MRI and image quantitation for drug assessment - Growth effects of anabolic steroids and precursors

MRI and image quantitation play an expanding role in modern drug research, because MRI offers high resolution and non-invasive ability, and provides excellent soft tissue contrast. Moreover, with development of effective image segmentation and analysis methods, in-vivo and serial tissue growth measurements could be assessed. In the study, MR image acquisition and analysis protocol were established and validated for investigating the effects of anabolic steroids and precursors on muscle growth and body composition in a guinea pig model. Semi-automatic and interactive segmentation methods were developed to accurately label the tissue of interest for tissue volume estimation. In addition, a longitudinal tissue area outlining procedure was proposed for study of tissue geometric features in relation to tissue growth. Finally, a fully automatic data retrieval and analysis scheme was implemented to facilitate the overall huge amount of image quantitation, statistical analysis, as well as study group comparisons. As a result, highly significant differences in muscle and organ growth were detected between intact and castrated guinea pigs using the selected anabolic steroids, indicating the viability of employing such protocol to assess other anabolic steroids. Furthermore, the anabolic potential of selected steroid precursors and their effects on muscle growth, in comparison with that in respective positive control groups of castrated guinea pigs, were evaluated with the proposed protocol. © 2005 IEEE.published_or_final_versio

Reductions in cardiovascular, cerebrovascular, and respiratory mortality following the national Irish smoking ban: Interrupted time-series analysis

Copyright @ 2013 Stallings-Smith et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.This article has been made available through the Brunel Open Access Publishing Fund.Background: Previous studies have shown decreases in cardiovascular mortality following the implementation of comprehensive smoking bans. It is not known whether cerebrovascular or respiratory mortality decreases post-ban. On March 29, 2004, the Republic of Ireland became the first country in the world to implement a national workplace smoking ban. The aim of this study was to assess the effect of this policy on all-cause and cause-specific, non-trauma mortality. Methods: A time-series epidemiologic assessment was conducted, utilizing Poisson regression to examine weekly age and gender-standardized rates for 215,878 non-trauma deaths in the Irish population, ages ≥35 years. The study period was from January 1, 2000, to December 31, 2007, with a post-ban follow-up of 3.75 years. All models were adjusted for time trend, season, influenza, and smoking prevalence. Results: Following ban implementation, an immediate 13% decrease in all-cause mortality (RR: 0.87; 95% CI: 0.76-0.99), a 26% reduction in ischemic heart disease (IHD) (RR: 0.74; 95% CI: 0.63-0.88), a 32% reduction in stroke (RR: 0.68; 95% CI: 0.54-0.85), and a 38% reduction in chronic obstructive pulmonary disease (COPD) (RR: 0.62; 95% CI: 0.46-0.83) mortality was observed. Post-ban reductions in IHD, stroke, and COPD mortalities were seen in ages ≥65 years, but not in ages 35-64 years. COPD mortality reductions were found only in females (RR: 0.47; 95% CI: 0.32-0.70). Post-ban annual trend reductions were not detected for any smoking-related causes of death. Unadjusted estimates indicate that 3,726 (95% CI: 2,305-4,629) smoking-related deaths were likely prevented post-ban. Mortality decreases were primarily due to reductions in passive smoking. Conclusions: The national Irish smoking ban was associated with immediate reductions in early mortality. Importantly, post-ban risk differences did not change with a longer follow-up period. This study corroborates previous evidence for cardiovascular causes, and is the first to demonstrate reductions in cerebrovascular and respiratory causes

Integrative genome-wide expression profiling identifies three distinct molecular subgroups of renal cell carcinoma with different patient outcome

