X-Message-Number: 11883
Date: Fri, 4 Jun 1999 00:44:39 -0700 (PDT)
From: Doug Skrecky <>
Subject: could ultrasound be useful in cryonics?

Citations: 1-5
  Wu J.  Chappelow J.  Yang J.  Weimann L.
  Department of Physics, University of Vermont, Burlington 05405, USA.
  Defects generated in human stratum corneum specimens by
  Ultrasound in Medicine & Biology.  24(5):705-10, 1998 Jun.
  Over the last two decades, ultrasound (US) has been applied
  to enhance transdermal drug delivery. This method is called sonophoresis. The
  physical mechanism of the enhancement is far from being fully understood. It
  has been shown in our study that 168-kHz continuous US of spatially averaged
  pressure amplitude of 1.9 x 10(5) Pa induced a new structural state and
  generated defects (entrapped air pockets) in human stratum corneum specimens.
  The dimensions of the defects were found to be about 20 microns, large enough
  to allow the transdermal passage of high-molecular-weight drug molecules that
  normally elude the unenhanced transdermal drug delivery.

  Johnson ME.  Mitragotri S.  Patel A.  Blankschtein D.  Langer R.
  Department of Chemical Engineering, Massachusetts Institute of Technology,
  Cambridge 02139, USA.
  Synergistic effects of chemical enhancers and therapeutic
  ultrasound on transdermal drug delivery.
  Journal of Pharmaceutical Sciences.  85(7):670-9, 1996 Jul.
  The effects of (i) a series of chemical enhancers and (ii) the combination of
  these enhancers and therapeutic ultrasound (1 MHz, 1.4
  W/cm2, continuous) on transdermal drug transport are investigated. A series
  of chemical enhancer formulations, including (i) polyethylene glycol 200
  dilaurate (PEG), (ii) isopropyl myristate (IM), (iii) glycerol trioleate
  (GT), (iv) ethanol/pH 7.4 phosphate buffered saline in a 1:1 ratio (50%
  EtOH), (v) 50% EtOH saturated with linoleic acid (LA/EtOH), and (vi)
  phosphate buffered saline (PBS), as a control, are evaluated using
  corticosterone as a model drug. LA/EtOH is the most effective of these
  enhancers, increasing the corticosterone flux by 900-fold compared to that
  from PBS. Therapeutic ultrasound (1 MHz, 1.4 W/cm2,
  continuous) increases the corticosterone permeability from
  all of the enhancers examined by up to 14-fold (LA/EtOH) and increases the
  corticosterone flux from the saturated solutions by up to 13,000-fold
  (LA/EtOH), relative to that from PBS. Similar enhancements are obtained with
  LA/EtOH with and without ultrasound for four other model
  drugs, dexamethasone, estradiol, lidocaine, and testosterone. The
  permeability enhancements for all of these drugs resulting
  from the addition of linoleic acid to 50% EtOH increase with increasing drug
  molecular weight. Likewise, the permeability enhancement
  attained by ultrasound and LA/EtOH relative to passive EtOH
  exhibits a similar size dependence. A mechanistic explanation of this size
  dependence is provided. It is suggested that bilayer disordering agents, such
  as linoleic acid and ultrasound, transform the SC lipid
  bilayers into a fluid lipid bilayer phase or create a separate bulk oil
  phase. The difference in diffusivity of a given solute in SC bilayers and in
  either fluid bilayers or bulk oil is larger for larger solutes, thereby
  producing greater enhancements for larger solutes.

  Patrick JT.  Nolting MN.  Goss SA.  Dines KA.  Clendenon JL.  Rea MA. 
  Heimburger RF.
  Department of Neurology, Indiana University School of Medicine, Indianapolis.
  Ultrasound and the blood-brain barrier.
  Advances in Experimental Medicine & Biology.  267:369-81, 1990.
  High intensity focused ultrasound was employed to modify the
  permeability of the normal feline and canine blood-brain
  barrier (BBB) to a circulating vital dye--Evans blue (EB). The threshold
  doses (W sec/cm2) for focally increasing the permeability of
  the BBB in white matter (WM) and gray matter (GM) were as follows: internal
  capsule (WM)--340 to 680; thalamus (GM)--approximately 1326; and caudate
  nucleus (GM)--2284 to 2952. In the presence of supralesioning doses of
  ultrasound, the cross sectional area occupied by the EB was
  consistently greater than that of the attendant nonhemorrhagic lesion--thus
  suggesting that BBB changes may be inducible at sublesioning doses. These
  findings, in conjunction with those of others, suggest that high intensity
  focused ultrasound may have a role in the treatment of brain
  tumors based on cell destruction by two mechanisms: (a) direct, by the
  ultrasound and (b) indirect, by an antineoplastic agent
  which is delivered via an ultrasonically modified BBB.

  Velling VA.  Shklyaruk SP.
  Physiological Division, I.P. Pavlov Scientific Research Institute of
  Experimental Medicine, Academy of Medical Sciences of the USSR, Leningrad.
  Modulation of the functional state of the brain with the aid of focused
  ultrasonic action.
  Neuroscience & Behavioral Physiology.  18(5):369-75, 1988 Sep-Oct.
  We investigated the possibility of modifying the functional state of the
  brain with the aid of focused ultrasound and studied various
  regimes of its action. A specific pattern in the effect of focused ultrasonic
  action was discovered with regard to its intensity: the effect is absent at
  low (less than 0.1 mW/cm2) intensities; activation of bioelectrical activity
  in the brain takes place at intensities from 1 to 100 mW/cm2; and suppression
  of the ECoG takes place at intensities from 1 to 100 W/cm2. On the basis of
  our own data and the data in the literature, we suggest that the mechanism of
  ultrasound action is based upon changes in the
  permeability of neuronal membranes leading, after a chain of
  intracellular molecular reactions, to a subsequent general de- or
  hyperpolarization of the membranes of neuronal populations and to a change in
  the bioelectrical activity of the brain.

  Velling VA.  Shkliaruk SP.
  [Modulation of the functional state of the brain using focused
  ultrasound]. [Russian]
  Fiziologicheskii Zhurnal SSSR Imeni I. M. Sechenova.  73(6):708-14, 1987 Jun.
  The effects of focused ultrasonic action (SUA) on the brain functional state
  was found to depend on the intensity: there was no effect at 0.1 mWt/cm2
  whereas an activation of the brain activity occurred at 1-100 mWt/cm2. The
  SUA 1-100 Wt/cm2 suppressed the ECoG. The mechanism of the SUA effect is
  supposed to be based on a change in permeability of neuronal
  membrane leading through a chain of intracellular molecular reactions to
  general de- or hyperpolarization of membranes of the neuronal populations and
  to a change in the brain activity.

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