Cortisone Acetate Research Articles

Adrenal Insufficiency in Australia: Is it Possible that the Use of Lower Dose, Short-Acting Glucocorticoids has Increased the Risk of Adrenal Crises?

Morbidity from adrenal insufficiency (AI) in Australia is poorly described. The objective of this study was to evaluate AI morbidity patterns in adults between 1999/2000 and 2011/2012 using national databases. A descriptive study of hospitalisations for AI and adrenal crises (AC) in adults and trends in prescriptions for 2 short-acting glucocorticoids (GC) was designed. The setting was the Australian healthcare system. Main outcome measures are the trends in hospitalisation and prescription rates. There were 7,378 hospital admissions for treatment of AI in adults between 1999/00 and 2011/12. Of these, 29.5% were for an AC. Admission rates for AC increased from 9.5 to 12.4 admissions/10(6)/year (p < 0.05). There was a 5.8% decrease in admission rates for AI (excluding AC), from 27.0 to 25.5/10(6)/year (p = ns). Short-acting GC [hydrocortisone (HCT) and cortisone acetate (CA)] prescription rates increased significantly (p < 0.001) from 3,176.1/10(6) to 3,463.8/10(6). Prescription rates for CA decreased by 22.4% (p < 0.001) but HCT prescription rates increased to 77.1% (p < 0.001). The increase in AC admission rates was positively correlated with the rise in both the total GC prescription rate (r = 0.63, p < 0.05) and the HCT prescription rate (r = 0.74, p< 0.01). Over the 13-year study period, there was a 30.8% increase in hospitalisation rates for ACs and a concomitant 77.1% increase in prescribing of HCT. The association between AC events and HCT use and/or reduced effective GC dose is plausibly causal, but confirmatory studies are required before suggesting any change to GC replacement in AI.

Effect of Natural Cyclodextrins on Cell Growth, Activity and Permeability of &lt;i&gt;Arthrobacter simplex&lt;/i&gt;

In this study, the biotransformation which from cortisone acetate (CA) to prednisone acetate (PA) by Arthrobacter simplex (ASP) was selected as a model system for evaluating the effects of natural cyclodextrins (α-CD, β-CD and γ-CD, referred as CDs) on cell growth, dehydrogenase activity, permeability of Arthrobacter simplex. The results showed that the cavity size of cyclodextrins on ASP cell growth were quite different, the with smaller cavity significantly inhibited ASP growth. CDs reduced the dehydrogenase activity of ASP and increased the cell permeability. Initial conversion rate of cells after treated by CDs were higher than the control cells. The study provided basic datas for the application of cyclodextrin in the steroid biotransformation.

A novel fungus concentration-dependent rat model for acute invasive fungal rhinosinusitis: an experimental study.

BackgroundAcute invasive fungal rhinosinusitis is a lethal infectious process afflicting immunocompromised individuals. Knowledge about this disease is still limited due to the scarcity of animal models designed to study the pathogenesis of this infection. Mast cells are tissue-resident immune cells that participate in a variety of allergic and inflammatory conditions. Limited attention has been given to the role of mast cells in acute invasive fungal rhinosinusitis. Therefore, the objectives of this study were to create a rat model of acute invasive fungal rhinosinusitis based on analyzing the impact of different fungal concentrations on establishing infection, and to observe the changes of mast cells in rats with this disease.MethodsSprague–Dawley rats were divided randomly into four groups, three of which were experimental and received different concentrations of Aspergillus fumigatus inoculations, and one was a control group (D). The inoculated Aspergillus fumigatus concentrations were 5 × 107 conidia/ml in group A, 107 conidia/ml in group B, and 106 conidia/ml in group C. Before fungal inoculation, rats were immunosuppressed using cyclophosphamide and cortisone acetate, and had Merocel sponges inserted into the right nares. Hematology and histopathology investigations were then performed.ResultsAn acute invasive fungal rhinosinusitis rat model was established successfully with an incidence rate of 90% in group A, 50% in group B and 10% in group C. Aspergillus fumigatus invasion was observed in 20% of the lungs in group A, but was not seen in the remaining groups. In addition, no fungi invaded the orbital tissue, brains, livers, spleens or kidneys of any rat. Compared with the control set, the total number of mast cells in the experimental groups was not significantly increased, but mast cell degranulation, on the other hand, was only found in infected nasal cavities.ConclusionsThis investigation illustrates that various fungal concentrations have different effects on the incidence of acute invasive fungal rhinosinusitis, and it also demonstrates the feasibility of using this model to study the process of fungal rhinosinusoidal invasion. In addition, the results suggest that mast cells may play a role in the protection of sinuses against acute Aspergillus fumigatus infection and in the clearance of established hyphal masses.Electronic supplementary materialThe online version of this article (doi:10.1186/s12879-014-0713-y) contains supplementary material, which is available to authorized users.

