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 <1> Authors Wu J. Chappelow J. Yang J. Weimann L. Institution Department of Physics, University of Vermont, Burlington 05405, USA. Title Defects generated in human stratum corneum specimens by ultrasound. Source Ultrasound in Medicine & Biology. 24(5):705-10, 1998 Jun. Abstract 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. <2> Authors Johnson ME. Mitragotri S. Patel A. Blankschtein D. Langer R. Institution Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge 02139, USA. Title Synergistic effects of chemical enhancers and therapeutic ultrasound on transdermal drug delivery. Source Journal of Pharmaceutical Sciences. 85(7):670-9, 1996 Jul. Abstract 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. <3> Authors Patrick JT. Nolting MN. Goss SA. Dines KA. Clendenon JL. Rea MA. Heimburger RF. Institution Department of Neurology, Indiana University School of Medicine, Indianapolis. Title Ultrasound and the blood-brain barrier. Source Advances in Experimental Medicine & Biology. 267:369-81, 1990. Abstract 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. <4> Authors Velling VA. Shklyaruk SP. Institution Physiological Division, I.P. Pavlov Scientific Research Institute of Experimental Medicine, Academy of Medical Sciences of the USSR, Leningrad. Title Modulation of the functional state of the brain with the aid of focused ultrasonic action. Source Neuroscience & Behavioral Physiology. 18(5):369-75, 1988 Sep-Oct. Abstract 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. <5> Authors Velling VA. Shkliaruk SP. Title [Modulation of the functional state of the brain using focused ultrasound]. [Russian] Source Fiziologicheskii Zhurnal SSSR Imeni I. M. Sechenova. 73(6):708-14, 1987 Jun. Abstract 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. Rate This Message: http://www.cryonet.org/cgi-bin/rate.cgi?msg=11883