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At least 91 records · Page 5Linked to original sources
PubMed2006

[Efficacy of combination of intravenous cyclosporin A and steroid therapy versus prolonged intravenous steroid therapy alone in patients with severe ulcerative colitis refractory to initial intravenous steroid therapy].

BACKGROUND/AIMS: Maximal duration of intravenous (IV) corticosteroid (CS) treatment and efficacy of cyclosporin A (CsA) have not been clarified for patients with severe ulcerative colitis. We aimed to evaluate and compare the effectiveness of CS and CsA combination therapy with prolonged CS therapy alone in patients with severe UC refractory to initial CS therapy. METHODS: We retrospectively reviewed the medical records of 84 episodes of severe UC in 59 patients between April 1999 and May 2005. RESULTS: Among 84 episodes with IV CS therapy, 45 (53.6%) experienced an early response, while 39 (46.4%) did not respond within 2 weeks. The remaining 36 episodes excluding 3 which underwent colectomy were assigned to either combination therapy of IV CS and CsA or prolonged IV CS treatment alone for additional 2 weeks. Twelve of 16 episodes (75.0%) responded to therapy with combinations of IV CsA and CS, and 16 of 20 episodes (80.0%) to prolonged IV CS treatment alone. There was no statistical difference in response and colectomy rate after 4 weeks between CsA-use group and CsA-non-use group (p=1.00). CONCLUSIONS: These results suggest that CS and CsA combination has no additional benefit over prolonged CS therapy alone in terms of short-term response and that CS can be safely prolonged even after the first 14 days of treatment for severe UC.

Adult↗
PubMed1987

Interaction of different steroid hormones during progression of tumour cells to steroid autonomy.

Progression to steroid insensitivity poses a major problem in therapy of breast cancer, but studies of the origin of steroid-insensitive cells have been few and have concentrated in any one system on the loss of response to only one steroid. Since both normal and tumour mammary cells have complex endocrine requirements, we wondered how different steroids might interact during loss of steroid sensitivity. Cloned cells from the androgen-responsive Shionogi 115 mouse mammary carcinoma respond in vitro to both androgens and glucocorticoids in terms of both cellular and molecular parameters but, following prolonged absence of any steroid, these cells become unresponsive. We show here that 2 steroids can interact to prevent the progression to steroid insensitivity since the S115 cells can be protected against any loss of response to either androgen or glucocorticoid with either steroid alone. Androgen protects against loss of glucocorticoid sensitivity and glucocorticoid protects against loss of androgen sensitivity. The clinical implications are discussed.

Animals↗
PubMed2003

Membrane-initiated steroid signaling (MISS): genomic steroid action starts at the plasma membrane.

UNLABELLED: Plasma membrane (PM) steroid recognition sites are thought to be responsible only for rapid, non-genomic responses without any link to the nuclear receptor-mediated genomic effects of steroids. We focused on a PM "glucocorticoid-importer" (GC-importer) that imports GC into rat liver cells. This site interacts also with particular gestagens (progesterone, P; medroxyprogesterone, MP; ethynodiol, Ethy) and estrogens (ethinylestradiol, EE(2); mestranol), which do not bind to the nuclear GC receptor (GR). To elucidate the role of the GC-importer, we transfected a rat wild-type hepatocyte (CC-1) and a hepatoma cell line, unable to import GC (MH 3924), with a GC<-->GR-responsive luciferase (luc)-reporter gene. Selected steroids were tested for their ability to induce or inhibit luc expression. Corticosterone (B) and dexamethasone (Dex), but also the GC-antagonists cortexolone (Cortex), P and MP, induced luc. Even the PM-impermeable BSA-derivatives of B, Dex and Cortex did so to almost the same extent as the free steroids. MH 3924 cells respond stronger than CC-1 to luc inducing steroids. Luc expression was inhibited by RU 38 486, but also by EE(2) and Ethy. The thiol reactive mesylate-derivatives of B, Dex and Cortex induced to a considerably lesser extent than the free or BSA-steroids. The thiol reagent mersalyl blocks cellular entry of GC and inhibits luc induction in CC-1 cells. Incubation with EE(2) and B of PM-vesicles, isolated from liver cells, resulted in a decrease of the density of two 75 and 52kDa G-proteins reflecting a diminished exchange of GDP by GTP. CONCLUSION: the PM-residing GC-importer, now renamed "Steroid Hormone Recognition and Effector Complex" (SHREC) is an interdependent part of the complete GC signal propagation in which G-proteins are involved. Free SH-groups of SHREC are a prerequisite for genomic GC activity. Specific interactions between SHREC and GC-agonist/-antagonist trigger steroid-dependent signaling. However, import of the ligand into the cell terminates it. Thus, the PM-related non-genomic steroid responses are clearly linked to the GR-related genomic effects.

