Binary mixtures of surfactants build a binary mixed micelle in which the ratio of surfactants usually differs from the initial ratio of surfactants in their binary mixture. The thermodynamic stabilization of the binary mixed micellar pseudophase about the hypothetical ideal state (intermolecular interactions between the different particles and the conformational states of the particles are identical to those of monocomponent states) is described by the molar excess Gibbs free energy (gE). The dependence of gE on the molar fraction of surfactant i (xi) from the binary mixed micelle can be described by a symmetric function (symmetry is described to the line parallel to the y-axis and passes through xi = 0.5) or by an asymmetric function. Theoretical analysis (canonical partition function, conformational analysis) examines how the presence of different polar functional groups, some of which are sterically shielded from the steroid skeleton of bile salt (surfactant), affect the symmetry of the function gE of the binary mixed micelle of the cholic acid anion (bile salt) and classical cationic surfactant (hydrophobic tail and polar head). Suppose the steroid skeleton of the bile salt contains non-sterically shielded polar groups (or the temperature is relatively high). In that case, gE is a symmetric function. At the same time, if the steroid skeleton also contains sterically shielded polar groups, then the gE function is asymmetric.

In vitro studies show that diclofenac inhibits enzymatic steroid glucuronidation. This study was designed to investigate the influence of diclofenac on the excretion of stanozolol and 3'-hydroxystanozolol via analyses in hair, blood and urine in vivo in a rat study. Brown Norway rats were administered with stanozolol (weeks 1-3) and diclofenac (weeks 1-6). Weekly assessment of steroid levels in hair was complemented with spot urine and serum tests. Levels of both stanozolol and 3'-hydroxystanozolol steadily increased in hair during stanozolol treatment and decreased post-treatment, but remained readily detectable for 6 weeks. In contrast, compared to control rats, diclofenac significantly reduced urinary excretion of 3’-hydroxystanozolol which was undetectable in most samples. This is the first report of diclofenac altering steroid metabolism in vivo, detrimentally affecting detection in urine, but not in hair which holds considerable advantages over urinalysis for anti-doping tests.

Cardiotonic glycoside toxins, originally isolated from plants or amphibians, have been proposed as mammalian cardiotonic hormones. This paper is a review and update of the discovery of [i] a new class of steroid hormones, [ii] the path for their biosynthesis and [iii] some preliminary data on their function. The compounds are phosphoester conjugates and share a characteristic structural feature, a lactone ring, with [a] one class of synthetic potassium sparing diuretics and with [b] plant and amphibian cardiotonic steroids. Purification was initially monitored by cross reaction with steroid sulfate assays and later with digoxin-specific assays. Six compounds were purified by HPLC to near homogeneity and characterized by Tandem mass spectroscopy (MS-MS) and 31P-NMR. Three were digoxin-like materials (DLM) with 23 carbon atoms. The two extra carbon atoms form a spiral lactone E-ring. Several additional spiral lactones have been identified by MS-MS. In a pilot study, based on MS analysis, we evaluated phosphocholine steroid levels in individual serum samples in patients with pre-eclampsia (n=20). The control group of normotensive pregnant women (n=20) was used to estimate the mean and standard deviation. Twelve of the women with pre-eclampsia had a z-score over 2 for at least one of the four phosphocholine steroids. In contrast, only 1 sample from the normotensive women had a z-score over 2. The observation that there are two patterns, one with elevated phosphocholine steroid levels and one without the elevation, suggests that there may be two different underlying causes of pre-eclampsia. We now need to extend the study to determine which pattern predicts progression to life-threatening hypertension in pregnant women. This pilot study illustrates that it is possible to evaluate individual endogenous cardiotonic hormones without relying on antibodies developed to plant or amphibian toxins.

Bird Fancier’s Syndrome is a rare, non-atopic immunologic response to repeated or intense inhalation of avian (bird) proteins/antigens found in the feathers or droppings of many species of birds, which leads to an immune mediated inflammatory reaction in the respiratory system. Although this is the most common type of hypersensitivity pneumonitis reported in adults, it is one of the classification of a rare subtype of interstitial lung disease that occurs in the pediatric age group of which few case reports are available in the literature. The pathophysiology of hypersensitivity pneumonitis is complex; numerous organic and inorganic antigens can cause immune dysregulation, leading to an immune related antigen-antibody response (immunoglobulin G–IgG- against the offending antigen). Diagnosing Bird Fancier’s disease in the pediatric age group is challenging, history of exposure is usually missed by health care providers, symptoms and clinical findings in such cases are nonspecific and often misdiagnosed during the acute illness with other common diseases such asthma, or acute viral lower respiratory tract infection, and the lack of standardization of criteria for diagnosing such condition, or sensitive radiological or laboratory test. Treatment, on the other hand, is also controversial. Avoidance of the offending antigen could be the sole or most important part of treatment, particularly in acute mild and moderate cases. Untreated cases can result in irreversible lung fibrosis. In this case report, we highlight how children presenting with an acute viral lower respiratory tract infection can overlap with hypersensitivity pneumonitis. Early intervention with pulse steroids markedly improves the patient’s clinical course.

