Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “STEROIDS”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 37 records · Page 2Linked to original sources
PubMed1983

Steroids in Porifera. II. Steroid derivatives from two sponges of the family Halichondriidae. Sokotrasterol sulfate, a marine steroid with a new pattern of side chain alkylation.

A trisulfated derivative of 24,25,26,26-tetramethyl-5 alpha-cholest-23E-ene-2 alpha, 3 beta, 6 alpha-triol (sokotrasterol sulfate) has been isolated from the sponge Halichondriidae gen. sp., collected near Sokotra Island (Arabian Sea), and its structure has been elucidated. The side chain of the new steroid involves a "normal" alkylation at C-24 and the unprecedented addition of two extra methyl groups at C-26 and one extra methyl group at C-25. A free sterol fraction contained only 24-isopropyl-5-cholesten-3 beta-ol and 24-isopropyl-5, 22E-cholestadien-3 beta-ol. 24-Isopropyl-5, 22E-cholestadien-3 beta-ol as sole monohydroxy sterol and halistanol sulfate as major polyhydroxylated steroid derivative have been detected in Halichondria sp., a Madagascar sponge.

Animals↗
PubMed1999

Analysis of the steroid binding domain of rat steroid 5alpha-reductase (isozyme-1): the steroid D-ring binding domain of 5alpha-reductase.

We have previously shown that the photoactive 4-azasteroid, [1,2 3H]N-4(benzylbenzoyl)-3-oxo-4-aza-4-methyl-5alpha-androst an-17beta-carboxamide is an effective probe of rat steroid 5alpha-reductase (isozyme-1) (5alphaR-1). In the current investigation, PEG-fractionated (6.5%) detergent-solubilized preparations containing 5alphaR-1 activity were ultraviolet (UV)-photolyzed with [3H]-4MABP and subsequently purified by 8.75% preparative sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The fractions corresponding to the radioactive peak following the dye front were analyzed by 10% sodium dodecyl sulfate-polyacrylamide gel electrophoresis and showed the presence of a single, labeled, 26 KDa protein band, the apparent molecular weight of 5alphaR-1. TCA precipitation of the labeled fractions, followed by long-term digestion of the TCA pellet with chymotrypsin and high-performance liquid chromatography analysis, indicated that the majority of the radioactivity eluted with a peak retention time of 55-56 min. Rechromatography of this fraction using a modified gradient (elution 54-55 min), followed by sequence analysis, yielded a single N-terminal tetrapeptide with the sequence, -L-E-G-F-, corresponding to residues 15-18 of the 5alphaR-1 sequence. Site-directed mutagenesis studies indicated that mutant F18L showed an approximately 12-fold increase in the Km for testosterone, whereas the Km for reduced nicotinomide adenine dinucleotide phosphate remained virtually unaltered.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed2000

Oral or topical nasal steroids for hearing loss associated with otitis media with effusion in children.

BACKGROUND: OME is common and may cause hearing loss with associated developmental delay. Treatment remains controversial. The effect of both systemic and intra-nasal steroids on effusions has been assessed by randomised controlled trials. OBJECTIVES: To examine evidence for or against treating children with hearing loss associated with OME with systemic or topical nasal steroids. SEARCH STRATEGY: Searches were conducted in February 2000. We searched the Cochrane Controlled Trials Register using the terms 'otitis-media', 'otitis media with effusion', 'glue ear', or 'OME', and 'steroids', 'glucocorticoids, synthetic', 'glucocorticoids, topical', 'anti-inflammatory agents, steroidal'. EMBASE and MEDLINE were also searched for additional information. SELECTION CRITERIA: Randomised controlled trials of oral and topical nasal steroids, either alone or in combination with another agent such as an antibiotic, were included. EXCLUSIONS: publications in abstract form only since adequate appraisal was not possible; uncontrolled, non-randomised or retrospective studies; studies reporting outcomes with ears (rather than children) as the unit of analysis. DATA COLLECTION AND ANALYSIS: Data were extracted from the published reports by the two authors independently (CCB and JH van der V) using standardised data extraction forms and methodology. The methodological quality of the included studies were independently assessed by the two authors using the scheme described in the Cochrane Handbook. Dichotomous results were expressed as an odds ratio using a fixed effects model together with the 95% confidence intervals. Continuous data were analysed using the weighted mean difference in a fixed effects model. Tests for heterogeneity between studies were performed using a Mantel-Haenszel approach. In trials with a cross over design, post-crossover treatment data were not used. MAIN RESULTS: No study prospectively documented hearing loss associated with OME prior to randomisation. Follow up was short term. No serious or lasting side effects were reported in the four studies that did mention side effects. Most comparisons involved small numbers of subjects. The odds ratio for OME persisting after short term follow up for children treated with oral steroids plus antibiotic compared to control plus antibiotic was 0.32 (95% CI 0.20 to 0.52). However there was significant heterogeneity between studies (p<0.01). Trends favoured steroids for most other comparisons, but confidence intervals included unity. There was no evidence of benefit for steroid treatment in the longer term, and no study assessed effect of steroid treatment on language development. REVIEWER'S CONCLUSIONS: There is evidence that steroids combined with an antibiotic lead to a quicker resolution of OME in the short term. However, there is not evidence for long term benefit from treating hearing loss associated with OME with either oral or topical nasal steroids. These treatments are therefore not recommended at the present time. Future studies should document hearing loss associated with OME before the start of study treatment. Follow up should be longer and ideally include symptom, audiometry and developmental outcomes. Data should not be presented with ears as the unit of analysis.

