Classical Steroid Research Articles

Evaluation of biologically active constituents of ethanol extracts of <em>H. verticillata</em> leave, <em>L. aestuans </em>leave and seeds of <em>L. aestuans</em>

There has been a great interest in the study of products of natural origin as an alternative and an adjunct to the chemically synthesized drugs for various therapeutic roles owing to the vast array of their medicinal activities and structural differences that abound in plants secondary metabolites. The preliminary analysis of the phytonutrients presents in the ethanol extracts of Hydrocotyle verticillata and Laportea aestuans showed the presence of saponins, various classes of alkaloids, Cardiac glycosides, Steroids, Phenolic chemicals, Tannins, Flavonoids, but Coumarins, Proteins and Quinines were lacking in both extracts. Noteworthy is that, tannins and alkaloids were predominant compared to other phytochemicals in the ethanol extract of Hydrocotyle verticillata leave. In the same vain, tannins and alkaloids were the more abundant phytochemicals in the Laportea aestuans leave extract. Analysis of the extract using combined chromatographic and spectrometric (GCMS) approach of Hydrocotyle verticillata leaves identified 3 major chemicals in descending order as 3. beta. 17.beta.-dihydroxyestr-4-ene [10.89%]; Hexadecanoic acid, ethyl ester [7.49%]; and 1-Methylbicyclo [3.2.1] octane [7.28%]. On the other hand, the 3 highest occurring chemical compounds identified in the ethanol extract of L. aestuans leaves are Diazoprogesterone [9.45%]; hexadecanoic acid, ethyl ester [8.29%]; and linoleic acid ethyl ester [7.31%]. It has been established that these chemical constituents were found to exert useful biological effects ranging from cellular, anticarcinogenic, anti-cholinergic effects, antioxidant, virus antagonists, anti-inflammatory as well as having profound effects on bacterial infections. Due to the numerous listed biological effects, the extracts could be used as an adjunct in a diverse number of diseases.

Simultaneous investigation of urinary and faecal glucocorticoid metabolite concentrations reveals short- versus long-term drivers of HPA-axis activity in a wild primate (Papio ursinus)

Glucocorticoids (GCs), a class of steroid hormones released through activation of the hypothalamic–pituitary–adrenal (HPA) axis, perform many vital functions essential for survival, including orchestrating an organism’s response to stressors by modulating physiological and behavioural responses. Assessing changes and variation in GC metabolites from faecal or urine samples allows for the non-invasive monitoring of HPA-axis activity across vertebrates. The time lag of hormone excretion differs between these sample matrices, which has implications for their suitability for studying effects of different temporal nature on HPA-axis activity. However, simultaneous comparisons of predictors of faecal and urinary GC metabolites (fGCs and uGCs, respectively) are lacking. To address this gap, we employ frequent non-invasive sampling to investigate correlates of fGCs and uGCs in wild chacma baboons (Papio ursinus) (n = 17), including long-term (dominance rank, season, female reproductive state) and short-term (time of day, daily weather conditions) factors. Correlated with increasing day length, fGCs gradually decreased from winter to summer. No seasonal effect on uGCs was found but ‘rain days’ were associated with increased uGCs. Pregnant females had significantly higher fGCs compared to cycling and lactating females, whereas uGCs were not statistically different across reproductive states. A circadian effect was observed in uGCs but not in fGCs. Dominance rank did not affect either fGCs or uGCs. Our study highlights the difference in inherent fluctuation between uGCs and fGCs and its potential consequences for HPA-axis activity monitoring. While uGCs offer the opportunity to study short-term effects, they undergo more pronounced fluctuations, reducing their ability to capture long-term effects. Given the increasing use of urine for biological monitoring, knowledge of this potential limitation is crucial. Where possible, uGCs and fGCs should be monitored in tandem to obtain a comprehensive understanding of short- and long-term drivers of HPA-axis activity.

