Concentrations Of Hydrocortisone Research Articles

Differential effects of acute and chronic hydrocortisone treatment on pyroptosis

Pyroptosis is a programmed and inflammation-inducing cell death that occurs predominantly in macrophages. It is characterized by the inflammasome-mediated activation of caspase-1, leading to cell lysis. During pyroptosis, pro-inflammatory mediators such as IL-1β are released extracellularly to further recruit and activate other immune cells. Thus, pyroptosis plays a crucial role in the prevention of the spread of pathogens. The clinically applied synthetic glucocorticoid, hydrocortisone (HC), has strong immunoregulatory properties. It may act as an immunosuppressive agent by negatively regulating pro-inflammatory gene transcription but has also shown immune-sensitizing properties. The conditions that determine the immunosuppressive or immune-sensitizing actions of HC during an infection are not fully clear. We hypothesized that the outcome may differ depending on the onset and duration of its administration. Therefore, we investigated the impact of acute (treatment upon infection) and chronic (24 h pre-treatment before infection) HC treatment on pyroptosis induction and execution in THP-1 macrophage-like cells. The focus was on pyroptosis-associated signaling pathways, inflammasome assembly and activation, IL-1β, and cell death. Physiological HC concentration and HC deprivation were used as controls. Compared to the physiological concentration, cells displayed augmented inflammasome activation and IL-1β release following acute HC treatment. Conversely, the whole pyroptosis machinery was suppressed by chronic HC administration.These in vitro investigations demonstrate pro-inflammatory actions of acute HC exposure and the immunosuppressive effects of chronic treatment. These differential effects on pyroptosis emphasize the importance of individualized HC medication in patients upon infection, and suggest the inclusion of IL-1β as a marker for current immune capacities.

The Physicochemical Compatibility of Sildenafil Injection with Parenteral Medications Used in Neonatal Intensive Care Settings.

Sildenafil is used to treat pulmonary hypertension in neonatal intensive care unit (NICU) settings. As multiple intravenous (IV) medications are co-administered in NICU settings, we sought to investigate the physicochemical compatibility of sildenafil with a range of IV drugs. Sildenafil 600 mcg/mL or 60 mcg/mL was mixed 1:1 with the secondary drug solution to simulate Y-site co-administration procedures. Physical compatibility was evaluated by visual observation against a black and white background and under polarized light for two hours for changes in colour, precipitation, haze and evolution of gas. Chemical compatibility was determined from sildenafil concentrations, using a validated, stability-indicating high-performance liquid chromatography assay. Sildenafil 600 mcg/mL was physicochemically compatible with 29 of the 45 drugs tested at 'high-end' clinical concentrations and physically incompatible with 16 drugs and six '2-in-1' parenteral nutrition solutions. Sildenafil 600 mcg/mL was compatible with lower, clinically relevant concentrations of calcium gluconate, heparin and hydrocortisone. Aciclovir, amoxicillin, ampicillin, ibuprofen lysine, indometacin, phenobarbitone and rifampicin were incompatible with sildenafil 600 mcg/mL, however these IV medications were compatible with sildenafil 60 mcg/mL. Sildenafil 600 mcg/mL and 60 mcg/mL were incompatible with amphotericin, flucloxacillin, furosemide, ibuprofen, meropenem and sodium bicarbonate. Sildenafil compatibility with commonly used syringe filters was also investigated. Sildenafil solution was compatible with nylon syringe filters, however, absorption/adsorption loss occurred with polyethersulfone and cellulose ester filters.

Effectiveness of a New Active Tear Substitute Containing 0.2% Hyaluronic Acid and 0.001% Hydrocortisone on Signs and Symptoms of Dry Eye Disease by Means of Low- and High-Tech Assessments.

