Search Results (125)

Bioconversion of cortisone leads to the synthesis of the steroid derivatives 1,9β,17,21-tetrahydroxy-4-methyl-19-nor-9β-pregna-1,3,5(10)-trien-11,20-dione (SCA) and 1,9β,17,20β,21-pentahydroxy-4-methyl-19-nor-9β-pregna-1,3,5(10)-trien-11-one (SCB), which have been identified as biologically active molecules in affections associated with oxidative stress and inflammation, particularly in the skin and eye. To date, the synthesis of SCA and SCB can only be achieved through a biocatalytic approach, following a biotransformation process catalyzed by Rhodococcus rhodnii DSM 43960, a synthetic pathway that adheres to the principles of green chemistry. To further enhance the sustainability of this process, this study demonstrated that SCA and SCB can be synthesized by bioconversion in a complex medium derived from a dual upcycling process involving olive leaves (UOLM). By formulating a medium based on olive leaves, a by-product derived from the previously reported biotechnological production of lactic acid, and using a concentration of 10% v/v UOLM and 1 g/L cortisone at pH 7.5, bioconversion yields of 90 ± 4.5% were achieved, with a predominance of SCB. Investigations into the addition of supplements, such as tryptone, peptone, and corn steep liquor (CSL), to assess potential improvements in yield were conducted, but no significant positive variations were observed. For the first time, bioactive steroids were synthesized from a medium obtained through a dual upcycling process of olive leaves, introducing an innovative method that opens new possibilities for the investigation of a second generation of biosteroids synthesized from lignocellulosic feedstocks. Full article

Background: Inadequate dietary intake of vitamin D, vitamin K, and calcium, as well as sub-optimal sunlight exposure, can lead to bone loss in the general population, and more so in patients with ulcerative colitis, who are burdened by additional predisposing factors for osteoporosis, such as chronic inflammation and cortisone use. However, micronutrient deficiencies, if present, are easily corrected by nutritional intervention. While the relation between calcium and vitamin D and bone metabolism is well known, fewer data are available for vitamin K, for both healthy individuals and patients. The aim of this review is to provide an overview of recent reports focusing on nutritional deficits relevant to the development of osteoporosis/osteopenia in patients affected by ulcerative colitis. Methods: A systematic electronic search of the English literature up to January 2025 was performed using Medline and the Cochrane Library. Results: Despite being central in bone mineralization, data on dietary calcium intake in ulcerative colitis are relatively scarce, deriving mostly from mixed inflammatory bowel disease cohorts. Although lower than controls, dietary calcium intake approaches the recommended daily allowance, which establishes the necessary daily intake of nutrients. Conversely, vitamin D and vitamin K deficiencies are highly prevalent in ulcerative colitis patients. The widely shared opinion that milk and lactose-containing foods, as well as vegetables, worsen diarrhea is a prime determinant of inadequate vitamin D and vitamin K intake. Conclusions: Increased awareness of the importance of nutrition and the common occurrence of nutritional deficits represents the first step for the development of dietary intervention strategies to counteract the increased risk of osteoporosis in ulcerative colitis patients. Full article

Burnout syndrome, which significantly impacts both individual and societal quality of life, is primarily characterized by three key criteria: depersonalization, emotional exhaustion, and low personal accomplishment, all linked to work-related stress. Purpose: Comparative evaluation of urine metabolite patterns that may discriminate the burnout levels and the effects of night shifts on healthcare professionals. The Maslach Burnout Inventory survey was administered to 64 physicians and nurses working day and night shifts, with scores for each criterion recorded. Methods: Urine samples were collected, and metabolomic patterns were analyzed using UHPLC-QTOF-ESI+-MS technology. This analysis employed both untargeted and semi-targeted metabolomics, coupled with multivariate and ANOVA statistics, utilizing the online Metaboanalyst 6.0 platform. Partial Least Squares Discriminant Analysis (PLSDA) was performed, along with VIP values, Random Forest graphs, and heatmaps based on 79 identified metabolites. These were further complemented by biomarker analysis (AUC ranking) and pathway analysis of metabolic networks. Results: The findings highlighted the biochemical effects of night shifts and their correlation with burnout scores from each dimension. Conclusions: This study demonstrated the involvement of three major metabolic pathways in diagnosing burnout: lipid metabolism, particularly related to steroid hormones (cortisol, cortisone, and androsterone metabolites); energetic metabolism, involving long-chain acylated carnitines as transporters of free fatty acids, which play a role in burnout control; and a third pathway affecting catecholamine metabolism (neurotransmitters derived from tyrosine, such as dopamine, adrenaline, and noradrenaline), as well as tryptophan metabolism (serotonin and melatonin metabolites) and amino acid metabolism (including aspartate, arginine, and valine). Full article

