Search

Rationale: Chronic alcohol intake down-regulates GABAergic transmission and reduces levels of neuroactive steroids. These changes are associated with greater stress dysregulation and high alcohol craving which in turn increases relapse risk. Objectives: This study tested whether potentiation of the neurosteroid system with pregnenolone (PREG), a precursor to neuroactive steroids and known to increase GABAergic transmission, will normalize chronic alcohol-related stress adaptations in the hypothalamic–pituitary–adrenal (HPA) axis and autonomic responses and reduce alcohol craving to significantly impact relapse risk. Methods: Forty-three treatment-seeking individuals with alcohol use disorder (AUD) were randomized to placebo (PBO) or supraphysiologic pregnenolone doses of 300 mg or 500 mg treatment using a parallel-between subject design as part of a larger 8-week pilot clinical trial. In week 2, they participated in a 3-day laboratory experiment where on each day they self-administered the assigned study drug in the laboratory and were then exposed to 5-min personalized guided imagery provocation of stress, alcohol, or neutral/relaxing cues, one condition per day on separate days, in a random, counterbalanced order. Repeated assessments of alcohol craving, anxiety, HPA axis, heart rate (HR), systolic (SBP), and diastolic blood pressure (DBP) and serum pregnenolone levels were made on each day. Results: Pregnenolone levels were significantly increased in the PREG groups versus PBO. PREG treatment decreased stress- and alcohol cue- induced craving and dose-specifically reduced stress-induced anxiety in the 300 mg/day group. Both PREG doses compared to PBO also normalized CORT/ACTH and increased stress-induced HR, stress- and cue-induced SBP, and in the 300 mg PREG group cue-induced DBP responses relative to neutral condition. Conclusions: Findings indicate that pregnenolone decreases stress- and alcohol cue-provoked craving and normalizes HPA axis and autonomic arousal in individuals with AUD, thereby supporting the need for further assessment of pregnenolone in the treatment of AUD. [ABSTRACT FROM AUTHOR]

Background: Clinically, depigmentation after local corticosteroid injection is not rare. But there are less articles about its reflectance confocal microscopy (RCM) and histological features. This study aimed to define the RCM features and histopathologic findings of hypopigmentation after local corticosteroid injection and to analyze the correlations between the above two methods. Methods: Forty cases with hypopigmentation after local corticosteroid injection were used to analyze the clinical and RCM features. Subsequently, for 20 of 40, an excision biopsy of the same imaged areas for histopathologic examination was executed. Results: Our results showed that all 40 cases had round or ellipse hypopigmented macules with obscure boundary and 26 of 40 lesions' long diameter went along limbs. The RCM features and the histological findings revealed all patients had variable degrees of epidermal thinning, flattening rete ridges, reduced melanin, and no inflammatory cell infiltration. MART‐1 analysis revealed the number of melanocytes was normal but with no or less melanin by Fontana‐Masson staining. Conclusions: Depigmentation after local corticosteroid injection was a kind of disease with intact melanocytes, whose function was impaired. RCM features offer a high consistency with histopathologic findings. It thus constitutes a promising adjuvant tool for its diagnosis and for therapeutic follow‐up. [ABSTRACT FROM AUTHOR]

Purpose: We sought to determine if administration of antenatal corticosteroids in early preterm births (<34 weeks) is associated with an increased risk of developing neonatal hypoglycemia (<40 mg/dL) within the first 48 h of neonatal life.Materials and Methods: Retrospective cohort of all indicated singleton preterm births (23-34 weeks) in a single tertiary center from 2011 to 2014. The primary outcome was neonatal hypoglycemia (<40 mg/dL) within the first 48 h of life. The outcome was compared by antenatal corticosteroids received at any point during the gestation, within 2-7 d of delivery, and whether the patient received a partial, full, or repeat course of antenatal corticosteroids. Logistic regression was used to adjust for confounders.Results: Six hundred thirty-five patients underwent an indicated preterm birth during the study period. Six hundred and four (95%) received antenatal corticosteroids prior to delivery and 31 (5%) did not. The incidence of neonatal hypoglycemia within 48 h of life was not significantly different between those who received any antenatal corticosteroids and those who did not (23.0 versus 16.1%, adjusted odds ratio [OR] 1.3, 95%CI 0.5-3.6). Infants who received a full antenatal corticosteroid course within 2-7 d of delivery had similar incidences of hypoglycemia compared with those who received antenatal corticosteroids more than 7 d before delivery (20.4 versus 25.4%, adjusted OR 1.5, 95% confidence interval(CI) 0.8-2.9). Neonatal hypoglycemia was not increased by the number of antenatal corticosteroid doses (partial, full, or repeat course) administered. There was not a correlation between timing of antenatal corticosteroid administration before delivery, up to 250 h, and the lowest neonatal blood sugar in the first 48 h of life.Conclusion: Our findings suggest antenatal corticosteroid administration in indicated early preterm infants (<34 weeks) may not increase the risk of developing neonatal hypoglycemia within the first 48 h of life. Further studies should validate our findings. [ABSTRACT FROM AUTHOR]

Purpose: We sought to determine if administration of antenatal corticosteroids in early preterm births (<34 weeks) is associated with an increased risk of developing neonatal hypoglycemia (<40 mg/dL) within the first 48 h of neonatal life.Materials and Methods: Retrospective cohort of all indicated singleton preterm births (23-34 weeks) in a single tertiary center from 2011 to 2014. The primary outcome was neonatal hypoglycemia (<40 mg/dL) within the first 48 h of life. The outcome was compared by antenatal corticosteroids received at any point during the gestation, within 2-7 d of delivery, and whether the patient received a partial, full, or repeat course of antenatal corticosteroids. Logistic regression was used to adjust for confounders.Results: Six hundred thirty-five patients underwent an indicated preterm birth during the study period. Six hundred and four (95%) received antenatal corticosteroids prior to delivery and 31 (5%) did not. The incidence of neonatal hypoglycemia within 48 h of life was not significantly different between those who received any antenatal corticosteroids and those who did not (23.0 versus 16.1%, adjusted odds ratio [OR] 1.3, 95%CI 0.5-3.6). Infants who received a full antenatal corticosteroid course within 2-7 d of delivery had similar incidences of hypoglycemia compared with those who received antenatal corticosteroids more than 7 d before delivery (20.4 versus 25.4%, adjusted OR 1.5, 95% confidence interval(CI) 0.8-2.9). Neonatal hypoglycemia was not increased by the number of antenatal corticosteroid doses (partial, full, or repeat course) administered. There was not a correlation between timing of antenatal corticosteroid administration before delivery, up to 250 h, and the lowest neonatal blood sugar in the first 48 h of life.Conclusion: Our findings suggest antenatal corticosteroid administration in indicated early preterm infants (<34 weeks) may not increase the risk of developing neonatal hypoglycemia within the first 48 h of life. Further studies should validate our findings. [ABSTRACT FROM AUTHOR]

The brain is continuously exposed to varying levels of adrenal corticosteroid hormones such as corticosterone in rodents and cortisol in humans. Natural fluctuations occur due to ultradian and circadian variations or are caused by exposure to stressful situations. Brain cells express two types of corticosteroid receptors, i.e. mineralocorticoid and glucocorticoid receptors, which differ in distribution and affinity. These receptors can mediate both rapid non-genomic and slow gene-mediated neuronal actions. As a consequence of these factors, natural (e.g. stress-induced) shifts in corticosteroid level are associated with a complex mosaic of time- and region-dependent changes in neuronal activity. A series of experiments in humans and rodents have revealed that these time- and region-dependent cellular characteristics are also reflected in distinct cognitive patterns after stress. Thus, directly after a peak of corticosteroids, attention and vigilance are increased, and areas involved in emotional responses and simple behavioral strategies show enhanced activity. In the aftermath of stress, areas involved in higher cognitive functions become activated allowing individuals to link stressful events to the specific context and to store information for future use. Both phases of the brain's response to stress are important to face a continuously changing environment, promoting adaptation at the short as well as long term. We argue that a balanced response during the two phases is essential for resilience. This balance may become compromised after repeated stress exposure, particularly in genetically vulnerable individuals and aggravate disease manifestation. This not only applies to psychiatric disorders but also to neurological diseases such as epilepsy. [ABSTRACT FROM AUTHOR]

