Predictors of stricture after endoscopic submucosal dissection of the esophagus and steroids application

BACKGROUND Endoscopic submucosal dissection(ESD)is a reliable method to resect early esophageal cancer.Esophageal stricture is one of the major complications after ESD of the esophagus.Steroid prophylaxis for esophageal strictures,particularly local injection of triamcinolone acetonide(TA),is a relatively effective method to prevent esophageal strictures.However,even with steroid prophylaxis,stenosis still occurs in up to 45%of patients.Predicting the risk of stenosis formation after local TA injection would enable additional interventions in risky patients.AIM To identify the predictors of esophageal strictures after steroids application.METHODS Patients who underwent esophageal ESD and steroid prophylaxis and who were comprehensively assessed for lesion-and ESD-related factors at Southeast University Affiliated Zhongda Hospital between February 2018 and March 2023 were included in the study.The univariate and multivariate regression analyses were conducted to identify the predictors of stricture among patients undergoing steroid prophylaxis.RESULTS A total of 120 patients were included in the analysis.In the oral prednisone and oral prednisone combined with local tretinoin injection groups,the stenosis rates were 44/53(83.0%)and 56/67(83.6%),respectively.Among them,univariate analysis showed that the lesion circumference(P=0.01)and submucosal injection solution(P=0.04)showed significant correlation with the risk of stenosis formation.Logistic regression analyses were then performed using predictors that were significant in the univariate analyses and combined with known predictors from previous reports,such as additional chemoradiotherapy and tumor location.We identified a lesion circumference<5/6(OR=0.19;P=0.02)and submucosal injection of sodium hyaluronate(OR=0.15;P=0.03)as independent predictors of on esophageal stricture formation.CONCLUSION Steroid prophylaxis effectively prevents stenosis.Moreover,the lesion circumference and submucosal injection of sodium hyaluronate were independent predictors of esophageal strictures.Additional interventions should be considered in high-risk patients.

Steroids, Tri- and Meroterpenoids with a Quinone Structure—A Review

Terpenoids with quinoid structures are found as natural products. This includes steroidal quinones, quinones with a secosteroid structure and meroterpenoid quinones. Importantly, catechol estrogens as endogenous metabolites of estradiol and estrone are precursors of reactive quinones and semiquinones, which are thought to contribute to estrogen-induced carcinogenesis. On the other hand, a number of quinones that include substituted naphthoquinones and anthraquinones are highly cytotoxic and have been used in cancer treatment. This makes the structures interesting synthetic targets. The following is a review of important natural and synthetic terpenoid and steroid quinone hybrids.

Specific alterations of regional myocardial work in strength-trained athletes using anabolic androgenic steroids compared to athletes with genetic hypertrophic cardiomyopathy

Background:Strength-trained athletes using anabolic androgenic steroids(AAS)have left ventricular(LV)hypertrophy and myocardial fibrosis that can lead to sudden cardiac death.A similar feature was described in athletes with hypertrophic cardiomyopathy(HCM),which complicates the diagnosis for clinicians.In this context,we aimed to compare the LV function of the 2 populations by measuring global and regional strain and myocardial work using speckle-tracking imaging.Methods:Twenty-four strength-trained asymptomatic athletes using AAS(AAS-Athletes),22 athletes diagnosed with HCM(HCM-Athletes),and 20 healthy control athletes(Ctrl-Athletes)underwent a resting echocardiography to assess LV function.We evaluated LV global and regional strains and myocardial work,with an evaluation of the constructive work(CW),wasted work,and work efficiency(WE).Results:Compared to Ctrl-Athletes,both AAS-Athletes and HCM-Athletes had a thicker interventricular septum,with maj ored values in HCM-Athletes.LV strain was reduced in AAS-Athletes and even more in HCM-Athletes.Consequently,global WE was significantly diminished in both AAS and HCM-Athletes(93%±2%in Ctrl-Athletes,90%±4%in AAS-Athletes,and 90%±5%in HCM-Athletes(mean±SD);p<0.05).Constructive work and WE regional analysis showed specific alterations,with the basal septal segments preferentially affected in AAS-Athletes,and both septal and apical segments affected in HCM-Athletes.Conclusion:The regional evaluation of myocardial work reported specific alterations of the major LV hypertrophy induced by the regular use of AAS compared to the LV hypertrophy due to HCM.This finding could help clinicians to differentiate between these 2 forms of pathological hypertrophy.

