Longitudinal in vivo tracking of adverse effects following topical steroid treatment.
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ABSTRACT:
SUBMITTER: Bower AJ
PROVIDER: S-EPMC4864142 | biostudies-literature | 2016 May
REPOSITORIES: biostudies-literature
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Longitudinal in vivo tracking of adverse effects following topical steroid treatment.
Bower Andrew J AJ Arp Zane Z Zhao Youbo Y Li Joanne J Chaney Eric J EJ Marjanovic Marina M Hughes-Earle Angela A Boppart Stephen A SA
Experimental dermatology 20160213 5
Topical steroids are known for their anti-inflammatory properties and are commonly prescribed to treat many adverse skin conditions such as eczema and psoriasis. While these treatments are known to be effective, adverse effects including skin atrophy are common. In this study, the progression of these effects is investigated in an in vivo mouse model using multimodal optical microscopy. Utilizing a system capable of performing two-photon excitation fluorescence microscopy (TPEF) of reduced nicot ...[more]
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Project description:PurposeTo compare clinical outcomes and patient preference for the dexamethasone intracanalicular insert (DEX) versus topical loteprednol (LOT) or olopatadine (OLO) for the treatment of allergic conjunctivitis in a real-world model of allergen exposure.MethodsThis was a prospective comparative trial. Adults with testing-confirmed bilateral allergic conjunctivitis received DEX in the more symptomatic eye and either LOT 2 times daily or OLO once daily for 30 days in the fellow eye. The primary outcome was patient preference for treatment. Clinical outcomes included ocular itching and hyperemia, lid swelling, and watering/tearing. Safety outcomes included intraocular pressure (IOP).ResultsThirty patients participated and completed the study. All received DEX in the eye with worse symptoms and 15 received LOT and the other 15 received OLO in the other eye. Patients preferred DEX (10/15; 66.7%) over LOT (4/15; 26.7%), with one patient having no preference (p = 0.0103). Patients had no preference between DEX (8/15; 53.3%) and OLO (6/15; 40%), with one patient having no preference (p = 0.1044). In the DEX/LOT cohort, ocular itching and hyperemia improved more with DEX than LOT (p ≤ 0.009), while in the DEX/OLO cohort, the DEX eyes showed greater improvement in conjunctival hyperemia (p < 0.0001) but not itching (p = 0.074). No between-group differences were seen in eyelid swelling or tearing/watering in either cohort. Mean change in IOP was similar between the DEX and LOT eyes (p = 0.4921), and mean IOP rose more in the DEX eyes than the OLO eyes (by <1 mmHg; p = 0.0403).ConclusionOverall, this real-world study demonstrated that the dexamethasone intracanalicular insert was as effective as a topical antihistamine/mast cell stabilizer and more effective than topical steroids in relieving the signs and symptoms of allergic conjunctivitis. This insert should be considered as an alternative to topical therapy for the treatment of allergic conjunctivitis.
| S-EPMC10875166 | biostudies-literature
Project description:OBJECTIVE:The aim of this prospective multicenter randomized controlled trial was to compare the efficacy of silver nitrate cauterization against that of topical steroid ointment in the treatment of neonatal umbilical granuloma. METHODS:An open-label, non-inferiority randomized controlled trial was conducted from January 2013 to January 2016. The primary endpoint for the silver nitrate cauterization and topical steroid ointment groups was the healing rate after 2 weeks of treatment, applying a non-inferiority margin of 10%. The healing rate was evaluated until completion of 3 weeks of treatment. RESULTS:Participants comprised 207 neonates with newly diagnosed umbilical granuloma, randomized to receive silver nitrate cauterization (n = 104) or topical steroid ointment (n = 103). Healing rates after 2 weeks of treatment were 87.5% (91/104) in the silver nitrate cauterization and 82% (82/100) in the topical steroid ointment group group. The difference between groups was -5.5% (95% confidence interval, -19.1%, 8.4%), indicating that the non-inferiority criterion was not met. After 3 weeks of treatment, the healing rate with topical steroid ointment treatment was almost identical to that of silver nitrate cauterization (94/104 [90.4%] vs. 91/100 [91.0%]; 0.6% [-13.2 to 14.3]). No major complications occurred in either group. CONCLUSIONS:This study did not establish non-inferiority of topical steroid ointment treatment relative to silver nitrate cauterization, presumably due to lower healing rates than expected leading to an underpowered trial. However, considering that silver nitrate cauterization carries a distinct risk of chemical burns and that the overall efficacy of topical steroid ointment treatment is similar to that of silver nitrate cauterization, topical steroid ointment might be considered as a good alternative in the treatment of neonatal umbilical granuloma due to its safety and simplicity. To clarify non-inferiority, a larger study is needed.