Antrodia camphorata mycelium is used in traditional Chinese medicine in Taiwan. The wild-type mycelium is rare and expensive, so a solid-state-cultured mycelium of A. camphorata (SCMAC) has been developed. Previous studies have found SCMAC to have anti-inflammatory effects. However, the immunomodulatory effects of SCMAC and of its active phytosterol compounds EK100 and 9A on asthma remain unknown. In this study, BALB/c mice were repeatedly exposed to Dermatogoides pteronyssinus (Der p) at 1-week intervals and were orally administered crude SCMAC extract before the Der p challenge. The mice were sacrificed 72 h after the last challenge to examine the airway remodeling, inflammation, and expression profiles of cytokines and various genes. Then, 30-µg/mL Der p-stimulated MH-S cells with 9A or EK100 were collected for real-time PCR analysis, and the effects of 9A and EK100 on macrophages were evaluated. The crude extract reduced Der p-induced airway hyperresponsiveness, total serum immunoglobulin E levels, and recruitment of inflammatory cells to the bronchoalveolar lavage fluid through cytokine downregulation and Th1/Th2/Th17 response modulation. Additionally, 9A and EK100 inhibited IL-1β and IL-6 expression in alveolar macrophages. These results indicate that the pharmacologically active compounds in a crude SCMAC extract exert synergistic effects on multiple targets to relieve asthma symptoms. [ABSTRACT FROM AUTHOR]

Background: DeQuervain tenosynovitis, refractory to medical conservative treatment, has been traditionally treated by a simple division of the pulley, a procedure associated with several complications. Many authors attempted to prevent these complications by describing techniques of pulley reconstruction after its release necessitating suturing the different flaps and subsequently promoting extensor tendons adhesions. The authors present an alternative procedure for the first extensor compartment pulley decompression: 'Omegaplasty'. Methods: 25 Patients with 29 DeQuervain tenosynovitis cases were enrolled in a prospective, nonrandomized clinical trial from 2012 to 2016. At enrollment they were offered the option of Omegaplasty as a surgical treatment modality for their cases. The procedure is based on liberating the anterior attachment of the pulley from the anterior lip of the styloïd process while respecting its continuity with the periosteal flap as well as promoting expansion of the tunnel volume. All operated patients were evaluated using the 'Opposition Kapandji Score'. Results: The authors present the results of 29 different 'Omegaplasty' procedures. Based on the Kapandji opposition score, twenty cases scored 10/10 while the remaining nine cases yielded an 8/10 score each. Conclusions: The described technique is simple, reliable and respects the extensor tendons gliding physiology and biodynamics. By preserving the anatomical continuity of the first extensor compartment pulley at the wrist, the risk of adhesion formation is reduced. The preliminary results are encouraging and provide the 'Ω' plasty the potential to be considered as a surgical option for treatment of De Quervain Tenosynovitis. [ABSTRACT FROM AUTHOR]

Background and Aims: Inhaled corticosteroids (ICSs) are crucial antiinflammatory medications for chronic airway diseases. Studies investigating the relationship between ICSs and fractures in Asian populations are scant. We investigated whether ICSs increased the risk of low-energy fractures in patients with chronic airway diseases. Methods: We used the Longitudinal Health Insurance Database to select patients aged 20 years and older with chronic airway diseases (asthma and COPD) between 2000 and 2011 as the base cohort. We identified ICS users and ICS non-users matched by propensity score method at 1:1 ratio. Cox proportional hazard regression models were used to calculate the adjusted hazard ratio (aHR) and 95% confidence interval (CI) for factors associated with the risk of fracture. Results: A total of 1,182 ICS users and 1,182 controls were enrolled. After adjustment for age, gender, annual exacerbation number of acute respiratory events, comorbidity and medications, the risk of fracture was 1.10 for ICS users (aHR=1.20; 95% CI=1.10-1.31) compared with ICS non-users. The ICS users exhibited significantly 1.63-fold risk of hip fracture and 1.24-fold risk of ulna and radius fracture than did the ICS non-users. Patients with medium and high doses of ICS use were associated with significantly increased risks of fracture (aHR=1.48, 95% CI=1.25-1.76 for medium dose and aHR=1.55, 95% CI=1.39-1.72 for high dose) compared with those in ICS non-users. Conclusions: Patients with medium and high doses of ICS use are associated with an increased risk of fracture. [ABSTRACT FROM AUTHOR]

Summary: Background: Atopic dermatitis is a chronic inflammatory skin disease that may require systemic therapy. Ciclosporin A (CsA) is a widely used, potent immunosuppressant but it is not effective in all patients with atopic dermatitis, and side‐effects limit its use. Dupilumab, a fully human anti‐interleukin 4 receptor‐alpha monoclonal antibody, inhibits signaling of IL‐4 and IL‐13, key drivers of Type 2/Th2‐mediated inflammation, and is approved in the U.S.A. and the European Union for the treatment of inadequately‐controlled moderate‐to‐severe atopic dermatitis in adults. Objectives: To evaluate efficacy and safety of dupilumab with concomitant topical corticosteroids (TCS) in adults with atopic dermatitis with inadequate response to/intolerance of CsA, or for whom CsA treatment was medically inadvisable. Methods: In this 16‐week, double‐blind, randomized, placebo‐controlled, phase III trial, patients were randomized 1 : 1 : 1 to subcutaneous dupilumab 300 mg weekly (qw) or every 2 weeks (q2w) or placebo. All received concomitant medium‐potency TCS from Week −2 through Week 16; dosage could be tapered if lesions cleared, or stopped for adverse reactions to TCS. Results: In total, 390 patients were screened, 325 were randomized, and 318 completed the trial. Treatment groups had similar baseline characteristics. Significantly more patients in the dupilumab qw + TCS and q2w + TCS groups achieved ≥ 75% improvement from baseline in the Eczema Area and Severity Index at Week 16 vs. the placebo + TCS group (primary end point) (59·1% and 62·6% vs. 29·6%, respectively; P < 0·001 vs. placebo + TCS, both doses). Other clinical outcomes and atopic dermatitis symptoms were significantly improved in the dupilumab qw + TCS and q2w + TCS groups, including pruritus, pain, sleep disturbance, symptoms of anxiety and depression, and quality of life (QoL). Treatment groups had similar overall rates of adverse events (qw + TCS, q2w + TCS and placebo + TCS groups: 69·1%, 72·0% and 69·4%, respectively) and serious adverse events (1·8%, 1·9% and 1·9%, respectively). Conjunctivitis was more frequent with dupilumab + TCS; skin infections were more frequent with placebo + TCS. Conclusions: Dupilumab + TCS significantly improved signs and symptoms of atopic dermatitis and QoL in adults with a history of inadequate response to/intolerance of CsA, or for whom CsA treatment was medically inadvisable. No new safety signals were identified. [ABSTRACT FROM AUTHOR]

Acute stress has been shown to enhance learning and memory ability, predominantly through the action of corticosteroid stress hormones. However, the valuable targets for promoting learning and memory induced by acute stress and the underlying molecular mechanisms remain unclear. Acid-sensing ion channels (ASICs) play an important role in central neuronal systems and involves in depression, synaptic plasticity and learning and memory. In the current study, we used a combination of electrophysiological and behavioral approaches in an effort to explore the effects of acute stress on ASICs. We found that corticosterone (CORT) induced by acute stress caused a potentiation of ASICs current via glucocorticoid receptors (GRs) not mineralocorticoid receptors (MRs). Meanwhile, CORT did not produce an increase of ASICs current by pretreated with GF109203X, an antagonist of protein kinase C (PKC), whereas CORT did result in a markedly enhancement of ASICs current by bryostatin 1, an agonist of PKC, suggesting that potentiation of ASICs function may be depended on PKC activating. More importantly, an antagonist of ASICs, amiloride (10 μM) reduced the performance of learning and memory induced by acute stress, which is further suggesting that ASICs as the key components involves in cognitive processes induced by acute stress. These results indicate that acute stress causes the enhancement of ASICs function by activating PKC signaling pathway, which leads to potentiated learning and memory. [ABSTRACT FROM AUTHOR]

