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At least 199 records · Page 11Linked to original sources

The porous titanium steroid eluting electrode: a double blind study assessing the stimulation threshold effects of steroid.

A transvenous pacing lead with a porous electrode which slowly elutes the steroid, dexamethasone sodium phosphate, has been developed. Previous investigations show low and constant stimulation thresholds persisting over at least the first two years post-implantation. As it is not known whether this low threshold results from the steroid or electrode configuration, a double blind study was designed to compare the same electrode configuration with and without steroid over a 2-year follow-up period. There were ten patients in each group with similar age, sex, indications for pacing and implantation data. Regular measurements of postoperative pulse duration thresholds were performed using a customized VVIM pulse generator programmed to 1.5 V output. For the first two days post-implantation, there were no statistical differences in the pulse duration thresholds between the two pacing leads. From 2 weeks to 2 years the pulse duration thresholds for the steroid leads remained almost constant, whereas the leads without steroid showed a typical rise. The difference in pulse duration thresholds between the two groups of leads from two weeks onwards confirmed that it was the steroid rather than the electrode configuration which prevented the rise in chronic stimulation threshold.

Aged↗

Studies on steroid fever. II. Pyrogenic and anti-pyrogenic activity in vitro of some endogenous steroids of man.

The pyrogenic properties of some C-19 and C-21 steroids were examined by in vitro incubation of human blood leukocytes with serum-buffer solutions of the steroids and injection of the 18-hr supernatants into rabbits. In previous studies this method demonstrated release of leukocyte endogenous pyrogen by etiocholanolone. With two exceptions, steroids known to cause fever in man, such as 11beta-OH etiocholanolone and 3alpha-hydroxy-5beta-pregnane-20-one were also pyrogenic in vitro. All steroids tested which are nonpyrogenic in man, such as androsterone, 3beta-OH etiocholanolone, and 3alpha, 17alpha-dihydroxy-5beta-pregnan-20-one were also nonpyrogenic in vitro. Solubility in aqueous solution did not correlate with pyrogenic capacity. Inhibition of pyrogen release from human leukocytes in vitro by hydrocortisone and estradiol was demonstrated. Hydrocortisone-treated leukocytes released less pyrogen than did normal leukocytes when stimulated either by etiocholanolone or by phagocytosis of heat-killed staphylococci. On the other hand, estradiol-treated blood leukocytes and mononuclear cells showed significant suppression of pyrogen release when phagocytosis, but not etiocholanolone, was used as the stimulus. When blood cells were incubated with progesterone, greater than normal amounts of pyrogen were released following phagocytosis, and the inhibiting effect of estradiol could be partially reversed. Neither estradiol nor hydrocortisone appeared to act on rabbit leukocytes. These studies indicate that a variety of naturally-occurring steroids may alter pyrogen release from leukocytes. Alterations in steroid balance in man may influence normal temperature regulation and contribute to clinical fevers.

Androsterone↗

Serum binding of steroid tracers and its possible effects on direct steroid immunoassay.

We studied the serum protein binding of 3H-labelled progesterone, oestradiol and testosterone, and five 125I-labelled analogues of these steroids. All tracers investigated appeared to be bound by proteins in every serum sample tested. The addition of blocking agents caused a substantial reduction in serum protein binding of 3H-labelled steroids, but had relatively little effect on the binding of analogue steroid tracers. Use of analogue steroid tracers in conventional direct immunoassays for oestradiol and progesterone produced anomalous results for some patient samples when compared to extraction radioimmunoassays, but assays where tracer binding to serum constituents was prevented by adoption of two-step procedures appeared to avoid anomalous results. The results suggest that serum protein binding of steroid analogue tracers may be a source of interference in some direct steroid immunoassays.

Blood Proteins↗

Anti-androgen TSAA-291. II. Manifestation of the anti-androgenic action of a steroid ester TSAA-330 (16 beta-ethyl-17 beta-hydroxy-4-oestren-3-one caproate) and elucidation of its long-lasting mechanism using a simple steroid determination technique.

