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At least 109 records · Page 6Linked to original sources
PubMed2003

Formoterol (Foradil) and medium-high doses of inhaled corticosteroids are more effective than high doses of corticosteroids in moderate-to-severe asthma.

This double-blind, randomised, multi-centre, parallel-group study compared the effect of adding Foradil (formoterol fumarate) to existing medium-high doses of inhaled corticosteroids (ICS) with that of doubling the dose of ICS in patients with sub-optimally controlled asthma. After a run-in period, 203 patients with moderate-to-severe asthma who remained symptomatic despite treatment with 500 microg beclomethasone twice daily, were randomised to receive either 12 microg formoterol twice daily (Foradil Aerolizer), Novartis) in addition to beclomethasone 500 microg twice daily, or beclomethasone 1000 microg twice daily and placebo for 12 weeks. The primary efficacy variable was mean morning pre-medication peak expiratory flow (PEF) during the last seven days of treatment. The difference in PEF between treatments was 27.78 l/min in favour of the formoterol/beclomethasone combination (95% CI 13.42, 42.14 l/min, p=0.0002, intention-to-treat population). Significant differences in the urinary cortisol/creatinine ratio between treatment groups at 12 weeks (p=0.001) indicated suppression of the hypothalamic-pituitary-adrenal axis in the patients on beclomethasone 1000 microg twice daily. The addition of formoterol 12 microg twice daily to beclomethasone in patients with asthma who were poorly controlled with beclomethasone 500 microg twice daily was more effective than doubling the ICS dose and resulted in less suppression of the hypothalamic-pituitary-adrenal axis.

Administration, Inhalation↗
PubMed2006

The differential expression of corticosteroid receptor isoforms in corticosteroid-resistant and -sensitive patients with rheumatoid arthritis.

OBJECTIVE: A proportion of patients with rheumatoid arthritis (RA) fail to respond adequately to corticosteroid (CS) therapy. Using an in vitro CS sensitivity bioassay, we have subdivided RA patients into steroid-sensitive (SS) and -resistant (SR) subgroups and this correlates with clinical responses to CS therapy. CSs exert their effects via the CS receptor (CR), which exists as two main isoforms, CRalpha and CRbeta. CRbeta can function as a negative inhibitor of CRalpha. We have hypothesized that steroid resistance in RA patients is due in part to a relative over-expression of the CRbeta. METHODS: Peripheral blood mononuclear cells (PBMCs) were isolated from SS and SR RA patients. CRalpha and CRbeta mRNA expression was determined by quantitative real time polymerase chain reaction (qRT-PCR). The ratio of CRbeta/CRalpha mRNA expression was determined. CRalpha and CRbeta protein expression by PBMCs was analysed by flow cytometry. RESULTS: qRT-PCR analysis showed a trend towards higher expression of both CRbeta and basal CRbeta/CRalpha ratio in SR RA patients. Stimulation of PBMCs in vitro with concanavalin-A induced a significantly higher CRbeta mRNA expression, and CRbeta/CRalpha ratio in SR RA patients compared with SS patients, which was not inhibited by hydrocortisone. Flow cytometry showed that the percentage of PBMCs staining for CRbeta protein was significantly lower in the SS RA group (SS 43.3 +/- 14.8% vs SR 88.6 +/- 8.6%; P < 0.0010). The mean intensity of fluorescence CRbeta staining was higher in the SR RA patients (P < 0.001). CONCLUSION: We show for the first time that CRbeta is over-expressed in SR RA patients and that hydrocortisone fails to inhibit concanavalin-A stimulated increase in CRbeta mRNA in SR RA patients. This mechanism may contribute in part to the CS hyporesponsiveness seen in some RA patients.

Adrenal Cortex Hormones↗
PubMed2005

Comparison of inhaled corticosteroid combined with theophylline and double-dose inhaled corticosteroid in moderate to severe asthma.

