Long-term Prednisone Treatment Research Articles

Long-term prednisone treatment causes fungal microbiota dysbiosis and alters the ecological interaction between gut mycobiome and bacteriome in rats.

Glucocorticoids (GCs) are widely used in the treatment of immune-mediated diseases due to their anti-inflammatory and immunosuppressive effects. Prednisone is one of the most commonly used GCs. However, it is still unknown whether prednisone affects gut fungi in rats. Herein we investigated whether prednisone changed the composition of gut fungi and the interactions between gut mycobiome and bacteriome/fecal metabolome in rats. Twelve male Sprague-Dawley rats were randomly assigned to a control group and a prednisone group which received prednisone daily by gavage for 6 weeks. ITS2 rRNA gene sequencing of fecal samples was performed to identify differentially abundant gut fungi. The associations between gut mycobiome and bacterial genera/fecal metabolites obtained from our previously published study were explored by using Spearman correlation analysis. Our data showed that there were no changes in the richness of gut mycobiome in rats after prednisone treatment, but the diversity increased significantly. The relative abundance of genera Triangularia and Ciliophora decreased significantly. At the species level, the relative abundance of Aspergillus glabripes increased significantly, while Triangularia mangenotii and Ciliophora sp. decreased. In addition, prednisone altered the gut fungi-bacteria interkingdom interactions in rats after prednisone treatment. Additionally, the genus Triangularia was negatively correlated with m-aminobenzoic acid, but positively correlated with hydrocinnamic acid and valeric acid. Ciliophora was negatively correlated with phenylalanine and homovanillic acid, but positively correlated with 2-Phenylpropionate, hydrocinnamic acid, propionic acid, valeric acid, isobutyric acid, and isovaleric acid. In conclusion, long-term prednisone treatment caused fungal microbiota dysbiosis and might alter the ecological interaction between gut mycobiome and bacteriome in rats.

Integrative Analysis of Gut Microbiota and Fecal Metabolites in Rats after Prednisone Treatment.

ABSTRACTPrednisone (PRED) is a synthetic glucocorticoid (GC) widely used in immune-mediated diseases for its immunosuppressive and anti-inflammatory properties. The effects of GC are achieved by genomic and nongenomic mechanisms. However, the nongenomic effects are largely unknown. Thus, we aimed to investigate how long-term prednisone therapy changes the composition of the gut microbiota and fecal metabolites in rats. Male Sprague-Dawley rats were randomly assigned to a control (CON) group and a PRED group, which received prednisone treatment daily for 6 weeks by gavage. The V3 to V4 regions of bacterial 16S rRNA genes were amplified and sequenced after the total bacterial DNA was extracted from fecal samples. The alpha and beta diversities were calculated. The compositional alteration of the gut microbiota at different taxonomic levels was analyzed using the Metastats method. Meanwhile, the fecal metabolites were quantitated in an ultra-performance liquid chromatography system. Similar microbial richness and diversity between the CON and PRED groups were indicated by the alpha diversity results. The gut microbial communities differed significantly between two groups. The relative abundances of the genera Eisenbergiella, Alistipes, and Clostridium XIVb decreased, whereas that of Anaerobacterium increased significantly in rats after the 6-week prednisone treatment. In total, 11 downregulated and 10 upregulated fecal metabolites were identified. Differential fecal metabolites were enriched in the pathways, including phenylalanine metabolism, butanoate metabolism, and propanoate metabolism. The lowered production of short-chain fatty acids was associated with the decreased relative abundance of the genera Alistipes and Clostridium XIVb and increased abundance of the genus Anaerobacterium. The composition of the gut microbiota and fecal metabolites was changed after long-term prednisone treatment. This may help us to understand the pharmacology of prednisone.IMPORTANCE Prednisone is widely used in chronic glomerular diseases, immunological disorders, and rheumatic diseases for its anti-inflammatory and immunosuppressive properties. It is a synthetic glucocorticoid (GC) that shows therapeutic effects after conversion to prednisolone by the liver. Prolonged GC therapy causes anti-inflammatory effects; it also results in a variety of adverse events, including obesity, hypertension, psychiatric symptoms, and dyslipidemia. The therapeutic effects and adverse events of GCs may be associated with changes in the gut microbiota, as the host might be affected by the metabolites generated by the altered gut microbes. Thus, we investigated how long-term prednisone therapy changed the composition of the gut microbiota and fecal metabolites in rats. This study may shed new light on the pharmacology of prednisone.