The undesirable endocrine effects associated with pharmacological therapy with corticosteroids administered orally or parenterally are well-known in medical practice. However, the degree of vigilance is lower when compartmental corticosteroids are used, and it is a widely held assumption that local glucocorticoids rarely produce adrenal insuffi ciency or exogenous Cushing syndrome. The two cases that we present here demonstrate the appearance of major adrenal suppression and Cushing exogenous syndrome after inadequate use of topical corticosteroids and, the combination of inhaled corticosteroids with nasal glucocorticoids, respectively. The following mini-review shows, from the endocrinologist point of view, the main aspects to be considered by practitioners who recommend local glucocorticoid treatments - i.e. inhaled, topical (cutaneous, oral, nasal, ophthalmic) or intraarticular - to prevent the occurrence of major endocrine syndromes that are met after corticosteroid therapy, tertiary adrenal insuffi ciency and exogenous Cushing syndrome. [ABSTRACT FROM AUTHOR]

Summary: Asthma is a common chronic inflammatory condition of the airways affecting over 300 million people world‐wide. In 5%‐10% of cases, it is severe, with disproportionate healthcare resource utilization including costs associated with frequent exacerbations and the long‐term health effects of systemic steroids. Characterization of inflammatory pathways in severe asthma has led to the development of targeted biological and small molecule therapies which aim to achieve disease control while minimizing corticosteroid‐associated morbidity. Herein, we review currently licensed agents and those in development, and speculate how drug therapy for severe asthma might evolve and impact on clinical outcomes in the near future. [ABSTRACT FROM AUTHOR]

Background: Understanding the risk factors that predict the prognosis of Morton's neuroma after corticosteroid injection would help clinicians determine the appropriate treatment protocol. However, the cut-off values for the risk factors are unknown. The aim of this study was to identify the risk factors and cut-off values that predict failure of corticosteroid injection in treatment of Morton's neuroma.Method: Among 201 patients who had corticosteroid injection for Morton's neuroma, 40 underwent further treatment after injections. Injection was performed with ultrasound guidance following ultrasound confirmation of the diagnosis. We compared demographic information, size of the neuroma, and other comorbidities between the patients who did and did not undergo further treatment after injection in order to determine the risk factors of failure. Receiver operating characteristic (ROC) curves were constructed to determine optimal cutoff values for each risk factor.Results: Stepwise logistic regression analysis showed that larger neuromas (p < 0.001) and younger patients (p = 0.026) predicted the failure of corticosteroid injection. The optimal cutoff value for the size of the neuroma was 6.3 mm (sensitivity, 81%; specificity, 95%; positive predictive value, 84%; negative predictive value, 88%) for predicting the failure of corticosteroid injection. Age was not associated with a specific cutoff value.Conclusions: This study found that, with a cut-off value of 6.3 mm, larger Morton's neuromas were associated with failure of corticosteroid injection. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Prolonged use of systemic corticosteroids leads to reduced bone mineral density and osteoporosis, in turn increasing the risk of minimal trauma fractures with their associated morbidity and mortality in elderly populations. However, the effect of inhaled corticosteroids on bone mineral density has been debated in the medical literature. Objectives: We aimed to determine the effect of inhaled corticosteroids on bone mineral density measured using calcaneal quantitative ultrasonography in a cohort of older Australians. Methods: Data was collected from the Hunter Community Study, a longitudinal cohort of Australians aged 55‐85. Simple and multiple linear regression methods were used to test the cross‐sectional association between inhaled corticosteroids and calcaneal bone mineral density measured with quantitative ultrasound at baseline. A causal diagram was used to determine the minimally sufficient number of co‐variates necessary to determine the unconfounded effect of inhaled corticosteroids on bone mineral density; these included gender, body mass index, smoking, asthma, alcohol use, age, physical activity, and diet. Results: There were 152 (6.8%) patients on inhaled corticosteroids and 2098 (93%) controls. Simple and multiple linear regression methods showed a non‐significant effect of inhaled steroids on BMD with slight decrease of BMD −0.010 g/cm2 (95% CI −0.042 to 0.022, P = .55) and −0.013 g/cm2 (95% CI −0.062 to 0.036, P = .61) respectively. Age, gender, body mass index, and smoking were stronger predictors of BMD. Conclusions: No statistically significant relationship was detected between the use of inhaled corticosteroids and reduced bone mineral density in this observational study of a cohort of older Australians. [ABSTRACT FROM AUTHOR]

The H (hypothalamic)-P (pituitary)-I (interrenal) axis is critical in the stress response and other activities of fish. To further investigate cadmium (Cd) toxicity on the H-P-I axis and to identify its potential regulatory genes in fish, the adult female rare minnows ( Gobiocypris rarus ) were exposed to subchronic (5 weeks) levels of waterborne Cd in the present study. This kind of treatment caused dose-dependent decline in fish growth, with significance in the high dose group (100 μg/L). Correspondingly, low dose (5–50 μg/L) waterborne Cd disrupted the endocrine system of H-P-I axis just at the secretion level, while high dose Cd disrupted both the secretion and synthesis of cortisol and its downstream signals in rare minnows, revealed by the significantly upregulation and positive correlation of corticosteroidogenic genes including MC2R , StAR , CYP11A1 , and CYP11B1 in the kidney (including the interrenal tissue) ( P < 0.05), and the significant alteration of Glcci1 , Hsp90AA and Hsp90AB in the hepatopancreas, gill and intestine as well ( P < 0.05). The expression of Glcci1 was significantly decreased in hepatopancreas, gill and intestine of tested fish following treatment, and its positive correlation with GR (Glucocorticoid receptor) suggested its potential regulation on the cortisol and/or H-P-I axis in fish. The expression of FKBP5 in the intestine was positively and significantly correlated with that of Hsp90AA ( P < 0.05), and the Hsp90AB transcript in the hepatopancreas was positively correlated with that of Hsp90AA ( P < 0.05), which indicated that Hsp90AA and Hsp90AB were more likely to serve as cofactors of GR and FKBP5 in response to Cd exposure. [ABSTRACT FROM AUTHOR]

Objective: To evaluate prenatal corticosteroid use in women experiencing spontaneous preterm labor and preterm delivery.Methods: The present cross-sectional multicenter study analyzed interview data from patients attending 20 hospitals in Brazil owing to preterm delivery between April 1, 2011 and July 30, 2012. Patients were stratified based on preterm delivery occurring before 34 weeks or at 34-36+6  weeks of pregnancy, and the frequency of prenatal corticosteroid use at admission was compared. Prenatal corticosteroid use, sociodemographic data, obstetric characteristics, and neonatal outcomes were examined.Results: There were 1455 preterm deliveries included in the present study; 527 (36.2%) occurred before 34 weeks of pregnancy and prenatal corticosteroids were used in 285 (54.1%) of these pregnancies. Among neonates delivered at 32-33+6  weeks, prenatal corticosteroid use was associated with lower pneumonia (P=0.026) and mortality (P=0.029) rates. Among neonates delivered at 34-36+6  weeks, prenatal corticosteroid use was associated with longer neonatal hospital admission (P<0.001), and an increased incidence of 5-minute Apgar scores below 7 (P=0.010), endotracheal intubation (P=0.042), surfactant use (P=0.006), neonatal morbidities (P=0.048), respiratory distress (P=0.048), and intraventricular hemorrhage (P=0.023).Conclusion: Preterm labor and late preterm delivery were associated with worse neonatal outcomes following prenatal corticosteroids. This could reflect a sub-optimal interval between administration and delivery. [ABSTRACT FROM AUTHOR]

Oesophageal stricture is a rare disorder in foals. The following manuscript describes the successful treatment of oesophageal strictures with balloon dilation in 5 foals aged 3 weeks to 4 months. Three of the foals presented due to recurrent oesophageal obstruction, one due to dysphagia, and one due to weight loss, pytalism and bruxism. The strictures were diagnosed via endoscopy. In 2 cases, the use of intraoesophageal corticosteroid injection was performed to reduce the incidence of oesophageal stricture reoccurrence. In all cases, a satisfactory outcome with resolution of clinical signs was achieved. [ABSTRACT FROM AUTHOR]