Animals↗
PubMed2005

Leukocytapheresis therapy for steroid-naïve patients with active ulcerative colitis: its clinical efficacy and adverse effects compared with those of conventional steroid therapy.

BACKGROUND: Steroid administration currently plays a central role in the medical management of ulcerative colitis (UC); however, long-term steroid usage causes adverse effects, which necessitates stoppage of drug intake, leading to worsening of the disease. A steroid-sparing, well-tolerated treatment is therefore required. As several investigators have reported the efficacy of leukocytapheresis (LCAP) combined with steroid therapy, we investigated the clinical usefulness and safety of LCAP for steroid-naïve patients with active UC for comparison with those of conventional steroid therapy. METHODS: Twenty-nine Japanese patients with active UC without a history of steroid usage were selected to be treated with LCAP (n = 9) or prednisolone (PSL) (n = 20). LCAP administration continued for 10 weekly cycles. In the PSL group, patients with moderately severe disease received 0.5 mg/kg per day of PSL and those with severe disease 1.0 mg/kg per day. The PSL dosage was gradually tapered in accordance with improvement. RESULTS: Eight (88.9%) of the LCAP group and 16 (80.0%) of the PSL group showed clinical improvement and three (33.3%) of the LCAP group and seven (35.0%) of the PSL group achieved remission. As for the treatment complications, three major adverse effects were observed in the PSL group, but none were observed in the LCAP group. CONCLUSION: The results of this study suggest that the efficacy and safety of LCAP are equivalent, and in terms of severe adverse effects, superior to those of steroid therapy. LCAP therapy may thus be a promising candidate therapy for steroid-naïve patients with active UC.

Adolescent↗
PubMed2002

Double blind, placebo controlled trial of the remission inducing and steroid sparing properties of an ICAM-1 antisense oligodeoxynucleotide, alicaforsen (ISIS 2302), in active steroid dependent Crohn's disease.

BACKGROUND AND AIMS: To evaluate the safety and efficacy of the intercellular adhesion molecule 1 (ICAM-1) antisense phosphorothioate oligonucleotide alicaforsen (ISIS 2302) in Crohn's disease. METHODS: Active (Crohn's disease activity index (CDAI) 200-350), steroid dependent (prednisone 10-40 mg) Crohn's patients were randomised into three treatment groups: placebo versus ISIS 2302 (2 mg/kg intravenously three times a week) for two or four weeks. Patients were treated in months 1 and 3, with steroid withdrawal attempted by week 10. The primary end point (steroid free remission) was a CDAI <150 off steroids at the end of week 14. RESULTS: A total of 299 patients were enrolled, with a mean baseline CDAI of 276 and steroid dose of 23 mg/day. Rates of steroid free remission were equivalent for the two and four week ISIS 2302 groups (20.2% and 21.2%) and the placebo group (18.8%). At week 14, steroid withdrawal was successful in more ISIS 2302 patients compared with placebo treated patients (78% v 64%; p=0.032). Steroid free remission was highly correlated with exposure (p=0.0064). Other clinical responses were correlated with exposure, with significant results versus placebo being observed in the highest area under the curve subgroup. CDAI scores decreased by 136 (112) at week 14 versus 52 (107) for placebo (p=0.027) and inflammatory bowel disease score questionnaire improved by 43 (31) versus 15 (36) for placebo (p=0.027). CONCLUSIONS: Although the primary outcomes failed to demonstrate efficacy, pharmacodynamic modelling suggests that alicaforsen (ISIS 2302) may be an effective therapy for steroid dependent Crohn's disease.

