E A R L Y A S 1 5 M I N U T E S A F T E R A D M I N I S T R A T I O N (C H A L K O F F A N D T A U R O G , 1 9 4 9 ; W L L L I A M S A N D V L C K E R Y , 1 9 6 5 ) ; ( 3 ) T H E O R G A N I C A L L Y B O U N D R A D I O I O D I N E I S S O O N R E L E A S E D F R O M T H E T H Y R O I D G L A N D (NADL'E-R A N D L E B L O N D , 1 9 5 5 A N D 1 9 5 8 ) . A 2 4 - H O U R - U P T A K E T E S T I S W I D E L Y U S E D A N D I S B A S E D ON T H E A S S U M P T I O N T H A T T H E M A X I M U M L E V E L OF , 1 3 1 , 1 3 1 T H Y R O I D A L I A C C U M U L A T I O N I S R E P R E S E N T E D B Y T H E . L E V E L OF T H Y R O I D A L I 131 2 4 H O U R S A F T E R A D M I N I S T R A T I O N OF I ( W A H L B E R G , 1 9 5 5 ; H A M I L T O N AND S O L E Y , 1 9 4 0 ; R O S E N B E R G _ET _ A L . , 1 9 6 3 ) . S O M E I N V E S T I G A T O R S C O M M E N T T H A T S I N C E ( 1 ) T«M E R E I S R E L E A S E OF I N O R G A N I C I O D I N E F R O M T H E G L A N D ( H A L M I A N D P L T T - R L V E R S , 1 9 6 2 ) ; ( 2 ) R A D I O I O D I N E I N T H E T H Y R O I D G L A N D I S E A S I L Y A F F E C T E D B Y T H E L E V E L O F I O D I N E I N T H E D I E T ( R O S E N BE RG _ET _AL . , 1 9 6 4 ) ; ( 3 ) I O D I N E I S M E T A B O L I Z E D I N T H E T H Y R O I D G L A N D I N A H E T E R O G E N E O U S M A N N E R ( R O S E N B E R G E T A L . , 1 9 6 6 ) ; T H E V A L I D I T Y OF U P T A K E OR R E L E A S E M E A S U R E M E N T S A S A N I N D E X OF . 1 3 1 T H Y R O I D A C T I V I T Y A C C O R D I N G L Y B E C O M E S Q U E S T I O N A B L E . N E V E R T H E L E S S , I U P T A K E A N D R E L E A S E B Y T H E T H Y R O I D A R E E M P L O Y E D R A T H E R W I D E L Y AS C O M P A R A T I V E I N D I C E S OF T H Y R O I D A C T I V I T Y S I N C E T H E S P E C I F I C R A D I O A C T I V I T Y OF T H E I O D I N E D E M O N S T R A T E D I N T H E T H Y R O I D T I S S U E I S E A S I L Y M O D I F I E D B Y C I R C U M S T A N C E S W I T H I N T H E N O R M A L V A R I A T I O N OF T H E P H Y S I O L O G Y OF T H E A N I M A L S . T H E U P T A K E OF R A D I O I O D I N E B Y T H E G L A N D D O E S NOT I N D I C A T E T H E A B S O L U T E A M O U N T OF I O D I N E P I C K E D U P , B U T M E R E L Y R E P R E S E N T S T H E P E R C E N T A G E O F T H E T O T A L S T A B L E I O D I D E P O O L T R A P P E D ( S I L VE R JET _AL . , 1 9 5 5 ; A N D R E W S , 1 9 5 7 ) . 1 0 V I T A M I N E A N D O X Y G E N C O N S U M P T I O N OF T I S S U E S V I T A M I N E D E F I C I E N C Y H A S B E E N SHOWN TO I N F L U E N C E O X Y G E N C O N S U M P T I O N B U T T H E E F F E C T V A R I E S W I T H T H E T Y P E O F T I S S U E S T U D I E D . M A R K E D I N C R E A S E S I N O X Y G E N C O N S U M P T I O N F R O M V A R I O U S S P E C I E S O F V I T A M I N E D E F I C I E N T A N I M A L S H A V E B E E N R E P O R T E D ( V I C T O R , 1934J M A D S E N , 1 9 3 6 ; F R I E D M A N A N D M A T T I L L , 1 9 4 1 ; H O U C H I N A N D M A T T I L L , 1 9 4 2 A , B , C ; H O U C H I N , 1 9 4 2 ; K A U N I T Z A N D P A P P E N H E I M E R , 1 9 4 3 ; R O D E R U C K _ET _ A L . , 1 9 4 9 ; H I M M E L AND M E L V I L L E , 1 9 5 1 ; R O S E N K R A N T Z , 1 9 5 5 ; B I R D _ E T _ A L . , 1 9 6 3 ) . R A B B I T S , H A M S T E R S , R A T S , A N D G U I N E A P I G S WERE U S E D A S T H E E X P E R I M E N T A L A N I M A L S I N T H E S E S T U D I E S . V I C T O R (1934) O B S E R V E D NO E F F E C T OF V I T A M I N E D E F I C I E N C Y ON T H E O X Y G E N C O N S U M P T I O N OF D U C K M U S C L E . R O S E N K R A N T Z (1955) F O U N D T H A T R A B B I T A D R E N A L C O R T E X A N D L I V E R S L I C E S SHOWED A D E F I N I T E I N C R E A S E I N O X Y G E N C O N S U M P T I O N W H E R E A S O X Y G E N C O N S U M P T I O N OF H E A R T . A N D K I D N E Y T I S S U E S R E M A I N E D U N C H A N G E D I N V I T A M I N E D E F I C I E N C Y . G R I G O R Y E V A A N D S H C H U K I N A (1967) O B S E R V E D T H A T O X Y G E N C O N S U M P T I O N F O R T H E O X I D A T I O N OF DR K E T O - G L U T A R I C AND S U C C I N I C A C I D S P E R MG OF P R O T E I N I N M I T O C H O N D R I A F R O M D Y S T R O P H I C M U S C L E I N V I T A M I N E D E F I C I E N C Y WAS S I M I L A R TO T H A T F R O M N O R M A L T I S S U E . V I T A M I N E A N D M I T O C H O N D R I A M I T O C H O N D R I A C O N T A I N M U C H OF T H E V I T A M I N E P R E S E N T I N C E L L S ( W l S S _ET _ A L . , 1 9 6 2 ) . OL I V E I RA E_T _AL . (1968) F O U N D T O C O P H E R O L TO BE P R E S E N T - I N A L L T H E E N Z Y M A T I C A L L Y A C T I V E L I P O - P R O T E I N C O M P L E X E S OF T H E E L E C T R O N T R A N S P O R T S Y S T E M OF I N N E R M I T O C H O N D R I A . F U R T H E R , T H E Y D E M O N S T R A T E D T H A T T H E T O C O P H E R O L D I D NOT A P P E A R TO H A V E A D I R E C T Q U A N T I T A T I V E R E L A T I O N S H I P W I T H T H E A C T I V I T Y OF E N Z Y M E S , S U C H A S C Y T O C H R O M E O X I D A S E , N A D H - AND , S U C C I N A T E - C Y T O C H R O M E C R E D U C T A S E S . M I T O C H O N D R I A C O N T A I N A B O U T 2 5 $ L I P I D 11 ( S W A N S O N A N D A R T O M , 1 9 5 0 ) , M U C H OF W H I C H I S U N S A T U R A T E D A N D G R E A T E R T H A N 90$ i s P H O S P H O L I P I D . M O S T O F T H E L I P I D O C C U R S I N T H E M I T O C H O N D R I A L M E M B R A N E ( F L E I S C H E R " A N D R O U S E R , 1965j F L E I S C H E R , 1967j C H A P M A N A N D L E S L I E , 1 9 7 0 ) . S A L K I N A N D T A P P E L ( i 9 6 0 ) R E P O R T E D T H A T I N V I V O P E R O X I D A T I O N O C C U R S I N T H E L I V E R A N D K I D N E Y OF V I T A M I N E D E F I C I E N T R A B B I T S . L I P I D P E R O X I D A T I O N I S C A T A L Y Z E D B Y H E M A T I N C O M P O U N D S , S U C H A S T H E C Y T O C H R O M E S C O N T A I N E D I N M I T O C H O N D R I A ( T A P P E L A N D Z A L K I N , 1 9 5 9 B ) . A N E L E C T R O N M I C R O S C O P I C S T U D Y H A S SHOWN M I T O C H O N D R I A L A L T E R A T I O N S I N S K E L E T A L M U S C L E OF Y O U N G C H I C K S F E D A V I T A M I N E D E F I C I E N T D I E T ( C H E V I L L E , 1 9 6 6 ) . F U R T H E R , V A N V L E E T E T A L • (1968) S U G G E S T E D T H A T T I S S U E I N W H I C H V I T A M I N . E HAS B E E N D E P L E T E D , S K E L E T A L M U S C L E M I T O C H O N D R I A U N D E R W E N T L I P I D P E R O X I D A T I O N W I T H R E S U L T I N G D E S T R U C T I O N O F T H E I N N E R M E M B R A N E S . F R A G M E N T A T I O N OF C R I S T A E , M I T O C H O N D R I A L S W E L L I N G D U E TO A L T E R E D M E M B R A N E P E R M E A B I L I T Y , F O R M A T I O N OF 1 N T R A M I T O C H O N D R I A L M Y E L I N - F I G U R E - L I KE M E M B R A N O U S P R O F I L E S , A N D A C C U M U L A T I O N OF I N T R A M I T O - C H O N D R I A L D E N S E G R A N U L E S R E S U L T E D . E X P E R I M E N T 1 T H Y R O I D A L R E S P O N S E TO E X C E S S D I E T A R Y V I T A M I N E TWO E X P E R I M E N T S WERE C O N D U C T E D TO S T U D Y T H E E F F E C T S OF E X C E S S V I T A M I N E I N R E L A T I O N TO T H Y R O I D A C T I V I T Y . |N ONE E X P E R I M E N T , - C H I C K S WERE F E D N O R M A L A N D E X C E S S L E V E L S OF V I T A M I N E A N D WERE S U B J E C T E D TO D I F F E R E N T T E M P E R A T U R E S . T H E G O I T R O G E N I C E F F E C T OF T H I O U R A C I L WAS M E A S U R E D . |N A ,131 S E C O N D E X P E R I M E N T , T H E R A T E S O F I U P T A K E A N D R E L E A S E WERE C O M P A R E D I N C H I C K S W I T H N O R M A L A N D E X C E S S I N T A K E OF V I T A M I N E . . E X P E R I M E N T 1A M A T E R I A L S A N D M E T H O D S T H I S E X P E R I M E N T WAS S T A R T E D I N N O V E M B E R , 1 9 6 9 . E I G H T Y D A Y - O L D M A L E W H I T E L E G H O R N C H I C K S WERE W I N G - B A N D E D AND D I S T R I B U T E D AT R A N D O M I N T O 3 G R O U P S I N E L E C T R I C A L L Y H E A T E D B A T T E R Y B R O O D E R S . T H E C O N S T I T U E N T S OF B A S A L E X P E R I M E N T A L D I E T I S SHOWN I N T A B L E 1 A . G R O U P A R E C E I V E D O N L Y T H E B A S A L D I E T ( W I T H O U T S U P P L E M E N T A R Y V I T A M I N E ) , G R O U P B R E C E I V E D A N E X C E S S V I T A M I N E L E V E L O F 2 2 0 I . U . P E R K G . O F D I E T A N D G R O U P C R E C E I V E D T H E B A S A L D I E T P L U S E T H O X Y Q U I N ^ ( E Q ) A T 0 . 2 5 $ OF T H E D I E T . ROOM T E M P E R A T U R E WAS T H E R M O S T A T I C A L L Y C O N T R O L L E D AT 2 2 ° C . T H E E X P E R I M E N T A L D I E T S A N D W A T E R WERE F E D AD L I B I T U M . 1 , 2 D I H YD R 0 - 6 - E T H 0 X Y - 2 , 2 , 4 - T R I M E T H Y L Q U I N O L I N E . 1 2 1 3 A T 2 3 D A Y S OF A G E , A L L T H E B I R D S OF T H E 3 G R O U P S WERE W E I G H E D A N D 2 4 C H I C K S F R O M E A C H G R O U P WERE S E L E C T E D B Y A S Y S T E M A T I C P R O C E D U R E A C C O R D I N G TO T H E I N D I V I D U A L B O D Y W E I G H T S I N O R D E R TO R E D U C E T H E V A R I A T I O N S O F T H E I N I T I A L B O D Y W E I G H T S OF T H E E X P E R I M E N T A L C H I C K S A M O N G T H E 3 G R O U P S . E A C H G R O U P WAS D I V I D E D I N T O 2 S U B G R O U P S F O R T H E HOT AND C O L D E N V I R O N M E N T A L C H A M B E R S . T H E C O L D E N V I R O N M E N T A L C H A M B E R WAS R E G U L A T E D AT 1 4 . 5 ° C A N D T H E HOT E N V I R O N M E N T A L C H A M B E R AT 3 1 . 5 ° C . T H E V A R I O U S G R O U P S OF. C H I C K S WERE P L A C E D I N T H E E N V I R O N M E N T A L C H A M B E R S FOR 2 D A Y S A D A P T A T I O N B E F O R E T H E E X P E R I M E N T WAS S T A R T E D . E A C H S U B G R O U P WAS D I V I D E D I N T O 2 L O T S OF 6 C H I C K S E A C H . ONE L O T WAS M A I N T A I N E D ON T H E O R I G I N A L E X P E R I M E N T A L D I E T A N D T H E O T H E R L O T R E C E I V E D 0 . 1 $ T H I O U R A C I L ( TU ) I N T H E E X P E R I M E N T A L D I E T . T H E T R E A T M E N T S A R E S U M M A R I Z E D A S F O L L O W S : . E X P E R I M E N T A L P E S I G N E X C E S S E X C E S S V I T A M I N E EQ B A S A L TU Vi TAM I N E +JJJ EQ +TU 1 4 . 5 ° C 6 * 6 6 6 6 6 3 1 . 5 ° C 6 6 6 6 6 6 * N U M B E R O F C H I C K S . T H E T E M P E R A T U R E S I N T H E 2 E N V I R O N M E N T A L C H A M B E R S WERE R E C O R D E D B Y A R E C O R D I N G T H E R M O G R A P H . F E E D C O N S U M P T I O N WAS A L S O R E C O R D E D . T H E E X P E R I M E N T A L P E R I O D WAS 1 4 D A Y S . AT T H E E N D O F T H E E X P E R I M E N T , A L L C H I C K S WERE W E I G H E D A N D K I L L E D . T H E T H Y R O I D G L A N D S WERE R E M O V E D A N D W E I G H E D . 14 E X P E R I M E N T 1 B T H I S E X P E R I M E N T WAS S T A R T E D I N J U L Y , 1 9 7 0 . T H E P R O C E D U R E A N D T H E T R E A T M E N T S WERE T H E S A M E AS E X P E R I M E N T 1A W I T H E X C E P T I O N OF L A R G E R P O P U L A T I O N (15 I N D I V I D U A L S ) I N E A C H L O T A N D T E M P E R A T U R E (22°C) I N T H E E T H O X Y Q U I N - T R E A T E D B I R D S . T H E B A S A L D I E T WAS A L S O M O D I F I E D A S SHOWN I N T A B L E 1 B , B E C A U S E T H E D I E T S F E D I N E X P E R I M E N T 1A WERE AC C I D E N T L Y F O R M U L A T E D W I T H O U T A D E Q U A T E C A L C I U M S U P P L E M E N T A T I O N . R E S U L T S A N D D I S C U S S I O N . T H E R E S U L T S FOR E X P E R I M E N T S 1A AND 1B A R E S U M M A R I Z E D I N T A B L E S 2 A N D 3 . A V E R A G E V A L U E S A R E E X P R E S S E D ± S A M P L E S T A N D A R D D E V I A T I O N . I N B O T H E X P E R I M E N T S , T H E T H Y R O I D W E I G H T S OF T H E C H I C K S P E R 100 G M . B O D Y W E I G H T WERE S I G N I F I C A N T L Y G R E A T E R I N T H E 1 4 . 5 ° C E N V I R O N M E N T A L C H A M B E R T H A N T H O S E I N T H E 31 . 5 ° C E N V I R O N M E N T A L C H A M B E R ( P s g O . 