Administration Of Cortisone Research Articles

The Safety of Antirheumatic Drugs.

Drug therapy for rheumatic diseases has changed fundamentally in recent decades with the introduction of many new agents. As these drugs may have to be taken for many years, and many of them are of similar efficacy, their safety profiles play an important role in therapeutic decisionmaking. This review is based on pertinent literature retrieved by a selective search on the safety profiles of selected antirheumatic drugs. Non-steroidal antirheumatic drugs, glucocorticoids, conventional disease-modifying drugs such as methotrexate, biological agents, and janus kinase (JAK) inhibitors are all used to treat rheumatic diseases. Register and trial data show that antirheumatic treatments are relatively safe. Infections, in particular, are much less common than initially expected. Cortisone administration is an exception because of its severe long-term sequelae. Biological agents are associated with severe infectious events at a rate of 4-5 events per 100 patient years. Screening before treatment with biological agents has been shown to lower the rate of tuberculosis from 564 to 95 cases per 100 000 patient years. JAK inhibitors have a good safety profile, with respect to infections as well, but there is evidence of their association with cardiovascular problems, malignancies, and thrombosis. A suitable, safe antirheumatic drug can be chosen for each patient in consideration of individual risk profiles. Regular monitoring enables the early detection of adverse effects. The risk profile of JAK inhibitors, in particular, will be studied in further trials.

Controverse de diagnostic și tratament în sindromul Marshall

Defined by recurrent febrile episodes af angina, adenitis and stomatitis, Marshall syndrome is frequently encountered in clinical practice in children. The diagnosis is clinical, aided by the dramatic resolution of the symptoms after administration of oral cortisone. The authors report 2 cases of Marshall syndrome and discuss their treatment, based on clinical datas from literature and their own experience in a children emergency department.

Exacerbation of myasthenia gravis following corticosteroid treatment: what is the evidence? A systematic review.

Corticosteroids (CS) are among the most widely- used immunosuppressive agents for immune-mediated conditions, including myasthenia gravis (MG). While their effectiveness in MG is documented and supported in the clinical practice over several decades, one of the main drawbacks of treatment results from the notion that MG patients may experience symptom worsening following CS treatment initiation. This may lead to the administration of lower than necessary doses of CS for the disorder, or even avoiding them altogether. As a consequence, some patients may not receive the optimal treatment to control their disease. In the present review, we analyzed 27 relevant publications and determined the prevalence of clinical exacerbation following CS treatment, its' severity and relation to the type and dose of CS. The rate of MG exacerbation is highest with the administration of cortisone, intermediate with prednisone, and lowest with methylprednisolone. High dose daily or alternate-day prednisone is associated with exacerbation more frequently than low-dose treatment, but most exacerbations are of mild to moderate severity. Other factors related to increased risk of an initial exacerbation include older age, generalized MG, bulbar symptoms, disease severity, presence of thymoma, and thymectomy. However, the current information is based mostly on heterogeneous studies of low quality, and prospective clinical trials designed to compare between the various agents and doses and assess the rate and severity of the exacerbation by a unified scale are warranted.

Certain perspectives about the use of corticosteroids for managing hospitalized patients with rheumatic diseases.

The administration of cortisone to a bedridden patient with rheumatoid arthritis (RA) 70years ago was a transformative event in modern medicine. We have since struggled to balance the near-miraculous anti-rheumatic with the yet all-too-frequent devastating side effects of glucocorticoids (GC). With the current availability of newer disease-modifying and biologic anti-rheumatic agents, we were rather surprised to note that 94% of sick hospitalized patients with systemic rheumatic diseases at our medical center were on corticosteroids during a 3-month observation period. Comparing contemporary with past practices from historical references, we confirmed a perhaps paradoxical trend of increasing steroid usage in certain contexts over the years. Sixty-seven percent of our hospitalized lupus patients were started on GC of greater than 30mg prednisone equivalent compared with 50% in the 1950s. Seventy-five percent of our RA inpatients had their GC dose increased on discharge. Both (2/2) our new RA patients were started on GC, compared with 69% in the 2000s and just 36% in the 1990s. This likely reflects both improved abilities to keep sick patients alive and inability of other anti-rheumatic therapies to consistently induce or sustain disease remission compared with the usually highly efficacious yet inexpensive GC in these particular patients. Administration of glucocorticoids to ill, often infected, patients with systemic rheumatic diseases remains more art than science. Current perspectives view glucocorticoids as considerably less salutary than previously thought; we are still challenged to keep our patients from developing preventable complications. These observations emphasize the need for more and better therapeutic alternatives to glucocorticoids. There are now several examples-disease-modifying and biologic medications for RA and biologics for lupus and vasculitis-that suggest the possibility of caring for our patients without the historical reliance on corticosteroids. We have made enormous progress since steroids were first offered to a patient with RA in 1948. We are hopeful the future will bring us interventions of comparable or better efficacy that are safer.