An innovative eye drops formulation containing 0.2% hyaluronic acid and a low concentration of hydrocortisone (0.001%; hereafter HALH) has been recently placed on the market (Idroflog®, Alfa Intes, Italy) to manage the dysregulated parainflammation in patients with dry eye disease (DED). In the present paper, the effectiveness of HALH on the signs and symptoms of DED was retrospectively evaluated and compared with that one obtained using standard tear substitutes (STS) by means of low- and high-tech (Keratograph®) assessments. This was a multicenter retrospective study carried out between February and April 2023, involving adult patients with DED diagnosis owing to post-cataract surgery, meibomian gland dysfunction, allergy, or glaucoma medications. The primary aim was to compare the changes induced by different therapies on Keratograph® parameters (noninvasive Keratograph tear breakup time [NIKBUT], tear meniscus height [TMH], eyelid meibography, conjunctival hyperemia, and conjunctivochalasis) or collected by traditional low-tech measures (tear breakup time [TBUT], Schirmer test, Efron score, and epithelial alterations) and the Ocular Surface Disease Index score. Data from 155 patients were analyzed. The effectiveness of HALH and STS was reported by both high- and low-tech measures. NIKBUT-first showed a significant improvement in the HALH group versus the STS one at 15days (6.4 ± 3.6 vs 5.4 ± 3.7s, p = 0.02), whereas this difference was latent with low-tech TBUT until 45days (6.8 ± 2.6 vs 5.6 ± 2.3s, p = 0.03). Patients with DED occurring after cataract surgery reported an enhanced activity of HALH versus STS, particularly for NIKBUT-first, TMH, Schirmer test, and hyperemia stage. These findings highlighted the effectiveness of HALH in all DED subtypes, especially in patients with post-cataract surgery, as well as its superiority versus STS in terms of tear film stability improvement. We recommend longer observation (i.e., 3-6months) to fully ascertain whether the early improvement detected by high-tech measures will be confirmed in subsequent time points even using low-tech tests.

MXene fibers-based molecularly imprinted disposable electrochemical sensor for sensitive and selective detection of hydrocortisone

A molecularly imprinted electrochemical sensor based on MXene fibers was proposed in this work. Firstly, the wet spinning technique prepared MXene fibers with a large aspect ratio, which can make the sheet-like MXene uniformly arranged, avoiding the agglomeration of MXene and improving the electrical conductivity. Afterwards, molecularly imprinted polymers (MIPs) with specific recognition sites were synthesized on the surface of MXene fibers using the electro-polymerization method. The electrochemical sensor utilized the advantages of MXene fibers and molecular imprinting techniques to gain superior selectivity and sensitivity of hydrocortisone (HC). Electrochemical tests with different concentrations of HC (0.5 nM–10.0 μM) under optimal measurement conditions exhibited excellent linearity and a limit of detection (LOD) of 0.17 nM. Furthermore, the electrochemical sensor displayed excellent selectivity, interference resistance, reproducibility, stability and outstanding application performance in serum. This work has promising applications in trace analysis in real sample.

Towards point-of-care manufacturing and analysis of immediate-release 3D printed hydrocortisone tablets for the treatment of congenital adrenal hyperplasia

Hydrocortisone (HC) is the preferred drug in children with congenital adrenal hyperplasia due to its lower potency as well as fewer reports of side effects. Fused deposition modelling (FDM) 3D printing holds the potential to produce low-cost personalised doses for children at the point of care. However, the compatibility of the thermal process to produce immediate-release bespoke tablets for this thermally labile active is yet to be established. This work aims to develop immediate-release HC tablets using FDM 3D printing and assess drug contents as a critical quality attribute (CQA) using a compact, low-cost near-infrared (NIR) spectroscopy as a process analytical technology (PAT). The FDM 3D printing temperature (140 °C) and drug concentration in the filament (10%-15% w/w) were critical parameters to meet the compendial criteria for drug contents and impurities. Using a compact low-cost NIR spectral device over a wavelength of 900–1700 nm, the drug contents of 3D printed tablets were assessed. Partial least squares (PLS) regression was used to develop individual calibration models to detect HC content in 3D printed tablets of lower drug contents, small caplet design, and relatively complex formula. The models demonstrated the ability to predict HC concentrations over a wide concentration range (0–15% w/w), which was confirmed by HPLC as a reference method. Ultimately, the capability of the NIR model had preceding dose verification performance on HC tablets, with linearity (R2 = 0.981) and accuracy (RMSECV = 0.46%). In the future, the integration of 3DP technology with non-destructive PAT techniques will accelerate the adoption of on-demand, individualised dosing in a clinical setting.

