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Anesthesiology Sep 1999This multicenter, assessor-blinded, randomized study was done to confirm and extend a pilot study showing that intramuscular rocuronium can provide adequate tracheal... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
BACKGROUND
This multicenter, assessor-blinded, randomized study was done to confirm and extend a pilot study showing that intramuscular rocuronium can provide adequate tracheal intubating conditions in infants (2.5 min) and children (3 min) during halothane anesthesia.
METHODS
Thirty-eight infants (age range, 3-12 months) and 38 children (age range, 1 to 5 yr) classified as American Society of Anesthesiologists physical status 1 and 2 were evaluated at four investigational sites. Anesthesia was maintained with halothane and oxygen (1% end-tidal concentration if <2.5 yr; 0.80% end-tidal concentration if >2.5 yr) for 5 min. One half of the patients received 0.45 mg/kg intravenous rocuronium. The others received 1 mg/kg (infants) or 1.8 mg/kg (children) of intramuscular rocuronium into the deltoid muscle. Intubating conditions and mechanomyographic responses to ulnar nerve stimulation were assessed.
RESULTS
The conditions for tracheal intubation at 2.5 and 3 min in infants and children, respectively, were inadequate in a high percentage of patients in the intramuscular group. Nine of 16 infants and 10 of 17 children had adequate or better intubating conditions at 3.5 and 4 min, respectively, after intramuscular rocuronium. Better-than-adequate intubating conditions were achieved in 14 of 15 infants and 16 of 17 children given intravenous rocuronium. Intramuscular rocuronium provided > or =98% blockade in 7.4+/-3.4 min (in infants) and 8+/-6.3 min (in children). Twenty-five percent recovery occurred in 79+/-26 min (in infants) and in 86+/-22 min (in children).
CONCLUSIONS
Intramuscular rocuronium, in the doses and conditions tested, does not consistently provide satisfactory tracheal intubating conditions in infants and children and is not an adequate alternative to intramuscular succinylcholine when rapid intubation is necessary.
Topics: Androstanols; Child, Preschool; Female; Humans; Infant; Injections, Intramuscular; Intubation, Intratracheal; Laryngoscopy; Male; Neuromuscular Junction; Neuromuscular Nondepolarizing Agents; Rocuronium; Time Factors
PubMed: 10485771
DOI: 10.1097/00000542-199909000-00012 -
Journal of Andrology 2009Benign prostatic hyperplasia (BPH) is an age-dependent prostatic disease affecting male humans and dogs. In dogs, the combined administration of estrogens and androgens...
Benign prostatic hyperplasia (BPH) is an age-dependent prostatic disease affecting male humans and dogs. In dogs, the combined administration of estrogens and androgens synergistically increases prostate weight, and continued treatment leads to the development of glandular hyperplasia. The aim of the present study was to examine the immunohistochemical expression of androgen receptor (AR), estrogen receptor alpha (ER alpha), and estrogen receptor beta (ER beta) in the different cell types of the prostate gland in an experimental model. Five male beagle dogs were castrated and treated with 25 mg of 5 alpha-androstane-3 alpha and 17beta-diol and 0.25 mg 17beta-estradiol for 30 weeks. Prostate specimens were surgically obtained every 45 days (experimental stages M0 to M6: 0, 12, 18, 24, 30, and 36 weeks from the beginning of the hormonal treatment). The control group consisted of 3 noncastrated dogs treated with a vehicle, from which specimens were only taken at the time points M0, M1, M4, and M6. Immunohistochemical data revealed high AR and ER alpha expression in the epithelial and stromal cell nuclei of all the experimental and control specimens. Weak staining of the cytoplasm was observed only in epithelial cells. The suspension of hormone treatment led to a significant reduction in the expression of both receptors. On the contrary, ER beta was expressed only in epithelial cell nuclei, with no significant differences in the percentages of stained nuclei between control and hormonally treated or atrophic prostates. Results indicate that AR, ER alpha, and ER beta are differently expressed in canine prostate tissue and that they show specific expression patterns in response to the hormonal induction of BPH.