Administration, Intranasal↗
PubMed2000

Inhaled vs oral steroids for adults with chronic asthma.

OBJECTIVES: To determine therapeutically equivalent doses of inhaled versus oral steroids for adults with chronic asthma. SEARCH STRATEGY: The Cochrane Airways Group trials register was searched using the terms: (drug delivery systems OR ((nebuli* OR inhal* OR MDI) AND oral*)) AND ( steroid* OR corticosteroid* OR glucocorticoid* OR beclomethasone OR betamethasone OR fluticasone OR cortisone OR dexamethasone OR hydrocortisone OR prednisolone OR prednisone OR triamcinolone). SELECTION CRITERIA: Randomised controlled trials were selected of at least 4 weeks duration and included patients over the age of 15 years with chronic asthma. Trials compared inhaled steroids and oral prednisolone or prednisone; where the maximum dose for inhaled steroids was 2000 mcg/day and prednisolone 60 mg (on alternate days). DATA COLLECTION AND ANALYSIS: Two independent reviewers screened 1285 titles and abstracts from the electronic search, bibliography searches and other contacts. Of these, 10 trials met previously defined inclusion criteria. Two reviewers independently extracted study characteristics, and outcome measures. MAIN RESULTS: All trials were small and no data could be pooled. Carry-over effects were present in at least one cross-over trial. Data from six trials produced the same pattern, in which prednisolone 7.5-12 mg/day appeared to be as effective as inhaled steroid 300-2000 mcg/day. In two trials, inhaled steroid 300-400 mcg/day was more effective than prednisolone 5 mg/day. All doses of inhaled steroid appeared to be more effective than alternate day doses of prednisolone up to 60 mg on alternate days. Side-effect data were reported too variably to permit comparisons. A 30% incidence was reported in one study in patients receiving prednisolone 5 mg/day, none were reported in patients on inhaled steroids. REVIEWER'S CONCLUSIONS: A daily dose of prednisolone 7.5-10 mg/day appears to be equivalent to moderate-high dose inhaled corticosteroids. Side-effects may be present on low doses, so if there is no alternative to oral steroids, the lowest effective dose should be prescribed.

Administration, Inhalation↗
PubMed1982

The effect of a novel, non-steroidal anti-inflammatory compound, nabumetone (BRL 14777), on cellular infiltration into 24-hour polyvinyl sponge implants in the rat, compared with some steroidal and non-steroidal anti-inflammatory drugs.

The time-course of cell migration into saline-soaked sponge implants over 5 days showed peak polymorphonuclear leucocyte (PMNL) infiltration at 24 h. In common with the corticosteroids dexamethasone and hydrocortisone, and the non-steroidal anti-inflammatory drugs indomethacin, (+)-naproxen, BW 755C and benoxaprofen, nabumetone decreased cell migration into the sponges. PMNLs and mononuclear cells were reduced at 24 h, and there was a parallel decrease in exudate levels of the lysosomal acid hydrolase beta-N-acetyl glucosaminidase [NAG ECB, 3, 2, 1, 30]. Impregnation of sponges with lambda-carrageenan (1%) caused a 2-3 fold increase in cell numbers, with a relatively greater proportion of PMNLs; drug effects were more marked in these implants.

Animals↗
PubMed1992

New concepts in steroid hormone action: transcription factors, proto-oncogenes, and the cascade model for steroid regulation of gene expression.

