Phyto-oestrogens: where are we now?

Phyto-oestrogens have emerged from their esoteric role in animal husbandry following the hypothesis that the human Western diet is relatively deficient in these substances compared with societies where large amounts of plant foods and legumes are eaten. Evidence is beginning to accrue that they may begin to offer protection against a wide range of human conditions, including breast, bowel, prostate and other cancers, cardiovascular disease, brain function, alcohol abuse, osteoporosis and menopausal symptoms. Of the two main classes of these weak oestrogens, the isoflavones are under intensive investigation due to their high levels in soyabean. Like the 'anti-oestrogen' Tamoxifen, these seem to have oestrogenic effects in human subjects in the cardiovascular system and bone. Although previously only available from food, isoflavones are now being marketed in health-food supplements or drinks, and tablets may soon be available over the counter as 'natural' hormone-replacement therapy. In cancer, anti-oestrogenic effects are thought to be important, although genistein especially has been shown to induce wide-ranging anti-cancer effects in cell lines independent of any hormone-related influence. There are few indications of harmful effects at present, although possible proliferative effects have been reported. In infants, the effects of high levels in soya milk formulas are uncertain. The second group, lignans, have been less investigated despite their known antioestrogenic effects and more widespread occurrence in foods. Investigation of the possible benefits of phyto-oestrogens is hampered by lack of analytical standards and, hence, inadequate methods for the measurement of low levels in most foods. This problem may prove to be a major dilemma for regulatory authorities, clinicians and others wishing to advise the general public on whether these compounds really do have the health benefits attributed to them.     

Assessing enzyme substrate specificity using combinatorial libraries and electrospray ionization-Fourier transform ion cyclotron resonance mass spectrometry

A model experiment for the 'on-line' screening of substrate libraries by enzymes using combinatorial libraries in combination with electrospray ionization-Fourier transform ion cyclotron resonance (ESI-FTICR) mass spectrometry has been performed. The reaction between the electrophilic substrate 1-chloro-2,4-dinitrobenzene and component of a H-gamma-Glu-Cys-Xxx-OH library, catalyzed by glutathione-S-transferase, has been monitored. It shows the feasibility of 'two-dimensional' screening of substrate libraries by ESI-FTICR mass spectrometry.     

A bereavement intervention for parents following the sudden, violent deaths of their 12-28-year-old children: description and applications to clinical practice

This report describes a randomized clinical trial with a longitudinal design involving parents bereaved by the violent deaths of their 12-28-year-old children, with a view to applying selected components of the study to clinical practice. Parents of children who died in the previous two to seven months by accident, homicide, or suicide were identified through the death certificates of the children. Of the 261 parents recruited and randomized to intervention and control conditions, 171 were mothers and 90 were fathers. Among the most important findings were: gender differences in both baseline distress and treatment response; and a very slow rate of reduction in distress over time, irrespective of participation in the intervention. Regardless of study group assignment and measurement period, mothers reported higher mental distress, more evidence of trauma, poorer loss accommodation, poorer physical health, and less marital satisfaction than did fathers. Among mothers, 85% met mental distress caseness criteria at baseline (2 to 7 months post-death), 81% met the criteria immediately following the treatment (5 to 10 months post-death), and 67% met the criteria six months later (11 to 16 months post-death). For fathers, 63% met mental distress caseness criteria at baseline, 71% met the criteria immediately post-treatment, and 69% met criteria six months later. Recommendations concern program planning, recruiting and retaining participants, screening and orientation of participants, program format, and evaluation.     

