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Clinical and Experimental Medicine Nov 2023Metabolic reprogramming in breast cancer involves changes in steroid hormone synthesis and metabolism. Alterations in estrogen levels in both breast tissue and blood may...
Metabolic reprogramming in breast cancer involves changes in steroid hormone synthesis and metabolism. Alterations in estrogen levels in both breast tissue and blood may influence carcinogenesis, breast cancer growth, and response to therapy. Our aim was to examine whether serum steroid hormone concentrations could predict the risk of recurrence and treatment-related fatigue in patients with breast cancer. This study included 66 postmenopausal patients with estrogen receptor-positive breast cancer who underwent surgery, radiotherapy, and adjuvant endocrine treatment. Serum samples were collected at six different time points [before the start of radiotherapy (as baseline), immediately after radiotherapy, and then 3, 6, 12 months, and 7-12 years after radiotherapy]. Serum concentrations of eight steroid hormones (cortisol, cortisone, 17α-hydroxyprogesterone, 17β-estradiol, estrone, androstenedione, testosterone, and progesterone) were measured using a liquid chromatography-tandem mass spectrometry-based method. Breast cancer recurrence was defined as clinically proven relapse/metastatic breast cancer or breast cancer-related death. Fatigue was assessed with the QLQ-C30 questionnaire. Serum steroid hormone concentrations measured before and immediately after radiotherapy differed between relapse and relapse-free patients [(accuracy 68.1%, p = 0.02, and 63.2%, p = 0.03, respectively, partial least squares discriminant analysis (PLS-DA)]. Baseline cortisol levels were lower in patients who relapsed than in those who did not (p < 0.05). The Kaplan-Meier analysis showed that patients with high baseline concentrations of cortisol (≥ median) had a significantly lower risk of breast cancer recurrence than patients with low cortisol levels (
Topics: Humans; Female; Breast Neoplasms; Cortisone; Hydrocortisone; Neoplasm Recurrence, Local; Steroids; Recurrence
PubMed: 37395895
DOI: 10.1007/s10238-023-01109-x -
Psychopharmacology Sep 2014The neurosteroid pregnenolone sulfate (PregS) acts as a cognitive enhancer and modulator of neurotransmission, yet aligning its pharmacological and physiological effects... (Review)
Review
RATIONALE
The neurosteroid pregnenolone sulfate (PregS) acts as a cognitive enhancer and modulator of neurotransmission, yet aligning its pharmacological and physiological effects with reliable measurements of endogenous local concentrations and pharmacological and therapeutic targets has remained elusive for over 20 years.
OBJECTIVES
New basic and clinical research concerning neurosteroid modulation of the central nervous system (CNS) function has emerged over the past 5 years, including important data involving pregnenolone and various neurosteroid precursors of PregS that point to a need for a critical status update.
RESULTS
Highly specific actions of PregS affecting excitatory N-methyl-D-aspartate receptor (NMDAR)-mediated synaptic transmission and the pharmacological effects of PregS on various receptors and ion channels are discussed. The discovery of a high potency (nanomolar) signal transduction pathway for PregS-induced NMDAR trafficking to the cell surface via a Ca(2+)- and G protein-coupled receptor (GPCR)-dependent mechanism and a potent (EC50 ~ 2 pM) direct enhancement of intracellular Ca(2+) levels is discussed in terms of its agonist effects on long-term potentiation (LTP) and memory. Lastly, preclinical and clinical studies assessing the promnestic effects of PregS and pregnenolone toward cognitive dysfunction in schizophrenia, and altered serum levels in epilepsy and alcohol dependence, are reviewed.
CONCLUSIONS
PregS is present in human and rodent brain at physiologically relevant concentrations and meets most of the criteria for an endogenous neurotransmitter/neuromodulator. PregS likely plays a significant role in modulation of glutamatergic excitatory synaptic transmission underlying learning and memory, yet the molecular target(s) for its action awaits identification.
Topics: Animals; Humans; Neuronal Plasticity; Neurotransmitter Agents; Nootropic Agents; Pregnanolone; Synapses
PubMed: 24997854
DOI: 10.1007/s00213-014-3643-x -
Molecules (Basel, Switzerland) Aug 2022For our interest in the potential biologically active and structurally unique steroidal glycosides, continued phytochemical investigation of was carried out; twelve new...
