Unbearable wearables.

As wearable devices play an increasing role in the management of health and disease, adverse skin reactions to wearables have become more common. However, the management of allergic contact dermatitis is challenging and new treatment options more compatible with wearable devices are needed. In a 40-year-old woman with contact dermatitis to a continuous glucose monitoring device, topical clobetasol propionate 0.05% spray proved to be an effective treatment that was compatible with the application of adhesive wearables. This case demonstrates that spray formulations of topical steroids are a good option for the treatment of dermatitis under wearable devices such as continuous glucose monitors or ostomy appliance.

Early-life perturbations in glucocorticoid activity impacts on the structure, function and molecular composition of the adult zebrafish (Danio rerio) heart.

BACKGROUND: Transient early-life perturbations in glucocorticoids (GC) are linked with cardiovascular disease risk in later life. Here the impact of early life manipulations of GC on adult heart structure, function and gene expression were assessed. METHODS AND RESULTS: Zebrafish embryos were incubated in dexamethasone (Dex) or injected with targeted glucocorticoid receptor (GR) morpholino knockdown (GR Mo) over the first 120 h post fertilisation (hpf); surviving embryos (>90%) were maintained until adulthood under normal conditions. Cardiac function, heart histology and cardiac genes were assessed in embryonic (120 hpf) and adult (120 days post fertilisation (dpf)) hearts. GR Mo embryos (120 hpf) had smaller hearts with fewer cardiomyocytes, less mature striation pattern, reduced cardiac function and reduced levels of vmhc and igf mRNA compared with controls. GR Mo adult hearts were smaller with diminished trabecular network pattern, reduced expression of vmhc and altered echocardiographic Doppler flow compared to controls. Dex embryos had larger hearts at 120 hpf (Dex 107.2 ± 3.1 vs. controls 90.2 ± 1.1 µm, p < 0.001) with a more mature trabecular network and larger cardiomyocytes (1.62 ± 0.13 cells/µm vs control 2.18 ± 0.13 cells/µm, p < 0.05) and enhanced cardiac performance compared to controls. Adult hearts were larger (1.02 ± 0.07 µg/mg vs controls 0.63 ± 0.06 µg/mg, p = 0.0007), had increased vmhc and gr mRNA levels. CONCLUSION: Perturbations in GR activity during embryonic development results in short and long-term alterations in the heart.

A nonsteroidal glucocorticoid receptor agonist inhibits allergen-induced late asthmatic responses.

RATIONALE: Effective antiinflammatory therapies are needed for the treatment of asthma, but preferably without the systemic adverse effects of glucocorticosteroids. OBJECTIVES: We evaluated the effect of an inhaled nonsteroidal glucocorticoid receptor agonist, AZD5423, on allergen-induced responses. METHODS: Twenty subjects with mild allergic asthma were randomized to receive 7 days of treatment with nebulized AZD5423 (75 or 300 µg) once daily, budesonide 200 µg twice daily via Turbuhaler, or placebo in a double-blind, four-period, crossover design study. Allergen challenge was performed on Day 6. MEASUREMENTS AND MAIN RESULTS: FEV1 was measured repeatedly for 7 hours after allergen challenge for early and late asthmatic responses. Sputum inflammatory cells was measured before and at 7 and 24 hours after allergen challenge, and methacholine airway responsiveness was measured before and 24 hours after allergen challenge. AZD5423 significantly attenuated the fall in FEV1 during the late asthmatic response (both doses led to an 8.7% fall) versus placebo (14% fall) (P < 0.05) with no effect of budesonide (12.5% fall) versus placebo (P > 0.05). There was no effect on the fall in FEV1 during early asthmatic response. AZD5423 300 and 75 µg significantly attenuated allergen-induced sputum eosinophilia by 63 and 61% at 7 hours, respectively, and by 46 and 34% at 24 hours after allergen challenge, respectively, versus placebo (all P < 0.05). Budesonide did not reduce allergen-induced sputum eosinophilia versus placebo. AZD5423 at 300 µg significantly attenuated allergen-induced airway hyperresponsiveness at 24 hours after allergen challenge versus placebo (P < 0.05). Both doses of AZD5423 were well tolerated. CONCLUSIONS: Seven-day treatment with inhalation of the nonsteroidal glucocorticoid receptor agonist AZD5423 effectively reduced allergen-induced responses in subjects with mild allergic asthma. Clinical trial registered with www.clinicaltrials.gov (NCT01225549).