0 5 ) . T H I S R E S U L T I S I N A G R E E M E N T W I T H P R E V I O U S L Y R E P O R T E D F I N D I N G S ( H O F F M A N N A N D S H A F F N E R , 1 9 5 0 ; J O I N E R A N D H U S T O N , 1 9 5 7 ; H U S T O N _ET _ A L . , 1 9 6 2 ) . T H I O U R A C I L C A U S E S G O I T E R B Y E N H A N C I N G T S H O U T P U T I N R E S P O N S E TO A B L O C K I N T H E S Y N T H E S I S O F T H Y R O X I N E B Y T H E T H Y R O I D G L A N D ( D E M P S E Y AND A S T W O O D , 1 9 4 3 ) . T H E E X T E N T OF W H I C H T H Y R O I D W E I G H T I N C R E A S E S I N R E S P O N S E TO T H E F E E D I N G OF T H I O U R A C I L V A R I E S W I T H T H E R A T E OF S E C R E T I O N OF T S H ( B A R K E R , 1 9 5 5 ; B R O W N - G R A N T , 1 9 5 7 ) . T H E R A T E O F S E C R E T I O N OF T S H i s , I N T U R N , • D E P E N D E N T U P O N T H E N O R M A L R A T E AT W H I C H T H Y R O X I N E I S S E C R E T E D B Y T H E A N I M A L . A C C O R D I N G L Y T H E R E S P O N S E OF T H E T H Y R O I D G L A N D TO T H I O U R A C I L I N T H E P R E S E N T E X P E R I M E N T S I S C O N S I D E R E D TO BE AN I N D I C A T I O N O F T H E R A T E OF T H Y R O X I N E S E C R E T I O N U N D E R T H E E X P E R I M E N T A L T R E A T M E N T S I M P O S E D , '15 I . E . D I F F E R E N T E N V I R O N M E N T A L T E M P E R A T U R E S AND D I E T A R Y L E V E L S OF V I T A M I N E . E X C E S S V I T A M I N E D I D NOT A F F E C T T H E T H Y R O I D S I Z E OF T H E C H I C K S F E D T H E D I E T W I T H O U T T H I O U R A C I L AT E I T H E R T E M P E R A T U R E ( T A B L E S 2 AND 3 , F I G U R E S 1 A N D 2 ) . T H Y R O I D S I Z E I S NOT A P A R T I C U L A R L Y S E N S I T I V E P A R A M E T E R OF T H Y R O I D A C T I V I T Y OR T S H S E C R E T I O N R A T E . I T I S KNOWN T H A T H I G H E R L E V E L S OF T S H A R E R E Q U I R E D TO I N C R E A S E T H Y R O I D S I Z E T H A N I S N E E D E D TO I N C R E A S E T H Y R O X I N E S E C R E T I O N R A T E . E X C E S S V I T A M I N E D I D A F F E C T T H Y R O I D W E I G H T OF T H E T H I O U R A C I L - T R E A T E D C H I C K S ( F I G U R E S 1 AND 2 ) . I N E X P E R I M E N T 1 A , T H E T H I O U R A C I L - T R E A T E D C H I C K S F E D E X C E S S V I T A M I N E E X H I B I T E D A L E S S E R T H Y R O I D R E S P O N S E T H A N D I D T H E T H I O U R A C I L - T R E A T E D C H I C K S F E D T H E LOW V I T A M I N E . T H E D I F F E R E N C E I N R E S P O N S E WAS NOT S T A T I S T I C A L L Y S I G N I F I C A N T ( T A B L E 4) AND M A Y H A V E B E E N DUB TO S M A L L N U M B E R S OF C H I C K S E M P L O Y E D I N T H E E X P E R I M E N T . T H E E X P E R I M E N T W A S , T H E R E F O R E , R E P E A T E D W I T H A L A R G E R P O P U L A T I O N . T H E R E S U L T S OF T H I S S E C O N D E X P E R I M E N T C O N F I R M E D T H E E V I D E N C E OF E X P E R I M E N T 1 A . T H E D I F F E R E N C E I N T H Y R O I D A L R E S P O N S E OF C H I C K S F E D T H E D I F F E R E N T L E V E L S OF V I T A M I N E WAS S T A T I S T I C A L L Y S I G N I F I C A N T ( P ^ 0 . 0 1 ) A S SHOWN I N TABLE 5 . I T WAS C O N C L U D E D T H A T T H E R A T E OF TSH S E C R E T I O N I N T H E C H I C K S F E D E X C E S S V I T A M I N E WAS L E S S T H A N T H A T I N T H E C H I C K S F E D T H E D I E T S W I T H O U T V I T A M I N E S U P P L E M E N T A T I O N A N D A S A C O N S E Q U E N C E , E X C E S S V I T A M I N E I N D I R E C T L Y D E P R E S S E D T H Y R O I D A C T I V I T Y . ONE H Y P O T H E S I S C O N S I D E R E D F O R T H Y R O I D R E S P O N S E TO D I E T A R Y V I T A M I N E WAS B A S E D ON T H E F A C T T H A T LOW V I T A M I N E C A U S E D A D E C R E A S E I N C I R C U L A T I N G T H Y R O X I N E L E V E L DUE TO I N C R E A S E D P E R I P H E R A L D E I O D I N A TI ON I N T H E L I V E R A N D M U S C L E ( G A L T O N A N D HlNGBAR, 1 9 6 5 ) . G A L T O N A N D HlNGBAR (1965) O B S E R V E D B A S A L E X C E S S v I T A M I N E 0 . 2 5 $ E T H O X Y Q U I N 31 1 4 . 5 U C 3 1 . 5 U C 1 4 . 5 ° C 1 4 . 5 ° C 31 . 5 ^ 1 4 . 5 U C 31 .5°C W I T H O U T T H I O U R A C I L I N T H E D I E T W I T H T H I O U R A C I L I N T H E D I E T F I G . 1 . T H Y R O I D R E S P O N S E OF C H I C K S R E C E I V I N G TWO L E V E L S OF V I T A M I N E A N D / O R E T H O X Y Q U I N TO T H I O U R A C I L A T D I F F E R E N T A M B I E N T T E M P E R A T U R E S I N E X P E R I M E N T 1 A . 5 0 4 0 3 0 2 0 1 0 17 B A S A L E X C E S S v I T A M i N E 0 . 2 5 $ E T H O X Y Q U 1 N 1 4 . 5 ° C 3 1 , 5 ° C 2 2 ° C 1 4 . 5 ° C 3 1 . 5 ° C 2 2 ° C W I T H O U T T H I O U R A C I L I N T H E D I E T W I T H T H I O U R A C I L I N T H E D I E T F I G . 2 . T H Y R O I D A L R E S P O N S E O F C H I C K S R E C E I V I N G TWO L E V E L S OF V I T A M I N E A N D / O R E T H O X Y Q U I N TO T H I O U R A C I L AT D I F F E R E N T A M B I E N T T E M P E R A T U R E S I N E X P E R I M E N T 1 B . 18 T H A T D E 1 0 D I N A T I 0 N OF T H Y R O X I N E V/AS I N C R E A S E D I N H O M O G E N A T E S OF M U S C L E A N D L I V E R S F R O M V I T A M I N E D E F I C I E N T A N I M A L S AND T H A T L A R G E D O S E S OF T O C O P H E R O L , E I T H E R A D M I N I S T E R E D I N V I V O OR A D D E D TO T I S S U E H O M O G E N A T E S I N V I T R O , G R E A T L Y D E C R E A S E D H E P A T I C OR M U S C U L A R DE IOD I NAT I N G A C T I V I T Y I N B O T H N O R M A L A N D V I T A M I N E D E F I C I E N T R A T S . G R U E N S T E I N (1970) HAS R E C E N T L Y P R O P O S E D A T H E O R Y F O R T H E M E C H A N I S M OF A C T I O N OF T H Y R O X I N E . HE S U G G E S T S T H A T T H Y R O X I N E A S S O C I A T E S W I T H T H E L I P I D S OF T H E C E L L M E M B R A N E , W H E R E U P O N IT I S D E G R A D E D B Y A F R E E R A D I C A L M E C H A N I S M , R E S U L T I N G I N T H E R E L E A S E OF S O M E OR A L L OF T H E I O D I N E I N T H E + 0 / F O R M OF I OR I . S E V E R A L I N V E S T I G A T O R S ( R O S E N B E R G AND J E N D R A S I A K , 1 9 6 8 ; F l N D E L S T E I N " A N D C A S S , 1968) HAD P R E V I O U S L Y S U G G E S T E D T H A T A P O S I T I V E I O N , I OR A F R E E R A D I C A L I , R E L E A S E D F R O M T H E T H Y R O X I N E M A Y I N T E R A C T W I T H P H O S P H O L I P I D S A N D C H O L E S T E R O L OF T H E M E M B R A N E , C H A N G I N G T H E P H Y S I C A L , S T R U C T U R A L A N D / O R C H E M I C A L P R O P E R T I E S OF T H E S E L I P I D S S O T H A T T H E E L E C T R I C A L R E S I S T A N C E OF T H E M E M B R A N E I S D E C R E A S E D . T H E S T U D I E S OF W Y N N ( 1 9 6 8 A , B ) ON T H Y R O X I N E D E G R A D A T I O N I N R A T L I V E R H A V E SHOWN T H A T S O M E OR A L L OF T H E I O D I N E O F T H Y R O X I N E I S R E L E A S E D A S P A R T OF T H E I N I T I A L M E T A B O L I S M OF T H E H O R M O N E A F T E R I T R E A C H E S T A R G E T T I S S U E S F R O M T H E P L A S M A . HE F U R T H E R D E M O N S T R A T E D T H A T T H Y R O X I N E F U N C T I O N S A S A N E X T R E M E L Y P O T E N T A N T I O X I D A N T , C A P A B L E OF P R E V E N T I N G P E R O X I D A T I O N OF L E C I T H I N D E R I V E D F R O M T H E M I C R O S O M A L M E M B R A N E A T E V E N L O W E R C O N C E N T R A T I O N S T H A N V I T A M I N E ( W Y N N , 1 9 6 8 A ) . C A S H E T A L . (1966) R E P O R T E D T H E A N T I O X I D A N T P R O P E R T I E S OF T H Y R O X I N E I N P R E V E N T I N G T H E P E R O X I D A T I O N OF P H O S P H O L I P I D S I N M I T O C H O N D R I A L M E M B R A N E . W Y N N ( 1 9 6 8 A ) H A S SHOWN T H A T D U R I N G T H E A N T I OX I DAT I ON R E A C T I O N I N T H E P R E S E N C E OF M E T A L I O N (FE ) , O X Y G E N A N D P H O S P H O L I P I D , T H Y R O X I N E I S I T S E L F D E G R A D E D ^ TO 19 R E L E A S E I T S I O D I N E . V I T A M I N E I S G E N E R A L L Y ' C O N S I D E R E D TO BE A B I O L O G I C A L A N T I O X I D A N T . THE R E S U L T S OF T H E P R E S E N T E X P E R I M E N T S S U G G E S T T H A T E X C E S S V I T A M I N E M A Y R E P L A C E T H Y R O X I N E I N ITS. A N T I O X I D A N T F U N C T I O N A N D D E I O D I A N T I ON OF T H Y R O X I N E M I G H T , T H E R E F O R E , BE R E T A R D E D . THE D E P R E S S I O N OF D E I O D I N A T I O N O F . T H Y R O X I N E C O U L D T H E N R E D U C E T H E R A T E AT W H I C H T H Y R O I D H O R M O N E I S R E M O V E D F R O M T H E C I R C U L A T I O N , T H U S M A I N T A I N I N G T H E L E V E L OF T H E H O R M O N E I N T H E C I R C U L A T I O N A N D , T H E R E F O R E , S U P P R E S S I N G S E C R E T I O N OF T S H . G R O W T H R A T E A N D F E E D C O N S U M P T I O N WERE S I M I L A R F O R LOW AND E X C E S S V I T A M I N E T R E A T E D B I R D S K E P T A T TWO T E M P E R A T U R E S . T H E S E R E S U L T S I N D I C A T E T H A T M E T A B O L I C R A T E S WERE S I M I L A R I N B I R D S ON B O T H T R E A T M E N T S D E S P I T E D I F F E R E N C E S I N T H Y R O I D A C T I V I T Y . TH I S S H O U L D S U G G E S T T H A T T I S S U E R E S P I R A T I O N I N B I R D S F E D E X C E S S V I T A M I N E C A N BE M A I N T A I N E D W I T H A R E D U C E D S U P P L Y OR T U R N O V E R OF T H Y R O X I N E . ON T H E O T H E R H A N D , A N B A R _ET _ A L . (1965) R E P O R T E D T H E R E S U L T S OF E X P E R I M E N T S W H I C H I N D I C A T E D D I S S O C I A T I O N O F T H E C A L O R I G E N I C E F F E C T OF T H Y R O I D H O R M O N E F R O M D E I O D I N A T I O N . T H E Y F O U N D T H A T F O L L O W I N G T H E I N J E C T I O N OF T H Y R O X I N E TO R A T S , B A S A L M E T A B O L I C R A T E WAS S T I M U L A T E D P R I O R TO D E I O D I N A T I O N OF T H Y R O X I N E A N D T H A T B A S A L M E T A B O L I C R A T E S T I M U L A T I O N HAD L A R G E L Y D I M I N I S H E D B Y T H E T I M E P E A K D E I O D I N A T I O N A C T I V I T Y WAS O B S E R V E D . |F I N C R E A S E D D E I O D I N A T I O N R A T E I S A C O N S E Q U E N C E OF A C C E L E R A T E D R E S P I R A T I O N R A T H E R T H A N T H E C A U S E , T H E N S O M E O T H E R E X P L A N A T I O N F O R T H E E F F E C T OF V I T A M I N E I N R E D U C I N G T H Y R O I D A C T I V I T Y I S N E C E S S A R Y . |T I S I N T E R E S T I N G T H A T 0 . 2 5 $ EQ E X E R T E D A G R E A T E F F E C T ON T H E T H Y R O I D A L R E S P O N S E ( T A B L E S 2 A N D 6 , F I G U R E S 1 AND 2 ) , B U T T H E R E V E R S E 2 0 E F F E C T O F T H A T WAS O B T A I N E D W I T H E X C E S S V I T A M I N E , A L T H O U G H B O T H V I T A M I N E A N D EQ A R E A N T I O X I D A N T S . A T A L E V E L OF 0 . 2 5 $ EQ I S T O X I C ( M A R C H E T A L . , 1 9 6 8 ) . T H E M E C H A N I S M B Y W H I C H E Q I N C R E A S E S T H E G O I T R O G E N I C I T Y OF T H I O U R A C I L I S O B S C U R E . E X P E R I M E N T 1c ,131 T H I S E X P E R I M E N T WAS D E S I G N E D TO S T U D Y T H E R A T E S OF I U P T A K E A N D R E L E A S E B Y T H E T H Y R O I D G L A N D I N C H I C K S I N R E S P O N S E TO F E E D I N G D I E T S C O N T A I N I N G LOW A N D E X C E S S I V E L E V E L S OF V I T A M I N E . M A T E R I A L S A N D M E T H O D S T H E C O M P O S I T I O N O F T H E B A S A L D I E T A N D T H E L E V E L OF V I T A M I N E S U P P L E M E N T A T I O N WERE T H E S A M E A S I N E X P E R I M E N T 1 B . TWO H U N D R E D D A Y - O L D W H I T E L E G H O R N M A L E C H I C K S WERE D I S T R I B U T E D A T R A N D O M I N T O TWO G R O U P S O F O N E H U N D R E D . ONE G R O U P WAS F E D T H E B A S A L D I E T , A N D T H E O T H E R G R O U P T H E V I T A M I N E S U P P L E M E N T E D D I E T . A T 2 3 D A Y S OF A G E , A L L T H E B I R D S O F T H E TWO G R O U P S WERE W E I G H E D I N D I V I D U A L L Y A N D 40 C H I C K S F R O M E A C H G R O U P WERE S E L E C T E D S Y S T E M A T I C A L L Y A S I N E X P E R I M E N T 1 A . ROOM T E M P E R A T U R E WAS T H E R M O S T A T I C A L L Y C O N T R O L L E D A T 2 2 - 2 3 ° C . THE 4 0 C H I C K S OF E A C H G R O U P WERE D I S T R I B U T E D S Y S T E M I C A L L Y I N T O 5 L O T S OF 8 C H I C K S E A C H . T H E C H I C K S WERE 1 31 I N J E C T E D I N T R A V E N O U S L Y W I T H 0 . 