OBJECTIVE: Recent studies have found that theophylline exerts anti-inflammatory and immunomodulatory effects. This study was performed to compare the efficacy of inhaled corticosteroids (ICS) combined with slow-release theophylline (SRT) with that of double-dose ICS in asthma control, anti-inflammatory activity and safety. METHODOLOGY: In a randomized, open, parallel, control trial, 41 patients with asthma were randomly treated with either beclomethasone dipropionate 500 microg b.i.d. (BDP group) or a combination of BDP 250 microg b.i.d and SRT 0.2 g b.i.d. (SRT/BDP group) for 6 weeks. At the start and at the end of treatment, lung function testing and sputum induction were performed, and plasma cortisol levels were measured. Sputum was analyzed for cell differential counts and the interleukin (IL)-5 level. Patients kept a record of peak expiratory flow (PEF), symptom score, and beta2-agonist use. RESULTS: Significant increases in the morning and the evening PEF and FEV1 were observed (P < 0.05), together with an obvious reduction in symptom score and beta2-agonist use (P < 0.01). Significant decreases in the percentage eosinophils and IL-5 level in induced sputum also occurred (P < 0.05). However, there was no difference between the two groups for all these parameters. There was no significant change in the plasma cortisol level for either group. CONCLUSIONS: Both ICS combined with SRT and double-dose ICS had the same effect on asthma control, improving symptoms and ameliorating lung function. Both therapies had similar anti-airway inflammatory effects and therapeutic safety. Combining SRT with ICS may allow a reduction in ICS dose when treating asthma.

Administration, Inhalation↗
PubMed2002

Mechanisms of corticosteroid resistance in rheumatoid arthritis: a putative role for the corticosteroid receptor beta isoform.

Corticosteroids (CSs) have potent immunosuppressive effects and are commonly used to treat a range of immunological and inflammatory diseases such as rheumatoid arthritis (RA). These effects are mediated by the ability of CSs to modulate gene expression. CSs act by binding to the CS receptor (CR), which exists as alpha and beta isoforms. Only CRalpha binds CS. CRbeta functions as an endogenous inhibitor of CS and is expressed in several tissues. The CS/CRalpha complex binds to the glucocorticosteroid response element in the nucleus and also interferes with AP-1 and NF-kappaB binding. Thus, CSs inhibit the transcription of AP-1 and NF-kappaB inducible genes, such as interleukin (IL)-2, IL-6, IL-8, IL-1beta, and tumor necrosis factor (TNF) alpha, as well as T-cell proliferation. In clinical practice, a proportion of RA patients do not respond adequately to CS therapy. On this basis, RA patients can be divided on clinical grounds and on the ability of CSs to inhibit concanavalin A (conA)-induced peripheral blood T-cell proliferation in vitro into CS-sensitive (SS) and CS-resistant (SR) subgroups. The in vitro defined SS and SR subgroups correlate with the clinical responses to CS therapy. The mechanisms of the SR in RA patients remain unknown but may include the following: dysregulation of CRalpha function, alterations in the intracellular signaling mechanisms and/or utilization of various other cellular activation pathways, perturbations of the cytokine milieu, and inhibition of lipocortin. In SR subjects, CSs fail to significantly inhibit conA-induced IL-2 and IL-4 secretion and LPS-induced IL-8, IL-1beta secretion in vitro. CS therapy fails to reduce the circulating levels of IL-8, IL-1beta, and TNFalpha in SR RA patients. Peripheral blood mononuclear cells (PBMCs) from SR significantly overexpress activated NF-kappaB and IkappaBalpha. In vitro CSs fail to significantly inhibit conA-induced NF-kappaB activation in PBMCs from SR RA patients. Our preliminary observations show enhanced CRbeta expression by PBMCs from SR RA patients. It is most likely that other molecular mechanisms such as enhanced AP-1 expression are involved, and we currently are investigating such possibilities.

Adrenal Cortex Hormones↗
PubMed2005

Moderate dose inhaled corticosteroids plus salmeterol versus higher doses of inhaled corticosteroids in symptomatic asthma.

