Hydrocortisone Hemisuccinate Research Articles

Biotransformation of hydrocortisone succinate with whole cell cultures of Monascus purpureus and Cunninghamella echinulata

Hydrocortisone succinate (1) is a synthetic anti-inflammatory drug and key intermediate in the synthesis of other steroidal drugs. This work is based on the fungal biotransformation of 1, using Monascus purpureus and Cunninghamella echinulata strains. Comopound 1 was transformed into four metabolites, identified as hydrocortisone (2), 11β-hydroxyandrost-4-en-3,17-dione (3), Δ1-cortienic acid (4), and hydrocortisone-17-succinate (5), obtained through side chain cleavage, hydrolysis, dehydrogenation, and oxidation reactions. These compounds have previously been synthesized either chemically or enzymatically from different precursors. Though this is not the first report on the biotransformation of 1, but it obviously is a first, where the biotransformed products of compound 1 have been characterized structurally with the help of modern spectroscopic techniques. It is noteworthy that these products have already shown biological potential, however a more thorough investigation of the anti-inflammatory properties of these metabolites would be of high value. These results not only emphasize upon the immense potential of biotransformation in catalysis of reactions, otherwise not-achievable chemically, but also holds promise for the development of novel anti-inflammatory compounds.

Neurodevelopment at 24 months corrected age in extremely preterm infants treated with dexamethasone alternatives during the late postnatal period: a cohort study

The administration of dexamethasone has been associated with suboptimal neurodevelopment. We aimed to compare the development of extremely premature infants treated or not with alternatives to dexamethasone: betamethasone, hydrocortisone hemisuccinate. This retrospective cohort study included infants born before 29 weeks of gestational age, treated or not with late (day ≥ 7) postnatal steroids (betamethasone, hydrocortisone hemisuccinate). The neurodevelopment outcome was evaluated at 24 months corrected age, after adjustment on comorbidities of extreme prematurity. In order to analyse their overall development, data about growth and respiratory outcomes were collected. Among the 192 infants included, 59 (30.7%) received postnatal steroids. Suboptimal neurodevelopment concerned 37/59 (62.7%) postnatal steroid-treated and 43/133 (38.1%; p = 0.002) untreated infants. However, in multivariable analysis, only severe neonatal morbidity (p = 0.007) and male gender (p = 0.027) were associated with suboptimal neurodevelopment outcome at 24 months. Conclusions: Betamethasone or hydrocortisone hemisuccinate treatment was not an independent risk for suboptimal neurological development, growth and respiratory outcomes assessed at 24 months corrected age in extremely premature infants. Registration number: The study was registered on the ClinicalTrials.gov register: NCT05055193.What is Known:• Late postnatal steroids are used to treat bronchopulmonary dysplasia• Meta-analyses warned against the neurological risk of dexamethasone use during neonatal period. Early or late hydrocortisone hemisuccinate has been evaluated in multiple studies, none of which have reported an adverse effect on neurodevelopment at least to 2 years. Data about the use of betamethasone are scarce.What is New:• The risk of suboptimal neurodevelopment was higher among extremely premature infants who received postnatal steroids when compared to those who did not.• Betamethasone and hydrocortisone hemisuccinate treatment was not an independent risk factor for suboptimal neurodevelopment at 24 months corrected age.

Hypersensitivity to intravenous succinate corticosteroids in patients with nonsteroidal anti-inflammatory drug-exacerbated respiratory disease.

Although there are many case reports of asthma exacerbations with intravenous corticosteroids, especially hydrocortisone succinate, in nonsteroidal anti-inflammatory drug-exacerbated respiratory disease (N-ERD), the frequency and mechanism remain unclear. We hypothesized that N-ERD patients are potentially hypersensitive to succinates, especially succinate corticosteroids, based on the results of previous provocation studies and considered specific mechanisms. The objective of this study was to determine the frequency and mechanism of succinate corticosteroids hypersensitivity in patients with N-ERD. Eleven patients with stable, moderate to severe N-ERD were tested with hydrocortisone sodium succinate (HCs), hydrocortisone sodium phosphate (HCp), methylprednisolone sodium succinate (MPSLs), prednisolone sodium succinate (PSLs), and chloramphenicol sodium succinate (CPs, without a steroidal chemical structure) at doses below the normal dose through intravenous administration using a single-blind test. As a comparison, seven patients with aspirin-tolerant asthma (ATA) also underwent an intravenous provocation test of HCs. The positive intravenous provocation test rates of HCs 100-500 mg, HCp 500 mg, MPSLs 80 mg, PSLs 20 mg, and CPs 500 mg in N-ERD patients were 82% (9/11), 9% (1/11), 50% (5/10), 33% (1/3), and 86% (6/7), respectively. Most positive reactions began with a severe cough within 5 min of intravenous injection. The course of these hypersensitivity symptoms differed from those seen with the usual aspirin challenge test. The HCs 100-500 mg intravenous test was negative in all seven patients with ATA. In conclusion, patients with N-ERD have high rates of potential hypersensitivity to the succinate ester structure, which is not linked to the corticosteroid structure, but to the succinate ester structure. We hypothesized that the mechanism of hypersensitivity observed during rapid intravenous administration of succinate corticosteroids is mast cell activation via succinate receptor stimulation, rather than due to the corticosteroid itself.