Parallel targeted and non-targeted quantitative analysis of steroids in human serum and peritoneal fluid by liquid chromatography high-resolution mass spectrometry

We developed and validated a liquid chromatography high-resolution mass spectrometry method for the absolute quantification of 51 steroids for clinical analysis of human serum and, for the first time, peritoneal fluid. Data acquisition was performed in both targeted and untargeted mode simultaneously, thus allowing the accurate and precise quantification of the main components of the classical steroid pathways (17 steroids) as well as the analysis of 34 additional non-classical steroids. For targeted analysis, validation was performed according to FDA guidelines, resulting, among other parameters, in accuracy < 13% RSD and precision < 10% relative error, for both inter- and intra-day validation runs. By establishing steroid-specific response factors, the calibration curves of the targeted analytes can be extended to untargeted analytes. This approach opens novel possibilities for the post hoc analysis of clinical samples as the data can be examined for virtually any steroid even after data acquisition, enabling facile absolute quantification once a standard becomes available. We demonstrate the applicability of the approach to evaluate the differences in steroid content between peripheral serum and peritoneal fluid across the menstrual cycle phases, as well as the effect of the synthetic gestagen dienogest on the steroid metabolome.Graphical abstract

Glucocorticoids and Risk of Venous Thromboembolism in Asthma Patients Aged 20-59 Years in the United Kingdom's CPRD 1995-2015.

BackgroundGlucocorticoids, the class of steroids used in management of asthma, have been observed to be associated with adverse events such as increased coagulation and inhibition of fibrinolysis. This study evaluated the risk of VTE in relation to the use of glucocorticoids in patients with asthma.MethodsWe conducted a nested case–control study among patients aged 20–59 years with asthma who received at least one glucocorticoid prescription during 1995–2015 in the UK-based Clinical Practice Research Datalink GOLD. We used descriptive analyses and conditional logistic regression to evaluate the risk of VTE associated with glucocorticoid use.ResultsThe adjusted ORs (aORs) (95% CI) for VTE in patients exposed to glucocorticoids were 1.9 (1.6–2.3), 1.4 (1.1–1.8), and 1.2 (0.9–1.5) for current, recent, and past glucocorticoid users, respectively, compared to the unexposed. The aORs (95% CI) for VTE in patients exposed to systemic glucocorticoid and inhaled glucocorticoids, compared to the unexposed, were 3.5 (2.7–4.5) and 1.5 (1.3–1.8), respectively.ConclusionCurrent and systemic glucocorticoid use was associated with a dose-response increased risk of incident idiopathic VTE.

Analytical Method Development and Validation for Estimation of Mifepristone in Pure and Pharmaceutical Dosage Form

Mifepristone structurally belongs to the class of anti-progesterone steroids, which are used as an oral contraceptive. The reverse phase HPLC method was designed in a simplified and rapid way for the estimation of Mifepristone in bulk as well as tablets. The method was established using a Kromasil C18 column of dimensions of 250mm×4.6mm and a particle size of 5m.The used mobile phase was Acetonitrile: Water (70:30, v/v). The pump was pumped at 1 ml/min at a temperature of about 30 ± 2 °C and the eluted analyte was identified at 305 nm. Mifepristone eluted with a mean retention time of 6.27 minutes. The intended method was validated as per ICH (International Council for Harmonisation) guidelines, indicating a high degree of specificity, system suitability, accuracy, precision, and robustness. The LOD (Limit of detection) was found to be 0.7238 ppm and the limit of measurement was 0.9562 ppm. The method linearity was found to be between 1-6µg/ml, with an R2 of 0.9923. In accuracy studies, the percent recovery was found to be between 99.39% - 100.50%. The method was discovered to be precise as the values of the percent RSD were found to be less than 2.0% for both intraday and interday. The method was discovered to be reliable and robust. Mifepristone in marketed pharmaceutical tablet dosage form was effectively quantified using the established Reverse Phase HPLC method.

