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Phytochemistry Sep 2023A phytochemical investigation of the dichloromethane soluble fraction of the ethanolic extract obtained from the roots of Marsdenia tenacissima led to the discovery of...
A phytochemical investigation of the dichloromethane soluble fraction of the ethanolic extract obtained from the roots of Marsdenia tenacissima led to the discovery of the sixteen undescribed pregnane C steroids (1-16) and isolation of eleven known C steroidal analogues (17-27). Their chemical structures were elucidated by one- and two-dimensional nuclear magnetic resonance spectroscopy and, high resolution-electrospray ionization mass spectrometry and their absolute configurations were determined using electronic circular dichroism or single-crystal X-ray diffraction. The in vitro anti-proliferative effects of 1-16 were evaluated against HepG2 (human hepatocellular cancer), A549 (lung cancer), and MCF-7 (human breast cancer) cell lines. Even though some of them showed moderate cytotoxic activities, marsectohexol derivative 12 exhibited significant cytotoxicity against A549 cells with an IC value of 5.2 μM.
Topics: Humans; Marsdenia; Steroids; Pregnanes; Plant Extracts; Antineoplastic Agents
PubMed: 37451564
DOI: 10.1016/j.phytochem.2023.113782 -
The American Journal of Sports Medicine Sep 2023Intra-articular corticosteroid or hyaluronic acid (HA) is commonly prescribed for frozen shoulder. However, few studies have investigated histological and molecular...
BACKGROUND
Intra-articular corticosteroid or hyaluronic acid (HA) is commonly prescribed for frozen shoulder. However, few studies have investigated histological and molecular changes after injection.
PURPOSE
To compare the effectiveness of intra-articular injections of triamcinolone and HA in a frozen shoulder rat model and verify a greater effect of triamcinolone in passive shoulder abduction compared with HA.
STUDY DESIGN
Controlled laboratory study.
METHODS
Twenty male Sprague-Dawley rats were randomly allocated into 4 groups (n = 5 in each): control group, which did not receive cast immobilization or injection, and 3 experimental groups, which received 3 weeks of unilateral shoulder immobilization followed by intra-articular injections (normal saline, triamcinolone, or HA) at the immobilized shoulder. Passive shoulder abduction angle, histological and immunohistochemical staining, and Western blotting results were assessed 2 weeks after injection. The intensity and extent of staining were converted to semiquantitative scores for further analysis.
RESULTS
Shoulder abduction angles before sacrifice were 153.0°± 2.7° (control group), 107.0°± 5.7° (saline group), 139.0°± 9.6° (triamcinoline group), and 110.0°± 10.6° (HA group), showing significant differences between control and saline groups, control and HA groups, saline and triamcinoline groups, and triamcinoline and HA groups ( < .001) but not between control and triamcinoline groups ( = .053). Histologic evaluation revealed an increase in synovial folds and thickening of the capsular membrane in the saline and HA groups; this change was not evident in the triamcinolone group. A comparison of semiquantitative scores revealed greater expression levels of proteins involved in fibrosis and angiogenesis in the saline and HA groups compared with the control and triamcinolone groups. In Western blotting, the expression of inflammatory cytokines and the receptor for advanced glycation end products was significantly lower in the triamcinolone and HA groups than in the saline group.
CONCLUSION
Triamcinolone injection was more effective than normal saline or HA injection in improving range of motion and reversing fibrotic and angiogenic features of frozen shoulder. Both triamcinolone and HA injections elicited anti-inflammatory effects.
CLINICAL RELEVANCE
The antifibrotic and antiangiogenic properties of triamcinolone and the anti-inflammatory properties of both triamcinolone and HA should be considered when performing injections in clinical settings.
Topics: Male; Animals; Rats; Triamcinolone; Hyaluronic Acid; Saline Solution; Rats, Sprague-Dawley; Bursitis; Anti-Inflammatory Agents; Injections, Intra-Articular; Range of Motion, Articular; Treatment Outcome
PubMed: 37551671
DOI: 10.1177/03635465231188524 -
Endocrine Sep 2023The diagnosis and management of adrenocorticotropic hormone-independent Cushing's syndrome (AICS) with bilateral adrenal lesions remain challenging. Some studies have...
