Environmental oestrogens and breast cancer: long-term low-dose effects of mixtures of various chemical combinations

The incidence of breast cancer has risen worldwide to unprecedented levels in recent decades, making it now the major cancer of women in many parts of the world.1 Although diet, alcohol, radiation and inherited loss of BRCA1/2 genes have all been associated with increased incidence, the main identified risk factors are life exposure to hormones including physiological variations associated with puberty/pregnancy/menopause,1 personal choice of use of hormonal contraceptives2 and/or hormone replacement therapy.3–6 On this basis, exposure of the human breast to the many environmental pollutant chemicals capable of mimicking or interfering with oestrogen action7 should also be of concern.8 Hundreds of such environmental chemicals have now been measured in human breast tissue from a range of dietary and domestic exposure sources7 ,9 including persistent organochlorine pollutants (POPs),10 polybrominated diphenylethers and polybromobiphenyls,11 polychlorinated biphenyls,12 dioxins,13 alkyl phenols,14 bisphenol-A and chlorinated derivatives,15 as well as other less lipophilic compounds such as parabens (alkyl esters of p-hydroxybenzoic acid),16 but studies investigating any association between raised levels of such compounds and the development of breast cancer remain inconclusive.7–16 However, the functionality of these chemicals has continued to be assessed on the basis of individual chemicals rather than the environmental reality of long-term low-dose exposure to complex mixtures. This misses the potential for individuals to have high concentrations of different compounds but with a common mechanism of action. It also misses the complex interactions between chemicals and physiological hormones which together may act to alter the internal homeostasis of the oestrogenic environment of mammary tissue.

A mathematical approach to chemical equilibrium theory for gaseous systems—I: theory

Equilibrium theory occupies an important position in chemistry and it is traditionally based on thermodynamics. A novel mathematical approach to chemical equilibrium theory for gaseous systems at constant temperature and pressure is developed. Six theorems are presented logically which illustrate the power of mathematics to explain chemical observations and these are combined logically to create a coherent system. This mathematical treatment provides more insight into chemical equilibrium and creates more tools that can be used to investigate complex situations. Although some of the issues covered have previously been given in the literature, new mathematical representations are provided. Compared to traditional treatments, the new approach relies on straightforward mathematics and less on thermodynamics, thus, giving a new and complementary perspective on equilibrium theory. It provides a new theoretical basis for a thorough and deep presentation of traditional chemical equilibrium. This work demonstrates that new research in a traditional field such as equilibrium theory, generally thought to have been completed many years ago, can still offer new insights and that more efficient ways to present the contents can be established. The work presented here can be considered appropriate as part of a mathematical chemistry course at University level.

A mathematical approach to chemical equilibrium theory for gaseous systems—II: extensions and applications

Straightforward mathematical techniques are used innovatively to form a coherent theoretical system to deal with chemical equilibrium problems. For a systematic theory it is necessary to establish a system to connect different concepts. This paper shows the usefulness and consistence of the system by applications of the theorems introduced previously. Some theorems are shown somewhat unexpectedly to be mathematically correlated and relationships are obtained in a coherent manner. It has been shown that theorem 1 plays an important part in interconnecting most of the theorems. The usefulness of theorem 2 is illustrated by proving it to be consistent with theorem 3. A set of uniform mathematical expressions are associated with theorem 3. A variety of mathematical techniques based on theorems 1–3 are shown to establish the direction of equilibrium shift. The equilibrium properties expressed in initial and equilibrium conditions are shown to be connected via theorem 5. Theorem 6 is connected with theorem 4 through the mathematical representation of theorem 1.

Chemical ligation by ring opening of oxo-thiomorpholines

The invention discloses processes for preparing compounds comprising an #-amino acid motif. The compounds are useful in e.g. the chemical ligation of peptides.