Dispersibility and surface properties of hydrocortisone-incorporated self-assemblies

The ability of lipidic self-assembly systems to solubilize hydrophobic drugs allows for the enhancement of the delivery of poorly water-soluble drugs. Hydrophobic molecules are incorporated into the lipidic part of the self-assemblies, which alters their structure and surface properties, affecting their dispersibility. The effects of the incorporation of hydrophobic molecules on the structure of aqueous dispersions of amphiphiles should be precisely investigated. However little work has been done regarding the effects of drug incorporation on the surface and internal properties of lipidic self-assemblies. Herein, the effects of the incorporation of the hydrophobic drug, hydrocortisone (HC), on dispersions composed of monoolein (MO), oleic acid (OA), and Pluronic F127 (F127) are investigated. Via Raman spectroscopic analysis, HC was shown to be homogeneously distributed in the particles. This revealed that the incorporated HC had minimal effects on the lipid packing state in the self-assemblies. The HC-incorporated particles were dispersive for at least 24 h, although aggregation might happen after long incubation (couple of days). Cryogenic transmission electron microscopy images revealed particles with altered inner structure after HC incorporation. HC increased the size of the particles, suggesting that HC could reorganize the molecules in the dispersions. The absolute zeta potential values of the particles decreased by increasing the HC loading, suggesting an increased hydrophobicity of the HC-loaded particles. Laurdan fluorescence analysis revealed that the localized polarity of the dispersions turned to be more hydrophobic with increased HC concentrations. These results suggest that hydrophobic drugs, like HC, certainly influence the surface properties and inner structure of the self-assemblies, resulting in the changes in the particles’ dispersibility. The characterization method using fluorescent probe-based analysis and Raman spectroscopy is effective in revealing how the physicochemical properties of the self-assemblies contribute to understanding the dispersibility of nanocarriers encapsulating hydrophobic drugs.

Evaluation of the effect of glucocorticoid treatment on adrenocortical functions by monitoring endogenous hydrocortisone in horses.

Glucocorticoid preparations have anti-inflammatory effects, and are commonly used in the equine clinical setting; however, such treatments can cause a number of side effects. Adrenal insufficiency is an adverse effect induced by the suppression of adrenal function following drug administration. This study aimed to investigate the influence of two glucocorticoid preparations, dexamethasone and hydrocortisone, on adrenocortical function in horses. The usual doses of dexamethasone and hydrocortisone preparations in equine practice were administered intramuscularly to six horses, and peripheral blood was collected at different time points. Concentrations of dexamethasone and hydrocortisone in the plasma, before and after drug administration, were measured using liquid chromatography-tandem mass spectrometry. Considering circadian rhythms in endogenous hydrocortisone levels, hormone concentrations, before and after drug administration, were compared at the same time of the day. Plasma dexamethasone concentrations were below the limit of quantification at 72 hr post-administration. Plasma hydrocortisone concentrations were significantly lower from 1 to 72 hr after administration. After hydrocortisone preparation administration, plasma hydrocortisone levels were significantly higher until 9 hr, and significantly lower at 24 and 48 hr. The suppression rate of endogenous hydrocortisone ranged over 2.2-5.3% with dexamethasone treatment and 17.5-45.7% with hydrocortisone treatment. The study clearly indicated the effects of glucocorticoids on adrenocortical function in horses and provided basic knowledge about the selection and prescription of glucocorticoid preparations and setting the withdrawal times in equine clinical setting.

Cortisol modulates Ca2+ signaling and acrosome reaction in human sperm.