PURPOSE
The diagnosis and management of adrenocorticotropic hormone-independent Cushing's syndrome (AICS) with bilateral adrenal lesions remain challenging. Some studies have explored the value of adrenal vein sampling (AVS) in patients with AICS; however, more investigations are needed to assess its benefits for diagnosis and treatment planning in this population.
METHODS
Thirteen patients with clinical, biochemical and imaging evidence of AICS with bilateral adrenal lesions underwent AVS in our department from 2017-2022 were recruited. Only the data from nine patients for whom AVS succeeded were finally included in this study and further analyzed. Blood samples were successfully collected from both adrenal veins (AV) and inferior vena cava (IVC) in these nine patients, and the levels of plasma total cortisol (PTC) and plasma aldosterone concentrations (PAC) were measured. The ratio of the PAC of the AV to the IVC was calculated, and the PTC to PAC ratios were compared between AV. The surgical strategy was chosen according to the results of AVS. Postoperative histology and immunohistochemistry of the adrenal tissues were performed. The prognosis was evaluated based on the improvement of clinical symptoms and biochemical parameters (including PTC and ACTH measurements).
RESULTS
Patients with AICS were clinically diagnosed based on clinical signs, results of functional tests and the presence of bilateral adrenal lesions as observed on computed tomography imaging. An AV to IVC PAC ratio greater than 2 confirmed successful AVS. The PTC to PAC ratio (high side to low side) was greater than 2 in four patients, and less than 2 in five patients. The postoperative pathological results were consistent with clinical diagnosis and AVS. During the mean follow-up of 33 months, all nine patients achieved varying degrees of clinical improvement.
CONCLUSION
Our study showed that AVS helped to distinguish unilateral and bilateral lesions, identify the laterality of the autonomous hypercortisolism, and improve therapeutic strategy selection in patients with AICS and bilateral adrenal lesions.
Topics: Humans; Cushing Syndrome; Diagnosis, Differential; Hydrocortisone; Retrospective Studies; Adrenal Glands; Aldosterone; Adrenocorticotropic Hormone; Clinical Protocols; Hyperaldosteronism
PubMed: 37354283
DOI: 10.1007/s12020-023-03395-7 -
Journal of the Formosan Medical... Mar 2024Confirmatory tests for diagnosis of primary aldosteronism (PA) play an important role in sparing patients with a false-positive aldosterone-to-renin ratio (ARR)... (Review)
Review
Confirmatory tests for diagnosis of primary aldosteronism (PA) play an important role in sparing patients with a false-positive aldosterone-to-renin ratio (ARR) screening test from undergoing invasive subtyping procedures. We recommend that patients with a positive ARR test should undergo at least one confirmatory test to confirm or exclude the diagnosis of PA before directly proceeding to subtype studies, except for patients with significant PA phenotypes, including spontaneous hypokalemia, plasma aldosterone concentration >20 ng/dL plus plasma renin activity below a detectable level. Although a gold standard confirmatory test has not been identified, we recommend that saline infusion test and captopril challenge test, which were widely used in Taiwan. Patients with PA have been reported to have a higher prevalence of concurrent autonomous cortisol secretion (ACS). ACS is a biochemical condition of mild cortisol overproduction from adrenal lesions, but without the typical clinical features of overt Cushing's syndrome. Concurrent ACS may result in incorrect interpretation of adrenal venous sampling (AVS) and may lead to adrenal insufficiency after adrenalectomy. We recommend screening for ACS in patients with PA scheduled for AVS examinations as well as for adrenalectomy. We recommend the 1-mg overnight dexamethasone suppression test as screening method to detect ACS.
