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Jefferson City, AR, United States

Xie Z.,Pfizer | Liachenko S.,NCTR FDA | Chiao P.-C.,Pfizer | Carvajal-Gonzalez S.,Pfizer | And 2 more authors.
Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics)

We present a new approach for quantifying the degradation of knee cartilage in the medial meniscal tear (MMT) model of osteoarthritis in the rat. A statistical strategy was used to guide the selection of a region of interest (ROI) from the images obtained from a pilot study. We hypothesize that this strategy can be used to localize a region of cartilage most vulnerable to MMT-induced damage. In order to test this hypothesis, a longitudinal study was conducted in which knee cartilage thickness in a pre-selected ROI was monitored for three weeks and comparisons were made between MMT and control rats. We observed a significant decrease in cartilage thickness in MMT rats and a significant increase in cartilage thickness in sham-operated rats as early as one week post surgery when compared to pre-surgery measurements. © 2010 Springer-Verlag. Source

Monteiro J.P.,University of Sao Paulo | Wise C.,National Center for Toxicological Research (NCTR) | Morine M.J.,University of Trento | Teitel C.,National Center for Toxicological Research (NCTR) | And 15 more authors.
Genes and Nutrition

Micronutrient research typically focuses on analyzing the effects of single or a few nutrients on health by analyzing a limited number of biomarkers. The observational study described here analyzed micronutrients, plasma proteins, dietary intakes, and genotype using a systems approach. Participants attended a community-based summer day program for 6–14 year old in 2 years. Genetic makeup, blood metabolite and protein levels, and dietary differences were measured in each individual. Twenty-four-hour dietary intakes, eight micronutrients (vitamins A, D, E, thiamin, folic acid, riboflavin, pyridoxal, and pyridoxine) and 3 one-carbon metabolites [homocysteine (Hcy), S-adenosylmethionine (SAM), and S-adenosylhomocysteine (SAH)], and 1,129 plasma proteins were analyzed as a function of diet at metabolite level, plasma protein level, age, and sex. Cluster analysis identified two groups differing in SAM/SAH and differing in dietary intake patterns indicating that SAM/SAH was a potential marker of nutritional status. The approach used to analyze genetic association with the SAM/SAH metabolites is called middle-out: SNPs in 275 genes involved in the one-carbon pathway (folate, pyridoxal/pyridoxine, thiamin) or were correlated with SAM/SAH (vitamin A, E, Hcy) were analyzed instead of the entire 1M SNP data set. This procedure identified 46 SNPs in 25 genes associated with SAM/SAH demonstrating a genetic contribution to the methylation potential. Individual plasma metabolites correlated with 99 plasma proteins. Fourteen proteins correlated with body mass index, 49 with group age, and 30 with sex. The analytical strategy described here identified subgroups for targeted nutritional interventions. © 2014, Springer-Verlag Berlin Heidelberg. Source

Binienda Z.K.,NCTR FDA | Ross I.A.,CFSAN FDA | Gough B.,NCTR FDA | Riccio T.,NCTR FDA | And 2 more authors.
Neuroscience Letters

In order to clarify the mechanism of action of cerulenin analog, C75, known to suppress feeding behavior, food intake was measured in adult CD-1 male mice n = 5 per group, treated i.p. with 10 and 20 mg/kg of C75. Animals in both treatment groups had significantly lower 24 h food consumption rate relative to the control group injected with vehicle. Striatal monoamine neurotransmitters and striatal as well as liver long chain free fatty acids concentrations were subsequently evaluated in another group treated i.p. with 20 mg/kg C75. Acute exposure to C75 at 20 mg/kg led to approximately 50% increase in the striatal dopamine levels and a decrease in dopamine turnover for up to 24 h following the injection. The concentration of serotonin remained unchanged. Concentration of saturated fatty acids in the liver and striatum did not change, while striatal unsaturated myristoleic acid (cis-9-tetradecenoic acid) levels were significantly higher as early as 2 h post-injection and remained elevated at 24 h post-injection. These preliminary data suggest a central regulatory role of unsaturated fatty acids under dopaminergic control in the C75-induced anorexia. Pharmacological alterations in fatty acid metabolism may prove beneficial in the treatment of obesity. Source

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