Cortisol, known as the “stress hormone”, is vital for stress response, metabolism regulation, and immune function, and salivary cortisone reflects serum cortisol levels. The measurement of salivary cortisone levels has been proposed as an effective alternative method for estimating serum cortisol levels. Objective: This study aimed to evaluate the use of Fourier Transform Infrared Spectroscopy (FTIR) for salivary cortisone identification and quantification and to assess the impact of adding the surfactant TWEEN 80 to the analysis. Methods: Initially, cortisone was diluted in chloroform and methanol (5,000,000 µg/dL). FTIR spectra were obtained, and absorbance characteristics and peaks were identified. The spectrum of this initial dilution was processed using the Savitzky-Golay filter to evaluate peak heights at 1655 cm⁻¹ and 1700 cm⁻¹, and the effect of signal processing on these peaks was assessed. Additionally, two series of dilutions were performed by adding the surfactant TWEEN 80 at two different concentrations, and the effect of the surfactant on the cortisone spectra was evaluated to reduce noise and enhance the signal. Results: The spectra obtained from the cortisone solution were similar to those found in the literature for solid samples. The peak corresponding to the wavenumber range of 1600–1680 cm⁻¹, related to the stretching bands of C=C, was found to be reliable for use in cortisone quantification studies. The standard deviation between the spectra of the same sample was less than 0.01. It was not possible to detect cortisone when TWEEN 80 was added; however, with signal processing, TWEEN 80 could be detected in quantities as low as 0.0033% of the solution. Conclusions: FTIR demonstrates potential as a non-invasive method for cortisone analysis. While Tween 80 aids in the dilution of cortisone in water, it obscures its spectrum. Full article

Background and Clinical Significance: In multiple sclerosis (MS), there are many therapeutic options, but most of the available drugs can cause drug-induced liver injury (DILI) after the first infusions. A wide group of other drugs may induce liver injury, from simple anti-pyretic medication like Acetaminophen to various dietary herb supplements like Ashwagandha. Case Presentation: A 39-year-old female patient, diagnosed with MS, has been previously treated with Glatiramer Acetate and interferon-beta, and is currently undergoing immunomodulatory treatment with natalizumab (infusion no. 81). She had a recent history of an airway infection for which she took 4–5 capsules of Acetaminophen per day for 7 days, along with the consumption of dietary supplement with Ashwagandha herb. She presented with jaundice, pruritus, and lower limb ecchymoses. The laboratory results revealed higher aminotransferase levels, total bilirubin, and alkaline phosphatase. The screening for autoimmune and infectious hepatitis was negative. The scenario of toxic hepatitis induced by recently used drugs (Ashwagandha dietary herb supplement and Acetaminophen) was adequate to start therapy with oral cortisone. The clinical and laboratory results gradually improved, with normal levels of liver enzymes and bilirubin, with no further increase after the discontinuation of corticosteroid therapy and dietary herb supplements. Conclusions: This case highlights the challenges in determining the multiple etiologies and managing acute liver injury in an MS patient on natalizumab, an immunomodulatory drug that can induce liver injury after the first infusions, especially in the context of recent ingestion of hepatotoxic drugs. Full article

