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Lewis, Brandon W., Devine Jackson, Stephanie A. Amici, et al. "Corticosteroid insensitivity persists in the absence of STAT1 signaling in severe allergic airway inflammation." American Journal of Physiology-Lung Cellular and Molecular Physiology 321, no. 6 (2021): L1194—L1205. http://dx.doi.org/10.1152/ajplung.00244.2021.
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Corticosteroid insensitivity in asthma limits the ability to effectively manage severe asthma, which is characterized by persistent airway inflammation, airway hyperresponsiveness (AHR), and airflow obstruction despite corticosteroid treatment. Recent reports indicate that corticosteroid insensitivity is associated with increased interferon-γ (IFN-γ) levels and T-helper (Th) 1 lymphocyte infiltration in severe asthma. Signal transducer and activator of transcription 1 (STAT1) activation by IFN-γ is a key signaling pathway in Th1 inflammation; however, its role in the context of severe allergic airway inflammation and corticosteroid sensitivity remains unclear. In this study, we challenged wild-type (WT) and Stat1−/− mice with mixed allergens (MA) augmented with c-di-GMP [bis-(3′-5′)-cyclic dimeric guanosine monophosphate], an inducer of Th1 cell infiltration with increased eosinophils, neutrophils, Th1, Th2, and Th17 cells. Compared with WT mice, S tat1−/− had reduced neutrophils, Th1, and Th17 cell infiltration. To evaluate corticosteroid sensitivity, mice were treated with either vehicle, 1 or 3 mg/kg fluticasone propionate (FP). Corticosteroids significantly reduced eosinophil infiltration and cytokine levels in both c-di-GMP + MA-challenged WT and Stat1−/− mice. However, histological and functional analyses show that corticosteroids did not reduce airway inflammation, epithelial mucous cell abundance, airway smooth muscle mass, and AHR in c-di-GMP + MA-challenged WT or Stat1−/− mice. Collectively, our data suggest that increased Th1 inflammation is associated with a decrease in corticosteroid sensitivity. However, increased airway pathology and AHR persist in the absence of STAT1 indicate corticosteroid insensitivity in structural airway cells is a STAT1 independent process.
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Lewis, Brandon W., Maria L. Ford, Lynette K. Rogers, and Rodney D. Britt. "Oxidative Stress Promotes Corticosteroid Insensitivity in Asthma and COPD." Antioxidants 10, no. 9 (2021): 1335. http://dx.doi.org/10.3390/antiox10091335.
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Corticosteroid insensitivity is a key characteristic of patients with severe asthma and COPD. These individuals experience greater pulmonary oxidative stress and inflammation, which contribute to diminished lung function and frequent exacerbations despite the often and prolonged use of systemic, high dose corticosteroids. Reactive oxygen and nitrogen species (RONS) promote corticosteroid insensitivity by disrupting glucocorticoid receptor (GR) signaling, leading to the sustained activation of pro-inflammatory pathways in immune and airway structural cells. Studies in asthma and COPD models suggest that corticosteroids need a balanced redox environment to be effective and to reduce airway inflammation. In this review, we discuss how oxidative stress contributes to corticosteroid insensitivity and the importance of optimizing endogenous antioxidant responses to enhance corticosteroid sensitivity. Future studies should aim to identify how antioxidant-based therapies can complement corticosteroids to reduce the need for prolonged high dose regimens in patients with severe asthma and COPD.
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Tanaka, Takao, Mari Shigeta, and Masahiko Usui. "BCG inoculation and corticosteroid sensitivity." Ocular Immunology and Inflammation 9, no. 3 (2001): 207–10. http://dx.doi.org/10.1076/ocii.9.3.207.3970.
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Lauerma, A. I. "Screening for corticosteroid contact sensitivity." Contact Dermatitis 24, no. 2 (1991): 123–30. http://dx.doi.org/10.1111/j.1600-0536.1991.tb01664.x.
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Flores, Saul, Ilias Iliopoulos, Rohit S. Loomba, et al. "Glucocorticoid Receptor Polymorphisms in Children Undergoing Congenital Heart Surgery with Cardiopulmonary Bypass." Journal of Pediatric Intensive Care 09, no. 04 (2020): 241–47. http://dx.doi.org/10.1055/s-0040-1709658.
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AbstractWe conducted a candidate gene association study to test the hypothesis that different gene polymorphisms will be associated with corticosteroid responsiveness and study outcomes among children undergoing congenital heart surgery. This is a prospective observational cohort study at a large, tertiary pediatric cardiac center on children undergoing corrective or palliative congenital heart surgery. A total of 83 children were enrolled. DNA was isolated for three polymorphisms of interest namely N363 (rs56149945) and 9β (rs6198) associated with increased sensitivity to corticosteroids and BclI (rs41423247) associated with decreased sensitivity to corticosteroids. Duration of inotropic use, low cardiac output scores (LCOS), and vasoactive inotrope scores were examined in relation to these three polymorphisms. Using Kaplan–Meier analysis, heterozygous individuals showed longer transcriptional intermediary factor (TIF) compared with wild type for N363 polymorphism (p = 0.05). In multivariable Cox regression, heterozygous alleles for 9β polymorphism showed significantly shorter TIF compared with wild type (hazard ratio = 2.04 [1.08–3.87], p = 0.03). The relationship between lower LCOS scores and alleles groups was significant for 9β heterozygous polymorphism only (1.5 [1–2.2], p = 0.01) in comparison to wild type and homozygous. The presence of heterozygote alleles for the increased corticosteroid sensitivity is associated with longer TIF compared with wild type. Conversely, the presence of heterozygous alleles for the decreased sensitivity to corticosteroids is associated with shorter TIF compared with wild type.
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Kimura, Genki, and Yasuo Kizawa. "Corticosteroid sensitivity in intractable respiratory disease." Folia Pharmacologica Japonica 145, no. 6 (2015): 329. http://dx.doi.org/10.1254/fpj.145.329.
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Gaucher, Louis, Leslie Adda, Alice Séjourné, et al. "Impact of the corticosteroid indication and administration route on overall survival and the tumor response after immune checkpoint inhibitor initiation." Therapeutic Advances in Medical Oncology 13 (January 2021): 175883592199665. http://dx.doi.org/10.1177/1758835921996656.
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Background: Based on their indications, systemic corticosteroids appear to negatively affect clinical outcomes in immune checkpoint inhibitor (ICI)-treated patients. There are few data on the influence of topical and inhaled corticosteroids on the ICIs’ effectiveness. Methods: In a single-center study, we retrospectively investigated the impact of systemic corticosteroids according to their indication [an immune-related adverse event (irAE) or another indication] on overall survival (OS) and the tumor response in all consecutive patients after initiation of ipilimumab, nivolumab or pembrolizumab over a 9-year period. The impacts of topical and inhaled corticosteroids were also examined. Results: Three hundred and seventy-two patients were included. The mean ± standard deviation age was 64.0 ± 12.1 years. The most frequently prescribed ICI was nivolumab (in 58.3% of the patients) and the most frequent indications were lung cancer (44.6%) and melanoma (29.6%). Systemic corticosteroid use for an irAE did not have a negative impact on OS [adjusted hazard ratio (HR) [95% confidence interval (CI)] 1.04 (0.56–1.95), p = 0.902] or the best overall tumor response [adjusted odds ratio (OR) (95% CI) 1.69 (0.52–6.56), p = 0.413], while systemic corticosteroid use for another indication was associated with shorter OS [adjusted HR (95% CI) 1.34 (1.05–2.03), p = 0.046] and a poor best overall tumor response [adjusted OR (95% CI) 2.04 (1.07–5.80), p = 0.039] with a cumulative dose cut-off of 3215 mg prednisolone equivalent (specificity 71.4%; sensitivity 65.3%) and a time cut-off of 132 days (specificity 71.4%; sensitivity 89.8%). The use of topical corticosteroids was associated with a longer OS; this was probably due to dermatological irAEs. Inhaled corticosteroid use did not influence OS. Conclusion: Systemic corticosteroid use for an irAE does not impact OS or the tumor response, whereas use for other indications (themselves often associated with a worse prognosis) does. Topical and inhaled steroids do not have a negative impact on OS.
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Notari, Lorella, Roxane Kirton, and Daniel S. Mills. "Psycho-Behavioural Changes in Dogs Treated with Corticosteroids: A Clinical Behaviour Perspective." Animals 12, no. 5 (2022): 592. http://dx.doi.org/10.3390/ani12050592.