Topics: Androstanes; Animals; Dogs; Estrogen Receptor alpha; Estrogen Receptor beta; Estrogens; Immunohistochemistry; Male; Prostatic Hyperplasia; Receptors, Androgen
PubMed: 19136389
DOI: 10.2164/jandrol.108.006775 -
Fertility and Sterility Jul 2001To determine the pharmacokinetics of testosterone following its administration using transdermal gel or buccal lozenges.
OBJECTIVE
To determine the pharmacokinetics of testosterone following its administration using transdermal gel or buccal lozenges.
DESIGN
Pilot study.
SETTING
University-based hospital.
PATIENT(S)
Ten bilaterally oophorectomized women.
INTERVENTION(S)
Daily micronized testosterone gel (1 mg) and testosterone propionate lozenge (1 mg).
MAIN OUTCOME MEASURE(S)
Total testosterone, androstenedione, dihydrotestosterone, 3alpha-androstanediol glucuronide, and sex hormone-binding globulin were measured in serum by specific radioimmunoassays; free testosterone levels were also calculated.
RESULT(S)
Before treatment, serum testosterone levels in the groups using the lozenge and gel were 16 +/- 4.0 and 20 +/- 6.0 ng/dL, respectively. Mean maximum testosterone levels obtained with the lozenge occurred 1 hour after administration on days 1 (692 +/- 236 ng/dL) and 14 (836 +/- 309 ng/dL) of treatment and fell precipitously thereafter. In contrast, testosterone levels obtained with the gel showed a prolonged rise reaching maximal levels of 97 +/- 78 and 100 +/- 60 ng/dL after 18 hours. The serum level patterns of free testosterone, dihydrotestosterone, and 3alpha-androstanediol glucuronide were similar to the corresponding total testosterone levels.
CONCLUSION(S)
Administration of testosterone lozenge by buccal absorption produced a rapid and brief elevation of testosterone levels, with levels reaching upper limits of the male range. In contrast, transdermal testosterone gel absorption resulted in a prolonged elevation of testosterone levels, which were in the hyperandrogenic female range but resembled steady state pharmacokinetics.
Topics: Absorption; Administration, Cutaneous; Administration, Oral; Androstane-3,17-diol; Cheek; Dihydrotestosterone; Female; Gels; Humans; Middle Aged; Ovariectomy; Pilot Projects; Testosterone; Time Factors
PubMed: 11438316
DOI: 10.1016/s0015-0282(01)01827-1 -
The Journal of Biological Chemistry May 1975The sulfate-specific hydroxylase system in liver microsomes from rats has been investigated with respect to its substrate specificity. Eighteen different C18, C19, C21,... (Comparative Study)
Comparative Study
The sulfate-specific hydroxylase system in liver microsomes from rats has been investigated with respect to its substrate specificity. Eighteen different C18, C19, C21, and C27 steroid sulfates and the coresponding free steroids have been incubated with microsomal preparations from male and female rats. The sulfate-specific system was only present in preparations from female rats and primarily catalyzed hydroxylation in position 15beta but also in position 7beta. In contrast to this, male liver microsomes were more efficient than female liver microsomes in hydroxylating free steroids; these were hydroxylated in positions 2alpha,2beta,6alpha,6beta,7alpha,7beta,16alpha, and 18. The sulfate-specific hydroxylase system in female liver microsomes was found to have rigid requirements c concerning the structure of ring D in the substrate molecule; only 17beta-sulfates (C18 and C19 steroids) and 21-sulfates (C21 steroids) were hydroxylated. Less rigid criteria, however, exist concerning the structure of ring A. The following K-m values were determined for microsomal 15beta-hydroxylation: 5alpha-androstane-3alpha,17beta-diol disulfate, 17.2 muM; 5beta-androstane-3alpha,17beta-diol disulfate, 16muM;5alpha-androstane-3alpha,17beta-diol 17-sulfate, 26 muM; and estradiol 17-sulfate, 181 muM. Some of the regulatory mechanism controlling the activity of the sex-specific 15beta-hydroxylase system also have been studied and compared to the mechanism controlling the activities of the less specific 2alpha-, 7alpha-, and 18-hydroxylase systems active on 5alpha-[4-14C]androstane-3alpha,17beta-diol. Biliary drainage did not affect the 15beta-hydroxylase activity, whereas the 2alpha- and 7alpha-hydroxylase activities decreased..