Stress and elevated cortisol levels have negative effects on fertility, although there is controversy about the effect of cortisol on human sperm. One study reported that hydrocortisone (HC), the synthetic form of cortisol, does not activate CatSper channel but is able to inhibit its activation by progesterone (Pg). However, subsequent reports showed that HC has an agonist effect on CatSper, producing intracellular Ca2+ ([Ca2+ ]i ) increases. These studies were performed using only electrophysiological techniques and fluorometric measurements of Ca2+ . Therefore, it is important to evaluate the effects of different HC concentrations on human sperm physiology using other approaches and techniques. To analyze the effects of different HC concentrations on human sperm physiology and to evaluate the association of perceived stress, anxiety and depression with acrosome reaction (AR), and semen quality. In capacitated human sperm, we tested the effects of HC on [Ca2+ ]i mobilization and AR. Furthermore, the perceived stress and symptoms of anxiety and depression were evaluated with standardized psychometric tests. HC induces a low increase in [Ca2+ ]i compared to Pg response while, at higher concentrations, HC inhibits the Pg-induced Ca2+ response. Also, low concentrations of HC induce AR and when co-incubating it with Pg, the percentages of AR are decreased. Finally, the anxiety symptoms are negatively correlated with Pg induced AR and semen quality. HC has an agonist effect on [Ca2+ ]i mobilization and AR. However, our data also suggest that HC may compete for the binding site of Pg. Additionally, the association between anxiety and decreased AR could be explained by high cortisol levels. Our data showed that HC interferes with the Pg action. Therefore, the negative correlation between anxiety symptoms and Pg-induced AR is due to the accompanying high cortisol levels of this condition and its competitive action with Pg.

Hydrocortisone-Containing Animal-Derived Food Intake Affects Lipid Nutrients Utilization.

As the tremendous increases in consumption of animal-derived food, endogenous hydrocortisone migrating along the food chain to organism arouses extensive attention. This study aims to investigate the cumulative impacts of dietary hydrocortisone intake and mechanistic understanding on metabolism of lipid nutrients. A total of 120 porcine muscles samples with different concentrations of hydrocortisone are collected at three time points. An operational food chain simulation framework is constructed and 175 lipid molecules are identified by UHPLC-Q-Orbitrap HRMS. Compared to the control group, 66 lipid molecules are significantly different, including 17 triglycerides and 31 glycerophospholipids. Integrated analyses of lipidomics and proteomics indicate that hydrocortisone promotes adipose triglyceride lipase and hormone sensitive lipase activity to precondition for triglycerides hydrolysis. Quantitative lipidomics analysis shows the presence of hydrocortisone decreases the concentration of docosahexaenoic acid (3.66 ± 0.15-3.09 ± 0.12mgkg-1 ) and eicosapentanoic acid (0.54 ± 0.09-0.48 ± 0.06mgkg-1 ). A noteworthy increase of most saturated triglycerides concentration with the prolonging of time is observed. Hydrocortisone originating from animal-derived food induces glycerophospholipids degradation and triglycerides hydrolysis through promoting adipose triglyceride lipase, hormone sensitive lipase, and phosphoglycerate kinase activity and further intervenes lipid nutrients utilization.

Hydrocortisone을 담지한 Chitosan silver nanoparticles의 약물흡수 및 방출

The final goal of this research was to improve a treatment for allergy rhinitis using chitosan-hydrocortisone silver nanoparticles based on hydrocortisone-deposited chitosan. The nanoparticles were produced by depositing hydrocortisone in chitosan, generating a reaction with highly reactive silver, and placing the nanoparticles into the nasal mucosa. Silver nanoparticles were manufactured after chitosan deposition and the optimal hydrocortisone concentration supporting the highest drug delivery efficiency was identified. For efficient DDS(Drug Delivery Systems applications, an adsorption experiment was performed before silver nanoparticle production according to the hydrocortisone concentration. In addition, a release experiment with different amounts of silver salt was performed to determine the optimal hydrocortisone and silver salt concentrations for producing chitosan-hydrocortisone silver nanoparticles. The amount released was investigated as a parameter of time. When the hydrocortisone concentration was 0.05g, the chitosan adsorption rate was highest at 48%. A release experiment was conducted at 36℃ in PBS, which is similar to the human body condition, while changing the silver salt amount. At approximately 60 hours, the absorbance was constant, indicating that hydrocortisone was emitted from the chitosan particles. In the cases of the 50㎕ reaction and 100㎕ reaction, the release rate was 14.17% and 12.92%, respectively. Otherwise, in the case of using 10㎕ silver salt solution for the reaction, 99.6% of the amount absorbed was released, showing the highest efficiency as a drug delivery agent.

