An Equation for the Prediction of Human Skin Permeability of Neutral Molecules, Ions and Ionic Species

yesExperimental values of permeability coefficients, as log Kp, of chemical compounds across human skin were collected by carefully screening the literature, and adjusted to 37 °C for the effect of temperature. The values of log Kp for partially ionized acids and bases were separated into those for their neutral and ionic species, forming a total data set of 247 compounds and species (including 35 ionic species). The obtained log Kp values have been regressed against Abraham solute descriptors to yield a correlation equation with R2 = 0.866 and SD = 0.432 log units. The equation can provide valid predictions for log Kp of neutral molecules, ions and ionic species, with predictive R2 = 0.858 and predictive SD = 0.445 log units calculated by the leave-one-out statistics. The predicted log Kp values for Na+ and Et4N+ are in good agreement with the observed values. We calculated the values of log Kp of ketoprofen as a function of the pH of the donor solution, and found that log Kp markedly varies only when ketoprofen is largely ionized. This explains why models that neglect ionization of permeants still yield reasonable statistical results. The effect of skin thickness on log Kp was investigated by inclusion of two indicator variables, one for intermediate thickness skin and one for full thickness skin, into the above equation. The newly obtained equations were found to be statistically very close to the above equation. Therefore, the thickness of human skin used makes little difference to the experimental values of log Kp

The prediction of blood–tissue partitions, water–skin partitions and skin permeation for agrochemicals

YesBACKGROUND: There is considerable interest in the blood–tissue distribution of agrochemicals, and a number of researchershave developed experimental methods for in vitro distribution. These methods involve the determination of saline–blood andsaline–tissue partitions; not only are they indirect, but they do not yield the required in vivo distribution.RESULTS: The authors set out equations for gas–tissue and blood–tissue distribution, for partition from water into skin andfor permeation from water through human skin. Together with Abraham descriptors for the agrochemicals, these equationscan be used to predict values for all of these processes. The present predictions compare favourably with experimental in vivoblood–tissue distribution where available. The predictions require no more than simple arithmetic.CONCLUSIONS: The present method represents a much easier and much more economic way of estimating blood–tissuepartitions than the method that uses saline–blood and saline–tissue partitions. It has the added advantages of yielding therequired in vivo partitions and being easily extended to the prediction of partition of agrochemicals from water into skin andpermeation from water through skin

A simple method for estimating in vitro air-tissue and in vivo blood-tissue partition coefficients

YesA simple method is reported for the estimation of in vivo air-tissue partition coefficients of VOCs and of in vitro blood-tissue partition coefficients for volatile organic compounds and other compounds. Linear free energy relationships for tissues such as brain, muscle, liver, lung, kidney, heart, skin and fat are available and once the Abraham descriptors are known for a compound, no more than simple arithmetic is required to estimate air-tissue and blood-tissue partitions

The assessment of intramolecular hydrogen bonding in ortho-substituted anilines by an NMR method

YesWe describe the Δlog P method for the assessment of intramolecular hydrogen bonds (IMHBs), and show that it is not a very general method of distinguishing between molecules in which there is an IMHB and molecules in which there is no IMHB. The ‘double’ Δlog P method of Shalaeva et al. is a much more reliable method for the assessment of IMHB but requires the synthesis of a model compound and the determination of no less than four water-solvent partition coefficients. In addition, it is difficult to apply to compounds that contain more than one hydrogen bond acidic group capable of IMHB. We then describe our NMR method of assessing IMHB, based on 1H NMR chemical shifts in solvents DMSO and CDCl3. We have determined 1H NMR chemical shifts for a number of ortho-substituted anilines and show that the only compound we have studied that forms an IMHB is methyl 2-methylaminobenzoate though there is no IMHB present in methyl 2-aminobenzoate. This apparently anomalous result is supported by both MM and ab initio calculations. The NMR method is much simpler and less time consuming than other methods for the assessment of IMHB. It provides a quantitative assessment of IMHB and can be applied to molecules with more than one hydrogen bond acidic group