Adolescent↗
PubMed1997

Low-dose methotrexate spares steroid usage in steroid-dependent asthmatic patients: a meta-analysis.

STUDY OBJECTIVES: To determine if treatment with low-dose methotrexate spares oral steroids in adult, steroid-dependent, asthmatic patients. DESIGN: Articles identified by computer search were excluded if they (1) did not contain original data relating to the primary question, (2) had no controls, or (3) described subjects younger than 18 years of age. MEASUREMENTS: From each article, the following was abstracted: reference citation; type of control; whether study incorporated a run-in period in which the baseline level of prednisone was reduced to the lowest possible dose; dosage and length of methotrexate therapy; baseline dosage; and type of steroid. Also, the following was determined during both placebo and methotrexate arms of each study: steroid dosage, FEV1, serious side effects, and alteration in level of serum aspartate aminotransferase. RESULTS: Eleven eligible studies were identified. Methotrexate treatment resulted in a decrease in prednisone or prednisolone usage by an average of 4.37 mg/d or 23.7% of the initial dosage. The summary effect size in standard deviations (SDs) was -0.53 (95% confidence interval=-0.29 to -0.77). Subgroup analysis showed that patients treated with prolonged (6-month) therapy with methotrexate, those with low long-term usage of steroids (< or = 20 mg/d), and those whose study design incorporated a run-in period, tended to have the greatest steroid-sparing effects with methotrexate. CONCLUSIONS: Low-dose methotrexate has a significant steroid-sparing effect in steroid-dependent asthmatic patients. The greatest effect was evident in patients in whom an effort was made to reduce baseline steroid dosage and in whom methotrexate was used for 24 weeks.

Adult↗
PubMed1982

Steroid-binding properties of the rat seminal vesicle androgen receptor: short-term and long-term competition of various steroids with radioactive dihydrotestosterone.

Competition of 22 steroids with [3H]-dihydrotestosterone for the binding to the androgen receptor of the rat seminal vesicle has been studied. The effect of each competitor was determined in short term (1 h) and long term (67 h) incubations, and the results were evaluated by considering the kinetic aspects of competition. This approach made possible to investigate separately the ligand specificity of the association and dissociation parts of the steroid-receptor interaction. According to competitory behavior, the investigated steroids could be divided into three groups. In Group I, the association and dissociation rates of the competitors are close to that of 5 alpha-dihydrotestosterone. Steroids in Group II can still associate at a remarkable rate with the receptor, but the resulting complexes are much less stable than the 5 alpha-dihydrotestosterone-receptor complex. Finally, steroids of Group III do not exhibit significant binding. By correlating the binding characteristics and the structure of the test compounds it was possible to assess the significance of certain features of steroid molecules in the binding. Moreover, other correlations between the competitive behavior and some known biological activities of these steroids point to the potential usefulness of our procedure in the screening of synthetic steroids.

Animals↗
PubMed1982

Some theoretical questions of the peptide and steroid hormone regulation. Part I.: The receptor-steroid variable complex (RSVC) hypothesis of genetic regulation.

Steroids exert their known biological and biochemical effects in connection with specific receptors. These effects are so various and complex that it is impossible to explain them on the basis of a concept supposing the presence of only one unique receptor molecule in the target organs. The heterogeneity in the function of steroids requires a heterogeneity in the molecular composition of the receptor-steroid complexes. Direct and indirect evidence is presented to support a multiplex, heterogene receptor theory. The possible origin of this complexity is analyzed and a new concept of specific gene regulation by heterogene receptor-steroid complexes is suggested. in this theory the distribution and sequence of one or more steroids on the receptor can carry and serve highly specific and unique information capable or recognizing and binding to the acceptor site of the chromatin and regulating gene expressions specific for steroids. The formation of such Receptor-Steroid Variable Complexes (RSVC) has been mathematically analyzed and the properties of a chromatin protein capable of detecting both the DNA and the steroid sequences on the receptor are discussed.

Animals↗
PubMed1985

Isolation of unliganded steroid receptor proteins by high-performance size-exclusion chromatography. An investigation of steroid-dependent structural alterations.

