Zyflamend Reduces the Expression of Androgen Receptor in a Model of Castrate-Resistant Prostate Cancer

Prostate cancer is the most commonly diagnosed solid malignancy, and tumor cells eventually transform to castrate resistance through multiple pathways including activation of the androgen receptor via insulin-like growth factor receptor (IGF-1R) signaling involving phospho-AKT (pAKT). In this study, a mixture of herbal extracts, Zyflamend®, was used as a treatment in a model of castrate-resistant prostate cancer using CWR22Rv1 cells. Zyflamend reduced androgen receptor and IGF-1R expression along with a reduction of IGF-1-mediated proliferation of CWR22Rv1 cells. IGF-1 induced downstream AKT phosphorylation; however, the induction of pAKT was not associated with androgen receptor expression. Further, constitutively active form of AKT had no effect on nuclear expression of androgen receptor, indicating that upregulation of pAKT did not promote androgen receptor expression or nuclear translocation in castrate-resistant CWR22Rv1 cells. Conversely, Zyflamend reduced androgen receptor expression following IGF-1 stimulation and in cells overexpressing pAKT. These results demonstrated that Zyflamend inhibited IGF-1-stimulated cell growth, IGF-1R expression, and androgen receptor expression and its nuclear localization, but these effects were not dependent upon phosphatidylinositol 3-kinase/pAKT signaling. In conclusion, Zyflamend decreased cell proliferation and inhibited IGF-1R and androgen receptor expression in a phosphatidylinositol 3-kinase/pAKT independent manner.     

Unravelling the Mystery of Pain,Suffering, and Relief With Brain Imaging

In humans, the experience of pain and suffering is conveyed specifically by language. Noninvasive neuroimaging techniques now provide an account of neural activity in the human brain when pain is experienced. Knowledge gleaned from neuroimaging experiments has shaped contemporaneous accounts of pain. Within the biopsychosocial framework, nociception is undoubtedly required for survival, but is neither necessary nor sufficient for the consciousness of pain in humans. Pain emerges from the brain, which also exerts a top-down influence on nociception. In the brains of patients with chronic pain, neuroimaging has revealed subtle but significant structural, functional, and neurochemical abnormalities. Converging evidence suggests that the chronic pain state may arise from dysfunction of the frontal-limbic system. Further research in the clinical pain population will continue to identify neural mechanisms that contribute to the experience and consequence of pain, which may then be targeted therapeutically.     

Using the cardiac depression scale in men recovering from coronary artery bypass surgery

Aims. To examine the utility and validate the use of the Cardiac Depression Scale in patients who had first‐time coronary artery bypass graft surgery. Background. The Beck Depression Inventory, though frequently used, may not be sufficiently sensitive for use in cardiac patients. The Cardiac Depression Scale has been shown to identify the range of depression in medical cardiac patients. Design. Survey. Methods. The Beck Depression Inventory and Cardiac Depression Scale were administered to 120 men at hospital discharge, as well as six, 12 and 36 weeks postoperatively. Cronbach’s α scores were calculated for the measures at each point. Changes in scores over time were analysed using repeated measures analysis of variance. Associations between the measures scores were calculated using Pearson product–moment correlations. Agreement between the measures’ dichotomised scores (depression/no depression) was examined using Cohen’s Kappa statistic. Results. Internal consistency was similar for the Beck Depression Inventory (0·793–0·904) and Cardiac Depression Scale (0·859–0·910). Depression scores decreased over time with the Beck Depression Inventory [F(2·50, 175·29) = 22·27, p < 0·001] and Cardiac Depression Scale [F(2·68, 190·37) = 13·18, p < 0·001]. The measures had similar power [Cohen’s f = 0·65 (Beck Depression Inventory) and 0·43 (Cardiac Depression Scale)] to reveal changes over time. The continuous scores were highly correlated at each point [0·737 (p < 0·001)–0·819 (p < 0·001)]. However, when dichotomised scores were compared, the chance corrected level of agreement was less impressive [0·198 (p = 0·014)–0·381 (p < 0·001)]. Conclusions. The Cardiac Depression Scale may have utility for use with surgical cardiac patients. However, continued examination of this measure of depression is warranted. Relevance to clinical practice. Given the prevalence of depression and its negative impact on coronary artery disease, it is important to identify even mild depression in cardiac patients. Using a measure of depression specifically for cardiac patients, rather than a generic measure, may best accomplish this goal.     

Pioglitazone administration decreases cardiovascular disease risk factors in insulin-resistant smokers

Insulin sensitivity varies in cigarette smokers, and there is evidence that cardiovascular disease (CVD) risk is greatest in those smokers who are also insulin resistant. To extend these observations, we sought to (1) compare CVD risk factors in smokers who do not plan to stop smoking, divided into insulin-resistant (IR) and insulin-sensitive (IS) subgroups, and (2) evaluate the ability of drug-induced changes in insulin sensitivity to decrease CVD risk. Thirty-six cigarette smokers were divided into IR (n = 19) and IS (n = 17) subgroups by determining their steady-state plasma glucose (SSPG) concentrations during the insulin suppression test (the higher the SSPG, the more insulin resistant the individual). In addition, baseline measurements were made of fasting lipid and lipoprotein concentrations; inflammatory markers; and daylong glucose, insulin, and free fatty acid responses to test meals. All subjects were treated with pioglitazone for 12 weeks, after which all baseline measurements were repeated. Baseline triglyceride and high-density lipoprotein cholesterol concentrations were significantly different in IR as compared with IS smokers (P < .05) both before and after adjustment for differences in sex and body mass index. After pioglitazone treatment, SSPG concentration significantly fell in the IR smokers (P < .001), associated with a significant improvement in the atherogenic lipoprotein profile seen at baseline (P ≤ .03) and a decrease in soluble intercellular adhesion molecule 1 and C-reactive protein concentrations (P = .01 and .02, respectively), whereas the IS smokers only had a significant increase in high-density lipoprotein cholesterol (P = .004) and a decrease in soluble intercellular adhesion molecule 1 (P = .02) and CRP (P = .07) levels. In conclusion, cigarette smokers have profound differences in CVD risk factors related to their degree of insulin sensitivity. It is suggested that, in addition to smoking cessation efforts, attention should be given to identifying the subgroup of smokers most at risk for CVD, but unwilling or unable to stop smoking, and to initiating appropriate therapeutic interventions to decrease CVD in this high-risk group.     

Evidence‐based recommendations for the monitoring and treatment of ankylosing spondylitis: results from the Australian 3E initiative in rheumatology

Aim: To develop a set of Australian recommendations for the monitoring and treatment of ankylosing spondylitis (AS) through systematic literature review combined with the opinion of practicing rheumatologists. Methods: A set of eight questions, four in each domain of monitoring and treatment, were formulated by voting and the Delphi method. The results of a systematic literature review addressing each question were presented to the 23 participants of the Australian 3E meeting. All participants were clinical rheumatologists experienced in the daily management of AS. Results: After three rounds of breakout sessions to discuss the findings of the literature review, a set of recommendations was finalized after discussion and voting. The category of evidence and strength of recommendation were determined for each proposal. The level of agreement among participants was excellent (mean 84%, range 64–100%). Conclusions: The 12 recommendations developed from evidence and expert opinion provide guidance for the daily management of AS patients. For most recommendations, we found a paucity of supportive evidence in the literature highlighting the need for additional clinical studies.