Thyroid hormones regulate tissue metabolism establishing an energy balance in the cell, in particular by affecting oxidative phosphorylation. Their long-term impact is mainly associated with changes in gene expression, while the short-term effects may differ in mechanism. Our work is devoted to short-term effects of hormones T2, T3, and T4 on mitochondrial cytochrome c oxidase (CcO) mediated by a direct contact with the enzyme. The data obtained indicate the existence of two separate sites of CcO interaction with thyroid hormones differing in location, affinity and specificity to hormone binding. It is shown that T3 and T4 but not T2 inhibit oxidase activity of CcO in solution and on membrane preparations with Кi≈100–200 M. In solution, T3 and T4 compete in a 1:1 ratio with the detergent dodecyl-maltoside for binding to the enzyme. Peroxidase and catalase partial activities of CcO are not sensitive to hormones while electron transfer from heme a to the oxidized binuclear center is affected. We believe that T3 and T4 are ligands of the Bile Acid Binding Site found in the 3D structure of CсO by Ferguson-Miller’s group, and hormone induced inhibition is associated with dysfunction of the K- proton channel. Similar conclusion we made recently with regard to steroid-like compounds. It is found that T2, T3, and T4 inhibit superoxide generation by oxidized CcO in the presence of excess Н2О2. Inhibition is characterized by Ki values of 0.3 – 5 M and apparently affects the formation of О2• at the protein surface. The second binding site for thyroid hormones presumably coincides with the point of tight T2 binding on the Va subunit described in the literature.

Steroid analysis is important in the clinical assessment of endocrine function in health and disease. Although tandem mass spectrometry methods coupled with chromatographic separation are considered the gold standard analytical technique in this setting, enabling profiling of multiple steroids in a single sample, sample processing can be labour-intensive. Here we present a simple, efficient automated 96-well Supported Liquid Extraction method with dichloromethane/isopropanol as organic solvent, carried out on a Extrahera automated sample handler (Biotage), which completes sample preparation of 80 plasma samples (200µL) in 90 minutes. Compounds were separated on a Kinetex C18 column (150x3mm;2.6um) using a mobile phase of methanol and water (0.1% formic acid). The run time was 16 minutes on a Nexera uHPLC system (Shimadzu) with a QTrap 6500+ linear ion trap mass spectrometer (AB Sciex). Precisions ranged 8.1 to 18.1% RSD, bias -10.1-5.8%, and extraction recoveries 73.5-111.9%. LOQs ranged between 0.025–0.500 ng/mL.

Background: To evaluate the effect of systemic erythropoietin, as well as oral steroids, in the management of recent onset non-arteritic anterior ischemic optic neuropathy (NAION). Method: Ninety-nine eyes of 99 patients diagnosed with NAION within 5 days of onset were included in this single masked randomized clinical trial. Thirty-four patients were randomized into group 1 (systemic erythropoietin), group 2 (oral steroids), and group 3 (control). Group A received 10,000 units of erythropoietin twice a day for three days. Group B received oral prednisone 75 mg daily for two weeks followed by a tapering dose (70 mg for 5 days, 60 mg for 5 days, and 5 mg reductions thereafter every 5 days). Functional and structural outcomes were analyzed at 3 and 6 months following treatment. Best corrected visual acuity (BCVA) was the main outcome measure, and mean deviation (MD) of visual field (VF) test and peripapillary retinal nerve fiber layer thickness (PRNFLT) were secondary outcome measures. Results:The mean BCVA (±SD) at the time of presentation was 1 ± 0.56, 1.01 ± 0.6, and 0.94 ± 0.47 logMAR in groups A, B, and C, respectively (P = 0.140); corresponding values were 0.72 ± 0.45, 0.83 ± 0.46, and 0.78 ± 0.4 logMAR (P = 0.417), and at 6-month follow-up, they were 0.70 ± 0.44, 0.73 ± 0.35, and 0.75 ± 0.39 logMAR, respectively (P = 0.597). Fifty-five percent of patients in group A vesus 34.3% in group B, and 31.2% in group C had an improvement of at least 3 lines in the BCVA values at the 6th-month follow-up visit. (P= 0.04) The mean deviation (MD) at the time of presentation was 19.67 ± 6.2, 20.83 ± 4.83, and 18.94 ± 6.92 decibels (db), respectively (P= 0.483).The corresponding values at month 3 were 18.22 ± 7.5, 19.82 ± 7.15, and 17.65 ± 7.22 db, (P = 0.848); and at month 6 they were 16.56 ± 7.08, 18.15 ± 6.57, and 15.9 ± 5.97 db, respectively. (P = 0.699) PRNFLT at presentation was 189 ± 58, 193 ± 64, and 199 ± 62 micrometers, respectively (P = 0.779), which decreased to 110 ± 45, 127 ± 37, and 119 ± 37 at month 3 (P = 0.423). The corresponding values for month 6 were 88 ± 12, 74 ± 25, and 71 ± 18, respectively (P = 0.041). Conclusion: The findings of our study indicate the beneficial effects of systemic erythropoietin in preserving the function and structure of the optic nerve in recent onset NAION.