Androgenic-anabolic steroids and the Olympic Games

Androgenic-anabolic steroids （AAS） have been misused by athletes at the Olympic Games, both before and after they were prohibited in sport in 1974. Systematic doping with AAS occurred in the German Democratic Republic （GDR） from 1965 to 1989 which assisted that country to win many medals at Olympic Games, especially in female events. Currently, AAS are the most frequent category of prohibited substances detected in the urine of athletes both globally and at the last two Summer Olympic Games. Scientific confirmation that AAS are effective in enhancing sports performance was difficult because ethical approval was difficult for research involving male subjects taking massive doses of androgens as some athletes and bodybuilders did. Methods to detect AAS have evolved gradually over the past three decades and currently, despite an impressive array of sophisticated analytical equipment and methods, anti-doping authorities and analytical scientists continue to face challenges as have occurred from the use by athletes of designer AAS during the past few years. The future development and use of selective androgen receptor modulators （SARMs） can be anticipated to pose problems in the years ahead. Endocrinologists should be aware that on occasions, replacement testosterone （T） therapy may be authorized in sport as a therapeutic use exemption （TUE） and these circumstances are discussed.

Treatment of eosinophlic esophagitis with swallowed topical corticosteroids

Eosinophilic esophagitis(EoE)is an emerging chronic local immune-mediated disease of the esophagus.Beside proton pump inhibitors and food-restrictiondiets swallowed topical corticosteroids(STC)can be offered as a first line therapy according to current guidelines.This review describes the background and practical management of STCs in EoE.So far,mainly asthma inhalers containing either budesonide or fluticasone have been administered to the esophagus by swallowing these medications“off label”.Recently esophagus-targeted formulations of topical steroids have been developed showing clinicopathological response rates up to 85%-an orodispersible tablet of budesonide has been approved as the first“in label”medication for EoE in Europe in June 2018.Whereas it was shown that disease remission induction of EoE by STCs is highly effective,there is still a lack of data regarding long-term and maintenance therapy.However,current studies on STC maintenance therapy add some movement into the game.

SELECTIVE REDUCTION OF 3,17—DIOXO—STEROIDS TO 17β-HYDROXY-3-OXO-STEROIDS

11β-Hydroxy-androst-4-en-3,17-dione(1a),androst-4,9(11)-dien-3,17- dione-(2a),androst-4-en-3,11,17-trione(3a),11α-methoxy-androst-4-en-3,17-dione (4a)and 11β-metboxy-androst-4-en-3,17-dione(Sa)were selectively reduced to the corresponding 17β-OH derivatives in one step without the protection of 3- oxo(and 11-oxo,in the case of 3a)group with the yields ranging from 65% to 79%.In these reactions,the ditute NaBH_4(or KBH_4)solution in methanol was added dropwise to the 3,17-dioxo-steroids solution in methanol-benzene-pyridine, while the reaction mixtures were well stirred at -5～5℃.Acid(such as gtacial acetic acid)was added to quench the reactions.The resulted testosterone derivatives(1b～5b)were purified by flash chromatography. This method appties to the reduction of other 3,17-dioxo-steroids such as△~1 -3-one,△^(1.4)-3-one,△^(4.6)-3-one,△^(1.4.6)-3-one containing compounds.