| S-EPMC5811027 | biostudies-literature
Project description:Commensal microbes are exposed to enterohepatically circulated steroids such as bile acids and hormones in the gastrointestinal, vaginal, and urinary tracts. Since commensal microbes are exposed to these molecules exclusively in association with their host, we hypothesized that they may serve as effectors to identify and characterize genetic pathways involved in the commensal-host relationship. Host specific and some ingested steroids (phytoestrogens) are enterohepatically circulated through the lumen of the small intestine. Bile acid steroids are present at high concentrations, approximating 4 to 20 mM in the duodenum, and are released in bile from the common bile duct. Steroid hormones are secreted in bile at levels approximating 6 to 13 mg per day once conjugated to glucuronide or sulfate by the liver. Re-absorption of steroids by the terminal ileum is an incomplete process: for example, 200 to 600 mg of bile acid steroids per day in humans escape to the colon where complex microbial populations exist. We have shown that steroid hormones estradiol, progesterone, and hydrocortisone serve as strong substrates for the major RND- and MFS-type (except hydrocortisone) tripartite multidrug efflux systems, AcrAB-TolC and EmrAB-TolC respectively, even though such molecules fail to demonstrate antimicrobial properties in this bacterial background (Elkins and Mullis [2006] J. Bacteriol. 188:1191-1195). Although bile acids are subject to efflux, they are also known to directly interact with intracellular global regulators such as MarR (Prouty et al. [2004] Microbiol. 150:775-783) and Rob (Rosenberg et al., [2003] Mol. Microbiol. 48:1609-1619) consequently altering antimicrobial and bile resistance profiles. In our present study, whole-genome DNA microarrays of E. coli were used to determine what general effect steroids, both bile acid and hormones, may have on the transcriptome in relation to the human commensal environment. Keywords: Comparative Chemical Class Treatment
2008-03-14 | GSE10811 | GEO
Project description:Even though cutaneous atrophy is the major adverse effect of topical glucocorticoids, its molecular mechanisms are poorly understood. We found that glucocorticoids strongly increased the expression of REDD1 (regulated in development and DNA damage response 1), a stress-inducible inhibitor of mTOR, in mouse and human epidermis. We found that REDD1 knockout animals are partially resistant to glucocorticoid-induced epidermal and subcutaneous adipose atrophy which correlated with the protection of CD34+ follicular epithelial stem cells as well as p63+ keratinocyte progenitors in REDD1 knockout epidermis during chronic steroid treatment. At the same time, REDD1 knockout did not affect anti- inflammatory effect of glucocorticoids, as evaluated by ear edema test. Expression profiling revealed that ~ 50% of the glucocorticoid receptor (GR) target genes were not activated in epidermis of REDD1 knockouts, however, the negative effect of glucocorticoids on gene expression was similar to that in w.t. animals. Overall, our findings reveal a novel pathway in GR activation by its target gene/protein REDD1; and indicate an important role of REDD1 in glucocorticoid-induced skin atrophy, and maintenance of the epidermis and subcutaneous adipose. In addition, our findings form the foundation for the development of safer topical glucocorticoid treatment regimens by combining this therapy with REDD1 inhibitors. Seven wk old B6D2 females in the telogen stage of the hair cycle were shaved, and treated 3 days later. Glucocorticoid FA was applied topically (2 ug/animal) in 200 ul acetone to the back skin once or up to four applications every third day as described previously (Chebotaev et al., 2007b). Control animals were treated with acetone only. Skin was harvested 24 h after last FA application or 4-8 h after single FA application as indicated in Figure legends. To evaluate the anti-inflammatory effect of glucocorticoid FA in REDD1 KO and w.t. B6x129 mice, we used ear edema test (Schoepe et al., 2010; Schäcke et al., 2004; Park et al., 2006). Seven wk old female animals were pretreated with FA or vehicle applied to the back of the ear lobe one h before application of nonspecific contact irritant croton oil . Mice were sacrificed