Stress exposure in early post-natal life reduces telomere length: an experimental demonstration in a long-lived seabird

Exposure to stressors early in life is associated with faster ageing and reduced longevity. One important mechanism that could underlie these late life effects is increased telomere loss. Telomere length in early post-natal life is an important predictor of subsequent lifespan, but the factors underpinning its variability are poorly understood. Recent human studies have linked stress exposure to increased telomere loss. These studies have of necessity been non-experimental and are consequently subjected to several confounding factors; also, being based on leucocyte populations, where cell composition is variable and some telomere restoration can occur, the extent to which these effects extend beyond the immune system has been questioned. In this study, we experimentally manipulated stress exposure early in post-natal life in nestling European shags (Phalacrocorax aristotelis) in the wild and examined the effect on telomere length in erythrocytes. Our results show that greater stress exposure during early post-natal life increases telomere loss at this life-history stage, and that such an effect is not confined to immune cells. The delayed effects of increased telomere attrition in early life could therefore give rise to a ‘time bomb’ that reduces longevity in the absence of any obvious phenotypic consequences early in life

Safety and efficacy of fluticasone propionate in the topical treatment of skin diseases

Fluticasone propionate - the first carbothioate corticosteroid - has been classified as a potent anti-inflammatory drug for dermatological use. It is available as 0.05% cream and 0.005% ointment formulations for the acute and maintenance treatment of patients with dermatological disorders such as atopic dermatitis, psoriasis and vitiligo. This glucocorticoid is characterized by high lipophilicity, high glucocorticoid receptor binding and activation, and a rapid metabolic turnover in skin. Although skin blanching following fluticasone propionate exceeds that of corticosteroids of medium strength, several clinical trials demonstrate a low potential for cutaneous and systemic side-effects, even in difficult-to-treat areas like the face, the eyelids and intertriginous areas. Even among paediatric patients with atopic dermatitis, fluticasone propionate proved to be safe and effective. These pharmacological and clinical properties are reflected by the high therapeutic index of this glucocorticoid

Parental age influences offspring telomere loss

1. The age of the parents at the time of offspring production can influence offspring longevity, but the underlying mechanisms remain poorly understood. The effect of parental age on offspring telomere dynamics (length and loss rate) is one mechanism that could be important in this context. 2. Parental age might influence the telomere length that offspring inherit or age-related differences in the quality of parental care could influence the rate of offspring telomere loss. However, these routes have generally not been disentangled. 3. Here, we investigated whether parental age was related to offspring telomere dynamics using parents ranging in age from 2 to 22 years old in a free-living population of a long-lived seabird, the European shag (Phalacrocorax aristotelis). By measuring the telomere length of offspring at hatching and towards the end of the post-natal growth period, we could assess whether any potential parental age effect was confined to the post-natal rearing period. 4. There was no effect of maternal or paternal age on the initial telomere length of their chicks. However, chicks produced by older mothers and fathers experienced significantly greater telomere loss during the post-natal nestling growth period. We had relatively few nests in which the ages of both parents were known, and individuals in this population mate assortatively with respect to age. Thus, we could not conclusively determine whether the parental age effect was due to maternal age, paternal age, or both; however, it appears that the effect is stronger in mothers. 5. These results demonstrate that in this species, there was no evidence that parental age was related to offspring hatching telomere length. However, telomere loss during nestling growth was reduced in the offspring of older parents. This could be due to an age-related deterioration in the quality of the environment that parents provide, or because parents that invest less in offspring rearing live to an older age

Cromoglycate and Nedocromil: Influence on Airway Reactivity

Although basic mechanisms of bronchial hyper-responsiveness (BHR) are still incompletely understood, inflammation of airways is likely to play a fundamental role in modulating BHR in patients with asthma. The involvement of several inflammatory cells (eosinophils, mast cells, lymphocytes, neutrophils, macrophages and platelets) and of bioactive mediators secreted by these cells in the pathogenesis of asthma is well documented. Sodium cromoglycate and nedocromil sodium are two pharmacological agents which have anti-allergic and anti-inflammatory properties. Their clinical effectiveness in mild to moderate asthma, and the capacity to reduce BHR under different natural and experimental conditions, make them valuable drugs for maintenance therapy in patients with asthma