On the postoperative steroid replacement in patients with ACTH independent Cushing's Syndrome

Objective To investigate the preoperative factors in influencing the postoperative steroid replacement in patients with ACTH-independent Cushing's syndrome.Methods One hundred and eighty-one patients with adrenal cortical adenoma underwent unilateral adrenalectomy from 2003 to 2013.All preoperative and postoperative follow-up clinical parameters were acquired and analyzed.Results All patients need glucocorticoid (GC) replacement during and after surgery.At the median follow-up of 32 months (14-64 months),104 patients withdrew the cortisone acetate replacement,with a median replacement duration of 12 months (6-15 months) and an average cumulative dosage of(8.12 ± 5.07) g.Spearman correlation analysis showed that the age at diagnosis was positively correlated with the duration of GC replacement therapy (r =0.250,P =0.010) as well as the cumulative dosage of GC(r=0.244,P =0.013).Multiple stepwise regression analysis indicated that age at diagnosis was the independent factor that influenced both the duration and cumulative dosage of postoperative cortisone acetate replacement(P＜0.05).Plasma ACTH levels gradually increased and peaked during the 9th month,there was a lag of several months in the recovery of normal adrenal responsiveness.After that period,corticosteroid rose to normal levels,and followed by plasma ACTH concentrations,which fell to normal.2.88％ (3/104) of the patients presented with steroid withdrawal syndrome (SWS).Most features of hypercortisolism resolved within 6 months after surgery.Conclusion An empirical experience in Ruijin hospital in using cortisol replacement therapy for patients with ACTH-independent Cushing's syndrome after unilateral adrenalectomy was herewith reported.The older patients tended to prolong the replacement therapy of steroids and thus had to deal with a larger cumulative dosage.We should be aware of the risk of development of SWS postoperatively. Key words: Cushing's syndrome ; Adrenalectomy ; Steroid replacement therapy ; Hypothalamic-pituitary-gonad axis

The effect of ethanol on cell properties and steroid 1-en-dehydrogenation biotransformation of Arthrobacter simplex.

Resting cells of Arthrobacter simplex with 1-en-dehydrogenation ability were prepared and treated by ethanol at subinhibitory concentrations (4%-15%, v/v), then added into the ethanol-free system containing low concentration of cortisone acetate (1 g L(-1)) to produce prednisone acetate by C1,2 dehydrogenation reaction. Results showed that, within the range of ethanol concentration, the initial conversion rate was varied significantly with the concentration of ethanol and the maximum was obtained at 8% (v/v) ethanol, which was increased by 32.6% compared with the control. A series of cell features closely relevant to biotransformation efficiency were further analyzed. It indicated that ethanol acting on cell wall and membrane could be used as a mediator to enhance cell permeability, which facilitated the penetration of substrate across cell barrier within a short time, resulting in the elevated initial conversation rate. The observation of fatty acids composition suggested that the increased unsaturated fatty acids, especially cis-isomers, in the presence of ethanol led to the disorganization of the native arrangement of lipids and thus increased cell permeability. Our findings demonstrated that another facilitation of ethanol was to promote substrate transport into cells by permeabilization, which would provide the guidance in the practical application of organic solvents in steroid biotransformation.

