Chitosan/Pomegranate Seed Oil Emulgel Composition as a New Strategy for Dermal Delivery of Hydrocortisone.

Multifunctional delivery systems capable of modulating drug release and exerting adjunctive pharmacological activity have attracted particular attention. Chitosan (CS) and pomegranate seed oil (PO) appear to be attractive bioactive components framing the strategy of complex therapy and multifunctional drug carriers. This research is aimed at evaluating the potential of CS in combination with PO in studies on topical emulgels containing hydrocortisone as a model anti-inflammatory agent. Its particular goal was to distinguish alterations in anti-inflammatory action followed with drug dissolution or penetrative behavior between the designed formulations that differ in CS/PO weight ratio. All formulations favored hydrocortisone release with up to a two-fold increase in the drug dissolution rate within first 5 h as compared to conventional topical preparations. The clear effect of CS/PO on the emulgel biological performance was observed, and CS was found to be prerequisite for the modulation of hydrocortisone absorption and accumulation. In turn, a greater amount of PO played the predominant role in the inhibition of hyaluronidase activity and enhanced the anti-inflammatory effect of preparation E-3. Emulgels showed a negligible reduction in mouse fibroblasts' L929 cell viability, confirming their non-irritancy with skin cells. Overall, the designed formulation with a CS/PO ratio of 6:4 appeared to be the most promising topical carrier for the effective treatment of inflammatory skin diseases among the tested subjects.

The Association between the rs3747406 Polymorphism in the Glucocorticoid-Induced Leucine Zipper Gene and Sepsis Survivals Depends on the SOFA Score.

The variability in mortality in sepsis could be a consequence of genetic variability. The glucocorticoid system and the intermediate TSC22D3 gene product-glucocorticoid-induced leucine zipper-are clinically relevant in sepsis, which is why this study aimed to clarify whether TSC22D3 gene polymorphisms contribute to the variance in sepsis mortality. Blood samples for DNA extraction were obtained from 455 patients with a sepsis diagnosis according to the Sepsis-III criteria and from 73 control subjects. A SNP TaqMan assay was used to detect single-nucleotide polymorphisms (SNPs) in the TSC22D3 gene. Statistical and graphical analyses were performed using the SPSS Statistics and GraphPad Prism software. C-allele carriers of rs3747406 have a 2.07-fold higher mortality rate when the sequential organ failure assessment (SOFA) score is higher than eight. In a multivariate COX regression model, the SNP rs3747406 with a SOFA score ≥ 8 was found to be an independent risk factor for 30-day survival in sepsis. The HR was calculated to be 2.12, with a p-value of 0.011. The wild-type allele was present in four out of six SNPs in our cohort. The promoter of TSC22D3 was found to be highly conserved. However, we discovered that the C-allele of rs3747406 poses a risk for sepsis mortality for SOFA Scores higher than 6.

The effects of yohimbine and hydrocortisone on selective attention to fearful faces: An fMRI study.

INTRODUCTION: Selective attention to salient emotional information can enable an advantage in the face of danger. The present study aims to investigate the influence of the stress neuromodulators, norepinephrine and cortisol, on selective attention processes to fearful faces and its neuronal activation. METHODS AND MATERIALS: We used a randomized, double-blind, placebo-controlled design. 167 healthy men between 18 and 35 years (mean [SD] age: 25.23 [4.24] years) participated in the study. Participants received either: (A) yohimbine (n= 41), (B) hydrocortisone (n = 41), (C) yohimbine and hydrocortisone (n = 42) or (D) placebo only (n= 43) and participated in a dot-probe task with fearful and neutral faces in an fMRI scanner. RESULTS: We found an attentional bias toward fearful faces across all groups and related neuronal activation in the left cuneus. We did not find any differences between experimental treatment groups in selective attention and its neuronal activation. DISCUSSION: Our results provide evidence that fearful faces lead to an attentional bias with related neuronal activation in the left cuneus. We did not replicate formerly reported activation in the amygdala, intraparietal sulcus, dorsal anterior cingulate cortex, and thalamus. Suitability of the dot-probe task for fMRI studies and insignificant treatment effects are discussed.