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Arousal and distress are often important factors in problematic behaviours, and endogenous corticosteroids are important mediators in the associated stress responses. Exogenous corticosteroid treatments have been reported to change behaviour in human patients and laboratory animals, with similar changes also noted in pet dogs. These behaviours not only potentially adversely impact the welfare of the dogs, but also the quality of life of their owners. Indeed, corticosteroids can bias sensitivity towards aversion in dogs. A decrease in behaviours associated with positive affective states, such as play and exploratory behaviours, together with an increase in aggression and barking have also been described in dogs. According to the available literature, human patients with pre-existing psychiatric disorders are more at risk of developing behavioural side effects due to corticosteroid treatments. It is reasonable to consider that the same may happen in dogs with pre-existing behavioural problems. In this paper, the possible behavioural side effects of exogenous corticosteroids are summarised to help inform and support veterinarians prescribing these drugs.
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Beam, William R., Robert D. Ballard, and Richard J. Martin. "Spectrum of Corticosteroid Sensitivity in Nocturnal Asthma." American Review of Respiratory Disease 145, no. 5 (1992): 1082–86. http://dx.doi.org/10.1164/ajrccm/145.5.1082.
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Bittar, Jan, Carlos Kamiya-Matsuoka, Pedro C. Barata, Soo-Hyun Lee-Kim, Adriana Olar, and Ivo W. Tremont-Lukats. "Corticosteroid sensitivity in gliomatosis cerebri delays diagnosis." Practical Neurology 15, no. 4 (2015): 309–11. http://dx.doi.org/10.1136/practneurol-2015-001125.
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Mizutani, Mirai, Julie Bérubé, Heather G. Ahlgren, et al. "Corticosteroid-resistant inflammatory signalling in Pseudomonas-infected bronchial cells." ERJ Open Research 3, no. 2 (2017): 00144–2016. http://dx.doi.org/10.1183/23120541.00144-2016.
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Decreasing the inflammatory response that leads to tissue damage during cystic fibrosis (CF) lung disease has been a long-standing goal of CF therapy. While corticosteroids are widely used anti-inflammatory drugs, their efficacy in CF lung disease remains debated. The complex interaction between the colonising bacteria and the host environment may impact corticosteroid responsiveness.In this study, sputum samples from adult CF patients were collected at baseline and during pulmonary exacerbation episodes. Lung function measurements and sputum microbiological analyses were performed. In parallel, the inflammatory response and corticosteroid sensitivity of airway epithelial cells to Pseudomonas-derived exoproducts was investigated.We report that adult CF patients colonised with mucoid Pseudomonas aeruginosa have higher levels of baseline inflammation, more frequent exacerbations and worse lung function compared with patients colonised with nonmucoid P. aeruginosa. Moreover, mucoid P. aeruginosa activates NF-κB via Toll-like receptor (TLR) 2, which acts in an additive manner to TLR5 to drive inflammation in airway epithelial cells. Furthermore, TLR2-mediated intracellular signalling is more resistant to the anti-inflammatory effects of corticosteroid when compared with other TLR signalling pathways.Overall, these results suggest that airway inflammation triggered by mucoid P. aeruginosa is less responsive to the anti-inflammatory action of corticosteroids. Whether this translates into a diminished response of CF patients to corticosteroid therapy should be examined in future clinical studies.
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Sasaki, Eiko. "Corticosteroid sensitivity and cross-sensitivity A review of 18 cases 1967-1988." Contact Dermatitis 23, no. 5 (1990): 306–15. http://dx.doi.org/10.1111/j.1600-0536.1990.tb05164.x.
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Chen, Yung-Fu, Chih-Sheng Lin, Kuo-An Wang, et al. "Design of a Clinical Decision Support System for Fracture Prediction Using Imbalanced Dataset." Journal of Healthcare Engineering 2018 (2018): 1–13. http://dx.doi.org/10.1155/2018/9621640.
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More than 1 billion people suffer from chronic respiratory diseases worldwide, accounting for more than 4 million deaths annually. Inhaled corticosteroid is a popular medication for treating chronic respiratory diseases. Its side effects include decreased bone mineral density and osteoporosis. The aims of this study are to investigate the association of inhaled corticosteroids and fracture and to design a clinical support system for fracture prediction. The data of patients aged 20 years and older, who had visited healthcare centers and been prescribed with inhaled corticosteroids within 2002–2010, were retrieved from the National Health Insurance Research Database (NHIRD). After excluding patients diagnosed with hip fracture or vertebrate fractures before using inhaled corticosteroid, a total of 11645 patients receiving inhaled corticosteroid therapy were included for this study. Among them, 1134 (9.7%) were diagnosed with hip fracture or vertebrate fracture. The statistical results showed that demographic information, chronic respiratory diseases and comorbidities, and corticosteroid-related variables (cumulative dose, mean exposed daily dose, follow-up duration, and exposed duration) were significantly different between fracture and nonfracture patients. The clinical decision support systems (CDSSs) were designed with integrated genetic algorithm (GA) and support vector machine (SVM) by training and validating the models with balanced training sets obtained by random and cluster-based undersampling methods and testing with the imbalanced NHIRD dataset. Two different objective functions were adopted for obtaining optimal models with best predictive performance. The predictive performance of the CDSSs exhibits a sensitivity of 69.84–77.00% and an AUC of 0.7495–0.7590. It was concluded that long-term use of inhaled corticosteroids may induce osteoporosis and exhibit higher incidence of hip or vertebrate fractures. The accumulated dose of ICS and OCS therapies should be continuously monitored, especially for patients with older age and women after menopause, to prevent from exceeding the maximum dosage.
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Pavlovic, D., N. Viires, C. Zedda, M. Fournier, and M. Aubier. "Effects of corticosteroids on epithelial structure and smooth muscle function of rat trachea." European Respiratory Journal 11, no. 3 (1998): 575–82. http://dx.doi.org/10.1183/09031936.98.11030575.
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Corticosteroids, efficient drugs for the treatment of severe asthma, may have numerous side effects. We investigated the effects of 7 days of treatment with triamcinolone (1.2 mg x kg(-1) x day(-1)) on the epithelial structure, tracheal smooth muscle cross-sectional area and contractility in the rat. The corticosteroid-injected rats were compared to pair-fed, and pair-weighed animals. Histological studies were performed on transverse sections of glutaraldehyde-fixed tracheal blocks embedded in plastic. In the preparations taken from corticosteroid-injected, pair-fed and pair-weighed animals, pharmacological stimulation with single (10(-3) M) or cumulative (10(-8)-10(-3) M) concentrations of carbachol (in corticosteroid-injected and pair-fed animals), either inside (In) or outside (Out) of the tracheal lumen, was performed and contractions of the tracheal smooth muscle were recorded. We found that triamcinolone administration: 1) reduced the number of epithelial cells and the tracheal smooth muscle cross-sectional area; 2) induced a decrease in maximal tension (Tmax (g); Out: 2.42+/-0.17, 1.03+/-0.1 in pair-fed and corticosteroid-injected, respectively; In: 2.55+/-0.16, 1.1+/-0.16, respectively) without affecting the sensitivity of the tracheal smooth muscle; and 3) reduced the time required to reach 50% Tmax in carbachol (In) preparations. We conclude that the observed changes resulted from atrophy of tracheal smooth muscle induced by undernutrition and atrophy of tracheal smooth muscle and tracheal epithelium induced by corticosteroid treatment.
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Ellington, B., J. T. McBride, and D. C. Stokes. "Effects of corticosteroids on postnatal lung and airway growth in the ferret." Journal of Applied Physiology 68, no. 5 (1990): 2029–33. http://dx.doi.org/10.1152/jappl.1990.68.5.2029.
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To investigate the influence of corticosteroids on postnatal lung and airway growth, young male ferrets were given cortisone acetate (20 mg/kg im daily) beginning at 8 wk of age. At 19 wk of age pulmonary function was measured. The lungs were excised for measurements of recoil pressures and wet and dry weights. The dimensions of central and peripheral airways were estimated from analysis of bronchial casts. Corticosteroid-treated animals were shorter and tended to be lighter than control animals but were heavier in relation to length. Total lung capacity was reduced in proportion to the reduction in body size. Lung recoil and wet-to-dry weight ratios were nearly identical. Maximal expiratory flows were reduced in proportion to the reduction in body size. Size-corrected airway conductance was reduced, suggesting a sensitivity of central airways to growth suppression by corticosteroids. Peripheral airways, on the other hand, were not smaller in treated animals and were larger in proportion to body size. In the ferret corticosteroid administration is associated with a suppression of lung parenchymal growth similar to that of overall body growth. The peripheral airways may be less sensitive and the central airways more sensitive to the effect of corticosteroids on growth.
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Raff, H., J. Shinsako, C. E. Wade, L. C. Keil, and M. F. Dallman. "Acute volume expansion decreases adrenocortical sensitivity to ACTH and angiotensin II." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 249, no. 5 (1985): R611—R616. http://dx.doi.org/10.1152/ajpregu.1985.249.5.r611.