The past 6 years have seen a significant increase in our understanding of steroid receptor-mediated regulation of gene transcription. As a means to understanding receptors as transcriptional activators, several steroid receptor genes have been identified, cloned, and are now known to belong to a receptor superfamily. All steroid receptors possess conserved domains which confer various aspects of receptor function such as those that regulate DNA and steroid binding. In addition to the distinct intrinsic functions of these domains, nonreceptor proteins associated with the unactivated forms of the receptor appear to play a crucial role in receptor function. One such protein, hsp90, is speculated to stabilize the unactivated form of the receptor in the absence of hormone. Posttranslational modification also appears to be important in regulating the transcriptional activity of steroid receptors. Steroid receptors may exist in several phosphorylation states, each intimately linked to steps involved in the conversion of the newly synthesized protein to the steroid-bound form capable of transcriptional activation. The activated steroid-receptor complexes bind to chromatin "acceptor sites", the composition of which is presently under investigation. Steroid response elements, DNA-binding "acceptor" proteins in the nuclear matrix, and transcription factors and their elements appear to play a role in this binding and in the transcriptional control of genes exerted by steroid receptors. Different genes utilize different elements and factors for each particular steroid receptor species, reflecting the steroid- and gene-specific patterns of regulation of gene expression. In this review, a cascade model is used to explain how the receptor interaction with specific sites upstream of "regulatory (early) genes" may regulate a variety of steps in gene expression from transcription and mRNA half-life to protein processing. This model not only accounts for the paradoxical "lag phase" observed between steroid treatment and structural gene transcription, but also shows how steroid-regulated gene expression may occur an posttranscriptional steps. The rapid regulation of the nuclear proto-oncogenes, e.g., c-myc, c-fos, and c-jun, are used as examples of these early regulatory genes in steroid-regulated, receptor-mediated gene transcription.

Animals↗
PubMed2006

Cyclodextrins sequester neuroactive steroids and differentiate mechanisms that rate limit steroid actions.

BACKGROUND AND PURPOSE: Neuroactive steroids are potent modulators of GABA(A) receptors and are thus of interest for their sedative, anxiolytic, anticonvulsant and anaesthetic properties. Cyclodextrins may be useful tools to manipulate neuroactive effects of steroids on GABA(A) receptors because cyclodextrins form inclusion complexes with at least some steroids that are active at the GABA(A) receptor, such as (3alpha,5alpha)-3-hydroxypregnan-20-one (3alpha5alphaP, allopregnanolone). EXPERIMENTAL APPROACH: To assess the versatility of cyclodextrins as steroid modulators, we investigated interactions between gamma-cyclodextrin and neuroactive steroids of different structural classes. KEY RESULTS: Both a bioassay based on electrophysiological assessment of GABA(A) receptor function and optical measurements of cellular accumulation of a fluorescent steroid analogue suggest that gamma-cyclodextrin sequesters steroids rather than directly influencing GABA(A) receptor function. Neither a 5beta-reduced A/B ring fusion nor a sulphate group at carbon 3 affected the presumed inclusion complex formation between steroid and gamma-cyclodextrin. Apparent dissociation constants for interactions between natural steroids and gamma-cyclodexrin ranged from 10-60 microM. Although gamma-cyclodextrin accommodates a range of natural and synthetic steroids, C(11) substitutions reduced inclusion complex formation. Using gamma-cyclodextrin to remove steroid not directly bound to GABA(A) receptors, we found that cellular retention of receptor-unbound steroid rate limits potentiation by 3alpha- hydroxysteroids but not inhibition by sulphated steroids. CONCLUSIONS AND IMPLICATIONS: We conclude that gamma-cyclodextrins can be useful, albeit non-specific, tools for terminating the actions of multiple classes of naturally occurring neuroactive steroids.

Animals↗
PubMed1984

Implications of subcellular steroid binding sites in endometrial cancer, determined by an immunofluorescent steroid-antibody technique and biochemical assay.

A discrepancy has been found between the progestogen level necessary for treatment of endometrial cancer and the steroid receptor level detected for the response indicator. Therefore the relationships between the steroid binding quantity detected biochemically and the steroid reactivity determined immunofluorescently was evaluated subcellularly in the endometrial cancers. Estradiol-17 beta and progesterone fluorescences were not always related to the classical steroid receptor binding quantities. These two steroids bound to the nuclear components directly, but heterogeneously. In the biochemical method using fractionated dispersed cancer cells, cellular heterogeneity of the steroid receptor mechanism in a given endometrial cancer tissue was proved. Steroid fluorescence was not related to the steroid-receptor complex quantity in the normal endometrial nucleus. This suggests that the binding of steroid antibody to the steroid-receptor bound already to the nucleus seems to be inhibited due to steric hindrance. Therefore the nuclear steroid fluorescence did not always give the nuclear steroid-receptor complex quantity. These results indicate heterogeneity in the estrogen and progestogen receptor mechanism in endometrial cancer, when studied by the biochemical and immunofluorescent techniques, and that these steroids bind to the nucleus directly and may influence the nuclear mechanism. Therefore, in endometrial cancer progestogen does not always have a therapeutic effect through the progestogen receptor and does not affect the therapeutic effect on any of the cells.