Photocatalytic decomposition of cortisone acetate in aqueous solution

The photocatalytic decomposition of cortisone 21-acetate (CA), a model compound for the commonly used steroid, cortisone, was studied. CA was photocatalytically decomposed in a slurry reactor with the initial rates between 0.11 and 0.46mgL−1min−1 at 10mgL−1 concentration, using the following heterogeneous photocatalysts in decreasing order of their catalytic activity: ZnO>Evonik TiO2 P25>Hombikat TiO2>WO3. Due to the lack of ZnO stability in aqueous solutions, TiO2 P25 was chosen for further experiments. The decomposition reaction was found to be pseudo-first order and the rate constant decreased as a function of increasing initial CA concentration. Changing the initial pH of the CA solution did not affect the reaction rate significantly. The decomposition reaction in the presence of the oxidizing sacrificial agent sodium persulfate showed an observed decomposition rate constant of 0.004min−1, lower than that obtained for TiO2 P25 (0.040min−1). The highest photocatalytic degradation rate constant was obtained combining both TiO2 P25 and S2O82− (0.071min−1) showing a synergistic effect. No reactive intermediates were detected using LC–MS showing fast photocatalytic decomposition kinetics of CA.

Amphiphilic polymeric micelle as pseudostationary phase in electrokinetic chromatography for analysis of eight corticosteroids in cosmetics

Amphiphilic polymeric micelle, as a novel pseudostationary phase in EKC was used to determine eight kinds of corticosteroids namely hydrocortisone, prednisolone, hydrocortisone acetate, prednisone, cortisone acetate, prednisolone acetate, dexamethasone, and triamcinolone acetonide in cosmetics. Amphiphilic random copolymer poly(methyl methacrylate-co-methacrylic acid) (P(MMA-co-MAA)) was micellizated via neutralization in alkaline aqueous solution. The influences of the molar ratio of monomer MMA to MAA, the concentration of polymer and pH on the polymeric micelle microstructure and EKC performances were investigated. As molar ratio of MMA to MAA in P(MMA-co-MAA) increased, both CMC and environmental polarity of the inner core in polymeric micelle decreased dramatically. With increasing monomer ratio, the size of polymeric micelles increased firstly, and then decreased, finally increased again. ζ potential of the micelle had a slight decline trend. As increment of polymer concentration, the size of the polymeric micelle increased steadily. By optimizing the monomer ratio, the polymer concentration, and pH of the running buffer, as well as operation conditions such as separation voltage and temperature, the eight analytes could be separated within 16.5 min using 7.5 mg/mL polymer with the monomer ratio of 7:3 dissolved in pH 9.2 borax buffer as the running buffer. The method has been used for analysis of corticosteroids in cosmetic samples with simple extraction; the recoveries for eight analytes were between 85.9 and 106%. This method was of accuracy, repeatability, pretreatment simplicity, and could be applied to the quality control of cosmetics.

Cortisone Acetate Induced Acute Flare-Up of HBV Infection in A Growth Hormone Deficient Patient

Reactivation of hepatitis B virus is a known complication of immunosuppressive therapy and may cause liver failure and even death. A twenty-year-old male patient visited the endocrinology department because of short stature and diagnosed as growth hormone deficient. Somatropin and cortisone acetate were initiated. After six months, HBV reactivation was occurred. Antiviral treatment with lamivudine was initiated after the increase in transaminases. After a six months’ initiating lamivudine therapy, his physical examination and laboratory test results were found to be normal. In conclusion, every patient who are planned to be received immunosuppressive therapy should be screened for HBV infection.

