BackgroundIn patients with acute respiratory failure, gas exchange is impaired due to the accumulation of fluid in the lung airspaces. This life-threatening syndrome is treated with mechanical ventilation, which is adjusted to maintain gas exchange, but can be associated with the accumulation of carbon dioxide in the lung. Carbon dioxide (CO2) is a by-product of cellular energy utilization and its elimination is affected via alveolar epithelial cells. Signaling pathways sensitive to changes in CO2 levels were described in plants and neuronal mammalian cells. However, it has not been fully elucidated whether non-neuronal cells sense and respond to CO2. The Na,K-ATPase consumes ∼40% of the cellular metabolism to maintain cell homeostasis. Our study examines the effects of increased pCO2 on the epithelial Na,K-ATPase a major contributor to alveolar fluid reabsorption which is a marker of alveolar epithelial function.Principal FindingsWe found that short-term increases in pCO2 impaired alveolar fluid reabsorption in rats. Also, we provide evidence that non-excitable, alveolar epithelial cells sense and respond to high levels of CO2, independently of extracellular and intracellular pH, by inhibiting Na,K-ATPase function, via activation of PKCζ which phosphorylates the Na,K-ATPase, causing it to endocytose from the plasma membrane into intracellular pools.ConclusionsOur data suggest that alveolar epithelial cells, through which CO2 is eliminated in mammals, are highly sensitive to hypercapnia. Elevated CO2 levels impair alveolar epithelial function, independently of pH, which is relevant in patients with lung diseases and altered alveolar gas exchange.

Inhaled colistin may achieve high drug concentrations in the lung. However, a dose of 80 mg of inhaled CMS every 8 h may not be adequate for the treatment of lower respiratory tract infections due to multi-drug resistant GNB.

The prevalence and significance of sleep-disordered breathing (SDB) in dialysis-independent chronic renal failure (CRF) remains unknown. We studied the presence of SDB in nondialyzed CRF patients. Diagnostic polysomnography was performed in consecutive stable nondialyzed CRF patients. Inclusion criteria were age 70% pr, absence of neurologic disease or hypothyroidism, and calculated creatinine clearance <40 ml/min. Thirty-five patients (19 male, 16 female) were studied. An apnea-hypopnea index (AHI) >or=5/h was present in 54.3% (almost exclusively obstructive events). AHI correlated with urea (r = 0.35, p = 0.037), age (r = 0.379, p = 0.025), and body mass index (BMI) (r = 0.351, p = 0.038), but not with creatinine clearance. AHI or SDB were unrelated to gender. In nondiabetics (n = 25), AHI correlated with urea (r = 0.608, p = 0.001) and creatinine clearance (r = -0.50, p = 0.012). Nondiabetics with severe CRF (calculated GFR < 15 ml/min/1.73 m(2)) had a significantly higher AHI compared with less severe CRF. Restless legs syndrome (RLS) was present in 37.1% and periodic limb movements in 28.6%. Daytime sleepiness was not associated with respiratory events, but was more common in patients with RLS. The prevalence of SDB and RLS is high in dialysis-independent CRF. SDB weakly correlates with indices of kidney function and this association becomes stronger in nondiabetics.

Linezolid is a new antimicrobial agent effective against drug-resistant gram-positive pathogens commonly responsible for central nervous system (CNS) infections in neurosurgical patients hospitalized in intensive care units. In order to study the penetration of this antimicrobial into the cerebrospinal fluid (CSF) of such patients, the disposition of linezolid in serum and CSF was studied in 14 neurosurgical patients given linezolid at 600 mg twice daily (1-h intravenous infusion) for the treatment of CNS infections caused by gram-positive pathogens or for prophylactic chemotherapy. Serum and CSF linezolid steady-state concentrations were analyzed by high-pressure liquid chromatography, and the concentration-time profiles obtained were analyzed to estimate pharmacokinetic parameters. The mean ؎ standard deviation (SD) linezolid maximum and minimum measured concentrations were 18.6 ؎ 9.6 g/ml and 5.6 ؎ 5.0 g/ml, respectively, in serum and 10.8 ؎ 5.7 g/ml and 6.1 ؎ 4.2 g/ml, respectively, in CSF. The mean ؎ SD areas under the concentration-time curves (AUCs) were 128.7 ؎ 83.9 g · h/ml for serum and 101.6 ؎ 59.6 g · h/ml for CSF, with a mean penetration ratio for the AUC for CSF to the AUC for serum of 0.66. The mean elimination half-life of linezolid in CSF was longer than that in serum (19.1 ؎ 19.0 h and 6.5 ؎ 3.6 h, respectively). The serum and CSF linezolid concentrations exceeded the pharmacodynamic breakpoint of 4 g/ml for susceptible target pathogens for the entire dosing interval in the majority of patients. These findings suggest that linezolid may achieve adequate concentrations in the CSF of patients requiring antibiotics for the management or prophylaxis of CNS infections caused by gram-positive pathogens.Linezolid is the first member of a new synthetic class of antimicrobials, the oxazolidinones, to be used in clinical practice. It acts by selectively inhibiting the initiation of bacterial protein synthesis with a unique mechanism that precludes cross-resistance to currently available agents (10). In vitro and in vivo studies have demonstrated that linezolid has significant bacteriostatic activity against multiresistant gram-positive pathogens, such as coagulase-negative Staphylococcus species, Staphylococcus aureus, vancomycin-resistant enterococci, and Streptococcus pneumoniae, with MIC 90 s generally ranging from 0.5 to 4 g/ml (5, 26).Gram-positive cocci, mainly staphylococci, are the most frequent pathogens involved in central nervous system (CNS) postneurosurgical infections (26). Severe CNS infections caused by gram-positive pathogens may also be related to head trauma with skull fracture in neurosurgical patients, especially in the presence of an external drainage or ventriculoperitoneal shunt. Thus, these patients require antibiotics either for the management of infections or for prophylaxis against such infections. The frequency of CNS infections subsequent to neurosurgical procedures is estimated to be ϳ4% (25). As the epidemiology of CNS infection in neurosurgical patients evolves and the pr...