For our interest in the potential biologically active and structurally unique steroidal glycosides, continued phytochemical investigation of was carried out; twelve new seco-pregnane glycosides, cynataihosides I-L (-), M-T (-), and two known glycosides, glaucoside A () and atratcynoside F (), were isolated from the 95% ethanol extract of . Two new aglycones were found among compounds , , , and . The structures of the glycosides were elucidated based on 1D and 2D NMR spectroscopic data, HR-ESI-MS analysis, and chemical evidence. The cytotoxicity of compounds against three human tumor cell lines (HL60, THP-1, and PC-3) were evaluated by MTT assay. Compound displayed significant cytotoxicity against THP-1 and PC-3 cell line with IC values of 5.08 and 22.75 μm, respectively. Compounds and exhibited moderate and selective cytotoxicity on HL60 and THP-1 with IC values of 17.78 and 16.02 μm, respectively.
Topics: Cynanchum; Glycosides; Humans; Molecular Structure; Plant Roots; Pregnanes
PubMed: 36080268
DOI: 10.3390/molecules27175500 -
The Cochrane Database of Systematic... Sep 2014Until recently, phimosis has been treated surgically by circumcision or prepuceplasty; however, recent reports of non-invasive treatment using topical corticosteroids... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Until recently, phimosis has been treated surgically by circumcision or prepuceplasty; however, recent reports of non-invasive treatment using topical corticosteroids applied for four to eight weeks have been favourable. The efficacy and safety of topical corticosteroids for treating phimosis in boys has not been previously systematically reviewed.
OBJECTIVES
We aimed to 1) compare the effectiveness of the use of topical corticosteroid ointment applied to the distal stenotic portion of the prepuce in the resolution of phimosis in boys compared with the use of placebo or no treatment, and 2) determine the rate of partial resolution (improvement) of phimosis, rate of re-stenosis after initial resolution or improvement of phimosis, and the rate of adverse events of topical corticosteroid treatment in boys with phimosis.
SEARCH METHODS
We searched the Cochrane Renal Group's Specialised Register through contact with the Trials' Search Co-ordinator using search terms relevant to this review. Date of last search: 16 June 2014.
SELECTION CRITERIA
We included all randomised controlled trials (RCTs) that compared use of any topical corticosteroid ointment with placebo ointment or no treatment for boys with phimosis.
DATA COLLECTION AND ANALYSIS
Two authors independently assessed titles, abstracts and the full-text of eligible studies, extracted data relating to the review's primary and secondary outcomes, and assessed studies' risk of bias. Statistical analyses were performed using the random-effects model and results were expressed as risk ratios (RR) for dichotomous outcomes with 95% confidence intervals (CI). We contacted authors of primary articles asking for details of study design and specific outcome data.
MAIN RESULTS
We included 12 studies that enrolled 1395 boys in this review. We found that both types of corticosteroids investigated and treatment duration varied among studies.Compared with placebo, corticosteroids significantly increased complete or partial clinical resolution of phimosis (12 studies, 1395 participants: RR 2.45, 95% CI 1.84 to 3.26). Our analysis of studies that compared different types of corticosteroids found that these therapies also significantly increased complete clinical resolution of phimosis (8 studies, 858 participants: RR 3.42, 95% CI 2.08 to 5.62). Although nine studies (978 participants) reported that assessment of adverse effects were planned in the study design, these outcomes were not reported.Overall, we found that inadequate reporting made assessing risk of bias challenging in many of the included studies.Selection bias, performance and detection bias was unclear in the majority of the included studies: two studies had adequate sequence generation, none reported allocation concealment; two studies had adequate blinding of participants and personnel and one had high risk of bias; one study blinded outcome assessors. Attrition bias was low in 8/12 studies and reporting bias was unclear in 11 studies and high in one study.
AUTHORS' CONCLUSIONS
Topical corticosteroids offer an effective alternative for treating phimosis in boys. Although sub optimal reporting among the included studies meant that the size of the effect remains uncertain, corticosteroids appear to be a safe, less invasive first-line treatment option before undertaking surgery to correct phimosis in boys.
Topics: Administration, Topical; Adrenal Cortex Hormones; Beclomethasone; Betamethasone; Clobetasol; Glucocorticoids; Humans; Hydrocortisone; Male; Mometasone Furoate; Ointments; Phimosis; Pregnadienediols; Randomized Controlled Trials as Topic; Triamcinolone
PubMed: 25180668
DOI: 10.1002/14651858.CD008973.pub2 -
The European Respiratory Journal Sep 2017
Topics: Acute Disease; Administration, Inhalation; Altitude Sickness; Asthma; Bronchodilator Agents; Budesonide; Dexamethasone; Humans
PubMed: 28890440
DOI: 10.1183/13993003.01355-2017 -
International Journal of Environmental... Mar 2021Engaging with nature can profoundly impact psychological and physiological health of persons across the lifespan. Greenspace interventions (GSI) encompass a broad range... (Review)
Review
BACKGROUND
Engaging with nature can profoundly impact psychological and physiological health of persons across the lifespan. Greenspace interventions (GSI) encompass a broad range of strategic, nature-based activities for overall health and wellbeing. Within the past 20 years there has been a growing interest in the access to and management of greenspace to mediate the deleterious impact of acute and chronic stress, particularly, physiologic biomarkers of stress such as cortisol.