Background: Our previous comparison of peripheral blood mononuclear cells (PBMCs) from long-term Transcendental Meditation^® (TM^®) practitioners and matched non-practitioner controls found 200 differentially expressed (DE) genes. Bioinformatics analyses of these DE genes suggested a reduced risk of diseases associated with stress and aging in the TM group. Here we assessed additional signs of reduced stress and aging. Methods: A sample of 15 of the 200 DE genes was studied using qPCR in PBMCs from 40-year TM practitioners (“Old TM”, n = 23) compared to a “Young Control” group (n = 19) and an “Old Control” group (n = 21) of non-meditators. In these three groups, plus a “Young TM”, 12-year practitioner group (n = 26), we also studied EEG-based parameters of cognitive function (the Brain Integration Scale (BIS), and latency of three components of the event-related potential (ERP)). Finally, using LC/MS/MS, we compared persistent levels of cortisol (F) and its inactive congener, cortisone (E), in hair. Results: qPCR analysis showed that 13 of the 15 genes were more highly expressed in Old Controls than in Young Controls. In the Old TM group, 7 of these 13 were lower than in Old Controls. Both TM groups had higher BIS scores than their age-matched controls. The Old TM group had shorter N2, P3a, and P3b latencies than the Old Control group, and latencies in the Old TM group were not longer than in the Young Control group. The Hair F/Hair E ratio was higher in the control subgroups than in their age-matched TM subgroups, and Hair F was higher in the Young Control and combined control groups than in the Young TM and combined TM groups. Conclusions: These results are consistent with reductions in biomarkers of chronic stress and biological age in long-term TM meditators. They are also consistent with results from the previous study suggesting that TM practice lowers energy consumption or leads to more efficient energy metabolism. Full article

Immunotherapy has been widely applied to treat metastatic renal cell cancer patients. Managing the side effects of immunotherapy can be a challenge. Here, we describe a rare presentation of cutaneous anguillulosis during immunotherapy. The patient experienced a rash eruption after receiving immunotherapy for metastatic renal cell cancer. The diagnosis of skin toxicity caused by immunotherapy was rejected after the failure of treatment by cortisone. The travelling history and a laboratory test confirmed the presence of anguillulosis infection. A diagnosis of cutaneous anguillulosis was established. Satisfactory treatment with ivermectin was achieved for cutaneous lesions. Immunotherapy was restored without any skin symptoms. We suggested the possible mechanism of cutaneous demonstration of immune inflammatory syndrome during the immunotherapy of a cancer patient with parasitic infection. It was concluded that a comprehensive search for previous infectious pathogens should be performed to ensure a correct diagnosis and timely treatment. Full article

Background/Objectives: This literature review aims to provide guidance on the treatment of recurrent aphthous stomatitis (RAS) based on studies published over the past 10 years. Methods: This study included randomized clinical trials involving human patients from 2013 and 2023, published in any language. The trials examined both pharmacological and non-pharmacological treatments for aphthous lesions, mainly focusing on the adult population, with pain management as the primary outcome. The research was conducted using PubMed, EMBASE, and CINHAL databases. Results: Most of the 45 analyzed studies focused on non-pharmacological therapies, which led to positive results with minimal adverse effects or contraindications, even when compared to cortisone-based treatments. Laser therapy also showed excellent results, particularly in the immediate post-treatment period. Non-pharmacological therapies appeared to offer the best risk–benefit ratio for patients suffering from RAS. Conclusions: Treatment should be individualized based on the patient’s specific form of RAS, and laser therapy can be used either as a standalone treatment or as an adjunct to other treatments considered in the review. Full article

Background: Native knee joint infections, while uncommon, present a serious condition predominantly instigated by bacteria such as Staphylococcus aureus. Without timely intervention, they can result in joint destruction or sepsis, with risk factors encompassing preexisting medical conditions and iatrogenic procedures. The diagnostic process includes a comprehensive patient history, clinical evaluation, laboratory testing, imaging studies, and microbiological investigations. Treatment typically involves joint aspiration and arthroscopy. This study aims to examine and establish correlations between diagnostic criteria and treatment modalities, enhancing the speed and specificity of future therapeutic strategies. Materials and methods: The present study is a retrospective cohort study conducted at a 1200-bed university clinic between 2007 and 2017, with an in-depth examination of patient details, symptoms, treatments, and outcomes. A scoring system was developed to classify the severity of knee joint impairment, categorizing patients on the basis of hospital stay duration, surgeries, and postoperative factors such as recurring symptoms, pain, and range of motion. Results: This study of 116 patients with knee joint infections revealed that clinical symptoms such as pain, swelling, and effusion are common but not definitive for diagnosis. Laboratory analysis revealed no significant differences in CRP or leukocyte counts between cultures positive or negative for pathogens. Hospital stay and disease severity are influenced by factors such as age, sex, presence of polyarthritis, neutrophil count, and type of pathogen, with higher weight and cortisone treatment associated with poorer outcomes. Conclusions: This study highlights the diagnostic challenges in native knee joint infections, revealing the need for comprehensive approaches given the nonspecificity of clinical symptoms and laboratory findings. This underscores the importance of advancing research through standardized methodologies and prospective studies to increase the accuracy of diagnosis and the effectiveness of treatment in this field. Full article