Using a simple steroid determination technique, in situ steroid absorption from a subcutaneously injected sesame oil solution in rats was pursued following the time-course changes in the steroid concentration. Based on the knowledge thus obtained, the anti-androgenic effect of a steroidal compound, TSAA-330, could be manifested in the subcutaneous route. (1) Anti-androgenic steroid TSAA-291 and its esters in the subcutaneously injected sesame oil solution were selectively absorbed into the general circulation at different rates according to their chemical nature and structures, while the oil itself remained at the injected site for a considerably long period. At the injected site where subcutaneous doses of steroids molar equivalent to 50 mg of TSAA-291 were administered in 5 ml/rat of sesame oil, TSAA-291 decreased to the level of 10% of the initial concentration on the 4th day. TSAA-328 decreased slowly to the 50% and 20% levels on the 7th and 21st day, respectively. TSAA-335 decreased more slowly to the 50% level on the 14th day. TSAA-330 decreased most slowly only to the 70% level on the 49th day. (2) A single subcutaneous administration of 200 mg of TSAA-330 suppressed the weight increase of the accessory sex organs caused by a single subcutaneous injection of testosterone caproate (10 mg) in the immature orchiectomized rat. The suppressive effect was obvious from 2 weeks after the administration, and seemed to last for more than two weeks. The levator ani weight was not affected by the administration of TSAA-330. (3) Dose-dependent inhibitions of the accessory sex organs were obtained three weeks after a single subcutaneous administration of 50 to 400 mg of TSAA-330 in the adult male rat. (4) Daily oral administrations of 50 mg of TSAA-291 or TSAA-330 to the adult male rat for 8 days resulted in depression of the accessory sex organs to almost the same extent obtained with either agent. One week after the last administration, however, the weight of the accessory sex organs of the TSAA-291-administered animals recovered to almost the comparable level with the control, whereas a significant after-effect of the inhibition was still evident in the TSAA-330-administered animals.

Absorption↗

Efficacy and safety of aerosolized triamcinolone acetonide in steroid-dependent and steroid-independent chronic asthmatic patients.

Fourteen steroid-dependent and 16 steroid-independent asthmatic patients received aerosol triamcinolone acetonide for 12 weeks (two 200-micrograms inhalations four times daily). The mean daily oral steroid dose for the steroid-dependent patients was reduced from 12.5 mg at baseline to 1.34 mg after 12 weeks of aerosol therapy. In both groups of patients, FEV1.0, FVC and FEF25-75% values improved during therapy, usually at a statistically significant rate. Highly significant improvement occurred in shortness-of-breath, wheezing tightness-in-chest, and cough symptoms in all patients. However, changes in serum cortisol levels were not statistically significant. Side effects included transient hoarseness (seven patients), dry throat (one), and sore throat (one). No oral candidiasis was observed and no patient discontinued therapy because of side effects. Steroid withdrawal symptoms, which gradually abated, were experienced by half of the steroid-dependent patients. Aerosolized triamcinolone acetonide was therefore considered a safe and effective modality in the management of chronic asthma.

Adolescent↗

Reevaluation of steroid tapering after steroid pulse therapy for heart rejection.

A retrospective analysis was conducted to determine the efficacy and complications resulting from steroid pulse therapy, with or without a steroid taper, in 93 episodes of heart transplant rejection that occurred in 72 patients (58 men, 14 women; mean age, 47.6 years). Each rejection episode was classified according to severity (Texas Heart Institute endomyocardial biopsy scale) and the treatment. Group 1 included 25 episodes of grade 7, 8, 9, or 10 rejection (International Society for Heart Transplantation [ISHT] grade IIIB or IV) that were treated with high-dose methylprednisolone (2.5 to 3.0 gm) and a steroid taper of 1.75 gm over 30 days. Group 2 included 16 episodes of rejection, with the severity of rejection and methylprednisolone pulse therapy being similar to that in group 1, but without a steroid taper. The results of treatment in group 1 were compared with those in group 2. Group 3 included 12 episodes of grade 5, 6, or 7 rejection (ISHT grade IIIA or IIIB) that were treated with moderate-dose methylprednisolone (1.0 to 2.0 gm) and a steroid taper, as described. Group 4 included 40 episodes of rejection, with the severity of rejection and methylprednisolone therapy being similar to that of group 3, but without a steroid taper. The results of treatment in group 3 were compared with those in group 4. No statistically significant differences were found among the groups regarding subsequent episodes of rejection or infection within 3 months of treatment. No statistically significant difference was noted among the groups in the number of rejection episodes requiring additional therapy to control the rejection.(ABSTRACT TRUNCATED AT 250 WORDS)

Female↗

[Influence of steroid therapy local injection of steroidal in the region of the stylomastoid foramen and physiotherapy on the recovery of stapedial reflex in patients with facial nerve paralysis].

