﻿552 
  ANNUAL 
  REPORT 
  SMITHSONIAN 
  INSTITUTION, 
  194 
  3 
  

  

  greatly 
  influenced 
  by 
  the 
  composition 
  of 
  the 
  medium. 
  In 
  the 
  presence 
  

   of 
  glucose 
  (or 
  some 
  other 
  substrates), 
  phosphate, 
  and 
  potassium, 
  low 
  

   concentrations 
  of 
  gramicidin 
  markedly 
  stimulate 
  the 
  respiration 
  of 
  

   various 
  cells. 
  Small 
  amounts 
  of 
  certain 
  substances, 
  e. 
  g., 
  the 
  am- 
  

   monium 
  ion, 
  prevent 
  this 
  stimulatory 
  effect. 
  Higher 
  concentrations 
  

   of 
  gramicidin 
  may 
  cause 
  complete 
  inhibition 
  of 
  respiration. 
  It 
  is 
  

   known 
  that 
  the 
  cellular 
  oxidation 
  of 
  carbohydrate 
  is 
  brought 
  about 
  

   by 
  means 
  of 
  certain 
  phosphoric 
  acid 
  compounds. 
  Recently 
  there 
  has 
  

   been 
  procured 
  evidence 
  that 
  the 
  formation 
  of 
  one 
  of 
  these 
  compounds, 
  

   adenosine 
  triphosphoric 
  acid, 
  may 
  be 
  inhibited 
  by 
  gramicidin. 
  This 
  

   agent 
  thus 
  does 
  not 
  behave 
  as 
  a 
  gross 
  protoplasmic 
  poison 
  but 
  appears 
  

   to 
  exert 
  its 
  bacteriostatic 
  effect 
  through 
  an 
  interference 
  with 
  the 
  

   energy-supplying 
  processes 
  of 
  the 
  cell. 
  

  

  The 
  antibacterial 
  activity 
  of 
  both 
  gramicidin 
  and 
  tyrocidine 
  is 
  

   reduced 
  by 
  serum 
  and 
  tissue 
  extracts. 
  Tyrocidine 
  is 
  inhibited 
  also 
  by 
  

   proteins 
  and 
  peptones. 
  Of 
  a 
  large 
  number 
  of 
  pure 
  substances 
  which 
  

   have 
  been 
  tested, 
  only 
  a 
  few, 
  belonging 
  to 
  the 
  class 
  of 
  phospholipides, 
  

   have 
  been 
  found 
  to 
  possess 
  the 
  ability 
  of 
  diminishing 
  the 
  gramicidin 
  

   potency. 
  A 
  gramicidin-neutralizing 
  fraction 
  rich 
  in 
  phospholipides 
  

   can 
  also 
  be 
  obtained 
  from 
  Gram-negative 
  bacilli 
  ; 
  whether 
  this 
  ma- 
  

   terial 
  plays 
  a 
  role 
  in 
  the 
  nonsusceptibility 
  of 
  Gram-negative 
  organ- 
  

   isms 
  to 
  gramicidin 
  has 
  not 
  yet 
  been 
  established. 
  

  

  Both 
  gramicidin 
  and 
  tyrocidine 
  are 
  quite 
  toxic 
  when 
  administered 
  

   intravenously 
  or 
  intraperitoneally. 
  This, 
  together 
  with 
  the 
  lowered 
  

   effectiveness 
  in 
  the 
  presence 
  of 
  various 
  biological 
  substances, 
  would 
  

   appear 
  to 
  preclude 
  the 
  therapeutic 
  application 
  in 
  systemic 
  infections. 
  

   For 
  the 
  treatment 
  of 
  many 
  types 
  of 
  localized 
  infections 
  the 
  prospects 
  

   are 
  much 
  brighter. 
  A 
  considerable 
  number 
  of 
  clinical 
  trials 
  with 
  

   very 
  favorable 
  results 
  have 
  already 
  been 
  reported. 
  In 
  vivo, 
  gramicidin 
  

   is 
  a 
  much 
  more 
  active 
  agent 
  than 
  tyrocidine. 
  In 
  practice 
  the 
  mix- 
  

   ture 
  of 
  the 
  two 
  — 
  tyrothricin 
  — 
  has 
  been 
  used 
  much 
  more 
  extensively 
  

   than 
  gramicidin 
  itself, 
  inasmuch 
  as 
  it 
  appears 
  to 
  possess 
  some 
  ad- 
  

   vantages, 
  as 
  well 
  as 
  being 
  much 
  more 
  easily 
  produced. 
  Tyrothricin 
  

   is 
  now 
  commercially 
  available. 
  

  

  Among 
  the 
  diseases 
  which 
  have 
  shown 
  favorable 
  response 
  to 
  tyro- 
  

   thricin 
  therapy 
  are 
  inflammations 
  of 
  the 
  nose 
  and 
  sinuses, 
  bladder 
  

   infections, 
  empyema 
  due 
  to 
  streptococci, 
  postoperative 
  wounds, 
  and 
  

   burns. 
  Skin 
  ulcers 
  which 
  had 
  persisted 
  for 
  years, 
  despite 
  various 
  

   forms 
  of 
  treatment, 
  have 
  healed 
  after 
  a 
  few 
  weeks, 
  or 
  even 
  days, 
  of 
  

   tyrothricin 
  therapy. 
  In 
  general, 
  streptococcal 
  infections 
  are 
  more 
  

   amenable 
  than 
  those 
  clue 
  to 
  staphylococci 
  or 
  pneumococci. 
  Good 
  re- 
  

   sults 
  have 
  been 
  obtained 
  also 
  in 
  the 
  treatment 
  of 
  bovine 
  mastitis, 
  a 
  

   streptococcal 
  infection 
  of 
  the 
  cow's 
  udder. 
  

  

  