We report the case of a 78-year-old female patient who received palliative immunotherapy with pembrolizumab and lenvatinib as a treatment of pulmonary and osseous metastatic endometrial carcinoma. Under this therapy, the patient developed dysphagia, thyroiditis with hypothyroidism, myositis, and myocarditis, which required, due to third-degree AV block, the installation of a pacemaker. The patient received high-dose cortisone therapy, a thyroid hormone substitution, and pyridostigmine for symptom control. With this therapy, we saw a significant but not complete regression of symptoms. Ultimately, we could discharge the patient home for an outpatient treatment. The case report is followed by a discussion of the management of immune-related adverse events (irAEs) during pembrolizumab therapy from a geriatric perspective. Elderly patients on pembrolizumab therapy require close monitoring for irAEs, which can present atypically or without symptoms and may be fatal. Non-invasive diagnostics and minimizing hospital stays are essential to preserve the fitness of this vulnerable population. Full article

Grape seed procyanidin extract (GSE) is widely used to promote cardiovascular health and has purported anti-inflammatory properties. Chronic inflammation in the lungs caused by environmental toxins such as tobacco smoking plays a pivotal role in lung cancer development. In a modified phase I lung cancer chemoprevention study conducted in heavy active and former smokers using leucoselect phytosome (LP), a standardized grape seed procyanidin extract complexed with soy phospholipids to enhance bioavailability, three months of LP treatment favorably modulated a variety of surrogate endpoint biomarkers, including markers of cell proliferation. In this correlative study, we further analyzed the effects of LP on cytochrome P450 3A4 (CYP3A4) activities by comparing the endogenous conversions of cortisol and cortisone to 6-beta-hydroxycortisol and 6-beta-hydroxycortisone, respectively, before and after LP treatment and the anti-inflammatory effects of LP in the lung microenvironment of these participants by comparing a profile of inflammatory cytokines and chemokines in matched pre- and post-treatment bronchoalveolar lavage (BAL) fluids. LP treatment did not significantly alter CYP3A4 activity, and three months of LP treatment significantly decreased tumor necrosis factor (TNF), C-C Motif Chemokine Ligand 3 (CCL3) and granzyme B in BAL fluids. Furthermore, post-LP-treatment BAL fluids significantly reduced migration/invasion of various human lung neoplastic cells in vitro. Our findings support the anti-inflammatory effects of GSE/LP in the lung microenvironment and its potential utility for reducing cancerizing forces, as well as driving forces for other common respiratory diseases such as chronic obstructive pulmonary disease and asthma, in the lungs of heavy former and active smokers. Full article

The hydrocortisone-type corticosteroid (HTC) group includes valuable active pharmaceutical ingredients (APIs) such as hydrocortisone, hydrocortisone acetate, cortisone acetate, tixocortol pivalate, prednisolone, methylprednisolone, and prednisone. Unfortunately, those APIs are characterized by low solubility, which hampers their application and reduces their therapeutic efficacy. The low polarity of HTC molecules allows them to form inclusion complexes with various cyclodextrins (CDs); however, as shown in this review, the type of applied CDs has a major impact on the final properties of the formed complex. HTC–CD complexes have been routinely used for over 40 years to achieve various aims. Most frequently, CDs have been utilized as HTC solubilizers and absorption enhancers in pharmaceutical formulations, as well as for separation and analysis by chromatographic and electrophoretic methods. This article reviews the studies describing the synthesis as well as the biological, physiochemical, and structural properties of the inclusion complexes formed between HTC and various cyclodextrins. Full article

