﻿572 
  ANNUAL 
  REPORT 
  SMITHSONIAN 
  INSTITUTION, 
  1943 
  

  

  many 
  of 
  the 
  unpleasant 
  and 
  dangerous 
  complications 
  of 
  sulfapyridine 
  

   and 
  is 
  somewhat 
  more 
  effective. 
  Sulfadiazine, 
  the 
  latest 
  of 
  this 
  group, 
  

   is 
  about 
  as 
  effective 
  as 
  sulfathiazole 
  but 
  is 
  less 
  toxic 
  and 
  is 
  easily 
  tol- 
  

   erated 
  by 
  most 
  people. 
  Up 
  to 
  this 
  point 
  the 
  usefulness 
  of 
  these 
  

   drugs 
  has 
  been 
  evaluated 
  for 
  systemic 
  diseases 
  like 
  pneumonia, 
  men- 
  

   ingitis, 
  or 
  infection 
  of 
  the 
  blood 
  stream 
  with 
  streptococcus. 
  In 
  these 
  

   cases 
  sulfonamides 
  are 
  given 
  by 
  mouth 
  and 
  the 
  drug 
  is 
  distributed 
  

   through 
  the 
  body. 
  A 
  localized 
  infection 
  in 
  one 
  part 
  of 
  the 
  body 
  like 
  

   a 
  limb 
  or 
  the 
  abdomen 
  can 
  be 
  treated 
  by 
  placing 
  the 
  drug 
  directly 
  in 
  

   the 
  wound 
  in 
  contact 
  with 
  the 
  infection 
  zone. 
  This 
  provides 
  a 
  high 
  

   concentration 
  of 
  drug 
  immediately 
  in 
  the 
  dangerous 
  infection 
  zone 
  

   without 
  subjecting 
  the 
  entire 
  body 
  to 
  the 
  treatment. 
  

  

  There 
  are, 
  however, 
  certain 
  practical 
  difficulties. 
  These 
  drugs 
  do 
  

   not 
  dissolve 
  well 
  and 
  tend 
  to 
  lump 
  or 
  "cake" 
  when 
  poured 
  into 
  wounds. 
  

   In 
  addition, 
  pus 
  and 
  partly 
  devitalized 
  tissues 
  are 
  excellent 
  nourish- 
  

   ment 
  for 
  the 
  bacteria 
  and 
  sometimes 
  interfere 
  with 
  the 
  action 
  of 
  the 
  

   sulfonamides. 
  

  

  Studies 
  in 
  this 
  laboratory 
  were 
  focused 
  on 
  the 
  local 
  use 
  of 
  these 
  

   drugs 
  as 
  a 
  problem 
  of 
  military 
  importance. 
  It 
  soon 
  became 
  apparent 
  

   that 
  the 
  order 
  of 
  increasing 
  therapeutic 
  potency 
  — 
  sulfanilamide, 
  sul- 
  

   fapyridine, 
  sulfathiazole, 
  and 
  sulfadiazine 
  — 
  was 
  a 
  consequence 
  of 
  a 
  

   single 
  physicochemical 
  characteristic 
  : 
  increasing 
  degrees 
  of 
  ionization 
  

   of 
  these 
  weak 
  acids. 
  It 
  was 
  of 
  further 
  interest 
  that 
  the 
  more 
  ef- 
  

   fective 
  drugs 
  were 
  likewise 
  more 
  effective 
  in 
  overcoming 
  the 
  block- 
  

   ing 
  effect 
  of 
  PAB. 
  It 
  was 
  then 
  found 
  that 
  acidity 
  which 
  reduced 
  

   the 
  ionization 
  of 
  these 
  drugs 
  likewise 
  reduced 
  their 
  activity 
  against 
  

   bacteria. 
  In 
  addition, 
  acidity 
  also 
  reduced 
  the 
  solubility 
  of 
  these 
  

   substances. 
  

  

  Measurements 
  at 
  the 
  bedside 
  showed 
  that 
  infected 
  wounds 
  usually 
  

   become 
  extremely 
  acidic. 
  This 
  acidity 
  is 
  sufficient 
  to 
  reduce 
  markedly 
  

   the 
  antibacterial 
  activity 
  of 
  sulfanilamide 
  and 
  sulfapyridine 
  and 
  to 
  

   prevent 
  sulfathiazole 
  or 
  sulfadiazine 
  powder 
  from 
  freely 
  dissolving 
  

   in 
  the 
  infection 
  zone. 
  In 
  addition, 
  this 
  acidity 
  tends 
  to 
  destroy 
  the 
  

   white 
  blood 
  corpuscles 
  or 
  leucocytes. 
  Since 
  these 
  cells 
  are 
  needed 
  

   to 
  dispose 
  of 
  the 
  sulfonamide-treated 
  bacteria, 
  they 
  must 
  be 
  preserved 
  

   to 
  help 
  eradicate 
  invading 
  bacteria. 
  Clinical 
  trials 
  have 
  shown 
  that 
  

   by 
  using 
  the 
  soluble 
  sodium 
  salts 
  of 
  sulfathiazole 
  or 
  sulfadiazine 
  (in- 
  

   stead 
  of 
  the 
  insoluble 
  acids 
  themselves) 
  the 
  interference 
  of 
  wound 
  

   acidity 
  can 
  be 
  minimized 
  and 
  wound 
  infections 
  can 
  be 
  controlled. 
  

   The 
  chemically 
  "activated" 
  drug 
  is 
  held 
  in 
  solution 
  in 
  the 
  infection 
  

   zone 
  ; 
  and, 
  with 
  the 
  cooperation 
  of 
  the 
  leucocytes, 
  speedily 
  eradicates 
  

   the 
  bacteria. 
  

  

  It 
  is 
  important 
  to 
  realize 
  that 
  this 
  can 
  be 
  accomplished 
  without 
  

   harming 
  the 
  tissues. 
  On 
  the 
  other 
  hand, 
  antiseptics 
  such 
  as 
  iodine 
  

  

  