Structural and solution speciation studies on selected [Cu(NN)(OO)] complexes and an investigation of their biomimetic activity, ROS generation and their cytotoxicity in normoxic, hypoxic and anoxic environments in MCF-7 breast cancer-derived cells.

Reactive oxygen species(ROS) generation with subsequent DNA damage is one of the principle mechanisms of action assigned to copper-based anticancer complexes. The efficacy of this type of chemotherapeutic may be reduced in the low oxygen environment of tumours. In this study the cytotoxicity of three complexes, [Cu(dips)(phen)] (1), [Cu(ph)(phen)]·2H2O (2) and [Cu(ph)(bpy)]·H2O (3) (disp: 3,5-diisopropylsalicylate, phen: 1,10- phenanthroline, ph: phthalate, bpy: 2,2'-bipyridyl) were assessed for anticancer activity in the breast-cancer derived MCF-7 line under normoxic, hypoxic and anoxic conditions. In an immortalised keratinocyte HaCaT cell line, the cytotoxicity of complexes 2 and 3 was significantly reduced under both normoxic and hypoxic conditions, whilst the cytotoxicity of complex 1 was increased under hypoxic conditions. The ability of the complexes to generate ROS in the MCF-7 cell line was evaluated as was their ability to act as superoxide dismutase(SOD) and catalase mimics using a yeast cell assay. ROS generation was significant for complexes 2 and 3, less so for complex 1 though all three complexes had SOD mimetic ability. Given the ternary nature of the complexes, solution speciation studies were undertaken but were only successful for complex 3, due to solubility issues with the other two complexes. The concentration distribution of various species, formed in aqueous solution, was evaluated as a function of pH and confirmed that complex 3 is the dominant species at physiological pH in the mM concentration range. However, as its concentration diminishes, it experiences a progressive dissociation, leading to the formation of binary complexes of bpy alongside unbound phthalate.

Copper(II) complexes of coumarin-derived Schiff base ligands: Pro- or antioxidant activity in MCF-7 cells?

A series of copper(II) complexes of Schiff base-derived ligands (1-7) were studied for their pro- and antioxidant behaviour in the MCF-7 human breast cancer cell line. The coordination modes of two of the copper(II) complexes were investigated by pH-potentiometry, EPR and UV-Vis spectroscopic methods. The solution studies indicated that monomeric species are present in the Cu(II) - L1 system at neutral pH, whereas dinuclear species were observed in the case of the Cu(II) - L7 system. This difference in speciation was reflected in their relative cytotoxicities with the copper(II) complex of L1, showing significant cytotoxicity against MCF-7 cells whilst the complex of L7 was inactive. In fact, only three of the seven complexes studied in this series were cytotoxic to MCF-7 cells but this cytotoxicity did not correlate with their ability to bind to DNA, cleave DNA or act as a pro-oxidant. In contrast to previous copper(II) complexes studied by our group, the compounds studied here do not appear to lead to intracellular reactive oxygen species generation at any significant level. In a yeast-based assay, all of the copper complexes had the ability to protect Saccharomyces cerevisiae against menadione-induced oxidative stress but not hydrogen peroxide-induced stress, indicating a lack of catalase activity. Given that the adaptive mechanisms induced by hypoxia in cancer cells have selective effects, with a fine-tuned protection against damage and stress of many kinds, particularly against oxidative stress, chemotherapeutic compounds which are not pro-oxidants may offer a therapeutic advantage.

Psychiatrists' experiences of being stalked: a qualitative analysis.

Stalking is a well-recognized social phenomenon, one that particularly affects health care professionals, especially psychiatrists and other mental health workers; however, the nature and effects of stalking of psychiatrists have not been examined in detail. This study is a qualitative thematic analysis of the free-text responses of 2,585 psychiatrists in the United Kingdom (approximately 25% of all U.K. psychiatrists), almost 11 percent of whom described being stalked according to a strict research definition, and 21 percent of whom perceived themselves as having been stalked. It demonstrates that threat minimization, negative psychological impact, awareness of vulnerability, and difficulty obtaining help were major themes in how psychiatrists viewed their experiences of being stalked. It shows how some psychiatrists coped better than others and makes suggestions for appropriate professional support.

Psychological factors contributing to perceptions pain intensity after acute orthopaedic injury.

Psychological factors are capable of influencing an individual's perception of pain and may mediate the evolution from acute to chronic pain. Personality characteristics, such as alexithymia and anxiety sensitivity, can also influence perception of pain by somatising psychological distress associated with acute pain. The aim of this study was to understand if alexithymia and anxiety sensitivity interact with psychological distress at an early stage of recovery from orthopaedic injury, to accentuate perception of pain intensity and potentially mediate the development of chronic pain disorder. 62 patients who had recently suffered orthopaedic injury completed the British Pain Society Pain Rating Scale plus the Hospital Anxiety and Depression Scale, as well as measures of alexithymia and anxiety sensitivity. Pain intensity correlated with each of the psychological measures but a regression analysis found that only depression, in combination with anxiety sensitivity, contributed to a significant amount of the variance in pain scores. The authors suggest that early screening after orthopaedic injury could identify those vulnerable to developing persisting pain disorders. This could lead to effective early intervention using psychological methods of pain management to reduce the risk of acute pain evolving into a chronic pain disorder.