Ecdysteroids

Ecdysteroid: member of a class of polyhydroxylated steroids found in invertebrate animals (zooecdysteroids; moulting hormones), plants (phytoecdysteroids) and fungi (mycoecdysteroids). Over 500 structural analogues are currently known. Biosynthetically, they derive from C27-, C28- or C29-sterols. The most frequently encountered analogue (in arthropods and plants) is 20-hydroxyecdysone (2β,3β,14α,20R,22R,25-hexahydroxycholest-7-en-6-one). In arthropods, ecdysteroids occur universally and regulate development by inducing moulting and reproduction, where their action is mediated by high-affinity binding to an intracellular member of the class of nuclear receptor (NR) proteins (ecdysteroid receptor; EcR) dimerised with a second NR (USP/RxR). This receptor complex binds to specific DNA promoter sites and regulates gene expression. In plants, ecdysteroids are a class of secondary compounds, occurring in varying amounts in certain species, but not all in others. Phytoecdysteroids are believed to contribute to the reduction of invertebrate predation by acting as feeding deterrents or endocrine disruptors. Ecdysteroids also possess a wide range of positive pharmacological effects in mammals, where the mode of action involves moderate-affinity binding to plasma-membrane-bound receptors and not interaction with the classical NRs for vertebrate steroid hormones.

Removal of dexamethasone by oxidative processes: Structural characterization of degradation products and estimation of the toxicity

Dexamethasone (DEX) belongs to a class of steroid hormones that can potentially be harmful due to their endocrine disrupting properties. The efficient elimination of DEX during the treatment of drinking water is needed to ensure that the health of both human and aquatic species are protected. Thus different oxidative processes were investigated in order to assess the effect of these procedures and conditions on DEX. Aqueous solutions of DEX were treated by conventional chlorination ([NaClO]=10 mg L−1) and advanced oxidative processes (ozonation – [O3]=8 mg L−1; photocatalysis – [TiO2]=120 mg L−1 and UV-C; photolysis – UV-C). The most and least efficient processes for DEX removal were ozonation (95%) and chlorination (54%), respectively. In total, 16 degradation products were identified and characterized by high-resolution mass spectrometry and only two have been proposed in previous reports. Chemical structures of the degradation products were proposed and alcohol oxidation, ozonolysis and decarboxylation were the main chemical transformations observed. The toxicities of DEX and its derivatives were evaluated by following methods: MTT assay (HepG2 cell), ECOSAR (acute and chronic toxicity) and molecular docking (AutoDock). MTT assay results demonstrated that only a mixture DEX and the chlorinated derivative were toxic at high concentrations. ECOSAR analysis showed that products formed from dehydration and fluoride elimination were more toxic than intact DEX, mainly for fish and Daphnid and to a lesser extent for green algae. The docking study revealed that these degradation products were not capable of making hydrogen bonds with residual amino acids GLN570, GLN642 and CYS736, but were stable at the glucocorticoid receptor indicating the possibility of being toxic to humans.

Expression Patterns of the Neuropeptide Urocortin 3 and Its Receptor CRFR2 in the Mouse Central Auditory System.

Sensory systems have to be malleable to context-dependent modulations occurring over different time scales, in order to serve their evolutionary function of informing about the external world while also eliciting survival-promoting behaviors. Stress is a major context-dependent signal that can have fast and delayed effects on sensory systems, especially on the auditory system. Urocortin 3 (UCN3) is a member of the corticotropin-releasing factor family. As a neuropeptide, UCN3 regulates synaptic activity much faster than the classic steroid hormones of the hypothalamic-pituitary-adrenal axis. Moreover, due to the lack of synaptic re-uptake mechanisms, UCN3 can have more long-lasting and far-reaching effects. To date, a modest number of studies have reported the presence of UCN3 or its receptor CRFR2 in the auditory system, particularly in the cochlea and the superior olivary complex, and have highlighted the importance of this stress neuropeptide for protecting auditory function. However, a comprehensive map of all neurons synthesizing UCN3 or CRFR2 within the auditory pathway is lacking. Here, we utilize two reporter mouse lines to elucidate the expression patterns of UCN3 and CRFR2 in the auditory system. Additional immunolabelling enables further characterization of the neurons that synthesize UCN3 or CRFR2. Surprisingly, our results indicate that within the auditory system, UCN3 is expressed predominantly in principal cells, whereas CRFR2 expression is strongest in non-principal, presumably multisensory, cell types. Based on the presence or absence of overlap between UCN3 and CRFR2 labeling, our data suggest unusual modes of neuromodulation by UCN3, involving volume transmission and autocrine signaling.

