The combination of microfluidic cell trapping devices with ion mobility-mass spectrometry offers the potential for elucidating in real time the dynamic responses of small populations of cells to paracrine signals, changes in metabolite levels, and delivery of drugs and toxins. Preliminary experiments examining peptides in methanol and recording the interactions of yeast and Jurkat cells with their superfusate have identified instrumental setup and control parameters and on-line desalting procedures. Numerous initial experiments demonstrate and validate this new instrumental platform. Future outlooks and potential applications are addressed, specifically how this instrumentation may be used for fully automated systems biology studies of the significantly interdependent, dynamic internal workings of cellular metabolic and signaling pathways.
Systemic inflammatory responses after cardiopulmonary bypass were associated with activation of p38 and nuclear factor-κB pathways in circulating leukocytes. Inflammatory responses to cardiopulmonary bypass can be reduced by sulforaphane, which reduced leukocyte activation and protected against renal injury.
Surgery on the thoracic aorta is challenging and historically associated with significant mortality and morbidity. In recent times, there has been increased emphasis on the importance of health-related quality of life (HRQOL) measures. It is seen as a development beyond isolated markers of outcome such as operative mortality and is particularly applicable to aortic surgery given the number of asymptomatic patients operated on (for prognostic grounds), and rapidly advancing endovascular technologies which require proper assessment. This systematic review provides an outline of all available literature detailing HRQOL in patients receiving intervention (both open and endovascular) on the thoracic aorta. In total, 30 studies were identified encompassing 4746 patients undergoing a variety of procedures from aortic root replacement to thoracoabdominal aortic aneurysm repair. While there were deficiencies in the underlying literature such as lack of baseline HRQOL assessment, the majority of the studies confirm that HRQOL after major aortic surgery (including on the elderly and in emergency situations) is acceptable and compares well to matched general populations. Strategies for improving the HRQOL in aortic surgery are summarized and include the need for surgeons to plan cerebral protection methods more carefully and to develop operative strategies to avoid reoperation or reintervention, as this is associated with deterioration of long-term HRQOL. Randomized studies measuring baseline and follow-up HRQOL at specific set points are needed. Innovative research methods could be employed in future studies with the aim of correlating HRQOL with imaging or physiological/inflammation biomarkers, or other end points such as aortic stiffness or wall shear stress to characterize disease progression and prognosis.
Cytometric studies utilizing flow cytometry or multi-well culture plate fluorometry are often limited by a deficit in temporal resolution and a lack of single cell consideration. Unfortunately, many cellular processes, including signaling, motility, and molecular transport, occur transiently over relatively short periods of time and at different magnitudes between cells. Here we demonstrate the multitrap nanophysiometer (MTNP), a low-volume microfluidic platform housing an array of cell traps, as an effective tool that can be used to study individual unattached cells over time with precise control over the intercellular microenvironment. We show how the MTNP platform can be used for hematologic cancer cell characterization by measuring single T cell levels of CRAC channel modulation, non-translational motility, and ABC-transporter inhibition via a calcein-AM efflux assay. The transporter data indicate that Jurkat T cells exposed to indomethacin continue to accumulate fluorescent calcein for over 60 minutes after calcein-AM is removed from the extracellular space.
Both p38-MAPK activation and ROS were attenuated with the use of mCPB compared with cCPB, providing a potential mechanism for reduced inflammation in association with CPB miniaturization.
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