Mesenchymal stem cells protect from hypoxia-induced alveolar epithelial-mesenchymal transition.

Administration of bone marrow-derived human mesenchymal stem cells (hMSC) reduces lung inflammation, fibrosis, and mortality in animal models of lung injury, by a mechanism not completely understood. We investigated whether hMSC would prevent epithelial-mesenchymal transition (EMT) induced by hypoxia in primary rat alveolar epithelial cell (AEC). In AEC cultured on semipermeable filters, prolonged hypoxic exposure (1.

Conditioned media from mesenchymal stromal cells restore sodium transport and preserve epithelial permeability in an in vitro model of acute alveolar injury.

Mesenchymal stromal cells (MSCs) or their media (MSC-M) were reported to reverse acute lung injury (ALI)-induced decrease of alveolar fluid clearance. To determine the mechanisms by which MSC-M exert their beneficial effects, an in vitro model of alveolar epithelial injury was created by exposing primary rat alveolar epithelial cells (AECs) to hypoxia (3% O2) plus cytomix, a combination of IL-1β, TNF-α, and IFN-γ. MSC-M were collected from human MSCs exposed for 12 h to either normoxia (MSC-M) or to hypoxia plus cytomix (HCYT-MSC-M).

Neural mechanisms underlying breathing complexity.

Breathing is maintained and controlled by a network of automatic neurons in the brainstem that generate respiratory rhythm and receive regulatory inputs. Breathing complexity therefore arises from respiratory central pattern generators modulated by peripheral and supra-spinal inputs. Very little is known on the brainstem neural substrates underlying breathing complexity in humans.

Hypoxia-induced inhibition of epithelial Na(+) channels in the lung. Role of Nedd4-2 and the ubiquitin-proteasome pathway.

Transepithelial sodium transport via alveolar epithelial Na(+) channels (ENaC) and Na(+),K(+)-ATPase constitutes the driving force for removal of alveolar edema fluid. Alveolar hypoxia associated with pulmonary edema may impair ENaC activity and alveolar Na(+) absorption through a decrease of ENaC subunit expression at the apical membrane of alveolar epithelial cells (AECs). Here, we investigated the mechanism(s) involved in this process in vivo in the β-Liddle mouse strain mice carrying a truncation of β-ENaC C-terminus abolishing the interaction between β-ENaC and the ubiquitin protein-ligase Nedd4-2 that targets the channel for endocytosis and degradation and in vitro in rat AECs.

Idiopathic interstitial lung disease with anti-SSA antibody.

Objectives: Consensus is lacking on the immunological tests to perform for diagnosis of interstitial lung diseases (ILDs). In particular, the value of detecting anti-SSA antibody in this context is unknown. We aimed to determine whether the detection of anti-SSA antibody in patients with ILD can identify a subgroup of patients with CTD.

Ventilatory chaos is impaired in carotid atherosclerosis.

Ventilatory chaos is strongly linked to the activity of central pattern generators, alone or influenced by respiratory or cardiovascular afferents. We hypothesized that carotid atherosclerosis should alter ventilatory chaos through baroreflex and autonomic nervous system dysfunctions. Chaotic dynamics of inspiratory flow was prospectively evaluated in 75 subjects undergoing carotid ultrasonography: 27 with severe carotid stenosis (>70%), 23 with moderate stenosis (<70%), and 25 controls.

Effect of neutrophil elastase and its inhibitor EPI-hNE4 on transepithelial sodium transport across normal and cystic fibrosis human nasal epithelial cells.

Background: Hyperactivity of the epithelial sodium (Na+) channel (ENaC) and increased Na+ absorption by airway epithelial cells leading to airway surface liquid dehydration and impaired mucociliary clearance are thought to play an important role in the pathogenesis of cystic fibrosis (CF) pulmonary disease. In airway epithelial cells, ENaC is constitutively activated by endogenous trypsin-like serine proteases such as Channel-Activating Proteases (CAPs). It was recently reported that ENaC activity could also be stimulated by apical treatment with human neutrophil elastase (hNE) in a human airway epithelial cell line, suggesting that hNE inhibition could represent a novel therapeutic approach for CF lung disease.

