Dexamethasone regulates glutamine synthetase expression in rat skeletal muscles

The regulation of glutamine synthetase by glucocorticoids in rat skeletal muscles was studied. Administration of dexamethasone strikingly enhanced glutamine synthetase activity in plantaris and soleus muscles. The dexamethasone-mediated induction of glutamine synthetase activity was blocked to a significant extent by orally administered RU38486, a glucocorticoid antagonist, indicating the involvement of intracellular glucocorticoid receptors in the induction. Northern blot analysis revealed that dexamethasone-mediated enhancement of glutamine synthetase activity involves dramatically increased levels of glutamine synthetase mRNA. The induction of glutamine synthetase was selective in that glutaminase activity of soleus and plantaris muscles was not increased by dexamethasone. Furthermore, dexamethasone treatment resulted in only a small increase in glutamine synthetase activity in the heart. Accordingly, there was only a slight change in glutamine synthetase mRNA level in this tissue. Thus, glucocorticoids regulate glutamine synthetase gene expression in rat muscles at the transcriptional level via interaction with intracellular glutamine production by muscle and to mechanisms underlying glucocorticoid-induced muscle atrophy

Simultaneous measurement of flight time and energy of large matrix-assisted laser desorption ionization ions with a superconducting tunnel junction detector

We evaluated a cryogenically cooled superconducting Nb-Al2O3-Nb tunnel junction (STJ) for use as a molecular ion detector in a matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometer. The STJ responds to ion energy and theoretically should detect large molecular ions with a velocity-independent efficiency approaching 100%. The STJ detector produces pulses whose heights are approximately proportional to ion energy, thus the height of a pulse generated by the impact of a doubly charged ion is about twice the height of a singly charged ion pulse. Measurements were performed by bombarding the STJ with human serum albumin (HSA) (66,000 Da) and immunoglobulin (150,000 Da) ions. We demonstrate that pulse height analysis of STJ signals provides a way to distinguish with good discrimination HSA+ from 2HSA2+, whose flight times are coincident. The rise time of STJ detector pulses allows ion flight times to be determined with a precision better than 200 ns, which is a value smaller than the flight time variation typically observed for large isobaric MALDI ions detected with conventional microchannel plate (MCP) detectors. Deflection plates in the flight tube of the mass spectrometer provided a way to aim ions alternatively at a MCP ion detector

Clinical decision support recommending ventilator settings during noninvasive ventilation

NIV therapy is used to provide positive pressure ventilation for patients. There are protocols describing what ventilator settings to use to initialize NIV; however, the guidelines for titrating ventilator settings are less specific. We developed an advisory system to recommend NIV ventilator setting titration and recorded respiratory therapist agreement rates at the bedside. We developed an algorithm (NIV advisor) to recommend when to change the non-invasive ventilator settings of IPAP, EPAP, and FiO(2) based on patient respiratory parameters. The algorithm utilized a multi-target approach; oxygenation, ventilation, and patient effort. The NIV advisor recommended ventilator settings to move the patient's respiratory parameters in a preferred target range. We implemented a pilot study evaluating the usability of the NIV advisor on 10 patients receiving critical care with non-invasive ventilation (NIV). Respiratory therapists were asked their agreement on recommendations from the NIV advisor at the patient's bedside. Bedside respiratory therapists agreed with 91% of the ventilator setting recommendations from the NIV advisor. The POB and VT values were the respiratory parameters that were most often out of the preferred target range. The IPAP ventilator setting was the setting most often considered in need of changing by the NIV advisor. The respiratory therapists agreed with the majority of the recommendations from the NIV advisor. We consider the IPAP recommendations informative in providing the respiratory therapist assistance in targeting preferred POB and Vt values, as these values were frequently out of the target ranges. This pilot implementation was unable to produce the results required to determine the value of the EPAP recommendations. The FiO(2) recommendations from the NIV advisor were treated as ancillary information behind the IPAP recommendations

Patients alter power of breathing as the primary response to changes in pressure support ventilation

The patient-ventilator relationship is dynamic as the patient's health fluctuates and the ventilator settings are modified. Spontaneously breathing patients respond to mechanical ventilation by changing their patterns of breathing. This study measured the physiologic response when pressure support (PS) settings were modified during mechanical ventilation. Subjects were instrumented with a non-invasive pressure, flow, and carbon dioxide airway sensor to estimate tidal volume, respiratory rate, minute ventilation, and end-tidal CO . Additionally, a catheter was used to measure esophageal pressure and estimate effort exerted during breathing. Respiratory function measurements were obtained while PS settings were adjusted 569 times between 5 and 25 cmH O. Data was collected on 248 patients. The primary patient response to changes in PS was to adjusting effort (power of breathing) followed by adjusting tidal volume. Changes in respiratory rate were less definite while changes in minute ventilation and end-tidal CO appeared unrelated to the change in PS. The data indicates that patients maintain a set minute ventilation by adjusting their breathing rate, volume, and power. The data indicates that the subjects regulate their Ve and PetCO by adjusting power of breathing and breathing pattern

Trauma-induced heme release increases susceptibility to bacterial infection

Infection is a common complication of major trauma that causes significantly increased morbidity and mortality. The mechanisms, however, linking tissue injury to increased susceptibility to infection remain poorly understood. To study this relationship, we present a potentially novel murine model in which a major liver crush injury is followed by bacterial inoculation into the lung. We find that such tissue trauma both impaired bacterial clearance and was associated with significant elevations in plasma heme levels. While neutrophil (PMN) recruitment to the lung in response to Staphylococcus aureus was unchanged after trauma, PMN cleared bacteria poorly. Moreover, PMN show > 50% less expression of TLR2, which is responsible, in part, for bacterial recognition. Administration of heme effectively substituted for trauma. Finally, day 1 trauma patients (n = 9) showed similar elevations in free heme compared with that seen after murine liver injury, and circulating PMN showed similar TLR2 reduction compared with volunteers (n = 6). These findings correlate to high infection rates