Topics: Androstanes; Androstenediols; Animals; Bile; Common Bile Duct; Estradiol; Female; Hypophysectomy; Kinetics; Ligation; Male; Microsomes, Liver; Pregnenolone; Progesterone; Rats; Steroid Hydroxylases; Structure-Activity Relationship; Sulfuric Acids; Testosterone
PubMed: 1123349
DOI: No ID Found -
Cellular and Molecular Life Sciences :... May 2007In this study we have assessed the effect of testosterone (T), dihydrotestosterone (DHT) and 5alphaandrostan-3alpha, 17beta-diol (3alpha-diol) therapies on diabetic...
In this study we have assessed the effect of testosterone (T), dihydrotestosterone (DHT) and 5alphaandrostan-3alpha, 17beta-diol (3alpha-diol) therapies on diabetic neuropathy. Diabetes was induced in adult male rats by the injection of streptozotocin and resulted in decreased T and increased 3alpha-diol levels in plasma and in decreased levels of pregnenolone and DHT in the sciatic nerve. Moreover, a reduced expression of the enzyme converting Tinto DHT (i.e., the 5alpha-reductase) also occurs at the level of sciatic nerve, suggesting that the decrease of DHT levels could be due to an impairment of this enzyme. Chronic treatment for 1 month with DHT or 3alpha-diol increased tail nerve conduction velocity and partially counteracted the increase of thermal threshold induced by diabetes. Treatment with DHT increased tibial Na(+),K(+)-ATPase activity and the expression of myelin protein P0 in the sciatic nerve.DHT, 3alpha-diol and T reversed the reduction of intra-epidermal nerve fiber density induced by diabetes. These observations indicate that T metabolites can reverse behavioral, neurophysiological, morphological and biochemical alterations induced by peripheral diabetic neuropathy.
Topics: Anabolic Agents; Androstane-3,17-diol; Animals; Diabetes Mellitus, Experimental; Diabetic Neuropathies; Dihydrotestosterone; Male; Neuroprotective Agents; Rats; Rats, Sprague-Dawley; Testosterone
PubMed: 17417742
DOI: 10.1007/s00018-007-7002-5 -
Fertility and Sterility May 1991To determine if among hyperandrogenic women acne may be differentiated from hirsutism by markers of peripheral androgen metabolism.
OBJECTIVE
To determine if among hyperandrogenic women acne may be differentiated from hirsutism by markers of peripheral androgen metabolism.
DESIGN
Prospective outpatient study of 36 hyperandrogenic women and controls divided into groups based on the presence or absence of significant hirsutism and the presence or absence of moderate to severe acne. Serum levels of adrenal and ovarian derived androgens were elevated but similar in all patient groups.
INTERVENTIONS
Measurement of serum androgens including metabolites of 5 alpha-reductase activity: 3 alpha-androstanediol glucuronide and sulfate and androsterone (A) glucuronide and sulfate.
RESULTS
3 alpha-androstanediol glucuronide and sulfate were elevated in all groups (P less than 0.05) and could differentiate between hirsute and nonhirsute patients but were similar in patients with and without acne. Serum A glucuronide and sulfate were only significantly elevated in patients with acne (P less than 0.01) and were higher than levels in controls and hirsute patients without acne. Ratios of precursor androgens to A glucuronide and sulfate were significantly higher in patients with acne compared with patients without acne (P less than 0.05).
CONCLUSIONS
Altered peripheral metabolism in acne may favor the formation of A conjugates, which may help differentiate acne from hirsutism among hyperandrogenic women.