The impact of bariatric surgery on comorbidities and medication use among obese patients.

Background: The risks and benefits of bariatric surgery have rarely been evaluated in large multiyear patient samples. This study identifies the short- and long-term impact of bariatric surgery on comorbidities and medication use among obese patients.

Methods: A comprehensive analysis of 5,502 obese patients who underwent bariatric surgery was performed.

Predictive factors of weight loss 1 year after laparoscopic gastric bypass in obese patients.

Background: Substantial weight loss is achieved in majority of severely obese subjects undergoing laparoscopic gastric bypass (LGBP) but some fail to obtain expected results. Our aim was to identify preoperative factors that could influence weight loss (WL) 1 year after LGBP.

Methods: We studied the predictive value of clinical, biological, and dietary preoperative factors on weight loss in obese patients referred for LGBP.

Multispecies breath analysis faster than a single respiratory cycle by optical-feedback cavity-enhanced absorption spectroscopy.

We demonstrate a first application, of optical-feedback cavity-enhanced absorption spectroscopy (OF-CEAS) to breath analysis in a medical environment. Noninvasive monitoring of trace species in exhaled air was performed simultaneous to spirometric measurements on patients at Bichat Hospital (Paris). The high selectivity of the OF-CEAS spectrometer and a time response of 0.

ENaC-mediated alveolar fluid clearance and lung fluid balance depend on the channel-activating protease 1.

Sodium transport via epithelial sodium channels (ENaC) expressed in alveolar epithelial cells (AEC) provides the driving force for removal of fluid from the alveolar space. The membrane-bound channel-activating protease 1 (CAP1/Prss8) activates ENaC in vitro in various expression systems. To study the role of CAP1/Prss8 in alveolar sodium transport and lung fluid balance in vivo, we generated mice lacking CAP1/Prss8 in the alveolar epithelium using conditional Cre-loxP-mediated recombination.

Traditional anthropometric parameters still predict metabolic disorders in women with severe obesity.

It is well established that fat distribution rather than the total quantity of fat is the major determinant of cardiovascular risk in overweight subjects. However, it is not known whether the concept of fat distribution still makes sense in severely obese subjects. Particularly, the role of visceral fat accumulation and/or of adipocyte hypertrophy in insulin resistance (IR) has not been studied in this population.

Chaotic dynamics of cardioventilatory coupling in humans: effects of ventilatory modes.

Cardioventilatory coupling (CVC), a transient temporal alignment between the heartbeat and inspiratory activity, has been studied in animals and humans mainly during anesthesia. The origin of the coupling remains uncertain, whether or not ventilation is a main determinant in the CVC process and whether the coupling exhibits chaotic behavior. In this frame, we studied sedative-free, mechanically ventilated patients experiencing rapid sequential changes in breathing control during ventilator weaning during a switch from a machine-controlled assistance mode [assist-controlled ventilation (ACV)] to a patient-driven mode [inspiratory pressure support (IPS) and unsupported spontaneous breathing (USB)].

Gene regulation in the adaptive process to hypoxia in lung epithelial cells.

Lung alveolar epithelial cells are normally very well oxygenated but may be exposed to hypoxia in many pathological conditions such as pulmonary edema, acute respiratory distress syndrome, chronic obstructive pulmonary diseases, or in some environmental conditions such ascent to high altitude. The ability of alveolar epithelial cells to cope with low oxygen tensions is crucial to maintain the structural and functional integrity of the alveolar epithelium. Alveolar epithelial cells appear to be remarkably tolerant to oxygen deprivation as they are able to maintain adequate cellular ATP content during prolonged hypoxic exposure when mitochondrial oxidative phosphorylation is limited.

Nutritional consequences of adjustable gastric banding and gastric bypass: a 1-year prospective study.