Osteonecrosis: The perils of steroids. A review of the literature and case report

Non-traumatic osteonecrosis is a cause of joint pain and deformity, not uncommonly caused by corticosteroid use. Despite this, corticosteroid induced osteonecrosis is poorly represented in the literature. We performed a detailed review of corticosteroid induced osteonecrosis, including aetiology, prevention, screening, clinical presentation, investigations, staging systems and treatment. We present this in the context of a patient at our institution who developed bilateral hip, shoulder and knee osteonecrosis following high dose corticosteroid therapy for dermatomyositis.

Apoptosis in Granulosa cells during follicular atresia:relationship with steroids and insulin-like growth factors

It is well known that during mammalian ovarian follicular development, the majority of follicles undergo atresia at various stages of their development. However, the mechanisms controlling this selection process remain unknown. In this study, we investigated apoptosis in granulosa cells during goat follicular atresia by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL). The changes in the levels of steroids, insulin-like growth factors (IGFs) and IGF receptors were studied by radioimmunoassay (RIA) and semi-quantitative reverse transcrip-tion-PCR. We found that the percentage of apoptotic granulosa cells in the atretic (A) follicles was significantly higher than that in the slightly atretic (SA) and healthy (H) follicles. The level of estradiol and the ratio of estradiol to progesterone in H follicles were significantly higher than those in A follicles. On the other hand, the level of progesterone was not significantly different among these follicle types. We also found that the level of IGF-Ⅰ in H follicles was higher than in SA and A follicles, whereas the amount of IGF-Ⅱ did not vary significantly. The expression of IGF receptor also decreased in A follicles as compared to that in H and SA follicles. These results suggested that estradiol and IGF-Ⅰ might be involved in controlling apoptosis in granulosa cells during follicular atresia.

Clinical trials on corticosteroids for diabetic macular edema

Diabetic macular edema(DME)is a common cause of visual impairment in diabetic patients.It is caused by an increase in the permeability of the perifoveal capillaries and a disruption of the blood retinal-barrier.The pathogenesis of DME is multifactorial.Several therapeutic modalities have been proposed for the treatment of DME.Corticosteroid treatments have emerged as an alternative therapy for persistent DME or refractory to conventional laser photocoagulation and other modalities,due to anti-inflammatory,anti-vascular endothelial growth factor and anti-proliferative effects.Many studies have demonstrated the beneficial therapeutic effect of corticosteroids with improvement to both retinal thickness and visual acuity in short-term on the treatment of DME.Peribulbar and intravitreal injections have been used to deliver steroids for DME with frequent injections due to the chronic and recurrent nature of the disease.Steroid-related side effects include elevated intraocular pressure,cataract,and injection related complications such as endophthalmitis,vitreous hemorrhage,and retinal detachment particularly with intravitreal steroid injections.In order to reduce the risks,complications and frequent dosing of intravitreal steroids,intravitreal implants have been developed recently to provide sustained release of corticosteroids and reduce repeated intravitreal injections for the management of DME.

Chromatographic finger print analysis of steroids in Aerva lanata L by HPTLC technique

Objective:To determine the chemical profile and steroids composition of the medicinally important plant Aerva lanata(A.lanata) L.Methods:Preliminary phytochemicul screening was done by the method as Harborne described.HPTLC studies were canied out as Harborne and Wagner et al described.The Ethyl acetate-ethanol-water(8:2:1.2) was employed as mobile phase for glycosides.Results:The desired aim was achieved using Chloroform-acetone(8:2) as the mobile phase.The methanolic extract of stem,leaves,root,flower and seeds of A.lanata showed the presence of 30 different types of steroids with 30 different Rf values from 0.04 to 0.97. Maximum number(11) of steroids has been observed in leaves followed by root(10).Conclusions: HPTLC profile of steroids has been chosen here to reveal the diversity existing in A.lanata.Such finger printing is useful in differentiating the species from the adulterant and act as biochemical markers for this medicinally important plant in the pharma industry and plant systematic studies.