Aged↗
PubMed2003

Outpatient treatment of moderately severe active ulcerative colitis with pulsed steroid therapy and conventional steroid therapy.

Pulsed steroid therapy may induce rapid remission in patients with moderately severe ulcerative colitis in outpatient clinics. A total of 19 patients with moderately severe active ulcerative colitis who refused hospitalization were treated between October 1999 and September 2001 in the outpatient clinic. Patients were treated with either conventional oral steroid therapy or intravenous pulsed steroid therapy followed by conventional oral steroid therapy. Eight patients received conventional steroid therapy and 11 patients received pulsed steroid therapy followed by conventional steroid therapy. The efficacies of the two types of steroid therapy were equal, but patients with active colitis responded more quickly to pulsed steroid therapy than to conventional steroid therapy. No serious adverse effects were observed. Moderately severe colitis can be safely treated with either conventional or pulsed steroid therapy in the outpatient clinic, but pulsed steroid therapy may induce clinical remission more quickly than conventional steroid therapy.

Administration, Oral↗
PubMed2003

Increased expression of cytotoxic effector molecules: different interpretations for steroid-based and steroid-free immunosuppression.

Cytotoxic T lymphocyte (CTL) effector molecules have been studied as markers of acute rejection in renal allograft recipients on steroid-based immunosuppression. We hypothesized that basal CTL gene expression may vary with time post-transplantation as well as with different immunosuppression protocols (steroid-based or steroid-free). Variations in CTL gene expression may thus impact on the ability to predict acute allograft rejection. We used the non-invasive method of quantitative competitive-reverse transcription-polymerase chain reaction (QC-RT-PCR) to quantify the amounts of CTL effector molecules (granulysin, GL; perforin, P; granzyme B, GB) in serial peripheral blood lymphocyte (PBL) samples from steroid-free and steroid-based adult and pediatric renal allograft recipients. Patients on both protocols were clinically monitored by protocol biopsies at 1, 3, 6, and 12 months post-transplantation and for graft function at 1 yr post-transplantation in a separate clinical study. Steroid-free patients with stable graft function showed an increase in GL, P, and GB gene expression over time post-transplantation with the increase being seen largely by the first post-transplant month. A further increase in GL expression was noted at the end of the first post-transplant year in the absence of acute rejection, whereas GB and P levels were unchanged. At comparative time-points post-transplantation, CTL genes were found to be higher in steroid-free patients with stable graft function, compared to steroid-based recipients with either clinically stable graft function or acute rejection. This study suggests that levels of CTL gene expression, although important in a steroid-based regimen to monitor the risk of acute rejection, may not be similarly applied in patients on steroid-free immunosuppression. The early increase in levels seen in steroid-free patients appears to correlate with the total absence of steroids. As steroid-free patients seem to have a lower incidence of acute rejection and better long-term graft function at 1 yr, the early increase in CTL genes in the absence of acute rejection may suggest an early adaptive immune activation response, promoting early graft acceptance in this protocol.

Adult↗
PubMed2004

Co-evolution of steroidogenic and steroid-inactivating enzymes and adrenal and sex steroid receptors.

Receptors for the adrenal and sex steroids arose by a series of gene duplications from an ancestral nuclear receptor in a primitive vertebrate, at least 540 million years ago. Sequence analysis indicates many steroidogenic and steroid-inactivating enzymes, including cytochrome P450s and hydroxysteroid dehydrogenases (HSDs), arose at the same time. The estrogen receptor (ER) appears to be the ancestral steroid receptor. Initially, the redundant duplicated ER had a low specificity for its new ligand. This raises the question: "How was specificity for responses to different steroids regulated early in the evolution of steroid receptors?" Selective expression of these steroid-metabolizing enzymes provided specificity for different steroid responses in primitive vertebrates. 17 beta-Hydroxysteroid dehydrogenase-type 1 (17 beta-HSD-type 1) and 17 beta-HSD-type 2, which preferentially catalyze the reduction and oxidation at C17 of androgens and estrogens, respectively, provide an example of this mechanism. Selective expression of either 17 beta-HSD-type 1 or 17 beta-HSD-type 2 can regulate synthesis or inactivation of androgens or estrogens in specific cells. Steroids also were important in the evolution of land animals, which began about 400 million years ago. Steroidogenic and steroid-inactivating enzymes were recruited to regulate steroid-mediated responses as organ function became more complex. For example, in the kidney 11 beta-HSD-type 2 prevents binding of glucocorticoids to the mineralocorticoid receptor (MR), which is crucial for aldosterone-mediated regulation of electrolyte transport in the distal tubule. We propose that Delta 5 steroids, such as dehydroepiandrosterone and its metabolites, were the ligands for the ancestral ER. Understanding the actions of Delta 5 steroids in amphioxus and lamprey may shed light on adrenarche and neurosteroid actions in humans.