Consensus statement on the diagnosis, treatment and follow‐up of patients with primary adrenal insufficiency

Primary adrenal insufficiency (PAI), or Addison's disease, is a rare, potentially deadly, but treatable disease. Most cases of PAI are caused by autoimmune destruction of the adrenal cortex. Consequently, patients with PAI are at higher risk of developing other autoimmune diseases. The diagnosis of PAI is often delayed by many months, and most patients present with symptoms of acute adrenal insufficiency. Because PAI is rare, even medical specialists in this therapeutic area rarely manage more than a few patients. Currently, the procedures for diagnosis, treatment and follow-up of this rare disease vary greatly within Europe. The common autoimmune form of PAI is characterized by the presence of 21-hydroxylase autoantibodies; other causes should be sought if no autoantibodies are detected. Acute adrenal crisis is a life-threatening condition that requires immediate treatment. Standard replacement therapy consists of multiple daily doses of hydrocortisone or cortisone acetate combined with fludrocortisone. Annual follow-up by an endocrinologist is recommended with the focus on optimization of replacement therapy and detection of new autoimmune diseases. Patient education to enable self-adjustment of dosages of replacement therapy and crisis prevention is particularly important in this disease. The authors of this document have collaborated within an EU project (Euadrenal) to study the pathogenesis, describe the natural course and improve the treatment for Addison's disease. Based on a synthesis of this research, the available literature, and the views and experiences of the consortium's investigators and key experts, we now attempt to provide a European Expert Consensus Statement for diagnosis, treatment and follow-up.

Efficacy of aerosolized liposomal amphotericin B against murine invasive pulmonary mucormycosis

Invasive pulmonary mucormycosis is a life-threatening fungal infection encountered in immunocompromised patients. An intravenous high-dose lipid formulation of amphotericin B, such as liposomal amphotericin B (L-AMB), is the recommended treatment. The efficacy of inhaled L-AMB against mucormycosis has not been evaluated. We evaluated the efficacy of inhaled aerosolized L-AMB in murine invasive pulmonary mucormycosis. ICR female mice were immunosuppressed with cortisone acetate and cyclophosphamide and challenged on day 0 with 1 × 10⁶ conidia of Rhizopus oryzae (TIMM 1327) intratracheally. Infected mice were assigned to one of the following 3 treatment groups: (i) control, (ii) treatment only (aerosolized L-AMB from day 1-5 after challenge), and (iii) prophylaxis followed by treatment (aerosolized L-AMB from day -2 to 5 before and after challenge). Survival was monitored until 12 days after challenge. For fungal-burden and histopathological examination, mice were sacrificed 4 h after treatment on day 3. Numbers of colony-forming units per lung were calculated. To study the distribution of AMB after inhalation of L-AMB, immunohistochemical studies using AMB antibody were performed. Aerosolized L-AMB significantly improved survival rate and decreased fungal burden compared with control group, and histopathology findings were superior to those of control group. However, no significant differences were detected between the treatment-only and prophylaxis followed by treatment groups. Immunohistochemical analysis showed that L-AMB was promptly distributed in lung tissue after inhalation therapy. Aerosolized L-AMB showed modest efficacy against R. oryzae infection in mice treated after fungal challenge. Prophylaxis with aerosolized L-AMB was not effective in this animal model.

Construction of engineered Arthrobacter simplex with improved performance for cortisone acetate biotransformation

Arthrobacter simplex 156 is a microorganism that is used for steroid drug biotransformation of cortisone acetate (CA) to prednisone acetate (PA). The enzyme 3-ketosteroid-△(1)-dehydrogenase encoded by the ksdD gene plays an important role in the bioconversion process. To further improve the biotransformation efficiencies of the industrial strain, a genetic manipulation system for A. simplex 156 was developed. Additional copies of the ksdD gene under the control of the cat promoter (from pXMJ19) were transferred into the strain A. simplex 156 and integrated into the 16S rDNA sites, yielding a series of recombinant strains. One of these recombinant strains, designated A. simplex M158, exhibited superior properties for CA biotransformation. At the substrate concentration of 83.6 g/l, the highest PA production of the recombinant strain reached 66.7 g/l, which is approximately 32.9 % higher than that of wild-type strains, and the incubation time for CA to PA bioconversion was reduced by 20 h. Southern blotting analysis of the recombinant strain indicated two copies of deregulated ksdD genes were integrated into the 16S rDNA sites, which means two of five 16S rRNA operons were insertionally disrupted in the recombinant strain. However, the disruption of the two 16S rRNA operons did not affect the growth rate of the recombinant strain, which survived and thrived under desired conditions. In addition, the new strain was genetically stable for more than 100 generations without the use of antibiotics for selection. These superior characteristics make the new strain more suitable than the wild-type strain for PA production.