and ears were harvested nine hours after CO application, the time point at which we observed maximum ear edema in F1 C57Bl x 129 animals (data not shown). Four mm ear punch biopsies were immediately weighted to assess ear edema. Animals were injected i.p. with bromodeoxyuridine 1 hr before skin was harvested. Total RNA from murine epidermis and whole human skin was isolated with RiboPure kit (Ambion). Total RNA from murine s.c. adipose was isolated with RNeasy Lipid Tissue Kit (Qiagen). The RNA samples were treated with TURBOTM DNase (Ambion). Purity of RNA samples isolated from epidermis and s.c. fat was confirmed by the expression of adipose and keratinocyte cell markers.
2014-08-01 | E-GEOD-59151 | biostudies-arrayexpress
Project description:ObjectivesCurrent guidelines recommend topical steroids as first-line treatment for patients with eosinophilic esophagitis (EoE). However, the evidence for this approach has been inconsistent in earlier reports. This meta-analysis aimed to clarify the efficacy of topical steroid treatment in active EoE using updated evidence.MethodsCENTRAL, MEDLINE and EMBASE databases were searched for randomized controlled trials (RCTs) published up to May 2014 that compared topical steroids with control treatments for active EoE. Study bias was assessed using the Cochrane Collaboration Tool, and outcomes were pooled using random effects models. The primary outcome was the mean change in eosinophil counts. Secondary outcomes were symptom responses and adverse events.ResultsIn total, seven RCTs (226 patients) were included. Topical steroids were associated with a significant reduction in esophageal mucosal eosinophil counts compared with control therapy although substantial heterogeneity between studies was observed (weighted mean difference (WMD) -27.2, 95% confidence interval (CI) -45.3 to -9.1, I(2)=56.2%). Subgroup analysis indicated the reduction in eosinophil counts was only present in studies where a proton pump inhibitor (PPI) trial was used to exclude other diagnoses (WMD -46.3, 95% CI -61.3 to -31.4, I(2)=0.0%). Subdivision of studies on the use of a PPI trial also accounted for the majority of heterogeneity among RCTs. No clear trends in symptom resolution were observed. Eleven out of 127 patients who received topical steroids developed asymptomatic esophageal candidiasis.ConclusionsThese data provide updated high-quality evidence that support current guidelines for first-line EoE treatment with topical steroids after an initial PPI trial to exclude non-EoE pathologies (PROSPERO ID: CRD42014008828).
| S-EPMC4816205 | biostudies-literature
Project description:ObjectiveTo explore the phenomenon of topical corticosteroid (TCS) phobia and comprehensively understand the factors driving TCS concerns, in particular pertaining to steroid addiction and withdrawal.DesignProspective qualitative study using 1:1 in-depth semistructured interviews and analysed using grounded theory.ParticipantsPatients with a prior experience of TCS use for a dermatological condition recruited from a tertiary academic dermatology clinic, or through word of mouth and online social media platforms.Results26 participants encompassing those with positive, neutral and negative opinions towards TCS were interviewed. 13 reported having topical steroid addiction or withdrawal. The drivers of TCS concerns could be categorised into seven themes: attitudes towards TCS (comprising beliefs and knowledge about TCS), availability of alternatives, treatment inconvenience, personality, patient's ongoing evaluation of clinical response to TCS, doctor-patient relationship and healthcare-seeking behaviour. Of mention, patients placed high value and trust on their own experiences with TCS, such as their perceived experienced side effects. The doctor who failed to acknowledge the patient's opinions and instead emphasised the safety of TCS was often viewed as dismissive, resulting in a deteriorating patient-doctor relationship.ConclusionProvision of knowledge and education is important but may be ineffective if the basis for TCS concern regarding safety is reasonable, or when the patient has a firmly established belief supporting his/her concern. In such instances, failure to acknowledge and respect the patient's decision to avoid TCS could worsen the doctor-patient relationship.