Low-energy electron ionization optimization for steroidomics analysis using high-resolution mass spectrometry.

Systematic electron ionization fragmentation studies of steroids have been performed to elucidate and trace their characteristic fragmentation patterns. However, the electron ionization source setting at 70 eV electron energy is much higher than the ionization potential (7-15 eV) of most organic compounds, leading to extensive fragmentation. We present a multifactorial study on optimizing a low-energy electron ionization source to maximize molecular ion formation while minimizing the extent of fragmentation to improve the analytical sensitivity of steroids, especially the more thermolabile ones, while preserving the information that can be extracted from the data. Twenty-seven steroid reference materials, chosen to cover four main classes of urinary steroids, were considered; gas chromatography/quadrupole time-of-flight (GC/qTOF) analyses were carried out using an Agilent Technologies model 8890 gas chromatograph coupled to an Agilent Technologies model 7250 accurate-mass quadrupole time-of-flight (GC/qTOF) instrument. The effects of electron energy, emission current, and source temperature, as well as their potential interactions on steroid fragmentation pathways, have been assessed in full factorial experimental designs. Three parameters were specifically evaluated to improve the chromatographic/spectrometric response of the selected steroids: (i) degree of fragmentation; (ii) relative abundance of the molecular ion; and (iii) peak width. The first two were evaluated by screening designs that highlighted collision energy and source temperature as the most influential factors on the analytical responses of the considered steroids, while emission current always showed a non-significant influence. Then, an optimization design was performed to select the final source setting by searching for the combination of factors that minimize peak tailing. The proposed analytical approach permits a faster selection of optimal experimental conditions for steroidomics analysis using low-energy electron ionization and high-resolution mass spectrometry. The development of these designs of experiments (DoE) in full factorial design (FFD) allowed multiple inputs to be monitored at the same time, highlighting the possible interactions and estimating the effects of a factor in the different levels of the other factors considered.

Pleiotropic Effects of Glucocorticoids on the Immune System in Circadian Rhythm and Stress.

Glucocorticoids (GCs) are a class of steroid hormones secreted from the adrenal cortex. Their production is controlled by circadian rhythm and stress, the latter of which includes physical restraint, hunger, and inflammation. Importantly, GCs have various effects on immunity, metabolism, and cognition, including pleiotropic effects on the immune system. In general, GCs have strong anti-inflammatory and immunosuppressive effects. Indeed, they suppress inflammatory cytokine expression and cell-mediated immunity, leading to increased risks of some infections. However, recent studies have shown that endogenous GCs induced by the diurnal cycle and dietary restriction enhance immune responses against some infections by promoting the survival, redistribution, and response of T and B cells via cytokine and chemokine receptors. Furthermore, although GCs are reported to reduce expression of Th2 cytokines, GCs enhance type 2 immunity and IL-17-associated immunity in some stress conditions. Taken together, GCs have both immunoenhancing and immunosuppressive effects on the immune system.