There are much more publications which informates about positive effects of advisability propose steroid's cure in patients with facial nerve palsy. The aim of the studies was to evaluate the influence of steroidal and physical treatment on the recovery of stapedial reflex and of functions of the damaged nerve. The studies were performed on 37 patients with palsy of facial nerve. Taking into account the stapedial reflex (before the beginning of the treatment) and local injection of steroidal in the region of the stylomastoid foramen, the patients were divided into two groups: I group--21 persons with lacking stapedial reflex, who were not given steroid, II group--16 persons with lacking stapedial reflex who received steroid. Evaluation of results of treatment was performed by means of the Pietruski, House and Brackmann scales, registration of stapedial reflex and accommodation coefficient. The results indicate that local steroid in palsy facial nerve is the treatment of choice in cases of intratemporal branches injury (lack of stapedial reflex) and shortens of duration of stapedial reflex and the nerve function recovery.

Adolescent↗

Combined orbital irradiation and systemic steroids compared with systemic steroids alone in the management of moderate-to-severe Graves' ophthalmopathy: a preliminary study.

OBJECTIVE: To assess the efficacy and safety of combined orbital irradiation and systemic steroids in the management of moderate-to-severe Graves' ophthalmopathy. DESIGN: Single-blind randomised prospective study. SETTING: Regional hospital, Hong Kong. PATIENTS: Sixteen patients with active moderate-to-severe Graves' ophthalmopathy who were randomly assigned to steroid therapy (ST group) or combination therapy of orbital irradiation and systemic steroids (SRT group) between June 2000 and June 2003. MAIN OUTCOME MEASURES: NOSPECS scoring system, total eye score, subjective eye score, and extra-ocular muscle thickness as determined by either computed tomographic or magnetic resonance imaging scans. RESULTS: The study was completed by 15 of 16 patients. Both groups experienced improvement in total eye score, soft tissue swelling, ocular motility, visual acuity, and subjective eye score at 52-week follow-up. Total eye score improved earlier in the SRT group, achieving statistical significance (P<0.05) at as early as 4 weeks of follow-up. Improvement in ocular parameters was greater and led to a significantly greater reduction in total eye score than in the ST group at weeks 16, 24, and 52. Maximum extra-ocular muscle thickness was significantly reduced in the SRT group only. No change was observed in proptosis in either group. No serious adverse effect was observed with the addition of orbital irradiation to steroid therapy. CONCLUSION: A combination of orbital irradiation and systemic steroids is well tolerated and more effective than steroids alone in the treatment of active moderate-to-severe Graves' ophthalmopathy. It achieves greater and more rapid improvement in soft tissue swelling, ocular motility, and visual acuity.

Administration, Oral↗

Translational regulation by steroids. Identification of a steroid modulatory element in the 5'-untranslated region of the myelin basic protein messenger RNA.

Although steroids have been implicated in post-transcriptional regulation, their effects on mRNA translation rates have been uncertain. We have used a cell-free translation system programmed with synthetic messages to show that steroids can alter the translation rates of a number of myelin protein mRNAs and the mRNA encoding a non-myelin protein, the estrogen receptor. Through the use of deletion analysis, site-directed mutagenesis, and chimeric mRNAs we have identified a 9-nucleotide segment in the 5'-untranslated region of one myelin protein mRNA that is necessary for steroid action. Steroid-mediated translational regulation is discussed in terms of myelination where subtle developmental changes in protein composition of the membrane have significant consequences on its morphology and function. We propose that the modulation of mRNA translation rates by steroids is a more general phenomenon that may serve as another mechanism by which steroids can regulate gene expression.