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This study examined the plasma aldosterone and corticosteroid responses to a 60-min infusion of adrenocorticotropin (ACTH) or angiotensin (ANG) II started immediately after an acute isotonic saline volume expansion (0.5 ml . kg-1 . min-1 for 30 min). Five conscious dogs of either sex with exteriorized carotid loops were used in this repeated-design study. Volume expansion per se caused a 10% decrease in hematocrit, a 12.5% decrease in plasma protein, and a 2.7-mmHg increase in central venous pressure with no change in mean arterial pressure, heart rate, or plasma sodium. Volume expansion per se also resulted in significant reductions in vasopressin, plasma renin activity, ACTH, aldosterone, and corticosteroid levels. The aldosterone responses to ACTH and ANG II were significantly inhibited (46-71%) by acute volume expansion. The corticosteroid response to ACTH was 19-29% inhibited by volume expansion. We conclude that acute volume expansion significantly inhibits the adrenocortical sensitivity to its tropic hormones probably via alterations of synergistic factors.
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Phillips, Mark, Christopher Vannabouathong, Tahira Devji, et al. "Differentiating factors of intra-articular injectables have a meaningful impact on knee osteoarthritis outcomes: a network meta-analysis." Knee Surgery, Sports Traumatology, Arthroscopy 28, no. 9 (2020): 3031–39. http://dx.doi.org/10.1007/s00167-019-05763-1.
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Abstract Purpose There are a number of developments in intra-articular therapies that have been determined to be differentiating factors within the classes of treatments. This study evaluated the efficacy and safety of intra-articular treatments of primary knee osteoarthritis in the short term (3 months follow-up), using a network meta-analysis design, while taking within-class differentiating factors into consideration. Methods A literature search of MEDLINE (through OVID), EMBASE (through OVID), Cochrane Central Register of Controlled Trials for all trials comparing intra-articular therapies was conducted on November 12, 2018. The treatments assessed were high molecular weight and low molecular weight hyaluronic acid injections, extended-release corticosteroids, standard-release corticosteroids, platelet-rich plasma, and saline. A frequentist network meta-analysis was conducted for each outcome. Results Sixty-four articles (9710 patients) met the inclusion criteria. High molecular weight hyaluronic acid (− 0.53, 95% CI − 0.81 to − 0.25) and PRP (− 0.79, 95% CI − 1.32 to − 0.26) were the only treatments with a confidence interval that lay completely above the MID threshold; however, PRP results varied within sensitivity analyses. For the function analysis, high molecular weight hyaluronic acid (SMD − 0.76, 95% CI − 1.30 to − 0.22) was the only treatment with a confidence interval entirely above the MID. Extended-release corticosteroid demonstrated a possible benefit in functional improvement (SMD − 0.98, 95% CI − 1.79 to − 0.17) compared to that of standard-release corticosteroid (SMD − 0.14, 95% CI − 0.72 to 0.44). Conclusion High molecular weight HA was the only treatment to surpass the MID for both pain and function outcomes. Extended-release corticosteroids may provide additional clinical benefit over standard-release corticosteroids. Platelet-rich plasma demonstrated possibly beneficial results; however, wide confidence intervals and sensitivity analyses made the conclusions of efficacy uncertain. Level of evidence Level 1. Systematic review of level 1 evidence.
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Kobayashi, Yoshiki, Kazuhiro Ito, Akira Kanda, Koich Tomoda, Nicolas Mercado, and Peter J. Barnes. "Impaired Dual-Specificity Protein Phosphatase DUSP4 Reduces Corticosteroid Sensitivity." Molecular Pharmacology 91, no. 5 (2017): 475–81. http://dx.doi.org/10.1124/mol.116.107656.
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Barry, Luke Evan, Ciaran O’Neill, and Liam G. Heaney. "Association between asthma, corticosteroids and allostatic load biomarkers: a cross-sectional study." Thorax 75, no. 10 (2020): 835–41. http://dx.doi.org/10.1136/thoraxjnl-2019-214139.
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BackgroundAllostatic load, a measure of early ageing or ‘wear and tear’ from adapting to environmental challenges, has been suggested as a framework with which to understand the stress-related disruption of multiple biological systems which may be linked to asthma. Considering the socioeconomic context is also critical given asthma and allostatic overload are more common in lower socioeconomic groups.AimsEstimate the relationship between allostatic load and its constituent biomarkers, asthma and corticosteroid prescribing while controlling for socioeconomic status.MethodsData from Understanding Society (a nationally representative survey of UK community-dwelling adults) waves 1–3 (2009–2012) allowed the identification of a sex-specific risk profile across 12 biomarkers used to construct an Allostatic Load Index for a sample of 9816 adults. Regression analyses were used to examine the association of asthma status and corticosteroid prescriptions with allostatic load and its constituent biomarkers while controlling for socioeconomic status (n=9805).ResultsSubjects with currently treated asthma and no corticosteroid prescription have an allostatic load 1.21 times higher than those without asthma (p<0.001). Asthmatic subjects in receipt of inhaled corticosteroids had an allostatic load, approximately 1.12 times higher than those without asthma (p<0.001). This association persisted in sensitivity analyses and appeared to be driven by an association with specific biomarkers (dehydroepiandrosterone-sulfate, waist-to-height ratio and C-reactive protein).ConclusionEarly ageing, in the form of a higher allostatic load, was present even in the mildest asthma group not receiving inhaled corticosteroids. Allostatic load is helpful in understanding the increased all-cause mortality and multimorbidity observed in asthma.
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Packer, Claire H., Clarice G. Zhou, Alyssa R. Hersh, Allison J. Allen, Amy C. Hermesch, and Aaron B. Caughey. "Antenatal Corticosteroids for Pregnant Women at High Risk of Preterm Delivery with COVID-19 Infection: A Decision Analysis." American Journal of Perinatology 37, no. 10 (2020): 1015–21. http://dx.doi.org/10.1055/s-0040-1713145.
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Objective Antenatal corticosteroids given prior to preterm deliveries reduce the risk of adverse neonatal outcomes. However, steroid administration in the setting of a viral respiratory infection can worsen maternal outcomes. Therefore, the decision to administer corticosteroids must balance the neonatal benefits with the potential harm to the mother if she is infected with the novel coronavirus disease 2019 (COVID-19). This study aimed to determine the gestational ages for which administering antenatal corticosteroids to women at high risk of preterm labor with concurrent COVID-19 infection results in improved combined maternal and infant outcomes. Study Design A decision-analytic model using TreeAge (2020) software was constructed for a theoretical cohort of hospitalized women with COVID-19 in the United States. All model inputs were derived from the literature. Outcomes included maternal intensive care unit (ICU) admission and death, along with infant outcomes of death, respiratory distress syndrome, intraventricular hemorrhage, and neurodevelopmental delay. Quality-adjusted life years (QALYs) were assessed from the maternal and infant perspectives. Sensitivity analyses were performed to determine if the results were robust over a range of assumptions. Results In our theoretical cohort of 10,000 women delivering between 24 and 33 weeks of gestation with COVID-19, corticosteroid administration resulted in 2,200 women admitted to the ICU and 110 maternal deaths. No antenatal corticosteroid use resulted in 1,500 ICU admissions and 75 maternal deaths. Overall, we found that corticosteroid administration resulted in higher combined QALYs up to 31 weeks of gestation in all hospitalized patients, and up to 29 weeks of gestation in ICU patients. Conclusion Administration of antenatal corticosteroids at less than 32 weeks of gestation for hospitalized patients and less than 30 weeks of gestation for patients admitted to the ICU resulted in higher combined maternal and infant outcomes compared with expectant management for women at high risk of preterm birth with COVID-19 infection. These results can guide clinicians in their counseling and management of these pregnant women. Key Points
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Lee, Jong Wook, Jun Ho Jang, Je-Hwan Lee, et al. "Ineffective Corticosteroid Treatment for Hemolysis Management of Paroxysmal Nocturnal Hemoglobinuria." Blood 124, no. 21 (2014): 5151. http://dx.doi.org/10.1182/blood.v124.21.5151.5151.