Topics: Humans; Aldosterone; Hyperaldosteronism; Renin; Hydrocortisone; Captopril; Hypertension
PubMed: 37173227
DOI: 10.1016/j.jfma.2023.04.022 -
Current Problems in Cardiology Jul 2024Several randomized controlled trials (RCTs) have examined mineralocorticoid receptor antagonists (MRAs) in heart failure (HF) with reduced ejection fraction (HFrEF).... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Several randomized controlled trials (RCTs) have examined mineralocorticoid receptor antagonists (MRAs) in heart failure (HF) with reduced ejection fraction (HFrEF). This systematic review and network meta-analysis (NMA) evaluated the comparative efficacy and safety of MRAs in HFrEF.
MATERIALS AND METHODS
MEDLINE(Pubmed), Scopus, Cochrane and ClinicalTrials.gov were searched until April 8, 2024 for RCTs examining the efficacy and/or safety of MRAs in HFrEF. Double-independent study selection, extraction and quality assessment were performed. Random-effects frequentist NMA models were used. Evidence certainty was assessed via Grading of Recommendations Assessment, Development and Evaluation (GRADE).
RESULTS
Totally, 32 RCTs (15685 patients) were analyzed. Eplerenone ranked above spironolactone in all-cause mortality (hazard ratio {HR}=0.78, 95% confidence interval {CI} [0.66,0.91], GRADE:"Moderate"), cardiovascular death (HR=0.74, 95%CI [0.53, 1.04], GRADE:"Low") and in all safety outcomes. Spironolactone was superior to eplerenone in the composite of cardiovascular death or hospitalization (HR=0.67, 95%CI [0.50,0.89], GRADE:"Moderate"), HF hospitalization (HR=0.61, 95%CI [0.43,0.86], GRADE:"Moderate"), all-cause hospitalization (HR=0.51, 95%CI [0.26,0.98], GRADE:"Moderate") and cardiovascular hospitalization (HR=0.56, 95%CI [0.37,0.84], GRADE:"Moderate"). Canrenone ranked first in all-cause mortality, the composite outcome and HF hospitalization. Finerenone ranked first in hyperkalemia (risk ratio [RR]=1.56, 95%CI [0.89,2.74], GRADE:"Moderate"), renal injury (RR=0.56, 95%CI [0.24,1.29]), any adverse event (RR=0.84, 95%CI [0.75,0.94], GRADE:"Moderate"), treatment discontinuation (RR=0.89, 95%CI [0.64,1.23]) and hypotension (RR=1.06, 95%CI [0.12,9.41]).
CONCLUSIONS
MRAs are effective in HFrEF with certain safety disparities. Spironolactone and eplerenone exhibited similar efficacy, however, eplerenone demonstrated superior safety. Finerenone was the safest MRA, while canrenone exhibited considerable efficacy, nonetheless, evidence for these MRAs were scarce.
Topics: Mineralocorticoid Receptor Antagonists; Humans; Heart Failure; Stroke Volume; Randomized Controlled Trials as Topic; Network Meta-Analysis; Spironolactone; Eplerenone; Treatment Outcome
PubMed: 38692445
DOI: 10.1016/j.cpcardiol.2024.102615 -
Environmental Pollution (Barking, Essex... Aug 2023The widespread use of phthalates (PAEs) has drawn increasing attention due to their endocrine disruption and reproductive toxicity, while the steroid metabolome is...
