Polypyridyl Zinc(II)-Indomethacin Complexes with Potent Anti-Breast Cancer Stem Cell Activity.

Cancer stem cells (CSCs) are thought of as a clinically pertinent subpopulation of tumors, partly responsible for cancer relapse and metastasis. Research programs aimed at discovering anti-CSC agents have largely focused on biologics and purely organic molecules. Recently, we showed that a family of redox-active copper(II) complexes with phenanthroline-based ligands and nonsteroidal anti-inflammatory drugs (NSAIDs) such as indomethacin, are capable of potently and selectively killing breast CSCs. Herein we present analogous redox-inactive, zinc(II)-phenanthroline-indomethacin complexes with the ability to kill breast CSCs and bulk breast cancer cells with equal potency (in the submicro- or micromolar range). A single dose of the zinc(II) complexes could theoretically be administered to eliminate whole tumor populations. Excitingly, some of the zinc(II) complexes decrease the growth and viability of mammospheres to a comparable or higher degree than salinomycin, a compound known to effectively kill breast CSCs. As far as we are aware this is the first report to examine the anti-breast CSC activity of zinc(II)-containing compounds.

Blood Pressure and Heart Rate Changes During Clozapine Treatment.

People with schizophrenia are 3-4 times more likely to die from cardiovascular disease than the general population. Clozapine (CLZ) is the gold standard of treatment for refractory schizophrenia. It has been associated with tachycardia and recent evidence shows individuals prescribed CLZ may develop blood pressure (BP) elevation and hypertension. The purpose of this study was to examine the effects of CLZ on BP and heart rate (HR). This was a retrospective chart review of patients 18-75 years old with a DSM IV diagnosis of Schizophrenia or Schizoaffective disorder. Primary outcomes were systolic blood pressure (SBP), diastolic blood pressure (DBP), and HR measured 12 weeks before and 24 weeks during CLZ treatment. Eighteen patient records were included in this study. The mean stabilized CLZ dose was 441.7 ± 171.8 mg/day. DBP (t = 1.02, df = 79.5, = 2.00, 0.049) and HR (t = 1.32, df = 355  = -4.61, < 0.0001) were significantly higher after CLZ initiation. A trend was noted for increase in SBP (p = 0.071). 22 % of patients met criteria for hypertension before CLZ and 67 % during CLZ treatment (Chi Square = 6.25, df = 1, p = 0.0124). No significant changes in weight or renal function occured during CLZ treatment. No patients had evidence of cardiomyopathy. The data suggest CLZ may be associated with a rise in BP and HR. The results of this study support previous literature that found an increase in SBP/DBP regardless of CLZ dose, occurring early in treatment. Due to high risk of cardiovascular morbidity and mortality, more work is needed to determine risk factors and understand the mechanism of action that may cause this side effect.

The prevalence and risk of non-infectious comorbidities in HIV-infected and non-HIV infected men attending general practice in Australia.

BACKGROUND: Non-AIDS-related mortality rates among HIV-infected patients still exceed those of their uninfected peers. A major driver of this excess mortality is a higher risk of non-infectious comorbidities, including cardiovascular disease, chronic kidney disease, type 2 diabetes mellitus, osteoporosis and cancer. The prevalence of mental illness and other chronic non-infectious comorbidities is identified as a primary concern of antiretroviral prescribers in Australia. METHODS: We conducted a cross-sectional, observational study using data from MedicineInsight, a large-scale Australian primary care database comprising longitudinal data from electronic clinical information systems. The HIV-infected cohort included all men with a recorded diagnosis of HIV. The non-HIV-infected cohort comprised all other men from the same practices. The prevalence and risk of cardiovascular disease, chronic kidney disease, type 2 diabetes mellitus, osteoporosis, cancer, anxiety and depression were compared between the groups. RESULTS: We included 2,406 HIV-infected males and 648,205 males with no record of HIV diagnosis attending primary care in this study. HIV-infected men were less socioeconomically disadvantaged and more urban-dwelling than men in the primary care cohort. We found that HIV-infected men attending primary care in Australia are at increased risk of chronic kidney disease, cancer, osteoporosis, anxiety and depression. There appears to be a risk of premature onset of cardiovascular disease, osteoporosis and cancer among younger HIV-infected patients. There is a high prevalence of anxiety and depression among HIV-infected men. CONCLUSIONS: Increased prevalence of non-infectious comorbidities among HIV-infected men has broad implications for the effective management of those with these chronic conditions. Education to raise awareness among both HIV-infected men and their care providers, together with a greater focus on risk reduction, monitoring and preventive care, may be effective strategies in primary healthcare settings to further narrow the gap in health outcomes between people living with HIV and their uninfected counterparts.