Neuroactive steroids and depression in early pregnancy

Progesterone (P4) can be metabolized to two general classes of neuroactive steroids (NAS) -those like allopregnanolone (ALLO) and pregnanolone (PA) which are positive allosteric modulators of the Gamma Aminobutyric Acid type A (GABAA) receptor and those like isoallopregnanolone (ISOALLO) and epipregnanolone (EPI) which are negative allosteric modulators of the GABAA receptor. While exogenous administration of ALLO is effective in treating postpartum depression, knowledge gaps remain in the dynamic interplay of NAS across the perinatal period. In particular little is known about ALLO and PA in relation to depression earlier in pregnancy, and the role of ISOALLO and EPI in relation to depression at any point in the perinatal period. In a prospective, nested case/control study in low-income women of color, we compared the metabolism of P4 to four NAS (i.e., ratios ALLO:P4, PA:P4, ISOALLO:P4, EPI:P4) in pregnant women with depression at either or both of the first and second trimesters (cases) and women without depression at either time point (controls). Fifty women (36% depressed, 56% Black, 28% Latina) completed depression screening using a computerized adaptive test of mental health (CAT-MH™) and provided blood serum samples in both trimesters. In longitudinal mixed effects models of both trimesters, PND cases showed higher ratios of ALLO:P4 (p = .002) and PA:P4 (p = .03) compared to controls. In regression models of only first trimester data, there was no significant difference in NAS ratios between cases and controls (p > .05). Conversely, in models of the second trimester, ratios of PA:P4 (p = .002) and ISOALLO:P4 (p = .01) were significantly higher in cases compared to controls, and ratios of ALLO:P4 (p = .08) and EPI:P4 (p = .1) also trended higher in cases. The most severe cases, those with depression at both trimesters, showed an increase in ALLO:P4 (p = .06) and EPI:P4 (p < .001) ratios from the first to the second trimester, whereas controls showed a decrease in these ratios. Secondary analyses confirmed higher levels of ALLO (p = .04) and PA (p = .07) overall in cases compared to controls, along with higher levels of PA (p = .005) and ISOALLO (p = .02) in the second trimester alone. This work suggests a dynamic relationship between NAS and PND; whereas low ALLO levels have been previously associated with postpartum depression, earlier in pregnancy a higher metabolism of P4 to ALLO (and higher ALLO levels) is associated with depression. Some women may show a hormone-sensitive depressive response to acute increases in NAS metabolism in early pregnancy.

Therapeutic approach with squaric acid dibutylester for steroid resistant-alopecia areata incognita: A pilot study of a single center.

Topical immunotherapy is widely used in the treatment of alopecia areata (AA). Alopecia areata incognita (AAI) is a relatively common disorder, predominantly affecting females, characterized by widespread hair thinning in the absence of typical alopecic patches. AAI can have a chronic relapsing course and in some cases can be resistant to current standard treatments. Topical immunotherapy has been used in the management of AA with encouraging results, but to date there are no literature studies reporting the efficacy of topical immunotherapy with squaric acid dibutylester (SADBE) in AAI. The aim of our study is to evaluate the efficacy and tolerance of topical immunotherapy with SADBE in AAI not responding to conventional steroid therapy. A total of 12 patients were enrolled in our Hair Disease Outpatient Service, with a proved histological diagnosis of AAI, and resistant to classical steroid therapy. Each patient underwent global photography, pull test, and trichoscopy at beginning and during the follow-ups. The efficacy of topical immunotherapy with SADBE was assessed by evaluating the changes of clinical and trichoscopic signs. Complete regrowth was achieved in 66.7% of cases (8/12), three patients remained unchanged on clinical evaluation but showed subclinical improvement on trichoscopy, whereas one patient progressed and worsened both on clinical and trichoscopic examination. All patients reported scalp diffuse mild erythema and itching the day after the application of SADBE, which were well tolerated. Three patients developed reactive cervical lymphoadenomegaly. No other side effects were observed. Topical immunotherapy with SADBE is widely used in the management of patchy AA and can be considered an effective alternative in resistant AAI, providing visible clinical and trichoscopic improvement in the majority of cases. Further studies are warranted to confirm and validate our findings.

Coagulation changes in COVID-19 infection and its implication in management

COVID-19 infection causes substantial changes in blood coagulation. Understanding this process helps management of the patient with least injury through therapeutic misadventurism. At the heart of the disease process, there is widespread endothelial and pulmonary alveolar epithelial cell damage related to the entry and proliferation of the virus and subsequent cellular response to virus invasion. The virus directly triggers fibrinolytic system which positively increase cellular viral load, cytokine generation, exudation in the alveoli, and both intravascular and extravascular blood coagulation and fibrinolysis. The major coagulation catastrophe comes from immunocoagulation and contribution by specific and non-specific cells (lymphocytes, monocytes, and neutrophils) augmenting the process. Hypoxia also contributes and plays an independent role. Platelet activation, complement activation, and vasculitis or vasculitis-mimics take part in the process. Some of these mechanisms are well established and some are yet to be worked out. COVID-19 infection unequivocally points out the great role of cellular activation and cytokines play in coagulation process; indicates classical anticoagulants, antiplatelets, statins, complement inhibitors, and steroids in managing this infection. The author concentrates on the pathobiology of blood coagulation with perspectives on how to manage each of these steps.