Analysis of High Dose and Long-Term Prednisone Therapy on Trap 5B Level Change in Children with Steroid Sensitive Nephrotic Syndrome

Nephrotic syndrome is a condition which is characterized by protein leakage from the blood to the urine through glomeruli. It leads to hypoproteinemia and generalised oedema. Patients with nephrotic syndrome need high dose and long term glucocorticoid such as prednisone. High dose and long term glucocorticoid can increase bone resorption. Biological marker is a valuable tool to evaluate efficacy of therapy. TRAP 5B is a sensitive biological marker for bone resorption because it reflects the number of osteoclasts. TRAP 5B is not affected by renal dysfunction and food. It also has a low diurnal variation than other bone resorption marker. The aim of this study was to analyze the changes of TRAP 5B levels at induction and alternate phase in children with steroid sensitive nephrotic syndrome. This observational prospective study was conducted from May to October 2016. Venous blood samples obtained at 08.00-10.00 am. TRAP5B levels were measured before and after induction phase and after alternate phase using ELISA. Fifteen patients were included in this study (60% boys). Majority of their age was 6 - <12 years and 40% were dependent steroid NS. TRAP 5B serum levels in induction phase increased by 37.41%±56.22%. In alternate phase, TRAP 5B serum levels increased by 28.75%±66.55% compared to the induction phase. However, the level change of both phases were not significant. As a conclusion, TRAP 5B levels increased in induction and alternate phase after high dose and long-term prednisone treatment in nephrotic syndrome.

Therapeutic effects of glucocorticoids on the children nephrotic syndrome caused by acute nephritis after streptococcal infection

Objective To investigate the effects of glucocorticoids (GC) on the nephrotic syndrome (NS) caused by acute nephritis after streptococcal infection (PSAGN) in children. Methods Sixty-three children with the NS caused by PSAGN were studied controlly, all of them were administrated with standard long-term prednisone treatment based on the conventional treatment. The treatment outcome was compared with that of the conventional treatment group. Results 95. 2% (60/63) of patients in the GC group, the urinary protein became negative at the end of six months, 100% (63/63) negative at the end of twelve months.And in the conventional group the negative rates were 74% (37/50) and 80% (40/50) respectively at the same time. 95. 2% ( 60/63 ) of patients in the GC group microscopic hematuria disappeared at the end of twelve months, 100% (63/63) disappeared at the end of eighteen months. And in the conventional group the disappearance rates were 72% (36/50) and 84% (42/50) respectively at the same time. 92. 1 % (35/38)of patients in the GC group blood pressure returned to normal at the end of two months, 100% (38/38) normal at the end of three months. And in the conventional group the normal rates were 72.7% (24/33) and 84. 8% (28/33) respectively at the same time. 91. 7% (11/12) of patients in the GC group showed normal renal function at the end of one month, 100% (12/12) normal at the end of two months. And in the conventional group the normal rates were 42. 9% (3/7) and 57. 1% (12/12) at the same time. There were significant differences in the outcomes between the two groups( P ＜ 0.05 or P ＜ 0. 01). Conclusion With the useof GC for the NS caused by PSAGN in children.it can effectively reduce the duration of urinary protein and microscopic hematuria,and promote rapid recovery of renal function and blood pressure,thereby improving the prognosis. Key words: Nephrotic syndrome; Acute nephritis; Streptococcal infection; Glucocorticoids; Children

Invasive Trichophyton Rubrum Infection Occurring with Infliximab and Long-Term Prednisone Treatment

A 64-year-old woman presented with erythematous plaques, tender nodules, and pustules of the dorsal right hand and both legs following long-term treatment with systemic steroids and infliximab. Skin biopsy demonstrated dermal inflammation with foci of necrosis and multinucleated giant cells containing fungal spores. Tissue culture grew Trichophyton rubrum. To report a case that demonstrates the pathophysiology of invasive T. rubrum infection, the mechanisms of action and uses of tumor necrosis factor alpha (TNF-alpha)-inhibiting drugs, and how these drugs may increase patients' risk of invasive dermatophytosis. Dermatophytes such as T. rubrum rarely cause invasive disease. This unusual presentation of invasive T. rubrum occurred with immunosuppression by infliximab and systemic steroids. Patients should have a thorough examination for signs of latent infection before TNF-alpha inhibitors are prescribed, including inspection of the skin and nails for signs of dermatophytosis.