A new rat model of chronic relapsing ulcerative colitis with traditional Chinese medicine syndrome of yang deficiency and dampness stagnation

IntroductionChronic relapsing ulcerative colitis (CRUC) is classified as an inflammatory bowel disease, and traditional Chinese medicine (TCM) has been recognized for its therapeutic benefits in treating CRUC. According to TCM principles, the prevailing syndromes in CRUC are yang deficiency and dampness stagnation (YDDS). The objective of this study is to establish a novel animal model of CRUC exhibiting the YDDS syndrome. MethodsInitially, the rats were administered hydrocortisone succinate sodium through subcutaneous injection, followed by the administration of senna folium granule solution. Subsequently, the rats underwent three cycles of dextran sulfate sodium solution ingestion. ResultsUpon completion of the modeling process, it was observed that the disease activity index, colonic mucosal damage index score, colon weight/length ratio, colonic histopathology score, and tissue damage index scores of the model rats were elevated, while the colon length and spleen index exhibited a decrease compared to the control group. The pathological alterations in the model rats included the presence of shallow or deep ulcers and acute or chronic inflammation throughout the process of CRUC modeling. Additionally, our findings indicate a correlation between the proximity of the ulcer to the anal verge, the severity of the lesion, and the presence of precancerous glands, glandular disappearance, crypt abscesses, and tissue destruction. Furthermore, the expression levels of IL6, IL10, IFNG, and TNFA in the colon tissues were significantly elevated in the model rats compared to the control group. Notably, the end-stage lesions observed in CRUC exhibited greater severity when compared to those observed in cases of acute ulcerative colitis. DiscussionIn conclusion, we have successfully developed a rat model of CRUC with YDDS syndrome, which can be utilized to investigate the effectiveness and underlying mechanisms of TCM in treating CRUC.

Adverse Events and Vaccination: Extensive Local Reaction after Anatoxin Vaccine—A Case Report

Post-vaccine adverse reactions are unwanted medical events that concern both the public and healthcare professionals. The objective of this paper is to present a detailed analysis of the case of an extensive local adverse reaction after the administration of a vaccine dose containing diphtheria–tetanus anatoxins. A good knowledge of post-vaccine side effects allows for complete and correct diagnosis, as well as appropriate individualized recommendations. Such an approach contributes to restoring public confidence in vaccines and vaccinations. The patient was a 6-year-old boy, with a history of asthma under chronic treatment with corticosteroids. He developed extensive local inflammatory lesions accompanied by functional disorders of the left arm, which began six hours after the administration of the fifth dose of the diphtheria–tetanus–pertussis–poliomyelitis vaccine. The lesions, which extended to the forearm, were locally treated with antiseptics and systemically treated with hydrocortisone hemisuccinate. They completely remitted within 14 days. Laboratory investigations revealed neutrophilia (6,870 neutrophils/µL), which could be related to the long-term treatment with steroids. The investigation needed the plasma concentration of diphtheria and tetanus anatoxins antibodies and the pro-inflammatory cytokines to be complete.

Protective Effects of Different Doses of Ginsenoside-Rb1 Experimental Cataract Model That in Chick Embryos