Adrenal Steroids Modulate Fibroblast-Like Synoviocytes Response During B. abortus Infection

Brucella abortus stimulates an inflammatory immune response that stimulates the endocrine system, inducing the secretion of dehydroepiandrosterone (DHEA) and cortisol. In humans, the active disease is generally present as osteoarticular brucellosis. In previous studies we showed that B. abortus infection of synoviocytes creates a proinflammatory microenvironment. We proposed to determine the role of cortisol and DHEA on synoviocytes and infiltrating monocytes during B. abortus infection. Cortisol inhibited IL-6, IL-8, MCP-1, and MMP-2 secretion induced by B. abortus infection in synovial fibroblast. Cortisol-mediated MMP-2 inhibition during B. abortus infection was reversed by IL-6. DHEA inhibited B. abortus-induced RANKL up-regulation in synovial fibroblast through estrogen receptor (ER). B. abortus infection did not modulate glucocorticoid receptor (GR) expression. Cell responses to cortisol also depended on its intracellular bioavailability, according to the activity of the isoenzymes 11β-hydroxysteroid dehydrogenase (HSD) type-1 and 11β-HSD2 (which are involved in cortisone-cortisol interconversion). B. abortus infection did not modify 11β-HSD1 expression and GRα/β ratio in the presence or absence of adrenal steroids. Supernatants from B. abortus-infected monocytes induced 11β-HSD1 in synovial cells. Administration of cortisone was capable of inhibiting the secretion of RANKL by synoviocytes mimicking cortisol's effect. These results go along with previous observations that highlighted the ability of synovial tissue to secrete active steroids, making it an intracrine tissue. This is the first study that contributes to the knowledge of the consequence of adrenal steroids on synoviocytes in the context of a bacterial infection.

Glucocorticoid-Induced, Morpho-Functional Alterations in Pancreatic Beta Cells of Wistar Rats

Background: Though prolonged use of glucocorticoids has been reported to promote adverse effects, traditionally, high-dose glucocorticoids have been implicated in immune-suppression following organ transplant with Cortisone being a well-known artificial glucocorticoid.
 Objectives: This study investigated the histo-architectural and functional changes in pancreatic beta cells due to Cortisone administration.
 Materials and Methods: Forty two (42) Wistar rats (140 – 200 kg) were assigned into seven groups of six (6) rats each with group A acting as a control. While groups B and C were respectively treated with 0.1 mg/kg and 0.3 mg/kg of Cortisone, groups D and E received 0.1 mg/kg and 0.3 mg/kg of Cortisone respectively plus 33 mg/kg of Ketoconazole; whereas, groups F and G were respectively given 0.1 mg/kg and 0.3 mg/kg of Cortisone alongside 150 mg/kg of Vitamin E each for twenty-eight (28) days. After 28 days of administration, rats were euthanized and blood samples collected for insulin assay. Pancreatic tissues were also harvested and observed for histo-morphological changes.
 Results: Analysis of variance (ANOVA) found Cortisone to have significantly (p < .05) increased glucose level in a dose dependent manner. This was however attenuated following co-administration of Ketoconazole and Vitamin E as Ketoconazole showed more potency in this ameliorating effect. Also, Cortisone was observed to significantly decrease (in dose dependent fashion), pancreatic β-cell functions, with attenuating effect seen following co-administration of Ketoconazole.
 Conclusion: It is recommended that caution is applied with the intake of glucocorticoids, especially in polypharmacy while treating certain ailments.

The 70th anniversary of glucocorticoids in rheumatic diseases: the second youth of an old friend.