The widespread use of phthalates (PAEs) has drawn increasing attention due to their endocrine disruption and reproductive toxicity, while the steroid metabolome is essential for follicular development. However, the mechanism by which PAE exposure affects ovarian reserve through the steroid metabolome remains unclear. This study recruited 264 childbearing-age women in Tianjin (China) from April 2019 to August 2020 in a cross-sectional design. Target metabolome analysis of 16 steroids was performed in follicular fluid (FF) to compare diminished ovarian reserve (DOR) against normal ovarian reserve (NOR) women and differential steroids were identified using binary logistic analyses. Further analysis of eleven PAE metabolites (mPAEs) in FF was conducted, and the retrieved oocyte number (RON) representing ovarian reserve was counted. Multiple linear regression and quantile-based g-computation (qgcomp) models were used to associate individual mPAEs and mPAE mixture with the DOR-related differential steroids in FF. Mediation analysis was used to discuss the mediating effect of DOR-related steroids on the association between mPAEs and RON. Androstenedione (A4), corticosterone (CORT), cortisol (COR) and cortisone were significantly down-regulated in FF from women with DOR. Nine mPAEs with detection frequencies greater than 60% and median concentrations of 0.02-4.86 ng/mL were incorporated into statistical models. Negative associations with COR and CORT were found for mono-ethyl phthalate (mEP), mono-(2-ethyl-5-oxohexyl) phthalate (mEOHP), and mono-2-ethylhexyl phthalate (mEHP). A positive association with cortisone was found for mEOHP, mEHP, monobutyl phthalate (mBP), and mono (2-isobutyl) phthalate (miBP). The qgcomp and mediation analyses revealed that mEP and mEOHP not only significantly contributed to the decline of COR and CORT in the mixed exposure but also indirectly reduced RON through the mediating effects of COR and CORT. In conclusion, PAE exposure may decrease ovarian reserve by downregulating COR and CORT.
Topics: Female; Animals; Follicular Fluid; Ovarian Reserve; Cortisone; Cross-Sectional Studies; Phthalic Acids; Metabolome; Corticosterone; Environmental Exposure; Environmental Pollutants
PubMed: 37116568
DOI: 10.1016/j.envpol.2023.121730 -
International Journal of Gynecological... Mar 2024The impact of surgery on the surgeon's well-being encompasses both physical and psychological aspects. Physically, surgeons are at risk of work-related musculoskeletal... (Review)
Review
The impact of surgery on the surgeon's well-being encompasses both physical and psychological aspects. Physically, surgeons are at risk of work-related musculoskeletal symptoms due to the nature of their work, and this risk can be impacted by theater environment, equipment design, and workload. Many symptoms will be self-limiting, but work related musculoskeletal symptoms can lead to the development of an injury, which can have far reaching effects, including the need for medical or surgical treatment, time away from work, or a change in clinical duties. Additionally, surgery can place a significant cognitive workload on the lead operator and this can be exacerbated, or alleviated, by the surgical environment, experience of the assistance, surgical modality, and case complexity. Measuring and quantifying the impact of surgery on the surgeon is a challenging undertaking. Tools such as motion capture, physiological markers, including heart rate variability and salivary cortisol, and questionnaires can provide insights into understanding the overall impact of surgery on the surgeon. A holistic approach that incorporates injury prevention strategies, communication, and support, is vital in assessing and mitigating risk factors. Injury prevention assessment tools and interventions that can be used within the busy surgical environment are needed, alongside increased ergonomic awareness. Addressing the impact of surgery on the surgeon is a multifaceted challenge, and long term positive changes can only be sustained with the support of the whole surgical team and healthcare organizations by developing and maintaining a supportive working environment.
Topics: Humans; Physical Examination; Surgeons; Communication; Equipment Design; Hydrocortisone
PubMed: 38438178
DOI: 10.1136/ijgc-2023-004594 -
Frontiers in Endocrinology 2023Previous studies demonstrated the inhibitory effect of allopregnanolone (3α,5α-THP) on the activation of inflammatory toll-like receptor 4 (TLR4) signals in RAW264.7...
BACKGROUND
Previous studies demonstrated the inhibitory effect of allopregnanolone (3α,5α-THP) on the activation of inflammatory toll-like receptor 4 (TLR4) signals in RAW264.7 macrophages and the brains of selectively bred alcohol-preferring (P) rats. In the current study, we investigated the impact of 3α,5α-THP on the levels of IL-10 and activation of the TRIF-dependent endosomal TLR4 pathway.
METHODS
The amygdala and nucleus accumbens (NAc) of P rats, which exhibit innately activated TLR4 pathways as well as RAW264.7 cells, were used. Enzyme-linked immunosorbent assays (ELISA) and immunoblotting assays were used to ascertain the effects of 3α,5α-THP on the TRIF-dependent endosomal TLR4 pathway and endosomes were isolated to examine translocation of TLR4 and TRIF. Additionally, we investigated the effects of 3α,5α-THP and 3α,5α-THDOC (0.1, 0.3, and 1.0 µM) on the levels of IL-10 in RAW264.7 macrophages. Finally, we examined whether inhibiting TRIF (using TRIF siRNA) in RAW264.7 cells altered the levels of IL-10.