Prostate cancer growth and progression are mainly dependent on androgens and many current prostate cancer treatment options target the synthesis or function of androgens. We have previously reported that resveratrol and synthetic analogs of resveratrol with a higher bioavailability inhibit the synthesis of androgens in human adrenocortical H295R cells. Now we have studied the antiandrogenic properties of resveratrol, piceatannol and analogs in two different prostate cell lines; LNCaP and RWPE. LNCaP carry a T877A mutation in the androgen receptor while RWPE has a wild-type androgen receptor. We found that resveratrol, piceatannol and all studied analogs were able to inhibit a dihydrotestosterone-induced activation of the androgen receptor, showing that they act as antiandrogens. In LNCaP cells, all studied compounds were able to statistically significantly decrease the androgenic signaling in concentrations ≥1 μM and the synthetic analogs trimethylresveratrol (RSVTM) and tetramethylpiceatannol (PICTM) were the most potent compounds. RWPE cells were not as responsive to the studied compounds as the LNCaP cells. A statistically significant decrease in the androgenic signaling was observed at concentrations ≤5 μM for most compounds and RSVTM was found to be the most potent compound. Further, we studied the effects of resveratrol, piceatannol and analogs on the levels of prostate-specific antigen (PSA) in LNCaP cells and found that all studied compounds decreased the level of PSA and that the synthetic analogs diacetylresveratrol (RSVDA), triacetylresveratrol (RSVTA) and RSVTM were the most potent compounds, decreasing the PSA level by approx. 50% at concentrations ≥10 μM. In a cell-free receptor binding assay we were unable to show binding of resveratrol or analogs to the ligand binding domain of the androgen receptor, indicating that the observed effects are mediated via other mechanisms than direct ligand competition. We conclude that the resveratrol, piceatannol and analogs are highly interesting for chemoprevention of prostate cancer, since they have a high potency both as inhibitors of androgen synthesis and androgen receptor activation. [ABSTRACT FROM AUTHOR]

Stress influences synaptic plasticity, learning and memory in a steroid hormone receptor dependent manner. Based on these findings it has been proposed that stress could be a major risk factor for the development of cognitive decline and dementia. Interestingly, evidence has been provided that stress also affects muscarinic, i.e., acetylcholine (ACh)- mediated neurotransmission. To learn more about the impact of stress and steroids on synaptic plasticity, in this study, we investigated the effects of stress on muscarinic long term potentiation (mLTP). We report that multiple, unpredictable exposure to stress depresses carbachol (0.5 mM)-induced mLTP, while this effect of stress is not observed in hippocampal slices prepared from mice exposed only to a single stressful procedure. Furthermore, we demonstrate that activation of distinct steroid hormone receptors is involved in stress-mediated alterations of mLTP. Activation of mineralocorticoid receptors (MR) promotes mLTP, while glucocorticoid receptor (GR) activity impairs mLTP. These effects of multiple unpredictable stress on mLTP are long-lasting since they are detected even two weeks after the last stressful experience. Thus, multiple unpredictable events rather than a single stressful experience affect mLTP in a steroid hormone receptor dependent manner, suggesting that chronic unpredictable stress can lead to lasting alterations in hippocampal cholinergic plasticity. [ABSTRACT FROM AUTHOR]

In endoscopic sinus surgery (ESS) synechiae formation and ostial stenosis are frequently encountered. This is not uncommon after frontal recess and ostium interventions due to the narrow recess and difficult anatomy of the region. The goal of this study is to evaluate the efficacy of the new cross-linked hyaluronan gel-PureRegen Gel Sinus-on wound healing and synechiae prevention in endoscopic frontal sinus surgery. The study consists of two groups of patients who underwent ESS, including frontal sinus surgery. In the study group of 37 patients, PureRegen Gel Sinus was applied to both the frontal recess and ostium at the end of the procedure. The control group consisted of 28 patients. In this group, nasal dressing material was not applied at the end of surgery-neither to the frontal recess nor to the ostium. Postoperatively, epithelization was found to be significantly better at 2 and 4 weeks in the study group when compared with the findings in patients where no postoperative dressing was applied. In the eighth week, there was no significant difference found between the two groups in terms of epithelization. Synechiae formation was significantly lower in the PureRegen Gel Sinus group than the control group at all 2, 4 and 8 weeks postoperative evaluations. The effects of PureRegen Gel Sinus on wound healing, especially in reepithelization, have shown to occur earlier in the postoperative period. Rapid reepithelization and control of infection related granulation tissue formation with antibiotics in the early postoperative period may explain the low stenosis rate in frontal sinus ostia in PureRegen Gel Sinus applied patients. [ABSTRACT FROM AUTHOR]

Introduction: Several studies report a decrease of fetal heart rate (FHR) short-term variation (STV) after corticosteroids for improvement of fetal maturity and advice not to deliver a fetus for low STV within 2-3days after corticosteroids. However, literature is not unanimous in this respect. This study intends to asses STV longitudinally after corticosteroid administration.Material and Methods: A retrospective cohort study in a tertiary perinatal centre from 2009 to 2015 included all women who had been treated with corticosteroids at gestational age of 26-34 weeks, had a computerized cardiotocography (cCTG) before and after medication and did not deliver within 48h. FHR and STV were stratified over 12-h periods and compared before and after corticosteroids. Women with imminent preterm labour (including PPROM) and women with placental problems (fetal growth restriction (FGR) or preeclampsia) (PE) were analysed separately. The effect of co-medication and gestational age was assessed.Results: The study included 406 women, 211 with imminent preterm labour, 195 with FGR-PE. After corticosteroids STV increased 1-2ms (median 1.4; IQR 0.1-3.1) during the first 36h after start of corticosteroids. Thereafter a small decrease of less than 1ms (median -0,6; IQR -1.6 to 0.3) compared to before CC was seen.Conclusions: The most conspicuous effect of corticosteroids is a short term increase of STV and decrease of FHR. A slight decrease after 48-71h is possible, but abnormally low values should be considered as a sign of fetal distress. The clinical guidance, given by some, not to intervene because of a low STV after corticosteroids appears invalid. [ABSTRACT FROM AUTHOR]

Preterm births account for approximately 10% of births worldwide, with the majority (∼80%) being moderate preterm. Our aim was to determine the effects of moderate preterm birth on survival and long-term growth of male and female offspring using an ovine model of preterm birth that was preceded by a clinically relevant dose of corticosteroids. Ewes were induced to deliver preterm or at term; those assigned to deliver preterm were administered antenatal betamethasone (11.4 mg, 2 doses, 24 hours apart). The growth (body weight and body dimensions) of offspring was monitored to adulthood (62 weeks) when the animals were humanely killed for organ collection. Survival in the immediate period following preterm birth was high (75% for both sexes). However, there were unexpected deaths between 5 and 12 weeks of age, as a result of vitamin E/selenium deficiency; this only occurred in preterm offspring. From birth until adolescence, preterm lambs were lighter than term lambs (controls). After this time, there was gradual catch-up in body weight in preterm females, whereas in preterm males, body weight remained lower than in controls. Preterm sheep were smaller in stature than controls throughout life. This clinically relevant model of preterm birth leads to equally high survival rates in both sexes and is an excellent animal model in which to examine the effects of moderate preterm birth on growth and development of organ systems into adulthood. [ABSTRACT FROM AUTHOR]

Background: A beneficial effect of rituximab (RTX) on focal segmental glomerulosclerosis (FSGS) in pediatric patients or in transplant recipients has been reported in isolated cases. However, the use of RTX in adult patients with idiopathic FSGS needs further investigation.Methods: Eight patients who had biopsy-proven FSGS (63.9 ± 14.0, range 40-81 years, 4 women, 4 men) with major risk factors precluding corticosteroids or conventional immunosuppression were treated with a high dose of RTX (8 weekly doses of 375 mg/m2) and prospectively followed up for at least 2 years (29.1 ± 8.8 months, range 24-42 months).Results: RTX failed to improve proteinuria in 7 out of 8 patients, who had persistent nephrotic proteinuria. In one case, a rapidly deteriorating renal function was also observed. Only one patient showed an improvement in renal function and a remarkable reduction in proteinuria. There were no differences in clinical or laboratory characteristics or in the CD20 B lymphocyte count after RTX between the responder and the 7 nonresponder patients.Conclusions: Only a minority (1 of 8) in our series of adult patients with FSGS showed positive effects of high doses of RTX. Future studies are warranted to investigate more promising therapeutic options in the management of FSGS. [ABSTRACT FROM AUTHOR]

