A comparison of novel organoiridium(III) complexes and their ligands as a potential treatment for prostate cancer

A range of 1,4-substituted 2-pyridyl-N-phenyl triazoles were synthesised and evaluated for their antiproliferative properties against lymph node cancer of the prostate (LNCaP) and bone metastasis of prostate cancer (PC-3) cells. Excellent-to-low IC50 values were determined (5.6-250 μM), and a representative group of 4 ligands were then complexed to iridium(III) giving highly luminescent species. Re-evaluation of these compounds against both cell lines was then undertaken and improved potency (up to 72-fold) was observed, giving IC50 values of 0.36-11 μM for LNCaP and 0.85-5.9 μM for PC-3. Preliminary screens for in vivo toxicity were conducted using a zebrafish model showing a wide range of induced toxicity depending of the compound evaluated. Apoptosis and Caspase-3 levels were also determined and showed no statistical difference between some of the treated specimens and the controls. This study may identify novel therapeutic agents for advanced stage of prostate cancer in humans.

A comparison of the dietary patterns derived by principal component analysis and cluster analysis in older Australians

BACKGROUND: Despite increased use of dietary pattern methods in nutritional epidemiology, there have been few direct comparisons of methods. Older adults are a particularly understudied population in the dietary pattern literature. This study aimed to compare dietary patterns derived by principal component analysis (PCA) and cluster analysis (CA) in older adults and to examine their associations with socio-demographic and health behaviours. METHODS: Men (n = 1888) and women (n = 2071) aged 55-65 years completed a 111-item food frequency questionnaire in 2010. Food items were collapsed into 52 food groups and dietary patterns were determined by PCA and CA. Associations between dietary patterns and participant characteristics were examined using Chi-square analysis. The standardised PCA-derived dietary patterns were compared across the clusters using one-way ANOVA. RESULTS: PCA identified four dietary patterns in men and two dietary patterns in women. CA identified three dietary patterns in both men and women. Men in cluster 1 (fruit, vegetables, wholegrains, fish and poultry) scored higher on PCA factor 1 (vegetable dishes, fruit, fish and poultry) and factor 4 (vegetables) compared to factor 2 (spreads, biscuits, cakes and confectionery) and factor 3 (red meat, processed meat, white-bread and hot chips) (mean, 95 % CI; 0.92, 0.82-1.02 vs. 0.74, 0.63-0.84 vs. -0.43, -0.50- -0.35 vs. 0.60 0.46-0.74, respectively). Women in cluster 1 (fruit, vegetables and fish) scored highest on PCA factor 1 (fruit, vegetables and fish) compared to factor 2 (processed meat, hot chips cakes and confectionery) (1.05, 0.97-1.14 vs. -0.14, -0.21- -0.07, respectively). Cluster 3 (small eaters) in both men and women had negative factor scores for all the identified PCA dietary patterns. Those with dietary patterns characterised by higher consumption of red and processed meat and refined grains were more likely to be Australian-born, have a lower level of education, a higher BMI, smoke and did not meet physical activity recommendations (all P < 0.05). CONCLUSIONS: PCA and CA identified comparable dietary patterns within older Australians. However, PCA may provide some advantages compared to CA with respect to interpretability of the resulting dietary patterns. Older adults with poor dietary patterns also displayed other negative lifestyle behaviours. Food-based dietary pattern methods may inform dietary advice that is understood by the community.

Effects of antidepressants on postmenopausal bone loss - a 5-year longitudinal study from the OSTPRE cohort

BACKGROUND: Osteoporosis and depression are major health problems worldwide. The association between antidepressants, a treatment for depression, and bone health needs more detailed exploration. OBJECTIVE: The present study investigates antidepressant medication use and postmenopausal bone loss over time. METHODS: A total of 1988 women (aged 57-67) participating in the Kuopio Osteoporosis Risk Factor and Prevention Study (OSTPRE) cohort responded to a postal enquiry and had their femoral neck bone mineral density (BMD) measured in 1999 and again in 2004. Data on antidepressant use was obtained from the National Prescription Register. Multiple regression techniques were used to test the associations, before and after adjustment for anthropometric, medical, physical and lifestyle factors. RESULTS: Over the five years of follow-up, 319 (16.0%) women purchased antidepressants. Mean baseline femoral neck BMD for the entire study group was 881mg/cm(2) (SD 123) and mean 5-year bone loss was 6.0mg/cm(2) (SD 4.7). After adjustments, users of tricyclic antidepressants (TCA) had greater annual BMD loss than non-users (-3.6mg/cm(2) vs. -1.1mg/cm(2); P=0.031). Accelerated bone loss was also associated with selective serotonin reuptake inhibitor's (SSRI) use (P=0.001) and use of other antidepressants in a dose-response way, with the latter only among women of low-weight and normal-weight women who had lost weight over the study period. CONCLUSIONS: In conclusion, the use of SSRIs seems to accelerate postmenopausal bone loss in a dose-response manner. Associations between TCA and other antidepressant use and bone loss may also exist. Thus, the possibility of increased risk of osteoporosis should be considered when prescribing antidepressants for postmenopausal women.