Chronobiology international
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The purpose of this pilot study was to explore the utility of the mammalian swine model under simulated intensive care unit (sICU) conditions and mechanical ventilation (MV) for assessment of the trajectory of circadian rhythms of sedation requirement, core body temperature (CBT), pulmonary mechanics (PM) and gas exchange (GE). Data were collected prospectively with an observational time-series design to describe and compare circadian rhythms of selected study variables in four swine mechanically ventilated for up to seven consecutive days. We derived the circadian (total variance explained by rhythms of τ between 20 and 28 h)/ultradian (total variance explained by rhythms of τ between 1 and <20 h) bandpower ratio to assess the robustness of circadian rhythms, and compare findings between the early (first 3 days) and late (subsequent days) sICU stay. ⋯ Individual subject observations were more informative than group data, and provided preliminary evidence that (a) circadian rhythms of multiple variables are lost or desynchronized in mechanically ventilated subjects, (b) robustness of circadian rhythm varies with subject morbidity and (c) healthier pigs develop more robust circadian rhythm profiles over time in the sICU. Comparison of biological rhythm profiles among sICU subjects with similar severity of illness is needed to determine if the results of this pilot study are reproducible. Identification of consistent patterns may provide insight into subject morbidity and timing of such therapeutic interventions as weaning from MV.
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Simultaneous analysis of the transcripts of thousands of genes by cDNA microarrays allows the identification of genetic regulatory mechanisms involved in disease pathophysiology. The circadian clock circuitry controls essential cell processes and the functioning of organ systems, which are characterized by rhythmic variations with 24-hour periodicity. The derangement of these processes is involved in the basic mechanisms of inflammatory, metabolic, degenerative and neoplastic diseases. ⋯ Conversely, ARNTL2, CRY1, CSNK1E, RORA and TIPIN were up-regulated, while NR1D2 and PER3 were down-regulated in UC. In conclusion, in CD and UC patients there are differences in the expression of circadian genes between normal and diseased intestinal mucosa. The deregulated genes evidenced by transcriptome analysis in the major IBDs may play a crucial role in the pathophysiological mechanisms and may suggest novel therapeutic approaches.