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Abstract Background: The primary clinical manifestations of paroxysmal nocturnal hemoglobinuria (PNH) are hemolytic anemia, bone marrow failure (BMF), and thromboembolism (TE). For optimum management, the contribution of both hemolysis and BMF to the complex anemia of PNH should be determined. The treatment of a hemolytic episode should aim at diminishing hemolysis and preventing complications. Corticosteroids as treatment, for both chronic hemolysis and acute hemolytic exacerbations have been used with a variety of side effects of long term use. In the Korean PNH population, corticosteroid (77.4%) represented the most common supportive care which provided with patients who had a history of corticosteroid use during the disease course (Lee JW et al. IJH. 2013 Jun; 97:749-57). There are no experimental data that provide a plausible explanation for why steroids should ameliorate the hemolysis of PNH. Aims: To evaluate the role of corticosteroid for treating chronic hemolysis in patients with PNH enrolled in the Korean prospective PNH registry. Methods: Korean patients with a diagnosis of PNH are eligible for inclusion in the prospective registry study designed to identify disease burden of PNH. Patient medical information data and other laboratory parameters were collected at the last 6 month follow-up.Here we analyzed patients with corticosteroid use within the past 6 months. 97 patients who were followed up at least 6 months after study enrollment was categorized into two groups. Patients have received eculizumab treatment or bone marrow transplantation (BMT) during the last 6month of follow up was excluded. Results: Among the 97 patients, 23% (22 patients) had corticosteroid therapy in the past 6 months. Mean age was 46 years (range 20-87; standard deviation, 16.3) and 51 patients (53 %) were female. At the time of analysis, 74 of 97 patients had recorded lactate dehydrogenase (LDH) levels. The mean LDH at 6months follow up after enrollment was 4.75-fold above the upper limit of normal (ULN) of the patients with corticosteroid use and 4.16-fold above ULN was reported in patients without corticosteroid use for the past 6 months (p=0.446). Hemolysis (LDH≥1.5 x ULN) was reported in 86% of patients with corticosteroid use and 77% of patients without corticosteroid use; there was no statistically significant difference between these two patient populations (p=0.420). The mean granulocyte clone size at enrollment in patients with corticosteroid use was 50.7% (range 1-98) and patients without corticosteroid use reported 52.3% (range 1-99) (p=0.850). The mean reticulocyte percent between two groups was 4.87% and 4.0%, respectively (p=0.317). Red blood cell was transfused to 15 (68.1%) of the 22 patients with corticosteroid use and 23 (30.7.%) of patients without corticosteroid use during the last 6 month follow-up; there was a significant difference between the two groups for mean unit of transfusion (p=0.005) (Table1). There was no new thromboembolism event reported during the past 6 months. Each group experienced abdominal pain and dyspnea during the last 6 months of follow up: patients with corticosteroid use vs. patients without corticosteroid use (p=0.121 and p= 0.055, respectively) (Table1). Conclusions: In the past, the main value of corticosteroids may have been to treat chronic hemolysis although it is limited by toxicity and the harm that can accrue from long term use. However, our results demonstrated that the management of hemolysis of PNH with corticosteroid could be ineffective and unsatisfactory. These data confirm that PNH patients with corticosteroid had ineffective hemolysis management (LDH ≥1.5 x ULN) and also suffer from disabling clinical signs and symptoms, such as continuous transfusion requirement with anemia, abdominal pain and dyspnea. Awareness of the potentially debilitating effects of corticosteroid myopathy and sensitivity to the disfiguring consequences of long term use are essential for proper management and also careful follow-up should be recommended. [Table 1] Total (N=97) Patients with corticosteroid use (n=22) Patients without corticosteroid use (n=75) p -value LDH fold above ULN (n=74), Mean (SD) Hemolysis (LDH ≥ 1.5xULN), n (%) 4.75 fold (3.02) 18/21 (85.7) 4.16 fold (2.89) 41/53 (77.4) 0.446 0.420 Transfusion (n=38), Mean unit (SD) 6.1 (9.43) 2.0 (3.99) 0.005 Abdominal pain (n=16) , n (%) 6/22 (27.3) 10/75 (11.2) 0.121 Dyspnea (n=11) , n (%) 5/22 (22.7) 6/75 (8.0) 0.055 Disclosures Lee: Alexion Pharmaceuticals: Consultancy. Jang:Alexion Pharmaceuticals: Consultancy. Lee:Alexion Pharmaceuticals: Consultancy. Jo:Alexion Pharmaceuticals: Consultancy. Kim:Alexion Pharmaceuticals: Consultancy.
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Goncalves, J., V. Macedo Silva, C. Macedo, et al. "P869 Deep ulcers in acute Ulcerative Colitis at index endoscopy predict corticosteroid resistance." Journal of Crohn's and Colitis 18, Supplement_1 (2024): i1606. http://dx.doi.org/10.1093/ecco-jcc/jjad212.0999.
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Abstract Background Ulcerative Colitis (UC) is a chronic inflammatory disease affecting the colon. Its acute form can be life-threatening, necessitating hospital admission and intravenous (IV) corticosteroid treatment. This study aimed to predict IV corticosteroid response in acute UC patients based on endoscopic findings at admission. Methods Individuals admitted to the hospital for acute UC for intravenous corticosteroid treatment were selected. Those with gastrointestinal infections and those without endoscopy at admission were excluded. Results A retrospective analysis was conducted on a cohort of 62 patients, of which 25.8% did not respond to IV steroids. No significant associations were found between demographic, clinical, and laboratory parameters and corticosteroid response at admission. Rectosigmoidoscopy was performed for all patients upon hospitalization, and the Mayo Endoscopic Score (MES) and Ulcerative Colitis Endoscopic Index of Severity (UCEIS) were obtained. The results revealed significant differences in median UCEIS scores between non-responders and responders (7, IQR 3 vs. 5, IQR 1, p=0.011). Notably, a UCEIS score of ≥5 demonstrated a sensitivity of 100% in identifying patients who did not respond to corticosteroids, although with a lower specificity of 22.7%. Furthermore, the MES exhibited a statistically significant association with treatment response (p=0.002), with a MES≤2 having a negative predictive value of 92.9% for IV steroid resistance. Importantly, the presence and type (small vs. large) of ulcers at the initial endoscopy were found to be the most effective predictive factor for corticosteroid response (AUC=0.745; 95%CI=0.594-0.896; p=0.005), as 57.1% of patients with deep ulcers were non-responders. Conclusion The importance of evaluating ulcer severity during endoscopic assessment in patients with acute ulcerative colitis is underscored by our findings. Notably, the presence of deep mucosal ulcerations should prompt consideration for intensifying therapy.
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Larrivée, Samuel, Frédéric Balg, Guillaume Léonard, Sonia Bédard, Michel Tousignant, and Patrick Boissy. "Wrist-Based Accelerometers and Visual Analog Scales as Outcome Measures for Shoulder Activity During Daily Living in Patients With Rotator Cuff Tendinopathy: Instrument Validation Study." JMIR Rehabilitation and Assistive Technologies 6, no. 2 (2019): e14468. http://dx.doi.org/10.2196/14468.
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Background Shoulder pain secondary to rotator cuff tendinopathy affects a large proportion of patients in orthopedic surgery practices. Corticosteroid injections are a common intervention proposed for these patients. The clinical evaluation of a response to corticosteroid injections is usually based only on the patient’s self-evaluation of his function, activity, and pain by multiple questionnaires with varying metrological qualities. Objective measures of upper extremity functions are lacking, but wearable sensors are emerging as potential tools to assess upper extremity function and activity. Objective This study aimed (1) to evaluate and compare test-retest reliability and sensitivity to change of known clinical assessments of shoulder function to wrist-based accelerometer measures and visual analog scales (VAS) of shoulder activity during daily living in patients with rotator cuff tendinopathy convergent validity and (2) to determine the acceptability and compliance of using wrist-based wearable sensors. Methods A total of 38 patients affected by rotator cuff tendinopathy wore wrist accelerometers on the affected side for a total of 5 weeks. Western Ontario Rotator Cuff (WORC) index; Short version of the Disability of the Arm, Shoulder, and Hand questionnaire (QuickDASH); and clinical examination (range of motion and strength) were performed the week before the corticosteroid injections, the day of the corticosteroid injections, and 2 and 4 weeks after the corticosteroid injections. Daily Single Assessment Numeric Evaluation (SANE) and VAS were filled by participants to record shoulder pain and activity. Accelerometer data were processed to extract daily upper extremity activity in the form of active time; activity counts; and ratio of low-intensity activities, medium-intensity activities, and high-intensity activities. Results Daily pain measured using VAS and SANE correlated well with the WORC and QuickDASH questionnaires (r=0.564-0.815) but not with accelerometry measures, amplitude, and strength. Daily activity measured with VAS had good correlation with active time (r=0.484, P=.02). All questionnaires had excellent test-retest reliability at 1 week before corticosteroid injections (intraclass correlation coefficient [ICC]=0.883-0.950). Acceptable reliability was observed with accelerometry (ICC=0.621-0.724), apart from low-intensity activities (ICC=0.104). Sensitivity to change was excellent at 2 and 4 weeks for all questionnaires (standardized response mean=1.039-2.094) except for activity VAS (standardized response mean=0.50). Accelerometry measures had low sensitivity to change at 2 weeks, but excellent sensitivity at 4 weeks (standardized response mean=0.803-1.032). Conclusions Daily pain VAS and SANE had good correlation with the validated questionnaires, excellent reliability at 1 week, and excellent sensitivity to change at 2 and 4 weeks. Daily activity VAS and accelerometry-derived active time correlated well together. Activity VAS had excellent reliability, but moderate sensitivity to change. Accelerometry measures had moderate reliability and acceptable sensitivity to change at 4 weeks.