Involvement of the Xenopus laevis Ro60 autoantigen in the alternative interaction of La and CNBP proteins with the 5'UTR of L4 ribosomal protein mRNA

In vertebrates the synthesis of ribosomal proteins is co-ordinately regulated at the translational level. The 5'-untranslated region (5'UTR) of this class of mRNAs contains conserved regions that are necessary and sufficient for translational regulation. Recently, we found that two proteins, the Xenopus laevis La autoantigen and the cellular nucleic acid binding protein (CNBP), are able to bind in vitro a pyrimidine tract at the 5' end and a downstream region, respectively. These regions are considered the common cis-acting elements of translational regulation. It was previously observed that the binding of both these putative trans-acting factors to their RNA sequences is assisted by a protease-sensitive factor(s) that dissociates from the complex after its formation. Here we provide evidence that the requirement for an ancillary factor assisting La binding to the pyrimidine tract of ribosomal protein mRNAs is typical of this RNA, and secondly that it may involve an RNA recognition motif of the La protein not clearly characterized previously. We also show that the Ro60 autoantigen is involved in the common factor activity necessary for the binding of La and CNBP proteins to their respective sequences. In addition, our findings suggest that an RNA also participates in this process. We show that CNBP can multimerise and that it binds to the 5'UTR as a dimer. Both La and CNBP compete for the interaction with the factor, and their binding to the 5'UTR is mutually exclusive. Our results from the binding analysis of mutations in the 5'UTR, which are known to disrupt the translational control in vivo, suggest a model in which the protein interactions and the 5'UTR RNA structure may co-operate in regulating the translational fate of ribosomal protein mRNAs.     

Long-term follow-up after bowel resection for necrotizing enterocolitis: factors affecting outcome

BACKGROUND: Necrotizing enterocolitis (NEC) is the most common surgical emergency among newborns and is associated with a high morbidity and mortality. This study evaluates the long-term survival of infants requiring surgical intervention for NEC and factors affecting outcome. METHODS: A retrospective review of infants requiring surgery for complications of NEC at a tertiary care, pediatric hospital over a 16-year period was performed. Patients were evaluated for early and late morbidity and mortality, length of intestinal resection, presence of the ileocecal valve (ICV), days of parenteral nutrition (PN), and growth. RESULTS: Two hundred forty-nine patients were included, with an average gestational age of 30 +/- 5 (+/- SD) weeks and birth weight of 1.50 +/- 0.89 kg. The surgical mortality rate was 45%, with survivors (137) being larger (P < .001) and older (P < .001) at time of birth than nonsurvivors. Mortality rates varied inversely with gestational age and birth weight. Surgical survivors had an average of 21 +/- 26 cm of intestinal length resected. The ileocecal valve was preserved in 45% of infants. Growth was similar between infants with or without an ICV. Stratification of length of intestine resected showed that infants with larger resections had greater requirements for parenteral nutrition, but this had no influence on long-term growth at follow-up. CONCLUSIONS: Survivors of NEC are characterized by greater gestational age, greater birth weight, and older postgestational age at surgery. Infants who underwent greater intestinal resections required longer periods of PN. The length of intestine resected or presence of the ileocecal valve had no overall bearing on long-term outcome.     

New cyclooxygenase-2/5-lipoxygenase inhibitors. 1. 7-tert-buty1-2,3-dihydro-3,3-dimethylbenzofuran derivatives as gastrointestinal safe antiinflammatory and analgesic agents: discovery and variation of the 5-keto substituent

A series of 5-keto-substituted 7-tert-buty1-2,3-dihydro-3,3- dimethylbenzofurans (DHDMBFs) were prepared and evaluated as potential nonsteroidal antiinflammatory and analgesic agents. Interest in this class of compounds arose when a DHDMBF was found to be an active metabolite of the di-tert-butylphenol antiinflammatory agent tebufelone. We have now found that a variety of 5-keto-substituted DHDMBFs have good in vivo antiinflammatory and analgesic activity after oral administration. These compounds inhibit both cyclooxygenase (COX) and 5-lipoxygenase (5-LOX) in vitro. The cyclooxygenase inhibition was found to be selective for the cyclooxygenase-2 isoform, and this combination of COX-2/5-LOX inhibition may be responsible for the gastrointestinal safety of compounds such as 30.