Seventy years ago, the first administration of cortisone in a patient with RA marked a milestone in the treatment of inflammatory diseases. However, the initial enthusiasm rapidly vanished as the administration of high doses for lengthy periods revealed worrisome adverse effects. It has taken several decades to overcome the (sometimes excessive) mistrust and to achieve a more differentiated evaluation of the benefit-risk profile and the adequate usage of glucocorticoids (GCs). Today, GCs remain indispensable for the treatment of many inflammatory conditions and their usefulness in RA as a disease-modifying low-dose co-medication is widely acknowledged. Recent studies show promising results concerning both traditional GCs and new formulations. Still, decades of relatively little scientific attention have resulted in a continuing lack of detailed evidence. Hence there is an ongoing need for further research regarding mechanisms of GC actions, the further optimization of treatment parameters for traditional GCs and new formulations.

Risk factors and predictors of carbapenem-resistant Pseudomonas aeruginosa and Acinetobacter baumannii mortality in critically ill bacteraemic patients over a 6-year period (2010-15): antibiotics do matter.

Purpose. Acinetobacter baumannii and Pseudomonas aeruginosa provoke serious infections, especially in intensive care unit (ICU) patients.Methodology. The risk factors and predictors of mortality for P. aeruginosa (n=84; 46 carbapenem-resistant) and A. baumannii (n=129; all carbapenem-resistant) bloodstream infections (BSIs) in an ICU were evaluated. Antibiotic susceptibility testing was performed using the agar disk diffusion method according to EUCAST guidelines. The minimum inhibitory concentration was determined by a gradient method (Etest). Multilocus sequence typing (MLST) was performed for P. aeruginosa during the carbapenem-resistant outbreak in 2014. Epidemiological data were collected from the patients' chart reviews.Results/Key findings. Hospitalization during the summer months, prior KPC-producing Klebsiella pneumoniae (KPC-Kp) BSI, and the administration of tigecycline, aminoglycosides and cortisone were independently associated with P. aeruginosa BSIs. MLST revealed the dissemination of clone ST227, including carbapenem-resistant P. aeruginosa strains. Hospitalization during the summer months, prior KPC-Kp BSI, and the administration of antibiotics, carbapenem and cortisone were independently associated with A. baumannii BSIs. The 30-day mortality rate for P. aeruginosa and A. baumannii BSI was 45.2 and 39.5 %, respectively. Sequential organ failure assessment (SOFA) score at onset, septic shock, age, and prior KPC-Kp BSI were significantly associated with P. aeruginosa BSI mortality. The administration of at least one active antibiotic was identified as a predictor of a good prognosis. Septic shock and simplified acute physiology score (SAPS) II at onset were independently associated with A. baumannii BSI mortality. The administration of at least one active antibiotic and colistin-vancomycin co-administration were identified as predictors of a good prognosis.Conclusion. KPC-Kp infection predisposes ICU patients to BSI by either A. baumannii or P. aeruginosa. The administration of at least one active antibiotic leads to better survival rates.

Relationship between fractional exhaled nitric oxide and bronchopulmonary dysplasia in extremely/very low birth weight infants