Introduction The epidemiology of immune thrombocytopenia (ITP) is not well characterized in an Asian population. Materials and methods From July 2010 to June 2014, ITP patients were identified using the Korean Health Insurance Review and Assessment Service database. Results The overall incidence rate of ITP was 5.3 per 100,000 person-years (95% CI: 5.1–5.5). The overall incidence rate ratios of children under 15 years old to adults and females to males were 3.8 (95% CI: 3.7–3.9) and 1.3 (95% CI: 1.2–1.4), respectively. Of the total 10,814 patients, 3388 patients (31%) needed treatment for ITP; of these, 54% continued treatment for more than three months. First-line therapy consisted of corticosteroids (CS) in 42%, immunoglobulin (IVIg) in 35%, CS with IVIg in 19%, and other immunosuppressive agents (ISA) in 4%. Among treated patients, 75% of adults and 33% of children continued treatment for more than three months. After three months, the most frequently used drug was CS alone in 63% of patients. Only 104 patients underwent splenectomy; of these, 51% received salvage treatment after a median of one month after surgery (range: 0–27). The proportion of patients who received platelet transfusions of 12 units or more per month for at least two consecutive months was significantly higher among patients treated for more than three months compared with patients who completed treatment within three months. Conclusions This population-based study is the first to describe the incidence of ITP and its treatment reality for patients in Korea. [ABSTRACT FROM AUTHOR]

Corticosteroids are critical for normal development and for mediating effects of stress during development in all vertebrates. Even though gene knockout studies in mouse and zebrafish have identified a number of developmental roles of corticosteroids and their receptors, the numerous pleiotropic actions of these hormones affecting various aspects of development are understudied. For the most part, neither the endogenous hormone(s) nor their receptor(s) regulating developmental processes during natural development have been determined. Here, we address this issue by elucidating the endogenous regulation of the transcription factor Krüppel-like factor 9 ( klf9 ) across tissues during development by corticosteroid hormones (aldosterone and corticosterone) and their nuclear receptors (type-I and type-II receptors). First, we measured the developmental expression profiles of klf9 and type-I and type-II corticosteroid receptors in key target tissues, brain, lungs, and tail, during larval and metamorphic stages in Xenopus tropicalis . We also studied the corticosteroid regulation of klf9 in these tissues in-vivo using exogenous hormone treatments and receptor antagonists. Klf9 and the corticosteroid receptors were expressed in each tissue and significantly increased in expression reaching a peak at metamorphic climax, except for the type-II receptor in brain and tail whose expression did not change significantly across stages. Both corticosteroid hormones induced klf9 in each tissue , although aldosterone required a five times higher dose than corticosterone to cause a significant induction. The upregulation of klf9 by both corticosteroids was completely blocked by the use of the type-II receptor antagonist RU486 and not the type-I receptor antagonist spironolactone. These results are consistent with previous in-vitro studies and indicate for the first time in-vivo that corticosteroid regulation of klf9 occurs exclusively via corticosterone and type-II receptor interaction across tissues. [ABSTRACT FROM AUTHOR]

Background To determine the short-term effects following corticosteroid injection into the shoulder. Methods Type-specific shoulder injection was administered, followed by physiotherapy 7 days to 10 days later. One hundred and sixteen adult patients were prospectively followed-up. The primary outcome was a visual analogue score (VAS) for pain. Scores were recorded immediately before injection, 30 minutes after, daily until day 7 and then at 6 weeks. Post injection pain was defined as an increase of 2 or more points in the VAS score after the injection. The secondary outcome was determined at 6 months as successful discharge or progression onto surgery. Results The VAS showed a significant reduction from the pre-injection score for all patients at day 1 and was maintained until week 6. Forty-one (35.3%) patients experienced post-injection pain. The mean duration of symptoms was 3.9 days. At 6 months, 81 (69.8%) patients were discharged successfully and, at a mean of 23.2 months, did not require re-referral; 29 (25%) had surgery; and six (5.2%) were referred for a spinal opinion. Conclusions One in three patients developed delayed post-injection pain. Flare phenomenon had no determinate effect on outcome. Patients’ pain response by 6 weeks is predictive of final outcome at 6 months and may help clinicians plan further treatment without delay. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to identify predictive factors of poor response to intra-flexoral sheath corticosteroid injection, as well as to identify factors associated with patients' decisions to undergo surgical treatment. Methods: Data from 112 patients who received steroid injection treatment for trigger finger were reviewed retrospectively. Logistic regression was used to assess the prognostic value of factors assumed to affect prognosis (age, sex, underlying disease, history of illness, presence of carpal tunnel syndrome, multiple digit involvement, and pre- and post-operative disability scores). Results: Multiple digits were affected in 42 patients. Associated and underlying conditions were carpal tunnel syndrome (n = 36), hypertension (n = 23), hyperlipidemia (n = 14), and history of malignant tumor (n = 10). Logistic regression analysis showed that multiple digit involvement and Froimson clinical severity score were factors significantly associated with surgical treatment after intra-flexoral sheath corticosteroid injection treatment. These two factors were also found to be associated with the patients' decisions to undergo surgical treatment. Conclusions: Although local corticosteroid injection is useful in most cases, providers need to counsel patients with multiple digit involvement and/or severe cases about the possibility of requiring additional surgical treatment. [ABSTRACT FROM AUTHOR]

Allergic diseases, including allergic rhinitis/ rhinoconjuctivitis, asthma, and urticaria, are common conditions in the adult population, affecting women at the fertile age. Although, ideally, pregnant women should not receive pharmacologic treatment because of associated risks for the unborn child, sometimes quality of life impairment or risks of associated complications make medication necessary. The benefit/risk ratios associated with treatment in allergic diseases are favourable and allow the safe administration of several pharmacological classes. Oral antihistamines, predominantly loratadine and cetirizine, have a good safety profile in pregnant women. Treating asthma is extremely important because of the risks associated with the disease, and the preferred treatment is inhaled corticosteroids, and other classes of antiasthmatic drugs can also be administered. Allergen-specific immunotherapy can be continued during pregnancy safely, and some studies suggest a possible protective effect on the subsequent development of allergic diseases in the child. [ABSTRACT FROM AUTHOR]

Hypersensitivity disorders are exaggerated immune reactions to foreign antigens. Allergic reactions' symptoms are alleviated with H1 blockers, mast cell stabilisers, anti-inflammatory corticosteroids and leucotriene inhibitors. Anaphylaxis is a severe allergic reaction and requires prompt emergency treatment with epinephrine. Immunotherapy can induce tolerance and is indicated when allergen exposure cannot be avoided and medication treatment is inadequate. [ABSTRACT FROM AUTHOR]

Background and purpose The role of corticosteroids in the treatment of patients with aneurysmal subarachnoid haemorrhage ( SAH) has remained controversial for decades. Recent studies have suggested that the administration of corticosteroids in SAH patients is associated with favourable outcomes. Given their significant adverse effects, it is essential to identify those patients who will benefit from treatment with corticosteroids. Methods A retrospective analysis of a prospectively collected cohort ( n = 306) with SAH who were treated by microsurgical clipping or endovascular intervention was performed. The role of dexamethasone administration was analysed with regard to clinical conditions and SAH-related complications. Outcome was assessed at discharge and during follow-up using the Glasgow Outcome Scale ( GOS). Results Patients treated with dexamethasone presented with more episodes of hyperglycaemia ( P < 0.001), more overall infections ( P < 0.001) and more ventriculostomy-related infections ( P = 0.004). Multivariate analysis demonstrated that treatment with dexamethasone was associated with an unfavourable outcome at discharge ( GOS 1-3) [odds ratio ( OR) 2.814, 95% confidence interval ( CI) 1.440-5.497, P = 0.002]. In the subgroup of microsurgically treated patients, dexamethasone administration was associated with a favourable outcome at follow-up ( OR 0.193, 95% CI 0.06-0.621, P = 0.006). A higher risk for unfavourable outcome ( OR 3.382, 95% CI 1.67-6.849, P = 0.001) at discharge was observed in endovascularly treated patients who received dexamethasone but this had no impact on the outcome at follow-up. Conclusions Treatment with dexamethasone seems to be associated with a risk reduction for an unfavourable outcome in those patients who underwent microsurgical clipping. Despite an increased frequency of adverse effects, glucocorticoids may have a potential benefit in this specific surgical subgroup compared to endovascularly treated SAH patients. [ABSTRACT FROM AUTHOR]

