Lipophilic aroylhydrazone chelator HNTMB and its multiple effects on ovarian cancer cells

<p>Abstract</p> <p>Background</p> <p>Metal chelators have gained much attention as potential anti-cancer agents. However, the effects of chelators are often linked solely to their capacity to bind iron while the potential complexation of other trace metals has not been fully investigated. In present study, we evaluated the effects of various lipophilic aroylhydrazone chelators (AHC), including novel compound HNTMB, on various ovarian cancer cell lines (SKOV-3, OVCAR-3, NUTU-19).</p> <p>Methods</p> <p>Cell viability was analyzed via MTS cytotoxicity assays and NCI60 cancer cell growth screens. Apoptotic events were monitored via Western Blot analysis, fluorescence microscopy and TUNEL assay. FACS analysis was carried out to study Cell Cycle regulation and detection of intracellular Reactive Oxygen Species (ROS)</p> <p>Results</p> <p>HNTMB displayed high cytotoxicity (IC50 200-400 nM) compared to previously developed AHC (oVtBBH, HNtBBH, StBBH/206, HNTh2H/315, HNI/311; IC50 0.8-6 μM) or cancer drug Deferoxamine, a hexadentate iron-chelator (IC50 12-25 μM). In a NCI60 cancer cell line screen HNTMB exhibited growth inhibitory effects with remarkable differences in specificity depending on the cell line studied (GI50 10 nM-2.4 μM). In SKOV-3 ovarian cancer cells HNTMB treatment led to chromatin fragmentation and activation of the extrinsic and intrinsic pathways of apoptosis with specific down-regulation of Bcl-2. HNTMB caused delayed cell cycle progression of SKOV-3 through G2/M phase arrest. HNTMB can chelate iron and copper of different oxidation states. Complexation with copper lead to high cytotoxicity via generation of reactive oxygen species (ROS) while treatment with iron complexes of the drug caused neither cytotoxicity nor increased ROS levels.</p> <p>Conclusions</p> <p>The present report suggests that both, non-complexed HNTMB as a chelator of intracellular trace-metals as well as a cytotoxic HNTMB/copper complex may be developed as potential therapeutic drugs in the treatment of ovarian and other solid tumors.</p

Maternal blood cadmium, lead and arsenic levels, nutrient combinations, and offspring birthweight

Abstract Background Cadmium (Cd), lead (Pb) and arsenic (As) are common environmental contaminants that have been associated with lower birthweight. Although some essential metals may mitigate exposure, data are inconsistent. This study sought to evaluate the relationship between toxic metals, nutrient combinations and birthweight among 275 mother-child pairs. Methods Non-essential metals, Cd, Pb, As, and essential metals, iron (Fe), zinc (Zn), selenium (Se), copper (Cu), calcium (Ca), magnesium (Mg), and manganese (Mn) were measured in maternal whole blood obtained during the first trimester using inductively coupled plasma mass spectrometry. Folate concentrations were measured by microbial assay. Birthweight was obtained from medical records. We used quantile regression to evaluate the association between toxic metals and nutrients due to their underlying wedge-shaped relationship. Ordinary linear regression was used to evaluate associations between birth weight and toxic metals. Results After multivariate adjustment, the negative association between Pb or Cd and a combination of Fe, Se, Ca and folate was robust, persistent and dose-dependent (p < 0.05). However, a combination of Zn, Cu, Mn and Mg was positively associated with Pb and Cd levels. While prenatal blood Cd and Pb were also associated with lower birthweight. Fe, Se, Ca and folate did not modify these associations. Conclusion Small sample size and cross-sectional design notwithstanding, the robust and persistent negative associations between some, but not all, nutrient combinations with these ubiquitous environmental contaminants suggest that only some recommended nutrient combinations may mitigate toxic metal exposure in chronically exposed populations. Larger longitudinal studies are required to confirm these findings

A Systematic Review of Healthcare Applications for Smartphones

<p>Abstract</p> <p>Background</p> <p>Advanced mobile communications and portable computation are now combined in handheld devices called “smartphones”, which are also capable of running third-party software. The number of smartphone users is growing rapidly, including among healthcare professionals. The purpose of this study was to classify smartphone-based healthcare technologies as discussed in academic literature according to their functionalities, and summarize articles in each category.</p> <p>Methods</p> <p>In April 2011, MEDLINE was searched to identify articles that discussed the design, development, evaluation, or use of smartphone-based software for healthcare professionals, medical or nursing students, or patients. A total of 55 articles discussing 83 applications were selected for this study from 2,894 articles initially obtained from the MEDLINE searches.</p> <p>Results</p> <p>A total of 83 applications were documented: 57 applications for healthcare professionals focusing on disease diagnosis (21), drug reference (6), medical calculators (8), literature search (6), clinical communication (3), Hospital Information System (HIS) client applications (4), medical training (2) and general healthcare applications (7); 11 applications for medical or nursing students focusing on medical education; and 15 applications for patients focusing on disease management with chronic illness (6), ENT-related (4), fall-related (3), and two other conditions (2). The disease diagnosis, drug reference, and medical calculator applications were reported as most useful by healthcare professionals and medical or nursing students.</p> <p>Conclusions</p> <p>Many medical applications for smartphones have been developed and widely used by health professionals and patients. The use of smartphones is getting more attention in healthcare day by day. Medical applications make smartphones useful tools in the practice of evidence-based medicine at the point of care, in addition to their use in mobile clinical communication. Also, smartphones can play a very important role in patient education, disease self-management, and remote monitoring of patients.</p