Assessment of Sub Lethal Toxicity of Hydrocortisone (C21H30O5): Physiological and Hematological Biomarker Reactions on Anabas Testudineus

Application of wide range of pharmaceuticals is a serious threat to the environment causing a significant deterioration of aquatic faunal health as well as its survival status. The widespread detection of various types of drugs (antibiotics, nonsteroidal anti-inflammatory drugs, beta-blockers, etc.) present in the aquatic ecosystem directly works on physiological parameters at different levels of aquatic organisms especially the bioindicators, fishes. The experiment was carried out to evaluate the exposure of sub lethal concentration of hydrocortisone on oxygen consumption, gill movement, haematological and percentage of bone calcium of the freshwater fish, Anabas testudineus . When compared to control, the exposed fishes exhibit significant alterations in their physiological activity. The rate of oxygen consumption is indirectly proportional to dosage concentration as well as exposure time. Both the rate of gill movement and oxygen consumption were decreased with increasing concentration of hydrocortisone. Under exposure, the marked decline was recorded in both RBCs and Hb count when compared to control (P < .05). The percentage of bone calcium level was significantly decreased by the toxicity of hydrocortisone. The current study stipulates that the exposure of sub lethal concentration of hydrocortisone on Anabas testudineus alters the physiological and hematological parameters. From the results, it is noteworthy that the steroid drug, hydrocortisone even at low concentrations causes deteriorative impacts on the health conditions of aquatic organism. KEYWORDS : Hydrocortisone, oxygen consumption, gill movement, haematology, bone calcium, Anabas testudineus.

Relationship among Serum Hydrocortisone and Impairment in Left Ventricle Diastolic Function with Subjects of Diabetes Mellitus

Background: Diabetes mellitus (DM) is considered main dangerous feature for the expansion of cardiac metabolic and coronary disorders. Chronic Heart failure along conserved ejection fraction (EF %) were distinguished by the dysfunction of left ventricle diastolic phase (LVDD). Aim: Aim of subjects with elevated serum cortisol or hydrocortisone level establish with Cushing’s syndrome has to be related with the progression of the LVDD. Methodology: We select 42 patients Diagnosed with (DM) and 40 subjects with no DM. Which was underwent echocardiography assessment at multiple hospitals of Lahore within two years of duration. The functions of left ventricle were estimate and the percentage of before time diastolic rate from inflow to trans-mitral before time diastolic rate be considered while guide for diastolic purpose. Concentration of serum cortisol in Plasma, glucose levels, serum fasting cholesterol and triglyceride levels, along by means of anti glycemic medications plus additional scientific distinctiveness was estimated, as well as along its relationship among E/A was resolute by means of only one variable and multiple variable analysis. Results: Multiple variable linear regression study illustrate that log of E/A were confidently associated by age factor (P=0.018), blood pressure systolic phase (P=0.003) and hydrocortisone (P=0.037), in subjects of diabetes mellitus. Multiple variable analysis illustrate that hydrocortisone were completely associated by means of age (P=0.016) and glycated hemoglobin (P=0.011). Therefore no relationship found among E/A and serum hydrocortisone levels in control subjects. Conclusion: Raised levels of hydrocortisone concentration might elevate the possibility of rising in subjects of diabetes mellitus. Keywords: Diabetes mellitus, left ventricle diastolic function, serum hydrocortis

Pharmacokinetic Modeling of Hydrocortisone by Including Protein Binding to Corticosteroid-Binding Globulin.