Disruption of fear memory through dual-hormone gene therapy.

BACKGROUND: The basolateral complex of the amygdala (BLA) is uniquely affected by steroid hormones. Whereas glucocorticoids (GCs)--the adrenal hormones released during stress--increase the excitability of BLA neurons, estrogen decreases it. METHODS: In this study, we used a vector designed to express a chimeric gene that contains the GC-binding domain of the GC receptor (GR) and the DNA binding domain of the estrogen receptor (ER) ("ER/GR") in infected neurons; as a result, it transduces GC signals into estrogenic ones. We microinfused ER/GR bilaterally into the BLA of rats to determine whether it would impair fear conditioning, a valuable BLA-dependent paradigm for studying the neural basis of emotional memory. RESULTS: Expression of ER/GR in the BLA caused robust expression of the transgene and a significant disruption of both auditory and contextual long-term fear memory consolidation, whereas fear learning and post-shock freezing remained intact. CONCLUSIONS: These data show that dual gene therapy with ER/GR might be a useful tool for understanding the role of steroid hormones in the storage of traumatic memories.

Low-dose dexamethasone alleviates lipopolysaccharide-induced acute lung injury in rats and upregulates pulmonary glucocorticoid receptors.

BACKGROUND AND OBJECTIVE: The major causes of mortality among patients who survive acute lung injury/ARDS (ALI/ARDS) are due to the extensive tissue remodelling and fibrosis. Use of high-dose glucocorticoids to reduce these inflammatory and fibroproliferative responses has been shown to do more harm than good. Recently, Meduri et al. found that the early use of low-dose prolonged methylprednisolone in patients with severe ALI/ARDS significantly relieved the systemic inflammatory response and improved pulmonary and extrapulmonary organ function. This study investigated the therapeutic effect of low-dose dexamethasone (Dex) on inflammation and fibrosis in LPS-induced ALI in rats and its influence on the expression of the pulmonary glucocorticoid receptor (GR). METHODS: Eighty Wistar rats were randomly divided into four groups: a control group (intraperitoneal normal saline injection (5 mL/kg) throughout experiment, n = 24); the LPS model group (LPS injection (5 mg/kg) for 3 days and normal saline thereafter, n = 24); the LPS + Dex group (LPS injection for 3 days and Dex solution (5 mg/kg) thereafter, n = 16); and the Dex group (normal saline injection (5 mL/kg) for 3 days and Dex solution (5 mg/kg) thereafter, n = 16). Levels of tumor necrosis factor-alpha, matrix metallopeptidase-9 and procollagen N-terminal propeptide type I in BAL fluid were examined by ELISA on the third, seventh and fourteenth days after injection. Pulmonary hydroxyproline content was measured and histological examination was performed with haematoxylin-eosin and Victoria blue-ponceau. Pulmonary distribution of GR-positive cells was examined immunohistochemically, and expression of GR mRNA and protein was determined by RT-PCR and western blot analysis. RESULTS: Histological assessments showed that pulmonary fibrosis occurred in parallel with inflammation in the rat ALI model. Compared with the LPS group, the inflammation and fibrosis parameters were significantly improved in the LPS + Dex group at different periods after injection (P < 0.05 or P < 0.01), although parameters in the LPS + Dex group were not as good as those of the control group. GR mRNA and protein expression in the LPS + Dex group were markedly higher than that of the LPS group on the seventh and the fourteenth days (both P < 0.01). Western blotting showed that Dex also promoted the nuclear translocation of GR protein. CONCLUSION: Low-dose Dex can reduce pulmonary inflammation and fibrosis after LPS-induced ALI in rats and can elevate GR expression in the lung, probably through upregulating GR levels and promoting the nuclear translocation of GR protein.