| S-EPMC8928312 | biostudies-literature
Project description:BackgroundVaccination is a key intervention to prevent COVID-19. Many vaccines are administered globally, yet there is not much evidence regarding their safety and adverse effects. Iran also faces this challenge, especially as data regarding the Sputnik V vaccine is sparse. Therefore, the aim of this study is to determine the adverse effects of the most commonly used vaccines in Iran.MethodsUsing a retrospective cohort study design, 6600 subjects aged 18 years or older who had received two doses of any of the three COVID-19 vaccines (Sinopharm, AstraZeneca, and Sputnik V) were selected using a random sampling method between March and August 2021. Subjects were asked about any adverse effects of the vaccines by trained interviewers via telephone interview. Vaccine-related adverse effects in individuals during the first 72 h and subsequently following both doses of the vaccines were determined. The demographic variables, type of administered vaccine, adverse effects, and history of the previous infection with COVID-19 were collected. Descriptive statistics (mean, standard deviation) and analytical statistics (Chi-squared and Wilcoxon tests) were performed at a 95% significance level using STATA software version 15 (STATA Corp, College Station, TX, USA).ResultsFrom 6600 participants, 4775 responded (response rate = 72.3%). Of the participants, 1460 (30.6%) received the AstraZeneca vaccine, 1564 (32.8%) received the Sinopharm vaccine and 1751 (36.7%) received the Sputnik V vaccine. 2653 participants (55.56%) reported adverse effects after the first dose and 1704 (35.7%) after the second dose. Sputnik V caused the most adverse effects with 1449 (82.7%) vaccine recipients reporting symptoms after the first or second dose, compared with 1030 (70.5%) for AstraZeneca and only 585 (37.4%) for the Sinopharm vaccine. The most common adverse effects after the first dose were fatigue (28.37%), chill/fever (26.86%), and skeletal pain (22.38%). These three adverse effects were the same for the second dose, although their prevalence was lower.ConclusionsIn this study, we demonstrate that the Sputnik V vaccine has the highest rate of adverse effects, followed by the AstraZeneca and Sinopharm vaccines. COVID-19 vaccines used in Iran are safe and there were no reports of serious adverse effects.
| S-EPMC9116064 | biostudies-literature
Project description:Cutaneous atrophy is the major adverse effect of topical glucocorticoids; however, its molecular mechanisms are poorly understood. Here, we identify stress-inducible mTOR inhibitor REDD1 (regulated in development and DNA damage response 1) as a major molecular target of glucocorticoids, which mediates cutaneous atrophy. In REDD1 knockout (KO) mice, all skin compartments (epidermis, dermis, subcutaneous fat), epidermal stem, and progenitor cells were protected from atrophic effects of glucocorticoids. Moreover, REDD1 knockdown resulted in similar consequences in organotypic raft cultures of primary human keratinocytes. Expression profiling revealed that gene activation by glucocorticoids was strongly altered in REDD1 KO epidermis. In contrast, the down-regulation of genes involved in anti-inflammatory glucocorticoid response was strikingly similar in wild-type and REDD1 KO mice. Integrative bioinformatics analysis of our and published gene array data revealed similar changes of gene expression in epidermis and in muscle undergoing glucocorticoid-dependent and glucocorticoid-independent atrophy. Importantly, the lack of REDD1 did not diminish the anti-inflammatory effects of glucocorticoids in preclinical model. Our findings suggest that combining steroids with REDD1 inhibitors may yield a novel, safer glucocorticoid-based therapies.
