Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.3.1.21 (CPT)
 4,580 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In elderly patients, an inadequately treated high blood pressure often leads to hypertrophied cardiomyocytes with various defects in gene expression. Due to a decreased expression of the transcription factor PPARalpha, fatty acid oxidation is reduced. If it can be compensated by an increased glucose oxidation, it has been considered as a favorable process. Nonetheless, reduced PPARalpha influences ensue involving e. g. anti-inflammatory mechanisms. The question arises thus whether drugs can normalize reduced PPARalpha effects without increasing fatty acid oxidation. As lead compound of these "fatty acid oxidation inhibitors with PPARalpha activation", the carnitine palmitoyltransferase-1 inhibitor etomoxir was characterized. An increased expression and activity of the Ca (2+) pump of sarcoplasmic reticulum, a faster relaxation and a slowed progression of heart failure was observed in animal experiments. It should, therefore, be examined whether the impaired function of pressure overloaded hypertrophied cardiomyocytes of particularly elderly patients should be a therapeutic target before progression of heart failure, neuroendocrine activation and symptoms such as shortness of breath occur.
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PMID:[Metabolism and the hypertrophied heart of the elderly]. 1577 59

Disease-onset time (DOT) and disease trajectory concepts were applied to derive an Alzheimer's disease (AD) progression population model using the clinical dementia rating scale-sum of boxes (CDR-SOB) from the AD neuroimaging initiative (ADNI) database. The model enabled the estimation of a DOT and a disease trajectory for each patient. The model also allowed distinguishing fast and slow-progressing subpopulations according to the functional assessment questionnaire, normalized hippocampal volume, and CDR-SOB score at study entry. On the basis of these prognostic factors, 81% of the mild cognitive impairment (MCI) subjects could correctly be assigned to slow or fast progressers, and 77% of MCI to AD conversions could be predicted whereas the model described correctly 84% of the conversions. Finally, synchronization of the biomarker-time profiles on estimated individual DOT virtually expanded the population observation period from 3 to 8 years. DOT-disease trajectory model is a powerful approach that could be applied to many progressive diseases.CPT: Pharmacometrics & Systems Pharmacology (2013) 2, e78; doi:10.1038/psp.2013.54; advance online publication 2 October 2013.
CPT Pharmacometrics Syst Pharmacol 2013 Oct 02
PMID:Modeling Alzheimer's Disease Progression Using Disease Onset Time and Disease Trajectory Concepts Applied to CDR-SOB Scores From ADNI. 2408 49