Search results for "glucocorticoid"
showing 10 items of 268 documents
Rapid acting antidepressant (2R,6R)-hydroxynorketamine (HNK) targets glucocorticoid receptor signaling: a longitudinal cerebrospinal fluid proteome s…
2020
AbstractDelayed onset of antidepressant action is a shortcoming in depression treatment. Ketamine and its metabolite (2R,6R)-hydroxynorketamine (HNK) have emerged as promising rapidacting antidepressants. However, their mechanism of action remains unknown. In this study, we first described the anxious and depression-prone inbred mouse strain, DBA/2J, as a animal model to assess the antidepressant-like effects of ketamine and HNK in vivo. To decode the molecular mechanisms mediating HNK’s rapid antidepressant effects, a longitudinal cerebrospinal fluid (CSF) proteome profiling of its acute and sustained effects was conducted using an unbiased, hypothesis-free mass spectrometry-based proteomi…
Pharmacological treatment of sensorineural hearing loss
2019
Sudden sensorineural hearing loss is a common and alarming symptom of about 360 million people that suffer from hearing impairment worldwide. The sudden sensorineural hearing loss usually arises unilaterally and it is habitually described as greater than 30dB hearing reduction, attributable to lesions of the cochlea, cranial nerve VIII, brainstem and temporal lobe. There are many factor that promote the onset of this lesions such us infections, circulatory diseases, inner ear neoplasia and neurological disorders. This pathology is characterized by primary symptoms such as the impairment of the comprehension of spoken language and the struggling to listen to music. Subsequently, secondary sy…
IκB kinase-driven nuclear factor-κB activation in patients with asthma and chronic obstructive pulmonary disease.
2011
Background Nuclear factor-κB (NF-κB) is a transcriptional factor of different inflammatory patterns involved in asthma and chronic obstructive pulmonary disease (COPD) that is tightly controlled by IκB kinase (IKK) complex. Objective We investigated the dysregulation of IKK-driven NF-κB activation in patients with asthma and COPD. Methods We assessed IKKα and IKKβ expression and activation, their regulation by glucocorticosteroids, and their involvement in IL-8 synthesis in PBMCs isolated from asthmatic patients, healthy smokers (HSs), patients with COPD, and control subjects. PBMCs from control subjects were stimulated with TNF-α and cigarette smoke extract in the presence or absence of fl…
GM-CSF restores innate, but not adaptive, immune responses in glucocorticoid-immunosuppressed human blood in vitro.
2003
Abstract Infection remains the major complication of immunosuppressive therapy in organ transplantation. Therefore, reconstitution of the innate immunity against infections, without activation of the adaptive immune responses, to prevent graft rejection is a clinically desirable status in transplant recipients. We found that GM-CSF restored TNF mRNA and protein expression without inducing IL-2 production and T cell proliferation in glucocorticoid-immunosuppressed blood from either healthy donors or liver transplant patients. Gene array experiments indicated that GM-CSF selectively restored a variety of dexamethasone-suppressed, LPS-inducible genes relevant for innate immunity. A possible ex…
MUC1-CT mediates corticosteroid responses in COPD
2016
Background: Corticosteroid resistance is an acquired condition in chronic obstructive pulmonary disease (COPD) patients and a challenge to develop new anti-inflammatory therapies. In previous reports we showed that cytoplasmic tail of the membrain tethered mucin 1 (MUC1-CT) interacts with glucocorticoid receptor (GR) mediating corticosteroid anti-inflammatory efficacy. Objectives: To analyze the role of MUC1-CT as a key marker of corticosteroid efficacy in COPD Methods: The expression of MUC1-CT and the anti-inflammatory role of dexamethasone were evaluated in neutrophils and bronchial epithelial cells from healthy and COPD patients. Anti-inflammatory effects of dexamethasone and glucocorti…
Metabolic comorbidities of adrenal insufficiency: Focus on steroid replacement therapy and chronopharmacology
2021
Adrenal insufficiency (AI) is characterized by higher mortality and morbidity compared with the general population. Conventional replacement steroid therapy, currently recommended for the treatment of AI, is associated with increased frequency of metabolic comorbidities due to daily overexposure. By contrast, dual-release hydrocortisone is associated with a decreased risk of metabolic comorbidities, providing an adequate release of hydrocortisone and mimicking the physiological profile of cortisol. These favorable effects are due to a reduced daily steroid exposure that does not affect the expression of the clock genes which are involved in metabolic pathways and are regulated by the normal…
Near-fatal asthma phenotype in the ENFUMOSA Cohort.
2007
Summary Background Near-fatal asthma (NFA) is characterized by severe asthma attacks usually requiring intensive care unit admission. This phenotype of asthma has been studied mainly in acute conditions. Methods The aim of our study was to compare the clinical, functional and inflammatory characteristics of NFA patients with mild to severe asthmatics in stable conditions. We recruited 155 asthmatic patients from five centres of the European Network for Understanding Mechanisms of Severe Asthma: 67 patients with mild-to-moderate asthma controlled by low/medium doses of inhaled corticosteroids; 64 with severe asthma that, despite treatment with high doses of inhaled corticosteroids, long-acti…
The Relationship between COVID-19 and Hypothalamic-Pituitary-Adrenal Axis: A Large Spectrum from Glucocorticoid Insufficiency to Excess-The CAPISCO I…
2022
Coronavirus disease 2019 (COVID-19) is a highly heterogeneous disease regarding severity, vulnerability to infection due to comorbidities, and treatment approaches. The hypothalamic–pituitary–adrenal (HPA) axis has been identified as one of the most critical endocrine targets of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that might significantly impact outcomes after infection. Herein we review the rationale for glucocorticoid use in the setting of COVID-19 and emphasize the need to have a low index of suspicion for glucocorticoid-induced adrenal insufficiency, adjusting for the glucocorticoid formulation used, dose, treatment duration, and underlying health problems. We a…
Methylprednisolone neutralizes the beneficial effects of erythropoietin in experimental spinal cord injury
2005
Inflammation plays a major pathological role in spinal cord injury (SCI). Although antiinflammatory treatment using the glucocorticoid methyprednisolone sodium succinate (MPSS) improved outcomes in several multicenter clinical trials, additional clinical experience suggests that MPSS is only modestly beneficial in SCI and poses a risk for serious complications. Recent work has shown that erythropoietin (EPO) moderates CNS tissue injury, in part by reducing inflammation, limiting neuronal apoptosis, and restoring vascular autoregulation. We determined whether EPO and MPSS act synergistically in SCI. Using a rat model of contusive SCI, we compared the effects of EPO [500-5,000 units/kg of bod…
Apolipoprotein AI and HDL are reduced in stable cirrhotic patients with adrenal insufficiency: a possible role in glucocorticoid deficiency
2015
Backgrounds and aims: Adrenal insufficiency (AI) has been reported in patients with stable cirrhosis. A lack of substrates has been suggested as a possible contributing pathogenic mechanism leading to glucocorticoid deficiency in these subjects. To better explore this hypothesis, we studied lipoproteins in cirrhotics with and without AI. Methods. A total of 81 cirrhotic patients and 30 normal volunteers were enrolled. The severity of liver disease was graded by Child-Pugh score. Total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglyceride (TG), and apolipoprotein AI (Apo-AI) levels were evaluated. HDL subfractions were measured by gradient gel electrop…