Corticosteroids as long-term regulators of the insulin effectiveness in mouse 3T3 adipocytes

Summary Since corticosteroid treatment is often accompanied by insulin resistance, we explored the role of corticosteroids in the regulation of the insulin effectiveness in cultured 3T3 (mouse) adipocytes. Exposure of the fat cells to dexamethasone or corticosterone (0–5 days) induced a time-, concentration-, and protein synthesis-dependent and reversible decrease in insulin binding and in basal and insulin-stimulated 2-deoxyglucose uptake. The decrease in binding (50%) was primarily due to a decrease in receptor affinity i. e. to an increase in the rate of dissociation of insulin from its receptors, and was independent from the effects of pH and temperature on the affinity. The reduction in the 2-deoxyglucose uptake (30–50%) was due to a decrease in the hexose transport capacity rather than to a decrease in the phosphorylation component of the 2-deoxyglucose uptake process. Lineweaver-Burk analysis revealed the dexamethasone induced a decrease in the apparent V_max of the transport system i. e. in the number or activity of the hexose transporters. The effect of dexamethasone seemed to be superimposed on that of long-term insulin treatment, suggesting a different mechanism. It is concluded that corticosteroids act as long-term regulators of the insulin effectiveness by influencing the rate at which insulin dissociates from its receptors and by altering the number or activity of the hexose transporters by a common mechanism, which differs from that of the long-term regulatory effect of insulin.     

Limited treatment adaptation despite poor asthma control in asthma patients treated with inhaled corticosteroids

Objective: Current asthma guidelines recommend use of inhaled corticosteroids (ICS) in patients with persistent disease. This study was designed to investigate (1) the proportion of patients prescribed ICS-containing maintenance treatment who achieve asthma control, (2) determinants of control and (3) how physicians adapt treatment to the level of control. Methods: General practitioners (GPs) and chest physicians (CPs) in France recruited patients consulting for asthma and prescribed an ICS. Over a 2-year follow-up period, asthma symptoms in the previous 3 months and treatments prescribed were documented at each visit. Variables independently associated with asthma control were determined by multiple logistic regression. Results: Data were available for 924 patients recruited by GPs and 455 recruited by CPs. Asthma control was acceptable in only 24% of patients at inclusion, and in 33.6% at the last follow-up visit. Five factors were independently associated with asthma control: age (or time since diagnosis), gender, smoking status, allergic aetiology of asthma and treatment. Most patients (56.3%) were prescribed the same ICS dose regimen at the end of follow-up as at inclusion. The intensity of controller therapy had been increased in only 12.2% of patients unacceptably controlled at inclusion. Conclusions: Asthma was unacceptably controlled in most patients receiving ICS-containing maintenance treatment and remained so during follow-up. Despite this, treatment adaptations by GPs and CPs were very infrequent. This unsatisfactory situation may be improved by adopting a more dynamic approach to tailoring controller therapy to the needs of the patient.     

Human Stimulus Factor Is a Promising Peptide for Delivery of Therapeutics

Fluticasone propionate uptake in the presence of a proprietary cell-penetrating peptide (human stimulus factor, [HSF]) based on the N-terminal domain of lactoferrin was studied, alone and in combination with salmeterol, using an air interface Calu-3 epithelial model. The HSF enhanced uptake and transport of fluticasone propionate across the epithelial barrier when alone and in presence of salmeterol. This was attributed to transcellular-mediated uptake. This HSF is a promising peptide for delivery of therapeutics where enhanced epithelial penetrating is required.     

The beneficial role of FeNO in association with GINA guidelines for titration of inhaled corticosteroids in adult asthma: A randomized study

PurposeThis study aimed to demonstrate the role of fractional concentration of exhaled nitric oxide (FeNO) in association with Global Initiative for Asthma (GINA) guidelines for treatment of adult patients with asthma.MethodsIt was a prospective and randomized study. The symptomatic asthmatic patients were randomly divided into two groups: GINA group (followed GINA guidelines; N = 86) or GINA + FeNO group (followed GINA guidelines + FeNO for titration of inhaled corticosteroids - ICS; N = 90). They were followed-up for 9 months.ResultsIn GINA group, 37.2% patients had no treatment and 62.8% patients discontinued treatment vs. 40.0% and 60.0% in GINA + FeNO, respectively. After 3, 6 and 9 months of treatment, the percentage of mild, moderate and severe asthma showed no significant difference between the two groups. At 9th month, Δ moderate asthma (reduction) in GINA + FeNO group was significantly higher than in the GINA group (−22.0% vs. −11.6%; P = 0.018). The improvement of asthma control test (ACT) score was not different between the groups at 9th month (12 ± 6 vs. 10 ± 5; P > 0.05); the level of FeNO reduction in GINA + FeNO group was significantly higher than that in GINA group (−42 ± 11 vs. −35 ± 9; P = 0.022). The daily dose of ICS in GINA + FeNO group was significantly lower than that in GINA group (397 ± 171 vs. 482 ± 240 mcg and 375 ± 203 vs. 424 ± 221 mcg; respectively) at the end of 6 and 9 months.ConclusionThe use of FeNO in association with GINA guidelines has a beneficial role for accurate daily dose of ICS in adult patients with asthma.     

Corticoterapia prenatal y morbimortalidad del prematuro tardío: estudio prospectivo

IntroductionLate preterm infants (34-36 weeks gestation) have a morbidity rate significantly higher than those born at term. However, few interventions have been undertaken to reduce this increased morbidity and mortality. Antenatal corticosteroid administration could be an effective preventive measure.ObjectiveThe aim of this study was to describe the morbidity associated with late prematurity in our institution, and determine if there are differences between those who received antenatal corticosteroids.Patients and methodsA prospective observational study was conducted on late preterm infants born in a tertiary hospital from October 2011 until September 2012. Two groups were formed according to whether or not they had received antenatal steroids. The rates of morbidity and mortality for each of the groups were analysed and compared.ResultsThere was a total of 4127 live newborns during the study period, of whom 3795 were term and 332 were preterm (the overall prematurity rate was 8.04%). There were 247 late preterm deliveries, representing 6% of live born infants, and 74.4% of all premature infants. Of late preterm infants, 63.2% were admitted to the Neonatal Unit and 29.6% had received antenatal steroids. The incidence of admission to the Neonatal Unit and Neonatal Intensive Care, transient tachypnea, need for respiratory support in the form of continuous positive pressure airway and oxygen therapy, incidence of hypoglycemia, feeding difficulty, and jaundice requiring phototherapy were significantly higher (P < .05) in the late preterm group that did not receive antenatal steroids.ConclusionsOur finding suggests that the administration of antenatal corticosteroids to patients at risk of 34-36 weeks delivery could significantly reduce the cost and acute morbidity associated with late preterm birth.     

Systemic use of non‐biologic corticosteroids in orofacial diseases

Systemic non‐biologic agents have long been in clinical use in medicine – often with considerable efficacy, albeit with some adverse effects – as with all medications. With the advent of biologic agents, all of which currently are restricted to systemic use, there is a growing need to ensure which agents have the better therapeutic ratio. The non‐biologic agents (NBAs) include a range of agents, most especially the corticosteroids (corticosteroids). This study reviews the corticosteroids in systemic use in management of orofacial mucocutaneous diseases; subsequent studies discuss corticosteroid‐sparing agents used in the management of orofacial diseases, such as calcineurin inhibitors used to produce immunosuppression; purine synthetase inhibitors; and cytotoxic and other immunomodulatory agents.