2 2 5 JiCI OF I I N 0 . 4 5 M L OF P H Y S I O L O G I C A L S A L I N E S O L U T I O N . F l V E , 1 0 , 2 4 , 48 AND 96 H O U R S A F T E R I N J E C T I O N , 8 C H I C K S F R O M E A C H G R O U P WERE W E I G H E D . THE C H I C K S WERE T H E N K I L L E D A N D T H E I R T J 3 1 T H Y R O I D S R E M O V E D A N D W E I G H E D . THE I R A D I O A C T I V I T Y OF E A C H P A I R OF G L A N D S WAS M E A S U R E D W I T H A D E E P - W E L L S C I N T I L L A T I O N D E T E C T O R . M E A S U R E M E N T S 21 O F R A D I O A C T I V I T Y WERE C O R R E C T E D F O R C O I N C I D E N C E L O S S , B A C K G R O U N D R A D I A T I O N A N D R A D I O A C T I V E D E C A Y . T H E C O R R E C T E D C O U N T S WERE E X P R E S S E D A S A P E R C E N T A G E OF T H E I N J E C T E D D O S E , T H E R A D I O A C T I V I T Y O F W H I C H WAS D E T E R M I N E D F R O M A S T A N D A R D . T H E S T A N D A R D WAS P R E P A R E D B Y D I L U T I N G 5 M L . O F T H E I N J E C T I O N S O L U T I O N I N T O 5 0 0 M L . OF P H Y S I O L O G I C A L S A L I N E S O L U T I O N . R A D I O A C T I V I T Y WAS M E A S U R E D I N A 1 M L . A L I Q U O T OF T H I S S O L U T I O N U S I N G A D E E P - W E L L S C I N T I L L A T I O N D E T E C T O R . ,131 T H E P E R C E N T I U P T A K E WAS E X P R E S S E D P E R B I R D AND. P E R M G . OF T H Y R O I D G L A N D . R E S U L T S AND D I S C U S S I O N T H Y R O I D A L R A D I O A C T I V I T Y AT D I F F E R E N T T I M E S A F T E R A D M I N I S T R A T I O N O F i 3 i I A R E SHOWN I N T A B L E 7 A N D I N F I G U R E S 3 A N D 4.. R E G A R D L E S S O F T H E M E T H O D O F E X P R E S S I N G T H Y R O I D A L R A D I O A C T I V I T Y ( .WHETHER P E R B I R D OR P E R M G . OF T H Y R O I D G L A N D ) T H E D A T A I N D I C A T E T H A T T H E A C T I V I T Y OF T H E T H Y R O I D G L A N D I S ,131 D E P R E S S E D I N B I R D S F E D E X C E S S V I T A M I N E . T H E L E V E L S OF I I N T H E T H Y R O I D G L A N D OF C H I C K S F E D S U P P L E M E N T A R Y V I T A M I N E WERE LOWER WHEN M E A S U R E D 5 A N D .131 _ 10 H O U R S A F T E R I I N J E C T I O N T H A N I N T H E C O N T R O L C H I C K S . T H E D I F F E R E N C E S B E T W E E N T H E C H I C K S R E C E I V I N G T H E R E S P E C T I V E L E V E L S OF V I T A M I N E WERE S T A T I S T I C A L L Y S I G N I F I C A N T AT 5 A N D 10 H O U R S A F T E R I N J E C T I O N WHEN C A L C U L A T E D ON T H E B A S I S O F R A D I O I O D I N E U P T A K E P E R B I R D A N D WERE S I G N I F I C A N T A T 5 , 10 A N D 24 H O U R S A F T E R I N J E C T I O N WHEN C A L C U L A T E D ON T H E B A S I S OF R A D I O I O D I N E U P T A K E P E R M G . OF T H Y R O I D T I S S U E . S U B S E Q U E N T TO 24 H O U R S A F T E R I N J E C T I O N ,131 T I M E , T H E R E WAS A R A P I D D E C L I N E I N T H Y R O I D A L I I N T H E C O N T R O L B I R D S W H E R E A S T H E L O S S OF R A D I O A C T I V I T Y F R O M T H E T H Y R O I D OF T H E B I R D S F E D E X C E S S V I T A M I N E WAS NOT S I G N I F I C A N T . T H I S E X P E R I M E N T C O N F I R M S T H E P R E V I O U S 131 F I N D I N G S ( V A L E N T I A N D B O T T A R E L L I , 1 9 6 5 ; D U R A N D _E_T _ A L , . , 1966) T H A T I U P T A K E B Y T H E T H Y R O I D G L A N D WAS R E D U C E D I N M A M M A L S G I V E N A S U B C U T A N E O U S I N J E C T I O N OF A N E X C E S S I V E L E V E L OF V I T A M I N E . |N T H I S E X P E R I M E N T , 0 . 5 $ I O D I Z E D S A L T WAS A D D E D TO T H E D I E T TO E N A B L E N O R M A L I O D I N E M E T A B O L I S M I N T H E T H Y R O I D G L A N D . K O B A Y A S H I AND G O R B M A N (1960) A N D R O S E N B E R G _ET _ A L . (1964) H A V E D E M O N S T R A T E D I N R A T S A N D C H I C K S T H A T T H E 22 .131 P E R C E N T OF I N J E C T E D I I N T H Y R O I D G L A N D * CO m i "n — "n H m PI o - l t~ m O SD "n I O n 33 X Z o m CO > CO V n o o n X - l — > o -< co • < n: — o —i c > 33 2 CO z > m H n o 33 z -1 — _ > I CO -< —1 33 O — — z C- > n (- o H o O o z z m ,—. CO c "0 H > > Z o 33 m r~ m > CO m £2 t/2 2 5 , 1 3 1 T I M E OF P E A K I U P T A K E WAS I N F L U E N C E D B Y T H E L E V E L OF D I E T A R Y I O D I N E . K O B A Y A S H I AND G O R B M A N ( I 9 6 0 ) H A V E SHOWN T H A T I N C H I C K S F E D A LOW I O D I N E D I E T T H Y R O I D A L R A D I O A C T I V I T Y F E L L R A P I D L Y A F T E R R E A C H I N G A P E A K A T 6 H O U R S . R O S E N B E R G _ET _ A L . ( 1 9 6 4 ) F O U N D T H A T I N C O C K E R E L S F E D A N I O D I D E S U P P L E M E N T E D 1 3 1 D I E T , A V E R A G E M A X I M A L I U P T A K E O F 1 3 $ OF T H E I N J E C T E D D O S E WAS R E A C H E D 1 2 H O U R S A F T E R I N J E C T I O N AND A V E R Y L O N G R E T E N T I O N OF T H Y R O I D A L R A D I O I O D I D E O C C U R E D . T H E R E S U L T S OF T H I S E X P E R I M E N T , W H I C H SHOWED T H A T B O T H T H E R A T E S OF I O D I N E U P T A K E A N D OF I O D I N E R E L E A S E B Y T H E T H Y R O I D G L A N D A R E D E P R E S S E D I N C H I C K S F E D E X C E S S V I T A M I N E , S U B S T A N T I A T E T H E C O N C L U S I O N S O F E X P E R I M E N T S 1 A , A N D B , W H E R E A S I N E X P E R I M E N T 1 , H O W E V E R , T H E D A T A I N D I C A T E D T H A T TSH S E C R E T I O N WAS R E D U C E D I N H Y P E R V I T A M I N O S I S E , E X P E R I M E N T 1C. P R O V I D E S 'D I R E C T E V I D E N C E T H A T T H Y R O I D S E C R E T I ON R A T E I S L E S S I N E X C E S S V I T A M I N E F E D C H I C K S . • E X P E R I M E N T I I R E S P I R A T I O N R A T E OF M U S C L E M I T O C H O N D R I A F R O M C H I C K S F E D E X C E S S D I E T A R Y V I T A M I N E T H E E X P E R I M E N T WAS D E S I G N E D TO S T U D Y T H E O X Y G E N C O N S U M P T I O N O F M U S C L E M I T O C H O N D R I A F R O M N O R M A L AND T H I O U R A C I L - T R E A T E D C H I C K S F E D N O R M A L A N D E X C E S S L E V E L S OF V I T A M I N E . M A T E R I A L S AND M E T H O D S S I X T Y D A Y - O L D M A L E W H I T E L E G H O R N C H I C K S WERE D I S T R I B U T E D I N T O TWO G R O U P S I N E L E C T R I C A L L Y H E A T E D B A T T E R Y B R O O D E R S . T H E C O N T R O L S R E C E I V E D T H E B A S A L D I E T W H I L E T H E O T H E R G R O U P WAS F E D T H E B A S A L D I E T S U P P L E M E N T E D W I T H 2 2 0 0 | . U . OF D L - O L - T O C O P H E R Y L A C E T A T E P E R K G . A F T E R 4 0 D A Y S , 1 5 C H I C K S OF E A C H G R O U P WERE F E D T H E R E S P E C T I V E D I E T W I T H T H E A D D I T I O N OF 0 . 1 $ OF T H I O U R A C I L . F I F T E E N D A Y S L A T E R , T H E C H I C K S ( 5 5 D A Y S O L D ) WERE K I L L E D AND T H E P E C T O R A L M U S C L E E X C I S E D I M M E D I A T E L Y F O R T H E I S O L A T I O N OF M I T O C H O N D R I A . P R E P A R A T I O N OF M I T O C H O N D R I A A P P R O X I M A T E L Y 1 5 GM OF M U S C L E F R O M E A C H C H I C K WAS I M M E R S E D I N I C E - C H I L L E D 0 . 1 5 M KC1 S O L U T I O N . T H E T I S S U E WAS T H E N H O M O G E N I Z E D W I T H 1 0 0 M L O F T H E I C E - C H I L L E D C H A P P E L L - P E R R Y T R I S - K C 1 M E D I U M ( 1 9 5 4 ) , U S I N G A V L R T I S H O M O G E N I Z E R AT A S E T T I N G OF 7 0 F O R 4 5 S E C O N D S . M Y O F I B R I L S , N U C L E I A N D U N B R O K E N C E L L S WERE R E M O V E D B Y TWO S U C C E S S I V E C E N T R I F U G A T I O N S A T 6 0 0 X G FOR 1 0 M I N U T E S AT 0 - 4 ° C ( A Z Z ONE E_T _AL . , 1 9 6 1 ) . T H E F I N A L 2 6 2 7 S U P E R N A T A N T F L U I D WAS T H E N C E N T R I F U G E D AT 8 5 0 0 X G FOR 1 0 M I N U T E S AT 0 - 4 ° C . T H E M I T O C H O N D R I A WERE W A S H E D T W I C E B Y R E S U S P E N S I O N I N T H E I S O L A T I O N M E D I U M A N D R E C E N T R I F U G E D AT 8 5 0 0 X G . T H E M I T O C H O N D R I A L P E L L E T WAS R I N S E D W I T H 0 . 1 5 M KC1 A T A C O N C E N T R A T I O N OF A P P R O X I M A T E L Y 3 M G . OF M I T O C H O N D R I A P E R M L . T H E P R O T E I N C O N T E N T OF T H E M I T O C H O N D R I A L S U S P E N S I O N WAS D E T E R M I N E D B Y T H E B I U R E T M E T H O D ( G 0 R N A L JET _AL . , 1 9 4 9 ) A F T E R C L E A R I N G T H E S U S P E N S I O N W I T H 0 . 5 $ S O D I U M D E O X Y C H O L A T E . C R Y S T A L L I N E B O V I N E S E R U M A L B U M I N WAS U S E D A S A S T A N D A R D TO P L O T A C A L I B R A T I O N C U R V E F O R P R O T E I N E S T I M A T I O N S . O X Y G E N U P T A K E B Y M I T O C H O N D R I A R E S P I R A T I O N OF M I T O C H O N D R I A WAS M E A S U R E D B Y T H E W A R B U R G M A N O M E T R I C T E C H N I Q U E ( U M B R I E T _E_T _A_L . , 1 9 5 9 ) . T H E M E D I U M U S E D WAS T H A T OF A Z Z O N E ( 1 9 6 1 ) WITH S O M E MOD I F1 C A T I O N . EACH V E S S E L C O N T A I N E D 2 5 MM T R I S B U F F E R ( P H 7 . 5 ) , 5 0 MM K C 1 , 6 MM M G C L 2 , 2 0 MM P I ( P H 7 . 5 ) , 0 . 0 1 MM O ( - K E T O - G L U T A R A T E , 0 . 0 2 MM C Y T O C H R O M E C , 1 MM A T P ( o I - N A - S A L T ) , 3 0 MM G L U C O S E A N D 0 . 3 3 M G . Y E A S T H E X O K I N A S E (SlGMA T Y P E V ) . T H E A D D I T I O N OF G L U C O S E , HE X O K I N A S E AND C Y T O C H R O M E C C A N S T I M U L A T E T H E R E S P I R A T I O N I N T H E M E D I U M D U R I N G I N C U B A T I O N P E R I O D ( H E D M A N , 1 9 6 5 ) . A T P WAS U S E D F O R P R E V E N T I O N OF M I T O C H O N D R I A L S W E L L I N G ( C H A P P E L AND P E R R Y , 1 9 5 4 ) . T H E T O T A L L I Q U I D V O L U M E WAS 3 ML P E R W A R B U R G V E S S E L . A L L F L A S K S WERE E Q U I L I B R A T E D A T 3 0 ° C F O R 5 M I N U T E S I M M E D I A T E L Y A F T E R A D D I T I O N OF 1 M L O F T H E M I T O C H O N D R I A TO T H E R E A C T I O N M I X T U R E . I N C U B A T I O N WAS AT 3 0 ° C W I T H O X Y G E N A S T H E G A S P H A S E F O R A P E R I O D O F 2 H O U R S . A L L D E T E R M I N A T I O N S WERE P E R F O R M E D I N D U P L I C A T E OR T R I P L I C A T E . T H E O X Y G E N U P T A K E O F T H E M I T O C H O N D R I A WAS M E A S U R E D AT 3 0 M I N U T E I N T E R V A L S F O R TWO H O U R S . O X Y G E N U P T A K E I S E X P R E S S E D A S U L / M G O F M I T O C H O N D R I A L P R O T E I N / H O U R . E L E C T R O N M I C R O S C O P I C S T U D Y OF M U S C L E M I T O C H O N D R I A A S M A L L S A M P L E OF A P E L L E T OF T H E F R E S H I S O L A T E D M I T O C H O N D R I A WAS T R A N S F E R R E D I N T O A M I C R O C E N T R I F U G E T U B E A C C O R D I N G TO T H E M E T H O D OF M A L A M E D (1963) AND T H E N F I X E D I N \FO OS 0^ W I T H A V E R ON A L - AC E T A TE I S O T O N I C B U F F E R AT PH 7 . 