Purpose There has been increased interest in phytochemical antioxidants to prevent protein damage and aggregate formation in cataract treatment. In this study, the protective effect of different doses of Rb1 (GRb1), one of the ginsenosides of Panax Ginseng, in the experimental cataract model formed in chick embryos was investigated. Methods Five different experimental groups were formed with 100 SPF fertilized eggs: Control (0.9% NaCl to physiological saline), hydrocortisone hemisuccinate sodium (HC), low dose (HC + L-GRb1 (1 mg/kg)), medium dose (HC+). M-GRb1 (2.5 mg/kg)), and high dose (HC + H-GRb1 (5 mg/kg)). All solutions were given to air sack at 15 days of incubation. On the 17th day, the bulbous oculi of the chick embryos were dissected. Cataract formations of the lenses, glutathione (GSH), malondialdehyde (MDA), total antioxidant (TAS), total oxidant (TOS) levels, Caspase-3 H-score, and TUNEL index were determined. In addition, crystalline alpha A (CRYAA) gene expression was evaluated. Results Cataracts were observed in the control, HC, HC + L-GRb1, HC + M-GRb1, and HC + H-GRb1 groups with a frequency of 0%, 100%, 75%, 56.25%, and 100%, respectively. There were statistically significant differences between the control and HC groups in terms of TAS, TOS, MDA, GSH, Caspase-3 H-score, and TUNEL index (p < .05). When the therapeutic effect of the GRb1 groups was evaluated, the HC group showed significant differences with the HC + L-GRb1 and HC + M-GRb1 groups in almost all parameters (p < .05), while there was no statistical difference with the HC + H-GRb1 group (p > .05). In addition, gene expression levels differed between the groups, although not statistically significant (p > .05). Conclusion 1 mg/kg and 2.5 mg/kg GRb1 applications show therapeutic properties on the HC-induced cataract model. This effect is more pronounced at 2.5 mg/kg.

An extract from the culture of a thermophilic &lt;i&gt;Staphylococcus aureus&lt;/i&gt; strain suppresses allergic inflammation in the airways &lt;i&gt;in vivo&lt;/i&gt; and degranulation of mast cells and basophils &lt;i&gt;in vitro&lt;/i&gt;

Aim. To study the anti-allergic effects of ruzam, an extract from the culture of a thermophilic Staphylococcus aureus strain, in an in vivo model of asthma and its influence on degranulation of mast cells and basophils in vitro.Materials and methods. Allergic asthma in guinea pigs was reproduced by two intraperitoneal injections of ovalbumin followed by a series of inhalations of this antigen for 1.5 months. Ruzam (6 μg / kg) or a reference drug (sodium cromoglycate, 3 mg / kg) was administered daily via a nebulizer during the last 6 days of immunization. One day after completion of inhalations with ovalbumin and compared drugs, changes in the airways were assessed using cytological, morphometric, and histologic methods. Rabbit blood basophils and rat peritoneal mast cells were used to determine the effect of ruzam on IgE-independent degranulation induced by the compound 48 / 80 in vitro. The effect of ruzam was compared with that of hydrocortisone hemisuccinate. Basophils from the blood of ovalbumin-sensitized guinea pigs were used to evaluate the effect of the drug on IgE-dependent degranulation induced by ovalbumin. Granules of mast cells and basophils were detected by alcian blue staining to calculate the degranulation index.Results. In the asthma model, ruzam reduced the degree of airway obstruction by increasing the bronchoalveolar lavage volume returned and suppressed neutrophilic and eosinophilic inflammation, while mobilizing other effector cells of the anti-pathogen immunity (lymphocytes and macrophages). Ruzam has proven to have a stronger anti-allergic effect than sodium cromoglycate by several parameters. At concentrations of 8.4–840 μg / ml, ruzam inhibited degranulation of mast cells and basophils, induced by the compound 48 / 80, equally to hydrocortisone hemisuccinate (10–3 M). At concentrations of 280 and 420 μg / ml, ruzam dose-dependently inhibited ovalbumin-induced degranulation of basophils in sensitized guinea pigs.Conclusion. The anti-allergic effect of ruzam was confirmed in test systems in vivo and in vitro. We speculate here that the TLR2 signaling pathway may be involved in biological and pharmacological effects of this drug.

Discovery of novel inhibitor of 11 beta-hydroxysteroid dehydrogenase type 1 using in silico structure-based screening approach for the treatment of type 2 diabetes.

The current study is aimed to perform structure-based screening of FDA-approved drugs that can act as novel inhibitor of the 11beta- hydroxysteroid dehydrogenase type 1 (11β-HSD1) enzyme. Structural analogs of carbenoxolone (CBX) were selected from DrugBank database and their Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) parameters were investigated by SwissADME. Molecular docking of CBX analogs against 11β-HSD1 was performed by AutoDock tool, their binding patterns were visualized using PyMOL and the interacting amino acids were determined by ProteinPlus tool. Molecular dynamics simulation was performed on the docked structure of 11β-HSD1 (Protein Data Bank (PDB) code: 2ILT) using GROMACS 2018.1. The binding energies of hydrocortisone succinate, medroxyprogesterone acetate, testolactone, hydrocortisone cypionate, deoxycorticosterone acetate, and hydrocortisone probutate were lower than that of substrate corticosterone. The molecular dynamics simulation of 11β-HSD1 and hydrocortisone cypionate docked structure showed that it formed a stable complex with the inhibitor. The Root mean square deviation (RMSD) of the protein (0.37 ± 0.05nm) and ligand (0.41 ± 0.06nm) shows the stability of the ligand-protein interaction. The docking study revealed that hydrocortisone cypionate has a higher binding affinity than carbenoxolone and its other analogs. The molecular dynamics simulation indicated the stability of the docked complex of 11β-HSD1 and hydrocortisone cypionate. These findings indicate the potential use of this FDA approved drug in the treatment of type 2 diabetes. However, validation by in vitro inhibitory studies and clinical trials on type 2 diabetes patients is essential to confirm the current findings.

