Hormones down under: Hormone therapy use after the Women's Health Initiative

Aims:  The primary objective was to describe the usage pattern of hormone therapy (HT) in a sample of urban Australian women in 2001 and to assess the characteristics of users vs. non-users. The second objective was to determine whether there had been any change in usage since the publication of the results of the combined oestrogen plus progestagen arm of the Women's Health Initiative (WHI) in 2002. Methods:  A cohort of 374 postmenopausal women aged 50–80 years participated in this substudy of the LAW (Longitudinal Assessment of Ageing in Women) project: a 5-year multidisciplinary, observational study. Participants completed an annual medical assessment including details of the use of HT and the reasons for use, as well as demographic and psychosocial data. Results:  In December 2001, 30.8% of the participants were using HT, whereas 55.4% were ever users. The management of vasomotor symptoms and mood disturbance were the primary reasons for use. Of those who had been using HT in December 2001 (24.4%) women ceased using HT in the 3 months following publication of the WHI results. The percentage of women using HT in December 2003 (13.9%) was less than half of that of December 2001. Conclusion:  The rate of HT use and the reasons for use, in 2001 in Brisbane was similar to that of other Australian regions. Usage of HT decreased since the publication of the WHI results in 2002 which may reflect changing attitudes by patients and practitioners regarding HT.

A fragment of the LG3 peptide of endorepellin is present in the urine of physically active mining workers : a potential marker of physical activity

Biomarker analysis has been implemented in sports research in an attempt to monitor the effects of exertion and fatigue in athletes. This study proposed that while such biomarkers may be useful for monitoring injury risk in workers, proteomic approaches might also be utilised to identify novel exertion or injury markers. We found that urinary urea and cortisol levels were significantly elevated in mining workers following a 12 hour overnight shift. These levels failed to return to baseline over 24h in the more active maintenance crew compared to truck drivers (operators) suggesting a lack of recovery between shifts. Use of a SELDI-TOF MS approach to detect novel exertion or injury markers revealed a spectral feature which was associated with workers in both work categories who were engaged in higher levels of physical activity. This feature was identified as the LG3 peptide, a C-terminal fragment of the anti-angiogenic / anti-tumourigenic protein endorepellin. This finding suggests that urinary LG3 peptide may be a biomarker of physical activity. It is also possible that the activity mediated release of LG3 / endorepellin into the circulation may represent a biological mechanism for the known inverse association between physical activity and cancer risk / survival.

Expression Pattern of the Alpha-Kafirin Promoter Coupled with a Signal Peptide from Sorghum bicolor L. Moench

Regulatory sequences with endosperm specificity are essential for foreign gene expression in the desired tissue for both grain quality improvement and molecular pharming. In this study, promoters of seed storage α-kafirin genes coupled with signal sequence (ss) were isolated from Sorghum bicolor L. Moench genomic DNA by PCR. The α-kafirin promoter (α-kaf) contains endosperm specificity-determining motifs, prolamin-box, the O2-box 1, CATC, and TATA boxes required for α-kafirin gene expression in sorghum seeds. The constructs pMB-Ubi-gfp and pMB-kaf-gfp were microprojectile bombarded into various sorghum and sweet corn explants. GFP expression was detected on all explants using the Ubi promoter but only in seeds for the α-kaf promoter. This shows that the α-kaf promoter isolated was functional and demonstrated seed-specific GFP expression. The constructs pMB-Ubi-ss-gfp and pMB-kaf-ss-gfp were also bombarded into the same explants. Detection of GFP expression showed that the signal peptide (SP)::GFP fusion can assemble and fold properly, preserving the fluorescent properties of GFP.

The role of insulin in advanced prostate cancer

Advanced prostate cancer is a common and generally incurable disease. Androgen deprivation therapy is used to treat advanced prostate cancer with good benefits to quality of life and regression of disease. Prostate cancer invariably progresses however despite ongoing treatment, to a castrate resistant state. Androgen deprivation is associated with a form of metabolic syndrome, which includes insulin resistance and hyperinsulinaemia. The mitogenic and anti-apoptotic properties of insulin acting through the insulin and hybrid insulin/IGF-1 receptors seem to have positive effects on prostate tumour growth. This pilot study was designed to assess any correlation between elevated insulin levels and progression to castrate resistant prostate cancer. Methods: 36 men receiving ADT for advanced prostate cancer were recruited, at various stages of their treatment, along with 47 controls, men with localised prostate cancer pre-treatment. Serum measurements of C-peptide (used as a surrogate marker for insulin production) were performed and compared between groups. Correlation between serum C-peptide level and time to progression to castrate resistant disease was assessed. Results: There was a significant elevation of C-peptide levels in the ADT group (mean = 1639pmol/L)) compared to the control group (mean = 1169pmol/L), with a p-value of 0.025. In 17 men with good initial response to androgen deprivation, a small negative trend towards earlier progression to castrate resistance with increasing C-peptide level was seen in the ADT group (r = -0.050), however this did not reach statistical significance (p>0.1). Conclusions: This pilot study confirms an increase in serum C-peptide levels in men receiving ADT for advance prostate cancer. A non-significant, but negative trend towards earlier progression to castrate resistance with increasing C-peptide suggests the need for a formal prospective study assessing this hypothesis.