4 F O R 2 H O U R S AT 4°C ( K A Y , 1 9 6 6 ) . T H E S L U R R Y OF M I T O C H O N D R I A WAS R E A G G R E G A T E D I N T O A M A N A G E A B L E P E L L E T I N 5 M I N U T E S OF C E N T R I F U G A T I O N . A F T E R D E H Y D R A T I O N I N A G R A D E D A L C O H O L S E R I E S A N D F I N A L L Y I N P R O P Y L E N E O X I D E , T H E S A M P L E S WERE E M B E D D E D I N E P O X Y 812 ( L U F T , 1 9 6 1 ) . U L T R A T H I N S E C T I O N S WERE M A D E W I T H M T - 2 M I C R O T O M E AND . M O U N T E D ON C A R B O N E D - C O L L O D I O N - C O A T E D 2 0 0 M E S H C O P P E R G R I D S . D O U B L E S T A I N I N G WAS U S E D W I T H U R A N Y L A C E T A T E F O R 2 0 M I N U T E S ( S T E M P A K A N D W A R D , 1964) F O L L O W E D B Y L E A D C I T R A T E F O R 15 M I N U T E S ( R E Y N O L D S , 1 9 6 3 ) . T H E S T A I N E D S E C T I O N S WERE E X A M I N E D W I T H A H L T A C H I - 7 8 E L E C T R O N M I C R O S C O P E . R E S U L T S A N D D I S C U S S I O N T H E . R E S U L T S SHOW A S I G N I F I C A N T D E C R E A S E I N T H E O X Y G E N C O N S U M P T I O N OF T H E M U S C L E M I T O C H O N D R I A OF T H E C H I C K S F E D E X C E S S I V E L E V E L OF V I T A M I N E , C O M P A R E D W I T H T H E C H I C K S F E D T H E C O N T R O L D I E T ( T A B L E 8 ) . THE D E P R E S S I O N I N R E S P I R A T I O N D U E TO E X C E S S V I T A M I N E WAS S I G N I F I C A N T E V E N WHEN M E T A B O L I C R A T E HAD B E E N R E D U C E D B Y T H E F E E D I N G OF T H I O U R A C I L . I T S H O U L D BE N O T E D T H A T T H E L E V E L OF V I T A M I N E S U P P L E M E N T A T I O N I N . T H I S E X P E R I M E N T WAS 10 T I M E S T H A T U S E D I N E X P E R I M E N T 1 . B E C A U S E T I S S U E R E S P I R A T I O N R A T E I S KNOWN TO BE A C C E L E R A T E D I N V I T A M I N E D E F I C I E N C Y , I T M A Y BE D E D U C E D T H A T T H E R E S P O N S E TO E X C E S S V I T A M I N E W I L L BE R E L A T I V E TO T H E L E V E L A D M I N I S T E R E D A N D T H A T A D E P R E S S I O N I N R E S P I R A T I O N R A T E WAS L I K E W I S E A S S O C I A T E D W I T H T H E R E D U C T I O N I N T H Y R O I D A C T I V I T Y W I T H T H E L E V E L O F V I T A M I N E F E D I N E X P E R I M E N T 1 . A P O S I T I V E I O N , I OR I R E L E A S E D D U R I N G T H Y R O X I N E D E G R A D A T I O N I N T E R A C T S W I T H T H E P H O S P H O L I P I D S OF C E L L U L A R M E M B R A N E , R E S U L T I N G I N A L O W E R I N G OF T H E E L E C T R I C A L R E S I S T A N C E OF T H E M E M B R A N E ( F L N K E L S T E I N A N D C A S S , 1968J R O S E N B E R G AND J E N D R A S I A K , 1 9 6 8 ) . T H I S L O W E R E D E L E C T R I C A L R E S I S T A N C E , W H I C H I S P O S T U L A T E D TO BE T H E P R I M A R Y A C T I O N OF T H Y R O X I N E , M A Y BE T H E R E S U L T OF E I T H E R I N C R E A S E D I O N I C C O N D U C T I V I T Y , OR I N C R E A S E D E L E C T R O N I C C O N D U C T I V I T Y , A N D M A Y L O W E R T H E R E S I S T A N C E E I T H E R T R A N S V E R S E OR P A R A L L E L TO T H E P L A N E OF T H E M E M B R A N E . M I T O C H O N D R I A T R A N S F E R E L E C T R O N S F R O M S U B S T R A T E S S U C H A S NADH OR S U C C I N A T E TO M O L E C U L A R O X Y G E N A L O N G T H E C Y T O C H R O M E C H A I N A S S O C I A T E D W I T H T H E M I T O C H O N D R I A L . M E M B R A N E ( G R E E N ET _ A L . , 1 9 6 4 ) . |T H A S B E E N SHOWN 29 30 T H A T P H O S P H O L I P I D FOR T H E A C T I V I T Y OF T H E E L E C T R O N T R A N S P O R T I N G S U B M I T O C H O N D R I A L F R A C T I O N S I, I I , I I I A N D IV WERE R E Q U I R E D I N T H E M E M B R A N E OF M I T O C H O N D R I A ( B R I E R L Y _ET _AL . , 1 9 6 2 ; B R I E R L Y A N D M E R O L A , 1 9 6 2 ; F L E I S C H E R AND F L E I S C H E R , ' 1 9 6 4 ) . G R U E N S T E I N (1970) S U G G E S T E D T H A T , B Y I N C RE AS I N G T H E C O N D U C T I V I T Y OF T H E P H O S P H O L I P I D S , T H Y R O X I N E M A Y E I T H E R F A C I L I T A T E T H E T R A N S F E R O F E L E C T R O N S F R O M C Y T O C H R O M E TO C Y T O C H R O M E , OR E V E N TO S O M E E X T E N T " S H O R T C I R C U I T " P A R T S OF T H E E L E C T R O N T R A N S P O R T C H A I N , T H U S C A U S I N G MORE R A P I D R E D U C T I O N OF O X Y G E N A N D P A R T I A L U N C O U P L I NG OF P H O S P H O R Y L A T I O N . T H I S A C T I O N I S I N A G R E E M E N T W I T H T H E O B S E R V E D I N C R E A S E D O X Y G E N C O N S U M P T I O N E F F E C T OF T H Y R O X I N E ( TA T A _ET _AL . , 1 963) . E X C E S S V I T A M I N E M A Y D E P R E S S T H E D E I 0 0 I NAT I ON OF T H Y R O X I N E ( G A L T O N A N D H L N G B A R , 1 9 6 5 ) . W I T H A L E S S E R A M O U N T OF | + OR | ° R E L E A S E D I N M E M B R A N E OF M U S C L E M I T C H O N D R I A , C O N D U C T I V I T Y OF T H E P H O S P H O L I P I D W I L L BE L O W E R , P H O S P H O R Y L A T I ON . R A T E W I L L BE R E D U C E D AND O X Y G E N U P T A K E I S D E C R E A S E D . I T I S C O N C L U D E D T H A T E X C E S S V I T A M I N E NOT O N L Y D E P R E S S E D T H E A C T I V I T Y O F T H Y R O I D G L A N D B U T A L S O R E D U C E T H E R E S P I R A T I O N R A T E OF M U S C L E M I T O C H O N D R I A . T H E GROWTH R A T E O F T H E C H I C K S F E D T H E E X C E S S L E V E L OF V I T A M I N E I N T H I S E X P E R I M E N T WAS M A R K E D L Y L O W E R T H A N T H A T OF T H E C O N T R O L C H I C K S . |T I S . S U G G E S T E D T H A T T H E C H I C K M A Y M A I N T A I N N O R M A L R E S P I R A T I O N R A T E WHEN F E D E X C E S S V I T A M I N E U P TO A C E R T A I N L E V E L T H R O U G H A R E D U C T I O N I N T H Y R O I D A C T I V I T Y ( S E E D I S C U S S I O N O F E X P E R I M E N T 1 ) . W I T H A L A R G E E X C E S S OF V I T A M I N E, H O W E V E R , NO F U R T H E R C O M P E N S A T I O N I S P O S S I B L E AND R E S P I R A T I O N R A T E I S D E P R E S S E D B E L O W N O R M A L . F R O M T H E E L E C T R O N M I C R O G R A P H S , S W O L L E N M I T O C H O N D R I A WERE C L E A R L Y 3 1 S E E N I N P R E P A R A T I O N S F R O M B O T H C O N T R O L C H I C K S AND C H I C K S F E D A N E X C E S S OF V I T A M I N E ( F I G U R E S 5 AND 6 ) . S O M E S P E C I M E N S , H O W E V E R , S H O W E D N O R M A L I N T A C T M I T O C H O N D R I A ( F I G U R E 7 ) . T H E S W O L L E N A P P E A R A N C E OF T H E M I T O C H O N D R I A M A Y BE D U E TO T H E S E V E R A L W A S H I N G S W I T H C H A P P E L AND P E R R Y T R I S - K C L M E D I U M . T A B L E 8 I N D I C A T E S T H A T T H E R E S P I R A T I O N R A T E OF T H E M I T O C H O N D R I A I N T H E P E R I O D OF 0 - 3 0 M I N U T E S A N D OF 3 0 - 6 0 M I N U T E S A R E N E A R L Y E Q U A L . O R D I N A R I L Y I T I S R E P O R T E D T H A T R E S P I R A T I O N R A T E D E C L I N E S I N S U C C E S S I V E 3 0 M I N U T E P E R I O D S . I T A P P E A R S T H A T T H E M I T O C H O N D R I A M A Y BE S W E L L I N G C O N T I N U O U S L Y D U R I N G T H E I N C U B A T I O N P E R I O D OF 0 - 3 0 M I N U T E S U N T I L A C E R T A I N A M O U N T OF A T P I S F O R M E D . T H E S W E L L I N G OF M U S C L E M I T O C H O N D R I A C A N BE R E V E R S E D B Y T H E P R E S E N C E O F * L O W C O N C E N T R A T I O N S OF A T P ( C H A P P E L A N D P E R R Y , 1 9 5 4 ) AND T H U S T H E M I T O C H O N D R I A U N D E R G O A N O R M A L R E S P I R A T I O N I N T H E P E R I O D OF 3 0 - 6 0 M I N U T E S . T H E E L E C T R O N M I C R O G R A P H A L S O S H O W S T H A T T H E M I T O C H O N D R I A P R E P A R A T I O N WAS C O N T A M I N A T E D W I T H S M A L L P A R T I C L E S W H I C H M I G H T BE S U B M I T O C H O N D R I A . |T A P P E A R S T H A T T H E M E T H O D OF P R E P A R A T I O N OF M I T O C H O N D R I A U S I N G T H E F R A C T I O N O B T A I N E D A T 8 5 0 0 X G I S NOT A GOOD M E T H O D F O R O B T A I N I N G I N T A C T M I T O C H O N D R I A F O R R E S P I R A T I O N S T U D I E S A L T H O U G H T H E M I T O C H O N D R I A L Y I E L D I S G O O D . H E D M A N ( 1 9 6 5 ) R E P O R T E D T H A T T H E 3 5 0 0 X G M I T O C H O N D R I A L F R A C T I O N R E P R E S E N T E D R E L A T I V E L Y I N T A C T M I T O C H O N D R I A B U T T H E M I T O C H O N D R I A L Y I E L D WAS R E D U C E D B Y A B O U T O N E T H I R D . |N T H E P R E S E N T E X P E R I M E N T , TWO A D V E R S E E F F E C T S OF H Y P E R V I TAM I N O S I S E WERE O B S E R V E D V I Z . B O N E F R A G I L I T Y A N D A N I N C R E A S E I N P R O T H R O M B I N T I M E . 32 F I G . 5 . E L E C T R O N M I C R O G R A P H OF B R E A S T M U S C L E M I T O C H O N D R I A F R O M A C H I C K F E D A N O R M A L L E V E L OF V I T A M I N E . T H E C O N C E N T R A T I O N OF M I T O C H O N D R I A WAS LOW AND T H E S U S P E N S I O N C O N T A M I N A T E D W I T H S U B M I T O C H O N D R I A . T H E S W O L L E N M I T O C H O N D R I A WERE C L E A R L Y S E E N . X 3 0 , 0 0 0 . 3 3 F I G . 6 . E L E C T R O N M I C R O G R A P H or A S E C T I O N OF M U S C L E M I T O C H O N D R I A F R O M A C H I C K F E D E X C E S S V I T A M I N E . T H E S W O L L E N M I T O C H O N D R I A WERE C L E A R L Y S E E N A N D T H E S U S P E N S I O N C O N T A M I N A T E D W I T H S U B M I T O C H O N D R I A x 3 0 , 0 0 0 . F I G . 7 . E L E C T R O N M I C R O G R A P H or A S E C T I O N or B R E A S T M U S C L E M I T O C H O N D R I A r ROM A C H I C K F E D A N O R M A L L E V E L OF V I T A M I N E S H O W I N G I N T A C T M I T O C H O N D R I A . NO S W E L L I N G P H E N O M E N O N WAS S E E N B U T T H E M I T O C H O N D R I A L S U S P E N S I O N WAS C O N T A M I N A T E D W I T H S U B M I T O C H O N D R I A x 3 6 , 0 0 0 . E X P E R I M E N T I I I S Y M P T O M S or H Y P E R V I T A M I N O S I s E I N C H I C K S T H I S E X P E R I M E N T WAS D E S I G N E D TO I N V E S T I G A T E T H E E F F E C T S OF E X C E S S V I T A M I N E I N C H I C K S F E D D I E T S D E F I C I E N T A N D A D E Q U A T E I N C A L C I U M . S L N C E T H E R E I S NO I N F O R M A T I O N A V A I L A B L E R E G A R D I N G T H E E F F E C T S OF L O N G T E R M A D M I N I S T R A T I O N OF E X C E S S V I T A M I N E TO C H I C K S , T H E E X P E R I M E N T WAS C O N D U C T E D W I T H C H I C K S F E D T H E D I F F E R E N T D I E T S F R O M H A T C H - TO 50 D A Y S OF A G E . I N E X P E R I M E N T I I , TWO A D V E R S E E F F E C T S OF H Y P E R V I T A M I N O S I S E WERE O B S E R V E D V I Z . B O N E F R A G I L I T Y AND AN I N C R E A S E I N P R O T H R O M B I N T I M E . T H E D I E T S F E D I N T H I S E X P E R I M E N T WERE A C C I D E N T L Y F O R M U L A T E D W I T H O U T A D E Q U A T E C A L C I U M S U P P L E M E N T A T I O N . T H E R E W A S , T H E R E F O R E , T H E P O S S I B I L I T Y OF A N I N T E R R E L A T I O N S H I P B E T W E E N T H E C A L C I U M D E F I C I E N C Y A N D E X C E S S V I T A M I N E I N T H E R E S P O N S E OF T H E C H I C K S I N T H I S E X P E R I M E N T . A S E A R C H OF T H E L I T E R A T U R E F O R R E L A T E D O B S E R V A T I O N S R E V E A L E D ONE R E P O R T T H A T H I G H D I E T A R Y L E V E L S OF E I T H E R V I T A M I N A OR V I T A M I N E D E P R E S S E D P R O T H R O M B I N L E V E L OF T H E B L O O D I N T H E RAT ( M E L L E T E A N D L E O N E , 1 9 6 0 ) . NO R E P O R T OF A N Y E F F E C T O F E X C E S S V I T A M I N E ON B O N E C A L C I F I C A T I O N WAS' F O U N D . M A T E R I A L S AND M E T H O D S D A Y - O L D W H I T E L E G H O R N M A L E C H I C K S WERE W I N G - B A N D E D AND D I S T R I B U T E D A T R A N D O M I N T O 8 L O T S OF 25 C H I C K S E A C H I N C O M P A R T M E N T S OF E L E C T R I C A L L Y H E A T E D B A T T E R Y B R O O D E R S . T H E F O U R D I F F E R E N T D I E T S U S E D I N T H E E X P E R I M E N T 3 5 36 A R E SHOWN I N T A B L E 9 . E A C H D I E T WAS F E D TO D U P L I C A T E L O T S OF C H I C K S . ROOM T E M P E R A T U R E WAS T H E R M O S T A T I C A L L Y C O N T R O L L E D A T 2 2 - 2 3 ° C . T H E F E E D AND W A T E R WERE S U P P L I E D AD L I B I T U M . A F T E R A P E R I O D OF 30 D A Y S , B L O O D S A M P L E S (1 M L P E R C H I C K ) OF 3 C H I C K S F R O M E A C H L O T WERE DRAWN AT R A N D O M F R O M T H E W I N G V E I N B Y U S I N G T U B E R C U L I N S Y R I N G E . B L O O D S A M P L E S . C 0 N T A I N E D S O D I U M O X A L A T E OR H E P A R I N F O R T H E D I F F E R E N T H E M A T O L O G I C A L D E T E R M I N A T I O N S . P R O T H R O M B I N T I M E S , H E M A T O C R I T V A L U E S A N D R E T I C U L O C Y T E C O U N T S WERE D E T E R M I N E D ON T H E B L O O D S A M P L E S . P R O T H R O M B I N T I M E T H E M E A S U R E M E N T OF P R O T H R O M B I N T I M E I S U S E D A S AN I M P O R T A N T S C R E E N I N G T E S T F O R T H E D E F I C I E N C Y OF T H E V A R I O U S F A C T O R S OF T H E P R O T H R O M B I N C O M P L E X S U C H A S P R O T H R O M B I N , F A C T O R S V , V I I A N D X ( Q U I C K , 1 9 6 1 ) . N I N E - T E N T H M L OF B L O O D WAS DRAWN I N A S Y R I N G E ' C O N T A I N I N G 0 . 