Background: Patients with adrenal insufficiency are treated with oral hydrocortisone (HC) to compensate for the loss of endogenous cortisol production. Intrinsic imperfections of cortisol replacement strategies in mimicking normal cortisol secretion are the underlying cause of the increased morbidity and mortality of patients suffering from secondary adrenal insufficiency (SAI). To improve oral hydrocortisone substitution therapy, a better understanding of its pharmacokinetics (PK) is necessary. The previous PK model did not include protein binding. It is known that protein binding can impact hydrocortisone pharmacokinetics. The aim of this study is to describe HC pharmacokinetics including the protein-binding state using Edsim++ (Mediware, Prague) pharmacokinetic modeling software, paving the way for an in-silico tool suitable for drug delivery design. Methods: A total of 46 patients with SAI participated in a randomized double-blind crossover study Patients randomly received a low dose of HC (0.2–0.3 mg/kg body weight/day) for 10 weeks, followed by a high dose (0.4–0.6 mg/kg body weight/day) for another 10 weeks, or vice versa. Plasma samples were obtained and analyzed for free and total hydrocortisone. Single compartment population pharmacokinetic analysis was performed using an extended Werumeus-Buning model built in Edsim++. This model includes a mathematical approach for estimating free cortisol by Nguyen et al., taking the protein binding of HC to albumin and hydrocortisone-binding globulin (CBG, transcortin) into consideration, as well as different states of CBG which affect binding kinetics to HC. The goodness of fit for observed versus predicted values was calculated. Results and conclusions: Nguyen’s formula for free cortisol estimation was successfully implemented in a pharmacokinetic model. The model shows high Spearman’s correlation for observed versus predicted hydrocortisone concentrations. Significantly higher correlations (Spearman’s r, 0.901 vs. 0.836) between total and free hydrocortisone AUC24 (area-under the curve over 24 h) are found when comparing new and old models. This new model was used to simulate the plasma concentration–time behavior of a more suitable hydrocortisone formulation.

Evaluation of the effect of hydrocortisone in 2D and 3D HEp-2 cell culture

Introduction: Cancer is one of the diseases with the highest incidence globally and that associated with the patient's emotional state, can act positively or negatively in the treatment. Cortisol is a principal primary stress hormone in the human body. The corticoids can increase cell proliferation and reactive oxygen species that contribute to DNA damage. Prolonged exposure to stress can contribute to tissues becoming insensitive to cortisol, the primary human stress hormone. Objective: This study explores cortisol's influence on tumor cell development, particularly in human cells of carcinoma of the human laryngeal (HEp-2). Methodology: HEp-2 cells were exposed to increasing cortisol (hydrocortisone) concentrations for 24 or 48 hours, and cytotoxicity (MTT assay) proliferation assay (crystal violet assay), and immunolabeled 3D culture for fibronectin and FAK were analyzed. Results: The group treated with hydrocortisone showed a significant increase in mitochondrial activity, as for the evaluation by the violet crystal, the treated group showed similar behavior to the control. The 3D culture showed dispersed cells within 24 hours with reduced FAK labeling; however, no changes were observed within 48 hours. Conclusion: Although some cases favored corticosteroid use in cancer patients, a more detailed analysis is necessary before prescribing them.

Measurements of hydrocortisone and cortisone for longitudinal profiling of equine plasma by liquid chromatography-tandem mass spectrometry.

The conventional detection of exogenous drugs in equine doping samples has been used for confirmation and subsequent prosecution of participants responsible. In recent years, alternative methods using indirect detection have been investigated due to the expanding number of pharmaceutical agents available with the potential of misuse. The monitoring of endogenous biomarkers such as hydrocortisone (HC) has been studied in equine urine with an international threshold of 1 μg/ml established; however, there is no current threshold for equine plasma. The aim of this research was to investigate plasma concentrations of HC and cortisone (C) in race day samples compared to an administration of Triamcinolone Acetonide (TACA). The reference population (n = 1150) provided HC (6 to 145 ng/ml) and C (0.7 to 13 ng/ml) levels to derive the HC to C ratio (HC/C). Population reference limits (PRLs) were proposed for HC/C values at 0.2 (lower) and 61 (upper). Administration of TACA resulted in down‐regulation of HC/C values below the estimated PRLs for up to 96 h post‐administration. This indirect detection period was longer than the detection of TACA for 72 h. The use of individual reference limits (IRLs) for HC/C values was investigated to support the Equine Biological Passport (EBP), an intelligence model developed by Racing NSW for longitudinal monitoring of biomarkers.

Hydrocortisone Long-term Treatment Effect on Immunomodulatory Properties of Human Adipose-Derived Mesenchymal Stromal/Stem Cells.