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) mainly afflicting young women. Various steroids can influence the onset and development of the disease or, on the contrary, mitigate its course; however, a systematic review of steroidomic changes in MS patients is lacking. Based on the gas chromatography tandem mass spectrometry (GC-MS/MS) platform and, in the case of estradiol, also using immunoassay, this study performed a comprehensive steroidomic analysis in 25 female MS patients aged 39(32, 49) years compared to 15 female age-matched controls aged 38(31, 46) years. A significant trend towards higher ratios of conjugated steroids to their unconjugated counterparts was found in patients, which is of particular interest in terms of the balance between excitatory and inhibitory steroid modulators of ionotropic receptors. Patients showed altered metabolic pathway to cortisol with decreased conversion of pregnenolone to 17-hydroxypregnenolone and 17-hydroxypregnenolone to 17-hydroxyprogesterone and increased conversion of 17-hydroxypregnenolone to dehydroepiandrosterone (DHEA), resulting in lower levels of 17-hydroxyprogesterone, as well as indications of impaired conversion of 11-deoxy-steroids to 11β-hydroxy-steroids but reduced conversion of cortisol to cortisone. Due to over-activation of hypothalamic-pituitary-adrenal axis (HPAA), however, cortisol and cortisone levels were higher in patients with indications of depleted cortisol synthesizing enzymes. Patients showed lower conversion of DHEA to androstenedione, androstenedione to testosterone, androstenedione to estradiol in the major pathway, and testosterone to estradiol in the minor pathway for estradiol synthesis at increased conversion of androstenedione to testosterone. They also showed lower conversion of immunoprotective Δ⁵ androstanes to their more potent 7α/β-hydroxy metabolites and had lower circulating allopregnanolone and higher ratio 3β-hydroxy-steroids to their neuroprotective 3α-hydroxy-counterparts. Full article

Background and Clinical Significance: Licorice (glycyrrhiza glabra) cough syrup intoxication is manifested with refractory hypokalemia, hypertension, and metabolic alkalosis. The transformation of glycyrrhiza glabra metabolic into glycyrrhetic acid after ingestion further inhibits the 11-β-hydroxysteroid dehydrogenase-2 enzyme, impeding the conversion of cortisol into cortisone. The accumulation of cortisol can also stimulate mineralocorticoid receptors, which leads to a pseudo-hyperaldosteronism-like effect. Case Presentation: We report a 60-year-old male patient with licorice intoxication due to the chronic consumption of licorice cough syrup. He exhibited a transient seizure lasting approximately one minute. Initially, hypokalemia (potassium level was 2.0 mmol/L), metabolic alkalosis, and QT interval prolongation with premature ventricular complexes were demonstrated on his electrocardiogram. Despite the administration of both intravenous and oral potassium supplements over two days, there was no significant improvement in hypokalemia. Spironolactone, an aldosterone receptor antagonist, was administered in addition to ongoing potassium supplementation from the 3rd day. This intervention led to a rapid normalization of hypokalemia in one day. The patient was ultimately discharged on the 6th day without any subsequent complications. Conclusions: The licorice-induced chronic intoxication, which led to pseudo-hyperaldosteronism and refractory hypokalemia, was successfully managed with aggressive potassium supplementation and spironolactone treatment. Full article

Pig homeostasis is challenged by stressful production practices, like road transportation. Glucocorticoids (GCs) are mediators of reactive homeostasis, and their concentrations are frequently used as a stress indicator. The adrenocortical activity of fattening female and castrated male pigs was monitored over a 5-day longitudinal study. A bi-factorial experimental design was applied on day 2; 18 pigs in pen 1 were transported for 3 h (T; 1.2 m²/pig), and 18 pigs were kept in pen 2 (NT). Ten pigs from each pen were treated with dexamethasone (T-D or NT-D), and eight with saline solution (T-SS or NT-SS). Adrenocortical activity was assessed by measuring the levels of faecal glucocorticoid metabolites (FGMs) and hair cortisol and cortisone. In T-SS pigs, the level of FGMs was higher after transportation than in NT-SS pigs. The level of FGMs of T-D pigs initially increased but then reached similar levels to those of NT-SS sooner than T-SS. In contrast, hair cortisol and cortisone did not respond to the treatments. Nevertheless, the hair cortisone/cortisol ratio increased due to transport and decreased after dexamethasone administration. Daily faecal sampling proved still more reliable than 60-day hair sampling for assessing adrenocortical activity. Transported pigs recovered their adrenocortical baseline levels within 24 h. Dexamethasone attenuated the response to transport. Full article