By T. Muntasir. The National Graduate School.
Varying the pulse shape according to the skin’s speciﬁc electrical impedance promotes the transdermal delivery of drugs as in classical iontophoresis super viagra 160mg erectile dysfunction over the counter, despite the fact that the average current is zero cheap super viagra 160 mg online erectile dysfunction surgery cost. Moreover, macromolecules are transdermally delivered from an iontophoretic device. The absence of a temporary pH change allows the use of microdermabrasion before dermoelectroporation application. Pretreatment with microdermabrasion promotes the transdermal delivery rate and ensures repeatability as a result of the standardization of the thickness and permeability of the stratum corneum. The pulse shapes operate at a much lower energy and penetrate even under high skin-impedance conditions. A capacitor is charged to a value of some hundred volts and then discharged on the tissue to be electroporated. If the load is purely resistive, the voltage waveform obtained is an exponential decay curve. The maximum peak current occurs at the begin- ning of the discharge and the value is given by the ratio, charge voltage/load resistance. Unfortunately, the living skin has a signiﬁcant capacitance in parallel to the resistive load. This means that at the beginning of the discharge the resulting current is very high for a short period of time until the skin capacitance is charged to a value close to the voltage of the electroporation capacitor; then the exponential current decay curve occurs. Moreover, the skin impedance and the resulting current are functions of several variables—skin condition, pressure of the electrode on the skin, moisture, stratum corneum thickness, etc. This occurs despite the fact that the current in the in vivo applica- tion is a critical parameter, because skin damage occurs when the current density is too high. The electric circuit based on the capacitor is intrinsically unsafe because the peak value current is unpredictable. Strict international rules limit the maximum current density ROLE OF DERMOELECTROPORATION & 293 applicable to the skin and this limits the practical application of classical electroporation. For this reason the authors experimented with a different type of circuit that is intrinsically safe, verifying if transdermal transport of molecules and macromolecules occurs as in clas- sical electroporation despite the limited density of current. The circuit uses an inductor instead of a capacitor as a means to store energy and obtain a pulse with exponential decay equivalent to the one obtained by the circuit based on a capacitor. The circuit with the inductor is able to deliver a pure resistance with the same waveform of the circuit based on the capacitor. The advantage occurs when the load is a resistance in parallel with a capacitance as in the living skin. In this case, at the beginning of the discharge, the value of the current is the maximum value during the pulse. The voltage waveform is variable and depends on the characteristics of the load. The parameters chosen are 2 mA, maximum peak pulse current of 5 mA (value at the beginning of the discharge), and 2 a drug-soaked electrode surface of 3. Such values are capable on a 20 kX load to generate a peak voltage value of 200 V. To maximize the effect and add an iontophoretic transport mechanism, the pulses have been grouped in bursts at a frequency of 2200 Hz. The burst is composed of a sequence of negative and positive symmetric pulses and no direct current is applied. To avoid the stimulation of muscles under the electrode area, a novel electrode geometry has been chosen. The return electrodes are designed around the active electrode soaked with the ionic substance to be transder- mally delivered. In this way the current ﬂows only inside the dermis and no current ﬂows into the muscles under the skin. The treatment requires bimonthly or monthly sessions—a total of four to eight—of a procedure consisting ﬁrst of superﬁcial microdermabrasion intended for the removal of the corneus layer and for vascularization. These crystals are then used with a manual massage to promote further mechanical smoothing of the skin. Immediately afterwards, active substances such as col- lagen, hyaluronic acid, amino acids, and elastin or, better, their precursors are introduced by means of the dermoelectroporation treatment as previously described. Cellulite requires integrated treatments according to the various pathologies described below. When the dermabra- sion treatment requires deeper effects that may cause pain, a session of dermoelectropora- tion treatment is used ﬁrst to introduce an anesthetic (2% lidocaine without epinephrine).
Echo or resonance techniques or the interferometric method are used for this purpose buy super viagra 160mg low cost erectile dysfunction causes mnemonic. These serve as a reﬁned means for the physical research of the structural properties of mat- ter discount super viagra 160 mg mastercard erectile dysfunction pills herbal. The applications of ultrasound in diagnosis, in which reﬂex signals (or transmitted sig- nals) are employed across tissues, are based on the quasioptical properties of ultrasound. It is easy to generate very intense ultrasonic waves. This enables their use to cause modiﬁcations and effects of a varied nature (physical, chemical, and biological) in the trea- ted medium. All these effects are due to strong mechanical stress linked to elastic waves of high intensity and their respective thermic effects. When the irradiated medium is a liquid and ultrasound intensity is enough to cause cavitation, cavitation seems to play a deter- mining role in the modiﬁcations induced by the treatment. The proper use of treatment requires an adequate selection of the ultrasound intensity. When the absolute pressure turns lower than the liquid vapor pressure, a violent develop- ment of vapor in the form of small bubbles takes place. At the same time (due to the effect of Henry’s law), a separation of water–dissolved air is produced. Cavitation can occur in a tube with a neck in which an increase in velocity means a decrease in pressure (Bernoulli’s theorem). Cavitation may occur toward the tips of the buckets of jet hydraulic turbine runners or pumps and on the blades of sea propellers. The rapid formation and destruction of vapor bubbles give rise to a rapid series of collisions, subjecting the metal walls to intense stress and causing great corrosion. It has been demonstrated that the pressure originated from bubble bursting can achieve, in situ, 1000 atm (explaining the strong corrosion). The following formula of the cavitation number describes the cavitation phenomenon: Pa þ Ps þ Pv n ¼ ðd=2ÞÂV2 where Pa, Ps, and Pv are pressure at the free surface of ﬂuid, hydrostatic pressure at the considered point, and vapor pressure, respectively; d is ﬂuid density and V is velocity of undisturbed ﬂuids. The tendency of ﬂuids to cavitate depends inversely on their intensity and velocity of movement, and directly on the pressures applied. The micromechanical unidirectional effects cause, through direct action, displace- ment of intracellular organic molecules with frequent diffusion into the extracellular space, rupture of macromolecular chromosomes, molecule conglomerates originating from the rupture of intermolecular bonds, modiﬁcation in protein spatial structure, formation of free radicals, denaturation of cell membrane components, and electrochemical modiﬁca- tions in cell surface. Ultrasonic waves can be compared to a strong wind striking biological materials with power proportional to ultrasound intensity. This wind causes, depending on its strength, displacements, ruptures, and variations in the shape of biological molecules. The mechanical drive may cause displacement of macromolecules out of their normal cell compartments and, thus, disorders in cell function. Biological functions of macromolecules are conditioned by their presence in the site of reaction. When mechanical waves achieve enough strength, macromolecule ﬂexion and even rupture can occur with its consequent functional loss. Formation of highly reactive oxygen free radicals is another mechanism involved in the damage of surrounding biological structures. The most common process of ultrasound micromechanical activity is protein denaturation. SURGICAL TREATMENT E: ULTRASONIC HYDROLIPOCLASIS & 243 From a stereochemical viewpoint, proteins are made up of primary, secondary, and tertiary structures. Primary structures are possible thanks to peptide bonds—covalent bonds requiring high energy supply to be split. On the other hand, the remaining struc- tures are possible thanks to weak bonds (polar, or hydrogen) requiring a certain spatial closeness of the constituent groups. Because they are weak bonds, weak energy is enough to split them and to separate the constituent chemical groups. Spatial distance hinders, then, the new formation of the same bonds. This causes serious functional damage because it is precisely due to secondary and tertiary structures that proteins form active loci.
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