Nebulized budesonide combined with systemic corticosteroid vs systemic corticosteroid alone in acute severe asthma managed in the emergency department: a randomized controlled trial

BackgroundThe additive benefit of inhaled corticosteroid when used with systemic corticosteroid in acute asthma is still unclear. The objective of this study was to assess the effect of high and repeated doses of inhaled budesonide when combined with the standard treatment of adult acute asthma.MethodsIt was a prospective double-blind randomized controlled study performed in the emergency department (ED) from May 1, 2010 to February 28, 2011 (ClinicalTrials.gov, NCT04016220). Fifty patients were included and were randomized to receive intravenous hydrocortisone hemisuccinate in association with nebulized budesonide (n = 23, budesonide group) or normal saline (n = 27, control group). Nebulization of budesonide or saline was done in combination with 5 mg of terbutaline every 20 min the first hour, then at 2 h (H2), and 3 h (H3). All patients received standard treatment. Efficacy and safety of inhaled budesonide were evaluated every 30 min for 180 min.ResultsA significant increase in peak expiratory flow (PEF) was observed in both treatment groups at evaluation times. The increase in PEF persisted significantly compared to the previous measurement in both groups. There was no significant difference in the PEF between the two groups at evaluation times. There was no significant difference between the two groups in the evolution in the respiratory rate and heart rate. There was also no statistically significant difference between the two groups in the rate of hospitalization, the discharge criteria before the end of the protocol.ConclusionsConsidering its limited power, our study suggests that the association of nebulized budesonide with hydrocortisone hemisuccinate has no additional effect over the use of hydrocortisone alone in adults’ acute asthma managed in the ED.

Daily multidisciplinary COVID-19 meeting: Experiences from a French university hospital

ObjectivesIn March 2020, the World Health Organization declared the coronavirus disease 2019 (COVID-19) a pandemic. In absence of official recommendations, implementing daily multidisciplinary team (MDT) COVID-19 meetings was urgently needed. Our aim was to describe our initial institutional standard operating procedures for implementing these meetings, and their impact on daily practice. MethodsAll consecutive patients who were hospitalized in our institution due to COVID 19, from March 31 to April 15, 2020, were included. Criteria to be presented at MDT meetings were defined as a proven COVID-19 by PCR or strongly suspected on CT scan, requiring hospitalization and treatment not included in the standard of care. Three investigators identified the patients who met the predefined criteria and compared the treatment and outcomes of patients with predefined criteria that were presented during MDT meeting with those not presented during MDT meeting. COVID-19 MDT meeting implementation and adhesion were also assessed by a hospital medical staff survey. ResultsIn all, 318 patients with confirmed or suspected COVID-19 were examined in our hospital. Of these, 230 (87%) were hospitalized in a COVID-19 unit, 91 (40%) of whom met predefined MDT meeting criteria. Fifty (55%) patients were presented at a MDT meeting versus 41 (45%) were not. Complementary exploration and inclusion in the CorImmuno cohort were higher in MDT meeting group (respectively 35 vs. 15%, P=0.03 and 80 versus 49%, P=0.0007). Prescription of hydrocortisone hemisuccinate was higher in group of patients not presented during MDT meeting (24 vs. 51%, P=0.007). Almost half of the patients fulfilling the inclusion criteria were not presented at MDT meeting, which can be partly explained by technical software issues. ConclusionsMultidisciplinary COVID-19 meetings helped implementing a single standard of care, avoided using treatments that were untested or currently being tested, and facilitated the inclusion of patients in prospective cohorts and therapeutic trials.