Objective To investigate the relationship between fractional exhaled nitric oxide (FeNO) and bronchopulmonary dysplasia (BPD) in extremely/very low birth weight infant (ELBWI/VLBWI). Methods Thirty-five ELBWI/VLBWI (gestational age <34 weeks at birth and birth weight <1 500 g), who were admitted to neonatal intensive care unit of Peking University Third Hospital from October 2014 to March 2015 with respiratory distress soon after birth, were enrolled into the study, and divided into BPD group (n=11) and non-BPD group 1 (n=24) according to the diagnosis at discharge. One day before they left the hospital, FeNO level was determined with Exhalyzer D, an equipment for pulmonary function test. Difference of FeNO and nitric oxide (NO) production between the two groups was compared with t-test or Fisher exact test, and the value of FeNO in predicting BPD was tested by receiver-operating characteristic (ROC) curve. Results The mean gestational age at birth in BPD group was significantly less than that in non-BPD group [(29.7±1.9) vs (32.0±1.5) weeks, t=4.005, P=0.000], and the duration of invasive ventilation [(53.0±91.3) vs (15.0±30.2) h, t=1.598, P=0.002] and oxygenation was longer [(42.1±7.8) vs (8.2±6.4) d, t=13.567, P=0.000]. There were more babies required surfactant treatment, prenatal cortisone administration, and inhalation of cortisone and bronchodilator during hospital stay in BPD group than in non-BPD group[10/11 vs 38%(9/24), 11/11 vs 58%(14/24) and 11/11 vs 21%(5/24), Fisher exact test, all P<0.05]. The age and body weight of the babies at the time of FeNO determination in BPD group were older or higher than those in non-BPD group [(46.4±16.3) vs (20.9±11.7) d, t=5.278, P=0.000; (2 090±164) vs (1 892±153) g, t=3.498, P=0.001], but the corrected gestational age was similar [(36.3±3.1) vs (35.0±2.3) weeks, t=1.407, P=0.169]. Both the mean FeNO level and NO production in BPD group were significantly higher than those in non-BPD group [(13.6±6.9) vs (8.0±3.6) ppb (1 ppb=1×10-9 mol/L), (25.6±10.1) vs (18.1±9.0) nl/min, t=2.967 and 2.478, P=0.006 and 0.018]. The area under the ROC curve was 0.749 (P=0.021, 95%CI: 0.539-0.953) which implied that FeNO provided medium power for discrimination of ELBWI/VLBWI with BPD from those without, with a sensitivity of 72.7% and specificity of 75.0% at the cut-off value of 11.55 ppb. Conclusions FeNO and NO production in BPD infants are significantly higher than non-BPD infants. Measurement of FeNO for ELBWI/VLBWI through mask before discharge is a simple, safe and invasive procedure to objectively evaluate pulmonary function early after birth. Key words: Bronchopulmonary dysplasia; Respiratory function tests; Nitric oxide; Infant, very low birth weight; Infant, extremely low birth weight

Tratamiento de las aplasias, atresias e hipoplasias vaginales con falos acrílicos

Consideramos brevemente nueve casos de pacientes operadas por defectos congénitos o adquiridos de la vagina en que se usaron falos acrílicos para mantener el lumen vaginal. En tres casos se usó el procedimiento de Kirschner-Wagner para crear neo-vaginas. En algunas pacientes se asoció a la intervención quirúrgica la administración de cortisona para disminuir la tendencia natural a la retracción de las paredes vaginales, de estrógenos y de vitaminas A para activar la nutrición y cicatrización de la mucosa vaginal o de los injertos de Thiersh colocados en la neo-vagina. La mortalidad ha sido nula y la morbilidad escasa y de poca importancia.

Estudio de la uropepsina en condiciones normales y patológicas

Se ha estudiado la concentración horaria de uropepsina en hombres y habiéndose obtenido un promedio de 32 unidades y en mujeres de 19, todos ellos normales. El estudio de la enzima en úlceras gástricas y duodenales dán resultados más altos que la media normal, en las neoplasias gástricas las cifras son bajas, pero como las variaciones individuales son amplias, es muy dudoso que esta determinación pueda prestar utilidad clínica, reemplazando al tubaje gástrico. El estudio de la uropepsina en los gastrectomizados revela que en la parcial por úlcera o cáncer la concentración disminuye. En las gastrectomías totales desaparece la uropepsina. En las anemias con aclorhidria del jugo gástrico, la investigación de la enzima presta gran utilidad diagnóstica; en las anemias perniciosas hay ausencia de uropepsina, en las de otro tipo, incluyendo la aplástica hasy disminución. La utilización de la hormona adrenocorticotrópica (A.C.T.H.) y Cortisona en el estudio de la excreción de uropepsina presta valiosos servicios. En sujetos normales, con la administración de 25 mgrs. de A.C.T.H. hemos obtenido un incremento de un 100% en la excreción de uropepsina. En los casos de anemia perniciosa el A.C.T.H. ni la cortisona son capaces de hacer aparecer a la enzima en la orina, pero en anemias de otro tipo el incremento es similar al de los sujetos normales. En la enfermedad de Addison la administración de A.C.T.H. no logra aumentar la uropepsina, pero en éstos casos la administración de cortisona incrementa la excreción de la enzima, por lo que consideramos que representa una prueba fácil de efectuarse, con fines de diagnóstico. Dada la sencillez del método y los útiles servicios que puede prestar, creemos que la determinación de uropepsina debe añadirse a los métodos de rutina en nuestros laboratorios clínicos.