Animals↗

The steroid-dependent regulatory element in the ovalbumin gene does not function as a typical steroid response element.

Transcription of the chicken ovalbumin gene is induced both in vivo and in vitro by four classes of steroid hormones. Recent experiments identified a steroid-dependent regulatory element (SDRE) in the 5'-flanking region of the ovalbumin gene between -900 and -521. To characterize the regulatory properties of the SDRE more precisely, additional mutations were created in this region, and fusion genes prepared by linking the ovalbumin 5'-flanking region and promoter to the chloramphenicol acetyltransferase structural gene. When the ovalbumin-chloramphenicol acetyltransferase fusion genes were transfected into steroid-responsive primary oviduct cells, mutants lacking sequences between -900 and -732 were no longer responsive to estrogen, corticosterone, progesterone, or dihydrotestosterone. The SDRE did not confer steroid-dependent expression on the heterologous thymidine kinase promoter by itself but did in conjunction with the negative regulatory element identified between -350 and -100. This suggests that the two elements act as a single functional entity and that the SDRE is not behaving as a typical steroid response element. Gel shift analyses revealed that two SDRE.protein complexes were formed when nuclear protein extracts were derived from estrogen-treated chicken oviduct but that only one complex was formed with extracts from estrogen-withdrawn oviduct or from other tissues. Neither an estrogen response element oligomer nor a glucocorticoid/progesterone response element oligomer competed for either of the DNA.protein complexes. Partially purified progesterone receptor also did not bind to the SDRE. These data indicate that induction of the ovalbumin gene by steroid hormones requires complex interactions involving both the SDRE and the negative regulatory element.

Animals↗

Evidence that the conserved region in the steroid binding domain of the glucocorticoid receptor is required for both optimal binding of hsp90 and protection from proteolytic cleavage. A two-site model for hsp90 binding to the steroid binding domain.

Steroid hormone receptors contain a conserved sequence of amino acids within the steroid binding domain, and we have previously speculated that this conserved region is the site of interaction of the glucocorticoid receptor with hsp90 (Danielsen, M., Northrop, J. P., and Ringold, G. M. (1986) EMBO J. 5, 2513-2522; Pratt, W. B., Jolly, D. J., Pratt, D. V., Hollenberg, S. M., Giguere, V., Cadepond, F. M., Schweizer-Groyer, G., Catelli, M.-G., Evans, R. M., and Baulieu, E.-E. (1988) J. Biol. Chem. 263, 267-273). In this work, we transfect COS-7 cells with three mutants of the mouse glucocorticoid receptor deleted for all or part of this conserved region. The mutant receptor missing the entire conserved region is very unstable and is found predominantly as cleavage products. Approximately one-third of the cleavage products have lost most or all of the steroid binding domain. This mutant receptor has a constitutive activity that is about one-third that of the steroid-bound wild type receptor in stimulating transcription from a reporter gene. We propose that the partial constitutive activity results from proteolytic cleavage of the steroid binding domain from the rest of the receptor, thus removing the functional repression determined by this domain. This mutant receptor is associated with hsp90 in cytosols prepared in the presence of molybdate but, when molybdate is not present, the receptor is unstable and there is very little receptor-associated hsp90. This observation is consistent with the proposal that binding of hsp90 helps to stabilize the glucocorticoid receptor against proteolysis, and it demonstrates that the site of molybdate interaction with the receptor lies outside of the conserved sequence. Our data are interpreted according to a two-site model in which hsp90 interacts with the steroid binding domain at two sites. One site is in the conserved sequence, and the other is at a transition metal oxyanion binding site, located between the conserved sequence and the COOH terminus.

Animals↗

Circadian rhythm of plasma aldosterone and plasma renin activity in steroid and non-steroid treated kidney transplanted patients.