RESULTS
3α,5α-THP administration facilitated activation of the endosomal TRIF-dependent TLR4 pathway in males, but not female P rats. 3α,5α-THP increased IL-10 levels (+13.2 ± 6.5%) and BDNF levels (+21.1 ± 11.5%) in the male amygdala. These effects were associated with increases in pTRAM (+86.4 ± 28.4%), SP1 (+122.2 ± 74.9%), and PI(3)K-p110δ (+61.6 ± 21.6%), and a reduction of TIRAP (-13.7 ± 6.0%), indicating the activation of the endosomal TRIF-dependent TLR4 signaling pathway. Comparable effects were observed in NAc of these animals. Furthermore, 3α,5α-THP enhanced the accumulation of TLR4 (+43.9 ± 11.3%) and TRIF (+64.8 ± 32.8%) in endosomes, with no significant effect on TLR3 accumulation. Additionally, 3α,5α-THP facilitated the transition from early endosomes to late endosomes (increasing Rab7 levels: +35.8 ± 18.4%). In RAW264.7 cells, imiquimod (30 µg/mL) reduced IL-10 while 3α,5α-THP and 3α,5α-THDOC (0.1, 0.3, and 1.0 µM) restored IL-10 levels. To determine the role of the TRIF-dependent TLR4 signaling pathway in IL-10 production, the downregulation of TRIF (-62.9 ± 28.2%) in RAW264.7 cells led to a reduction in IL-10 levels (-42.3 ± 8.4%). TRIF (-62.9 ± 28.2%) in RAW264.7 cells led to a reduction in IL-10 levels (-42.3 ± 8.4%) and 3α,5α-THP (1.0 µM) no longer restored the reduced IL-10 levels.
CONCLUSION
The results demonstrate 3α,5α-THP enhancement of the endosomal TLR4-TRIF anti-inflammatory signals and elevations of IL-10 in male P rat brain that were not detected in female P rat brain. These effects hold significant implications for controlling inflammatory responses in both the brain and peripheral immune cells.
Topics: Animals; Female; Male; Rats; Adaptor Proteins, Vesicular Transport; Endosomes; Interleukin-10; Neurosteroids; Pregnanolone; Signal Transduction; Toll-Like Receptor 4; RAW 264.7 Cells; Mice
PubMed: 38179300
DOI: 10.3389/fendo.2023.1299420 -
BMC Infectious Diseases Dec 2023Currently, some meta-analyses on COVID-19 have suggested that glucocorticoids use can reduce the mortality rate of COVID-19 patients, utilization rate of invasive... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Currently, some meta-analyses on COVID-19 have suggested that glucocorticoids use can reduce the mortality rate of COVID-19 patients, utilization rate of invasive ventilation, and improve the prognosis of patients. However, optimal regimen and dosages of glucocorticoid remain unclear. Therefore, the purpose of this network meta-analysis is to analyze the efficacy and safety of glucocorticoids in treating COVID-19 at regimens.
METHODS
This meta-analysis retrieved randomized controlled trials from the earliest records to December 30, 2022, published in PubMed, Embase, Cochrane Library, CNKI Database and Wanfang Database, which compared glucocorticoids with placebos for their efficacy and safety in the treatment of COVID-19, Effects of different treatment regimens, types and dosages (high-dose methylprednisolone, very high-dose methylprednisolone, Pulse therapy methylprednisolone, medium-dose hydrocortisone, high-dose hydrocortisone, high-dose dexamethasone, very high-dose dexamethasone and placebo) on 28-day all-caused hospitalization mortality, hospitalization duration, mechanical ventilation requirement, ICU admission and safety outcome were compared.