Association of KPC-producing Klebsiella pneumoniae colonization or infection with Candida isolation and selection of non-albicans species

Clinical specimens from 565 patients hospitalized in 2 intensive care units (ICUs A and B) during a 28-month period were cultured on appropriate media for isolation of Candida. Forty-nine (9%) patients had at least a Candida spp.–positive sample. Candida albicans was the predominant species isolated from 26 (53%) patients. Seventeen patients (3%) developed candidemia. Multivariate analysis showed that obesity, female gender, hospitalization during summer months, admission at ICU B, parenteral nutrition, administration of metronidazole, transplantation, and KPC-producing Klebsiella pneumoniae (KPC-Kp) infection were independently associated with Candida spp. isolation. Candidemia was associated with cortisone administration, KPC-Kp infection, and presence of colostomy or abdominal catheter. Administration of fluconazole was a protective factor for both Candida spp. isolation and infection, leading to selection of Candida non-albicans species. Among several risk factors, KPC-Kp infection and colonization are identified as statistically significant factors associated with Candida isolation, especially of non-albicans species.

Anaphylactic reaction to intravenous corticosteroids in the treatment of ocular toxoplasmosis: a case report

IntroductionThis case report presents for the first time an acute systemic allergic reaction to corticosteroids in a patient with ocular toxoplasmosis after treatment with intravenous cortisone, and discusses alternative treatments.Case presentationWe present the case of a 57-year-old Caucasian woman with an anaphylactic reaction after intravenous injection of prednisolone-21-hydrogensuccinate (Solu-Decortin® H) given for the treatment of toxoplasmosis-associated chorioretinitis. Immediately after the injection, she developed an acute erythema of the legs and abdomen, angioedema, hypotension (blood pressure 80/40mmHg), tachycardia (heart rate 140/minute), hyperthermia (38.8°C), and respiratory distress. Allergological examinations showed a positive skin-prick test to prednisolone and methylprednisolone. In addition, an oral exposure test with dexamethasone (Fortecortin®) and betamethasone (Celestamine®) was conducted to find alternative corticosteroids for future treatments. After oral application, no local or systemic reactions were observed for these two substances.ConclusionsThis case report demonstrates that systemic allergic reactions are possible in patients with uveitis or other inflammatory ophthalmological conditions treated with intravenous corticosteroids. Intravenous administration of cortisone, for example, in the treatment of ocular toxoplasmosis, should always be conducted with caution because of a possible allergic reaction. For patients who react to a particular steroid, it is necessary to undergo allergological testing to confirm that the compound in question is indeed allergenic, and to identify other corticosteroids that are safe for future anti-inflammatory treatments.

Immunoglobulin injection for the treatment of multiple oral ulcers in Stevens–Johnson syndrome

Stevens-Johnson syndrome (SJS) is a rare genetic disorder. The syndrome presents with severe purulent conjunctivitis, stomatitis with mucosal necrosis, and purpuric macules. This syndrome is associated with hypersensitive reaction usually stimulated by infection, vaccination, systemic diseases, physical agents, foods or drugs. However, only few cases reported can be related to infectious agents, but the causative role of infectious microorganisms seems relevant in paediatric patients. Authors want to underline the positive response of a new way of therapy by immunoglobulin injection. This case describes a 10-year-old girl with several erosions disseminated in the oral cavity mucosa. The girl had skin erosions that led to the clinical diagnosis of SJS. The past medical history of the patient revealed that those symptoms occured every 6months over the last 2years with 2 consecutive weeks of acute manifestations. At that moment, the paediatrician decided for cortisone administration in order to manage the acute symptoms, but after 6months a new acute episode was observed. For this reason the patient was referred to the Department of Genetics and Immunological Paediatrics. Oral ulcers had been topically treated with an oral balance gel. Intravenous injection of immunoglobulin was then applied and the patient was discharged after 5days of treatment with the total symptoms in remission. The patient was followed up 3monthly over the next 24months. At that time no relapse of the SJS was observed. The seriousness of this condition imposes a prompt recognition. Paediatric dentists should recognise the clinical signs of possible SJS as soon as possible in order to perform a quick diagnosis and initiate treatment.