The circadian rhythm of plasma aldosterone (PAC) and cortisol concentration (PCC), and renin activity (PRA) was measured in five steroid and five non-steroid treated kidney transplanted patients--all with denervated kidney grafts--and compared with four normal controls and two steroid-treated patients with non-renal disease and thus normal renal innervation. The non-steroid treated patients had a normal circadian thythm of PAC and PCC, but without variation of PRA, suggesting that denervation of the kidneys has no influence on the circadian rhythm of PAC. In both steroid treated groups the PAC showed an inverse diurnal variation--now correlating to the diurnal variation in PRA. The inverse circadian rhythm of PAC in patients with suppressed ACTH secretion remains unexplained, but is in accordance with the nocturnal peak of sodium and water excretion in steroid treated patients.

Adult↗

The proinflammatory function of lymphocytes in non-immune inflammation: effect of steroidal and non-steroidal anti-inflammatory agents.

Leucopenia rendered rats unresponsive to various inflammatory stimuli. The intensity of the inflammatory response in such animals was restored by i.v. administration of suspensions of lymphocytes, but not of granulocytes. This restorative effect was blocked by both steroidal and non-steroidal anti-inflammatory drugs. Utilizing carrageenin to induce inflammatory responses in the rat's paw, the effect of these drugs on lymphocytes was observed in two circumstances. First, following incubation of the cells with the drugs in concentrations not exceeding the peak plasma levels estimated for these substances in man or laboratory animals; the effect of the drugs seemed selective, since anti-histamine and anti-serotonin agents, as well as amethopterin, were devoid of action. Second, when lymphocytes were collected from rats previously treated with the various anti-inflammatory agents, injected 6-hourly during periods of 18 and 36 h, respectively, for steroidal and non-steroidal anti-inflammatory substances. The total amounts given were lower than those required to produce consistent anti-inflammatory effects in normal animals, when the drug was given as a single dose before injection of the irritant. It is concluded that the pro-inflammatory function of lymphocytes in non-immune inflammation can be blocked by steroidal and non-steroidal anti-inflammatory agents.

Animals↗

[Cellular heterogeneity of steroid reactivity in human endometrial carcinoma: an approach by an immunofluorescent steroid-antibody technique (author's transl)].

The dispersed cancer cells obtained from biopsy or surgical specimens of 12 patients with endometrial carcinoma were incubated with 5 x 10(-8) M estradiol-17 beta or progesterone in TC medium 199 containing 10% calf serum at 37 degrees C for 1 hr. The immunofluorescent steroid-antibody technique using FITC-labeled anti-rabbit IgG and steroid antibodies raised from rabbits immunized with estradiol-6-oxime-BSA and progesterone-3-oxime-BSA was applied to the smear specimens and freeze-dry sections that had been incubated with these steroids. In 6 cases, there was a mixed cell-population with or without nuclear fluorescence to estradiol and progesterone. The cellular heterogeneity with respect to nuclear fluorescence was confirmed by the immunofluorescent technique applied to the freeze-dry sections. Two cases showed weak cytoplasmic fluorescence to estradiol and progesterone, but nuclear fluorescence was negative. In 3 cases, there was no immunoreactivity to these steroids. One case exhibited the similar distributional patterns of cytoplasmic and nuclear fluorescence to those of normal endometrial cells. These results indicated that in endometrial cancer, there were some impairments of subcellular steroid dynamics in comparison with those of normal cells and that cellular heterogeneity of the steroid reactivity might exist in some cases.

Adult↗

Congenital adrenal hyperplasia caused by defect in steroid 21-hydroxylase. Establishment of definitive urinary steroid excretion pattern during first weeks of life.

The steroid excretion of two female infants with congenital adrenal hyperplasia due to 21-hydroxylase deficiency has been studied during the first weeks of life. The techniques used were gas chromatography on an open-tubular column and combined gas chromatography-mass spectrometry using selected ion recording. During the first days of life 3beta-hydroxy-5-ene steroids predominate and the levels found were considerably greater than those found in normal infants. Selected ion recording mass spectrometry permitted detection of pregnanetriol and 11-oxo-pregnanetriol several days before these steroids could be determined with accuracy by conventional gas chromatography. Pregnanetriol and 11-oxo-pregnanetriol were first detected on the third day of life. The results of this investigation demonstrate that 21-hydroxylase deficiency may be indicated during the first week of life by an increased 3beta-hydroxy-5-ene steroid excretion, but the definitive excretion pattern required for firm diagnosis may not develop for several days. The amounts of the definitive steroids excreted may not be sufficient to be detected by the more usual methods for several weeks.