Determination of lethal dose (LD50) of chromium (Cr), cobalt (Co) and nickel (Ni) in HepaRG cells. Comparison to concentrations found in liver from autopsied prosthesis-bearing patients

Many publications have highlighted the release of metal particles used in the composition of metal-metal prostheses, such as Cr, Co and Ni. They are stored in the liver and can accumulate there. Few data are available on their toxicity in this tissue when present. The cytotoxicity of these 3 heavy metals was investigated in cultures of human hepatocytes cell lines, in order to determine LD50s and to compare to the concentrations found in the liver from 10 autopsied prosthesis-bearing patients. HepaRG is a human hepatoma cell line commonly used as a model for toxicity studies. Cells were cultured in William's E medium with glutamine supplemented with 10% fetal bovine serum, human insulin, hydrocortisone hemisuccinate and penicillin/streptomycin. Differentiation was induced by adding 2% DMSO to nutrient medium. After 14 days, the cells were placed in a 24-well plate in a concentration of 500,000 cells/well. Solutions with ten increasing concentrations of NiCl 2 or CoCl 2 or Na 2 Cr 2 O 7 were incubated with cells for 48 hours at 37 °C. These concentrations were established based on literature data for other hepatocyte models [1] , [2] . Cell viability was evaluated by LDH release (Pierce LDH Cytotoxicity Assay Kit, ThermoFisher) and MTT assay (Vybrant ® MTT cell proliferation assay kit). Concentration response profiles were realized with GraphPad Prism 2.0. Measurements of the heavy metals in liver from autopsied patients were carried out using ICP-HRMS (Element XR, ThermoFisher) after mineralization by microwave (Ultrawave ® , ThermoFisher) [3] . Expected LD50 according to literature data were around 25, 500 and 1000 μM for Cr, Co and Ni, respectively. For Cr, testing concentrations were 0.5, 5, 10, 50, 100, 500, 1000, 5000, 10,000, 50,000 μM. For Co and Ni, they were 10, 50, 100, 250, 500, 1000, 2500, 5000, 10,000, 50,000 μM. The first cytotoxicity assay performed was the LDH release. It measures quantitatively the LDH released in the medium when cells are damaged. But William's E medium is pink and had altered the reading of absorbance. So, results could not be exploited. The MTT assay is carried out on the cell pellet and thus, makes it possible to overcome the culture medium. The dose/response curves for each metal could be realized. Experimental LD50s are 2 μM for Cr, 940 μM for Co, 1380 μM for Ni. The average Cr, Co, Ni concentrations found in the livers of the 10 dead patients carrying prostheses were 0.05, 0.03 and 0.035 μM, respectively. As expected, concentrations found in the liver of autopsied patients are much lower than the experimental LD50. The LD50s were determined for Cr, Co and Ni in HepaRG cells, much higher than concentrations found in the liver from 10 autopsied prosthesis-bearing patients. However, the impact of these elements on hepatocyte metabolism can be reasonably considered at low concentrations. Consequently, further researches using metabolomics approach will be performed.

Antioxidant effects of piperine in in-vivo chick embryo cataract model induced by steroids

Purpose: The etiopathogenesis of steroid-induced cataracts is unknown. One hypothesis is that the higher reactive oxygen species (ROS) levels play an important role in the pathogenesis of several disorders, including the evolution of cataracts. This study investigated the antioxidant effects of piperine in our steroid-induced chick embryo lens model.Methods: The study included 36 specific pathogen-free (SPF) fertilized eggs divided into six groups: phosphate buffer saline (PBS, pH 7.4 Saline Solution (0.9%) isotonic) group (G1), hydrocortisone succinate sodium (HC)-treated group (G2), 100 mg/kg piperine and HC treated group (G3), 50 mg/kg piperine and HC treated group (G4), 25 mg/kg piperine and HC treated group (G5), and 10 mg/kg piperine and HC treated group (G6). On the 15th day of incubation, the SPF eggs in the six groups were removed from the incubator; all were injected using insulin injectors into the chorioallantoic membrane. On day 17, all of the chick embryos were removed from the eggs and all lenses were dissected from the embryos. Cataract formation was evaluated in all lenses, and total antioxidant status (TAS), total oxidant status (TOS), reduced glutathione (GSH), and lipid peroxidation (MDA, malondialdehyde) levels were measured in all lens.Results: The lenses in the G1 group had higher levels of GSH and TAS (p < 0.01), and lower levels of MDA and TOS than the G2 group (p < 0.05 and p < 0.01, respectively). Group 3 had higher levels of GSH and TAS (p < 0.001 and p < 0.001 respectively), and lower levels of MDA and TOS than the G2 group (p < 0.01 and p < 0.001, respectively).Conclusion: Steroid therapy causes a decrease in GSH and TAS levels and an increase in TOS and MDA levels in lens tissues, indicating increased oxidative stress. Piperine exerts its effects as an antioxidant substance, in increasing doses.