KPC-producing Klebsiella pneumoniae enteric colonization acquired during intensive care unit stay: the significance of risk factors for its development and its impact on mortality

A prospective observational study of 226 intensive care unit (ICU) patients was conducted during a 25-month period. Rectal samples were taken at day 1, 4, and 7 and, afterwards, once weekly. Klebsiella pneumoniae was identified using standard techniques, whereas the presence of blaKPC gene was confirmed by PCR. During ICU stay, 72.6% of the patients were colonized with Klebsiella pneumoniae carbapenemases (KPC)–producing K. pneumoniae (KPC-Kp). Male gender, prior bed occupants, and patients in nearby beds colonized with KPC-Kp, tracheotomy, number of invasive catheters inserted, and number of antibiotics administered were the major risk factors for KPC-Kp colonization. ICU mortality (35.4%) was significantly related to Simplified Acute Physiology II score and respiratory insufficiency upon admission, cortisone administration, aminoglycoside administration, confirmed KPC-Kp infection, and severe sepsis or septic shock. The high prevalence of KPC-Kp enteric carriage in ICU patients and the significant mortality associated with KPC-Kp infection dictate the importance of early identification and isolation of such carriers.

Formation of Threohydrobupropion from Bupropion Is Dependent on 11β-Hydroxysteroid Dehydrogenase 1

Bupropion is widely used for treatment of depression and as a smoking-cessation drug. Despite more than 20 years of therapeutic use, its metabolism is not fully understood. While CYP2B6 is known to form hydroxybupropion, the enzyme(s) generating erythro- and threohydrobupropion have long remained unclear. Previous experiments using microsomal preparations and the nonspecific inhibitor glycyrrhetinic acid suggested a role for 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) in the formation of both erythro- and threohydrobupropion. 11β-HSD1 catalyzes the conversion of inactive glucocorticoids (cortisone, prednisone) to their active forms (cortisol, prednisolone). Moreover, it accepts several other substrates. Here, we used for the first time recombinant 11β-HSD1 to assess its role in the carbonyl reduction of bupropion. Furthermore, we applied human, rat, and mouse liver microsomes and a selective inhibitor to characterize species-specific differences and to estimate the relative contribution of 11β-HSD1 to bupropion metabolism. The results revealed 11β-HSD1 as the major enzyme responsible for threohydrobupropion formation. The reaction was stereoselective and no erythrohydrobupropion was formed. Human liver microsomes showed 10 and 80 times higher activity than rat and mouse liver microsomes, respectively. The formation of erythrohydrobupropion was not altered in experiments with microsomes from 11β-HSD1-deficient mice or upon incubation with 11β-HSD1 inhibitor, indicating the existence of another carbonyl reductase that generates erythrohydrobupropion. Molecular docking supported the experimental findings and suggested that 11β-HSD1 selectively converts R-bupropion to threohydrobupropion. Enzyme inhibition experiments suggested that exposure to bupropion is not likely to impair 11β-HSD1-dependent glucocorticoid activation but that pharmacological administration of cortisone or prednisone may inhibit 11β-HSD1-dependent bupropion metabolism.

Diffusion-weighted MR imaging of fetal lung maturation in sheep: effect of prenatal cortisone administration on ADC values

To assess changes in diffusion properties in the fetal lung after cortisone administration with diffusion-weighted imaging (DWI) in fetal sheep. DWI was performed on 11 pregnant sheep with singleton pregnancies on a 1.5-T MRI scanner. Four animals received cortisone injections before baseline imaging. Seven animals served as controls. Apparent diffusion coefficient (ADC) was measured on DWI in the fetal lungs by two independent readers. The Pearson test was used to correlate ADC and gestational age. A t-test was performed to compare differences in ADC values at the baseline and follow-up images within and between groups. Inter-rater reliability was calculated. In the cortisone group, ADC values increased about 10 % between the baseline and follow-up images (P = 0.039). Comparing the cortisone and control groups, ADC values of the baseline images did not differ; whereas in the follow-up imaging, ADC values were significantly higher in the cortisone group (P = 0.024). Lung ADC values did not correlate with gestational age (P = 0.970). Inter-rater reliability was high (0.970, P = 0.000). In this experimental model, MR-DWI can detect cortisone-induced changes in diffusion properties of the fetal lung. • Corticosteroids are frequently administered antenatally to prevent fetal lung immaturity at birth • DWI can detect changes in the fetal lung after corticosteroid administration • Changes can be detected as early as 5 days after treatment • Fetal MRI may offer a non-invasive method of monitoring lung maturation.