Objective: Asthma and corticosteroid use have been implicated as possible risk factors for schizophrenia. The retrospective cohort study herein aimed to investigate the association between asthma, corticosteroid use, and schizophrenia. Method: Longitudinal data (2000 to 2007) from adults with asthma (n = 50,046) and without asthma (n = 50,046) were compared on measures of schizophrenia incidence using Taiwan’s National Health Insurance Research Database (NHIRD). Incidence of schizophrenia diagnosis (ICD-9 codes 295.XX) between 2000 and 2007 were compared between groups. Competing risk-adjusted Cox regression analyses were conducted, adjusting for sex, age, residence, socioeconomic status, corticosteroid use, outpatient and emergency room visit frequency, Charlson comorbidity index, and total length of hospital stays days for any disorder. Results: Of the 75,069 subjects, 238 received a diagnosis of schizophrenia. The mean (SD) follow-up interval for all subjects was 5.8 (2.3) years. After adjusting for potential confounding factors, asthma was associated with significantly greater hazard ratio for incident schizophrenia 1.40 (95% CI = 1.05, 1.87). Additional factors associated with greater incidence of schizophrenia were rural residence, lower economic status, and poor general health. Older age (i.e. ≥65 years) was negatively associated with schizophrenia incidence. Corticosteroid use was not associated with increased risk for schizophrenia. Conclusions: Asthma was associated with increased risk for schizophrenia. The results herein suggest that a convergent disturbance in the immune-inflammatory system may contribute to the pathoetiology of asthma and schizophrenia. [ABSTRACT FROM AUTHOR]

Duchenne muscular dystrophy is a rare genetic disorder with life-limiting pathology. Drisapersen induces exon 51 skipping, thereby producing a shorter but functional dystrophin protein. The longest available data are from an open-label extension study (PRO051-02) treating 12 boys with drisapersen (6 mg/kg/week subcutaneously). The median change (range) from baseline to week 177 in six-minute walking distance (6MWD) was 8 (–263, 163) metres. The current analysis aimed to put the results from PRO051-02 in the context of natural progression by comparing the functional trajectory of drisapersen-treated subjects to a matched natural history (NH) cohort, treated by standard of care. Subjects were matched individually by age and 6MWD, as the primary analysis, and by age and rise from floor (RFF), as sensitivity analysis. A total of 75 NH subjects were available for 6MWD analysis, of which matching was possible for 9 ambulant drisapersen-treated subjects. None of the 6 “stable” (baseline 6MWD ≥330 metres) drisapersen-treated subjects lost ambulation vs 4 out of 10 matched NH subjects over a comparable timeframe (~3.4 years), compared with 2 out of 3 ambulant “in decline” drisapersen-treated subjects vs all 6 matched NH subjects. A total of 79 NH subjects were available for RFF analysis. For continuous ambulatory subjects (N = 4), the RFF decline was more pronounced in the NH cohort than in the drisapersen-treated subjects. In conclusion, a comparison of ambulant drisapersen-treated subjects with matched NH subjects showed a difference in functional trajectories over a timeframe of up to 3.4 years in favour of drisapersen. [ABSTRACT FROM AUTHOR]

Background: Topical corticosteroids have become available as over the counter drugs and are widely misused for various conditions. Objective: The aim of this study is to assess the clinical and epidemiological aspects of the unjustified use of topical corticosteroids for facial skin. Methods: A total of 200 patients with facial dermatoses and topical corticosteroid misapplication daily over face for not less than 30 days were included in the study. This was a prospective study conducted in a tertiary care dermatology outpatient centre of the Jammu region. A detailed clinical history regarding topical corticosteroid use was taken and adverse effects analysed. Results: A total of 166 patients were women and 34 were men. The predominant age was 31-40 years. A total of 170 patients (85%) were in the age group of 21-50 years. Duration of application was over 1 month up to 3 years, daily. Betamethasone or clobetasol ointments were used in 75 patients (37.5%) and momatasone was used in 15 patients (7.5%). Indication for using steroids were: general / cosmetic purposes (72 patients; 36.0%), acne (59; 29.5%), hyperpigmentation (41; 20.5%), tinea (6; 3%), undiagnosed dermatoses (28; 14.0%). The use of corticosteroids was attributed to the advice of pharmacists (69; 34.5%), friends and relatives (61; 30.5%), cosmetologists (22; 11.0%), non-dermatology physicians (30; 15.0%) and dermatologists (18; 9%). Adverse effects included acneiform lesions, telengiectasias, dyspigmentation, hypertrichosis, perioral dermatitis and tinea incognito. A total of 89 (44.5%) patients fulfilled the criteria of "topical steroid dependent face". These patients reported erythema, burning and itching on stopping the application of topical corticosteroids. Conclusion: Inmost cases the use prolonged use of topical corticosteroids on facial skin was recommended by non-professional persons. The adverse events ranged from transient to permanent. The results of this study underline the indispensable role of dermatology specialists in diagnosing and treating cutaneous disorders. [ABSTRACT FROM AUTHOR]

The majority of genes contributing to the heritable component of blood pressure remain unidentified, but there is substantial evidence to suggest that common polymorphisms at loci involved in the biosynthesis of the corticosteroids aldosterone and cortisol are important. This view is supported by data from genome-wide association studies that consistently link the CYP17A1 locus to blood pressure. In this review article, we describe common polymorphisms at three steroidogenic loci (CYP11B2, CYP11B1 and CYP17A1) that alter gene transcription efficiency and levels of key steroids, including aldosterone. However, the mechanism by which this occurs remains unclear. While the renin angiotensin system is rightly regarded as the major driver of aldosterone secretion, there is increasing evidence that the contribution of corticotropin (ACTH) is also significant. In light of this, we propose that the differential response of variant CYP11B2, CYP11B1 and CYP17A1 genes to ACTH is an important determinant of blood pressure, tending to predispose individuals with an unfavourable genotype to hypertension. [ABSTRACT FROM AUTHOR]

Omalizumab is marketed for chronic severe asthma patients who are allergic to perennial allergens. Our purpose was to investigate whether omalizumab is also effective in persistent severe asthma due to seasonal allergens. Thirty patients with oral corticosteroid-dependent asthma were treated with Omalizumab according to the dosing table. For each patient with asthma due to seasonal allergens, we recruited the next two consecutive patients with asthma due to perennial allergens. The dose of oral methyl prednisolone (MP) was tapered at a rate of 2 mg every two weeks after the start of treatment with omalizumab depending on tolerance. At each monthly visit, a forced spirometry and fractional exhaled nitric oxide (FeNO) measurement were performed and the accumulated monthly MP dose was calculated. At entry, there were no differences between groups in terms of gender, body mass index or obesity, year exacerbation rate, monthly dose of MP, FeNO and blood immunoglobuline E (IgE) values, or spirometry (perennial: FVC: 76%; FEV1: 62%; seasonal: FVC: 79%; FEV1: 70%). The follow-up lasted 76 weeks. One patient in each group was considered a non-responder. Spirometry did not worsen in either group. There was a significant intragroup reduction in annual exacerbation rate and MP consumption but no differences were detected in the intergroup comparison. Omalizumab offered the same clinical benefits in the two cohorts regardless of whether the asthma was caused by a seasonal or a perennial allergen. These results strongly suggest that allergens are the trigger in chronic asthma but that it is the persistent exposure to IgE that causes the chronicity. [ABSTRACT FROM AUTHOR]

A relationship between the development of osteonecrosis of the femoral head and systemic corticosteroids has been well established in the literature, particularly in adults. However, the link between osteonecrosis and inhaled corticosteroids is less researched and understood. We report an usual case report of a 10-year-old male who developed ipsilateral femoral head osteonecrosis after long-term inhalational corticosteroid and intermittent short courses of oral steroid usage with a unique presentation and delayed diagnosis. [ABSTRACT FROM AUTHOR]