1 M L OF S O D I U M O X A L A T E A N D M I X E D W E L L . P R O T H R O M B I N T I M E WAS E S T I M A T E D B Y T H E Q U I C K ONE S T A G E M E T H O D ( Q U I C K , 1936) W I T H M O D I F I C A T I O N B Y A L M Q U 1 S T ( 1 9 4 1 ) . H E M A T O C R I T V A L U E T H E D E T E R M I N A T I O N OF H E M A T O C R I T V A L U E ( O R P A C K E D C E L L V O L U M E ) I S U S E D A S A S I M P L E S C R E E N I N G . T E S T F O R A N E M I A . T H E M I C R O M E T H O D WAS A P P L I E D , ML C R O - HE .MATOC R I T T U B E S ( 1 . 1 - 1 . 2 M M . I N I . D . , 75 MM I N 1 L E N G T H ) WERE U S E D F O R T H E H E M A T O C R I T D E T E R M I N A T I O N S . T H E H E P A R I N I Z E D B L O O D S A M P L E WAS A L L O W E D TO E N T E R T H E T U B E B Y C A P I L L A R I T Y . T H E T U B E WAS T H E N S E A L E D W I T H P L A S T I C I N E . A F T E R C E N T R I F U G A T I O N F O R 3 M I N U T E S , U S I N G A I N T E R N A T I O N A L M I C R O - C A P I L L A R Y C E N T R I F U G E , M O D E L M . B . T H E H E M A T O C R I T V A L U E WAS M E A S U R E D U S I N G A R E A D I N G D E V I C E . 37 R E T I C U L O C Y T E C O U N T S T H E R E T I C U L O C Y T E S T A I N T E C H N I Q U E ( C O A T E S AND M A R C H , 1966) WAS U S E D F O R R E T I C U L O C Y T E C O U N T S . A T 30 D A Y S OF A G E , 4 C H I C K S F R O M E A C H L O T WERE W E I G H E D AND K I L L E D . T H E L E F T T I B I A OF E A C H C H I C K WAS T A K E N F O R A S H A N A L Y S I S . B O N E A S H , E X P R E S S E D ON A D R Y F A T - F R E E B A S I S , WAS U S E D TO SHOW T H E D E G R E E OF B O N E C A L C I F I C A T I O N I N T H E L E F T T I B I A A C C O R D I N G TO T H E A . O . A . C . P R O C E D U R E ( 1 9 6 5 ) , U S E D I N T H E C H I C K A S S A Y F O R V I T A M I N D . T H E R I G H T T I B I A S WERE C U T AND T H E A P P E A R A N C E OF T H E MARROW N O T E D . T H E S E O B S E R V A T I O N S WERE R E P E A T E D ^ ON T H E R E M A I N I N G C H I C K S OF 40 AND 50 D A Y S OF A G E . I N J E C T I O N OF V I T A M I N K A T T H E C O N C L U S I O N OF T H E E X P E R I M E N T , T H R E E B I R D S F E D E X C E S S V I T A M I N E WERE I N J E C T E D I N T R A M U S C U L A R L Y W I T H M E N A D I O N E (5 M G . / K G . O F B O D Y W E I G H T ) I N O I L S O L U T I O N . T W E N T Y - F O U R H O U R S A F T E R I N J E C T I O N , P R O T H R O M B I N T I M E WAS D E T E R M I N E D . P R O T H R O M B I N T I M E S WERE NOT M E A S U R E D A T 50 D A Y S OF A G E . R E S U L T S P R O T H R O M B I N T I M E T H E M E A N P R O T H R O M B I N T I M E O F T H E C H I C K S F R O M E A C H D I E T A R Y T R E A T M E N T A N D T H E S T A T I S T I C A L A N A L Y S I S O F T H E R E S U L T S A R E SHOWN I N T A B L E 1 0 . T H E A D D I T I O N OF E X C E S S V I T A M I N E TO E I T H E R T H E B A S A L D I E T OR TO T H E B A S A L D I E T S U P P L E M E N T E D W I T H A D D I T I O N A L C A L C I U M S I G N I F I C A N T L Y ( P $ 0 . 0 1 ) P R O L O N G E D P R O T H R O M B I N T I M E OF B L O O D F R O M T H E C H I C K S . A T 30 D A Y S OF A G E , T H E R E WAS AN E F F E C T OF D I E T A R Y C A L C I U M L E V E L ON P R O T H R O M B I N T I M E . A T 4 0 D A Y S OF A G E o E X C E S S V I T A M I N E L E N G T H E N E D P R O T H R O M B I N T I M E TO A G R E A T E R D E G R E E WHEN T H E D I E T WAS D E F I C I E N T I N C A L C I U M . C O M P A R I S O N S H O U L D NOT B E M A D E B E T W E E N T H E A B S O L U T E P R O T H R O M B I N T I M E S M E A S U R E D AT 30 AND 4 0 D A Y S OF A G E B E C A U S E OF A P O S S I B L E D I F F E R E N C E I N T H E A C T I V I T Y OF T H E T H R O M B O P L A S T I N P R E P A R A T I O N U S E D I N T H E TWO S E T S OF M E A S U R E M E N T S . H E M A T O C R I T V A L U E S T H E H E M A T O C R I T V A L U E S A R E A L S O SHOWN I N T A B L E 1 0 . E X C E S S V I T A M I N E R E S U L T E D I N D E C R E A S E D H E M A T O C R I T V A L U E S I N T H E P R E S E N T E X P E R I M E N T . S U P P L E M E N T A T I O N OF T H E B A S A L D I E T T O ' S U P P L Y A D E Q U A T E C A L C I U M I N C R E A S E D S I G N I F I C A N T L Y T H E H E M A T O C R I T V A L U E OF B L O O D S A M P L E S AT 30 D A Y S O F A G E ( P $ 0 . 0 1 ) . B Y 4 0 D A Y S OF A G E T H E D I F F E R E N C E S I N H E M A T O C R I T V A L U E S B E T W E E N T H E C H I C K S F E D T H E C A L C I U M D E F I C I E N T AND C A L C I U M - A D E Q U A T E D I E T S WERE NO L O N G E R S I G N I F I C A N T . A T 50 D A Y S O F A G E , T H E D I F F E R E N C E S I N H E M A T O C R I T V A L U E S O F B L O O D S A M P L E S F R O M T H E C H I C K S F E D N O R M A L A N D E X C E S S L E V E L S OF 3 8 3 9 V I T A M I N E, A L T H O U G H S T A T I S T I C A L L Y S I G N I F I C A N T ( P ^ G O . O L ) WERE S M A L L E R T H A N T H O S E O B S E R V E D W I T H Y O U N G E R B I R D S . R E T I C U L O C Y T E C O U N T S R E T I C U L O C Y T E C O U N T S O F T H E C H I C K S F E D T H E B A S A L D I E T A N D T H E B A S A L D I E T S U P P L E M E N T E D W I T H C A L C I U M A R E S I M I L A R ( T A B L E 1 0 ) . S U P P L E M E N T A T I O N OF T H E D I E T S W I T H E X C E S S . V I T A M I N E I N C R E A S E D R E T I C U L O C Y T E C O U N T S S I G N I F I - C A N T L Y ( P 0 . 0 1 ) I N T H E B L O O D F R O M C H I C K S F E D D I E T S OF E I T H E R C A L C I U M L E V E L . I N T H E B L O O D S A M P L E F R O M C H I C K S F E D E X C E S S V I T A M I N E , M A N Y E A R L Y R E T I C U L O C Y T E S W I T H A H E A V I L Y S T A I N I N G R E T I C U L U M WERE S E E N . T H E C E L L S O B S E R V E D I N M A N Y OF T H E B L O O D S M E A R S F R O M T H E C H I C K S F E D E X C E S S V I T A M I N E A P P E A R E D TO BE E R Y T H R 0 B L A S T S ( C O M P A R A B L E TO F I G U R E S 9 - 1 3 OR 1 2 1 - 1 2 4 , L U C A S A N D J A M R O Z , 1 9 6 1 ) . P H O T O G R A P H S OF R E P R E S E N T A T I V E C E L L S A R E SHOWN I N F I G U R E S 8 , 9 A N D 1 0 . B O N E MARROW T H E M A R R O W C A V I T Y OF THE T I B I A F R O M B I R D S F E D E X C E S S V I T A M I N E SHOWED R E S O R P T I O N OF A L L C A L C I F I E D T I S S U E A N D C O N T A I N E D O N L Y B L O O D Y M A T E R I A L . T H E T Y P I C A L A P P E A R A N C E I S SHOWN I N F I G U R E 11 F R O M A B I R D 5 0 D A Y S OF A G E . ! B O N E C A L C I F I C A T I O N D A T A R E L A T I N G TO T H E C A L C I F I C A T I O N OF B O N E A R E SHOWN I N T A B L E 1 2 . I N G R O U P S 3 AND 4 R E C E I V I N G ON A D E Q U A T E L E V E L OF C A L C I U M ( 1 $ C A L C I U M ) NO S I G N I F I C A N T D I F F E R E N C E I N B O N E A S H P E R C E N T A G E WAS D E T E C T E D I N H Y P E R - V I T A M I N O S I S E . I N C O M P A R I N G G R O U P S , 1 ( N O R M A L L E V E L OF V I T A M I N E ) A N D 2 ( H Y P E R V I T A M I N O S I S E ) , B O T H R E C E I V I N G A LOW L E V E L OF C A L C I U M F I G . 9 . R E T I C U L O C Y T E S F R O M A 4 0 - D A Y OLD V I T A M I N E x 1 0 0 0 . C H I C K F E D E X C E S S 41 F l G . 1 0 . E R Y T H R O B L A S T S O B S E R V E D ON T H E A 4 0 - D A Y O L D C H I C K X 1 0 0 0 . B L O O D S M E A R F R O M 42 E D F I G . 1 1 . A B N O R M A L B O N E MARROW OF C H I C K S F E D E X C E S S V I T A M I N E . A . N O R M A L B O N E MARROW F R O M T H E 5 0 - D A Y OLD C O N T R O L C H I C K . B . S E V E R E H Y P O P L A S T I C B O N E MARROW F R O M T H E 5 0 - D A Y OLD C H I C K F E D E X C E S S V I T A M I N E . C . M E D I A T E H Y P O P L A S T I C B O N E MARROW F R O M A 4 0 - D A Y OLD C H I C K F E D E X C E S S V I T A M I N E D I E T . D . S L I G H T L Y H Y P O P L A S T I C B O N E MARROW F R O M A 4 0 - D A Y OLD C H I C K F E D E X C E S S V I T A M I N E . 4 3 ( 0 . 5 9 $ C A L C I U M ) , T H E A S H P E R C E N T A G E WAS S I G N I F I C A N T L Y LOWER I N G R O U P 2 I N P E R I O D S OF 3 0 , 40 AND 50 D A Y S . B E C A U S E B O N E M I N E R A L I Z A T I O N I N C R E A S E D A S T H E C H I C K B E C A M E O L D E R , A N D H E A V I E R AND B E C A U S E E X C E S S V I T A M I N E D E P R E S S E D G R O W T H , A T L E A S T P A R T OF T H E D I F F E R E N C E I N B O N E A S H B E T W E E N T H E C H I C K S F E D T H E N O R M A L A N D E X C E S S L E V E L S OF V I T A M I N E M A Y H A V E B E E N D U E TO T H E D I F F E R E N C E I N B O D Y W E I G H T OF T H E B I R D S OF T H E TWO L E V E L S OF V I T A M I N E . P E R C E N T T I B I A A S H WAS A C C O R D I N G L Y G R A P H E D A G A I N S T B O D Y W E I G H T I N F I G U R E 1 2 B . F O R C O M P A R I S O N , A G R A P H WAS A L S O M A D E OF P E R C E N T T I B I A A S H R E L A T I V E TO A G E OF T H E B I R D S . U S I N G T H E V A L U E S F O R P E R C E N T A S H AT A B O D Y W E I G H T OF 3 0 0 G M . , I T W I L L BE S E E N T H A T , WHEN T H E D I E T WAS D E F I C I E N T I N C A L C I U M , AN E X C E S S OF V I T A M I N E D E P R E S S E D C A L C I F I C A T I O N . I N J E C T I ON O F VI T A M I N K T W E N T Y - F O U R H O U R S A F T E R I N J E C T I O N OF M E N A D I O N E , P R O T H R O M B I N T I M E O F T H E C H I C K S F E D E X C E S S V I T A M I N E WAS S H O R T E N E D TO T H A T OF C H I C K S F E D T H E N O R M A L L E V E L OF V I T A M I N E ( T A B L E 1 1 ) . D I S C U S S I O N T H E - P R O L O N G E D P R O T H R O M B I N T I M E I N T H E C H I C K S F E D E X C E S S V I T A M I N E A N D T H E S H O R T E N I N G O F P R O T H R O M B I N T I M E B Y A D M I N I S T R A T I O N O F M E N A D I O N E WERE I N D I C A T I V E O F V I T A M I N K - D E F I C I E N C Y ( A L M Q U I S T A N D S T . O K S T A D , 1 9 3 6 ) . T H E P R O L O N G E D P R O T H R O M B I N T I M E I N C H I C K S F E D E X C E S S V I T A M I N E C O N F I R M E D T H E O B S E R V A T I O N B Y M E L L E T E A N D L E O N E ( i 9 6 0 ) I N R A T S . T H E M E C H A N I S M B Y W H I C H H Y P O P R O T H R O M B I N E M I A I S C A U S E D MAY B E I N T E R P R E T E D I N ONE O F T H R E E W A Y S . ONE P O S S I B L E M E C H A N I S M I S T H A T A N E X C E S S I V E A M O U N T O F V I T A M I N E OR I T S M E T A B O L I T E S M A Y A N T A G O N I Z E T H E A C T I O N O F V I T A M I N K . I N T H E C O U R S E O F E A R L I E R S T U D I E S O N T H E M E T A B O L I S M O F o C - T O C O P H E R Y L - 5 - M E T H Y L - C I N A N I M A L S , T H R E E L A B E L E D M E T A B O L I T E S , oC- TOC O P H E R y L - P - QU I N O N E ( C S A L L A N Y _E_T _AL . , 1 9 6 2 ) , A D I M E R ( C S A L L A N Y A N D D R A P E R , 1963) AND A T R I M E R (D R A P E R _E_T _AL . , 1967) WERE I S O L A T E D F R O M T H E L I V E R T I S S U E . |T I S S U G G E S T E D T H A T T H E S T R U C T U R E O F T H E S E E N D M E T A B O L I T E S , H O W E V E R , A R E S I M I L A R T O T H A T O F V I T A M I N K A N D P R O B A B L Y C O M P E T E W I T H V I T A M I N K F O R C E R T A I N E N Z Y M E S I T E S . T H E S E C O N D P O S S I B L E M E C H A N I S M I S T H A T A N E X C E S S I V E A M O U N T O F V I T A M I N E MAY I N T E R F E R E W I T H T H E A B S O R P T I O N O F F A T S O L U B L E V I T A M I N S , S U C H A S V I T A M I N S K A N D D . T H E T H I R D I S T H A T E X C E S S I V E A M O U N T S OF V I T A M I N E M A Y R E T A R D T H E S Y N T H E S I S O F V I T A M I N K . E X C E S S V I T A M I N E D I D NOT E X E R T AN E F F E C T ON T H E B O N E F O R M A T I O N I N C H I C K S F E D A D E Q U A T E C A L C I U M D I E T . WHEN F E D A LOW C A L C I U M D I E T , P E R C E N T A S H I S S I G N I F I C A N T L Y LOWER I N C H I C K S F E D E X C E S S V I T A M I N E T H A N T H A T I N T H E C H I C K S F E D T H E B A S A L D I E T , SHOWN I N T A B L E 12 A N D F I G U R E S 12A A N D B . I T 44 P E R C E N T O F T I B I A A S H P E R C E N T OF T I B I A A S H CO r-i ro 00 O O ro - 1 — 1 o — I o CD p i > _ z > "n TO CO f - O X c O CO n -< o 70 z c p i o s: m p i > — O o — ^1 X < H p i P i X . •t» —i o CD o o PI o co —^ CD co o D < -< — s: > <J1 p i o — — o z X - 1 m O z CJ) -o o PI o X) o PI z H o •n CO 4* o J t D - 4* co ro —* + 00 CO + CO CO > > > > PI CO PI CO CO X > > X > > n r" r o pi m CO + + CO .