RESULTS
In this network meta-analysis, a total of 10,544 patients from 19 randomized controlled trials were finally included, involving a total of 9 glucocorticoid treatment regimens of different types and dosages. According to the analysis results, the 28-day all-cause mortality rate was the lowest in the treatment with pulse therapy methylprednisolone (OR 0.08, 95% CI 0.02, 0.42), but the use of high-dose methylprednisolone (OR 0.85, 95% CI 0.59, 1.22), very high-dose dexamethasone (OR 0.95, 95% CI 0.67, 1.35), high-dose hydrocortisone (OR 0.64, 95% CI 0.34, 1.22), medium-dose hydrocortisone (OR 0.80, 95% CI 0.49, 1.31) showed no benefit in prolonging the 28-day survival of patient. Compared with placebo, the treatment with very high-dose methylprednisolone (MD = -3.09;95%CI: -4.10, -2.08) had the shortest length of hospital stay, while high-dose dexamethasone (MD = -1.55;95%CI: -3.13,0.03) and very high-dose dexamethasone (MD = -1.06;95%CI: -2.78,0.67) did not benefit patients in terms of length of stay.
CONCLUSIONS
Considering the available evidence, this network meta‑analysis suggests that the prognostic impact of glucocorticoids in patients with COVID-19 may depend on the regimens of glucocorticoids. It is suggested that pulse therapy methylprednisolone is associated with lower 28-day all-cause mortality, very high-dose methylprednisolone had the shortest length of hospital stay in patients with COVID-19.
TRIAL REGISTRATION
PROSPERO CRD42022350407 (22/08/2022).
Topics: Humans; Glucocorticoids; COVID-19; Hydrocortisone; Network Meta-Analysis; Methylprednisolone; Dexamethasone
PubMed: 38124031
DOI: 10.1186/s12879-023-08874-w -
BMC Veterinary Research Jul 2023Corticosteroids are widely used with low rates of reported side effects and a broad level of comfort in the hands of most veterinarians. With a low side effect reporting...
BACKGROUND
Corticosteroids are widely used with low rates of reported side effects and a broad level of comfort in the hands of most veterinarians. With a low side effect reporting level of < 5% and high level of comfort there may be complacency and underestimation of the impact side effects of corticosteroids may have on a pet and pet owner.
OBJECTIVE
The objective of this clinical study was to describe the experience and perception of an owner who administered anti-inflammatory doses of oral prednisolone and prednisone to their dog for up to 14 days. We hypothesized dogs receiving anti-inflammatory doses of prednisone and prednisolone would experience much greater rates of side effects by day 14 then reported in current literature.
ANIMALS
There were 45 dogs initially enrolled in the study.
RESULTS
At each study point, 31 owners provided results. On day 5, 74% (23/31) reported at least 1 change in their dog's behavior including polyuria, polydipsia, polyphagia, polypnea and/or increased vocalization, with 11 individuals (35%) reporting these changes greatly increased. On day 14, 90% of owners (28/31) reported at least 1 change in their dog's behavior including polyuria, polydipsia, polyphagia, and/or polypnea as the most common changes noted. Overall, 61% (19/31) of owners reported an increase in filling of the water bowl over baseline and one-third (11/31) of pet owners reported cleaning up urinary accidents for pets who had been continent prior to the start of the study. Pet owner steroid satisfaction remained high through day 14 at 4.5/5 (1 = very unsatisfied, 5 = very satisfied).
CONCLUSION
This study highlights the impact short term anti-inflammatory doses of prednisone or prednisolone have on dog behaviour and confirms our hypothesis that by day 14, 90% of dogs experienced one or more behaviour changes, with polyuria and polydipsia most commonly reported. Adverse events were noted regardless of starting dosage or regimen. Although most pet owners expressed satisfaction with steroid treatment due to its high efficacy, 70% would select a more costly treatment if that treatment had fewer side effects.
Topics: Dogs; Animals; Prednisolone; Prednisone; Polyuria; Drug-Related Side Effects and Adverse Reactions; Hyperphagia; Polydipsia; Perception; Dog Diseases
PubMed: 37488543
DOI: 10.1186/s12917-023-03644-x