BACKGROUND: There is uncertainty as to the dose of inhaled corticosteroids (ICS) at which to start concomitant long acting beta agonist (LABA) treatment in patients with asthma not adequately controlled by ICS alone. METHODS: A meta-analysis was carried out of randomised, double blind clinical trials that compared the efficacy of adding salmeterol to moderate doses of ICS (fluticasone propionate 200 mug/day or equivalent) with increasing the ICS dose by at least twofold in symptomatic adult patients with asthma. The main outcome measures were the number of subjects withdrawn from the study due to asthma and the number of subjects with at least one moderate or severe exacerbation. RESULTS: Twelve studies with a total of 4576 subjects met the inclusion criteria for the analyses. The number of subjects withdrawn due to asthma and with at least one moderate or severe exacerbation was higher in the high dose ICS group (odds ratios 1.58, 95% CI 1.12 to 2.24 and 1.35, 95% CI 1.10 to 1.66, respectively). For the secondary outcome variables (forced expiratory volume in 1 second, morning and evening peak expiratory flow, and daytime beta agonist use) there was significantly greater benefit in the salmeterol group. CONCLUSIONS: This meta-analysis shows that the addition of salmeterol to moderate doses of ICS (fluticasone 200 mug/day or equivalent) in patients with asthma symptomatic at that dose results in significantly greater clinical benefit than increasing the dose of ICS by twofold or more.

Administration, Inhalation↗
PubMed1979

Synthesis and secretion of corticosteroid-binding globulin by rat liver. A source of heterogeneity of hepatic corticosteroid-binders.

Classical glucocorticoid receptors (type II) have a high affinity for synthetic and natural glucocorticoids. We have previously demonstrated an additional binding site in kidney cytosol (type III) which has a high affinity for corticosterone but a low affinity for dexamethasone. In many ways, this binder resembles plasma corticosteroid-binding globulin (CBG). The first goal of this study was to determine the organ distribution of the type III binding sites. Cytosol was prepared from isolated cells to avoid plasma contamination. Of the tissues examined, type III sites were found only in liver and kidney; sites were absent from thymocytes, IM-9 lymphocytes, adipocytes, and bone cells. The second goal of this study was to ascertain whether CBG is synthesized in liver and kidney. Liver and kidney slices were incubated in vitro and the concentration of type III sites was seen to rise in hepatic cytosol and incubating medium but not kidney. To verify the impression that liver was synthesizing and secreting CBG, the following experiments were performed: (a) To demonstrate that type III sites were CBG, steroid-binding profiles and migration on polyacrylamide gel electrophoresis were shown to be identical for hepatic type III sites and serum. (b) To indicate that the rise in type III sites was dependent on protein synthesis, it was shown that cycloheximide blocked the appearance of new type III sites. (c) To establish that the type III sites were being secreted, in situ liver perfusion experiments showed time-dependent release of new sites into the perfusate. In conclusion, liver synthesizes and secretes type III sites, a finding previously suspected but never proved. The presence of type III sites in kidney remains to be explained.

Animals↗
PubMed2006

Quality of life comparison between corticosteroid- and-mycofenolate mofetil and corticosteroid- and-oral cyclophosphamide in the treatment of severe lupus nephritis.

There is accumulating evidence that mycophenolate mofetil (MMF), when combined with corticosteroid, is an effective induction treatment for severe proliferative lupus nephritis and is associated with fewer adverse effects compared to cyclophosphamide (CTX), but the quality of life (QOL) associated with these regimens as perceived by the patient has not been compared. This study included patients who had experienced both treatment regimens, for distinct episodes of diffuse proliferative lupus nephritis. QOL parameters during the first six months of each treatment were assessed through SF36 and WHOQOL questionnaires. Twelve patients and 24 episodes of severe lupus nephritis were studied. CTX-treated and MMF-treated episodes showed comparable baseline characteristics and response rate, with complete remission occurring in 83.3%. MMF treatment was associated with higher numerical scores for all domains across both QOL instruments than CTX. MMF treatment was associated with significantly less fatigue, less impediment of physical and social functioning, and better psychological well being compared to CTX. When each patient served as her/his own control, most patients ascribed higher QOL domain scores to the MMF-treated episode. Seventy-five percent of patients found MMF treatment more acceptable and preferred when compared with CTX, and the complications that most concerned them included Cushingoid features, alopecia, menstrual disturbance and infections. These data showed that MMF-based induction immunosuppression for severe lupus nephritis was associated with better QOL than CTX as perceived by patients, which was most likely attributed to the reduced side-effects during MMF treatment.

Activities of Daily Living↗
PubMedDate not supplied

[Secondary side effects of corticosteroids and the management of corticosteroid therapy].

