Focal adhesion kinase (FAK) is a tyrosine kinase ubiquitously expressed in cells. It was initially shown to be the initiator of focal adhesion formation in adherent cells, after its binding to integrins which induce its autophosphorylation. However, it can be also activated by a great variety of other stimuli able to act on different intracellular signaling. Reactive oxygen species (ROS), which have been shown to act as external or internal cell stimuli, induce tyrosine phosphorylation of FAK. Its autophosphorylation is followed by a submembranous localization which is crucial for many of the biological roles of FAK, including cell spreading, cell migration, cell proliferation, and prevention of apoptosis. It plays an important role in development of tumor cells, its regulation could be thus a way of impairing cell proliferation in cancer. We describe in this review the structure, activity, and functions of FAK in different cells and how ROS are able, like other stimuli, to induce its phosphorylation and modification of cell morphology and structure. The link between ROS and FAK activation could explain the role of ROS in mediating cell proliferation, cell migration, or apoptosis.

Animals↗

PubMedDate not supplied

Can statins reduce the inflammatory response to cardiopulmonary bypass? A clinical study.

OBJECTIVE: In addition to lowering lipid levels, statins might reduce leukocyte-endothelial cell interactions. Therefore, we assessed whether this effect could limit the inflammatory response to cardiopulmonary bypass (CPB) in cardiac surgical patients. METHODS: Twenty patients undergoing valve or coronary operations with tepid (34 degrees C) CPB were randomized to receive an oral dose of atorvastatin (40 mg the evening before and 40 mg the morning of surgery) or to serve as controls. Pre- and post-CPB blood samples were assayed for neutrophil CD11b surface adhesion molecule and oxidative burst. Plasma levels of interleukins 6 and 8, P-selectin, soluble intercellular adhesion molecule-1, and lactoferrin were measured by enzyme-linked immunosorbent assay (ELISA). In addition, right atrial biopsies were taken before and at the end of CPB, and processed for the expression of the transcription nuclear factor-kappa B (NF-kappaB). RESULTS: The two groups did not differ with regard to pre- and intraoperative data. Except for P-selectin, postbypass values of all markers significantly increased over baseline values, but atorvastatin therapy failed to attenuate the magnitude of this increase. In the two groups, the expression of NF-kappaB significantly (p = 0.004) increased over baseline without group effect. Postoperative clinical outcomes did not differ either between the two groups. CONCLUSION: These data show that acute preoperative statin therapy fails to limit the inflammatory response to CPB; however, the data also document a major upregulation of NF-kappaB during cardiac operations, thereby providing a sound rationale for interventions targeted at inactivating this key component of the inflammatory cascade.

Aged↗

PubMedDate not supplied

[Acute sinusitus in adults. Management by general practitioners].

OBJECTIVE: Acute sinusitis is a common condition encountered in general practice and raises the question of appropriate management. Sufficient data are still lacking in the literature to provide a fully satisfactory response. METHODS: We conducted a survey among 193 physicians representative of the general practitioners in France to collect 755 cases of acute sinusitis treated in the outpatient setting from January 6 through March 15, 1999. We recorded clinical features and therapeutic management. RESULTS: Pain was the predominant clinical sign (97% of the patients). Facial pain with a highly suggestive localization and aggravated by pressure and headache were the most frequent. Most of the patients also had a nasal symptom (77%) and an infectious context (90%). Three circumstances had been pre-defined by the experts: unique acute sinusitis, acute episode of chronic sinusitis, and recurrent acute sinusitis. In 67% of the cases of unique acute sinusitis, the diagnosis of the general practitioner was confirmed a posterori by the experts. Few complementary tests were ordered (in 17% of the patients) mainly in fragile patients and mainly limited to a radiography of the sinus (81% of the complementary tests ordered). An oral antibiotic was almost always prescribed (96% of the patients) although antibiotics comprised only 29% of all prescriptions. General corticosteroid therapy (41%), local treatment (73%) and anti-cough or expectoration medications (52%) were also prescribed. Despite the painful nature of sinusitis, analgesics were only prescribed for 36% of the patients. CONCLUSION: This observational survey enabled us to describe the diagnostic and therapeutic strategy used by French general practitioners for acute sinusitis in adults. There was general agreement on the strategy that was well adapted to the patient profiles. An evaluation of the different classes of drugs prescribed, and their efficacy in the outpatient setting, that remains to be determined, was not however attempted.

Acute Disease↗