Cortisol is secreted in prolonged stress and has therapeutic effects in inflammatory diseases. Considering the immunomodulatory effects of mesenchymal stem cells, here we investigated the effect of hydrocortisone (HC) long-term treatment on immunomodulatory properties of human adipose-derived mesenchymal stromal/stem cells (ASCs). Isolated ASCs from healthy subjects were treated with different HC concentrations for 14 days. The effect of HC-treated ASCs on the proliferative response of peripheral blood mononuclear cells (PBMCs) was evaluated in ASCs/2-way mixed leukocyte reaction coculture using 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT)-assay. HC-treated ASCs were further divided into interferon gamma (IFN-γ) stimulated and unstimulated groups. Transforming growth factor beta 1 (TGF-β1) and interleukin (IL)-6 levels were measured in culture supernatants by enzyme-linked immunosorbent assay. Relative expression of cyclooxygenase-2 (COX-2), hepatocyte growth factor, indoleamine dioxygenase, and programmed death-ligand 1 genes was assessed by real-time PCR. Levels of TGF-β1 and COX-2 expression were elevated in unstimulated ASCs, while exposure to high concentration of HC significantly increased TGF-β1 levels and reduced COX-2 expression. Unstimulated HC-5-μM-treated ASCs increased PBMC proliferation ratio on day 2 of coculture compared to the control group (P = 0.05). In IFN-γ stimulated condition, pretreatment with HC-5 μM resulted in a significantly increased IL-6 and significantly decreased COX-2 expression compared to the HC untreated control group. In conclusion, our results showed various alterations of ASC immunomodulatory related features as a result of long-term exposure of different concentrations of HC. It seems that HC at low concentration pushed the balance toward extended immune response in ASCs, while this observation wasn't persistent in ASCs treated with higher concentrations of HC.

Effects of hydrocortisone-presensitized sugammadex on recovery from neuromuscular blockade induced by rocuronium: a rodent in vivo study.

BackgroundSugammadex is a specific antagonist of aminosteroidal neuromuscular blocking agents with 1:1 binding to guest molecules. Sugammadex can also bind to other drugs having a steroid component in its chemical structure. In this in vivo experiment, we investigated the differences in the recovery of rocuronium-induced neuromuscular blockade using sugammadex pre-exposed with two different concentrations of hydrocortisone.MethodsThe sciatic nerves and tibialis anterior muscles of 30 adult Sprague–Dawley rats were prepared for the experiment. The sciatic nerves were stimulated using a train-of-four (TOF) pattern with indirect supramaximal stimulation at 20 s intervals. After 15 min of stabilization, a 250 μg loading dose and 125 μg booster doses of rocuronium were serially administered until > 95% depression of the first twitch tension of TOF stimulation (T1) was confirmed. The study drugs were prepared by mixing sugamadex with the same volume of three different stock solutions (0.9% normal saline, 10 mg/ml hydrocortisone, and 100 mg/ml hydrocortisone). The recovery of rats from neuromuscular blockade was monitored by assessing T1 and the TOF ratio (TOFR) simultaneously until T1 was recovered to > 95% and TOFR to > 0.9.ResultsIn the group injected with sugammadex premixed with a high concentration of hydrocortisone, statistically significant intergroup differences were observed in the recovery progression of T1 and TOFR (P < 0.050).ConclusionsWhen sugammadex was pre-exposed to a high dose of hydrocortisone only, recovery from neuromuscular blockade was delayed. Delayed recovery from neuromuscular blockade is not always plausible when sugammadex is pre-exposed to steroidal drugs.

Screening for drugs potentially interfering with MCT8-mediated T3 transport in vitro identifies dexamethasone and some commonly used drugs as inhibitors of MCT8 activity.