Microstructure of microemulsion modified with ionic liquids in microemulsion electrokinetic chromatography and analysis of seven corticosteroids

In this work, the influences of ionic liquid (IL) as a modifier on microemulsion microstructure and separation performance in MEEKC were investigated. Experimental results showed that synergetic effect between IL 1-butyl-3-methylimidazolium tetrafluoro-borate (BmimBF4 ) and surfactant SDS gave a decreased CMC. With increment of IL in microemulsion, negative ζ potential of the microdroplets reduced gradually. The influence of IL on the dimensions of microdroplet was complicated. At BmimBF4 less than 8 mM, IL made microemulsion droplet smaller in size. While at BmimBF4 more than 10 mM, the size increased and reached to a maximum value at 12 mM, where the microdroplets were larger than that without IL. After that, the micreodroplet size decreased again. Relative fluorescence intensity of the first vibration band of pyrene to the third one (I1 /I3 ) enhanced as IL was added to microemulsion, which indicated that this addition increased environmental polarity in the inner core of microdroplets. Prednisone, hydrocortisone, prednisolone, hydrocortisone acetate, cortisone acetate, prednisolone acetate, and triamcinolone acetonide were analyzed with MEEKC modified with IL to evaluate the separation performance. Cortisone acetate and prednisolone acetate could not be separated at all in typical microemulsion. The seven analytes could be separated by the addition of 10 mM BmimBF4 into the microemulsion system. The method has been used for analysis of corticosteroids in cosmetic samples with simple extraction; the recoveries for seven analytes were between 86 and 114%. This method provides accuracy, reproducibility, pretreatment simplicity, and could be applied to the quality control of cosmetics.

Obesity and Familial Predisposition Are Significant Determining Factors of an Adverse Metabolic Profile in Young Patients with Congenital Adrenal Hyperplasia

Background/Aims: Glucocorticoid (GC) therapy is known to predispose to an adverse metabolic profile. Therefore, we investigated the prevalence of obesity and metabolic syndrome (MetS) in young patients with congenital adrenal hyperplasia (CAH) and to correlate this prevalence with GC treatment and family history. Methods: The study population consisted of 33 young CAH patients who received cortisone acetate during their growth periods; those who were salt wasters also received fludrocortisone. Obesity was defined by a body mass index (BMI) >95th percentile and MetS by the National Cholesterol Education Program Third Adult Treatment Panel modified criteria. Each patient's familial history of MetS components was assessed. The impact of GC therapy on the metabolic profile was analyzed by comparing CAH patients with BMI z-score-matched controls. Results: MetS and obesity were observed in 12.1 and 30.3% of the CAH patients, respectively, both of which were higher than in the reference population. A positive family history of MetS was found to be more prevalent in the obese patients compared with the nonobese CAH patients, and similar findings were observed for the controls. The metabolic profile did not differ between the CAH patients and matched subjects. Conclusion: CAH patients presented a higher prevalence of obesity and MetS, which were not correlated with the GC treatment. This study suggests that obesity and familial predisposition are significant determining factors for an adverse metabolic profile in CAH patients.