Metabolic alteration of neuroactive steroids and protective effect of progesterone in Alzheimer's disease-like rats

A correlation between metabolic alterations of neuroactive steroids and Alzheimer’s disease remains unknown. In the present study, amyloid beta （Aβ） 25-35 （Aβ25-35） injected into the bilateral campus CA1 region significantly reduced learning and memory. At the biochemical level, hippocampal levels of pregnenolone were significantly reduced with Aβ25-35 treatment. Furthermore, progesterone was considerably decreased in the prefrontal cortex and hippocampus, and 17β-estradiol was signifi-cantly elevated. To our knowledge, this is the first report showing that Aβ25-35, a main etiological factor of Alzheimer’s disease, can alter the level and metabolism of neuroactive steroids in the prefrontal cortex and hippocampus, which are brain regions significantly involved in learning and memory. Aβ25-35 exposure also increased the expression of inflammatory mediators, tumor necrosis factor-αand interleukin-1β. However, subcutaneous injection of progesterone reversed the upregulation of tumor necrosis factor-αand interleukin-1βin a dose-dependent manner. Concomitant with improved cognitive abilities, progesterone blocked Aβ-mediated inflammation and increased the survival rate of hippocampal pyramidal cells. We thus hypothesize that Aβ-mediated cognitive deficits may occur via changes in neuroactive steroids. Moreover, our findings provide a possible therapeutic strategy for Alzheimer’s disease via neuroactive steroids, particularly progesterone.

Sex steroids and glucose metabolism

Testosterone levels are lower in men with metabolic syndrome and type 2 diabetes mellitus （T2DM） and also predict the onset of these adverse metabolic states. Body composition （body mass index, waist circumference） is an important mediator of this relationship. Sex hormone binding globulin is also inversely associated with insulin resistance and T2DM but the data regarding estrogen are inconsistent. Clinical models of androgen deficiency including Klinefelter＇s syndrome and androgen deprivation therapy in the treatment of advanced prostate cancer confirm the association between androgens and glucose status. Experimental manipulation of the insulin/ glucose milieu and suppression of endogenous testicular function suggests the relationship between androgens and insulin sensitivity is bidirectional. Androgen therapy in men without diabetes is not able to differentiate the effect on insulin resistance from that on fat mass, in particular visceral adiposity. Similarly, several small clinical studies have examined the efficacy of exogenous testosterone in men with T2DM, however, the role of androgens, independent of body composition, in modifying insulin resistance is uncertain.

Two New C_(21) Steroids from Marsdenia tenacissima

Two new C21 steroids were isolated from the CHCl3 extract of the stem of Marsdenia tenacissima. On the basis of spectroscopic analysis and chemical methods, their structures were elucidated as 17β-tenacigenin B (2) and 3-O-6-deoxy-3-O-methyl-β-D-allopyranosyl-(1→4)-β-D- oleandropyranosyl-tenacigenin C (3). The structure of the known aglycon tenacigenin C was revised as 5α, 9α, 17β-pregnane-3β, 8β, 11α, 12β, 14β-pentanol-20-one. Compound 3 is the first reported glycoside of tenacigenin C.

Multi-Residue Determination of Eight Anabolic Steroids by GC-MS in Muscle Tissues from Pigs

