Protective role of PI3-kinase/Akt/eNOS signaling in mechanical stress through inhibition of p38 mitogenactivated protein kinase in mouse lung

Aim:

To test the hypothesis that PI3K/Akt/eNOS signaling has a protective role in a murine model of ventilation associated lung injury (VALI) through down-regulation of p38 MAPK signaling.

Methods:

Male C57BL/J6 (wild-type, WT) or eNOS knockout mice (eNOS^−/−) were exposed to mechanical ventilation (MV) with low (LV_T, 7 mL/kg) and high tidal volume (HV_T, 20 mL/kg) for 0−4 h. A subset of WT mice was administered the specific inhibitors of PI3K (100 nmol/L Wortmannin [Wort], ip) or of p38 MAPK (SB203580, 2 mg/kg, ip) 1 h before MV. Cultured type II alveolar epithelial cells C10 were exposed to 18% cyclic stretch for 2 h with or without 20 nmol/L Wort pretreatment. At the end of the experiment, the capillary leakage in vivo was assessed by extravasation of Evans blue dye (EBD), wet/dry weight ratio and lung lavage protein concentration. The lung tissue and cell lysate were also collected for protein and histological review.

Results:

MV decreased PI3K/Akt phosphorylation and eNOS expression but increased phospho-p38 MAPK expression along with a lung leakage of EBD. Inhibitions of phospho-Akt by Wort worsen the lung edema, whereas inhibition of p38 MAPK kinase restored activation of Akt together with alleviated capillary leakage. eNOS^−/− mice showed an exacerbated lung edema and injury. The stretched C10 cells demonstrated that Wort diminished the activation of Akt, but potentiated phosphorylation of MAPK p38.

Conclusion:

Our results indicate that PI-3K/Akt/eNOS pathway has significant protective effects in VALI by preventing capillary leakage, and that there is a cross-talk between PI3K/Akt and p38 MAPK pathways in vascular barrier dysfunction resulting from VALI.     

Pelvimetry — a Squatter''s View

Patients were X-rayed in supine and squatting positions in order to measure any increase in pelvic outlet diameters. An increase of less than 2% was found. Previous estimates of 20-30% increases in pelvic outlet area were not duplicated.     

Anticardiolipin antibodies in cluster headache

Antiphospholipid antibodies have occasionally been observed in migraine patients, but a recent study of a large series suggested the association was with other concurrent conditions, not specifically with migraine. We wondered about an association with other vascular headaches and measured anticardiolipin antibody levels in 20 cluster headache patients during the cluster period (three during an acute attack). Platelet counts were normal and VDRL negative in all patients. No elevated anticardiolipin antibody levels were found. There appears to be no important association between the presence of anticardiolipin antibodies and cluster headache, and we argue that there is no further rationale for seeking one.     

Psychiatric nursing management of medication-free psychotic patients

This article discusses how a team of psychiatric nurses manages acutely psychotic patients on a clinical research unit without the use of psychotropic medications. The article describes a schizophrenia research unit, identifies the behaviors of acutely psychotic patients, and provides examples of effective nursing interventions used on the unit. These interventions are grounded in principles of interpersonal psychiatric nursing practice and milieu therapy. The discussion is directed to psychiatric nurses and other health care professionals who are employed on research units.