Glucocorticoids and microbiota regulate ontogeny of intestinal fucosyltransferase 2 requisite for gut homeostasis

At weaning, the intestinal mucosa surface glycans change from predominantly sialylated to fucosylated. Intestinal adaptation from milk to solid food is regulated by intrinsic and extrinsic factors. The contribution by glucocorticoid, an intrinsic factor, and colonization by microbiota, an extrinsic factor, was measured as the induction of α1,2/3-fucosyltransferase and sucrase-isomaltase (SI) activity and gene expression in conventionally raised, germ-free, and bacteria-depleted mice. In conventionally raised mice, cortisone acetate (CA) precociously accelerated SI gene expression up to 3 weeks and fut2 to 4 weeks of age. In germ-free mice, CA treatment induces only SI expression but not fucosyltransferase. In post-weaning bacteria-deficient (germ-free and bacteria-depleted) mice, fut2 expression remains at low suckling levels. In microbiota deficient mice, intestinal fut2 (but not fut1, fut4 or fut7) was induced only by adult microbiota, but not immature microbiota or CA. Fut2 induction could also be restored by colonization by Bacteroides fragilis, but not by a B. fragilis mutant unable to utilize fucose. Restoration of fut2 expression (by either microbiota or B. fragilis) in bacteria-depleted mice is necessary for recovery from dextran sulfate sodium-induced mucosal injury. Thus, glucocorticoids and microbes regulate distinct aspects of gut ontogeny: CA precociously accelerates SI expression and, only in colonized mice, fut2 early expression. The adult microbiota is required for the fut2 induction responsible for the highly fucosylated adult gut phenotype and is necessary for recovery from intestinal injury. Fut2-dependent recovery from inflammation may explain the high incidence of inflammatory disease (Crohn's and necrotizing enterocolitis) in populations with mutant FUT2 polymorphic alleles.

Nystatin nanosizing enhances in vitro and in vivo antifungal activity against Candida albicans

In this study, we developed a nanoparticulate nystatin formulation and performed a comparative evaluation against a commercial nystatin preparation of its in vitro and in vivo antifungal activities. A nystatin nanosuspension was prepared from a commercially available suspension by wet-media milling. The nanosuspension was characterized for particle size by laser diffraction and assayed for content by HPLC. Its in vitro activity was evaluated against Candida albicans strains SC5314 and LAM-1 (12.5-5000 μg/mL) using an agar plate assay and its in vivo efficacy was evaluated using a murine model of oral candidiasis. Briefly, DBA/2 mice were immunosuppressed with cortisone acetate, orally infected with C. albicans strain LAM-1, and treated for 14 days with conventional nystatin suspension, nystatin nanosuspension or saline control. Efficacy endpoints were oral fungal burden, mouse survival and organ histopathology. A single-dose pharmacokinetic study was also performed. The median particle size of the nystatin suspension was reduced from 6577 to 137 nm. The HPLC assay demonstrated a nystatin content of 98.7% ± 0.8% of the label claim. In vitro activity was superior to that of the conventional nystatin suspension at 100-5000 μg/mL concentrations. Beginning on day 3 of treatment, lower oral burdens of C. albicans were found in the nanosuspension group compared with the suspension and control groups. Mouse survival was also superior in the nanosuspension group. No systemic absorption was observed. Taken together, these data reveal that nanonization of nystatin provides a novel approach to enhancing its efficacy in the treatment of oral candidiasis.

Microbiota and glucocorticoids regulate postnatal developmental of intestinal Fut2 gene expression