—- -—. co CO r- o O o < > > < c c - i o o > > > > 2 - — — Z z - n CD • ro > • o > — i -< — X CO CD PI — o > — z z > •n PI co r~ X X c "0 rn PI > z XI H n — PI 2 a PI — o z -n H pi pi XI X pi o z PI H CO co > CD < PI — CO • > Z rr l o z 13 PI XI r> z H O •n CO Q _ CO o -1^ o o CO o 4* O 4* CO ro —* + CO CO + CO CO > > > > PI co co PI CO CO X > > X > > (-) r" i - n p r - - PI pi CO + + co ,—. ,—̂ co CO r- r o o O O < > > < s. - i o o > > > > 2 2 — — z z r n m 4* cn 46 A P P E A R S T H A T E X C E S S V I T A M I N E M A Y A L S O I N T E R F E R E W I T H T H E A B S O R P T I O N OF V I T A M I N D OR S L O W DOWN T H E B O N E C A L C I F I C A T I O N P R O C E S S . RET I C U L O C Y T O S 1 S HAS B E E N R E P O R T E D TO O C C U R I N R E S P O N S E TO T O C O P H E R O L T R E A T M E N T OF V I T A M I N E - D E F I C I E N T M O N K E Y S ' , HUMAN I N F A N T S A N D C H I L D R E N ( . F I T C H , 1 9 5 8 ; H A S S A N r r A L , , 1 9 6 6 ) . M A R C H ZJ_ AL. (1969) O B S E R V E D T H A T R E C I C U L O C Y T O S I S O C C U R E D I N C H I C K S F E D E X C E S S V I T A M I N E (220 I . U . P E R KG OF D I E T ) OR O T H E R A N T I O X I D A N T S A N D A T T R I B U T E D THE C O N D I T I O N TO R E T A R D A T I O N OF T H E M A T U R A T I O N P R O C E S S OF T H E RED B L O O D C E L L S . M A R C H _E_T _AL. A L S O R E P O R T E D T H A T E R Y T H R O C Y T E T U R N O V E R WAS S L O W E R I N S O M E OF THE B I R D S F E D E X C E S S V I T A M I N E AND T H A T H E M A T O C R I T V A L U E S WERE NOT R E D U C E D . I T I S I N T E R E S T I NG* I N T H E P R E S E N T E X P E R I M E N T T H A T T H E L E V E L OF V I T A M I N E (2200 I . U . P E R KG OF D I E T OR 100 T I M E S T H E N O R M A L L E V E L ) R E S U L T E D I N T H E D E C R E A S E D H E M A T O C R I T V A L U E , . R E T I C U L O C Y T O S I S A N D A L T E R A T I O N OF B O N E M A R R O W . ONE P O S S I B L E M E C H A N I S M I S T H A T A N E X C E S S I V E A M O U N T OF V I T A M I N E NOT O N L Y R E T A R D S T H E M A T U R A T I O N OF T H E R E T I C U L O C Y T E S I N T H E B L O O D B U T A L S O S L O W S DOWN OR E V E N P R E V E N T S T H E E R Y T H R O P O I E S 1 S I N T H E B O N E M A R R O W , T H E R E F O R E , R E S U L T I N G I N T H E D E C R E A S E D H E M A T O C R I T V A L U E ( A N E M I A ) . |N S O M E S E V E R E C A S E S , J E L L Y - L I K E B L O O D Y M A T E R I A L WAS O B S E R V E D I N T H E MARROW C A V I T Y AND . E R Y T H R O B L A S T S WERE P R E S E N T I N T H E S M E A R S OF T H E C I R C U L A T I N G B L O O D I N D I C A T I N G A R E T A R D A T I O N OF E R Y T H R O P O I E S I S . U N F O R T U N A T E L Y , M I C R O S C O P I C S T U D I E S H A V E NOT B E E N C A R R I E D O U T FOR B O N E MARROW S M E A R . F U R T H E R S T U D I E S A R E R E Q U I R E D . SUMMARY A S T U D Y WAS M A D E O P T H E E F F E C T S OF F E E D I N G E X C E S S V I T A M I N E TO C H I C K S . T H R E E G R O U P S OF E X P E R I M E N T S WERE C O N D U C T E D TO I N V E S T I G A T E (1) T H Y R O I D A L R E S P O N S E TO E X C E S S V I T A M I N E , (2 ) R E S P I R A T I O N R A T E OF M U S C L E M I T O C H O N D R I A F R O M C H I C K S F E D E X C E S S V I T A M I N E , A N D (3) S Y M P T O M S OF H Y P E R V I T A M I NO I S E . IN TWO S E P A R A T E E X P E R I M E N T S , C H I C K S WERE F E D N O R M A L AND E X C E S S L E V E L S (220 I . U . / K C J . 0 F D I E T ) OF V I T A M I N E A N D WERE S U B J E C T E D TO T E M P E R A T U R E S OF 1 4 . 5 AND 3 1 . 5 ° C . T H E G O I T R O G E N I C E F F E C T OF T H I O U R A C I L ON T H E B I R D S I N T H E D I F F E R E N T T R E A T M E N T S WAS M E A S U R E D . A T B O T H T E M P E R A T U R E S T H E T H I O U R A C I L - T R E A T E D C H I C K S F E D E X C E S S V I T A M I N E E X H I B I T E D A L E S S E R E N L A R G E M E N T OF T H E T H Y R O I D G L A N D S T H A N D I D C H I C K S R E C E I V I N G A N O R M A L L E V E L OF V I T A M I N E . T H I S F I N D I N G I N D I C A T E S A R E D U C T I O N I N T H E S E C R E T I O N O F T H Y R O I D S T I M U L A T I N G H O R M O N E ( T S H ) I N B I R D S . F E D E X C E S S V I T A M I N E . T H E L E V E L OF V I T A M I N E W H I C H WAS F E D D I D NOT A F F E C T T H E GROWTH R A T E OR F E E D C O N S U M P T I O N AT E I T H E R T E M P E R A T U R E . I T , T H E R E F O R E , A P P E A R S T H A T T H E M E T A B O L I C R A T E S O F T H E C H I C K S F E D T H E LOW A N D E X C E S S L E V E L S OF V I T A M I N E W E R E S I M I L A R D E S P I T E D I F F E R E N C E S I N T H Y R O I D A C T I V I T Y A N D T H A T T I S S U E R E S P I R A T I O N I N B I R D S F E D E X C E S S V I T A M I N E C A N BE M A I N T A I N E D W I T H A R E D U C E D S U P P L Y OR T U R N O V E R OF T H Y R O I D H O R M O N E . T H E A C T I V I T Y OF T H E T H Y R O I D G L A N D I T S E L F WAS S T U D I E D I N R E S P O N S E , , 131^ TO E X C E S S V I T A M I N E I N A N O T H E R E X P E R I M E N T . U S I N G R A D I O I O D I N E [ I ) A S A 47 48 T R A C E R , I T WAS F O U N D T H A T T H E R A T E S OF I O D I N E U P T A K E A N D R E L E A S E B Y T H E T H Y R O I D G L A N D WERE B O T H S L O W E R I N B I R D S F E D E X C E S S V I T A M I N E ( 2 2 0 I . U . / K G . OF D I E T ) T H A N I N C O N T R O L B I R D S . B E C A U S E V I T A M I N E A C T S A S A B I O L O G I C A L A N T I O X I D A N T , I T M A Y , I N E X C E S S A M O U N T S , D E P R E S S T H E R A T E OF DEIODI N A T 1 ON OF T H Y R O X I N E I N T H E P E R I P H E R A L T I S S U E A T W H I C H T H Y R O I D H O R M O N E I S R E M O V E D F R O M T H E C I R C U L A T I O N . A S A C O N S E Q U E N C E , T H E S E C R E T I O N OF T S H WOULD B E R E D U C E D . |N O R D E R TO O B T A I N S O M E I N D I C A T I O N OF C A U S E AND E F F E C T I N T H E M E C H A N I S M B Y W H I C H T H E E X C E S S V I T A M I N E A F F E C T S T H Y R O T R O P I C H O R M O N E S E C R E T I O N R A T E A N D T H Y R O I D A C T I V I T Y , T H E R E S P I R A T I O N R A T E OF M I T O C H O N D R I A I S O L A T E D F R O M T H E P E C T O R A L M U S C L E O F C H I C K S W H I C H HAD B E E N F E D E X C E S S V I T A M I N E ( 2 2 0 0 I . U . / K G . OF D I E T ) WAS C O M P A R E D W I T H T H A T O F T H E C O N T R O L B I R D S . T H E R E S U L T S S H O W E D A S I G N I F I C A N T R E D U C T I O N I N O X Y G E N U P T A K E B Y T H E M U S C L E M I T O C H O N D R I A O F C H I C K S F E D T H E E X C E S S A M O U N T O F V I T A M I N E . T H E GROWTH R A T E OF T H E C H I C K S F E D T H E E X C E S S L E V E L OF V I T A M I N E I N T H I S E X P E R I M E N T WAS M A R K E D L Y L O W E R T H A N T H A T OF T H E C O N T R O L C H I C K S . I T I S S U G G E S T E D T H A T T H E C H I C K M A Y M A I N T A I N A N O R M A L R E S P I R A T I O N R A T E WHEN F E D E X C E S S V I T A M I N E U P TO A C E R T A I N L E V E L T H R O U G H A R E D U C T I O N I N T H Y R O I D A C T I V I T Y . WlTH A L A R G E E X C E S S OF V I T A M I N E, H O W E V E R , NO F U R T H E R C O M P E N S A T I ON I S P O S S I B L E A N D R E S P I R A T I O N R A T E I S D E P R E S S E D BE LOW N O R M A L . E X C E S S V I T A M I N E C A U S E D H Y P O P R O T H R O M B I N E M I A , I N D I C A T I V E OF V I T A M I N K - D E F I C I E N C Y . O T H E R S Y M P T O M S N O T E D WERE A R E D U C T I O N I N H E M A T O C R I T V A L U E S , R E C T I C U L O C Y T O S I S A N D A N A B N O R M A L L Y F L U I D A P P E A R A N C E OF T H E B O N E M A R R O W . B A S E D U P O N O B S E R V A T I O N S O F B O N E C A L C I F I C A T I O N T H E C A L C I U M R E Q U I R E M E N T A P P E A R E D TO BE I N C R E A S E D I N T H E P R E S E N C E OF E X C E S S V I T A M I N E . B I B L I O G R A P H Y A L M Q U I S T , H . J . , 1 9 4 1 . R E P O R T ON V I T A M I N K : A S S A Y B Y C U R A T I V E B I O L O G I C A L T E S T . J . A s s o c . O F F . A N A L . C H E M . 2 4 : 4 0 5 - 4 1 3 . A L M Q U I S T , H . J . A N D S T O K S T A D , E . L . R . , 1 9 3 6 . F A C T O R S I N F L U E N C I N G T H E I N C I D E N C E OF D I E T A R Y H E M O R R H A G I C D I S E A S E I N C H I C K S . J . N U T R I T I O N 1 2 : 3 2 9 - 3 3 5 . A N D R E W , G . A . , 1 9 5 7 . A FEW N O T I O N S I N V O L V E D I N T H E C L I N I C A L U S E O F R A D I O I S O T O P E S . A N N . I N T E R N . M E D . 4 7 : 9 2 2 - 9 3 8 . A N D I K , I . , B A L O G H , L . A N D D O N H O F F E R , S . , 1 9 4 9 . T H E E F F E C T OF T H Y R O X I N E I N T H Y R O I D E C T O M I Z E D R A T S T R E A T E D W I T H M E T H Y L T H I O U R A C I L . E X P E R I E N T I A 5 : 2 4 9 - 2 5 0 . A N B A R , A . , I N B A R , M . A N D T A T A , J . R . , 1 9 6 5 . D I S S O C I A T I O N OF T H E C A L O R I G E N I C A C T I O N OF T H Y R O I D H O R M O N E F R O M T H E D E I O D I N A T I O N OF L - T H Y R O X I N E I N v i v o . A C T A E N D O C R I N O L . 4 8 : 5 0 6 - 5 1 2 . , 1 9 6 5 . V I T A M I N S A N D O T H E R N U T R I E N T S . I N A S S O C I A T I O N OF O F F I C A L A G R I C U L T U R E C H E M I S T S . 10TH E D I T I O N . A S T W O O D , E . B . , 1 9 4 5 . C H E M O T H E R A P Y OF H Y P E R T H Y R O I D I S M . H A R V E Y L E C T . 4 0 : 1 9 5 - 2 3 5 . A Z Z O N E , G . F . , E E G - O L O F S S O N , 0 . , E R N S T E R , L . , L U F T , R . AND S Z A B O L C S I , G . , 1 9 6 1 . S T U D I E S ON I S O L A T E D H U M A N S K E L E T A L M U S C L E M I T O C H O N D R I A . E X P . C E L L R E S . 2 2 : 4 1 5 - 4 3 6 . B A R K E R , S . D . , 1 9 5 5 . T H E C I R C U L A T I N G T H Y R O I D H O R M O N E , P P . 7 4 - 8 9 . B R O O K H A V E N S Y M P O S I A I N B I O L O G Y #7, " T H E T H Y R O I D " B R O O K H A V E N N A T I O N A L L A B O R A T O R Y , U P T O N , NEW Y O R K . B A R K E R ^ S . B . , K I E L Y , C . E . A N D L I P N E R , H . J . , 1 9 4 9 . M E T A B O L I C E F F E C T S OF T H Y R O X I N E I N J E C T E D I N T O N O R M A L , T H I O U R A C I L - T R E A T E D AND T H Y R O I D - E C T O M I Z E D R A T S . E N D O C R I N O L O G Y 4 5 : 6 2 4 - 6 2 9 . B I R D , J . W . , S C H O T T E L I U S , D . D . A N D S C H O T T E L I U S , B . A . , 1 9 6 3 . O X Y G E N C O N S U M P T I O N OF S O L E U S M U S C L E S F R O M N O R M A L , V I T A M I N E S U P P L E M E N T A N D V I T A M I N E D E F I C I E N T G U I N E A P I G S D U R I N G R E S T A N D S T I M U L A T I O N . M E T A B O L I S M 1 2 : 5 7 0 - 5 7 5 . 4 9 50 B R I E R L E Y , G . P . A N D M E R O L A , A . J . , 1 9 6 2 . S T U D I E S OF T H E E L E C T R O N - T R A N S F E R S Y S T E M . X L V I I I . P H O S P H O L I P I D R E Q U I R E M E N T S I N C Y T O C H R O M E O X I D A S E . B I O C H I M . B I O P H Y S . A C T A . 6 4 : 2 0 5 - 2 1 7 . B R I E R L E Y , G . P . , M E R O L A , A . J . A N D F L E I S C H E R , S . , 1 9 6 2 . S T U D I E S O F T H E E L E C T R O N - T R A N S F E R S Y S T E M . L L I X . S I T E S OF P H O S P H O L I P I D I N V O L V E M E N T I N T H E E L E C T R O N - E L E C T R O N - T R A N S F E R C H A I N . B L O C H I M . B I O P H Y S . A C T A . 6 4 : 2 1 8 - 2 2 8 . B R O W N - G R A N T , K . , 1 9 5 7 . T H E " F E E D - B A C K " H Y P O T H E S I S OF T H E C O N T R O L OF T H Y R O I D F U N C T I O N . C I B A F O U N D . C O L L O Q . ON E N D O C R I N O L O G Y 1 0 : 9 7 - 1 1 4 . B U N Y A N , J . , G R E E N , J . , E D W I N , E . E . AND D I P L O C K , A . T . , 1 9 6 0 . S T U D I E S ON V I T A M I N E . 