The physicochemical properties of unliganded steroid receptor proteins remain largely unknown primarily due to receptor lability in the absence of specific ligand, especially during prolonged biochemical analyses. We have utilized high-performance size-exclusion chromatography (HPSEC) as a rapid means of investigating the structural properties of cytosolic estrogen receptor proteins in both the presence and absence of [3H]estradiol-17 beta. Cytosols prepared from immature calf uteri were analyzed by HPSEC on an Altex TSK-3000 SW column (600 mm X 7.5 mm I.D.) either before or after incubation with 10 nM [3H]estradiol-17 beta. Postcolumn detection of previously unliganded receptor was accomplished by incubation of fractions (0.38 ml) with 10 nM [3H]estradiol-17 beta for 2-18 h at 0 degrees C. Receptor-bound steroid was separated from free steroid by incubation with small pellets of hydroxylapatite. Nonspecific binding of [3H]estradiol-17 beta in parallel fractions was estimated using an unlabelled competitor (diethylstilbestrol) specific for the estrogen receptor. In low ionic strengths the receptor exists as a single, relatively stable, large form (retention time 34 min). The elution properties of this receptor configuration do not depend on bound steroid ligand. Analysis of receptor at elevated ionic strengths in the presence and absence of steroid ligand suggests that the salt-induced dissociation of receptor components to smaller forms (retention time 47 min) may be partially steroid-dependent. Characterization of receptor in 6 M urea demonstrates the presence of intermediate-sized receptor components (retention time 36-38 min). Analyses of receptor in 6 M urea-0.4 M potassium chloride suggests an inhibition of the more extensive salt-induced dissociation event seen in 0.4 M potassium chloride alone. Furthermore, the intermediate-sized receptor forms seen under these conditions (retention time 41-42 min) are generated in a steroid-dependent manner. The preparation of different molecular forms of biologically active, unliganded estrogen receptor by HPSEC should help further our investigations into the molecular mechanism(s) by which steroid hormones exert their receptor-mediated effects on target cells.

Animals↗
PubMed1981

Inactivation of delta 5-3-oxo steroid isomerase with active-site-directed acetylenic steroids.

Several steroid analogues containing conjugated acetylenic ketone groups as part of a seco-ring structure or as substituents on the intact steroid system are irreversible inhibitors of delta 5-3-oxo steroid isomerase (EC 5.3.3.1) from Pseudomonas testosteroni. Thus 10 beta-(1-oxoprop-2-ynyl)oestr-4-ene-3,17-dione (I), 5,10-seco-oestr-4-yne-3,10,17-trione (II), 17 beta-hydroxy-5,10-seco-oestr-4-yne-3,10-dione (III) and 17 beta-(1-oxoprop-2-ynyl)androst-4-en-3-one (IV) irreversibly inactivate isomerase in a time-dependent manner. In all cases saturation kinetics are observed. Protection against inactivation is afforded by the powerful competitive inhibitor 19-nortestosterone. The inhibition constants (Ki) for 19-nortestosterone obtained from such experiments are in good agreement with those determined from conventional competitive-inhibition studies of enzyme activity. These compounds thus appear to be active-site directed. In every case the inactivated enzyme could be dialysed without return of activity, indicating that a stable covalent bond probably had formed between the steroid and enzyme. Compound (I) is a very potent inhibitor of isomerase [Ki = 66.0 microM and k+2 = 12.5 x 10(-3) s-1 (where Ki is the dissociation constant of the reversible enzyme-inhibitor complex and k+2 is the rate constant for the inactivation reaction of the enzyme-inhibitor complex)] giving half-lives of inactivation of 30-45 s at saturation. It is argued that the basic-amino-acid residue that abstracts the intramolecularly transferred 4 beta-proton in the reaction mechanism could form a Michael-addition product with compound (I). In contrast, although compound (IV) has a lower inhibition constant (Ki = 14.5 microM), it is a relatively poor alkylating agent (k+2 = 0.13 x 10(-3) s-1). If the conjugated acetylenic ketone groups are replaced by alpha-hydroxyacetylene groups, the resultant analogues of steroids (I)-(IV) are reversible competitive inhibitors with Ki values in the range 27-350 microM. The enzyme binds steroids in the C19 series with functionalized acetylenic substituents at C-17 in preference to steroids in the C18 series bearing similar groups in the ring structure or as C-10 substituents. In the 5,10-seco-steroid series the presence of hydroxy groups at both C-3 and C-17 is deleterious to binding by the enzyme.