Topics: 3-Oxo-5-alpha-Steroid 4-Dehydrogenase; Acne Vulgaris; Adolescent; Adult; Androgens; Androstane-3,17-diol; Androstenedione; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Diagnosis, Differential; Female; Hirsutism; Humans; Prospective Studies; Testosterone
PubMed: 1827073
DOI: No ID Found -
Molecules (Basel, Switzerland) Jan 2021Glucose 6-phosphate dehydrogenase (G6PDH) fulfills an essential role in cell physiology by catalyzing the production of NADPH and of a precursor for the de novo...
Glucose 6-phosphate dehydrogenase (G6PDH) fulfills an essential role in cell physiology by catalyzing the production of NADPH and of a precursor for the de novo synthesis of ribose 5-phosphate. In trypanosomatids, G6PDH is essential for in vitro proliferation, antioxidant defense and, thereby, drug resistance mechanisms. So far, 16α-brominated epiandrosterone represents the most potent hit targeting trypanosomal G6PDH. Here, we extended the investigations on this important drug target and its inhibition by using a small subset of androstane derivatives. In , immunofluorescence revealed a cytoplasmic distribution of G6PDH and the absence of signal in major organelles. Cytochemical assays confirmed parasitic G6PDH as the molecular target of epiandrosterone. Structure-activity analysis for a set of new (dehydro)epiandrosterone derivatives revealed that bromination at position 16α of the cyclopentane moiety yielded more potent G6PDH inhibitors than the corresponding β-substituted analogues. For the 16α brominated compounds, the inclusion of an acetoxy group at position 3 either proved detrimental or enhanced the activity of the epiandrosterone or the dehydroepiandrosterone derivatives, respectively. Most derivatives presented single digit μM EC against infective and the killing mechanism involved an early thiol-redox unbalance. This data suggests that infective African trypanosomes lack efficient NADPH-synthesizing pathways, beyond the Pentose Phosphate, to maintain thiol-redox homeostasis.
Topics: Androsterone; Binding Sites; Cytosol; Dehydroepiandrosterone; Glucosephosphate Dehydrogenase; Humans; Life Cycle Stages; Models, Molecular; Oxidation-Reduction; Reproducibility of Results; Steroids; Trypanosoma brucei brucei
PubMed: 33445584
DOI: 10.3390/molecules26020358 -
The Journal of Clinical Investigation Jun 1987We compared the blood (PBDHT) and urine (PUDHT) production rate of dihydrotestosterone (DHT) in normal men and women to determine whether peripheral formation was... (Comparative Study)
Comparative Study
We compared the blood (PBDHT) and urine (PUDHT) production rate of dihydrotestosterone (DHT) in normal men and women to determine whether peripheral formation was totally reflected in blood. PBDHT was similar when measured at both sites in men (674 +/- 79 vs. 788 +/- 207 SE micrograms/d); however, PUDHT was greater than PBDHT in women (174 +/- 55 vs. 55 +/- 8 micrograms/d, P less than 0.02). Excretion rates of DHT and 3 alpha-androstanediol (3 alpha diol) were similar in both sexes despite major differences in blood levels. However, between sexes large differences were present in 3 alpha diol glucuronide (3 alpha diolG) in both plasma and urine. These observations indicate that peripheral (renal) formation of DHT and probably 3 alpha diol were not accurately determined by measurement of these steroids in blood. The large difference between blood and urine production rates in women suggests an important role of non-testosterone precursors of 5 alpha-reduced steroids. Measurements of 3 alpha diolG may provide more insight into these peripheral events.
Topics: Androstane-3,17-diol; Body Fluid Compartments; Circadian Rhythm; Dihydrotestosterone; Female; Humans; Male; Metabolic Clearance Rate; Sex Factors
PubMed: 3584464
DOI: 10.1172/JCI113003 -
Iranian Biomedical Journal 2012Testosterone and its metabolites have important roles in learning and memory. The current study has conducted to assess the effect of pre-training, post-training and...
BACKGROUND
Testosterone and its metabolites have important roles in learning and memory. The current study has conducted to assess the effect of pre-training, post-training and pre-probe trial intrahippocampal CA1 administration of 3α-anderostanediol (one of the metabolites of testosterone) and indomethacin (as 3α-hydroxysteroid dehydrogenase enzyme blocker) on acquisition, consolidation and retrieval in Morris water maze (MWM) task.