In Vitro Profile of Hydrocortisone Release from Three-Dimensionally Printed Paediatric Mini-Tablets.

Three-dimensional (3D) printing is quickly being adopted in pharmaceutics due to the many advantages it offers, including treatment, adaptability, the reduction in waste and the accelerated development of new formulations. In this study, micro-extrusion printing was implemented for the production of modified-release hydrocortisone (HCT) mini-tablets for paediatric patients. For the developed formulations, Gelucire® 44/14 and Precirol® ATO 5 were used as the main inks at three different ratios: 70%/30%, 60%/40% and 50%/50%, respectively. The printing parameters (temperature and pressure) were altered accordingly for each ratio to achieve printability. The printed mini-tablets exhibited excellent printing quality, featuring consistent layer thicknesses and smooth surfaces. Dissolution tests were performed, and the results indicated a successful modified release of HCT from the mini-tablets. In summary, micro-extrusion exhibited favourable processing abilities for powder blends, facilitating quick printing and the fabrication of potential personalized dosages.

The Prevention of Seroma Formation Following Modified Radical Mastectomy by Intravenous Hydrocortisone Injection.

Introduction Seroma formation is the most common complication after modified radical mastectomy (MRM). It leads to increased pain and discomfort, potentially prolonging morbidity and treatment. Various treatment modalities are being used to decrease the incidence of seroma formation. The objective of this study was to compare intravenous hydrocortisone injection versus placebo in patients undergoing MRM in terms of frequency of post-operative seroma formation. Methods This randomized, double-blinded, placebo-controlled study was conducted at Surgical Unit-I, Holy Family Hospital, Rawalpindi, Pakistan from January 2021 to December 2021. A total of 152 female patients were randomly assigned to each of the study and placebo groups. Group I patients received 100 mg of hydrocortisone intravenously while group II patients received one ml of 0.9% normal saline intravenously prior to induction of general anesthesia for MRM. The incidence of seroma formation after 10 days of MRM and total drain volume till their removal was measured in all patients. Results The mean age was 48.42±10.15 in Group I, while it was 47.67±10.75 in Group II. Mean drain output till removal was 99.14±31.01 ml in the hydrocortisone group and 177.57±63.37 ml in the placebo group. Forty-eight patients developed seroma (31.58%), of whom nine received intravenous hydrocortisone and 39 received normal saline (P=0.000). Conclusion Intravenous hydrocortisone is effective in terms of frequency of post-operative seroma formation as compared to placebo in patients undergoing MRM.

Association among childhood adversity and susceptibility to interference during varying salience: two studies in healthy males.

Childhood adversity, a prevalent experience, is related to a higher risk for externalizing and internalizing psychopathology. Alterations in the development of cognitive processes, for example in the attention-interference domain may link childhood adversity and psychopathology. Interfering stimuli can vary in their salience, i.e. ability to capture attentional focus, and valence. However, it is not known if interference by salience or valence is associated with self-reported adversity. In two independent study samples of healthy men (Study 1: n = 44; mean age [standard deviation (SD)] = 25.9 [3.4] years; Study 2: n = 37; 43.5 [9.7] years) we used the attention modulation task (AMT) that probed interference by two attention-modulating conditions, salience and valence separately across repeated target stimuli. The AMT measures the effects of visual distractors (pictures) on the performance of auditory discrimination tasks (target stimuli). We hypothesized that participants reporting higher levels of childhood adversity, measured with the childhood trauma questionnaire, would show sustained interference in trials with lower salience. Due to conflicting reports on the valence-modulation, we tested the valence condition in an exploratory manner. Linear mixed models revealed an interaction between reported childhood adversity and the salience condition across tone presentations in both study samples (Sample 1: p = .03; Sample 2: p = .04), while there were no effects for the valence condition across both studies. Our study suggests that higher self-reported childhood adversity is related to faster processing of target cues during high salience, but slower during low salience conditions. These results hint to the mechanisms linking childhood adversity and psychopathological symptoms in the attentional domain.

