The LCLAT1/LYCAT acyltransferase is required for EGF-mediated phosphatidylinositol-3,4,5-trisphosphate generation and Akt signaling.

Receptor tyrosine kinases such as EGF receptor (EGFR) stimulate phosphoinositide 3 kinases to convert phosphatidylinositol-4,5-bisphosophate [PtdIns(4,5)P] into phosphatidylinositol-3,4,5-trisphosphate [PtdIns(3,4,5)P]. PtdIns(3,4,5)P then remodels actin and gene expression, and boosts cell survival and proliferation. PtdIns(3,4,5)P partly achieves these functions by triggering activation of the kinase Akt, which phosphorylates targets like Tsc2 and GSK3β.

Pharmacokinetic/pharmacodynamic evaluation of urinary cortisol suppression after inhalation of fluticasone propionate and mometasone furoate.

Aim: Fluticasone propionate (FP) and mometasone furoate (MF) are inhaled corticosteroids that possess a high ratio of topical to systemic activity. The systemic bioavailability of MF has been claimed to be minimal (1%). FP has been shown to exhibit the same degree of systemic effects, but its systemic availability is between 13 and 17%.

Suspected lung cancer: its initial management and staging.

Lung cancer has traditionally been viewed as being difficult to treat and generally associated with a poor outcome. With new advances in technology and medicine in general, the public has come to expect a better prognosis from lung cancer. Once a patient has been referred with suspected lung cancer, it is important to confirm the diagnosis and to stage the cancer; in this way, one can ascertain whether or not the cancer is potentially operable.

A proof of concept study to evaluate stepping down the dose of fluticasone in combination with salmeterol and tiotropium in severe persistent asthma.

We conducted a double blind, randomised, placebo-controlled, crossover study evaluating the effects of halving inhaled steroid dosage plus salmeterol, or salmeterol and tiotropium. Eighteen life-long non-smoking severe asthmatics [mean FEV(1) 1.49 l (51%)] were run-in for 4 weeks on HFA-fluticasone propionate 1000 microg daily, and were subsequently randomised to 4 weeks of either (a) HFA-fluticasone propionate 500 microg BD/salmeterol 100 microg BD/HFA-tiotropium bromide18 microg od; or (b) fluticasone propionate 500 microg BD/salmeterol 100 microg BD matched placebo.

Long-acting beta2-agonists in asthma: not so SMART?

Asthma is a worldwide chronic disorder that is characterised by airway inflammation and hyper-responsiveness, which results in intermittent airflow obstruction and subsequent perception of symptoms and exacerbations. Inhaled corticosteroids are a fundamental component in the prevention of the short- and long-term complications associated with inadequately controlled asthma. However, many individuals experience persistent symptoms and exacerbations despite receiving low-to-medium doses of an inhaled corticosteroid (400-800 microg/day of beclometasone or equivalent).

Long-acting bronchodilator or leukotriene modifier as add-on therapy to inhaled corticosteroids in persistent asthma?

Despite the widespread use of inhaled corticosteroids, many asthmatic patients experience persistent symptoms. In such individuals, the addition of a long-acting beta2-agonist (LABA) is frequently more effective than doubling the dose of inhaled corticosteroid. However, the role of additional therapy with a leukotriene receptor antagonist (LTRA) as an alternative to an LABA has been the focus of attention in recent studies.

Addition of fexofenadine to inhaled corticosteroid therapy to reduce inflammatory biomarkers in atopic asthma.

Background: We previously showed that H1-antihistamines may shift the PC20 (provocation concentration that caused a decrease in forced expiratory volume in 1 second of 20%) threshold to adenosine monophosphate (AMP) challenge but may paradoxically prolong recovery.

Objectives: To measure AMP recovery using a constant predetermined AMP PC20 and to evaluate whether fexofenadine use confers add-on effects to treatment with either fluticasone propionate alone or combined fluticasone propionate-salmeterol.

Methods: Fourteen atopic patients with mild-to-moderate asthma (forced expiratory volume in 1 second of 76%) completed a double-blind, randomized, crossover study consisting of 3-week treatment blocks of either fluticasone propionate-salmeterol, 250 microg twice daily, or fluticasone propionate alone, 250 microg twice daily, in conjunction with either fexofenadine, 180 mg once daily, or matched placebo.

Effects of tiotropium and other long acting bronchodilators in chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) accounts for a major workload in both primary and secondary care. It is characterised by progressive airflow obstruction which does not fully reverse to inhaled or oral pharmacotherapy. The diagnosis should be considered in any current or former smoker who has symptoms of breathlessness, wheeze, cough, sputum production and impaired exercise tolerance.

Effects of dual therapy with corticosteroids plus long acting beta2-agonists in asthma.

Asthma is a common condition characterised by inflammation, airway hyperresponsiveness and reversible airflow obstruction. Effective pharmacotherapy must therefore be aimed at attenuating these underlying hallmark features. Despite the use of regular low-to-moderate doses of inhaled corticosteroids, many patients remain symptomatic and require further 2nd line controller therapy.