RESUMO
Ferrocene containing N-heterocyclic carbene (NHC) ligated gold(I) complexes of the type [Au(NHC)2]+ were prepared and found to be capable of regulating the formation of reactive oxygen species (ROS) via multiple mechanisms. Single crystal X-ray analysis of bis(1-(ferrocenylmethyl)-3-mesitylimidazol-2-ylidene)-gold(I) chloride (5) and bis(1,3-di(ferrocenylmethyl)imidazol-2-ylidene)-gold(I) chloride (6) revealed a quasi-liner geometry around the gold(I) centers, (i.e., the C-Au-C bond angle were measured to be ~177° and all the Au-Ccarbene bonds distances were in the range of 2.00 (7) - 2.03 (1) Å). A series of cell studies indicated that cell proliferation inhibition and ROS generation were directly proportional to amount of ferrocene contained within the [Au(NHC)2]+ complexes (IC50 of 6 < 5 < bis(1-benzyl-3-mesitylimidazol-2-ylidene)-gold(I) chloride (4)). Complexes 4-6 were also confirmed to inhibit thioredoxin reductase as inferred from lipoate reduction assays and increase chelatable intracellular zinc concentrations. RNA microarray gene expression assays revealed that 6 induces endoplasmic reticulum stress response pathways as a result of ROS increase.
RESUMO
BACKGROUND: Suicide rates are higher in the over 65s than in younger adults and there is a strong link between deliberate self harm (DSH) and suicide in older people. The association between personality disorder (PD) and DSH in older adults remains uncertain. Our objective was to describe this association. METHODS: A case control study was conducted in which participants were: (i) those who had undertaken an act of DSH and (ii) a hospital-based control group drawn from a geographical contiguous population. PD was assessed using the Standardised Assessment of Personality (SAP). RESULTS: Seventy-seven cases of DSH were identified; 61 (79.2%) of these participants were interviewed. There were 171 potential controls identified of whom 140 (81.9%) were included. An SAP was completed in 45/61 (73.8%) of cases and 100/140 (71.4%) of controls. The mean age was 79.8 years (SD = 9, range 65-103). The crude odds ratio for the association between PD and DSH was 5.91 [(95% CI 2.3, 14.9) p<0.0001]. There was a strong interaction with age stratified at 80 years. There was no association between PD and DSH after age 80. The adjusted odds ratio for PD in the group <80 years was 20.5 [(95% CI 3, 141) p = 0.002]. Borderline and impulsive PD traits tended to be associated with an episode of DSH more than other personality types. CONCLUSIONS: PD appears to be a strong and independent risk for an act of DSH in people aged between 65 and 80 years and should be looked for as part of any risk assessment in this population. Access to specialist services may be required to optimally manage this problem and reduce the subsequent risk of suicide.