Adrenal Cortex Hormones↗
PubMed2003

Basiliximab (anti-CD25) in combination with steroids may be an effective new treatment for steroid-resistant ulcerative colitis.

BACKGROUND: Steroid resistance represents a major clinical problem in the treatment of ulcerative colitis. In vitro, interleukin-2 renders lymphocytes steroid resistant. AIM: To explore the therapeutic potential of interleukin-2 receptor blockade in steroid-resistant ulcerative colitis with both in vitro measures and a pilot in vivo study. METHODS: Ten patients with steroid-resistant ulcerative colitis received a single bolus of 40 mg of intravenous basiliximab plus steroid treatment in an open-label, uncontrolled, 24-week study. The outcome was assessed using the Ulcerative Colitis Symptom Score, rectal biopsy and Inflammatory Bowel Disease Questionnaire. Lymphocyte steroid sensitivity was measured in vitro in 39 subjects in the presence or absence of basiliximab. RESULTS: Nine of the 10 patients achieved clinical remission within 8 weeks. At 24 weeks, seven patients were in clinical remission. Marked improvement in the Ulcerative Colitis Symptom Score was seen by 1 week (P = 0.004) and on rectal biopsy and Inflammatory Bowel Disease Questionnaire by 2 weeks (both P < 0.05). Improvements persisted to 24 weeks (Ulcerative Colitis Symptom Score, Inflammatory Bowel Disease Questionnaire, both P < 0.005). Eight of the nine responders relapsed (median, 9 weeks), but remission was re-achieved with further corticosteroids and the addition of azathioprine. At 24 weeks, seven patients were in full clinical remission, five off all steroid therapy. In vitro measurement of lymphocyte steroid sensitivity demonstrated steroid resistance in 22% of subjects. All were rendered steroid sensitive in the presence of basiliximab. CONCLUSIONS: Basiliximab appears to be effective at inducing remission in steroid-resistant ulcerative colitis. In vitro, basiliximab also produced a dramatic increase in lymphocyte steroid sensitivity in healthy subjects. Confirmation in randomized controlled studies is required.

Adult↗
PubMed1997

Azathioprine in steroid-resistant and steroid-dependent ulcerative colitis.

We evaluated, retrospectively, the outcome of 56 patients (39 male, 17 female; mean age, 34 years; age range, 14-65 years) who received azathioprine for either steroid-resistant (group A, n = 10) or steroid-dependent (group B, n = 46) ulcerative colitis. The patients were followed for a mean of 29 +/- 17 months (median, 27 months). Twenty-four had left-sided colitis, 5 had subtotal colitis, and 27 had total colitis. The mean duration of the disease was 51 months (range, 2-192 months). At the beginning of azathioprine treatment (time 0), all patients had clinically severe disease and were taking 40 mg prednisolone per day. Azathioprine was used in addition to steroid therapy at a dosage of 2 mg/kg. The need for steroids, expressed as the median cumulative steroid dose (mg/year), and the number of clinical relapses (requiring steroid therapy) in the 2 years before azathioprine treatment, were compared with those of the 3-year follow-up with azathioprine treatment. A positive response to azathioprine was defined as (a) avoidance of colectomy, (b) a significant decrease in the median cumulative steroid dose, and (c) a significant decrease in the number of clinical relapses (expressed as number/patient/year). One patient in group A withdrew due to painful dyspepsia, and two patients in group B were lost to follow-up. Remission with complete elimination of steroids was achieved in 36 of 53 (64%), 23 of 35 (66%), and 18 of 26 (69%) patients in the first, second, and third years, respectively, of azathioprine treatment. Compared with the 2 years before azathioprine treatment, a significant decrease was observed of about 75% both in steroid consumption and in the number of clinical relapses during the 3 years of azathioprine therapy. Two of nine patients in group A and 2 of 44 patients in group B had colectomy after mean periods of 15 months and 24 months, respectively. Azathioprine is effective and safe in avoiding colectomy in patients with steroid-resistant and steroid-dependent ulcerative colitis; its use decreases both steroid requirements and clinical relapses.

Adolescent↗