Estimation of tulathromycin depletion in plasma and milk after subcutaneous injection in lactating goats using a nonlinear mixed-effects pharmacokinetic modeling approach

Citation: Lin, Z. M., Cuneo, M., Rowe, J. D., Li, M. J., Tell, L. A., Allison, S., . . . Gehring, R. (2016). Estimation of tulathromycin depletion in plasma and milk after subcutaneous injection in lactating goats using a nonlinear mixed-effects pharmacokinetic modeling approach. Bmc Veterinary Research, 12, 10. https://doi.org/10.1186/s12917-016-0884-4Background: Extra-label use of tulathromycin in lactating goats is common and may cause violative residues in milk. The objective of this study was to develop a nonlinear mixed-effects pharmacokinetic (NLME-PK) model to estimate tulathromycin depletion in plasma and milk of lactating goats. Eight lactating goats received two subcutaneous injections of 2.5 mg/kg tulathromycin 7 days apart; blood and milk samples were analyzed for concentrations of tulathromycin and the common fragment of tulathromycin (i.e., the marker residue CP-60,300), respectively, using liquid chromatography mass spectrometry. Based on these new data and related literature data, a NLME-PK compartmental model with first-order absorption and elimination was used to model plasma concentrations and cumulative excreted amount in milk. Monte Carlo simulations with 100 replicates were performed to predict the time when the upper limit of the 95% confidence interval of milk concentrations was below the tolerance. Results: All animals were healthy throughout the study with normal appetite and milk production levels, and with mild-moderate injection-site reactions that diminished by the end of the study. The measured data showed that milk concentrations of the marker residue of tulathromycin were below the limit of detection (LOD = 1.8 ng/ml) 39 days after the second injection. A 2-compartment model with milk as an excretory compartment best described tulathromycin plasma and CP-60,300 milk pharmacokinetic data. The model-predicted data correlated with the measured data very well. The NLME-PK model estimated that tulathromycin plasma concentrations were below LOD (1.2 ng/ml) 43 days after a single injection, and 62 days after the second injection with a 95% confidence. These estimated times are much longer than the current meat withdrawal time recommendation of 18 days for tulathromycin in non-lactating cattle. Conclusions: The results suggest that twice subcutaneous injections of 2.5 mg/kg tulathromycin are a clinically safe extra-label alternative approach for treating pulmonary infections in lactating goats, but a prolonged withdrawal time of at least 39 days after the second injection should be considered to prevent violative residues in milk and any dairy goat being used for meat should have an extended meat withdrawal time

Relationship between exhaled air temperature and exhaled nitric oxide in childhood asthma

Airway inflammation is a characteristic of asthma. Exhaled nitric oxide (eNO) has been demonstrated to be related to actual levels of airway inflammation in asthmatic patients. The purpose of this study was to investigate whether the temperature of exhaled air is related to eNO levels. Temperature of exhaled air and eNO were measured in 52 asthmatic children with a cross-sectional design. A significant relationship was demonstrated between eNO and temperature of peak and plateau exhaled air temperature. The relationship between both the peak and the plateau values and eNO was more evident when it was corrected for environmental temperature. These results suggest a relationship between exhaled nitric oxide and the temperature of exhaled air in asthmatic patients not treated with systemic steroids

Flunisolide Decreases Exhaled Nitric Oxide and Nitrotyrosine Levels in Asthmatic Children

Background. Exhaled nitric oxide (FeNO) has been reported to be elevated in the oxidative stress involved in asthmatic patients, and the reaction of nitric oxide (NO) with superoxide anions results in the formation of nitrotyrosine. The purpose of this study was to investigate the effect of inhaled steroid treatment on nitrotyrosine levels collected by exhaled breath condensate (EBC) and on FeNO. Methods. This was a single-blind placebo-controlled study. The lung function, FeNO, and nitrotyrosine levels were evaluated in 10 asthmatic children. Results. The nitrotyrosine levels were stable during the placebo period (T0 = 1.16 ng/ml versus T1 = 1.05 ng/ml; NS.), whereas they decreased after the treatment with flunisolide (T2 = 1.14 ng/ml versus T3 = 0.88 ng/ml; P < .001). No significant reduction in FeNO levels was observed after placebo treatment (T0 = 38.4 ppb versus T1 = 34.7 ppb, NS.). In contrast, FeNO values decreased significantly being at T3 = 14.9 ppb (T1 versus T3; P = .024). Conclusions. This study shows that corticosteroid treatment reduces nitrotyrosine levels in EBC of asthmatic subjects