| S-EPMC4309667 | biostudies-literature
Project description:Background & aimsFew factors have been identified that can be used to predict response of patients with eosinophilic esophagitis (EoE) to topical steroid treatment. We aimed to determine whether baseline clinical, endoscopic, histologic, and molecular features of EoE can be used to predict histologic response.MethodsWe collected data from 97 patients with EoE, from 2009 through 2015, treated with a topical steroid for 8 weeks; 59 patients had a histologic response to treatment. Baseline clinicopathologic features and gene expression patterns were compared between patients with a histologic response to treatment (<15 eos/hpf) and non-responders (≥15 eos/hpf). We performed sensitivity analyses for alternative histologic response definitions. Multivariate logistic regression was performed to identify predictive factors associated with response to therapy, which were assessed with area under the receiver operator characteristic (AUROC) curves.ResultsBaseline dilation was the only independent predictor of non-response (odds ratio [OR], 0.30; 95% CI, 0.10-0.89). When an alternate response (<1 eos/hpf) and non-response (<50% decrease in baseline eos/hpf) definition was used, independent predictors of response status were age (OR, 1.08; 95% CI, 1.02-1.14), food allergies (OR, 12.95; 95% CI, 2.20-76.15), baseline dilation (OR, 0.17; 95% CI, 0.03-0.88), edema or decreased vascularity (OR, 0.20; 95% CI, 0.04-1.03), and hiatal hernia (OR, 0.07; 95% CI, 0.01-0.66). Using these 5 factors, we developed a predictive model that discriminated complete responders from non-responders with an AUROC of 0.88. Baseline gene expression patterns were not associated with treatment response and did not change with different histologic response thresholds.ConclusionsIn an analysis of 97 patients with EoE, we found dilation to be the only baseline factor associated with non-response to steroid treatment (<15 eos/hpf). However, a model comprising 5 clinical, endoscopic, and histologic factors identified patients with a complete response (<1 eos/hpf). A baseline gene expression panel was not predictive of treatment response at any threshold.
| S-EPMC6409124 | biostudies-literature
Project description:Radiogenomics is the study of genomic factors that are associated with response to radiation therapy. In recent years, progress has been made toward identifying genetic risk factors linked with late radiation-induced adverse effects. These advances have been underpinned by the establishment of an international Radiogenomics Consortium with collaborative studies that expand cohort sizes to increase statistical power and efforts to improve methodologic approaches for radiogenomic research. Published studies have predominantly reported the results of research involving patients treated with photons using external beam radiation therapy. These studies demonstrate our ability to pool international cohorts to identify common single nucleotide polymorphisms associated with risk for developing normal tissue toxicities. Progress has also been achieved toward the discovery of genetic variants associated with radiation therapy-related subsequent malignancies. With the increasing use of charged particle therapy (CPT), there is a need to establish cohorts for patients treated with these advanced technology forms of radiation therapy and to create biorepositories with linked clinical data. While some genetic variants are likely to impact toxicity and second malignancy risks for both photons and charged particles, it is plausible that others may be specific to the radiation modality due to differences in their biological effects, including the complexity of DNA damage produced. In recognition that the formation of patient cohorts treated with CPT for radiogenomic studies is a high priority, efforts are underway to establish collaborations involving institutions treating cancer patients with protons and/or carbon ions as well as consortia, including the Proton Collaborative Group, the Particle Therapy Cooperative Group, and the Pediatric Proton Consortium Registry. These important radiogenomic CPT initiatives need to be expanded internationally to build on experience gained from the Radiogenomics Consortium and epidemiologists investigating normal tissue toxicities and second cancer risk.
| S-EPMC6261418 | biostudies-literature