OBJECTIVE
This review aims to describe the impact of greenspace interventions on cortisol, to present the current state of the science on GSIs as they impact cortisol, and to uncover any limitations of current research strategies to best inform future research.
METHODS
A scoping methodology was conducted to systematically study this emerging field and inform future research by mapping the literature based on the GSI category, interventional design, cortisol metrics, and subsequent analysis of cortisol.
CONCLUSION
Considerable heterogeneity in research design, aim(s), interventional strategy, and cortisol metrics were identified from a total of 18 studies on GSIs and cortisol outcomes. While studies demonstrated a potential for the positive association between GSIs and stress relief, more rigorous research is needed to represent GSIs as an intervention to mitigate risks of stress.
Topics: Biomarkers; Hydrocortisone; Parks, Recreational
PubMed: 33801917
DOI: 10.3390/ijerph18062802 -
Indian Journal of Ophthalmology Oct 2023Refractory periorbital dermatitis has a chronic course with exacerbations leading to discomfort and cosmetic issues, yet characterization of treatment options is limited.
PURPOSE
Refractory periorbital dermatitis has a chronic course with exacerbations leading to discomfort and cosmetic issues, yet characterization of treatment options is limited.
AIMS
The objective was to present comprehensive demographic data and medical management of a series of patients with refractory periorbital dermatitis.
SETTINGS AND DESIGN
Retrospective review identified patients treated at a single institution from January 2010 to August 2020.
METHODS
Descriptive analyses were performed. Demographic data and treatment history were reviewed and data including medication, use, date of use and discontinued use, reason for discontinuation (if applicable), refractory status, formulation, concentration, and dose frequency were extracted.
STATISTICAL ANALYSIS USED
Descriptive analyses.
RESULTS
Forty-five patients were included. The average age at first diagnosis was 60.3 years (sd 14.9). 82.2% were women and 84.4% identified as Caucasian. Triamcinolone cream was most frequently used followed by tobramycin-dexamethasone, tacrolimus, and neomycin-polymyxin-dexamethasone. Less than 30% of patients on triamcinolone were refractory. 13.3% of patients used topical hydrocortisone, with over 80% of these patients experiencing refractory episodes of persistent irritation and erythema. Most patients were refractory during initial use or the first recurrence of periorbital dermatitis flare.
CONCLUSIONS
By better characterizing the diverse treatment regimens in a unique subset of refractory patients, we hope to better inform potential courses of medical management for periorbital dermatitis.
Topics: Humans; Female; Middle Aged; Male; Tacrolimus; Cosmetics; Triamcinolone; Dexamethasone; Dermatitis; Administration, Topical
PubMed: 37787240
DOI: 10.4103/IJO.IJO_2944_22 -
Drug Design, Development and Therapy 2021This paper reviews the current literature available for the efficacy and safety of allopregnanolone agonists and discusses considerations for their place in therapy. (Review)
Review
OBJECTIVE
This paper reviews the current literature available for the efficacy and safety of allopregnanolone agonists and discusses considerations for their place in therapy.
LITERATURE SEARCH
A literature search was conducted utilizing PubMed, clinicaltrials.gov, and the manufacturer's website.
DATA SYNTHESIS
One phase II trial and two phase III trials evaluating the efficacy and safety of brexanolone were identified. Brexanolone demonstrated efficacy through significantly reduced Hamilton Depression Rating Scale (HAM-D) scores compared to placebo in the treatment of postpartum depression (PPD). Noted adverse effects were somnolence and dizziness, excessive sedation, and loss of consciousness. One published phase II study and the interim results of two phase III trials and one phase II trial on zuranolone were included in this review. Zuranolone, an oral allopregnanolone agonist, is given as a single, 14-day course. A significant reduction in HAM-D scores was demonstrated in patients with major depressive disorder (MDD) at 15 and 28 days compared to placebo. Interim results for zuranolone in PPD and bipolar disorder (BPD) show promising reductions in HAM-D scores. Adverse effects included sedation, dizziness, and headache.
PLACE IN THERAPY
Allopregnanolone agonists seem to have a role in PPD when weighing the quick onset of action and potential risks of untreated PPD. The class of medications is limited by the single course for this indication and may fit as a bridge to maintenance therapy with selective serotonin reuptake inhibitors (SSRIs). Brexanolone, specifically, is hindered by the long infusion time, hospitalization associated with administration, and risk evaluation and mitigation strategy program. Zuranolone may also have a role in MDD or BPD, but more data are needed.