Immediate hypersensitivity reaction induced by hydrocortisone hemisuccinate – case report

Introduction. Corticosteroids are a category of drugs, extensively used in the treatment of various pathologies due to a powerful anti-inflammatory effect. Despite being one of the classes of drugs used for the treatment of allergic reactions, corticosteroids may also induce both immediate and delayed hypersensitivity reactions, type I and type IV being most commonly reported in current medical practice. Case report. We present the case of a patient who was admitted to our clinic to investigate an episode of papular erythematous, pruritic skin eruption accompanied by tachycardia and drop of blood pressure, and malaise. Symptomatology started a few minutes after intravenous administration of dexamethasone and hydrocortisone hemisuccinate (HHC) for some prurigo lesions on the lower limbs.The symptomatology resolved after the administration of intravenous adrenaline and H1 antihistamine. We evaluated the patient for atopic status, the investigations performed (total IgE, skin test to common aeroallergens) ruling out the atopic status. We performed prick and intradermal skin testing on HHC and dexamethasone. The evaluation revealed hypersensitivity to HHC and ruled out the one to dexamethasone. Since systemic corticosteroids represent a class of multiple‑use drugs, and there is no therapeutic alternative, we conducted an oral challenge test on dexamethasone, which was negative. Conclusions. Immediate hypersensitivity reactions to HHC are rare. In addressing such a case, cross-reactivities should be considered, and studying the classification of corticosteroid groups is indispensable for making the right decision, giving the patient the chance to use a very important therapeutic class.

SFE/SFEDP adrenal insufficiency French consensus: Introduction and handbook

The French endocrinology society (SFE) and the French pediatric endocrinology society (DFSDP) have drawn up recommendations for the management of primary and secondary adrenal insufficiency in the adult and child, based on an analysis of the literature by 19 experts in 6 work-groups. A diagnosis of adrenal insufficiency should be suspected in the presence of a number of non-specific symptoms except hyperpigmentation which is observed in primary adrenal insufficiency. Diagnosis rely on plasma cortisol and ACTH measurement at 8am and/or the cortisol increase after synacthen administration. When there is a persistant doubt of secondary adrenal insufficiency, insulin hypoglycemia test should be carried out in adults, adolescents and children older than 2 years. For determining the cause of primary adrenal insufficiency, measurement of anti-21-hydroxylase antibodies is the initial testing. An adrenal CT scan should be performed if auto-antibody tests are negative, then assay for very long chain fatty acids is recommended in young males. In children, a genetic anomaly is generally found, most often congenital adrenal hyperplasia. In the case of isolated corticotropin (ACTH) insufficiency, it is recommended to first eliminate corticosteroid-induced adrenal insufficiency, then perform an hypothalamic-pituitary MRI. Acute adrenal insufficiency is a serious condition, a gastrointestinal infection being the most frequently reported initiating factor. After blood sampling for cortisol and ACTH assay, treatment should be commenced by parenteral hydrocortisone hemisuccinate together with the correction of hypoglycemia and hypovolemia. Prevention of acute adrenal crisis requires an education of the patient and/or parent in the case of pediatric patients and the development of educational programs. Treatment of adrenal insufficiency is based on the use of hydrocortisone given at the lowest possible dose, administered several times per day. Mineralocorticoid replacement is often necessary for primary adrenal insufficiency but not for corticotroph deficiency. Androgen replacement by DHEA may be offered in certain conditions. Monitoring is based on the detection of signs of under- and over-dosage and on the diagnosis of associated auto-immune disorders.

Hydrocortisone relieves the immediate post-operative scrotal edema after inguinal varicocelectomy: A prospective clinical trial

This study aimed to assess the effect of a single IM injection of hydrocortisone succinate in relieving the immediate post-varicocelectomy scrotal edema. In all, 117 patients with grades II and III varicocele who developed post-varicocelectomy scrotal edema were randomly classified into group A (n=59) that received a single IM hydrocortisone sodium succinate injection plus ordinary post-operative treatment and Group B (n=58), which received the post-operative treatment alone. All patients were followed up to assess; changes in scrotal edema, the day of return to work and emergence of complications. Post-operative scrotal edema was assessed using a scrotal edema rating grades (SERG=0–3) score. In group A, scrotal edema disappeared 1day after steroid injection in 33 patients (55.9%), and after 2days in the remaining 26 patients (44.1%), and all patients were returned to work within 5–7days. In group B, the edema remained large in 36 patients (62.1%), moderate in 22 patients (37.9%), and disappeared after 9–12days; and those patients returned to work within 11–13days. It is concluded that a single IM hydrocortisone injection could be effective to reduce the immediate post-operative scrotal edema after inguinal varicocelectomy without obvious side effects.