Intestinal maturation is regulated by intrinsic (glucocorticoid) and extrinsic (resident microflora) factors and the goal of this study is to determine the relative contribution of these two regulators in the postnatal development of α1,2‐fucosyltransferase II (Fut2) and sucrase‐isomaltase (SI) gene expression. In conventional raised (CONV) mice, ontogeny of Fut2 and SI gene expression was completed by fourth week. In the absence of colonization in germ‐free (GF) and bacteria‐depleted (BD) mice, intestinal Fut2 expression returned to low suckling levels. Ten days after colonization with adult, but not with suckling, gut microbiome, expression of Fut2 mRNA, α1,2‐fucosyltransferase activity and fucose α1,2‐linked glycoconjugates expression is fully recovered. In the GF mice, the rate of Fut2 and SI ontogeny was significantly delayed. Cortisone acetate (CA) precociously accelerated both Fut2 and SI gene expression in conventionally raised suckling pups. In the GF suckling mice, CA treatment precociously induced development of SI but not Fut2 gene expression. Thus, both microbes and glucocorticoids regulate gut ontogeny, but only suckling gut responds to CA and Fut2 expression remains primarily sensitive to adult microbiome. Complete recovery from mucosal injury caused by DSS‐treatment was observed in the CONV, but not in BD mice. Lack of recovery in BD mice correlated with the level of Fut2 expression in the gut. Thus, colonization by adult microbiota stimulated mature Fut2 gene expression and fucosylated gut phenotype; this colonization‐dependent Fut2 induction is necessary for full recovery from intestinal injury. This may explain the significant association observed between individuals expressing low Fut2 gene expression because of specific Fut2 polymorphic alleles and Crohn's disease and necrotizing enterocolitis.Supported by D059126, HD013021, AI075563, and DK070260.

High-dose induction liposomal amphotericin B followed by de-escalation is effective in experimental Aspergillus terreus pneumonia

Aspergillus terreus is considered to be resistant to amphotericin B (AMB). However, it is unknown whether higher daily doses of liposomal AMB (L-AMB) can overcome this resistance in vivo. We evaluated the efficacy and total lung homogenate AMB concentrations of escalating intravenous doses of L-AMB (3-20 mg/kg daily) versus an induction-de-escalation dosing strategy (10 mg/kg/day ×3 days, then 3 mg/kg/day) in an experimental neutropenic murine model of A. terreus pneumonia. BALB/c mice were rendered neutropenic with cyclophosphamide and administered cortisone acetate prior to intranasal inoculation (3.5 × 10(6) conidia) with A. terreus (Etest MIC 8 mg/L). Mice were then treated with L-AMB regimens for 5-7 days. The efficacy was assessed by animal survival and quantitative PCR lung fungal burden. Total AMB lung homogenate concentrations were determined by HPLC. Compared with untreated controls, 10 mg/kg/day L-AMB prolonged survival (mean >7 versus 3-4 days, P < 0.003) and reduced A. terreus lung fungal burden (median log10 conidial DNA 5.0 versus 6.7, P < 0.05). Daily L-AMB regimens >10 mg/kg/day were associated with poorer survival and higher lung fungal burden. The induction-de-escalation strategy of 10 mg/kg/day ×3 days followed by 3 mg/kg/day was as effective as 10 mg/kg daily dosing, and resulted in higher mean AMB lung homogenate concentrations compared with a continuous 10 mg/kg regimen (23.2 ± 6.7 versus 16.4 ± 4.4 μg/g, P = 0.09). A high-dose induction-de-escalation L-AMB dosing strategy was an effective treatment for experimental A. terreus pneumonia in neutropenic mice.

Mineralocorticoid replacement during infancy for salt wasting congenital adrenal hyperplasia due to 21-hydroxylase deficiency

OBJECTIVE:The protocols for glucocorticoid replacement in children with salt wasting 21-hydroxylase deficiency are well established; however, the current recommendation for mineralocorticoid replacement is general and suggests individualized dose adjustments. This study aims to retrospectively review the 9-∝-fludrocortisone dose regimen in salt wasting 21-hydroxylase deficient children who have been adequately treated during infancy.METHODS:Twenty-three salt wasting 21-hydroxylase deficient patients with good anthropometric and hormonal control were followed in our center since diagnosis. The assessments of cortisone acetate and 9-∝-fludrocortisone doses, anthropometric parameters, and biochemical and hormonal levels were rigorously evaluated in pre-determined intervals from diagnosis to two years of age.RESULTS:The 9-∝-fludrocortisone doses decreased over time during the first and second years of life; the median fludrocortisone doses were 200 μg at 0-6 months, 150 μg at 7-18 months and 125 μg at 19-24 months. The cortisone acetate dose per square meter was stable during follow-up (median = 16.8 mg/m2/day). The serum sodium, potassium and plasma rennin activity levels during treatment were normal, except in the first month of life, when periodic 9-∝-fludrocortisone dose adjustments were made.CONCLUSIONS:The mineralocorticoid needs of salt wasting 21-hydroxylase deficient patients are greater during early infancy and progressively decrease during the first two years of life, which confirms that a partial aldosterone resistance exists during this time. Our study proposes a safety regiment for mineralocorticoid replacement during this critical developmental period.