Steroid psychosis in an adrenal insufficiency and hypothyroidism patient

Acute psychosis after corticosteroid treatment is not unusual; however, the induction of psychosis by a low dose of corticosteroid is uncommon. We describe the case of a 77-year-old man who had adrenal insufficiency and Hashimoto's thyroiditis who, with previous corticosteroid exposure, developed insomnia, sexual hallucinations, aggression and exhibited self-harm behavior after the administration of cortisone 25 mg in the morning and 12.5 mg in the evening. These psychiatric symptoms improved when the corticosteroid therapy was discontinued, but recurred after re-administering 5 mg prednisolone per day. Agitation persisted even at a very low dose of prednisolone, namely 2.5 mg per day. He recovered after corticosteroid treatment was stopped.

Carbon isotope ratio analysis of endogenous glucocorticoid urinary metabolites after cortisone acetate and adrenosterone administration for doping control

Glucocorticoids are listed on the World Anti-Doping Agency (WADA) Prohibited List of substances. The detection of the administration of hydrocortisone and cortisone is complicated by the fact that the human body also produces these steroids naturally. Gas chromatography-combustion-isotope ratio mass spectrometry can be utilized to determine the use of endogenous glucocorticoids by measuring the carbon isotope ratio (CIR) of their resulting metabolites in human urine samples. A comprehensive sample preparation protocol for the analysis of endogenous glucocorticoid urinary metabolites was developed and validated, incorporating the use of high performance liquid chromatography (HPLC) for purification and chemical oxidation for derivatisation. Target compounds were tetrahydrocortisol and tetrahydrocortisone, and 11β-hydroxyetiocholanolone, 11-oxoetiocholanolone and 11β-hydroxyandrosterone, while pregnanediol functioned as the endogenous reference compound. Urine samples from a population of 50 volunteers were analyzed to determine CIR reference limits. Excretion studies of the endogenous glucocorticoid preparation cortisone acetate (25 mg oral) and the dietary supplement adrenosterone (75 mg oral) were conducted with six male individuals. Variable changes in steroid metabolite isotopic composition were found across subjects after administration. The study also revealed that CIR analysis of the major glucocorticoid metabolites tetrahydrocortisol and tetrahydrocortisone is necessary to unambiguously distinguish administration of cortisone and adrenosterone, the former officially restricted to out-of-competition use by athletes, the latter not being restricted at the current time. Moreover, this study reaffirms that CIR methods for the doping control of endogenous steroids should not rely upon a single ERC, as the administration of an appropriate precursor to that ERC could cause complications during analysis.

Total glucosides of Danggui Buxue Tang attenuates bleomycin-induced pulmonary fibrosis via inhibition of extracellular matrix remodelling

This study was designed to investigate the antifibrosis effects and possible mechanism of action of total glucosides of Danggui Buxue Tang (DBTG) on bleomycin-induced pulmonary fibrosis in rats. DBTG was extracted from Radix Astragali and Radix Angelicae Sinensis. Pulmonary fibrosis was induced by intratracheal instillation of bleomycin (5 mg/kg) in Wistar rats. Subsequently, the rats received daily intragastric administration of DBTG (16, 32 or 64 mg/kg per day) or cortisone (3 mg/kg) 1 day after bleomycin instillation for 4 weeks. Histological changes in the lung were evaluated by hematoxylin and eosin and Masson's trichrome staining. Markers of fibrosis in serum were determined by radioimmunoassay. The mRNA expression of metalloproteinases 1 and 9 (MMP-1, MMP-9) and tissue inhibitor of metalloproteinase 1 (TIMP-1) in lung tissue were detected by reverse transcription PCR. DBTG administration attenuated the degree of alveolitis and lung fibrosis, and markedly reduced the elevated levels of hyaluronic acid, laminin, type III procollagen and type IV collagen in serum. DBTG decreased the mRNA levels of MMP-9 and TIMP-1. MMP-1 expression was only moderately decreased by DBTG. DBTG had an inhibitory effect on bleomycin-induced pulmonary fibrosis and its effect may be associated with the ability of DBTG to inhibit the synthesis of extracellular matrix and balance the MMP/TIMP-1 system.