A Comparison of Aerosolization and Homogenization Techniques for Production of Alginate Microparticles for Delivery of Corticosteroids to the Colon

Alginate microparticles incorporating hydrocortisone hemisuccinate were produced by aerosolization and homogenization methods to investigate their potential for colonic drug delivery. Microparticle stabilization was achieved by CaCl2 crosslinking solution (0.5 M and 1 M), and drug loading was accomplished by diffusion into blank microparticles or by direct encapsulation. Homogenization method produced smaller microparticles (45-50 μm), compared to aerosolization (65-90 μm). High drug loadings (40% wt/wt) were obtained for diffusion-loaded aerosolized microparticles. Aerosolized microparticles suppressed drug release in simulated gastric fluid (SGF) and simulated intestinal fluid (SIF) prior to drug release in simulated colonic fluid (SCF) to a higher extent than homogenized microparticles. Microparticles prepared using aerosolization or homogenization (1 M CaCl2, diffusion loaded) released 5% and 17% of drug content after 2 h in SGF and 4 h in SIF, respectively, and 75% after 12 h in SCF. Thus, aerosolization and homogenization techniques show potential for producing alginate microparticles for colonic drug delivery in the treatment of inflammatory bowel disease.

Effect of early low-dose hydrocortisone on survival without bronchopulmonary dysplasia in extremely preterm infants (PREMILOC): a double-blind, placebo-controlled, multicentre, randomised trial.

Bronchopulmonary dysplasia, a major complication of extreme prematurity, has few treatment options. Postnatal steroid use is controversial, but low-dose hydrocortisone might prevent the harmful effects of inflammation on the developing lung. In this study, we aimed to assess whether low-dose hydrocortisone improved survival without bronchopulmonary dysplasia in extremely preterm infants. In this double-blind, placebo-controlled, randomised trial done at 21 French tertiary-care neonatal intensive care units (NICUs), we randomly assigned (1:1), via a secure study website, extremely preterm infants inborn (born in a maternity ward at the same site as the NICU) at less than 28 weeks of gestation to receive either intravenous low-dose hydrocortisone or placebo during the first 10 postnatal days. Infants randomly assigned to the hydrocortisone group received 1 mg/kg of hydrocortisone hemisuccinate per day divided into two doses per day for 7 days, followed by one dose of 0·5 mg/kg per day for 3 days. Randomisation was stratified by gestational age and all infants were enrolled by 24 h after birth. Study investigators, parents, and patients were masked to treatment allocation. The primary outcome was survival without bronchopulmonary dysplasia at 36 weeks of postmenstrual age. We used a sequential analytical design, based on intention to treat, to avoid prolonging the trial after either efficacy or futility had been established. This trial is registered with ClinicalTrial.gov, number NCT00623740. 1072 neonates were screened between May 25, 2008, and Jan 31, 2014, of which 523 were randomly assigned (256 hydrocortisone, 267 placebo). 255 infants on hydrocortisone and 266 on placebo were included in analyses after parents withdrew consent for one child in each group. Of the 255 infants assigned to hydrocortisone, 153 (60%) survived without bronchopulmonary dysplasia, compared with 136 (51%) of 266 infants assigned to placebo (odds ratio [OR] adjusted for gestational age group and interim analyses 1·48, 95% CI 1·02-2·16, p=0·04). The number of patients needed to treat to gain one bronchopulmonary dysplasia-free survival was 12 (95% CI 6-200). Sepsis rate was not significantly different in the study population as a whole, but subgroup analyses showed a higher rate only in infants born at 24-25 weeks gestational age who were treated with hydrocortisone (30 [40%] of 83 vs 21 [23%] of 90 infants; sub-hazard ratio 1·87, 95% CI 1·09-3·21, p=0·02). Other potential adverse events, including notably gastrointestinal perforation, did not differ significantly between groups. In extremely preterm infants, the rate of survival without bronchopulmonary dysplasia at 36 weeks of postmenstrual age was significantly increased by prophylactic low-dose hydrocortisone. This strategy, based on a physiological rationale, could lead to substantial improvements in the management of the most premature neonates. Assistance Publique-Hôpitaux de Paris.

Thymic stromal lymphopoietin downregulates filaggrin expression by signal transducer and activator of transcription 3 (STAT3) and extracellular signal-regulated kinase (ERK) phosphorylation in keratinocytes

Thymic stromal lymphopoietin downregulates filaggrin expression by signal transducer and activator of transcription 3 (STAT3) and extracellular signal-regulated kinase (ERK) phosphorylation in keratinocytes

Stability of Hydrocortisone Preservative-Free Oral Solutions.