Hydrocortisone reduces altruistic punishment in healthy men.

Psychosocial stress modulates social cognition and behavior in humans. One potentially mediating factor is cortisol as part of the human endocrine stress response. With a double-blind, placebo-controlled between-subject study design, we tested possible dose-dependent effects of hydrocortisone (0 mg, 5 mg and 20 mg) in 85 healthy males. During a socio-economic decision-making task we measured trust, trustworthiness, sharing, punishment, and non-social risk behavior. Social value orientation (SVO) was also assessed. We observed significantly lower levels of punishment after hydrocortisone, especially in the 20 mg group. Drug-induced salivary cortisol correlated negatively with punishment behavior. None of the other facets of social behavior or the SVO were affected by hydrocortisone. Our results suggest that hydrocortisone reduces the propensity to punish unfair behavior. Future studies are needed to further disentangle the role played by various psychobiological mechanisms within the stress response as well as their complex interplay on social behavior and cognition.

Exploring sexual function in adrenal insufficiency: findings from the Dual RElease hydrocortisone versus conventionAl glucocorticoid replaceMent therapy in hypocortisolism (DREAM) trial.

BACKGROUND: Data on sexual function in patients with adrenal insufficiency are scarce and largely controversial. OBJECTIVES: To investigate sexual dysfunction in patients with primary and secondary adrenal insufficiency and the effects of switching to once-daily dual-release hydrocortisone on sexual function in outcome assessors blinded, randomized, multicenter, active comparator clinical trial. MATERIALS AND METHODS: Eighty-nine adrenal insufficiency patients on conventional, multiple daily doses of glucocorticoid replacement, enrolled in the Dual RElease hydrocortisone versus conventionAl glucocorticoid replaceMent in hypocortisolism (DREAM) trial, were randomly assigned to continue their therapy or to switch to an equivalent dose of dual-release hydrocortisone. Sixty-three patients (34 women) consented to sex steroid measurements and questionnaires completion for quality of life (Addison's disease-specific quality-of-life questionnaire) and sexual function evaluation (female sexual function index for women, International Index of Erectile Function-Erectile Function for men) at baseline and 24 weeks after randomization. RESULTS: At baseline, sexual dysfunction was observed in 41% of women and 59% of men with adrenal insufficiency. In both sexes, no associations were found between sexual function and hormone levels, whereas Addison's disease-specific quality-of-life questionnaire total and fatigue domain scores positively correlated with total female sexual function index and International Index of Erectile Function-Erectile Function scores. At 24 weeks, there was no significant difference either in sexual function or sex steroid levels between study groups. In the dual-release hydrocortisone group, the variation in the female sexual function index desire domain score was positively associated with the change in Addison's disease-specific quality-of-life questionnaire's symptom domain score (ρ = 0.478, p = 0.045). DISCUSSION: Sexual dysfunction is common in adrenal insufficiency patients and is likely explained by multiple factors. dual-release hydrocortisone treatment is not directly associated with sexual function improvement, but an indirect effect mediated by quality-of-life amelioration cannot be excluded.

Cardiac GR Mediates the Diurnal Rhythm in Ventricular Arrhythmia Susceptibility.