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Mahajan, Vikram K., Vikas Sharma, Neeraj Sharma, Monika Chandel, and Rohit Verma. "Allergic contact dermatitis caused by topical corticosteroids: A review for clinicoepidemiological presentation, evaluation, and management aspects." Cosmoderma 4 (February 8, 2024): 14. http://dx.doi.org/10.25259/csdm_233_2023.
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Dermatitis medicamentosa or contact dermatitis to topically applied medicaments, active ingredients or excipients, is encountered frequently in clinical practice and should be suspected in patients showing resistance to treatment despite adequate therapy and in patients, who complain of intolerance to a particular treatment. Topical corticosteroids are prescribed mostly in dermatology for their anti-inflammatory, antiproliferative, and immunosuppressive actions to treat various inflammatory dermatoses. These may act as allergens and produce immunoglobulin E-mediated immediate hypersensitivity (anaphylaxis, urticaria, angioedema, bronchospasm, vomiting, and cardiovascular collapse) or T-cell-mediated allergic contact dermatitis (ACD). Although it occurs less often and is not life threatening, ACD negatively impacts the quality of life by worsening preexisting dermatitis. The prevalence of hypersensitivity to these allergens varies across regions and periods of time depending on the clinical practice, prescribing habits, and types of cases studied. Over-the-counter availability of corticosteroids in multiple formulations in recent years may further compound the problem due to their indiscriminate and extensive use. Although about one-third of all cases of contact dermatitis are initiated or perpetuated by topical medicaments, the occurrence of contact dermatitis due to corticosteroids remains undersuspected. This is perhaps due to their anti-inflammatory and immunosuppressive properties that make it difficult to doubt and prove contact sensitivity that may be from a corticosteroid itself or to the additives and vehicles in the formulation. Patch testing can help identify the culprit agents in ACD but early diagnosis depends on clinical suspicion. Sensitization in contact dermatitis exhibits cross-reactivity patterns based on corticosteroid structure. Clinicoepidemiological presentation, evaluation, and management aspects of contact hypersensitivity reactions to corticosteroids are reviewed.
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Sun, Xianwen, Qingyun Li, Yi Gong, Lei Ren, Huanying Wan, and Weiwu Deng. "Low-dose theophylline restores corticosteroid responsiveness in rats with smoke-induced airway inflammation." Canadian Journal of Physiology and Pharmacology 90, no. 7 (2012): 895–902. http://dx.doi.org/10.1139/y2012-079.
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Patients with chronic obstructive pulmonary disease (COPD) respond poorly to corticosteroids. Histone deacetylase-2 (HDAC-2) plays a pivotal role in many cases of steroid insensitivity. The main aim of this study was to restore the smoking-induced reduction in corticosteroid sensitivity by increasing HDAC-2 activity using low-dose theophylline. Rats were exposed to cigarette smoke (CS) and treated with budesonide and two doses of theophylline. Besides the pathologic examination and cell counting in the bronchoalveolar lavage fluid (BALF), the expression of HDAC-2 and CXC chemokine ligand-8 (CXCL-8) were measured. Airway inflammation induced by CS was demonstrated by pathologic changes of lung tissue and increased level of CXCL-8. CS exposure also markedly decreased HDAC-2 expression. Moreover, a negative correlation was found between HDAC-2 activity and a lung destruction index. The index was restored to control levels with inhaled corticosteroid treatment in combination with a low, not a high, dose of theophylline. These results indicate that low-dose theophylline might provide protection from smoke damage and improve the anti-inflammatory effects of steroids by increasing HDAC-2 activity.
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Martinet, N., P. Vaillant, T. Charles, J. Lambert, and Y. Martinet. "Dexamethasone modulation of tumour necrosis factor-alpha (cachectin) release by activated normal human alveolar macrophages." European Respiratory Journal 5, no. 1 (1992): 67–72. http://dx.doi.org/10.1183/09031936.93.05010067.
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Recurrent infections of the lower respiratory tract are a frequent and serious side-effect of chronic corticosteroid treatment. Since alveolar macrophages (AM) are currently thought to play a central role in the protection of the lower respiratory tract against infectious agents, it is likely that a steroid-induced deficiency of AM is involved in this process. In this respect, when activated, AM are major producers of tumour necrosis factor-alpha (TNF or cachectin), a versatile cytokine with several biological properties including antiviral and anti-infectious activities. A deficit of TNF production induced by corticosteroid may be one mechanism of the sensitivity to infections. Thus normal human AM obtained by bronchoalveolar lavage were pretreated with dexamethasone (DXM) before activation with lipopolysaccharides (LPS) and the amounts of TNF released in culture were quantified. Pretreatment with DXM resulted in a marked decrease of TNF release in a dose-dependent fashion. In contrast, when AM were activated with LPS before DXM treatment, TNF release by AM was suppressed in a more limited fashion. Thus DXM suppression of LPS-activated AM ability to release TNF may play a role in the susceptibility to infections of patients chronically treated with corticosteroids.
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Bechmann, L., K. Busse, M. Stoppe, S. Cotte, B. Ettrich, and F. Then Bergh. "Corticosteroid receptor expression and in vivo glucocorticoid sensitivity in multiple sclerosis." Journal of Neuroimmunology 276, no. 1-2 (2014): 159–65. http://dx.doi.org/10.1016/j.jneuroim.2014.07.004.
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Azam, AA, PJ Barnes, and NM Mercado. "S66 Targeting anti-ageing molecule AMPK restores corticosteroid sensitivity in COPD." Thorax 68, Suppl 3 (2013): A36.1—A36. http://dx.doi.org/10.1136/thoraxjnl-2013-204457.73.
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Sun, Xue-Jiao, Zhan-Hua Li, Yang Zhang та ін. "Combination of erythromycin and dexamethasone improves corticosteroid sensitivity induced by CSE through inhibiting PI3K-δ/Akt pathway and increasing GR expression". American Journal of Physiology-Lung Cellular and Molecular Physiology 309, № 2 (2015): L139—L146. http://dx.doi.org/10.1152/ajplung.00292.2014.
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Corticosteroid insensitivity, which is induced by cigarette smoke extract (CSE), is a significant barrier when treating chronic obstructive pulmonary disease (COPD). Erythromycin (EM) has been shown to have an anti-inflammatory role in some chronic airway inflammatory diseases, particularly diffuse panbronchiolitis and cystic fibrosis. Here, we explored whether the combination therapy of EM and dexamethasone (Dex) reverses corticosteroid insensitivity and investigated the molecular mechanism by which this occurs. We demonstrated that the combination of EM and Dex restored corticosteroid sensitivity in peripheral blood mononuclear cells (PBMCs) from COPD patients and U937 cells after CSE exposure. Moreover, pretreatment with 10, 50, or 100 μg/ml EM reversed the HDAC2 protein reduction induced by CSE exposure in a dose-dependent manner. U937 cells exposed to CSE show a reduction in histone deacetylase (HDAC) activity, which was potently reversed by EM or combination treatment. Although 10 and 17.5% CSE increased phosphorylated Akt (PAkt) expression in a concentration-dependent manner, preapplication of EM and the combination treatment in particular blocked this PAkt increase. Total Akt levels were unaffected by CSE or EM treatments. Furthermore, the combination treatment enhanced glucocorticoid receptor (GR)α expression. Our results demonstrate that the combination therapy of EM and Dex can restore corticosteroid sensitivity through inhibition of the PI3K-δ/Akt pathway and enhancing GRα expression.
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Darlington, D. N., K. Kaship, L. C. Keil, and M. F. Dallman. "Vascular responsiveness in adrenalectomized rats with corticosterone replacement." American Journal of Physiology-Heart and Circulatory Physiology 256, no. 5 (1989): H1274—H1281. http://dx.doi.org/10.1152/ajpheart.1989.256.5.h1274.
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To determine under resting, unstressed conditions the circulating glucocorticoid concentrations that best maintain sensitivity of the vascular smooth muscle and baroreceptor responses to vasoactive agents, rats with vascular cannulas were sham-adrenalectomized (sham) or adrenalectomized (ADRX) and provided with four levels of corticosterone replacement (approximately 100 mg fused pellets of corticosterone: cholesterol 0, 20, 40, and 80% implanted subcutaneously at the time of adrenal surgery). Changes in vascular and baroreflex responses were determined after intravenous injection of varying doses of phenylephrine and nitroglycerin with measurement of arterial blood pressure and heart rate in the conscious, chronically cannulated rats. Vascular sensitivity was decreased, and resting arterial blood pressure tended to be decreased in the adrenalectomized rats; both were restored to normal with levels of corticosterone (40%), which also maintained body weight gain, thymus weight, and plasma corticosteroid binding globulin concentrations at normal values. The baroreflex curve generated from the sham group was different from the curves generated from the ADRX+0, 20, and 40% groups, but not different from that of the ADRX+80% group, suggesting that the baroreflex is maintained by higher levels of corticosterone than are necessary for the maintenance of the other variables. These data demonstrate that physiological levels of corticosterone (40% pellet) restore vascular responsiveness, body weight, thymus weight, and transcortin levels to normal in ADRX rats, whereas higher levels (80% pellet) are necessary for restoration of the baroreflex.
