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Biomedical subjects

I Ueda

Publications and source records attributed to I Ueda.

At least 181 records · Page 10Linked to original sources

Partition equilibrium of inhalation anesthetics and alcohols between water and membranes of phospholipids with varying acyl chain-lengths.

From the depression of the phase-transition temperature of phospholipid membranes, the partition coefficients of inhalation anesthetics (methoxyflurane, halothane, enflurane, chloroform and diethyl ether) and alcohols (benzyl alcohol and homologous n-alcohols up to C = 7) between phospholipid vesicle membranes and water were determined. The phospholipids used were dimyristoyl-, dipalmitoyl- and distearoylphosphatidylcholines. It was found that the difference in the acyl chain length of the three phospholipids did not affect the partition coefficients of the inhalation anesthetics and benzyl alcohol. The actions of these drugs are apparently directed mainly to the interfacial region. In contrast, n-alcohols tend to bind more tightly to the phospholipid vesicles with longer acyl chains. The absolute values of the transfer free energies of n-alcohols increased with the increase of the length of the alkyl chain of the alcohols. The increment was 3.43 kJ per each carbon atom. The numerical values of the partition coefficients are not identical when different expressions for solute concentrations (mole fraction, molality and molarity) are employed. The conversion factors among these values were estimated from the molecular weights and the partial molal volumes of the phospholipids in aqueous solution determined by oscillation densimetry.

Alcohols↗

Interfacial preference of anesthetic action upon the phase transition of phospholipid bilayers and partition equilibrium of inhalation anesthetics between membrane and deuterium oxide.

The half-height linewidth (v 1/2) of the 1H-NMR spectra of dipalmitoylphosphatidylcholine vesicles changes abruptly at the phase transition temperature. In the absence of inhalation anesthetics, proton signals from the choline head group (hydrophilic interface) and acyl-chain tails (lipid core) change at the same temperature of 39.6 degrees C. The present study compared the effect of four inhalation anesthetics, i.e., methoxyflurane, chloroform, halothane and enflurane, upon the ligand-induced phase transition of phosphatidylcholine vesicle membranes at 37 degrees C. The anesthetics showed differential action upon the phase transition of the phospholipid vesicle membranes between the lipid core and the hydrophilic interface. The concentrations of anesthetics which induced the phase transition of the lipid core were about 2-fold greater than those required for the phase transition of the interfacial choline head groups. From the area under the proton signals of inhalation anesthetics in the NMR spectra, the maximum solubilities of methoxyflurane, chloroform and halothane in 2H2O at 37 degrees C were determined to be 0.671 . 10(-4), 2.637 . 10(-4) and 1.398 . 10(-4) (expressed as mole fractions), or 3.35, 13.17 and 6.98 mmol/1000 g 2H2O, respectively. The solubilities of the anesthetic vapor in 2H2O expressed as mole fractions according to Henry's law ere 9.586 . 10(-4), 6.432 . 10(-4) and 2.311 10(-4)/atm (1.013 . 10(5) Pa) partial pressure, respectively. The presence of phospholipid vesicles in 2H2O increased the solubility of the inhalation anesthetics. From difference between solubility in 2H2O and a dipalmitoylphosphatidylcholine vesicle suspension, the partition coefficients of methoxyflurane, chloroform and halothane between the phospholipid vesicle membranes and 2H2O were estimated. These values, calculated from the mole fractions, were 3364, 1660 and 3850, respectively at 37 degrees C.

Anesthetics↗

Anesthetics and high-pressure interaction upon elastic properties of a polymer membrane.

Anesthetics expand cell membranes, and high pressures (about 10-15 MPa) antagonize the anesthetic action. It is also known that inhalation anesthetics expand elastomer membranes. The mechanism of pressure antagonism of anesthetic action on membrane expansion was investigated in the present study with Silastic membranes. Halothane increased the length of Silastic membrane (0.14% per kPa), with an accompanying decrease of Young's modulus (3.7.10(5) Newton/m2 per kPa). High pressure decreased the length of the membrane and increased Young's modulus. The magnitudes of the pressure effect on the length and Young's modulus of the Silastic membrane in the presence of the anesthetic were not identical with those observed in the absence of the anesthetic. In the presence of halothane at pressures common to clinical applications, the bulk modulus of the membrane decreased about 4.6-4.0%. These results suggest that the effects of pressure and anesthetic upon the elastomer may not be completely independent of each other.

Adsorption↗

Reaction kinetics in living systems.

In this report we treat reaction rates, equilibrium theory, and irreversible thermodynamics as different aspects of a single discipline. In biological reactions the rate is ultimately controlled by enzymes and other proteins of complex structure and high molecular weight. The needed formalism can be placed in one-to-one correspondence with appropriate electrical and mechanical networks. An enzyme molecule has zwitter ions anchored in the polypeptide chain, which enable it to distort the substrate by electrostatic polarization. Water weakens the induced or existing polar bonds and so speeds reaction. Several biological processes, such as luminescence, catalysis, nerve excitation, and anesthesia, in which enzymatic reactions play a major part are discussed from this point of view. We also have discussed the energy consumption and coupling effect in living systems. It is likely that a small fraction of bonds can become energy rich through the process of quenching and that unsymmetrical barriers in biological systems act like transistors in making the driving forces more efficient by a valve effect.