Cutaneous Adverse Drug Reactions in Hospitalized HIV/AIDS Patients

Background: Cutaneous adverse drug reaction (CADR) is the most common manifestation of drug hypersensitivity in humanimmunodeficiency virus (HIV), which presented as maculopapular rash. The incidence of CADR is found to be more commonin untreated HIV patients, and the frequency is higher in severe immunodeficiency status. Early diagnosis and appropriatetreatment give better outcomes. Purpose: To evaluate the incidence and management of CADR in HIV and acquired immunedeficiency syndrome (AIDS) patients. Methods: A retrospective descriptive study of HIV/AIDS patients with CADR whowere hospitalized at Intermediate Care and Infectious Disease Centre Dr. Soetomo General Academic Hospital. Result: Therewere more CADR cases in 2017, accounted 2.35% of the total Intermediate Care and Infectious Disease Centre RSUD Dr.Soetomo General Academic Teaching Hospital ward patients. There were more male patients (62.5%), with the mostcommonly found at the age of 25-44 years (64.3%), and which mostly (89.3%) originated from Surabaya. The most commondiagnosis was morbiliform eruption (60.7%), main complaint was red spots all over the body (45%), all of which are obscureerythematous macules. The most common causes were Duviral + Neviral antiretroviral (46%) and the most common treatmentwas dexamethasone injection. Conclusion: The incidence of CADR increased in 2017. The most frequent manifestation wasmorbilliform eruption due to Duviral+Neviral as the first line ARV treatment. Skin management varies widely in form oftopical, oral, and intravenous injection drugs, mostly using steroid class, dexamethasone intravenous injection in particular.

Biomedical Applications of Supramolecular Materials in the Controllable Delivery of Steroids.

Glucocorticoids are a class of steroid hormones secreted from the adrenal glands. The strong anti-inflammatory effects make it be one of the most popular and versatile drugs available to treat chronic inflammatory diseases. Additionally, supramolecular materials have been widely exploited in drug delivery, due to their biocompatibility, tunability, and predictability. Thus, steroid-based supramolecular materials and the release of steroids have been applied in the treatment of inflammatory diseases. This mini-review summarized recent advances in supramolecular materials loaded with glucocorticoid drugs in terms of hydrophobic interactions, electrostatic interactions, hydrogen bonding, and π-π stackings. We also discussed and prospected the application of the glucocorticoid drugs-based supramolecular system on chronic rhinosinusitis, multifactorial inflammatory disease of the nasal and paranasal sinuses mucosal membranes. Overall, supramolecular materials can provide an alternative to traditional materials as a novel delivery platform in clinical practice.

Inhibition of ABCC5-mediated cGMP transport by progesterone, testosterone and their analogues

The biodynamics and biokinetics of sex hormones are complex. In addition to the classical steroid receptors (nuclear receptors), these hormones act through several non-genomic mechanisms. Modulation of ABC-transporters by progesterone represents a non-genomic mechanism. In the present study, we employed inside out vesicles from human erythrocytes to characterize high affinity cGMP transport by ABCC5 (member 5 of the ATP-Binding Cassette subfamily C). Progesterone and testosterone inhibited the transport with respective Ki of 1.2 ± 0.3 and 2.0 ± 0.6 μmol/L. We used virtual ligand screening (VLS) to identify analogues to progesterone and testosterone. A large number of substances were screened in silico and the 19 most promising candidates were screened in vitro. Each substance was tested for a concentration of 10 μmol/L. The range of cGMP transport reduction was 21.5% to 86.2% for progesterone analogues and 8.6% to 93.8 % for testosterone analogues. Three of the most potent test compounds (TC) of each analogue class, in addition to progesterone and testosterone, were characterized for concentrations from 1 nanomol/L to 1 mmol/L. The progesterone analogues showed following Ki-values (μmol/L): TC-08: 0.61, TC-16: 0.66 and TC-15: 9.3. The Ki-values (μmol/L) for the testosterone analogues were: TC-18: 0.10, TC-07: 0.67 andTC-05: 2.0. The present study shows that VLS may be a versatile tool in the development of membrane transport modulating agents (MTMAs).