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Myers, Brent, and Beverley Greenwood-Van Meerveld. "Differential involvement of amygdala corticosteroid receptors in visceral hyperalgesia following acute or repeated stress." American Journal of Physiology-Gastrointestinal and Liver Physiology 302, no. 2 (2012): G260—G266. http://dx.doi.org/10.1152/ajpgi.00353.2011.
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Symptoms of irritable bowel syndrome (IBS) are exacerbated by stress. Previously, we demonstrated that the stress hormone corticosterone applied directly to the amygdala induced visceral hypersensitivity through the actions of glucocorticoid receptor (GR) and mineralocorticoid receptor (MR). However, the involvement of amygdaloid GR and MR in the regulation of visceral sensitivity following psychological stress is unknown; therefore, the goal of the present study was to determine the relative importance of amygdaloid GR and MR in the regulation of visceral sensitivity in a rodent model of behavioral stress. Male F-344 rats were stereotaxically implanted with micropellets bilaterally on the dorsal margin of the amygdala containing the GR antagonist mifepristone, the MR antagonist spironolactone, or cholesterol as a control. Animals were then exposed to 1 h of water-avoidance stress (WAS) or sham stress for 1 day (acute) or 7 days (repeated). Visceral sensitivity was assessed either 1 h or 24 h after the final session of WAS and quantified as the number of contractions of the external abdominal oblique, a visceromotor response, in response to colorectal distension at pressures of 0–60 mmHg. Acute stress induced transient visceral hyperalgesia, which was absent 24 h after WAS and independent of GR and MR. Conversely, repeated WAS induced sustained visceral hyperalgesia that was abolished by specifically targeting the amygdala with GR and MR antagonists. These results demonstrate that the amygdala corticosteroid system plays an essential role in mediating the effects of repeated WAS on visceral sensitivity. Furthermore, our findings suggest that amygdaloid GR and MR may be involved in IBS symptomatology.
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Mohan, Anand, Mohd Adil Khan, and Suresh Chandra. "Advance approaches in alopecia." Pharmaceutical and Biological Evaluations 4, no. 3 (2017): 135. http://dx.doi.org/10.26510/2394-0859.pbe.2017.21.
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Alopecia is characterized by hair loss mainly on scalp some time on other resign of the body that has negative psychological and social impact on patients. Androgenetic alopecia and alopecia areata are common disorders. Androgenetic alopecia is the sensitivity of scalp follicles to dihydrotestosterone and alopecia areata is an autoimmune disorder. Current studies have explained the efficacy of corticosteroid therapy or the combination of ultraviolet A therapy and systemic corticosteroids for severe AA. Finasteride opens up new possibilities for the treatment of androgenetic alopecia. Current drug treatment approaches use regrowth stimulators such as minoxidil and finasteride for androgenetic alopecia, as well as corticosteroids, PUVA therapy for alopecia areata. Targeted delivery to the Hair follicle units helps faster targeting to cells that accelerate drug action by faster availability of drug, novel combination treatments combinations like tretinoin with minoxidil shows better results, gene therapy are new approaches that are under developing stage and giving satisfactory results on animal as well as humans.
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Sari, Indri Widya, Rusmawardiana, and Fifa Argentina. "Ulceration of Corticosteroid-Induced StriaeDistensae in Children with Nephrotic Syndrome." Jurnal RSMH Palembang 2, no. 1 (2021): 113–18. http://dx.doi.org/10.37275/jrp.v2i1.15.
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Striaedistensae(SD) is linear scar tissue in the epidermis and dermis due to excessive stretching of the skin.Striaedistensaeoccurs due to dysfunction of extracellular matrix components that play a role in skin elasticity increasing sensitivity to minor trauma and ulceration. One of the causes is the long-term use of corticosteroids. Systemic corticosteroids are the mainstay of treatment for nephrotic syndrome, so long-term prescribing of corticosteroids should be carried out with caution. It is reported case of a 15-year-old boy with nephrotic syndrome complains of red streaks appearing on his abdomen, back, buttocks, and lower limbs after 2 months of corticosteroid treatment. Pus-filled nodules develop which become ulcers on the red lines of the back. On physical examination found striaedistensae in the abdominal region, posterior trunk, gluteus, femoral and proximal 1/3 bilateral cruris posterior. Found 3 ulcers on the striaedistensae on the posterior trunk, oval to round shape, size 1x1x0,5 cm to 2x1,5x1 cm, base of necrotic tissue, pus contents, wall echoing, edges are not raised, surrounding tissue is erythematous-livid, tenderness, odor, and no induration. On examination of the ulcer swab with Gram stain found Gram-positive bacteria. The culture results showed Staphylococcus aureus. The patient was treated with topical 0.05% retinoic acid every night at SD, and ulcers were treatedsystemic antibiotics of 2 grams ceftriaxone per day for 1 week, as well as ulcer treatment by compressing 1%0 salicylic acid solution, hydrogel, and foam dressing. After 4 weeks of therapy, there was clinical improvement, thinning striae and reduced ulcer size.
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Ozawa, Hitoshi, Fang Han, and Mitsuhiro Kawata. "Exocytosis sensitivity to growth hormone-releasing hormone in subsets of GH cells in rats under different corticosterone conditions. Ultrastructural study using microwave irradiation for fixation and immunocytochemistry." Journal of Endocrinology 183, no. 3 (2004): 507–15. http://dx.doi.org/10.1677/joe.1.05656.
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Growth hormone (GH) cells in the rat anterior pituitary have been morphologically classified into three subtypes: type I (mature) containing large secretory granules about 350 nm in diameter, type II (intermediate) containing a mixture of large and small granules, and type III (immature) containing small granules about 150 nm in diameter. However, the functional implications of morphological heterogeneity, especially the different sensitivities to growth hormone-releasing hormone (GRH) under different corticosteroid conditions have not been elucidated to date. In the present study, by application of microwave irradiation (MWI) for fixation and immunocytochemistry, new findings of the exocytotic response have been revealed among the subsets of GH cells following adrenalectomy (ADX), corticosterone treatment and/or GRH treatment. The MWI gave effective results for fixation, especially for the permeability of the fixative, and showed good results for immunoelectron microscopy using the protein-A gold method. Moreover, the use of MWI greatly shortened the fixation, processing and immunolabeling times without compromising the quality of ultrastructural preservation and the specificity of labeling. The number of exocytotic figures was low in all subtypes of GH cells in the sham-operated control rats. GRH treatment induced a significant increase in exocytosis in each subtype of GH cells, particularly in type I (mature) and type II (intermediate) GH cells in the control rats. GRH injection to rats for 4 days after ADX also showed an increase in exocytosis, but the degree was significantly less in comparison with the GRH injection in the control group. Corticosterone replacement given to ADX rats induced a clear recovery of the exocytotic response to GRH to the control level. Serum GH content measured by radioimmunoassay correlated with these morphological results. These results suggest that the secretion of GH stimulated by GRH is closely related to corticosteroids, and that the sensitivity to GRH differs among the three subtypes of GH cells.
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Sivapalan, Pradeesh, Andras Bikov, Charlotte Suppli Ulrik, et al. "Corticosteroid Resistance in Smokers—A Substudy Analysis of the CORTICO-COP Randomised Controlled Trial." Journal of Clinical Medicine 10, no. 12 (2021): 2734. http://dx.doi.org/10.3390/jcm10122734.
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The CORTICO-COP trial showed that eosinophil-guided corticosteroid-sparing treatment for acute exacerbation of chronic obstructive pulmonary disease was non-inferior to standard of care and decreased the accumulated dose of systemic corticosteroids that patients were exposed to by approximately 60%. Smoking status has been shown to affect corticosteroid responsiveness. This post hoc analysis investigated whether eosinophil-guided treatment is non-inferior to conventional treatment in current smokers. The main analysis of current smokers showed no significant difference in the primary endpoint, days alive, and out of hospital within 14 days between the control group (mean, 9.8 days; 95% confidence interval (CI), 8.7–10.8) and the eosinophil-guided group (mean, 8.7 days; 95% CI, 7.5–9.9; p = 0.34). Secondary analyses of the number of exacerbations or deaths, the number of intensive care unit admissions or deaths, lung function improvement, and change in health-related quality of life also showed no significant differences between the two groups. The results of a sensitivity analysis of ex-smokers are consistent with the main analysis. Our results suggest that eosinophil-guided treatment is non-inferior to standard of care in current smokers and ex-smokers. Because data on the impact of smoking status on eosinophil-guided treatments are sparse, more randomised trials are needed to confirm our results.