Background: Gastric bypass (GBP) is more efficient than adjustable gastric banding (AGB) on weight loss and comorbidities, but potentially induces more nutritional deficits. However, no study has compared the prevalence of nutritional deficiencies after these two bariatric procedures. WE PROSPECTIVELY COMPARED: To prospectively compare the prevalence of nutritional deficiencies after AGB and GBP.

Source of human ventilatory chaos: lessons from switching controlled mechanical ventilation to inspiratory pressure support in critically ill patients.

Ventilatory flow measured at the airway opening in humans exhibits a complex dynamics that has the features of chaos. Currently available data point to a neural origin of this feature, but the role of respiratory mechanics has not been specifically assessed. In this aim, we studied 17 critically ill mechanically ventilated patients during a switch form an entirely machine-controlled assistance mode (assist-controlled ventilation ACV) to a patient-driven mode (inspiratory pressure support IPS).

Low expression of the beta-ENaC subunit impairs lung fluid clearance in the mouse.

Transepithelial alveolar sodium (Na+) transport mediated by the amiloride-sensitive epithelial sodium channel (ENaC) constitutes the driving force for removal of fluid from the alveolar space. To define the role of the beta-ENaC subunit in vivo in the mature lung, we studied a previously established mouse strain harboring a disruption of the beta-ENaC gene locus resulting in low levels of beta-ENaC mRNA expression. Real-time RT-PCR experiments confirmed that beta-ENaC mRNA levels were decreased by >90% in alveolar epithelial cells from homozygous mutant (m/m) mice.

Modulation of epithelial sodium channel trafficking and function by sodium 4-phenylbutyrate in human nasal epithelial cells.

Sodium 4-phenylbutyrate (4-PBA) has been shown to correct the cellular trafficking of several mutant or nonmutant plasma membrane proteins such as cystic fibrosis transmembrane conductance regulator through the expression of 70-kDa heat shock proteins. The objective of the study was to determine whether 4-PBA may influence the functional expression of epithelial sodium channels (ENaC) in human nasal epithelial cells (HNEC). Using primary cultures of HNEC, we demonstrate that 4-PBA (5 mm for 6 h) markedly stimulated amiloride-sensitive sodium channel activity and that this was related to an increased abundance of alpha-, beta-, and gamma-ENaC subunits in the apical membrane.

Cardiovascular remodelling and extracellular fluid excess in early stages of chronic kidney disease.

Background: Patients with a mild to moderate decrease of glomerular filtration rate (GFR) are at risk of cardiovascular (CV) events and CV remodelling has been demonstrated in patients with advanced chronic kidney disease (CKD). However, early stages of CKD and the mechanisms involved in these modifications have not been studied.

Methods: A total of 104 patients with early CKD (mean GFR 60+/-21 ml/min/1.

beta-Liddle mutation of the epithelial sodium channel increases alveolar fluid clearance and reduces the severity of hydrostatic pulmonary oedema in mice.

Transepithelial sodium transport via alveolar epithelial Na(+) channels and Na(+),K(+)-ATPase constitutes the driving force for removal of alveolar oedema fluid. Decreased activity of the amiloride-sensitive epithelial Na(+) channel (ENaC) in the apical membrane of alveolar epithelial cells impairs sodium-driven alveolar fluid clearance (AFC) and predisposes to pulmonary oedema. We hypothesized that hyperactivity of ENaC in the distal lung could improve AFC and facilitate the resolution of pulmonary oedema.

Comparison of nutritional consequences of conventional therapy of obesity, adjustable gastric banding, and gastric bypass.

Background: Roux-en-Y gastric bypass (RYGBP) is more efficient than adjustable gastric banding (AGB) in weight loss and relieving co-morbidities, but nutritional complications of each surgical procedure have been poorly evaluated.

Methods: A cross-sectional study was performed to compare nutritional parameters in 201 consecutive obese patients, who had been treated either by conventional behavioral and dietary therapy (CT, n=110) or by bariatric surgery, including 51 AGB and 40 RYGBP.

Results: BMI was similar after AGB (36.