METHODS
Adult male rats were bilaterally cannulated into CA1 region of hippocampus and then received 3α-diol (0.2, 1, 3 and 6 mug/0.5 mul/side), indomethacin (1.5, 3 and 6 mug/0.5 mul/side), indomethacin (3 mug/0.5 mul/side) + 3α-diol (1 mug/0.5 mul/side), 25-35 min before training, immediately after training and 25-35 min before probe trial in MWM task.
RESULTS
Our results showed that injection of 3α-diol and indomethacin significantly increased the escape latency and traveled distance to find hidden platform in acquisition and consolidation stage, but did not have any effect on retrieval of spatial learning as compared with the control group.
CONCLUSION
It is concluded that intra-CA1 administration of 3α-diol and indomethacin could impair spatial learning and memory in acquisition and consolidation stage. Also, intrahippocampal injection of indomethacin + 3α-diol could not change spatial learning and memory impairment effect of indomethacin or 3α-diol in MWM task.
Topics: Aging; Androstanes; Animals; CA1 Region, Hippocampal; Dimethyl Sulfoxide; Indomethacin; Male; Maze Learning; Memory; Rats; Rats, Wistar
PubMed: 23023216
DOI: 10.6091/IBJ.1046.2012 -
The FEBS Journal Apr 2008CYP7B1, a cytochrome P450 enzyme, metabolizes several steroids involved in hormonal signaling including 5alpha-androstane-3beta,17beta-diol (3beta-Adiol), an estrogen...
CYP7B1, a cytochrome P450 enzyme, metabolizes several steroids involved in hormonal signaling including 5alpha-androstane-3beta,17beta-diol (3beta-Adiol), an estrogen receptor agonist, and dehydroepiandrosterone, a precursor for sex hormones. Previous studies have suggested that CYP7B1-dependent metabolism involving dehydroepiandrosterone or 3beta-Adiol may play an important role for estrogen receptor beta-mediated signaling. However, conflicting data are reported regarding the influence of different CYP7B1-related steroids on estrogen receptor beta activation. In the present study, we investigated CYP7B1-mediated conversions of dehydroepiandrosterone and 3beta-Adiol in porcine microsomes and human kidney cells. As part of these studies, we compared the effects of 3beta-Adiol (a CYP7B1 substrate) and 7alpha-hydroxy-dehydroepiandrosterone (a CYP7B1 product) on estrogen receptor beta activation. The data obtained indicated that 3beta-Adiol is a more efficient activator, thus lending support to the notion that CYP7B1 catalysis may decrease estrogen receptor beta activation. Our data on metabolism indicate that the efficiencies of CYP7B1-mediated hydroxylations of dehydroepiandrosterone and 3beta-Adiol are very similar. The enzyme catalyzed both reactions at a similar rate and the K(cat)/K(m) values were in the same order of magnitude. A high dehydroepiandrosterone/3beta-Adiol ratio in the incubation mixtures, similar to the ratio of these steroids in many human tissues, strongly suppressed CYP7B1-mediated 3beta-Adiol metabolism. As the efficiencies of CYP7B1-mediated hydroxylation of dehydroepiandrosterone and 3beta-Adiol are similar, we propose that varying steroid concentrations may be the most important factor determining the rate of CYP7B1-mediated metabolism of dehydroepiandrosterone or 3beta-Adiol. Consequently, tissue-specific steroid concentrations may have a strong impact on CYP7B1-dependent catalysis and thus on the levels of different CYP7B1-related steroids that can influence estrogen receptor beta signaling.
Topics: Aging; Androstane-3,17-diol; Animals; Cell Line; Cytochrome P-450 Enzyme System; Dehydroepiandrosterone; Estrogen Receptor beta; Estrogens; Female; Gene Expression Regulation; Humans; Hydroxylation; Kinetics; Male; Organ Specificity; Signal Transduction
PubMed: 18331353
DOI: 10.1111/j.1742-4658.2008.06336.x