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Valenta, C., and H. Janout. "Corticosteroid Analysis by HPLC with Increased Sensitivity by Use of Precolumn Concentration." Journal of Liquid Chromatography & Related Technologies 17, no. 5 (1994): 1141–46. http://dx.doi.org/10.1080/10826079408013391.
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Lo, Chun-Yu, Charalambos Michaeloudes, Pankaj K. Bhavsar, et al. "Increased phenotypic differentiation and reduced corticosteroid sensitivity of fibrocytes in severe asthma." Journal of Allergy and Clinical Immunology 135, no. 5 (2015): 1186–95. http://dx.doi.org/10.1016/j.jaci.2014.10.031.
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Myers, Brent, and Beverley Greenwood-Van Meerveld. "Corticosteroid receptor-mediated mechanisms in the amygdala regulate anxiety and colonic sensitivity." American Journal of Physiology-Gastrointestinal and Liver Physiology 292, no. 6 (2007): G1622—G1629. http://dx.doi.org/10.1152/ajpgi.00080.2007.
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Our previous studies have shown that stereotaxic implantation of corticosterone (Cort) onto the central amygdaloid nucleus increases both anxiety and colonic sensitivity. The goal of this study was to examine the relative importance of amygdaloid glucocorticoid (GR) and mineralocorticoid receptor (MR)-mediated mechanisms in the induction of anxiety and colonic hypersensitivity. In male Fischer 344 rats, Cort or cholesterol micropellets were stereotaxically implanted bilaterally at the dorsal boundary of the central amygdaloid nucleus either alone or in combination with a GR antagonist, mifepristone, or a MR antagonist, spironolactone. Anxiety was assessed on the elevated plus maze and quantified as the percentage of time spent in open arm exploration. Colonic sensitivity was measured by recording a visceromotor response, the number of abdominal muscle contractions in response to colorectal distension. In Cort-implanted rats there was a significant reduction in the percentage of time spent in the open arms of the elevated plus maze compared with cholesterol controls, indicating increased anxiety. Furthermore, colonic hypersensitivity was observed in response to colorectal distension compared with rats with cholesterol implants. In rats with Cort implants combined with either a GR or MR antagonist, there was a significant inhibition of anxiety and colonic hypersensitivity. Our data suggest that both GR and MR play a critical role in Cort-induced anxiety and colonic hypersensitivity.
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Kobayashi, Yoshiki, Akira Kanda, Dan Van Bui, et al. "Omalizumab Restores Response to Corticosteroids in Patients with Eosinophilic Chronic Rhinosinusitis and Severe Asthma." Biomedicines 9, no. 7 (2021): 787. http://dx.doi.org/10.3390/biomedicines9070787.
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Eosinophilic chronic rhinosinusitis (ECRS), which is a subgroup of chronic rhinosinusitis with nasal polyps, is characterized by eosinophilic airway inflammation extending across both the upper and lower airways. Some severe cases are refractory even after endoscopic sinus surgery, likely because of local steroid insensitivity. Although real-life studies indicate that treatment with omalizumab for severe allergic asthma improves the outcome of coexistent ECRS, the underlying mechanisms of omalizumab in eosinophilic airway inflammation have not been fully elucidated. Twenty-five patients with ECRS and severe asthma who were refractory to conventional treatments and who received omalizumab were evaluated. Nineteen of twenty-five patients were responsive to omalizumab according to physician-assessed global evaluation of treatment effectiveness. In the responders, the levels of peripheral blood eosinophils and fractionated exhaled nitric oxide (a marker of eosinophilic inflammation) and of CCL4 and soluble CD69 (markers of eosinophil activation) were reduced concomitantly with the restoration of corticosteroid sensitivity. Omalizumab restored the eosinophil-peroxidase-mediated PP2A inactivation and steroid insensitivity in BEAS-2B. In addition, the local inflammation simulant model using BEAS-2B cells incubated with diluted serum from each patient confirmed omalizumab’s effects on restoration of corticosteroid sensitivity via PP2A activation; thus, omalizumab could be a promising therapeutic option for refractory eosinophilic airway inflammation with corticosteroid resistance.
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Farhan, Mohammed A., Ahmed M. Moharram, Tareq Salah, and Omar M. Shaaban. "Types of yeasts that cause vulvovaginal candidiasis in chronic users of corticosteroids." Medical Mycology 57, no. 6 (2018): 681–87. http://dx.doi.org/10.1093/mmy/myy117.
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AbstractThe current study aims to compare between the types of yeasts that cause vulvovaginal candidiasis (VVC) in women using corticosteroid medication compared to nonusers and estimate their sensitivity to available commercial antifungal agents. In a descriptive analytical cross-sectional study, we recruited 41 chronic corticosteroid users diagnosed clinically to have VVC from Women's Health Hospital, Assiut University, Egypt. Forty-seven age-matched women with VVC were recruited as a control group. Full history and clinical examination were performed. Vaginal sterile swab obtained from the vagina of each participant was subjected to direct Gram-stained smear examination as well as a culture on Sabouraud's glucose agar and HiCrome Candida agar. Further identification of the isolates was done using traditional methods. Fifty out of 88 samples (56.8%) were positive in culture including 25 samples (61%) from corticosteroid users group and 25 (53.2%) from noncorticosteroid users with no statistically significant difference (P = .302). The chronic corticosteroid users had more incidence of recurrent VVC as compared to nonusers (65.9% vs 40.4%, respectively) (P = .015). There was a significantly higher rate of non-Candida albicans (NCA) infections in corticosteroid users compared with nonusers (48% vs 20%, respectively) (P = .036). A higher significant difference in resistance of the isolates against clotrimazole (P = .003) and ketoconazole (P = .017) was demonstrated in corticosteroid users compared to nonusers. Thus, chronic corticosteroid use causes frequent attacks of VVC and increases the frequency of infection by NCA strains. Also, it increases resistance to common antifungal agents especially azole group.
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Bannier, Michiel A. G. E., Sophie Kienhorst, Quirijn Jöbsis, et al. "Exhaled Breath Analysis for Investigating the Use of Inhaled Corticosteroids and Corticosteroid Responsiveness in Wheezing Preschool Children." Journal of Clinical Medicine 11, no. 17 (2022): 5160. http://dx.doi.org/10.3390/jcm11175160.
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Exhaled breath analysis has great potential in diagnosing various respiratory and non-respiratory diseases. In this study, we investigated the influence of inhaled corticosteroids (ICS) on exhaled volatile organic compounds (VOCs) of wheezing preschool children. Furthermore, we assessed whether exhaled VOCs could predict a clinical steroid response in wheezing preschool children. We performed a crossover 8-week ICS trial, in which 147 children were included. Complete data were available for 89 children, of which 46 children were defined as steroid-responsive. Exhaled VOCs were measured by GC-tof-MS. Statistical analysis by means of Random Forest was used to investigate the effect of ICS on exhaled VOCs. A set of 20 VOCs could best discriminate between measurements before and after ICS treatment, with a sensitivity of 73% and specificity of 67% (area under ROC curve = 0.72). Most discriminative VOCs were branched C11H24, butanal, octanal, acetic acid and methylated pentane. Other VOCs predominantly included alkanes. Regularised multivariate analysis of variance (rMANOVA) was used to determine treatment response, which showed a significant effect between responders and non-responders (p < 0.01). These results show that ICS significantly altered the exhaled breath profiles of wheezing preschool children, irrespective of clinical treatment response. Furthermore, exhaled VOCs were capable of determining corticosteroid responsiveness in wheezing preschool children.
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Li, Xiongjuan, Mohammed Shaqura, Doaa Mohamed, et al. "Pro- versus Antinociceptive Nongenomic Effects of Neuronal Mineralocorticoid versus Glucocorticoid Receptors during Rat Hind Paw Inflammation." Anesthesiology 128, no. 4 (2018): 796–809. http://dx.doi.org/10.1097/aln.0000000000002087.