Monocarboxylate transporter 8 (MCT8) is the first thyroid hormone transporter that has been linked to a human disease. Besides genetic alterations other factors might impair MCT8 activity. This study aimed at investigating whether some common drugs having a structural similarity with TH and/or whose treatment is associated with thyroid function test abnormalities, or which behave as antagonists of TH action can inhibit MCT8-mediated T3 transport. [125I]T3 uptake and efflux were measured in COS-7 cells transiently transfected with hMCT8 before and after exposure to increasing concentrations of hydrocortisone, dexamethasone, prednisone, prednisolone, amiodarone, desethylamiodarone, dronedarone, buspirone, carbamazepine, valproic acid, and L-carnitine. The mode of inhibition was also determined. Dexamethasone significantly inhibited T3 uptake at 10μM; hydrocortisone reduced T3 uptake only at high concentrations, i.e. at 500 and 1000μM; prednisone and prednisolone were devoid of inhibitory potential. Amiodarone caused a reduction of T3 uptake by MCT8 only at the highest concentrations used (44% at 50μM and 68% at 100μM), and this effect was weaker than that produced by desethylamiodarone and dronedarone; buspirone resulted a potent inhibitor, reducing T3 uptake at 0.1-10μM. L-Carnitine inhibited T3 uptake only at 500mM and 1M. Kinetic experiments revealed a noncompetitive mode of inhibition for all compounds. All drugs inhibiting T3 uptake did not affect T3 release. This study shows a novel effect of some common drugs, which is inhibition of T3 transport mediated by MCT8. Specifically, dexamethasone, buspirone, desethylamiodarone, and dronedarone behave as potent inhibitors of MCT8.

Kinetics of hydrocortisone sodium phosphate penetration into the human aqueous humor after topical application.

Aim of the studyHydrocortisone is a soft steroid with low anti‐inflammatory properties and a short duration of action, used to manage several ocular conditions. The clinical benefits and side effects associated with hydrocortisone are well documented, but its basic pharmacokinetic in the eye is yet to be fully elucidated. The purpose of this study is to investigate the anterior chamber penetration capabilities of hydrocortisone when used in different concentrations as eye drops treatment.Materials and MethodsThis is a double‐blind, single‐centre, randomised clinical trial performed at the Department of Medicine and Surgery of the University of Perugia (Italy) on consecutive patients who undergone phacoemulsification with intraocular lens implantation. Patients were randomly assigned on the morning of surgery to receive a single instillation of 0.33% (group A) or 0.001% (group B) hydrocortisone sodium phosphate solution. Group of patients C did not receive any treatment and was used to measure the hydrocortisone endogenous levels. Before surgery, one aliquot of aqueous humor for each patient was aspirated. The time of collection for each sample was recorded. Hydrocortisone concentrations were then stratified into six interval classes of 30 minutes each.ResultsThe mean concentration of hydrocortisone was significantly higher in group A (25.2 ± 12.4 ng/mL) compared with group B (7.11 ± 1.51 ng/mL) and compared with the mean hydrocortisone endogenous levels (3.92 ± 1.18 ng/mL) (P < .0001). No statistically significant differences of hydrocortisone mean concentrations between group B and the mean endogenous levels were found.ConclusionsConsidering the frequent need for prolonged topical steroid therapies and the possible consequent undesirable side effects, ophthalmologists should consider the lowest clinically effective dose of hydrocortisone useful to obtain the desired therapeutic effect and in an adequate time, to minimise the amount of steroids into the anterior chamber and to avoid side effects like intra‐ocular pressure increase or cataract development.

Development of a Highly Sensitive Imprinted Electrochemical Sensor for the Detection of Hydrocortisone in Wastewater

The existence of hydrocortisone in water resources is a serious threat to human health. However, the rapid and sensitive detection methods for hydrocortisone in wastewater are still lacking. Meanwhile, due to the weak redox activity of hydrocortisone, electrochemical technique cannot be used to detect hydrocortisone directly. Therefore, molecularly imprinted technique combined with prussian blue nanoparticles was synthesized for detecting HC indirectly in this work. We fabricated a novel and highly sensitive molecularly imprinted sensor based on the polydopamine/electro-reduced graphene oxide, which was used for the specific recognition of hydrocortisone in water samples. The prussian blue nanoparticles were introduced as probes to reflect the concentration of the target. The morphology of the prepared sensors was characterized by the scanning electron microscopy. And the feature of the imprinted electrode was performed by the cyclic voltammetry and differential pulse voltammetry. Under the optimal experimental conditions, the relative current signal of prussian blue decreased linearly with the increase of hydrocortisone concentration with a limit of detection 0.006 nM. Moreover, the imprinted sensor had a much higher affinity towards hydrocortisone than other analogues. Then, this system was successfully applied to determine hydrocortisone in real wastewater samples with workable results.