Anesthetics↗

Pressure-anesthetic antagonism on the phase separation of non-ionic surfactant micelles.

An aqueous solution of non-ionic surfactants becomes suddenly turbid when heated to a critical temperature, known as the cloud point, and concomitantly expands the volume. The volume expansion is caused by release of structured water molecules from the hydrophilic polyoxyethyelene moieties. Inhalation anesthetics decreased the cloud-point temperature of hexaoxyethylene dodecyl ether micelles. The concentrations of methoxyflurane, halothane and enflurane causing a 1 degree C depression of the cloud-point temperature were 0.51, 0.71 and 0.78 mmolal, respectively. Hydrostatic pressure increased the cloud-point temperature in the absence and presence of the anesthetics. The change of the apparent molal volume at the cloud point was estimated to be 2.2 cm3/mol in the absence of anesthetics. This value decreased in the presence of the anesthetics, dose dependently. The results indicate that the anesthetics favor dehydration of the hydrophilic surface of the non-ionic surfactant micelles.

Anesthetics↗

Surface activities of tertiary amine local anesthetics at air/water interface in the presence and absence of phospholipid monolayers.

Adsorption of procaine and tetracaine to the dipalmitoyl phosphatidylcholine monolayers at the air/water interface is analyzed in terms of two types of interaction: (1) between the phospholipid molecules and the ligand molecules, and (2) among the ligand molecules themselves. The presence of the phospholipid monolayer increases the surface concentration of the anesthetics. The interaction energy, omega AB, between the phospholipid molecules and the anesthetic molecules at the interface accounts for this excess adsorption. The values were --2.95 kT for procaine and --2.99 kT for tetracaine where k is the Boltzmann constant and T = 298 K. The adsorption of the local anesthetics to the interface was cooperative. The interaction energy, omega AA, between the anesthetics molecules on the surface determines the cooperativity. The values were --0.056 kT for procaine and --0.397 kT for tetracaine, where T = 298 K. This parameter determines the slope of the curve plotted relating the surface concentration (gamma) and the logarithm of the bulk concentration (log C). When (omega AA/kT) greater than or equal to 1, the adsorption follows the phase-transition. A parameter KA, which is related to the difference of the free energy of anesthetics between the surface and the bulk molecules, locates the take-off point of the adsorption curve at the log C axis. The values were 2.15 x 10(3) for procaine and 7.00 x 10(3) for tetracaine. In spite of the general assumption that the difference in the clinical potency among local anesthetics are attributable to their lipid solubility, the present results showed that the phospholipid-anesthetic interaction energies for procaine and tetracaine were similar. The larger surface concentration of tetracaine than procaine at the same bulk concentration was due to the combined effect of KA and omega AA. KA represents the tendency of the anesthetic molecules to escape from the hydrogen-bonded water phase, and omega AA determines the cooperativity factor causing these molecules to aggregate at the interface. It was also observed that the charged forms of the anesthetics have non-zero surface activities.

Adsorption↗

Immaturity of the enzyme activity and the response to inducers of rat liver cysteine dioxygenase during development.

Cysteine dioxygenase activity was not detected in the liver of either fetal or 2-day-old rat. The enzyme activity of neonatal rat liver gradually increased between the 4th and 12th postnatal days and then sharply increased to reach the adult level by the 28th postnatal day. No cysteine dioxygenase activity was observed in the fetal liver at the 18th day of gestation from a dam injected with hydrocortisone. Hydrocortisone-mediated induction was first observed in the livers of 4-day-old rats. The duration of hydrocortisone-mediated induction was much longer in the livers of 4- to 12-day-old rats than in those of adult rats. The enzyme half-life in livers of 10- and 20-day-old rats was 6.4 and 3.7 h, respectively. The half-life of the enzyme in 20-day-old rat liver was increased to 6.2 h by L-cysteine injection.

Aging↗

Antagonism between high pressure and anesthetics in the thermal phase-transition of dipalmitoyl phosphatidylcholine bilayer.

The antagonizing action of hydrostatic pressure against anesthesia is well known. The present study was undertaken to quantitate the effects of hydrostatic pressure and anesthetics upon the phase-transition temperature of dipalmitoyl phosphatidylcholine vesicles. The drugs used to anesthetize the phospholipid vesicles included an inhalation anesthetic, halothane, a dissociable local anesthetic, lidocaine and an undissociable local anesthetic, benzyl alcohol. All anesthetics decreased the phase-transition temperature dose-dependently. In the case of lidocaine, the depression was pH dependent and only uncharged molecules were effective. The application of hydrostatic pressure increased the phase-transition temperature both in the presence and the absence of anesthetics. The temperature-pressure relationship was linear over the entire pressure range studied up to 340 bars. Through the use of Clapeyron-Clausius equation, the volume change accompanying the phase-transition of the membrane was calculated to be 27.0 cm3/mol. Although the anesthetics decreased the phase-transition temperature, the molar volume change accompanying the phase-transition was not altered. The anesthetics displaced the temperature-pressure lines parallel to each other. The mole fraction of the anesthetics in the liquid crystalline membrane, calculated from the van't Hoff equation, was independent of pressure. This implies that pressure does not displace the anesthetics from the liquid membrane, and the partition of these agents remains constant. The volume change of the anesthetized phospholipid membranes is entirely dependent upon the phase-transition and not on the space occupied by the anesthetics.

Anesthetics↗