The physical and chemical stability of a preservative-free oral solution of hydrocortisone succinate was studied at different pH values and storage temperatures. Oral solutions of hydrocortisone 1 mg/mL were prepared by dissolving hydrocortisone succinate powder in citrate buffers at pH 4.0, 5.5, and 6.5, or with sterile water (pH 7.4) stored in amber glass vials. Three identical samples of the formulations were prepared and stored under refrigeration (3-7°C), ambient temperature (20-22°C) and high temperature (29-31°C). A 200-μL sample was withdrawn from each of the 3 samples immediately after preparation and at 1, 7, 14, 21, and 35 days. Samples were assayed in duplicate using stability-indicating liquid chromatography. Stability was determined by evaluating the percentage of the initial concentration remaining at each time point; stability was defined as the retention of at least 90% of the initial concentration of hydrocortisone succinate. At least 92% of the initial hydrocortisone succinate concentration in solutions pH 5.5, 6.5, and 7.4 remained throughout the 14-day study period under refrigeration. There were no detectable changes in color, odor, or pH and no visible microbial growth in these samples. In other storage conditions, hydrocortisone succinate was rapidly degraded. The hydrocortisone succinate preservative-free oral solutions at pH 5.5, 6.5, or 7.4 are chemically stable when stored under refrigeration for at least 14 days. They provide flexible and convenient dosage forms without any preservatives for pediatric patients.

Scorpion bite, a sting to the heart and to coronaries resulting in Kounis syndrome.

Sir, In the very interesting paper published in IJCCM,[1] the authors reported on a 14-year-old-boy who was bitten by scorpion and developed chest pain, vomiting, loose stools, cold sweating, raised jugular venous pressure, tachycardia and hypotension. Laboratory findings showed increased troponin T, proBNP and CPKMB, bilateral lung fluffy shadows, reduced ejection fraction, and ST segment elevation in II, III, aVF, V3, V4, V5, and V6, and T-wave inversion in I, aVL, V1 and V2 leads compatible with acute myocardial injury and pulmonary oedema. This case raises the following important questions on pathophysiology, treatment, and differential diagnosis of scorpion envenomation: Centruroides and parabuthus scorpions are associated primarily with neuromuscular toxicity, whereas androctonus, buthus, and mesobuthus scorpion envenomation is associated with cardiovascular involvement, resulting from hyperstimulation of autonomic centers release of catecholamines and vasoactive peptides. Since venom specific immunoglobulin E (IgEs) have been identified by using skin tests and IgE immunoblots and mast cell degranulation and histamine release are also involved in scorpion venom-induced-inflammatory pain, hypersensitivity cardiovascular involvement is also present[2] Myocardial infarction has been reported following scorpion envenomation on some occasions.[3,4] Scorpion envenomation may result in immediate late and delayed hypersensitivity reactions in susceptible individuals. Cardiovascular toxicity implies venom amount-dependent action with progressing effects, while hypersensitivity means inflammation causing either Kounis hypersenstivity-associated acute coronary syndrome or hypersensitivity myocarditis, which are not venom amount dependent and may arise at any time during or soon after envenomation. It seems likely that the described patient developed coronary vasospasm manifesting as Type I variant of Kounis syndrome progressing to myocardial injury.[5] Hypersensitivity or toxic myocarditis could not be confirmed because neither coronary angiography nor magnetic resonance imaging was available. Coronary angiography is normal in myocarditis while in Kounis syndrome may reveal the coronary spasm. Magnetic resonance imaging shows subendocardial concentration of gadolinium in Kounis syndrome while in myocarditis the gadoliniun is concentrated in subepicardial areas[5] Several studies have shown no significant difference in patients on steroids and in steroid-free patients in terms of mortality and intensive care unit length of stay. The hydrocortisone hemisuccinate regimen has limited effect in critically ill envenomated children and, therefore, it should not be recommended.[6] Antivenom combined with prazosin and dobutamine is indicated for cardiovascular effects and benzodiazepines for neuromuscular involvement. Adrenaline and fluid resuscitation – not glucocorticoids, antihistamines, or mast-cell stabilizers – are the mainstays of treatment for scorpion venom-induced anaphylaxis. However, administration of antihistamines and mast cell stabilizers, but not hydrocortisone, could be used as a supplementary treatment of life-threatening scorpion envenomation. The described patient developed a pulmonary edema and received corticosteroids but not prazosin. Alpha receptor stimulation plays an important role in the pathogenesis of pulmonary edema. The use of prazosin, a postsynaptic alpha blocker, is recommended for significant sympathetic symptoms. Cardiogenic pulmonary edema with arterial hypertension responds favorably to prazosin. Oral prazosin is fast acting, easily available, and highly effective. Corticosteroids are beneficial in interstitial noncardiogenic pulmonary edema. Scorpion envenomation is a complex condition, which requires rigorous action, meticulous treatment and careful follow-up.