Background: Hypophysitis is an umbrella term for a group of disorders involving inflammation of the pituitary gland. A rare occurrence in humans, hypophysitis can produce a range of clinical signs including (but not limited to) visual deficits and diabetes insipidus. Only five cases of canine hypophysitis exist in the literature, all presenting in mature dogs with no visual deficits and a grave outcome. This case report describes the clinical and advanced imaging features of blindness-inducing presumptive hypophysitis in a dog, which rapidly resolved with medical management. Case presentation: A 1-year-and-seven-month-old neutered male Standard Poodle presented with subacute blindness, ataxia, and polyuria/polydipsia (PUPD). Magnetic resonance imaging (MRI) detected a contrast-enhancing pituitary mass with perilesional oedema compromising the optic chiasm. Suspecting neoplasia, anti-inflammatory corticosteroid was commenced prior to radiation therapy planning. Complete resolution of neurological and visual deficits occurred within 12 days of starting steroid treatment. Repeated advanced imaging indicated macroscopic resolution of the lesion. An extended thyroid panel with insulin-like growth factor-1 analysis supported a diagnosis of hypophysitis. Resolution of PUPD was achieved with tapering courses of prednisolone and desmopressin; the dog has since been clinically normal for 14 months and treatment-free for 11 months. Conclusions: To the authors' knowledge, this is the first instance in which a canine pituitary mass has demonstrated long-term resolution with palliative medical treatment alone, alongside reversal of associated blindness and presumptive diabetes insipidus. We suspect this lesion to be a form of hypophysitis, which should be included among differential diagnoses for pituitary masses, and for subacute blindness in dogs. Where possible, we advocate biopsy-confirmation of hypophysitis prior to timely intervention with anti-inflammatory treatment. [ABSTRACT FROM AUTHOR]

Osteonecrosis is a well-recognized complication in patients treated with corticosteroids. The incidence of osteonecrosis in children treated for Hodgkin lymphoma is unknown because prospective whole-body magnetic resonance imaging ( MRI) studies are lacking in this patient population. Paediatric patients with newly diagnosed Hodgkin lymphoma who were treated according to a uniform paediatric Hodgkin protocol were eligible for inclusion in this prospective study. Whole-body MRI was performed in all 24 included patients (mean age 15·1 years, 12 girls) both before treatment and after 2 cycles of chemotherapy, and in 16 patients after completion of chemotherapy. Osteonecrosis was identified in 10 patients (41·7%, 95% confidence interval: 22·0-61·4%), with a total of 56 osteonecrotic sites. Osteonecrosis was detected in 8 patients after 2 cycles of OEPA (vincristine, etoposide, prednisone, doxorubicin), and in 2 additional patients after completion of chemotherapy. Epiphyseal involvement of long bones was seen in 4 of 10 children. None of the patients with osteonecrosis had any signs of bone collapse at the times of scanning. Whole-body MRI demonstrates osteonecrosis to be a common finding occurring during therapy response assessment of paediatric Hodgkin lymphoma. Detection of early epiphyseal osteonecrosis could allow for treatment before bone collapse and joint damage may occur. [ABSTRACT FROM AUTHOR]

Pseudotumor cerebri syndrome refers to elevated intracranial pressure associated with papilledema without an identified etiology for intracranial hypertension. Over the past few decades, several medications have been described to be associated with this syndrome. We searched the literature for those case reports and series and evaluated the evidence for the association of such medications with pseudotumor cerebri syndrome. [ABSTRACT FROM AUTHOR]

Objective: The objective of our study was to define the prevalence of osteoporosis and osteopenia in patients with noncystic fibrosis bronchiectasis (NCFB).Methods: We conducted a retrospective chart review of all patients with physician-diagnosed NCFB evaluated at Mayo Clinic Florida between January 1, 2011 and June 3, 2013.Results: A total of 113 patients with physician-diagnosed NCFB and confirmatory findings on computed tomography scan were identified. The cohort was overwhelmingly women (90%) with a mean age of 72 ± 10.6 and a body mass index of 24.8 ± 6.8. The medical history indicated that 30% (34) had osteoporosis, 39% (44) had osteopenia, and 9% (10) had normal bone density. In 25 (22%) of the subjects, bone density was unknown or undocumented. Most were never smokers (55.7%) or past smokers (41.6%) and airflow obstruction was present in 58% of the 84 subjects who had undergone pulmonary function tests. In total, 57 patients (50.44%) and 45 patients (39.82%) had been prescribed proton pump inhibitors and inhaled corticosteroids, respectively. Bone mineral density testing was performed during the study period in 70 (62%) of the subjects. Decreased bone density consistent with osteoporosis was present in 19 (27%); 41 (59%) had osteopenia, and bone density was normal in 10 (14%) subjects. Diminished bone density was present in 82.8% (24/29) of patients younger than age 70, with 27.6% (8/29) having osteoporosis. There was a greater incidence of diminished bone density in those with reduced body mass index (100% vs 82%), but this difference did not reach statistical significance (P = 0.10). Forty-seven and 32% of patients with diminished bone density were using proton pump inhibitor therapy and inhaled corticosteroids, respectively.Conclusions: This study suggested that diminished bone density is common in patients with bronchiectasis, with >85% of this cohort having osteoporosis or osteopenia confirmed by bone density testing. Although the prevalence of both bronchiectasis and diminished bone density increases with advancing age and female sex, these data suggest a greater prevalence than expected based on demographic risks. Medications that may predispose individuals to diminished bone density are not uncommonly prescribed in patients with bronchiectasis. Provider awareness of the substantial prevalence of diminished bone density in patients with bronchiectasis may improve patient care by prompting appropriate screening for and treatment of osteoporosis and osteopenia. In light of these observations, judicious use of medications that may predispose to diminished bone density is warranted. [ABSTRACT FROM AUTHOR]

Preterm, very low birthweight (VLBW) infants are prone to life-threatening hypotension secondary to hypothalamic-pituitary-adrenal axis immaturity, resulting in adrenocortical insufficiency. Clinical presentations of inotrope-resistant refractory hypotension are usually evident, but interpretation of serum cortisol may pose much difficulty to front-line neonatologists. This review examines the salient pathophysiology of adrenocortical insufficiency in the immediate postnatal period, characterises its endocrinological abnormalities, and describes the typical and variant clinical presentations. Based on existing evidence, a practical scheme is proposed for logical interpretation of circulating cortisol levels and management of inotrope-resistant refractory hypotension in VLBW infants. [ABSTRACT FROM AUTHOR]

Purpose The purpose of this study is to describe how the hospital influenced the practice of corticosteroids and aminophylline administration by applying strategic problem solving. Under five child mortality is a challenge in Rwanda. Although it has been shown that administering corticosteroids and aminophylline can reduce the mortality of premature neonates, the use of these medications were low at Mibilizi District Hospital in Rwanda.Design/methodology/approach This project used a pre- and post-intervention study design, utilizing patient file audit to evaluate the impact of our intervention on the compliance of corticosteroids administration to pregnant mothers in premature labour and aminophylline to premature neonates, using the Strategic Problem Solving approach.Findings The intervention significantly increased the rate of giving corticosteroids to mothers at risk of premature delivery from 26 per cent to 60 per cent p-value = 0.009. The provision of aminophylline to premature neonates under 34 weeks of gestation significantly increased from 65 per cent to 100 per cent p-value = 0.002.Practical implications This study illustrates how a multidisciplinary team was able to use the eight steps of strategic problem solving to increase the administration rates of corticosteroids and aminophylline. The hospital should continue to support quality improvement efforts using strategic problem solving approach to prevent premature neonatal deaths and improve quality of care.Originality/value Findings from this study may be useful for hospitals in resource-challenged settings seeking to improve the administration of corticosteroids and aminophylline to prevent premature neonatal deaths. [ABSTRACT FROM AUTHOR]