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Abstract Background In naive rats, corticosteroids activate neuronal membrane–bound glucocorticoid and mineralocorticoid receptors in spinal cord and periphery to modulate nociceptive behavior by nongenomic mechanisms. Here we investigated inflammation-induced changes in neuronal versus glial glucocorticoid and mineralocorticoid receptors and their ligand-mediated nongenomic impact on mechanical nociception in rats. Methods In Wistar rats (n = 5 to 7/group) with Freund’s complete adjuvant hind paw inflammation, we examined glucocorticoid and mineralocorticoid receptor expression in spinal cord and peripheral sensory neurons versus glial using quantitative reverse transcription-polymerase chain reaction (qRT-PCR), Western blot, immunohistochemistry, and radioligand binding. Moreover, we explored the expression of mineralocorticoid receptors protecting enzyme 11-betahydroxysteroid dehydrogenase type 2 as well as the nociceptive behavioral changes after glucocorticoid and mineralocorticoid receptors agonist or antagonist application. Results Hind paw inflammation resulted in significant upregulation of glucocorticoid receptors in nociceptive neurons of spinal cord (60%) and dorsal root ganglia (15%) as well as mineralocorticoid receptors, while corticosteroid plasma concentrations remained unchanged. Mineralocorticoid (83 ± 16 fmol/mg) but not glucocorticoid (104 ± 20 fmol/mg) membrane binding sites increased twofold in dorsal root ganglia concomitant with upregulated 11-betahydroxysteroid dehydrogenase type 2 (43%). Glucocorticoid and mineralocorticoid receptor expression in spinal microglia and astrocytes was small. Importantly, glucocorticoid receptor agonist dexamethasone or mineralocorticoid receptor antagonist canrenoate-K rapidly and dose-dependently attenuated nociceptive behavior. Isobolographic analysis of the combination of both drugs showed subadditive but not synergistic or additive effects. Conclusions The enhanced mechanical sensitivity of inflamed hind paws accompanied with corticosteroid receptor upregulation in spinal and peripheral sensory neurons was attenuated immediately after glucocorticoid receptor agonist and mineralocorticoid receptor antagonist administration, suggesting acute nongenomic effects consistent with detected membrane-bound corticosteroid receptors.
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Griffiths, S. D., D. T. Goodhead, S. J. Marsden, et al. "Interleukin 7-dependent B lymphocyte precursor cells are ultrasensitive to apoptosis." Journal of Experimental Medicine 179, no. 6 (1994): 1789–97. http://dx.doi.org/10.1084/jem.179.6.1789.
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We have compared the sensitivity of clonogenic interleukin 7 (IL-7)-dependent murine B cell precursors with that of clonogenic mature B cells and myeloid precursors to alpha-particles from plutonium-238 and X radiation. All three populations are relatively sensitive, but B cell precursors are ultrasensitive. This differential sensitivity is also observed with corticosteroid, etoposide, and cisplatin, all apoptosis-inducing drugs used in the treatment of leukemia and other cancers. Further, we show that x-rays and drugs induce the bulk of the B cell precursor population to undergo rapid apoptosis, despite the continued presence of IL-7. B cell precursors were found to express very low levels of BCL-2 protein compared with mature splenic B cells and their resistance to x-rays and corticosteroid could be enhanced by expression of a BCL-2 transgene. These data have important implications for normal lymphopoiesis and for the behavior of leukemic lymphoid precursor cells.
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Kadushkin, A. G., A. D. Taganovich, A. A. Arabey, L. M. Shishlo, A. P. Lyubetskaya, and L. V. Aleshkevich. "Sensitivity to glucocorticosteroids and heterogeneity of in vitro cell response in patients with chronic obstructive pulmonary disease." Russian Pulmonology 28, no. 5 (2018): 558–66. http://dx.doi.org/10.18093/0869-0189-2018-28-5-558-566.
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Inhaled corticosteroids are widely used for the treatment of chronic obstructive pulmonary disease (COPD), but their efficacy significantly varies between patients. The aim of the study was to establish approaches to reveal steroid-sensitive and steroid-resistant patients with COPD using the blood and lung cells. Methods. Forty five patients with COPD undergoing bronchoscopy were recruited for the study of cytokine secretion by alveolar macrophages under the influence of glucocorticoids. Alveolar macrophages isolated from bronchoalveolar lavage fluid were cultured with lipopolysaccharide (LPS) and different concentrations of dexamethasone (0.01 – 1000 nM) for 24 h. Then, supernatants were removed and analyzed for concentrations of interleukin 6 (IL-6), IL-8 and tumor necrosis factor α (TNF-α). Binding of the glucocorticoid with its receptors was investigated in 24 patients with COPD, 20 healthy smokers and 20 healthy non-smokers. Blood cells were cultured with fluorescein isothiocyanate (FITC)-labelled dexamethasone and monoclonal antibodies against surface antigens of lymphocyte and monocyte populations. Fluorescence intensity of FITC-labelled dexamethasone was analyzed in blood cells using flow cytometry. Results. Dexamethasone significantly inhibited IL-6, IL-8, and TNF-α production in alveolar macrophages in a dose dependent manner. The maximal inhibition of cytokine production was observed at dexamethasone concentration of 100 nM, and the maximal cell response variability was found at 10 nM. IL-8 was less sensitive to the corticosteroid compared to IL-6 and TNF-α. Dexamethasone at any concentration failed to reach >50% inhibition of LPS-induced production of IL-8, IL-6 and TNF-α in alveolar macrophages of 40.0%; 11.1% and 8.9% of COPD patients, respectively. The fluorescence intensity of FITC-labelled dexamethasone in blood lymphocytes and monocytes was lower in smokers with COPD compared to healthy smokers and healthy non-smokers. The binding of dexamethasone with its receptors in the blood cells was higher in healthy non-smokers compared to healthy smokers. Conclusion. In vitro response of alveolar macrophages to glucocorticoids in COPD patients is characterized by significant inter-individual variability. The weak corticosteroid-related inhibition of IL-8 production can contribute to neutrophilic inflammation in COPD. The capacity of glucocorticoid receptors to bind with their ligands in blood lymphocytes and monocytes is decreased in COPD patients.
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DeRijk, R. H. "Changes in corticosteroid sensitivity of peripheral blood lymphocytes after strenuous exercise in humans." Journal of Clinical Endocrinology & Metabolism 81, no. 1 (1996): 228–35. http://dx.doi.org/10.1210/jc.81.1.228.
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Runyon, Bruce A. "Exquisite Sensitivity to Small Decrements in Corticosteroid Dose in Autoimmune Chronic Active Hepatitis." Journal of Clinical Gastroenterology 9, no. 5 (1987): 541–42. http://dx.doi.org/10.1097/00004836-198710000-00010.
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DeRijk, R. H., J. Petrides, P. Deuster, P. W. Gold, and E. M. Sternberg. "Changes in corticosteroid sensitivity of peripheral blood lymphocytes after strenuous exercise in humans." Journal of Clinical Endocrinology & Metabolism 81, no. 1 (1996): 228–35. http://dx.doi.org/10.1210/jcem.81.1.8550757.
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Allen, David B. "Sense and sensitivity: assessing inhaled corticosteroid effects on the hypothalamic-pituitary-adrenal axis." Annals of Allergy, Asthma & Immunology 89, no. 6 (2002): 537–39. http://dx.doi.org/10.1016/s1081-1206(10)62097-2.
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Mitani, Akihisa, Aishah Azam, Chaitanya Vuppusetty, Kazuhiro Ito, Nicolas Mercado, and Peter J. Barnes. "Quercetin restores corticosteroid sensitivity in cells from patients with chronic obstructive pulmonary disease." Experimental Lung Research 43, no. 9-10 (2017): 417–25. http://dx.doi.org/10.1080/01902148.2017.1393707.
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Al-Zamil, Mustafa Kh, Natalia G. Kulikova, and Ekaterina S. Vasilieva. "Interstitial electrical nerve stimulation in combination with perineural injections of corticosteroids in the treatment of paresthetic meralgia." Russian Journal of Physiotherapy, Balneology and Rehabilitation 21, no. 3 (2022): 171–82. http://dx.doi.org/10.17816/rjpbr111791.
Full textAbstract:
BACKGROUND: Paresthetic meralgia is a neuropathy caused by compression, pinching or stretching of the lateral femoral cutaneous nerve between the inguinal ligament and the anterior superior iliac spine.
 AIM: to study the effectiveness of interstitial electrical nerve stimulation in combination with perineural corticosteroid injections in the treatment of paresthetic meralgia.
 MATERIALS AND METHODS: We observed 30 patients with bilateral paresthetic meralgia. All patients suffered from numbness, tingling, and pain in the lateral thighs. Our study included only patients with bilateral lesions and severe pain. Patients were divided into 3 groups. The first group ― 10 patients underwent drug therapy (control group). The 2nd group included 10 patients who, in addition to drug therapy, underwent a course of perineural corticosteroid injections. The third group included 10 patients who, in addition to drug therapy, underwent a course perineural corticosteroid injections and interstitial electrical nerve stimulation.
 RESULTS: The obtained results prove the high efficacy of perineural corticosteroid injections in the treatment of paresthetic meralgia in comparison with the exclusive use of medical therapy. At the same time, the analgesic effect increased by 2.17 times, the regression of positive sensory symptoms increased by 1.2 times, sensitivity improved by 2 times and the quality of life of patients in the physical and mental spheres significantly improved. The use of interstitial electrical nerve stimulation after perineural corticosteroid injections exceeded the effectiveness of perineural corticosteroid injections in reducing pain by 98%, regressing positive sensory symptoms by 63%, reducing the zone of hypesthesia by 2 times and improving the quality of life in the physical and mental components of SF-36 by an average of 2 times.
 CONCLUSIONS: It is recommended to perform perineural corticosteroid injections in the treatment of patients with paresthetic meralgia, followed by the use of interstitial electrical nerve stimulation.