5 . L I P I D P E R O X I D A T I O N I N D I A L U R I C A C I D - I N D U C E D H A E M O L Y S I S OF V I T A M I N E - D E F I C I E N T E R Y T H R O C Y T E S . B I O C H E M . J . 7 7 : 4 7 - 5 1 . C A L V E R T , C . C , N E S H E I M , M . C . AND S C O T T , M . L . , 1 9 6 2 . E F F E C T I V E N E S S OF S E L E N I U M I N P R E V E N T I O N OF N U T R I T I O N A L M U S C U L A R D Y S T R O P H Y I N T H E C H I C K . P R O C . S O C . E X P . B I O L . M E D . . 1 0 8 : 1 6 - 1 8 . C A P U T T O , R . , M C C A Y , P . B . A N D C A R P E N T E R , M . P . , 1 9 5 8 . R E Q U I R E M E N T OF M N + + A N D CA"1"*" F O R T H E S Y N T H E S I S OF A S C O R B I C A C I D B Y L I V E R E X T R A C T S OF A N I M A L S D E P R I V E D OF T O C O P H E R O L . J . B I O L . C H E M . 2 3 3 : 1 0 2 5 - 1 0 2 9 . C E N T U R Y , B . AND H O R W I T T , M . K . , 1 9 6 5 . B I O L O G I C A L A V A I L A B I L I T Y OF V A R I O U S F O R M S OF V I T A M I N E W I T H R E S P E C T TO D I F F E R E N T I N D I C E S OF D E F I C I E N C Y . F E D E R A T I O N P R O C . 2 4 : 9 0 6 - 9 1 1 . C E N T U R Y , B . A N D H O R W I T T , M . K . , 1 9 5 8 . S O M E F A C T O R S I N P R O D U C T I O N OF E N C E P H A L O M A L A C I A I N T H E V I T A M I N E D E F I C I E N T C H I C K . F E D E R A T I O N P R O C . 1 7 : 4 7 3 . C H A L K A F F , I. L . A N D T A U R O G , A . , 1 9 4 9 . T H E F O R M A T I O N OF O R G A N I C A L L Y - B O U N D I O D I N E C O M P O N E N T S I N T H E T H Y R O I D G L A N D AND T H E I R A P P E A R A N C E I N P L A S M A A S SHOWN B Y T H E U S E OF R A D I O A C T I V E I O D I N E . A N N . N . Y . A C A D . S c i . 5 0 : 3 7 7 - 4 0 2 . C H A P P E L L , J . B . AND P E R R Y , S . V . , 1 9 5 4 . B I O C H E M I C A L AND O S M O T I C P R O P E R T I E S OF S K E L E T A L M U S C L E M I T O C H O N D R I A . N A T U R E 1 7 3 : 1 0 9 4 - 1 0 9 5 . C H A P M A N , D . A N D L E S L I E , R . B . , 1 9 7 0 . S T R U C T U R E AND F U N C T I O N OF P H O S P H O L I P I D S I N M E M B R A N E S . |N M E M B R A N E S OF M I T O C H O N D R I A AND C H L O R O P L A S T S . P P . 9 1 - 1 2 6 . E D I T E D B Y R A C K E R , E . , V A N N A S T R A N D R E I N H O L D C O . , N . Y . C H E V I L L E , N . F . , 1 9 6 6 . T H E P A T H O L O G Y OF V I T A M I N E D E F I C I E N C Y I N T H E C H I C K . P A T H . V E T . 3 : 2 0 8 - 2 2 5 . C H R I S T E N S E N , F . , D A M , H . , G O R T N E R , R. A . AND S O N D E R G A A D , E . , 1 9 5 6 . IN V I T R O H E M O L Y S I S OF E R Y T H R O C Y T E S W I T H V I T A M I N E D E F I C I E N T R A T S A N D C H I C K S . A C T A P H Y S I O L . S C A N D I N A R I C A 3 5 : 2 1 5 - 2 2 4 . C O A T E S , V . A N D M A R C H , B . E . , 1 9 6 6 . ' R E C T I C U L O C Y T E C O U N T S I N T H E C H I C K S . P O U L T R Y S C I . 4 5 : 1 3 0 2 - 1 3 0 3 . C S A L L A N Y , A . S . A N D D R A P E R , H . H . A N D S H A N , S . N . , 1 9 6 2 . C O N V E R S I O N OF 14 D - O t - T O C O P H E R O L - C TO TOC O P H E R Y L - P - Q U I NON E I N V I V O . A R C H . B i o c H E M . B I O P H Y S . 9 8 : 1 4 2 - 1 4 5 . C S A L L A N Y , A . S . A N D D R A P E R , H . H . , 1 9 6 3 . D I ME R I Z A T I ON OF CCr TOC O P H E ROL I N v i v o . A R C H . B I O C H E M . B I O P H Y S . 1 0 0 : 3 3 5 - 3 3 7 . C U N N I N G H A M , L . W . , 1 9 6 4 . T H E R E A C T I O N OF ft-LACTOGLOBULIN S U L F E N Y L I O D I D E W I T H S E V E R A L A N T I T H Y R O I D A G E N T S . B I O C H E M I S T R Y ( W A S H . ) 3 : 1 6 2 9 - 1 6 3 4 . D A M , H . , P R A N G E , I. AND. S O N D E R G A A D , E . , 1 9 5 2 . T H E E F F E C T OF C E R T A I N S U B S T A N C E S ON V I T A M I N A S T O R A G E I N T H E L I V E R OF T H E R A T . A C T A P H A R M A C O L . T O X I C O L . 8 : 2 3 - 2 9 . D A M , H . , 1 9 5 7 . I N F L U E N C E OF A N T I O X I D A N T S AND R E D O X S U B S T A N C E S ON S I G N S OF V I T A M I N E D E F I C I E N C Y . P H A R M A C O L . R E V . 9 : 1 - 1 6 . D E M P S E Y , E . W . A N D A S T W O O D , E . B . , 1 9 4 3 . D E T E R M I N A T I O N OF T H E R A T E O F T H Y R O I D H O R M O N E S E C R E T I O N AT V A R I O U S E N V I R O N M E N T A L T E M P E R A T U R E S . E N D O C R I N O L O G Y 3 2 : 5 0 9 - 5 1 8 . D E M O L E , V . , 1 9 3 9 . P H A R M A K O L O G I S C H E S U B E R V I T A M I N E , V E R T R A G L I C H K E 1 T D E S S Y N T H E T I S C H E N D L - Oi-TOCOPHEROLS UND S E I N E S A C E T A T S . I N T E R N . Z . V i T A M i N F O R S C H 8 : 3 3 8 - 3 4 1 . D E S A I , I . D . , C A L V E R T , C . C , S C O T T , M . L . A N D T A P P E L , A . L . , 1 9 6 4 . P E R O X I D A T I O N A N D L Y S O S O M E S I N N U T R I T I O N A L M U S C U L A R D Y S T R O P H Y OF C H I C K S . P R O C . S O C . E X P . B I O L . M E D . 1 1 5 : 4 6 2 - 4 6 6 . D E S A I , I. D . A N D S C O T T , M . L . , 1 9 6 5 . M O D E OF A C T I O N OF S E L E N I U M I N R E L A T I O N TO B I O L O G I C A L A C T I V I T Y OF T O C O P H E R O L S . A R C H . B L O C H E M . B I O P H Y S . 1 1 0 : 3 0 9 - 3 1 5 . D E T W I L E R , T . C , G A R R E T T , R . H . AND N A S O N , A . , 1 9 6 6 . E F F E C T S OF D I G I T O N I N A N D T O C O P H E R O L ON B O V I N E H E A R T M U S C L E R E D U C E D D I P H O S - P H O P Y R I D I N E N U C L E O T I D E - A N D S U C C I N A T E - C Y T O C H R O M E C R E D U C T A S E AND C Y T O C H R O M E C O X I D A S E . J . B I O L . C H E M . 2 4 1 : 1 6 2 1 - 1 6 3 1 . 52 D R A P E R , H . H . , C S A L L A N Y , A . S . AND C H I U , M . , 1 9 6 7 . I S O L A T I O N OF A T R I M E R OF d-TOCOPHEROL F R O M M A M M A L I A N L I V E R . L I P I D S 2 : 4 7 - 5 4 . D U R A N D , N . , C Z Y H A , J . C , M O R N E X , R. AND R E R E S , G . , 1 9 6 8 . U P T A K E OF I 131 B Y T H Y R O I D OF G O L D E N H A M S T E R T R E A T E D W I T H V I T A M I N E A N D cL- T O C O P H E R Y L QU i N O N E . C . R. S o c . B i OL . 1 6 2 : 8 8 8 - 8 9 0 . C I T E D I N N U T R I T I O N A B S T . 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T H E E F F E C T OF T H I O U R A C I L ON T H E F O R M A T I O N OF T H Y R O X I N E A N D D I I O D O T Y R O S I N E B Y T H E T H Y R O I D G L A N D OF T H E R A T W I T H R A D I O A C T I V E I O D I N E A S I N D I C A T O R . E N D O C R I N O L O G Y 3 4 : 2 6 5 - 2 6 8 . F R I E D M A N , I . A N D M A T T I L L , H . A . , 1 9 4 1 . T H E O X Y G E N C O N S U M P T I O N OF S K E L E T A L M U S C L E F R O M A N I M A L S D E P R I V E D OF V I T A M I N E . A M E R . J . P H Y S I O L . . 1 3 1 : 5 9 5 - 6 0 0 . - G A L T O N , V . A . A N D I N G B A R , S . H . , 1 9 6 5 . E F F E C T S OF V I T A M I N D E F I C I E N C Y ON T H E J_N V I TRO AND J_N V I V O D E I O D I N A T I O N OF T H Y R O X I N E I N T H E R A T . E N D O C R I N O L O G Y 7 7 : 1 6 9 - 1 7 6 . G O R D O N , A . H . , G R O S S , J . , O ' C O N N O R , D . AND P I T T - R I V E R S , R . , 1 9 5 2 . N A T U R E OF T H E C I R C U L A T I N G T H Y R O I D H O R M O N E - P L A S M A P R O T E I N C O M P L E X . N A T U R E 1 6 9 : 1 9 - 2 0 . G O R N A L L , A . G . , B A R D A W I L L , C . J . AND D A V I D , M . M . , 1 9 4 9 . D E T E R M I N A T I O N OF S E R U M P R O T E I N B Y M E A N S OF T H E B I U R E T R E A C T I O N . J . B I O L . C H E M . 1 7 7 : 7 5 1 - 7 6 6 . G R E E N , J . , 1 9 6 2 . I N T E R R E L A T I O N S H I P S B E T W E E N V I T A M I N E A N D O T H E R V I T A M I N S A N D T H E U N I Q U I N O N E S . V I TAM |'NS A N D H O R M O N E S 2 0 : 4 8 5 - 4 9 1 . G R E E N , D . E . , W H A R T O N , D . C , T Z A G O L O F F , A . , R I E S K E , J . S . AND B R I E R L E Y , G . P . , 1 9 6 4 . T H E M I T O C H O N D R I A L E L E C T R O N - T R A N S F E R C H A I N , I N K I N G , T . E . , M A S O N , H . S . AND M O R R I S O N , M . , ( E D I T O R ) , O X I D A S E S A N D R E L A T E D R E D O X S Y S T E M S . 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S Y N D R O M E I N P R E M A T U R E I N F A N T S A S S O C I A T E D W I T H LOW P L A S M A V I T A M I N E L E V E L S A N D H I G H P O L Y U N S A T U R A T E D F A T T Y A C I D D I E T . A M E R . J . C L I N . N U T R I T I O N 1 9 : 1 4 7 - 1 5 7 . ' H E D M A N , H . , 1 9 6 5 . P R O P E R T I E S OF I S O L A T E D S K E L E T A L M U S C L E M I T O C H O N D R I A F R O M R A T . E x p . C E L L R E S . 3 8 : 1 - 1 2 . H E N D R I C H , C . E. A N D T U R N E R , C . W . , 1 9 6 3 . T I M E R E L A T I O N S I N T H E A L T E R A T I O N OF T H Y R O I D G L A N D F U N C T I O N I N F O W L S . P O U L T R Y S C I . 4 2 : 1 1 9 0 - 1 1 9 5 . H E N D R I C H , C . E . AND T U R N E R , C . W . , 1 9 6 4 . E S T I M A T I O N OF T H Y R O I D - S T I M U L A T I N G H O R M O N E ( T S H ) S E C R E T I O N R A T E S OF NEW H A M P S H I R E F O W L S . P R O C . S O C . E X P . B I O L . M E D . 1 1 7 : 2 1 8 - 2 2 2 . H E N D R I C H , C . E. AND T U R N E R , C . 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E F F E C T OF A N T I T H Y R O I D C O M P O U N D S ON T H E D E I O D I N A T I O N OF T H Y R O X I N E I N R A T S . E N D O C R I N O L O G Y 7 1 : 9 4 - 1 0 0 . H I L L M A N , R . W . , 1 9 5 7 . T O C O P H E R O L E X C E S S I N M A N . C R E A T I N U I A A S S O C I A T E D W I T H P R O L O N G E D I N G E S T I O N . A M E R . J . C L I N . N U T R I T I O N . 5 : 5 9 7 - 6 0 0 . H I M M E L , J . P . A N D M E L V I L L E , P . S . , 1 9 5 1 . R E S P I R A T I O N A N D G L Y C O L Y S I S OF R A B B I T M U S C L E I N V I T A M I N E D E F I C I E N C Y . J . B I O L . C H E M . 1 9 1 : 3 9 1 - 3 9 4 . H O F F M A N N , E . A N D S H A F F N E R , C . S . , 1 9 5 0 . T H Y R O I D W E I G H T A N D F U N C T I O N A S I N F L U E N C E D B Y E N V I R O N M E N T A L T E M P E R A T U R E . P O U L T R Y S C I . 2 9 : 3 6 5 - 3 7 6 . H O G N E S S , J . R . , W O N G , T . A N D W I L L I A M S , R . A F T E R I N J E C T I O N OF RAD I 0 - T H Y R O X I N E OR N O R M A L R A T S . M E T A B O L I S M 3 : 5 1 0 H O R W I T T , M. K . , H A R V E Y , C . C . AND H A R M A N , E . M . , 1 9 6 8 . L I P I D S , o C - T O C O P H E R O L A N D E R Y T H R O C Y T E H E M O L Y S I S . V I T A M I N S AND H O R M O N E S 2 6 : 4 8 7 - 4 9 9 . H O U C H I N , 0 . B . , 1 9 4 2 . T H E I N V I T R O E F F E C T OF O 6 - T O C O P H E R O L A N D I T S P H O S P H A T E D E R I V A T I VE - ON O X I D A T I O N I N M U S C L E T I S S U E . J . B L O L . C H E M . 1 4 6 : 3 1 3 - 3 2 1 . H O U C H I N , 0 . B . A N D M A T T I L L , H . A . , 1 9 4 2 A . T H E O X Y G E N C O N S U M P T I O N , C R E A T I N E A N D C H L O I D E C O N T E N T OF M U S C L E S F R O M V I T A M I N E - D E F I C I E N T A N I M A L S A S I N F L U E N C E D B Y F E E D I N G - T O C O P H E R O L . J . B I O L . C H E M . 1 4 6 : 3 0 1 - 3 0 7 . H O U C H I N , 0 . B . A N D M A T T I L L , H . A . , 1 9 4 2 B . T H E I N F L U E N C E OF P A R E N T E R A L A D M I N I S T R A T I O N 0 F c ( - T O C O P H E R O L P H O S P H A T E ON T H E M E T A B O L I C P R O C E S S E S I N D Y S T R O P H I C M U S C L E . J . B I O L . C H E M . 1 4 6 : 3 0 9 - 3 1 2 . H O U C H I N , 0 . B . A N D M A T T I L L , H . A . , 1 9 4 2 c . I N V I T R O E F F E C T OF ( ^ - T O C O P H E R O L P H O S P H A T E ON O X Y G E N C O N S U M P T I O N OF M U S C L E F R O M V I T A M I N E D E F I C I E N T A N I M A L S . P R O C . S O C . E X P . B I O L . M E D . 5 0 : 2 1 6 - 2 1 8 . H U M E , E . M . , 1 9 4 1 . S T A N D A R D I Z A T I O N OF V I T A M I N E . N A T U R E 1 4 8 : 4 7 2 - 4 7 3 . H U S T O N , T . M . , E D W A R D S , H . M . A N D W I L L I A M , J . J . , 1 9 6 2 . T H E E F F E C T S OF H I G H E N V I R O N M E N T A L T E M P E R A T U R E ON T H Y R O I D S E C R E T I O N R A T E OF D O M E S T I C F O W L . P O U L T R Y S c I . 4 1 : 6 4 0 - 6 4 4 . J L R O U S E K , L . A N D C U N N I N G H A M , L . M . , 1 9 6 8 . S T I M U L A T I O N OF T H I O U R A C I L B I N G I N G A N D T H E I O D I NAT I ON S Y S T E M I N B E E F T H Y R O I D M I C R O S O M E S . B I O C H I M . B I O P H Y S . A C T A 1 7 0 : 1 6 0 - 1 7 1 . H . , 1 9 5 4 . I E X C R E T I O N I N T O H Y P E R T H Y R O I D , H Y P O T H Y R O I D - 5 1 7 . 