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While Alzheimer’s disease (AD) and vascular dementia (VaD) may be accelerated by hypercholesterolemia, the mechanisms underlying this association is unclear. Using a novel, 3-step study design we examined the role of cholesterol catabolism in dementia by testing whether 1) the synthesis of the primary cholesterol breakdown products (bile acids (BA)) were associated with neuroimaging markers of dementia; 2) pharmacological modulation of BAs alters dementia risk; and 3) brain BA concentrations and gene expression were associated with AD. We found that higher serum concentrations of BAs are associated with lower brain amyloid deposition, slower WML accumulation, and slower brain atrophy in males. Opposite effects were observed in females. Modulation of BA levels alters risk of incident VaD in males. Altered brain BA signaling at the metabolite and gene expression levels occurs in AD. Dysregulation of peripheral cholesterol catabolism and BA synthesis may impact dementia pathogenesis through signaling pathways in the brain.

Purpose: The rcellminer R package provides a wide range of functionality to help R users access and explore molecular profiling and drug response data for the NCI-60. The package enables flexible programmatic access to CellMiner’s unparalleled breadth of NCI-60 data, including gene and protein expression, copy number, whole exome mutations, as well as activity data for ∼21K compounds, with information on their structure, mechanism of action and repeat screens. Functions are available to easily visualize compound structures, activity patterns and molecular feature profiles. Additionally, embedded R Shiny applications allow interactive data exploration. Availability and implementation: rcellminer is compatible with R 3.2 and above on Windows, Mac OS X and Linux. The package, documentation, tutorials and Shiny-based applications are available through Bioconductor (http://www.bioconductor.org/packages/rcellminer); ongoing updates will occur according to the Bioconductor release schedule with new CellMiner data. The package is free and open-source (LGPL 3). Contact: lunaa@cbio.mskcc.org or vinodh.rajapakse@nih.gov

Recent statistics reports by Centre for Disease Control and Prevention (CDC) and World Health Organization (WHO) have presented the facts that cardiovascular disease (CVD) accounts for 30% of all deaths.1 Genetic polymorphism, age, gender, smoking, inflammation, systolic blood pressure (SBP), cholesterol, physical inactivity, low socio-economic status, and psychosocial risk factors contribute to development of CVD.2 Inflammation-induced cardiac and vascular remodelling, oxidative stress, unregulated synthesis of nitric oxide, impaired immune cells signalling, and cytokines cascade contribute to cardiovascular damage. Sulfasalazine, an anti-cytokine drug, is reasonably accepted clinically for its efficacy in inflammatory diseases due to potential NF-kB and TNF-α inhibitory activity.3 However, none of the anti-cytokine drugs has been incorporated in a standard regimen for treatment of coronary artery disease (CAD). Our study aimed at controlling inflammation using sulfasalazine 500 mg, once a day for 24 weeks in stable CAD patients. A randomized, double-blind, placebo-controlled, parallel group study was carried out, under the Department of Pharmaceutical Sciences and Drug Research, after due approval from Institutional Ethics Committee of Punjabi University, Patiala. The study was performed in accordance with the declaration of Helsinki and the code of Good Clinical Practice. Written informed consent was obtained from each patient prior to recruitment in the study. Inclusion criteria were: male/female patients ( n = 50, ≥18 years …

We evaluated the use of a new lactate oxidase-based reagent for the determination of serum and plasma lactic acid levels with the Hitachi 911 (Roche Diagnostics, Indianapolis, IN) and the Beckman CX7 (Beckman Instruments, Brea, CA). Evaluation studies demonstrated on-board stability of at least 3 months and a calibration stability of more than 5 months. Within- and between-day imprecision of this reagent was less than 2% for both applications. The reagent is free of the deleterious effects of triglyceride up to levels of 1,400 mg/dL (15.8 mmol/L), bilirubin to concentrations of 24.6 mg/dL (420 mumol/L), and hemoglobin, from lysed erythrocytes, to levels of more than 0.3 g/dL (3.0 g/L). When used on the Hitachi 911 for the determination of plasma lactate concentrations, the reagent correlates with the Dade aca III (Dade International, Deerfield, IL). When applied to the Beckman CX7 for the determination of serum lactate levels, the method correlates with the Beckman method.