Nuclear androgen and progestin receptors inversely affect aggression and social dominance in male zebrafish (Danio rerio)

Aggression is a fundamental behavior displayed universally among animal species, but hyper- or hypo-aggressiveness can be maladaptive with negative consequences for individuals and group members. While the social and ecological significance of aggression is well understood, the specific neurobiological and hormonal mechanisms responsible for mediating aggression have not been fully elucidated. Previous studies have shown a relationship between aggressive acts and circulating gonadal steroids, but whether classical nuclear steroid receptors regulate aggression in animals is still uncertain. We examined whether the nuclear androgen receptor (Ar) and nuclear progestin receptor (Pgr) were necessary for aggressive behaviors and maintenance of a dominance relationship in male zebrafish (Danio rerio). Dyadic social interactions of Ar knockout (ArKO), Pgr knockout (PgrKO) and wildtype (WT) controls were observed for two weeks (2-weeks). ArKO zebrafish were significantly less aggressive and had a less defined dominance relationship, whereas PgrKO dominant zebrafish were significantly and persistently more aggressive with a robust dominance relationship. Our results demonstrate the importance of nuclear steroid hormone receptors in regulating aggression of adult male zebrafish and provide new models for understanding of the mechanisms of aggression.

BPS and Cell Fusion in the Human Placenta: A Separate Mechanism of Action?

BPS and Cell Fusion in the Human Placenta: A Separate Mechanism of Action?

Current Insights into the Steroidal Module of the Athlete Biological Passport.

For decades, the class of anabolic androgenic steroids has represented the most frequently detected doping agents in athletes’ urine samples. Roughly 50% of all adverse analytical findings per year can be attributed to anabolic androgenic steroids, of which about 2/3 are synthetic exogenous steroids, where a qualitative analytical approach is sufficient for routine doping controls. For the remaining 1/3 of findings, caused by endogenous steroid-derived analytical test results, a more sophisticated quantitative approach is required, as their sheer presence in urine cannot be directly linked to an illicit administration. Here, the determination of urinary concentrations and concentration ratios proved to be a suitable tool to identify abnormal steroid profiles. Due to the large inter-individual variability of both concentrations and ratios, population-based thresholds demonstrated to be of limited practicability, leading to the introduction of the steroidal module of the Athlete Biological Passport. The passport enabled the generation of athlete-specific individual reference ranges for steroid profile parameters. Besides an increase in sensitivity, several other aspects like sample substitution or numerous confounding factors affecting the steroid profile are addressed by the Athlete Biological Passport-based approach. This narrative review provides a comprehensive overview on current prospects, supporting professionals in sports drug testing and steroid physiology.

Stigmasterol and Stigmasterone from Methanol Extract of Calophyllum soulattri Burm. F. Stem Bark

Stigmasterol and Stigmasterone from Methanol Extract of Calophyllum soulattri Burm. F. Stem Bark. Calophyllum soulattri Burm. F. has been widely used for herbal medicine. Phytochemical investigation of C. soulattri contains a secondary metabolite of the steroid class. Steroid compounds have various biological activities, such as anti-inflammatory, antioxidant, antiproliferative, antibacterial, antimalarial, and anticancer. Two secondary metabolites steroids have been isolated and identified from the stem bark extract of C. soulattri. Isolation was carried out through the extraction (maceration), fractionation, and purification stages. Maceration is carried out using methanol as a solvent. Fractionation was carried out by vacuum liquid chromatography (VLC), and purification was by flash column chromatography. Identification of combined fractions and determination of pure isolates were used through thin-layer chromatography (TLC). The solvent used in the chromatography methods was a mixture of n-hexane and ethyl acetate. The structure isolates were identified by FTIR, 1H NMR, and 13C NMR and compared with literature data. Secondary metabolites steroids that have been isolated are identical compounds to stigmasterol and stigmasterone.