Azo dyes and the blood-brain barrier: Robert Aird's novel concept in chronic neurological disease (1903-2000).

The well-established medical involvement of derivatives of the azo dye industry lent credibility to the 1935 announcement by Stanley Cobb of the use of vital brilliant red dye as an anticonvulsant. Although in the fullness of time clinical experience would discard this concept, nevertheless it was to give rise to Robert Aird who posited that the mechanism of action of this dye was due to its ability to decrease the permeability of the blood-brain barrier. In a very prolonged exploration of this concept, Aird concluded that blood-brain barrier permeability underlay the causation of a long list of chronic neurological conditions--a concept that was eventually abandoned. This article examines the details and the effects of this concept and its impact upon neurology.

A case study of statistics in the regulatory process: the FD&C Red No. 40 experiments.

Unexpected findings in a mouse study in which the safety of FD&C No. 40 (Red 40) was examined led to additional experimentation and to new statistical analyses and models. The possibility of acceleration of tumors raised questions about an operational definition of acceleration and of appropriate statistical methods for assessing acceleration, especially in the face of data dredging. The evaluation of Red 40 was further complicated by cage and litter effects and the multigenerational design. In this report the investigations of these studies are reviewed and are used to illustrate how new scientific work can emerge through the regulatory process. A number of issues in animal experimentation that need to be examind are indicated.

Scarlet red.

Scarlet red-impregnated gauze is commonly used by plastic surgeons on granulating surfaces to promote epithelialization. Its mode of action is not fully understood.

Tetrazolium salts and formazans.

The history of the tetrazolium salts and formazans goes back 100 years, to when Friese (1875) reacted benzene diazonium nitrate with nitromethane, to produce a cherry-red "Neue Verbindung". This was the first formazan. 19 years later, Von Pechmann and Runge (1894) oxidised a formazan to produce the first tetrazolium salt. Many hundreds of tetrazolium salts and formazans were prepared in the following years, but only a handful have found applications in biological research. This article has attempted to describe the properties of these compounds, and to illustrate how the tetrazolium salt-formazan reaction has been exploited to serve an extremely wide variety of functions.