ARIA 2016:Care pathways implementing emerging technologies for predictive medicine in rhinitis and asthma across the life cycle

The Allergic Rhinitis and its Impact on Asthma (ARIA) initiative commenced during a World Health Organization workshop in 1999. The initial goals were (1) to propose a new allergic rhinitis classification, (2) to promote the concept of multi-morbidity in asthma and rhinitis and (3) to develop guidelines with all stakeholders that could be used globally for all countries and populations. ARIA-disseminated and implemented in over 70 countries globally-is now focusing on the implementation of emerging technologies for individualized and predictive medicine. MASK [MACVIA (Contre les Maladies Chroniques pour un Vieillissement Actif)-ARIA Sentinel NetworK] uses mobile technology to develop care pathways for the management of rhinitis and asthma by a multi-disciplinary group and by patients themselves. An app (Android and iOS) is available in 20 countries and 15 languages. It uses a visual analogue scale to assess symptom control and work productivity as well as a clinical decision support system. It is associated with an inter-operable tablet for physicians and other health care professionals. The scaling up strategy uses the recommendations of the European Innovation Partnership on Active and Healthy Ageing. The aim of the novel ARIA approach is to provide an active and healthy life to rhinitis sufferers, whatever their age, sex or socio-economic status, in order to reduce health and social inequalities incurred by the disease

ARIA 2016: Care pathways implementing emerging technologies for predictive medicine in rhinitis and asthma across the life cycle

The Allergic Rhinitis and its Impact on Asthma (ARIA) initiative commenced during a World Health Organization workshop in 1999. The initial goals were (1) to propose a new allergic rhinitis classification, (2) to promote the concept of multi-morbidity in asthma a

Short term efficacy of nebulized beclomethasone in mild-to-moderate wheezing episodes in pre-school children

<p>Abstract</p> <p>Background</p> <p>Few data are available on the usefulness of short term treatment with low-medium dose of inhaled corticosteroids (ICS) in pre-school children with wheezing exacerbations.</p> <p>Methods</p> <p>To compare the efficacy of one week treatment with 400 μg b.i.d. nebulized beclomethasone dipropionate (BDP), plus nebulized 2500 μg prn salbutamol (BDP group), versus nebulized b.i.d. placebo, plus nebulized prn 2500 μg salbutamol (placebo group), a post-hoc analysis was performed on data obtained in 166 pre-school children with multiple-trigger wheezing, recruited during an acute wheezing episode.</p> <p>Results</p> <p>The percentage of symptom-free days (SFDs) was significantly higher in the BDP group (54.7%) than in the placebo group (40.5%; p = 0.012), with a 35% relative difference. Day-by-day analysis showed that the percentage of SFDs was already higher in the BDP group after 2 days (7.4%), the difference reaching statistical significance at day 6 (12.3%; p = 0.035). Cough score was also reduced in the BDP group (0.11) as compared with the placebo group (0.39; p = 0.048), the difference reaching statistical significance after 5 days of treatment (0.18 and 0.47 respectively; p = 0.047). The mean number of nebulizations per day of prn salbutamol was lower in the BDP group as compared to the placebo group (0.26 and 0.34, respectively), but the difference was not significant (p = 0.366). There were no differences in positive effects of BDP treatment between children with and without risk factors for asthma.</p> <p>Conclusions</p> <p>A 1-week treatment with nebulized BDP and prn salbutamol is effective in increasing SFDs and improving cough in children with wheezing, providing a clinical rationale for the short term use of ICS in episodic wheeze exacerbations in pre-school children.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov (<a href="http://www.clinicaltrials.gov/ct2/show/NCT00497523">NCT00497523</a>)</p