RATIONALE: Ventricular arrhythmias (VAs) demonstrate a prominent day-night rhythm, commonly presenting in the early morning. Transcriptional rhythms in cardiac ion channels accompany this phenomenon, but their role in the morning vulnerability to VAs and the underlying mechanisms are not understood. OBJECTIVE: The objectives are to investigate the recruitment of transcription factors to time-of-day differentially accessible chromatin that underpins day-night ion channel rhythms and to assess the significance of this for the heart's day-night rhythm in VA susceptibility. METHODS AND RESULTS: Assay for transposase-accessible chromatin with sequencing performed in mouse ventricular myocyte nuclei at the beginning of the inactive (zeitgeber time, time of lights on, start of sleep period) and active (time of lights off, start of awake period [ZT12]) periods revealed differentially accessible chromatin sites annotating to rhythmically transcribed ion channels and transcription factor binding motifs in these regions. Notably, motif enrichment for the glucocorticoid receptor (GR; transcriptional effector of corticosteroid signaling) binding site in open chromatin profiles at ZT12 was observed, in line with the well-recognized ZT12 peak in circulating corticosteroids. Molecular, electrophysiological, and in silico biophysically detailed modeling approaches demonstrated GR-mediated transcriptional control of ion channels (including Scn5a underlying the cardiac Na+ current, Kcnh2 underlying the rapid delayed rectifier K+ current, and Gja1 responsible for electrical coupling) and their contribution to the day-night rhythm in the vulnerability to VA. Strikingly, both pharmacological block of GR and cardiomyocyte-specific genetic knockout of GR blunted or abolished ion channel expression rhythms and abolished the ZT12 susceptibility to pacing-induced VA in isolated hearts. CONCLUSIONS: Our study registers a day-night rhythm in chromatin accessibility that accompanies diurnal cycles in ventricular myocytes. Our approaches directly implicate the cardiac GR in the myocyte excitability rhythm and mechanistically link the ZT12 surge in glucocorticoids to intrinsic VA propensity at this time.

Thermosensitive In Situ Gelling Poloxamers/Hyaluronic Acid Gels for Hydrocortisone Ocular Delivery.

This study endeavored to overcome the physiological barriers hindering optimal bioavailability in ophthalmic therapeutics by devising drug delivery platforms that allow therapeutically effective drug concentrations in ocular tissues for prolonged times. Thermosensitive drug delivery platforms were formulated by blending poloxamers (F68 and F127) with low-molecular-weight hyaluronic acid (HA) in various concentrations and loaded with hydrocortisone (HC). Among the formulations examined, only three were deemed suitable based on their desirable gelling properties at a temperature close to the eye's surface conditions while also ensuring minimal gelation time for swift ocular application. Rheological analyses unveiled the ability of the formulations to develop gels at suitable temperatures, elucidating the gel-like characteristics around the physiological temperature essential for sustained drug release. The differential scanning calorimetry findings elucidated intricate hydrogel-water interactions, indicating that HA affects the water-polymer interactions within the gel by increasing the platform hydrophilicity. Also, in vitro drug release studies demonstrated significant hydrocortisone release within 8 h, governed by an anomalous transport mechanism, prompting further investigation for optimized release kinetics. The produced platforms offer promising prospects for efficacious ocular drug delivery, addressing pivotal challenges in ocular therapeutics and heralding future advancements in the domain.

Fabrication of 3D-Printed Hydrocortisone Triple Pulsatile Tablet Using Fused Deposition Modelling Technology.

Hydrocortisone (HC) is the optimal drug for adolescents diagnosed with congenital adrenal hyperplasia (CAH). Because traditional dosage regimens HC are inconvenient, our study used fused deposition modeling (FDM) three-dimensional (3D) printing technology to solve the problems caused by traditional preparations. First, we designed a core-shell structure tablet with an inner instant release component and an outer delayed release shell. The instant release component was Kollicoat IR: glycerol (GLY): HC = 76.5:13.5:10. Then, we used Affinisol® HPMC 15LV to realize delayed release. Furthermore, we investigated the relationship between the thickness of the delayed release shell and the delayed release time, and an equation was derived through binomial regression analysis. Based on that equation, a novel triple pulsatile tablet with an innovative structure was devised. The tablet was divided into three components, and the drug was released multiple times at different times. The dose and release rate of the tablets can be adjusted by modifying the infill rate of the printing model. The results indicated that the triple pulsatile tablet exhibited desirable release behavior in vitro. Moreover, the physicochemical properties of the drug, excipients, filaments, and tablets were characterized. All these results indicate that the FDM 3D printing method is a convenient technique for producing preparations with intricate structures.