We report the analysis of activation by corticosteroids and progesterone of full-length mineralocorticoid receptor (MR) from elephant shark, a cartilaginous fish belonging to the oldest group of jawed vertebrates. Based on their measured activities, aldosterone, cortisol, 11-deoxycorticosterone, corticosterone, 11-deoxcortisol, progesterone and 19-norprogesterone are potential physiological mineralocorticoids. However, aldosterone, the physiological mineralocorticoid in humans and other terrestrial vertebrates, is not found in cartilaginous or ray-finned fishes. Because progesterone is a precursor for corticosteroids that activate elephant shark MR, we propose that progesterone was an ancestral ligand for elephant shark MR. Although progesterone activates ray-finned fish MRs, progesterone does not activate human, amphibian or alligator MRs, suggesting that during the transition to terrestrial vertebrates, progesterone lost the ability to activate the MR. Comparison of RNA-sequence analysis of elephant shark MR with that of human MR suggests that MR expression in the human brain, heart, ovary, testis and other non-epithelial tissues evolved in cartilaginous fishes. Together, these data suggest that progesterone-activated MR may have unappreciated functions in elephant shark ovary and testis.

Introduction. A needle is inserted into a joint for arthrocentesis or injection of a therapeutic medication(s), commonly a corticosteroid. The aim of this paper is to discuss the first theme identified from a scoping review of corticosteroid injections for the pathology of the first metatarsophalangeal joint. Pathology. The two most common pathologies affecting the first metatarsophalangeal joint are osteoarthritis and bunions. An arthritic joint is regularly injected with a corticosteroid, but bunions are not. Other pathologies that may receive an injection include rheumatoid arthritis, gout, sesamoiditis and post-operative arthrofibrosis. Discussion. Most available evidence discusses corticosteroid injections for osteoarthritis, but there is a paucity of high-quality evidence, especially for corticosteroid use in other pathological conditions. Conclusion. Whilst the evidence base suggests that corticosteroid injections are safe short- and mid-term treatment options for a range of soft tissue and joint pathology, the specific indications, and short/long-term outcomes in the first metatarsophalangeal joint pathologies are not clear and warrant further study.

We set up this preliminary study to evaluate one main question: could strengthening the microbiome have potential benefits for patients suffering with adverse effects after stopping long term topical steroid use? We aim to turn it into a much larger study if the results show promise. After commonly being prescribed for eczema, cessation of topical steroid use, especially after long periods of inappropriate use, can leave lasting adverse effects on the body and skin, known by some as topical steroid withdrawal (TSW). Furthermore, the subsequent withdrawal the body experiences when coming off the drug can leave lasting adverse effects on the body and skin, known by some as topical steroid withdrawal (TSW). This preliminary study involved seven human participants suffering with skin problems associated with TSW who approached Dr. Anja Gijsberts-Veens of their own volition because they were interested in more natural recovery methods. Five completed the study in full. Progress in skin condition was tracked by self-assessed symptom severity questionnaires filled out at the beginning and end of the study. The skin microbiome was addressed by using a 100% natural product shown in previous work to significantly increase skin microbiome biodiversity. Three participants implemented dietary changes and supplementation in response to guidance after fecal sample analysis to improve their gut health and biodiversity. The average improvement in skin symptoms for all participants was 40% and average symptom improvement ranged from 14% for Patient 5 to 92% for Patient 1. On average, the participants saw an improvement in 85% of their symptoms and a stagnation or regression in 11% and 4% respectively. We believe these results show enough promise to warrant expansion of this research to use a larger sample size, preferably 50+ participants, in future work. We also aim to swab the skin of participants to assess the effect on the skin microbiome from skin and gut treatments, as well as including more in-depth analysis of skin and gut microbiomes.

Maintenance of integrity and function of the gastric mucosa (GM) requires a high regeneration rate of epithelial cells during the whole life span. The health of the gastric epithelium highly depends on redox homeostasis, antioxidant defense and activity of detoxifying systems within the cells as well as robustness of blood supply. Bioactive products of lipid peroxidation, in particular second messengers of free radicals, the bellwether of which is 4-hydroxynonenal (HNE), are important mediators in physiological adaptive reactions and signaling but they are also thought to be implicated in the pathogenesis of numerous gastric diseases. Molecular mechanisms and consequences of increased production of HNE and its protein adducts in response to stressors during acute and chronic gastric injury are well studied. However, several important issues related to the role of HNE in gastric carcinogenesis, tumor growth and progression, the condition of GM after eradication of Helicobacter pylori, or the relevance of antioxidants for HNE-related redox homeostasis in GM still need more studies and new comprehensive approaches. In this regard, preclinical studies and clinical intervention trials are required, which should also include the use of state-of-the-art analytical techniques such as HNE determination by immunohistochemistry and ELISA as well as modern mass-spectroscopy methods.