Synthetic corticosteroids may pose an environmental risk to fish. Here, we describe multiend point responses of adult zebrafish (8 months old) upon 21-day exposure to a commonly prescribed corticosteroid, fludrocortisone acetate (FLU), at concentrations between 0.006 and 42 µg/L. No remarkable reproductive impacts were observed, while physiological effects, including plasma glucose level and blood leukocyte numbers were significant altered even at 42 ng/L. Ovary parameters and transcriptional analysis of hypothalamic-pituitary-gonadal-liver axis revealed negligible effects. Significant alterations of the circadian rhythm network were observed in the zebrafish brain. Transcripts of several biomarker genes, including per1a and nr1d1, displayed strong transcriptional changes, which occurred at environmental relevant concentrations of 6 and 42 ng/L FLU. Importantly, the development and behavior of F1 embryos were significant changed. Heartbeat, hatching success and swimming behavior of F1 embryos were all increased even at 6 and 42 ng/L. All effects were further confirmed by exposure of eleuthero-embryos. Significant transcriptional changes of biomarker genes involved in gluconeogenesis, immune response and circadian rhythm in eleuthero-embryos confirmed the observations in adult fish. Hatching success, heartbeat, and swimming activity were increased at 81 ng/L and higher, as with F1 embryos. These results provide novel insights into the understanding of potential environmental risks of corticosteroids. [ABSTRACT FROM AUTHOR]

The objective of the study was to determine the evidence of intratympanic steroids injections (ITSI) for efficacy in the management of the following inner ear diseases: Ménière's disease, tinnitus, noise-induced hearing loss (NIHL) and idiopathic sudden sensorineural hearing loss (ISSNHL). The data sources were literature review from 1946 to December 2014, PubMed and Medline. A systematic review of the existing literature was performed. Databases were searched for all human prospective randomized clinical trials using ITSI in at least one treatment group. The authors identified 29 prospective randomized clinical trials investigating the benefits of an intratympanic delivery of steroids. Six articles on Ménière's disease were identified, of which one favored ITSI over placebo in vertigo control. Of the five randomized clinical trials on tinnitus therapy, one study found better tinnitus control with ITSI. The only available trial on NIHL showed significant hearing recovery with combination therapy (ITSI and oral steroids therapy). Seventeen studies were identified on ISSNHL, of which 10 investigated ITSI as a first-line therapy and 7 as a salvage therapy. Studies analysis found benefits in hearing recovery in both settings. Due to heterogeneity in treatment protocols and follow-up, a meta-analysis was not performed. Given the low adverse effects rates of ITSI therapy and good patient tolerability, local delivery should be considered as an interesting adjunct to the therapy of the ISSNHL and NIHL. Only one article over six where ITSI therapy offers potential benefits to patients with Ménière's disease in the control of tinnitus and vertigo was found. ITSI does not seem to be effective in the treatment of tinnitus. [ABSTRACT FROM AUTHOR]

The treatment of cutaneous lupus erythematous (CLE) remains a challenge. Most of the therapeutic options used in CLE have not been tested in randomized controlled studies and to date no agent has been approved. Therefore, CLE treatment is mostly based on personal experience. To better characterize therapeutic habits among physicians treating CLE patients, a questionnaire-based study about various aspects of topical and systemic treatment for CLE has been performed. The questionnaire was distributed among CLE experts, mostly from Japan, the USA, and Europe. A total of 82 completed questionnaires were assessed. High-potent and potent corticosteroids as well as calcineurin inhibitors were the most often recommended topical treatment for all CLE subtypes. The most relevant factors for initiation of systemic therapy were severity of skin lesions, concomitant involvement of internal organs, CLE subtype and lack of response to topical therapies. Corticosteroids and antimalarials were considered as the most suitable and effective systemic drugs for CLE patients. However, significant differences were observed between various CLE subtypes and between different countries regarding the assessment of various topical and systemic treatment options. In conclusion, great variability of obtained answers underlines the need of development of CLE treatment guidelines suitable for different disease subtypes. [ABSTRACT FROM AUTHOR]

Background Minimal persistent inflammation (MPI) contributes to hyperreactivity in allergic rhinitis. However, little is known regarding whether pre-onset activation of eosinophils and mast cells is present or not in Japanese cedar pollinosis (JCP). Furthermore, a prophylactic effect of intranasal corticosteroids on such MPI in JCP has not been investigated. Methods We designed a double-blinded, randomized, placebo-controlled, crossover trial. Twenty patients with JCP were examined outside the pollen season (UMIN000008410). Nasal provocation with paper discs containing extracts of Japanese cedar pollen was performed once a day for 3 consecutive days. Onset of nasal symptoms was monitored over 15 min after each provocation. The levels of eosinophil cationic protein (ECP) and tryptase in nasal secretions were examined. Fluticasone furoate nasal spray or placebo treatment was started one day before the first provocation. Results In the placebo group, 25% of the patients showed onset of nasal symptoms following provocation on the first day. In addition, 75% and 68% of the patients showed symptom onset on the second and third day of provocation, respectively. After the first provocation, the levels of ECP and tryptase in nasal secretions were significantly increased. These increases were seen not only in symptomatic but also in asymptomatic subjects in response to provocation, and the levels were similar between these subjects. Prophylactic treatment with fluticasone significantly suppressed the increase in nasal ECP and tryptase associated with repeated provocations. Conclusions These results suggest that pre-onset activation of eosinophils and mast cells is present in experimental JCP, and that prophylactic treatment with intranasal corticosteroids has the potential to control such activation. [ABSTRACT FROM AUTHOR]

Late preterm infants constitute the majority of preterm labors. The neonatal morbidity and mortality among late preterm infants are serious problems of obstetrical practice. This arises the question of antenatal corticosteroid administration beyond 34 week of gestation. In this review, need for antenatal corticosteroids after 34 weeks of gestation is studied. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a chronic and relapsing skin disease with severe eczematous lesions. Long-term topical corticosteroid treatment can induce skin atrophy, hypopigmentation and transepidermal water loss (TEWL) increase. A new treatment approach was needed to reduce the risk by dermal targeting. For this purpose, Betamethasone valerate (BMV)/Diflucortolone valerate (DFV)-loaded liposomes (220–350 nm) were prepared and incorporated into chitosan gel to obtain adequate viscosity (∼13 000 cps). Drugs were localized in stratum corneum + epidermis of rat skin inex-vivopermeation studies. The toxicity was assessed on human fibroblast cells. In point ofin-vivostudies, pharmacodynamic responses, treatment efficacy and skin irritation were evaluated and compared with previously prepared nanoparticles. Liposome/nanoparticle in gel formulations produced higher paw edema inhibition in rats with respect to the commercial cream. Similar skin blanching effect with commercial creams was obtained via liposome in gels although they contain 10 times less drug. Dermatological scoring results, prognostic histological parameters and suppression of mast cell numbers showed higher treatment efficiency of liposome/nanoparticle in gel formulations in AD-induced rats. TEWL and erythema measurements confirmed these results. Overview of obtained results showed that liposomes might be an effective and safe carrier for corticosteroids in skin disease treatment. [ABSTRACT FROM PUBLISHER]

Introduction: With the increasing use of intravitreal administration of corticosteroids in macular edema, steroid-induced intraocular pressure (IOP) rise is becoming an emergent issue. However, for patients in whom intravitreal steroids are indicated, there are no specific recommendations for IOP monitoring and management after intravitreal administration of corticosteroids. Method: An expert panel of European ophthalmologists reviewed evidence on corticosteroid-induced IOP elevation. The objective of the panel was to propose an algorithm based on available literature and their own experience for the monitoring and management of corticosteroid-induced IOP elevation, with a focus on diabetic patients. Results: Data from trials including diabetic patients with a rise of IOP after intravitreal steroid administration indicate that IOP-lowering medical treatment is sufficient for a large majority of patients; only a small percentage underwent laser trabeculoplasty or filtering filtration surgery. A 2-step algorithm is proposed that is based on the basal value of IOP and evidence for glaucoma. The first step is a risk stratification before treatment. Patients normotensive at baseline (IOP ≤ 21 mmHg), do not require additional baseline diagnostic tests. However, patients with baseline ocular hypertension (OHT) (IOP > 21 mmHg) should undergo baseline imaging and visual field testing. The second step describes monitoring and treatment after steroid administration. During follow-up, patients developing OHT should have baseline and periodical imaging and visual field testing; IOP-lowering treatment is proposed only if IOP is >25 mmHg or if diagnostic tests suggest developing glaucoma. Conclusion: The management and follow-up of OHT following intravitreal corticosteroid injection is similar to that of primary OHT. If OHT develops, IOP is controlled in a large proportion of patients with standard IOP treatments. The present algorithm was developed to assist ophthalmologists with guiding principles in the management of corticosteroid-induced IOP elevation. Funding: Alimera Sciences Limited. [ABSTRACT FROM AUTHOR]