Endoscopic Endonasal Trans-Sphenoidal Minimally Invasive Pituitary Surgery with Image Guided Navigation System (Igns): Learning Experience of Ent Surgeon: First Author.

Introduction- Endoscopic minimally invasive pituitary surgery (MIPS) is advantageous over microscopic technique, as it provides superior close up, wide angle view of surgical target area. Image guided navigation system (IGNS) guides the surgeon to localize the lesion. In the present study we analyzed the Image Guided Surgical procedure and outcome of Endoscopic minimally invasive pituitary surgery and shared our experiences regarding disease clearance. MATERIALS AND METHODS: During the period of April 2015 to August 2022 a total 104 patients, diagnosed with pituitary adenoma underwent surgery and further followed up in a multidisciplinary team approach in a tertiary care hospital of Kolkata, India. The data obtained were reviewed statistically to satisfy the study objectives. RESULTS: Total 104 operations were done on 98 patients and total cases taken for calculation and analysis was 98, which consist of 11 microadenomas, 81 macroadenomas. Among 35 patients with normal preoperative hormonal assay, one patient developed postoperative hypopituitarism. Among 6 patients with preoperative hypopituitarism 4 patients (66.6%) recovered after surgery. Overall, 85 cases had total disease clearance as detected on post-operative MRI. In functioning pituitary adenoma (FPA) clinical and endocrinological improvement occurred after primary surgery in 85.36% (n = 35) and after revision surgery it was 84.44% (n = 38). Macroadenomas, giant adenomas were found to have statistically significant higher risk of incomplete disease clearance but large adenomas do not have statistically higher risk of incomplete clearance. CONCLUSION: IGNS requires extra time for setup, but with proper registration of tracker instruments it adds precision to the surgery. IGNS supplements endoscopic visualization with localization of target lesion by real time stereotactic feedback using preset preoperative imaging data, thus increasing accuracy, safety and effectiveness of minimally invasive surgery.

Efficacy of Hydrocortisone, Povidone-Iodine, and Normal Saline as an Irrigating Solution During Surgical Removal of Impacted Mandibular Third Molars: A Randomized Controlled Trial.

Background The surgical removal of mandibular third molars is one of the most common procedures in dentistry. Researchers have extensively studied the treatment of postoperative sequelae such as pain, edema, trismus, and alveolar osteitis throughout the past six decades. Many approaches have been used to address clinical difficulties after third molar surgery, including various flap designs and irrigating solutions. The aim of this study was to compare the effects of three irrigating solutions, hydrocortisone, povidone-iodine, and normal saline, on pain, trismus, and edema following surgical removal of the impacted mandibular third molar. Methodology The study involved 105 participants who required surgical extraction of mandibular third molars. The patients' ages ranged from 18 to 40 years, and they fulfilled the inclusion criteria. Using a simple random sampling technique, they were divided into three groups (group 1: hydrocortisone, group 2: povidone-iodine, group 3: normal saline). The parameters evaluated were edema, pain, and trismus on the second and seventh postoperative days. All data were input into Microsoft Excel (Microsoft® Corp., Redmond, USA) worksheets and analyzed using Stata 17.0 (StataCorp LLC, College Station, USA). The visual analog scale (VAS) score was used to measure postoperative pain, and postoperative swelling was measured using linear measurements from four fixed anatomical points and compared to preoperative values. To assess trismus, the inter-incisal distance was measured in millimeters with a caliper. A p-value of <0.01 was considered statistically significant. Results The mean VAS score for pain in group 1 was lower than the other two groups. The effect of group 1 was significant on the second postoperative day but insignificant on the seventh postoperative day for swelling. The effect of all three groups on trismus was significant on the second and seventh days. Conclusions Hydrocortisone as an irrigating solution showed promising results in managing postoperative swelling in the first 48 hours, but its effect gradually declined by the seventh postoperative day. Additionally, it was effective in controlling postoperative pain and trismus. This suggests that utilizing hydrocortisone as an irrigating solution, compared to povidone-iodine, has been proven to be a significantly effective option in reducing postoperative pain, edema, and trismus resulting from the surgical removal of impacted teeth.