Observation on the therapeutic effect of scalp acupuncture and body acupuncture in combination with rehabilitation exercise for hemiplegia and shoulder pain after stroke

ObjectiveTo evaluate the therapeutic effect of scalp acupuncture and body acupuncture in combination with rehabilitation exercise for hemiplegia and shoulder pain after stroke. MethodsSixty cases were randomly divided into an acupuncture rehabilitation group (33 cases) and a routine treatment group (27 cases). Both two groups received rehabilitation exercise, acupuncture rehabilitation group was treated with scalp acupuncture and body acupuncture, and in body acupuncture, Píshu (▪ BL 20), Wèishu (▪ BL 21), Zúsānl▪ (▪ ST 36), Fēnglóng (▪ ST 40), Xuèh▪i (▪) SP 10), and accompanying points according to the symptoms were selected; in scalp acupuncture, B▪ihuì (▪ GV 20), Sìsháncōng (▪ EX-HN 1), motor area, vascular dilation and constriction area were selected. Routine treatment group was treated with western drugs, including dehydration with mannitol to reduce intracranial pressure, control blood pressure, and brain cell protective agent was given, triamcinolone acetate solution for shoulder pain or cortisone acetate solution for blocking treatment. The treatment was given once a day, four weeks were one course, and four courses were given in all. The hemorheological indices and the clinical effect of two groups were compared. ResultsThe effective rate of acupuncture rehabilitation group was 90.9% (30/33), better than that of 70.4% (19/27) in routine treatment group (P < 0.05); whole blood viscosity low shear and middle shear, plasma viscosity and hematocrit after the treatment became lowered than those before the treatment in acupuncture rehabilitation group (all P<0.05); whole blood viscosity and plasma viscosity after the treatment was also lowered than those before the treatment in routine treatment group (both P<0.05); whole blood viscosity low shear and middle shear, plasma viscosity and hematocrit after the treatment in acupuncture rehabilitation group were obviously lowered than those of routine treatment group (all P<0.05). ConclusionWith good therapeutic effect and better efficacy than routine medical treatment, scalp acupuncture and body acupuncture in combination with rehabilitation exercise can improve the movement, sensation and hemorheology of extremities of patients with hemiplegia and shoulder pain after stroke.

Therapy of adrenal insufficiency: an update

Adrenal insufficiency may be caused by the destruction or altered function of the adrenal gland with a primary deficit in cortisol secretion (primary adrenal insufficiency) or by hypothalamic-pituitary pathologies determining a deficit of ACTH (secondary adrenal insufficiency). The clinical picture is determined by the glucocorticoid deficit, which may in some conditions be accompanied by a deficit of mineralcorticoids and adrenal androgens. The substitutive treatment is aimed at reducing the signs and symptoms of the disease as well as at preventing the development of an addisonian crisis, a clinical emergency characterized by hypovolemic shock. The oral substitutive treatment should attempt at mimicking the normal circadian profile of cortisol secretion, by using the lower possible doses able to guarantee an adequate quality of life to patients. The currently available hydrocortisone or cortisone acetate preparations do not allow an accurate reproduction of the physiological secretion pattern of cortisol. A novel dual-release formulation of hydrocortisone, recently approved by EMEA, represents an advancement in the optimization of the clinical management of patients with adrenal insufficiency. Future clinical trials of immunomodulation or immunoprevention will test the possibility to delay (or prevent) the autoimmune destruction of the adrenal gland in autoimmune Addison's disease.