56 J O I N E R , W . P . A N D H U S T O N , T . M . , 1 9 5 7 . T H E I N F L U E N C E OF H I G H E N V I R O N - M E N T A L T E M P E R A T U R E ON I M M A T U R E D O M E S T I C F O W L . P O U L T R Y S c i . 3 6 : 9 7 3 - 9 7 8 . 1 31 J O N E S , S . L . A N D V A N M I D D L E S W O R T H , L . ; 1 9 6 0 . N O R M A L I L - T H Y R O X I N E M E T A B O L I S M I N T H E P R E S E N C E OF P O T A S S I U M P E R C H L O R A T E AND I N T E R R U P T E D B Y P R O P Y L T H I O U R A C I L . E N D O C R I N O L O G Y 6 7 : 8 5 5 - 8 6 1 . K A U N I T Z , H . AND P A P P E N H E I M E R , A . 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C Y T O L . 9 : 4 0 9 - 4 1 4 . M A D S E N , L . L . , 1 9 3 6 . T H E C O M P A R A T I V E E F F E C T S OF COD L I V E R O I L , COD T H E D E V E L O P M E N T OF N U T R I T I O N A L M U S C U L A R D Y S T R O P H Y . J . N U T R I T I O N 1 1 : 4 7 1 - 4 9 4 . M A L A M E D , S . , 1 9 6 3 . U S E OF A M I C R O C E N T R I F U G E F O R P R E P A R A T I O N OF I S O L A T E D M I T O C H O N D R I A AND C E L L S U S P E N S I O N S F O R E L E C T R O N M I C R O S C O P Y . J . C E L L B I O L . 1 8 : 6 9 6 - 7 0 0 . M A L O O F , F . AND S O O D A F , M . , 1 9 6 3 . I N T E R M E D I A R Y M E T A B O L I S M OF T H Y R O I D T I S S U E A N D T H E A C T I O N OF D R U G S . P H A R M A C O L . R E V . 1 5 : 4 3 - 9 5 . M A R C H , B . E . , B I E L Y , J . A N D C O A T E S , V . , 1 9 6 8 . T H E I N F L U E N C E OF D I E T ON T O X I C I T Y OF T H E A N T I O X I D A N T 1 , 2 - D I H Y D R O - 6 - E T H O X Y - 2 , 2 , 4 - T R I M E T H Y L Q U I N O L I N E . C A N A D . J . P H Y S I O L . P H A R M A C O L . 4 6 : 1 4 5 - 1 4 9 . M A S O N , K . E . , 1 9 4 9 . V I T A M I N E . A N N . N . Y . A C A D . S C I . 5 2 : 6 3 - 4 2 8 . M A T T I L L , H . A . , 1 9 5 2 . V I T A M I N E . N U T R I T I O N R E V . 1 0 : 2 2 5 - 2 2 6 . M E L L E T T E , S . J . AND L E O N E , L . A . , 1 9 6 0 . I N F L U E N C E OF A G E , ' S E X , S T R A I N OF R A T AND F A T S O L U B L E V I T A M I N S ON H E M O R R H A G I C S Y N D R O M E S I N R A T S F E D I R R A D I A T E D B E E F . F E D E R A T I O N P R O C . 1 9 : 1 0 4 5 - 1 0 4 9 . 57 M O O R E , T . , 1 9 5 9 . V I T A M I N E AND U B I Q U I N O N E . N A T U R E 1 8 4 : 6 0 7 - 6 0 8 . N A D L E R , N . AND L E B L O N D , C . P . , 1 9 5 5 . T H E S I T E AND R A T E OF F O R M A T I O N OF T H Y R O I D H O R M O N E . B R O O K H A V E N S Y M P O S I A 7 : 4 0 - 6 0 . O L I V E I R A , M . , W E G L I C K I , W. B . , N A S O N , A . A N D N A I R , P . P . , 1 9 6 9 . D I S T R I B U T I O N O F O C - T O C O P H E R O L I N B E E F H E A R T M I T O C H O N D R I A . B I O C H I M . B I O P H Y S . A C T A 1 8 0 : 9 8 - 1 1 3 . P R E M A C H A N D R A , B . N . , P I P E S , G . W . A N D T U R N E R , C . W . , 1 9 5 8 . T H Y R O X I N E S E C R E T I O N R A T E S OF TWO S T R A I N S OF NEW H A M P S H I R E C H I C K E N S S E L E C T E D F O R H I G H A N D LOW R E S P O N S E TO T H I O U R A C I L . P O U L T R Y S C I . 3 7 : 3 9 9 - 4 0 4 . P U D E L K I EW I C Z , W.' J . , W E B S T E R , L . A N D M A T T E R S O N , L . D . , 1 9 6 4 . E F F E C T S H I G H L E V E L S OF D I E T A R Y V I T A M I N A A C E T A T E ON T I S S U E T O C O P H E R O L A N D S O M E R E L A T E D A N A L Y T I C A L O B S E R V A T I O N S . J . N U T R I T I O N 8 4 : 1 1 3 - 1 . 1 7 . Q U I C K , A . J . , 1 9 3 6 . ON V A R I O U S P R O P E R T I E S OF T H R O M B O P L A S T I N . A M E R . J . P H Y S I O L . 1 1 4 : 2 8 2 - 2 9 6 . 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W . 31 . 5 C ° 6 . 2 0 ± 0 . 6 4 6 . 0 5 ± 0 . 8 9 F E E D C O N S U M E D P E R • C H I C K I N 13 1 4 . 5 C ° 549 561 D A Y S G M . 3 1 . 5 C ° . 362 357 E X C E S S V 1 T A M 1 N E T E M P E R A T U R E TH I O U R A C I L + T H 1 O U R A C 1 L T H Y R O I D W E I G H T 1 4 . 5 C ° 1 2 3 . 1 0 ± 2 5 . 3 0 1 0 5 . 6 3 ± 1 6 . 4 4 MG . 3 1 . 5 C ° 1 0 9 . 3 1 t 2 5 . 0 3 9 4 . 0 6 ± 1 6 . 6 9 B O D Y W E I G H T 1 4 . 5 C ° 335±35 342±34 G M . 3 1 . 5 C ° 350+31 353±32 T H Y R O I D W T . 1 4 . 5 C ° 34.03±5.11 3 0 . 9 8 ± 4 . 0 7 M G . / 1 0 0 G M . B . W . 31 . 5 C ° 3 1 . 0 9 ± 5 . 2 7 2 6 . 6 3 ± 4 . 3 6 F E E D C O N S U M E D P E R C H I C K I N 13 D A Y S G M . 1 4 . 5 C ° 3 1 . 5 C ° 4 2 3 328 416 3 3 3 6 4 T A B L E 4 . - - A N A L Y S I S o r V A R I A N C E O F T H Y R O I D A L R E S P O N S E TO THE E X C E S S V I T A M I N E A N D / O R T H I O U R A C I L AT D I F F E R E N T T E M P E R A T U R E S I N E X P E R I M E N T 1 A . S O U R C E D F M E A N S Q U A R E F T E M P E R A T U R E ( A ) 1 2 9 2 . 8 4 2 4 . 6 1 1 * V I T A M I N E ( B ) .1 1 6 5 . 1 6 9 2 . 6 0 1 T H I O U R A C I L ( C ) 1 6 0 0 5 . 4 5 0 9 4 . 5 6 0 * * AB 1 2 . 7 9 9 0 . 0 4 4 BC 1 . 1 6 7 . 1 7 9 2 . 6 3 2 AC 1 1 2 4 . 6 1 4 1 . 9 6 2 E R R O R 4 1 6 3 . 5 0 9 T O T A L . 4 7 S I G N I F I C A N T ( P « = 0 . 0 5 ) . H I G H L Y S I G N I F I C A N T ( P < 0 . 0 1 ) . 6 5 T A B L E 5 . - - A N A L . Y S I S OF V A R I A N C E OF T H Y R O I D A L R E S P O N S E TO T H E E X C E S S V I T A M I N E AND/oR T H I O U R A C I L AT D I F F E R E N T T E M P E R A T U R E S I N E X P E R I M E N T 1 B . S O U R C E D F M E A N S Q U A R E F T E M P E R A T U R E ( A ) 1 1 0 3 . 9 3 7 5 . 9 8 2 * V 1 T A M I N E ( B ) 1 1 6 6 . 5 1 9 9 . 5 8 4 * * T H I O U R A C I L ( C ) 1 1 7 5 2 3 . 5 1 2 1 0 0 8 . 6 0 6 * * A B 1 0 . 1 6 4 0 . 0 0 9 4 BC 1 • 1 7 8 . 2 0 2 1 0 . 2 5 7 * * AC . 1 2 3 8 . 7 5 4 1 3 . 7 4 2 * * E R R O R 1 0 9 1 7 . 3 7 4 T O T A L 1 1 5 S I G N I F I C A N T ( P < 0 . 0 5 ) . H I G H L Y S I G N I F I C A N T ( P < 0 . 0 1 ) . 6 6 T A B L E 6 . — A V E R A G E T H Y R O I D W E I G H T S , B O D Y W E I G H T S , F E E D C O N S U M P T I O N OF E Q - T R E A T E D C H I C K S AT 2 2 C ° I N E X P E R I M E N T 1 B . EQ EQ + T H 1 O U R A C I L C O N T R O L T H 1 O U R A C I L T H Y R O I D W E I G H T MG . 2 5 . 9 0 ± 6 . 0 9 1 3 8 . 2 8 ± 3 4 . 1 4 2 8 . 7 3 ± 7 . 1 1 4 9 . 8 2 ± 1 1 . 8 3 B O D Y W E I G H T G M . 3 0 7 ± 4 7 3 1 3 ± 3 6 3 5 3 ± 4 1 . 4 3 8 0 ± 3 0 T H Y R O I D W T . M G . / 1 0 0 G M . B . W . 8 . 5 0 ± 1 . 6 7 4 3 . 6 7 ± 7 . 7 C V 8 . 0 9 ± 1 . 5 8 1 3 . 2 2 ± 3 . 4 5 F E E D C O N S U M E D P E R C H I C K I N 1 3 D A Y S G M . 2 9 2 . 3 0 2 3 3 3 3 1 8 67 T A B L E 7 . - - E F F E C T OF E X C E S S D I E T A R Y V I T A M I N E ON T H Y R O I D A L I O D I N E ( l ) U P T A K E A N D R E L E A S E I N W H I T E L E G H O R N M A L E C H I C K S . A . M E A N VALUES, THYROIDAL LEVEL OF J 3 1 of 1 PER BIRD:$ OF INJECTED D O S E i S . D 5 HR 10 HR 24 HR 48 HR 96 HR B A S A L 1 1 . 7 5 ± 1 . 5 2 1 0 . 6 8 ± 2 . 03 1 1 . 1 7 ± 3 . 2 5 9 . 6 0 ± 2 . 5 7 7 . 1 7 ± 2 . 19 E X C E S S V1TAMIN E 8 . 1 1 ± 1 . 6 9 9 . 3 5 ± 2 . 19 1 0 . 2 6 ± 2 . 2 4 9 . 1 4 ± 2 . 1 6 9 . 8 6 ± 2 . 68 B . M E A N VALUES, THYROIDAL LEVEL OF I 131 I ifo OF INJECTED D O S E / M G . TH YRO I D±S . D . 5 HR 10 HR 24 HR 48 HR 96 HR B A S A L 0 .427±0.061 0 . 4 3 3 ± 0 . 0 3 7 E X C E S S V I T A M I N E 0 . 3 0 6 ± 0 . 0 4 7 0 .363±0.081 0 . 4 6 6 ± 0 . 0 6 3 0 . 3 5 5 ± 0 . 0 5 9 0 . 3 1 7 ± 0 . 0 4 5 0 . 3 6 2 ± 0 . 0 4 b 0 . 3 2 3 ± 0 . 0 5 3 0 . 3 4 2 ± 0 . 0 5 7 68 T A B L E 8 . - - R E S P I R A T I O N R A T E S OF M U S C L E M I T O C H O N D R I A F R O M T H E C H I C K S F E D THE C O N T R O L D I E T , E X C E S S V I T A M I N E A N D / O R T H I O U R A C I L . I N C U B A T I O N WAS A T 3 0 ° C . I N C U B A T I ON P E R i O D C O N T R O L D I E T A R Y T R E A T M E N T E X C E S S V t T A M i N E T H I O U R A C I L E X C E S S V I T A M i N E + T H I O U R A C I L 0 - 3 0 M I N . 3 0 - 6 0 M I N . 6 0 - 9 0 M I N . 9 0 - 1 2 0 M I N . T O T A L U L / H R / M G . P R O T E I N ( 7 ) ° 1 1 . 8 0 ± 2 . 7 8 12.03±1 . 1 8 1 0 . 7 1 ± 3 . 1 9 7 . 0 1 ± 2 . 6 2 (? ) 7 . 0 5 ± 3 . 2 8 7 . 7 0 ± 3 . 3 6 8 . 0 3 ± 4 . 6 5 4 . 6 4 ± 2 . 2 0 4 1 . 5 5 ± 8 . 2 2 A 2 7 . 4 2 ± 1 2 . 8 1 B 2 0 . 7 8 ± 4 . 1 1 A 13 .71±6.41 B (6) ' 8 . 5 0 ± 3 . 8 5 8 . 8 4 ± 2 . 8 9 8 . 5 1 ± 2 . 6 2 6 . 3 5 ± 2 . 4 7 3 2 . 2 0 ± 1 1 . 6 7 ' 1 6 . 1 0 ± 5 . 8 4 A (7) 5 . 3 7 ± 1 . 9 4 4 .84±2.21 4 .44±1.91 3 . 9 7 ± 2 . 0 6 1 8 . 6 3 ± 7 . 6 4 9 . 3 2 ± 3 . 8 2 E B B O D Y W E I G H T ( G M . ) 597±91 363±60 482±66 332±40 E X P R E S S E D A S U L 0^ U P T A K E P E R M G . M I T O C H O N D R I A L P R O T E I N ± S . D . D U R I N G S U C C E S S . ! V E 30 M I N U T E P E R I O D S . " V A L U E S W I T H I N A L I N E H A V I N G T H E S A M E S U P E R S C R I P T A R E NOT S T A T I S T I C A L L Y D I F F E R E N T A T T H E 5 $ L E V E L OF P R O B A B I L I T Y B Y T H E D U N C A N ' S M U L T I P L E R A N G E T E S T . ^ N U M B E R O F C H I C K S T E S T E D . T A B L E 9 . - - C O M P O S I T I O N OF T H E E X P E R I M E N T A L D I E T S . D I E T 1 B A S A L ' D I E T 2 +C A D I E T 3 + E X C E S S + V I T A M I N E D I E T 4 + E X C E S S +V I T A M I N E + C A % % % B A S A L D I E T 9 8 . 0 9 8 . 0 9 8 . 0 9 8 . 0 © C E L L U L O S E 2 . 0 2 . 0 B O N E M E A L 1 . 5 1 . 5 L I M E S T O N E 0 . 5 0 . 5 T O T A L 1 0 0 . 0 1 0 0 . 0 1 0 0 . 0 1 0 0 . 0 D L - O C - T O C O P H E R Y L A C E T A T E ( | . U . / K G ) 1 0 . 1 0 . 2 2 0 0 2 2 0 0 B A S A L D I E T WAS T H E S A M E A S SHOWN I N T A B L E 1 A . T A B L E 1 0 . . . — E - F F E C T OF E X C E S S V I T A M I N E ON H E M A T O C R I T V A L U E , P R O T H R O M B I N T I M E A N D R E C T I C U L O C Y T E C O U N T . A G E OF C H I C K S ( D A Y S ) B A S A L B A S A L + C A L C i U M D I E T E X C E S S V I T A M I N E E X C E S S V I T A M i N E + C A L C I U M H E M A T O C R I T ± S . D . 30 4 0 50 2 4 . 9 4 ± 1 . 5 7 2 5 . 0 8 ± 1 . 5 0 2 7 . 6 3 ± 1 . 7 8 28 .06±0.81 B 2 7 . 6 9 ± 0 . 7 2 2 7 . 0 0 ± 2 . 1 8 1 4 . 5 1 + 2 . 5 7 1 3 . 8 1 ± 3 . 5 4 B 21 . 6 7 + 2 . 1 8 B 1 8 . 1 3 ± 0 . 7 8 1 5 . 8 9 ± 2 . 3 7 2 3 . 5 8 ± 2 . 0 6 B B P R O T H R O M B I N T I M E ( S E C O N D S ) 30 40 5 6 . 9 4 ± 4 . 9 0 4 3 . 4 4 ± 5 . 1 9 5 1 . 9 0 ± 6 . 7 2 3 8 . 2 8 ± 5 . 5 8 9 6 . 3 6 ± 1 2 . 4 4 B 1 4 1 . 6 0 ± 1 8 . 7 8 9 2 . 3 4 ± 9 . 7 5 B 1 0 5 . 0 0 ± 1 8 . 3 3 R E C T I C U L O C Y T E ± S . D . 30 40 50 1 . 7 3 ± 0 . 9 5 1 2 . 9 8 ± 2 . 7 0 1 1 . 9 2 ± 3 . 2 5 10.68±1 . 0 2 9 . 6 5 ± 0 . 7 3 1 1 . 6 4 + 1 . 2 0 4 7 . 4 5 ± 3 . 9 9 B 4 2 . 0 8 ± 9 . 3 7 B 5 2 . 4 4 ± 5 . 0 2 4 4 . 5 0 ± 9 . 1 7 B 4 0 . 6 0 ± 1 9 . 0 7 2 4 . 3 8 ± 3 . 8 3 B B 1 V A L U E S W I T H I N A L I N E H A V I N G T H E S A M E S U P E R S C R I P T A R E NOT S T A T I S T I C A L L Y D I F F E R E N T A T T H E 1$ L E V E L OF P R O B A B I L I T Y B Y T H E D U N C A N ' S NEW M U L T I P L E R A N G E T E S T . 71 T A B L E 11 - - P R O T H R O M B I N T I M E OF C H I C K S F E D E X C E S S V I T A M I N E , 24 HOURS A F T E R I N J E C T I O N OF M E N A D I O N E . E X C E S S Y I T A M i N E E X C E S S (24 HR A F T E R I N J . C O N T R O L V I T A M I N E OF M E N A D I O N E ) P R O T H R O M B I N T I M E ( S E C O N D S ) 3 4 . 7 ± 3 . 8 7 7 . 9 ± 1 5 . 9 2 7 . 1 ± 3 . 2 72 T A B L E 1 2 . — E F F E C T OF E X C E S S V I T A M I N E ON B O N E C A L C I F I C A T I O N I N C H I C K S F E D D I E T S A D E Q U A T E AND D E F I C I E N T I N C A L C I U M . A G E OF C H I C K S B O D Y ( D A Y S ) W E I G H T A S H $ 30 229±81.7 3 5 . 7 4 ± 4 . 0 4 G R O U P 1 ' B A S A L 4 0 333±75 4 2 . 1 4 ± 0 . 5 2 5 0 497+110 4 3 . 9 7 ± 3 . 2 2 30 169±43 31 . 6 1 1 3 . 4 3 B A S A L G R O U P 2 E X C E S S 4 0 202±37 3 6 . 7 6 ± 2 . 4 2 + V 1 T A M 1 N E 5 0 338.9±38 3 7 . 8 3 ± 2 . 1 3 30 257±23 4 5 . 9 4 ± 0 . 8 7 B A S A L G R O U P 3 + C A L C 1 U M 40 307+42 4 6 . 7 1 ± 0 . 9 0 5 0 513±48 4 7 . 2 0 ± 2 . 3 9 3 0 231±28 4 5 . 5 4 ± 0 . 5 6 B A S A L G R O U P 4 + E X C E S S 4 0 250±32 4 8 . 2 0 ± 1 . 3 6 V 1 T A M 1 N E + C A L C 1 U M 5 0 416±55 4 6 . 9 2 ± 0 . 6 6

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