The side effects of glucocorticoids are the result of their biological effects and closely related to the dose administered and the duration of treatment. Whilst excessive amounts may result in the development of a clinical and biological Cushings syndrome, there exists also the problem of avoiding acute adrenal insufficiency when corticosteroids are stopped after a prolonged period of administration or during substitutive therapy for adrenal insufficiency. Aspects requiring surveillance are discussed.

Adrenal Insufficiency↗
PubMed2004

Frozen shoulder syndrome: comparison of oral route corticosteroid and intra-articular corticosteroid injection.

Twenty-six patients with frozen shoulder syndrome (Stage 2 and 3) were included in this study conducted at Dr. Kariadi General Hospital, Semarang, Indonesia and randomly allocated into 2 groups: 40 mg triamcinolone intra-articular injection and triamcinolone oral tablets. The result showed that triamcinolone intra-articular injection group "cured" rate was 5.8 times higher at week one compared to the triamcinolone tablet group. Sixty-two percent of the cases with triamcinolone intra-articular injection achieved their "cured" condition after one week of therapy, compared with only 14% of the triamcinolone tablets group. We conclude that, intra-articular corticosteroid injection provide faster improvement compared to oral route.

Administration, Oral↗
PubMed1986

Origin of corticosteroid-binding globulin in fetal rat. Comparative dynamics of corticosteroid-binding globulin, alpha-fetoprotein, and albumin secretion in primary cultures of fetal rat hepatocytes.

The origin of corticosteroid-binding globulin (CBG) and its evolution in comparison with alpha-fetoprotein (AFP) and albumin synthesis, during early development of rat liver (days 13 and 15 of fetal life), have been investigated using cultured fetal hepatocytes. Synthesis and secretion of CBG, AFP, and albumin is evidence by cycloheximide-sensitive [14C]leucine incorporation into immunoprecipitable polypeptides secreted by cultured hepatocytes into the medium, two-dimensional immunoelectrophoretic and autoradiographic identification of newly synthesized labeled proteins, corticosterone and estradiol-17 beta binding to CBG and AFP, respectively, and indirect immunofluorescence localization of AFP, albumin, and CBG in cultured fetal hepatocytes. CBG, albumin, and AFP accounted for 6, 11, and 25% (in 13-day-old rat fetuses) and 5, 15, and 28% (15-day-old rat fetuses), respectively, of the total secreted proteins in the culture medium. The rates of CBG, AFP, and albumin (counts/minute of secretion [14C]leucine incorporated per milligram of cell protein/hour of culture) in the hepatocytes of 15-day-old rat fetuses were 1.48-, 2.1-, and 2.57-fold higher, respectively, than in the 13-day-old rat fetuses. These results indicate that fetal liver is also active in CBG synthesis, along with AFP and albumin, as early as day 13 of fetal life and that the synthetic rates of these secretory proteins depend upon the developmental stage of the fetal liver. This developmental related change in the rate of synthesis of CBG by the fetal hepatocytes may regulate the level of free (active) glucocorticoid in the fetal circulation and thereby the initiation and regulation of glucocorticoid-dependent processes during the crucial stages of the differentiation of fetal liver and other developing tissues.

Albumins↗
PubMedDate not supplied

[Development and regression of dermal corticosteroid atrophy. 3. Results of discontinuous topical corticosteroid administration].

It was shown in two earlier communications that a reduction in skin thickness owing to daily topical corticosteroid application (under occlusion) for about 12 h was measurable within a few days. Dermal atrophy remitted within one week. In this study, an open mode of topical application with a 0.1% triamcinolone ointment (Tri) once a day was tested. A decrease in thickness was also registered in the first week under this treatment. The following non-continuous modes of application were tested in 5 test subjects: 7 d Tri, 7 d free of treatment (7:) and 3 d Tri, 4 d free of treatment (3:4). In the 7:7 mode of application, there was a marked decrease of skin thickness during Tri application which remitted in the treatment-free interval. In the 3:4 application, almost no dependence on the individual phases could be discerned. Skin thickness decreased for nearly 16 d and began to normalize despite continued interval administration. At the end of the investigation (6 weeks), the skin had almost regained its original thickness.

Administration, Topical↗