ABSTRACT: BACKGROUND: Renal cell carcinoma (RCC) is characterized by a number of diverse molecular aberrations that differ among individuals. Recent approaches to molecularly classify RCC were based on clinical, pathological as well as on single molecular parameters. As a consequence, gene expression patterns reflecting the sum of genetic aberrations in individual tumors may not have been recognized. In an attempt to uncover such molecular features in RCC, we used a novel, unbiased and integrative approach. METHODS: We integrated gene expression data from 97 primary RCCs of different pathologic parameters, 15 RCC metastases as well as 34 cancer cell lines for two-way nonsupervised hierarchical clustering using gene groups suggested by the PANTHER Classification System. We depicted the genomic landscape of the resulted tumor groups by means of Single Nuclear Polymorphism (SNP) technology. Finally, the achieved results were immunohistochemically analyzed using a tissue microarray (TMA) composed of 254 RCC. Results: We found robust, genome wide expression signatures, which split RCC into three distinct molecular subgroups. These groups remained stable even if randomly selected gene sets were clustered. Notably, the pattern obtained from RCC cell lines was clearly distinguishable from that of primary tumors. SNP array analysis demonstrated differing frequencies of chromosomal copy number alterations among RCC subgroups. TMA analysis with group-specific markers showed a prognostic significance of the different groups. Conclusion: We propose the existence of characteristic and histologically independent genome-wide expression outputs in RCC with potential biological and clinical relevance

In vivo MRI evaluation of anabolic steroid precursor growth effects in a guinea pig model

Anabolic steroids are widely used to increase skeletal muscle (SM) mass and improve physical performance. Some dietary supplements also include potent steroid precursors or active steroid analogs such as nandrolone. Our previous study reported the anabolic steroid effects on SM in a castrated guinea pig model with SM measured using a highly quantitative magnetic resonance imaging (MRI) protocol. The aim of the current study was to apply this animal model and in vivo MRI protocol to evaluate the growth effects of four widely used over-the-counter testosterone and nandrolone precursors: 4-androstene-3 17-dione (androstenedione), 4-androstene-3β 17β-diol (4-androsdiol), 19-nor-4-androstene-3β-17β-diol (bolandiol) and 19-nor-4-androstene-3 17-dione (19-norandrostenedione). The results showed that providing precursor to castrated male guinea pigs led to plasma steroid levels sufficient to maintain normal SM growth. The anabolic growth effects of these specific precursors on individual and total muscle volumes, sexual organs, and total adipose tissue over a 10-week treatment period, in comparison with those in the respective positive control testosterone and nandrolone groups, were documented quantitatively by MRI. © 2009 Elsevier Inc.link_to_subscribed_fulltex

In vivo MRI quantification of individual muscle and organ volumes for assessment of anabolic steroid growth effects

This study aimed to develop a quantitative and in vivo magnetic resonance imaging (MRI) approach to investigate the muscle growth effects of anabolic steroids. A protocol of MRI acquisition on a standard clinical 1.5 T scanner and quantitative image analysis was established and employed to measure the individual muscle and organ volumes in the intact and castrated guinea pigs undergoing a 16-week treatment protocol by two well-documented anabolic steroids, testosterone and nandrolone, via implanted silastic capsules. High correlations between the in vivo MRI and postmortem dissection measurements were observed for shoulder muscle complex (R = 0.86), masseter (R = 0.79), temporalis (R = 0.95), neck muscle complex (R = 0.58), prostate gland and seminal vesicles (R = 0.98), and testis (R = 0.96). Furthermore, the longitudinal MRI measurements yielded adequate sensitivity to detect the restoration of growth to or towards normal in castrated guinea pigs by replacing circulating steroid levels to physiological or slightly higher levels, as expected. These results demonstrated that quantitative MRI using a standard clinical scanner provides accurate and sensitive measurement of individual muscles and organs, and this in vivo MRI protocol in conjunction with the castrated guinea pig model constitutes an effective platform to investigate the longitudinal and cross-sectional growth effects of other potential anabolic steroids. The quantitative MRI protocol developed can also be readily adapted for human studies on most clinical MRI scanner to investigate the anabolic steroid growth effects, or monitor the changes in individual muscle and organ volume and geometry following injury, strength training, neuromuscular disorders, and pharmacological or surgical interventions. © 2008.link_to_subscribed_fulltex