A gas chromatography-mass spectrometry （GC-MS） method to determine eight anabolic steroids （diethylstilbestrol, methyltestosterone, norethindrone, 17α-ethynylestradiol, estradiol, 6α-methyl-17α-hydroxy-progesterone, estradiol benzoate, and chlormadinone acetate） was developed. Muscle samples were extracted with liquid-liquid extraction and clean-up was performed in two steps, the extracts obtained were derivatized with heptafluorbutyric （HBF） anhydride and analyzed by GC-MS. In the above method, the linear scope was 2.5-50 μg kg^-1. The range of the recoveries was 78.5-148% for diethylstilbestrol, 70.8-109% for methyltestosterone, 69.8-87.2% for norethindrone, 67.7-120% for 17α-ethynylestradiol, 82.8-103% for estradiol, 70.3-99.2% for 6α-methyl-17α-hydroxy-progesterone, 73.0-104% for estradiol benzoate, and 72.9- 91.8% for chlormadinone acetate. The range of the coefficients of variation within batches was 0.4-12%; the range of the coefficients of variation between batches was 6.4-11%. The limit of detections and the detection capability were 0.99 and 3.30 μg kg^-1 for diethylstilbestrol, 1.05 and 3.50 μg kg^-1 for methyltestosterone, 1.19 and 3.97 μg kg^-1 for norethindrone, 0.94 and 3.13 μg kg^-1 for 17α-ethynylestradiol, 1.45 and 4.83 μg kg^-1 for estradiol, 1.56 and 5.20 μg kg^-1 for 6α-methyl-17α- hydroxy-progesterone, 1.92 and 6.40 μg kg^-1 for estradiol benzoate, and 2.41 and 8.03 μg kg^-1 for chlormadinone acetate, respectively. These results showed that the method was widely available, accurate, and sensitive.

Corticosteroids or non-corticosteroids: a fresh perspective on alcoholic hepatitis treatment

BACKGROUND: Alcoholic hepatitis (AH) is a necrotizing inflammatory process caused by alcoholic liver injury. It carries a significant short-term mortality. The management of AH is challenging. Although corticosteroids have been demonstrated to exert anti-inflammatory and antifibrotic effects, their efficacy for the treatment of AH remains debatable. DATA SOURCES: A literature search was performed of MEDLINE, ScienceDirect, SpringerLink and Wiley InterScience using the key words 'alcoholic hepatitis', 'alcoholic liver disease', and 'corticosteroids'. The available data reported in the relevant literature were analyzed. RESULTS: More than 17 controlled trials and at least 13 meta-analyses have reported the efficacy of corticosteroids in the treatment of AH in the past 40 years. Many were poorly designed and used different inclusion/exclusion criteria, making it difficult to reach a consensus. In this review, we summarized all the controversial data in the past decade and analyzed the potential causes for the varying therapeutic effects of corticosteroids in AH. The focus of the controversy has changed from 'whether steroids are beneficial or harmful for AH patients' to 'how to accurately identify responders to steroids early and rationalize corticosteroid treatment'. An early response to glucocorticoids, as determined by calculating the Lille score after 7 days of treatment, has been shown to be a clinically useful indicator. Moreover, down-regulation of steroid sensitivity, risk of infection, and a rational therapeutic strategy of corticosteroids in AH patients are all crucial for therapeutic effect.CONCLUSIONS: An early and accurate determination of steroid sensitivity is important. Besides, we need to overcome the down-regulation of steroid sensitivity, reduce the infection risk and rationalize the therapeutic strategy of corticosteroids. A fresh perspective is needed on the use of corticosteroids in AH patients.

Severe ulcerative colitis: At what point should we define resistance to steroids?

Corticoesteroids are still the first-line treatment for active ulcerative colitis more than 50 years after the publication of trials assessing their beneficial effect, with about a 50% remission rate in cases of severe disease. The mortality related to severe attacks of ulcerative colitis has decreased dramatically, to less than 1%, in experienced centers, due to the appropriate use of intensive therapeutic measures (intravenous steroids, fluids and electrolytes, artificial nutritional support, antibiotics, etc), along with timely decision-making about second-line medical therapy and early identification of patients requiring colectomy. One of the most difficult decisions in the management of severe ulcerative colitis is knowing for how long corticosteroids should be administered before deciding that a patient is a non-responder. Studies assessing the outcome of acute attacks after steroid initiation have demonstrated that, in steroid-sensitive patients, the response generally occurs early on, in the first days of treatment. Different indexes to predict treatment failure, when applied on the third day of treatment, have demonstrated a high positive predictive value for colectomy. In contrast to this resolute approach, which is the most widely accepted, other authors have suggested that in some patients a completeand prolonged response to steroids may take longer. Either way, physicians taking care of these patients need to recognize that severe ulcerative colitis may be life-threatening, and they need to be careful with excessively prolonged medical treatment and delayed surgery.