Adrenocortical Hyperfunction↗

Conversion of 5 alpha-pregnane-3,20-dione, 3 alpha-hydroxy-5 alpha-pregnan-20-one and 3 beta-hydroxy-5 alpha-pregnan-20-one to delta 16-C19 steroids by the reconstituted delta 16-C19-steroid synthetase system.

The substrate specificity of the reconstituted delta 16-C19-steroid synthetase system, which catalyzes the formation of 5,16-androstadien-3 beta-ol or 4,16-androstadien-3-one from pregnenolone or progesterone, respectively, was studied. The reconstituted system consisted of a partially purified cytochrome P-450, NADPH-cytochrome P-450 reductase, cytochrome b5 and NADH-cytochrome b5 reductase all from pig testicular microsomes. It was found that 5 alpha-reduced C21 steroids such as 5 alpha-pregnane-3,20-dione, 3 alpha-hydroxy-5 alpha-pregnan-20-one and 3 beta-hydroxy-5 alpha-pregnan-20-one can be substrates for the enzyme system, resulting in the formation of 5 alpha-androst-16-en-3-one, 5 alpha-androst-16-en-3 alpha-ol and 5 alpha-androst-16-en-3 beta-ol, respectively. The results suggest that 5 alpha-reduced delta 16-C19 steroids might be synthesized from pregnenolone and progesterone via 5 alpha-reduced C21 steroids as intermediates. The pathways would bypass 5,16-androstadien-3 beta-ol and 4,16-androstadien-3-one which have been assumed as obligatory intermediates in the formation of 5 alpha-reduced delta 16-C19 steroids from pregnenolone and progesterone.

5-alpha-Dihydroprogesterone↗

Inhibition of steroid C17(20) lyase with C-17-heteroaryl steroids.

Steroids bearing a heteroaromatic substituent at C-17 were designed as inhibitors of C17(20) lyase. The thiazoles, furans, and thiophenes appended to the steroid nucleus were positioned on the alpha-face and the beta-face of the steroid, and conjugated with a 16,17-olefin, to test their ability to coordinate the heme iron of the P450 enzyme complex. The position of the heterocycle with respect to the steroid skeleton was determined to be important for optimum affinity and, in general, compounds with the heterocycle attached to a trigonal center at C-17, had the best affinity for C17(20) lyase. Simple molecular models were used to compare the three types of heterocyclic-substituted steroids.

Animals↗

Role of steroid 11 beta-hydroxylase and steroid 18-hydroxylase in the biosynthesis of glucocorticoids and mineralocorticoids in humans.

A gene encoding steroid 18-hydroxylase (P-450C18) was isolated from a human genomic DNA library. It was identified as CYP11B2, which was previously postulated to be a pseudogene or a less active gene closely related to CYP11B1, the gene encoding steroid 11 beta-hydroxylase (P-45011 beta) [Mornet, E., Dupont, J., Vitek, A. & White, P. C. (1989) J. Biol. Chem. 264, 20961-20967]. The nucleotide sequence of the promoter region of the P-450C18 gene is strikingly different from that of the P-45011 beta gene, although the sequences of their exons are 93% identical. The transient expression in Y-1 adrenal tumor cells of CAT constructs with a series of deletion mutants of promoter regions of both genes indicated that the two genes are regulated differently. P-450C18 as expressed in COS-7 cells exhibits steroid 18-hydroxylase activity to catalyze the synthesis of aldosterone and 18-oxocortisol and exhibits steroid 11 beta-hydroxylase activity as well. In contrast, P-45011 beta as expressed in the cultured cells exhibits steroid 11 beta-hydroxylase activity exclusively but fails to catalyze the synthesis of aldosterone and 18-oxocortisol. These results indicate that P-45011 beta and P-450C18 are products of two different genes and that the former participates in the synthesis of glucocorticoids whereas the latter participates in the synthesis of mineralocorticoids in humans.

Amino Acid Sequence↗