Impaired free recall of neutral but not negative material tested 105 min after cortisol administration.

Pharmacological studies have consistently shown memory retrieval impairment after administration of cortisol, particularly pronounced for emotional laboratory material (i.e. list of emotional words). However, it is unclear how pharmacological elevation of cortisol affects memory retrieval of ecologically-relevant emotional material (i.e. similar to a newspaper article about an emotional event). In the present study, we aimed to explore whether cortisol administration affects the recall of ecologically-relevant emotional and neutral material, and when memory retrieval occurs after a longer delay (105 min). In this double-blind, pseudo-randomized, placebo-control study, 79 participants learned a negative text and a neutral text. Twenty-four hours later, they were administrated either 10 mg of hydrocortisone or placebo. After 105 min, participants engaged in free recall of both texts. The group with cortisol administration showed significantly reduced free recall compared to the placebo group. Interestingly, this memory retrieval impairment was driven by significantly lower recall after cortisol vs. placebo administration for neutral texts, but not negative texts. The current finding suggests that cortisol administration impairs neutral ecologically-relevant material while leaving emotional material unaffected. These divergent findings, compared to existing literature, emphasize the necessity of employing more ecologically validated material to gain a more comprehensive understanding of the intricate interplay between cortisol administration and memory for ecological material.

Customizable orodispersible films: Inkjet printing and data matrix encoding for personalized hydrocortisone dosing.

The aim of this study was to exploit the versatility of inkjet printing to develop flexible doses of drug-loaded orodispersible films that encoded information in a data matrix pattern, and to introduce a specialised data matrix-generator software specifically focused on the healthcare sector. Pharma-inks (drug-loaded inks) containing hydrocortisone (HC) were developed and characterised based on their rheological properties and drug content. Different strategies were investigated to improve HC solubility: formation of ß-cyclodextrin complexes, Soluplus® based micelles, and the use of co-solvent systems. The software automatically adapted the data matrix size and identified the number of layers for printing. HC content deposited in each film layer was measured, and it was found that the proportion of co-solvent used directly affected the drug solubility and simultaneously played a role in the modification of the viscosity and surface tension of the inks. The formation of ß-cyclodextrin complexes improved the drug quantity deposited in each layer. On the contrary, micelle-based inks were not suitable for printing. Orodispersible films containing flexible and low doses of personalised HC were successfully prepared, and the development of a code generator software oriented to medical use provided an additional, innovative, and revolutionary advantage to personalised medicine safety and accessibility.

Corticosteroid in non-COVID-19 induced community-acquired pneumonia, a meta-analysis.

BACKGROUND: Corticosteroid treatment in non-COVID-19 induced Community-acquired pneumonia (CAP) remains inconclusive. OBJECTIVES: We aimed to assess the role of corticosteroid treatment in CAP. METHODS: We conducted a comprehensive search of online databases, including PubMed, Embase, and Cochrane, to identify articles published from January 1, 2000, to May 5, 2023. Double-blind RCTs were selected. Two authors screened studies and extracted data. The evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation approach. RESULTS: We analyzed data from 12 RCTs, involving 2446 patients. Corticosteroids therapy may reduce short-term mortality in patients with severe CAP (sCAP) and shorten the hospital length of stay in patients with CAP. Furthermore, corticosteroids treatment can decrease the risk of requiring mechanical ventilation, developing septic shock and multiple organ dysfunction syndrome (MODS). There were no significant differences between the corticosteroid and control groups concerning gastrointestinal bleeding and nosocomial infection. The use of corticosteroids could increase the risk of hyperglycemia. CONCLUSION: Corticosteroid treatment for sCAP has the potential to provide benefits in reducing short-term mortality, but this conclusion necessitates more evidence. Besides, we found no evidence that strongly prevents us from using corticosteroids in patients with sCAP or those at risk of progressing to sCAP.