Synthetic neurosteroids on brain protection

Neurosteroids, like allopregnanolone and pregnanolone, are endogenous regulators of neuronal excitability. Inside the brain, they are highly selective and potent modulators of GABAA receptor activity. Their anticonvulsant, anesthetics and anxiolytic properties are useful for the treatments of several neurological and psychiatric disorders via reducing the risks of side effects obtained with the commercial drugs. The principal disadvantages of endogenous neurosteroids adminis- tration are their rapid metabolism and their low oral bioavailability. Synthetic steroids analogues with major stability or endogenous neurosteroids stimulation synthesis might constitute prom- ising novel strategies for the treatment of several disorders. Numerous studies indicate that the 3ct-hydroxyl configuration is the key for binding and activity, but modifications in the steroid nucleus may emphasize different pharmacophores. So far, several synthetic steroids have been developed with successful neurosteroid-like effects. In this work, we summarize the properties of various synthetic steroids probed in trials throughout the analysis of several neurosteroids-like actions.

Steroids and Sesquiterpenes From Cultures of the Fungus Phellinus igniarius

Two new steroids,3a,17a,19,20-tetrahydroxy-4a-methylpregn-8-ene(1)and 3a,12a,17a,20-tetrahydroxy-4amethylpregn-8-ene(2)and three new sesquiterpenoids,12-hydroxy-a-cadinol(3),3a,12-dihydroxy-d-cadinol(4),and 3a,6a-dihydroxyspiroax-4-ene(5),have been isolated from cultures of the fungus Phellinus igniarius.Their structures were characterized based on extensive spectroscopic data.In preliminary in vitro assays,compounds 3 and 4 exhibited the vascular-activities against phenylephrine-induced vasoconstriction with the relaxing rates of 11.0%and 7.0%at 3910-4 M,respectively.

Structural Modification for Antitumor Nitrogenous Steroids

Natural steroids have been showing notable cytotoxic activities, which are quite interesting lead compounds for the development of anticancer drug including estramustine and prednimustine. Considering that these semi-synthetic molecules are nitrogen mustard functionalized steroidal derivatives, the present review is focused on the methodologies of introducing nitrogen atom or nitrogen-containing heterocycles on A^D rings or side chains of steroids, and analysis of the structure-activity relationship（SAR） for these man-made cytotoxic steroids.

Steroids in Maxillofacial Space Infection: A Retrospective Cohort Study

Maxillofacial space infection (MSI) is one of the most common conditions encountered in oral and maxillofacial surgery clinics. Early recognition and proper management of MSI could prevent a life-threatening event. Objectives: To report a series of MSI managed with antibiotics, surgical intervention and exogenous steroids as an adjunct, highlighting functional improvement following steroid administration. Methods: A retrospective cohort study was carried out from December 2013 to September 2016, involving 30 patients (n = 30, 22 males, 8 females) diagnosed with MSI. All patients were initially managed with intravenous empirical antibiotics, analgesics and removal of potential source of infection. A course of 3 doses of IV Dexamethasone 8 mg at an interval of 8 hours was started during the first day of hospital admission. Results: This series reports 30 patients presenting with MSI, who received prompt antibiotics and 3 doses of steroids as inpatients. Significant clinical improvement was noted in the form of amelioration of pain, rapid reduction in edema, and improved trismus, shortening hospital stay to an average of 3.5 days, and omission of surgical intervention in 50% of our cases. No adverse effects or drug reaction was noted. Conclusion: In conclusion, the value of synergistic use of corticosteroids with antibiotics in management of MSI is significant. Despite these promising findings, there is scarce evidence in the literature to fully support the use of corticosteroids in abscess management. The role of corticosteroids in treatment of MSI should be explored further.