Chronic Cough Due to Nonasthmatic Eosinophilic Bronchitis: ACCP Evidence-Based Clinical Practice Guidelines

Nonasthmatic eosinophilic bronchitis is a newly recognized cause of chronic cough. Our objective was to review the pathogenesis, natural history, diagnosis, and treatment of this condition. The current literature was reviewed using an Ovid MEDLINE and PubMed literature review for all studies published in the English language from 1963 to December 2004 using the medical subject heading term "eosinophilic bronchitis." Nonasthmatic eosinophilic bronchitis is a common cause of chronic cough. It is characterized by the presence of eosinophilic airway inflammation, similar to that seen in asthma. However, in contrast to asthma, nonasthmatic eosinophilic bronchitis is not associated with variable airflow limitation or airway hyperresponsiveness. The differences in functional association are related to differences in the localization of mast cells within the airway wall, with airway smooth muscle infiltration occurring in patients with asthma, and epithelial infiltration in patients with nonasthmatic eosinophilic bronchitis. Diagnosis is made by the confirmation of eosinophilic airway inflammation usually with induced sputum analysis after the exclusion of other causes for chronic cough on clinical, radiologic, and lung function assessment. The cough usually responds well to treatment with inhaled corticosteroids. The dose and duration of treatment differ between patients. The condition can be transient, episodic, or persistent unless treated, and occasionally patients may require long-term prednisone treatment. Further study of this condition may improve our understanding of airway inflammation and airway responsiveness, leading to novel targets for therapeutic agents for the treatment of both asthma and nonasthmatic eosinophilic bronchitis.

Recurrent Antiviral‐Resistant Genital Herpes in an Immunocompetent Patient

Herpes simplex virus type 2 (HSV-2) resistance to antiviral drugs has been described primarily in immunocompromised patients. We report an apparently immunocompetent, human immunodeficiency virus-negative male patient who has experienced repeated HSV-2 genital outbreaks despite receiving antiviral prophylaxis with several different drugs. Several of the HSV-2 genital isolates from this patient have been confirmed as resistant to acyclovir and penciclovir. Antiviral resistance occurred in the setting of long-term prednisone treatment and intermittent acyclovir prophylaxis at suboptimal doses and persisted despite the cessation of oral steroid treatment. The patient's genital herpes outbreaks were not controlled by high-dose prophylaxis with acyclovir, valacyclovir, and famciclovir. Cessation of antiviral prophylaxis resulted in reversion of this patient's HSV-2 isolates to acyclovir and penciclovir sensitivity, although resistant virus reappeared when antiviral prophylaxis was resumed. Transmission of a sensitive HSV-2 strain from this patient to a female sex partner was observed. These observations confirm previous reports that resistance to acyclovir may develop during prophylactic therapy in an otherwise well, immunocompetent patient. These findings support the conclusion that both drug-sensitive and drug-resistant HSV-2 strains established latency in this patient and that both strains are capable of frequent reactivation.

IMPACT OF PREDNISONE ON VENTILATION AND DIAPHRAGM MUSCLE CONTRACTILITY IN MDX MICE

The mdx mouse is an animal model of muscular dystrophy. The goal of this project was to determine the effects of long-term prednisone treatment on ventilation and in vitro diaphragm muscle contractility in mdx mice. Three groups were studied: control (C57BL/10J, n = 9); mdx mice treated with a placebo (mdx-sham, n = 9); and mdx mice treated daily with prednisone (1mg/kg S.C.) (mdx-pred, n = 9) for 6 mo. After the treatment period, ventilation was measured in awake mice during room air breathing and in response to 7% CO2 using the barometric technique. There was no difference between groups during room air breathing for either tidal volume (Vt), respiratory rate (RR), or minute ventilation (Ve). In response to 7% CO2, Vt, RR, and Ve were all significantly lower (P < 0.05) in mdx-sham compared with control. In contrast, there was no difference in the above parameters between control and mdx-pred. Maximal isometric force (Po) was significantly higher in control (14.6 N/cm2) compared with both mdx-sham (5.8 N/cm2) and mdx-pred (6.4 N/cm2). These data suggest that long-term prednisone treatment improves ventilation in response to hypercapnia in mdx mice above that of untreated mdx mice but not equal to that of normal healthy controls. Long-term prednisone treatment however does not seem to improve diaphragm contractility. Supported by the American Lung Association and New York Affiliate.