CONCLUSION
Allopregnanolone agonists present a novel mechanism of action in the treatment of depressive disorders. Clinical trials and interim results support significant reductions in depression scores for brexanolone in PPD, and for zuranolone in PPD, MDD, and BPD.
Topics: Antidepressive Agents; Bipolar Disorder; Depression, Postpartum; Depressive Disorder; Drug Combinations; Female; Humans; Pregnancy; Pregnanes; Pregnanolone; Psychiatric Status Rating Scales; Pyrazoles; beta-Cyclodextrins
PubMed: 34267503
DOI: 10.2147/DDDT.S240856 -
BMC Infectious Diseases May 2023The preferred agent of glucocorticoids in the treatment of patients with severe COVID-19 is still controversial. This study aimed to compare the efficacy and safety of... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The preferred agent of glucocorticoids in the treatment of patients with severe COVID-19 is still controversial. This study aimed to compare the efficacy and safety of methylprednisolone and dexamethasone in the treatment of patients with severe COVID-19.
METHODS
By searching the electronic literature database including PubMed, Cochrane Central Register of Controlled Trials, and Web of Science, the clinical studies comparing methylprednisolone and dexamethasone in the treatment of severe COVID-19 were selected according to the inclusion criteria and exclusion criteria. Relevant data were extracted and literature quality was assessed. The primary outcome was short-term mortality. The secondary outcomes were the rates of ICU admission and mechanical ventilation, PaO/FiO ratio, plasma levels of C-reactive protein (CRP), ferritin, and neutrophil/lymphocyte ratio, hospital stay, and the incidence of severe adverse events. Statistical pooling applied the fixed or random effects model and reported as risk ratio (RR) or mean difference (MD) with the corresponding 95% confidence interval (CI). Meta-analysis was performed using Review Manager 5.1.0.
RESULTS
Twelve clinical studies were eligible, including three randomized controlled trials (RCTs) and nine non-RCTs. A total of 2506 patients with COVID-19 were analyzed, of which 1242 (49.6%) received methylprednisolone and 1264 (50.4%) received dexamethasone treatment. In general, the heterogeneity across studies was significant, and the equivalent doses of methylprednisolone were higher than that of dexamethasone. Our meta-analysis showed that methylprednisolone treatment in severe COVID-19 patients was related to significantly reduced plasma ferritin and neutrophil/lymphocyte ratio compared with dexamethasone, and that no significant difference in other clinical outcomes between the two groups was found. However, subgroup analyses of RCTs demonstrated that methylprednisolone treatment was associated with reduced short-term mortality, and decreased CRP level compared with dexamethasone. Moreover, subgroup analyses observed that severe COVID-19 patients treated with a moderate dose (2 mg/kg/day) of methylprednisolone were related to a better prognosis than those treated with dexamethasone.
CONCLUSIONS
This study showed that compared with dexamethasone, methylprednisolone could reduce the systemic inflammatory response in severe COVID-19, and its effect was equivalent to that of dexamethasone on other clinical outcomes. It should be noted that the equivalent dose of methylprednisolone used was higher. Based on the evidence of subgroup analyses of RCTs, methylprednisolone, preferably at a moderate dose, has an advantage over dexamethasone in the treatment of patients with severe COVID-19.
Topics: Humans; Glucocorticoids; Methylprednisolone; COVID-19; COVID-19 Drug Treatment; Dexamethasone
PubMed: 37147596
DOI: 10.1186/s12879-023-08280-2 -
Oncotarget Jul 2023A practice-changing, randomized, controlled clinical study established that preoperative hydroxyprogesterone administration improves disease-free and overall survival in... (Randomized Controlled Trial)
Randomized Controlled Trial
A practice-changing, randomized, controlled clinical study established that preoperative hydroxyprogesterone administration improves disease-free and overall survival in patients with node-positive breast cancer. This research perspective summarizes evidences from our studies that preoperative hydroxyprogesterone administration may improve disease-free and overall survival in patients with node-positive breast cancer by modulating cellular stress response and negative regulation of inflammation. Non-coding RNAs, particularly , play a regulatory role in this process, along with the upregulation of the kinase gene and activation of the axis. Progesterone-induced modification of the progesterone receptor and estrogen receptor genomic binding pattern is also involved in orchestrating estrogen signaling in breast cancer, preventing cell migration and invasion, and improving patient outcomes. We also highlight the role of progesterone in endocrine therapy resistance, which could lead to novel treatment options for patients with hormone receptor-positive breast cancer and for those who develop resistance to traditional endocrine therapies.
Topics: Humans; Female; Breast Neoplasms; Progesterone; Receptors, Progesterone; Signal Transduction; Hydroxyprogesterones
PubMed: 37395734
DOI: 10.18632/oncotarget.28455