Bosons in anisotropic traps: ground state and vortices

We solve the Gross-Pitaevskii equations for a dilute atomic gas in a magnetic trap, modeled by an anisotropic harmonic potential. We evaluate the wave function and the energy of the Bose Einstein condensate as a function of the particle number, both for positive and negative scattering length. The results for the transverse and vertical size of the cloud of atoms, as well as for the kinetic and potential energy per particle, are compared with the predictions of approximated models. We also compare the aspect ratio of the velocity distribution with first experimental estimates available for $^{87}$Rb. Vortex states are considered and the critical angular velocity for production of vortices is calculated. We show that the presence of vortices significantly increases the stability of the condensate in the case of attractive interactions.Comment: 22 pages, REVTEX, 8 figures available upon request or at http://anubis.science.unitn.it/~dalfovo/papers/papers.htm

Stability of Bose condensed atomic Li-7

We study the stability of a Bose condensate of atomic $^7$Li in a (harmonic oscillator) magnetic trap at non-zero temperatures. In analogy to the stability criterion for a neutron star, we conjecture that the gas becomes unstable if the free energy as a function of the central density of the cloud has a local extremum which conserves the number of particles. Moreover, we show that the number of condensate particles at the point of instability decreases with increasing temperature, and that for the temperature interval considered, the normal part of the gas is stable against density fluctuations at this point.Comment: Submitted for publication in Physical Review

Low energy collective excitations in a superfluid trapped Fermi gas

We study low energy collective excitations in a trapped superfluid Fermi gas, that describe slow variations of the phase of the superfluid order parameter. Well below the critical temperature the corresponding eigenfrequencies turn out to be of the order of the trap frequency, and these modes manifest themselves as the eigenmodes of the density fluctuations of the gas sample. The latter could provide an experimental evidence of the presence of the superfluid phase.Comment: 5 pages, REVTeX, referencies correcte

Simultaneous Magneto-Optical Trapping of Two Lithium Isotopes

We confine 4 10^8 fermionic 6Li atoms simultaneously with 9 10^9 bosonic 7Li atoms in a magneto-optical trap based on an all-semiconductor laser system. We optimize the two-isotope sample for sympathetic evaporative cooling. This is an essential step towards the production of a quantum-degenerate gas of fermionic lithium atoms.Comment: 4 pages, 3 figure

Resonance Superfluidity: Renormalization of Resonance Scattering Theory

We derive a theory of superfluidity for a dilute Fermi gas that is valid when scattering resonances are present. The treatment of a resonance in many-body atomic physics requires a novel mean-field approach starting from an unconventional microscopic Hamiltonian. The mean-field equations incorporate the microscopic scattering physics, and the solutions to these equations reproduce the energy-dependent scattering properties. This theory describes the high-$T_c$ behavior of the system, and predicts a value of $T_c$ which is a significant fraction of the Fermi temperature. It is shown that this novel mean-field approach does not break down for typical experimental circumstances, even at detunings close to resonance. As an example of the application of our theory we investigate the feasibility for achieving superfluidity in an ultracold gas of fermionic $^6$Li.Comment: 15 pages, 10 figure

EFFECT OF CORTISOL TREATMENT ON HORMONAL RELATIONSHIPS IN CONGENITAL ADRENAL HYPERPLASIA

The temporal relationship between administration of cortisol and serum 17Α-hydroxyprogesterone was investigated in five patients aged 9-19 years with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. There was marked variability in the 17Α-hydroxyprogesterone response (determined hourly for 24 h) of individual patients to administration of cortisol. Mean concentration was less than 0.030 Μmol/l in one patient but 0.519Μ mol/l in another. Levels were higher in all patients while off treatment, and were greatest in those with salt-losing adrenal hyperplasia. Growth hormone secretion was not suppressed by treatment with cortisol. Withdrawal of cortisol for 3 days resulted in a significant decrease in the mean serum FSH/LH ratio and a rise in serum testosterone in all subjects. Episodic release of gonadotrophins persisted in the adolescent patients.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75713/1/j.1365-2265.1977.tb02002.x.pd