Alkynes↗
PubMed1997

Correlation between binding affinities of C21 steroids for the maturation-inducing steroid membrane receptor in spotted seatrout ovaries and their agonist and antagonist activities in an oocyte maturation bioassay.

The relative binding affinities of steroids for the maturation-inducing steroid (MIS) plasma membrane receptor in spotted seatrout (Cynoscion nebulosus) ovaries were compared to their relative potencies in inducing final oocyte maturation (FOM) of seatrout oocytes in vitro. The MIS receptor is specific for C21 steroids (pregnenes) lacking ketone or hydroxyl (OH) groups at the 11 position. The addition of single OH groups at the 17, 20, or 21 positions and two OHs at the 17, 20 and at the 17, 21 positions of both progesterone and pregnenolone derivatives decreased binding affinity. In contrast, the combination of OH at the 20beta and 21 positions increased affinity, and greatest binding affinity for a progesterone derivative was observed with three OHs at positions 17, 20beta, and 21 (17,20beta,21-trihydroxy-4-pregnen-3-one; 20beta-S), the natural MIS in this species. Germinal vesicle breakdown (GVBD) bioassays showed that 1-min exposure to 290 nM 20beta-S or 17,20beta-dihydroxy-4-pregnen-3-one (17,20beta-P) in vitro was sufficient to induce final maturation of follicle-enclosed oocytes of seatrout and a closely related species, Atlantic croaker (Micropogonias undulatus), whereas the other steroids tested were ineffective. 20Beta-S was more potent than 17,20beta-P in inducing GVBD after 1-min exposure at lower steroid concentrations (5 nM-100 nM), even though the follicular uptake of the two steroids was similar. Coincubation of seatrout oocytes for 1 min with other steroids at concentrations capable of displacing more than 80% of the bound 20beta-S from its receptor effectively blocked the induction of GVBD by 5 nM 20beta-S. The binding affinities of steroids for the MIS receptor correlated in general with either their agonist or their antagonist activities in the GVBD bioassays. These findings strongly support the concept that induction of FOM by the MIS in spotted seatrout is mediated solely through the ovarian plasma membrane 20beta-S receptor.

Animals↗
PubMed1998

Levamisole treatment in steroid-sensitive and steroid-resistant nephrotic syndrome.

Since 1992 we have treated 11 children with frequently relapsing steroid-sensitive (n=6) or steroid-resistant (n=5) nephrotic syndrome with levamisole. All had been non-responsive to other immunosuppressive medication before levamisole treatment. All steroid-sensitive patients had signs of steroid toxicity. At least 1 kidney biopsy had been performed prior to study in each patient. Five children had minimal glomerular changes and the other 6 focal segmental glomerular sclerosis. The patients were treated with levamisole (2.5 mg/kg per 48 h) for at least 2 months (up to 18 months, median 10 months). Two patients had additional immunosuppression (cyclosporine A) during levamisole treatment. All patients with steroid-sensitive nephrotic syndrome became free of proteinuria within 2 months and have remained in remission after discontinuation of levamisole (follow-up time 8-50 months, median 24 months). None of the children with steroid-resistant nephrotic syndrome experienced a remission. Side effects were observed in 2 patients and included a granulocytopenia and a severe psoriasis-like cutaneous reaction; both were reversible after discontinuation of levamisole. We conclude that levamisole is of benefit in steroid-sensitive nephrotic syndrome but not in steroid-resistant nephrotic syndrome.

Adjuvants, Immunologic↗
PubMed2006

Metabolism and excretion of anabolic steroids in doping control--new steroids and new insights.

