Short echo time MRI enables visualisation of the natural state of human stratum corneum water in vivo.

High resolution magnetic resonance imaging studies on skin have been limited by their inability to detect the low-moisture-content outer layers near the surface of the stratum corneum. The hydration of these outer layers is especially important physiologically. The present study shows that by using a short echo time of 5 ms it becomes possible to observe these layers in all but a few individuals with exceptionally dry skin. The quality of the images can be further improved by the use of separate transmit and receive coils, which reduces the rapid fall-off in signal intensity encountered with a single surface coil used both to transmit and receive.

Skin mechanics measured in vivo using torsion: a new and accurate model more sensitive to age, sex and moisturizing treatment.

Summary Measurements of skin mechanics are required to understand better cracking and flaking of the epidermis and loss of 'elasticity'with age in the dermis. Improvements in torsional testing are described here. The resulting data was fitted to algebraic models, the parameters of which can serve both as a concise description of the responses and as a means of relating them to skin structure and physiology. This investigation looks into the suitability of seven such algebraic models. Five of the models examined here appear to be new. Using the commercially available Dia-Stron DTM Torque Meter with our own software, model parameters were studied as indicators of the effects of age and sex in 41 people, and of skin moisturizing treatments in a further 10 people. The two models in the literature were both found to be substantially less accurate and sensitive representations of experimental data than one of the new models proposed here based on the Weibull distribution. This 'WB model'was consistently the one best able to distinguish differences and detect changes which were statistically significant. The WB model appears to be the most powerful and efficient available. Use of this model makes it possible to demonstrate in vivo a statistically significant mechanical difference between male and pre-menopausal female skin using only one parameter (p= 0.0163, with 18 males and 19 females) and to demonstrate a statistically significant mechanical difference between successive decades of age in female skin using only one parameter (p= 0.0124, n= 24). The two parameters of the model most sensitive to skin structure, function and treatment have been combined to form the axes of a 'Skin condition chart'. Any person can be located on this chart at a point indicating their overall skin condition in mechanical terms and any changes in that condition can be clearly demonstrated by movement across the plot.

Moisturization processes in living human skin studied by magnetic resonance imaging microscopy.

Summary Magnetic resonance imaging is a non-invasive, non-destructive and chemically specific imaging method widely used in medicine to reveal information about both tissue structure and function. It can measure water in tissue, but it has been difficult to achieve the necessary sensitivity and resolution when applying it to studies of the dry, thin stratum corneum. In this paper the use of magnetic resonance imaging to image the outer layers of the skin with a resolution of 0.06 mm is reported. Configuring the magnetic resonance imaging method in this way has made it possible for the first time to actually 'see'directly the moisturization in the stratum corneum. It is no longer necessary to rely upon methods which can only show side-effects of moisturization, such as changes in the appearance of the skin cells. As magnetic resonance imaging is harmless, it can be used repeatedly on the same skin and so produce a series of stills, or a time-lapse video, clearly showing the actual process of moisturization and related phenomena. The behaviour of skin has been observed during both hydration and dehydration; the two processes follow different time courses. Two layers have been observed in the stratum corneum, which appear to be different when the skin is hydrated. For the first time the actual surface of normal skin has been revealed on magnetic resonance images.

Ethics of human testing.

What should one do, and why? Anyone asking such questions--and everyone does so hundreds of time each day--is concerned with ethics. Product development and testing raise many ethical questions. Particularly since the rise of 'green consumerism', these are of increasing concern to people outside the cosmetics industry, and so should be of interest to those inside it. The major problem seems to be that of reaching agreement on moral and ethical issues. Overcoming this problem involves investigating what is meant by 'ethics', and how decisions depend not on facts but on 'facts-as-perceived'. These in turn depend on many factors, with one's philosophy being the most fundamental. The range of philosophical options is reviewed and it is proposed that wider discussion is the only just way to achieve agreement. Yet some things are not negotiable. There are certain key moral concepts in terms of which discussion must take place for it to be relevant. In ethics of human testing, 'respect for others', that is, avoiding exploitation, is the principal one. Some synthesis of the key moral concepts like that of Immanuel Kant is therefore recommended as the soundest and most widely acceptable basis for the necessary discussion. Defining the responsible use of human subjects covers a range of issues, moral, historical, legal and professional. For example, there may be ethical difficulties in deliberate damage induction as in SPF and irritancy testing. But above all, to avoid exploitation, there is a moral and also a legal requirement that subjects are truly volunteers. This is the basis of the concept of 'informed consent', required but not generally explained in current professional codes of practice. It is unjustified to exploit those who may be under duress, such as 'in-house volunteers' and those with low incomes. Hence in conclusion, criteria for obtaining valid informed consent are briefly reviewed. By considering issues such as these, we can help ensure that cosmetic scientists are true professionals, that is, those who recognise and are concerned with the ethical basis of their work.

Folate analogues. 21. Synthesis and antifolate and antitumor activities of N10-(cyanomethyl)-5,8-dideazafolic acid.

A close analogue of the antileukemic agent 5,8-dideaza-N10 propargylfolic acid (2) was synthesized by replacing the propargyl moiety of 2 with a cyanomethyl group. This compound, N10-(cyanomethyl)-5,8-dideazafolic acid (3), was evaluated for its antifolate and antitumor activities in several biological test systems. Alkylation of diethyl N-(4-aminobenzoyl)-L-glutamate with bromoacetonitrile gave diethyl N-[4-[(cyanomethyl)amino]benzoyl]-L-glutamate (7). Reaction of 7 with 2 amino-6-(bromomethyl)-4-hydroxyquinazoline (9) in dimethylacetamide gave the corresponding diethyl ester 11, which was hydrolyzed to the target compound 3. The known antileukemic agent 2 was also synthesized for comparative studies by employing a modified procedure, which resulted in a better yield of this product. Both compounds 2 and 3 were evaluated for their antifolate activities by using two folate-requiring microorganisms, Streptococcus faecium and Lactobacillus casei. They were further evaluated as inhibitors of thymidylate synthase and dihydrofolate reductase derived from the above organisms, as well as for their antitumor activity by using selected tumor cells in culture. Compound 2 was found to be as equally potent as methotrexate (MTX) against S. faecium, and it was an excellent inhibitor of L. casei thymidylate synthase. The cyanomethyl analogue 3 was less active than 2 in all the test systems, except the inhibition of dihydrofolate reductase.

Thermography of the nose and ear in relation to the skin lesions of lepromatous leprosy, tuberculosis, leishmaniasis, and lupus pernio.

The nasal and aural temperature patterns of 100 normal subjects have been investigated by infrared thermography, paying particular attention to possible errors of instrumentation and technique which may arise in such areas of complex morphology. Although by no means invariable, the pattern of themograms confirms that certain areas which are relatively cool are often affected in lepromatous leprosy, tuberculosis, leishmaniasis, and lupus pernio. In lepromatous leprosy, low temperature appears to govern the localization of disease in most parts of the body, and the possible reasons for this are discussed. Thermography may have a place in the investigation of other skin diseases in which the distribution of lesions on the body surface is unexplained.