IGF-I levels rise and GH responses to GHRH decrease during long-term prednisone treatment in man.

Glucocorticoid excess is associated with a blunted GH response to GHRH. IGF-I levels in hypercortisolism are controversial and have been reported as low, normal or high. The aim of this study was to evaluate longitudinally time-dependent changes in the GH response to GHRH, IGF-I, IGFBP-3 and albumin values in patients during corticotherapy. Six patients received GHRH before and after one week and one month of prednisone administration (20-60 mg/d, orally). IGF-I, IGFBP-3 and albumin were determined in each test, at time 0. Ten normal controls were also evaluated in one occasion. There were no differences in basal GH values, GH response to GHRH, IGF-I and IGFBP-3 levels between controls and patients before starting corticotherapy. Albumin (g/l; mean+/-SE) values were lower in patients before treatment (31+/-4) than in controls (43+/-1). After one week of prednisone administration there was a significant decrease in peak GH (microg/l) levels (before: 18.8+/-7.4; 1 week: 5.0+/-1.3), which was maintained after one month (8.1+/-3.5). IGF-I (microg/l) levels increased significantly, from 145+/-23 to 205+/-52 after one week of therapy, reaching levels of 262+/-32 after one month. IGFBP-3 (mg/l) values did not increase significantly (before: 2.1+/-0.2; 1 week: 2.5+/-0.3; 1 month: 2.8+/-0.2). Albumin levels showed a significant rise both after one week (36+/-4) and one month (42+/-3) of corticotherapy. In summary, we observed a marked decrease in the GH response to GHRH after one week and one month of prednisone administration associated with an increase in circulating IGF-I and albumin values. The physiological implications of these findings are still uncertain. It is possible that glucocorticoids increase hepatic IGF-I and albumin synthesis, although other mechanisms may have a role.

Long-term effects of steroid and cytostatic treatment on the clinical course of idiopathic membranous glomerulonephritis (retrospective study).

The clinical course of 30 patients with idiopathic membranous glomerulonephritis has been followed up for 8.1 +/- 3.4 (4-17) years. First, in each case a long-term prednisone treatment was administered. During this therapy 12 (40%) patients improved and 9 had remission. In the 18 (60%) steroid resistant cases the treatment was combined with cytostatic drugs. After a combined regime for 1.9 +/- 0.8 years, 8 patients have improved, 2 of whom remitted. It has been suggested that due to a long-term immunomodulator therapy the level of urinary protein excretion might be reduced in 77% of patients. There was no effect of the applied treatment in 7% of cases, still in 16% a gradual deterioration was observed. Relapsing nephrotic syndrome has occurred in 3 (10%) of the total cases. Side effects requiring cessation of treatment were not observed.

Intra-individual consistency of prednisolone kinetics during long-term prednisone treatment.

Eleven patients on long-term prednisone treatment were studied on two occasions separated by 45 to 325 days. In 10 patients the total body clearance of prednisolone only changed about 10%. In one case a 78.5% decrease was observed after stopping treatment with rifampicin and isoniazide. No association was found between the prednisone dose rate (mg/kg per month), patient age or mean endogenous plasma hydrocortisone level and prednisolone clearance/kg. The results indicate considerable intra-individual consistency of prednisolone kinetics if other conditions are not changed.

Alcoholic Hepatitis Superimposed on Cirrhosis. Clinical Significance and Effect of Long-term Prednisone Treatment

Of 483 patients with biopsy-verified cirrhosis who entered the controlled trial of prednisone treatment conducted by the Copenhagen Study Group for Liver Diseases, 99 had alcoholic hepatitis as defined by morphological criteria in the initial biopsy. The maximum period of observation varied from 5 to 12 years. The survival of prednisone-treated patients (median survival time 38 months) and placebo-treated patients (median survival time 34 months) with alcoholic hepatitis did not differ significantly. This was also true for each of the two subgroups comprising mild and severe cases respectively. The presence of morphologically defined alcoholic hepatitis was postively correlated with the daily consumption of alcohol but poorly correlated with the clinical syndrome usually attributed to alcoholic hepatitis.