The use of anabolic steroids in sports is prohibited by the World Anti-Doping Agency. Until the 1990s, anabolic steroids were solely manufactured by pharmaceutical companies, albeit sometimes on demand from national sports agencies as part of their doping program. Recently the list of prohibited anabolic steroids in sports has grown due to the addition of numerous steroids that have been introduced on the market by non-pharmaceutical companies. Moreover, several designer steroids, specifically developed to circumvent doping control, have also been detected. Because anabolic steroids are most often intensively subjected to phase I metabolism and seldom excreted unchanged, excretion studies need to be performed in order to detect their misuse. This review attempts to summarise the results of excretion studies of recent additions to the list of prohibited steroids in sports. Additionally an update and insight on new aspects for "older" steroids with respect to doping control is given.

Anabolic Agents↗
PubMed1984

Inhibition of 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) activities of human placenta by steroids and non-steroidal hormone agonists and antagonists.

Various naturally occurring steroids, synthetic steroid derivatives and non-steroidal hormone agonists and antagonists were assayed as inhibitors of human placental 17 beta-HSD activities. Microsomal 17 beta-HSD was inhibited by C18-, C19- and C21-steroids. Soluble 17 beta-HSD was highly specific for C18-steroids. In contrast to the soluble activity, the microsomal enzyme also had a strong affinity for ethinylestradiol (KI = 0.3 microM) and danazol (KI = 0.6 microM); anabolic steroids and norethisterone were weaker inhibitors. Of the non-steroids tested only diethylstilbestrol and o-demethyl CI-680 were inhibitors and they showed a greater affinity for soluble 17 beta-HSD. KI-values for estradiol-17 beta, (0.8 microM), progesterone (27.0 microM) and 20 alpha-dihydroprogesterone (1.5 microM) were comparable to reported tissue levels of these compounds, consistent with a possible competition in vivo among naturally occurring C18-, C19-, and C21-steroids for the active site of microsomal 17 beta-HSD.

17-Hydroxysteroid Dehydrogenases↗
PubMed1993

Steroid sparing effect of nedocromil sodium in asthmatic patients on high doses of inhaled steroids.

Nedocromil sodium is a non-steroidal prophylactic agent developed for the management of asthma. We have assessed the steroid sparing potential of inhaled nedocromil sodium 4 mg four times daily in a randomized, double blind, placebo controlled study in 69 asthmatic subjects controlled on inhaled beclomethasone dipropionate in the dose range 1000-2000 micrograms daily. Following a 4 week run-in period subjects added nedocromil sodium or placebo by metered dose inhaler to their usual medication for a further 4 weeks. The dose of inhaled steroid was then reduced at fortnightly intervals according to a predetermined schedule, with monitoring of asthma severity, symptom scores, bronchodilator use and peak flow recordings. Sixty subjects entered the steroid reduction phase and achieved median (range) % decreases in steroid dose of 80 (17-100)% with nedocromil sodium compared to 65 (0-100)% with placebo (P = 0.34) with 14 patients in the nedocromil sodium group and 10 in the placebo group being withdrawn completely from inhaled steroids. Subjective global assessment scores were significantly better with nedocromil sodium (mean 2.14) than with placebo (2.93; P < 0.02) though there was no difference between individual daily symptom scores. In this study therefore in asthmatic patients controlled on high doses of inhaled steroids, nedocromil sodium was well tolerated but the small differences in steroid sparing effect between nedocromil and placebo were not statistically significant.

Administration, Inhalation↗
PubMedDate not supplied

Steroid metabolism in obese children II. Steroid excretion of obese and normal weight children.

Comparative studies on adrenal function have been performed in 56 children, 31 obese and 25 of normal weight. Their body weight fell within the range between 80 and 215% of the ideal weight (100%). Nine steroids resp. steroid groups were measured by gas chromatography. The participants were grouped by degree of fatness, sex and presence of absence of puberty (Tanner I or higher than I). The urinary steroid excretion rate was corrected for weight. Altered steroid metabolism was found in obese children as compared with the normal groups: not only the excretion of cortisol metabolites was increased but also that of androgen metabolites and pregnenediol, metabolite of pregnanolone. There is a trend for increased excretion of all steroid groups, in certain cases this attains the level of statistical significance. Wide variability was observed in the steroid excretion of obese children, in about one third of them there was hypersecretion of some components of the steroid spectrum. This phenomenon was more frequently encountered in boys. Extension of the normal range of steroid excretion rates of obese children seems to be justified.

Adolescent↗